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=Hydatiform Degeneration In Tubal And Uterine Pregnancy=
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|[[File:Mark_Hill.jpg|50px|left]] This historic 1920 paper by Arthur William Meyer represents an early description of hydatiform moles (hydatiform mole, hydatid mole, molar pregnancy, gestational trophoblastic disease) using embryos from the [[Carnegie Collection]]. Some of these concepts are historic and have been updated with a better understanding of the genetics of this abnormal development.
  
By Arthur William Meyer.  
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<br>
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See also: [[Book_-_Contributions_to_Embryology_Carnegie_Institution_No.56-8|1921 Hydatiform Degeneration in Uterine Pregnancy]] | [[Book_-_Contributions_to_Embryology_Carnegie_Institution_No.56-9|1921 Hydatiform Degeneration in Tubal Pregnancy]]
  
Professor of Anatomy in the Lelaiul Stanford Jr. University.
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{{Mall Links}}
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<br>
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'''Modern Pages:'''
  
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'''Links:''' [[Abnormal_Development_-_Hydatidiform_Mole|Hydatidiform_Mole]] | [[Carnegie Collection]]
  
With six plates.  
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A type of fertilisation abnormality, when only the conceptus trophoblast layers proliferates and not the embryoblast, no embryo develops, this is called a "hydatidiform mole". Due to the continuing presence of the trophoblastic layer, this abnormal conceptus can also implant in the uterus or ectopically. The trophoblast cells will secrete human chorionic gonadotropin (hCG), as in a normal pregnancy, and may appear maternally and by pregnancy test to be "normal". Prenatal diagnosis by ultrasound analysis demonstrates the absence of a embryo.
  
:'''Links:''' [[Book_-_Contributions_to_Embryology|Carnegie Institution of Washington - Contributions to Embryology]]
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* Complete Mole - Only paternal chromosomes.
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* Partial Mole - 3 sets of chromosomes ( (triploidy) instead of the usual 2.
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|}
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{{Historic Disclaimer}}
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=Hydatiform Degeneration In Tubal And Uterine Pregnancy=
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[[File:Arthur William Meyer.jpg|thumb|alt=File:Arthur William Meyer.jpg|thumb|alt=Arthur William Meyer (1873 – 1966)|link=Embryology History - Arthur Meyer|Arthur William Meyer (1873 – 1966)]]
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By [[Embryology History - Arthur Meyer|Arthur William Meyer]].
  
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Professor of Anatomy in the Lelaiul Stanford Jr. University.
  
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Volume IX (1920) pp 327- 364 With six plates.
  
-----Content to be added----
 
 
 
{{Template:Historic Disclaimer}}
 
  
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:[[Book_-_Contributions_to_Embryology_Carnegie_Institution_No.40|'''Links''']]: [[:File:Meyer1920_Plate_1.jpg|Plate 1]] | [[:File:Meyer1920_Plate_2.jpg|Plate 2]] | [[:File:Meyer1920_Plate_3.jpg|Plate 3]] | [[:File:Meyer1920_Plate_4.jpg|Plate 4]] | [[:File:Meyer1920_Plate_5.jpg|Plate 5]] | [[:File:Meyer1920_Plate_6.jpg|Plate 6]] | [[Book_-_Contributions_to_Embryology_Carnegie_Institution_No.40|Contribution No.40]] | [[Book_-_Contributions_to_Embryology#Volume_IX|Volume IX]] | [[Book_-_Contributions_to_Embryology|Contributions to Embryology]] | [[Abnormal Development - Hydatidiform Mole|Hydatidiform Mole]] | [[Abnormal_Development_-_Ectopic_Implantation|Tubal Pregnancy]]
  
 
==Introduction==
 
==Introduction==
  
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The following study is an outgrowth of a survey (planned by Mall) of the embryological collection of the Carnegie Institution of Washington. It was my privilege to share in this undertaking and to be permitted to follow any matters of special interest to me. The following report concerns itself especially with the occurrence of hydatiform degeneration in abortuses and specimens in the Mall Collection which were obtained through operation and were classed as pathological. My attention was attracted to the subject while engaged in an examination of the Hofbauer cells, begun at the suggestion of Mall. For the purpose of convenience I shall discuss the tubal and uterine cases separately, including what is common to both with the latter.
  
The following study is an outgrowth of a survey (planned by Mall) of the
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==Tubal==
embryological collection of the Carnegie Institution of Washington. It was my
 
privilege to share in this undertaking and to be ])ermitted to follow any matters of
 
special interest to me. The following report concerns itself especially with the
 
occurrence of hydatiform degeneration in abortuses and specimens in the Mall
 
Collection which were obtained through operation and were classed as pathological.
 
My attention was attracted to the subject while engaged in an examination of the
 
Hofbauer cells, begun at the suggestion of MaU. For the purpose of convenience I
 
shall discuss the tubal and uterine cases separately, including what is common to
 
both with the latter.
 
  
==TUBAL==
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Strangely enough, the occurrence of chorio-epithelioma arising from tuba pregnancy seems to be better known and also better established than the occurrence of hydatiform mole within the tube. This is especially surprising in view of the stress laid by Marchand (1898) upon epithelial proliferation in cases of hydatiform mole and in view of the fact that trophoblast formation and epithelial proliferation in general have been regarded as being greater in tubal than in cases of uterine implantation. This is illustrated well by such cases as that of Fellner (1903), in which it was impossible to distinguish by histologic examination between the epithelial proliferation present in a case of tubal pregnancy and that from a chorio-epithelioma. From these circumstances alone it seems to me that one might expect hydatiform degeneration to be relatively more common in the tubes. Moreover, when it is recalled that experts still regard it as impossible to decide upon the question of malignancy or benignity in cases of suspected uterine chorio-epithelioma from histologic preparations alone, this surmise gains more in probability. The presence of hyperactivity in the trophoblast in many cases of tubal pregnancy as compared with the uterine was confirmed also by personal observation, and if, as stated by Teacher (1903), chorio-epithelioma arose in hydatiform moles in approximately 40 per cent of 287 cases, and according to Seitz (1904) and Fraenkel (1910) even in 50 per cent, the occurrence of hydatiform degeneration in tubal pregnancy can hardly be doubted because of this fact alone. Nevertheless, of the 7 cases of tubal hydatiform moles cited by him, Werth (1904) regards only the case reported separately by von ReckUnghausen (1889) and by Freund (1889) as well authenticated. Werth reserves judgment, however, on the case of Matwejew and Sykow (1901), a report upon which was accessible to him, and to me, in a short review only. Seitz, however, accepted the short review of this case as convincing, nor did he question the case of Otto (1871), or that of Wenzel (1893), and he incorrectly credited Wenzel with two cases. Werth, on the contrary, regarded these last two cases, and also that of Croom (1895), which is accepted also by Veit (1899), as undoubted instances of "simple hydropic degeneration of the connective tissue of the villi  so connnon in aborted chorionic vesicles, both from the tubes and from the uterus." Werth unfortunately does not state just what he means by simple hydropic degeneration, but since he speaks of it as common in aborted ova, one may conclude that he refers to changes in the chorionic vesicle which have followed its isolation within the uterus after complete detachment from its implantation site. For want of a better term, such changes may, I presume, be spoken of as maceration changes, although usually they occur under non-putrefactive conditions. However, I do not thereby imply that these changes are similar under sterile and under putrefactive conditions.
  
Strangely enough, the occurrence of chorio-epitheUoma arising from tuba
 
pregnancy seems to be better known and also better established than the occurrence
 
of hydatiform mole within the tube. Tliis is especially surprising in view of the
 
stress laid by Marchand (1898) upon epithelial proliferation in cases of hydatiform
 
mole and in view of the fact that trophoblast formation and epithehal proliferation
 
in general have been regarded as being greater in tubal than in cases of uterine
 
implantation. This is illustrated well by such cases as that of Fellner (1903), in
 
which it was impossible to distinguish by histologic examination between the
 
epithelial proliferation present in a case of tubal pregnancy and that from a chorio-
 
epithelioma. From these circumstances alone it seems to me that one might expect
 
hj'datiform degeneration to be relatively more common in the tubes. Moreover,
 
when it is recalled that experts still regard it as impossible to decide upon the
 
question of malignancy or benignity in cases of suspected uterine chorio-epithelioma
 
from histologic preparations alone, this surmise gains more in probabihty. The
 
presence of hyperactivity in the trophoblast in many cases of tubal pregnancy as
 
compared with the uterine was confirmed also by personal observation, and if, as
 
stated by Teacher (1903), chorio-epithelioma arose in hydatiform moles in approxi-
 
mately 40 per cent of 287 cases, and according to Seitz (1904) andFraenkel (1910)
 
even in 50 per cent, the occurrence of hydatiform degeneration in tubal pregnancy
 
can hardlj' be doubted because of this fact alone. Nevertheless, of the 7 cases of
 
tubal hydatiform moles cited by him, Werth (1904) regards only the case reported
 
separately by von ReckUnghausen (1889) and by Freund (1889) as well authenti-
 
cated. Werth reserves judgment, however, on the case of Matwejew and Sykow
 
(1901), a report upon which was accessible to him, and to me, in a short review only.
 
Seitz, however, accepted the short review of this case as convincing, nor did he question the c:ise of Otto (1871), or that of Wenzel (1893), and he incorrectly credited
 
Wenzel with two cases. Werth, on the contrary, regarded these last two cases, and
 
also that of Croom (1895), which is accepted also by Veit (1899), as undoubted
 
instances of "simple hydropic degeneration of the connective tissue of the vilh so
 
connnon in aborted chorionic vesicles, both from the tubes and from the uterus."
 
Werth unfortunately does not state just what he means by simjjlc hydroijic degen-
 
eration, but since he sjjeaks of it as common in aborted ova, one may conclude that
 
he refers to changes in the chorionic vesicle wliich have followed its isolation witliin
 
the uterus after complete detachment from its implantation site. For want of a
 
better term, such changes may, I presume, be spoken of as maceration changes,
 
although usually they occur under non-i)utrefactive conditions. However, I do not
 
thereby imply that these changes are similar under sterile and under i)utrefactive
 
conditions.
 
  
Since Werth speaks of simple hydropic degeneration in aborted ova he does  
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Since Werth speaks of simple hydropic degeneration in aborted ova he does not, I take it, refer to a dropsical condition of the villi possibly due to an obstruction of the venous return, for such a condition necessarily would be rare and not common. Moreover, this condition of necessity would have to arise before and not after the death of the embryo and detachment of the chorionic vesicle. As in one of the cases of Hiess (1914), such a specimen also should contain blood-vessels — for, as emphasized also by Ballantyne (1913), the hydatiform villus is not merely an edematous villus.
not, I take it, refer to a dropsical condition of the villi possiblj' due to an obstruction  
 
of the venous return, for such a condition necessarily would be rare and not com-
 
mon. Moreover, this condition of necessity would have to arise before and not  
 
after the death of the embryo and detachment of the chorionic vesicle. As in one  
 
of the cases of Hiess (1914), such a specimen also should contain blood-vessels —  
 
for, as emphasized also by Ballantyne (1913), the hydatiform villus is not merely  
 
an edematous villus.  
 
  
That any one at all familiar with hydatiform degeneration, in its earUer as
 
well as its later forms, upon gross and microscopic examination, could confuse it
 
with maceration changes in a fairly well-preserved specimen in any but its very
 
earliest stages does not seem possible to me. Normal villi contain capillaries, not
 
to mention other things characteristic of them. Hydatiform villi, on the contrary,
 
do not contain them, or only very rarely so, and in the early stages. When a villus
 
becomes hydatiform — that is, when hquefaction of the stroma occurs — this lique-
 
faction appears in more or less restricted portions of the villus, thus giving rise to
 
the long fusiform and later spherical vesicles so characteristic of hydatiform mole.
 
But when a villus becomes macerated the change is general, and usually also is
 
noticeable in the embryonic and chorionic membrane itself, or at least within the
 
epithelium. The latter usually is lifted from the stroma here and there, the caliber
 
of the entire villus is increased, and the cai)illaries and the stroma show maceration
 
changes as the villus becomes more translucent. This increase in cahber of the
 
entire villus is not due to local liquefaction of the stroma, but to the jiseudo-edema
 
occurring in a villus of normal structure and form. In hydatiform moles, on the
 
contrary, the epithelium not only is (irmly attached but usually hyperactive. The
 
changes characteristic of hydatiform degeneration may and often do appear in
 
the vilh wliile they still are imjilanted, and not only after the chorionic vesicles
 
are detached. Tliis docs not imi)ly, however, that the vilh of a detached hydati-
 
form mole can not also undergo maceration changes. They, of course, frcfjuently
 
do .so, and it is in such ca.ses as the.se that difTer(>ntiation may be difficult or impos-
 
sible, esjjecially if it is to be made from an examination of ill-pre.served fragments only. The same thing i.s true also of the villi in the early stages of hydatiform
 
degeneration and maceration, especially when the latter masks the former. The
 
(Ufficulty would be still greater in case of whole chorionic vosicI(>s which are almost
 
completely dissolved, leaving only a shadow picture formed by a coagulum without
 
nuclei, which nevertheless may retain almost perfectly the form of the chorionic
 
vesicle and of the individual villi. It may long be imjxjssilile to differentiate such
 
cases as these, but they form only a relatively small proportion of the whole. The
 
many cases both of uterine and tubal chorionic vesicles which still were implanted
 
and show exceedingly fine instances of hydatiform degeneration, as well as the many
 
splendid examples of groujis of villi which were still imiilanted in the tube or in the
 
decidua, and which were eciually good examples of hydatiform degeneration, leave
 
no room for doubt as to the frequency of occurrence of this condition, even after
 
due allowance is made for the doubtful cases.
 
  
Werth further concluded that not one of the 7 cases of chorio-epithelioma
+
That any one at all familiar with hydatiform degeneration, in its earlier as well as its later forms, upon gross and microscopic examination, could confuse it with maceration changes in a fairly well-preserved specimen in any but its very earliest stages does not seem possible to me. Normal villi contain capillaries, not to mention other things characteristic of them. Hydatiform villi, on the contrary, do not contain them, or only very rarely so, and in the early stages. When a villus becomes hydatiform — that is, when hquefaction of the stroma occurs — this liquefaction appears in more or less restricted portions of the villus, thus giving rise to the long fusiform and later spherical vesicles so characteristic of hydatiform mole. But when a villus becomes macerated the change is general, and usually also is noticeable in the embryonic and chorionic membrane itself, or at least within the epithelium. The latter usually is lifted from the stroma here and there, the caliber of the entire villus is increased, and the cai)illaries and the stroma show maceration changes as the villus becomes more translucent. This increase in cahber of the entire villus is not due to local liquefaction of the stroma, but to the pseudo-edema occurring in a villus of normal structure and form. In hydatiform moles, on the contrary, the epithelium not only is firmly attached but usually hyperactive. The changes characteristic of hydatiform degeneration may and often do appear in the villi  wliile they still are imjilanted, and not only after the chorionic vesicles are detached. This docs not imply, however, that the villi of a detached hydatiform mole can not also undergo maceration changes. They, of course, frequently do so, and it is in such cases as the.se that differentiation may be difficult or impossible, esjjecially if it is to be made from an examination of ill-preserved fragments only. The same thing is true also of the villi in the early stages of hydatiform degeneration and maceration, especially when the latter masks the former. The difficulty would be still greater in case of whole chorionic vesicles which are almost completely dissolved, leaving only a shadow picture formed by a coagulum without nuclei, which nevertheless may retain almost perfectly the form of the chorionic vesicle and of the individual villi. It may long be impossible to differentiate such cases as these, but they form only a relatively small proportion of the whole. The many cases both of uterine and tubal chorionic vesicles which still were implanted and show exceedingly fine instances of hydatiform degeneration, as well as the many splendid examples of groups of villi which were still implanted in the tube or in the decidua, and which were eciually good examples of hydatiform degeneration, leave no room for doubt as to the frequency of occurrence of this condition, even after due allowance is made for the doubtful cases.
regarded as having arisen from tubal pregnancies recorded before 1904 was suffi-  
 
ciently authenticated. Nevertheless, by 1910 Veit felt justified in saying that a
 
considerable number of cases of chorio-epithelioma arising from tubal pregnancies
 
had been described. He added that Risel (1895) gathered 11 cases from the litera-
 
ture and that the second case had been reported since Risel's paper. Since my
 
interest in the subject is largely incidental, I have not taken the trouble to gather
 
from the literature cases of chorio-epithelioma alleged to have arisen from tubal
 
pregnancies which may have been reported since Veit wrote. Moreover, I could
 
not presume to judge these cases critically. Hence I will accept the fact that chorio-  
 
epithelioma arising from tubal pregnancy is regarded as established by a number
 
of investigators. If the conception regarding the relation of chorio-epithelioma to
 
hj^datiform mole is justified, then the occurrence of hydatiform degeneration in  
 
tubal pregnancy must follow on a priori grounds alone. Moreover, whatever the  
 
causes of hydatiform degeneration may be, one possibly is safe in assuming that the
 
condition is not restricted to the uterus, and when I noticed that hydatiform
 
degeneration was so very common in young uterine abortuses the surmise that it
 
might he still more common in cases of tubal pregnancy seemed justified. Since
 
over 100 specimens of tubal pregnancies from the Mall Collection were included
 
in the survey originally planned by him, a study of these specimens formed an
 
excellent opportunity for observations on this subject.  
 
  
That the case of Otto, with its pathetic history, reaUy was one of hydatiform
 
mole, can not be doubted in view of the careful description of the whole case — its
 
clinical history, necrojxsy, and the histologic examination. This case is interesting
 
also because the degeneration was in its early stages, the hydatids being only as
 
large as a i>inhead and the embrA'o still being present. Moreover, from Otto's
 
description it is very Ukely that the specimen contained Hofbauer cells which I have
 
discussed elsewhere (Meyer, 1919).
 
  
The history of the case observed bj^ Wenzel in 1855 and reported in 1893 is
+
Werth further concluded that not one of the 7 cases of chorio-epithelioma regarded as having arisen from tubal pregnancies recorded before 1904 was sufficiently authenticated. Nevertheless, by 1910 Veit felt justified in saying that a considerable number of cases of chorio-epithelioma arising from tubal pregnancies had been described. He added that Risel (1895) gathered 11 cases from the literature and that the second case had been reported since Risel's paper. Since my interest in the subject is largely incidental, I have not taken the trouble to gather from the literature cases of chorio-epithelioma alleged to have arisen from tubal pregnancies which may have been reported since Veit wrote. Moreover, I could not presume to judge these cases critically. Hence I will accept the fact that chorio-epithelioma arising from tubal pregnancy is regarded as established by a number of investigators. If the conception regarding the relation of chorio-epithelioma to hydatiform mole is justified, then the occurrence of hydatiform degeneration in tubal pregnancy must follow on a priori grounds alone. Moreover, whatever the causes of hydatiform degeneration may be, one possibly is safe in assuming that the condition is not restricted to the uterus, and when I noticed that hydatiform degeneration was so very common in young uterine abortuses the surmise that it might he still more common in cases of tubal pregnancy seemed justified. Since over 100 specimens of tubal pregnancies from the Mall Collection were included in the survey originally planned by him, a study of these specimens formed an excellent opportunity for observations on this subject.
equally complete and equally pathetic, as could be surmised by all famiUar with
 
the history of tubal pregnancy. In this case the mole was as large as a "hen egg," the hydatids varied in size from a dot to a "bird cherry'' (wild? cherry), and the  
 
degeneration was universal, although the menstrual af2;e of this specimen was ^iven
 
as only 51 days. It is significant that \\'enzel expresses surjirise that even (!xcellent
 
handbooks of the day had nothing to say about hydatiform mole in cases of tubal  
 
pregnancy, except perhaps to refer to the case of Otto. Nor does the case of Wenzel
 
seem to be the first one observed or that of Otto the first one reported, for Storch
 
(1878), in truly epochal, though largely ignored, observations on hydatiform mole,  
 
cites Hennig (187G) as stating that two cases of moles in the tube w-ere rejjorted by
 
Bla.sius (\ery likely E. Blasius, 1802-75). Since Storch wrote on hydatiform mole
 
it is imjihed that Blasius saw one of these and not one of another type of mole, and  
 
since hydatiform mole is such a striking condition and has evoked much more
 
interest than the other forms, an observation regarding it in the tubes well might
 
travel down the decades, particularly since until recently the occurrence of hydati-
 
form degeneration in the tubes was regarded as extremely rare. This is indicated
 
also by the fact that Menu (1899) still referred to the case of Otto as a curiosity.  
 
  
Pazzi (1908') states that two cases of extrauterine moles have been described
 
each bj' Hennig (1872), Farell (1893), Donald (1902), and one case each by Otto,
 
Freund, Theileher, Maret, Matwjew (Matwejew?) and Sycow (Sykow?), Bland
 
Sutton, and one case of ovarian mole by Wenzel (1893). Wilkinson is said to have
 
described a case of rupture of the tube with reduction of the mole to the size of a
 
cherry, and Lob (1902) also gives a case of molar tubal pregnane}^ without cessation
 
of menstruation. Since I am quoting Pazzi essentially verbatim, it is evident that
 
he did not read the hterature critically or discriminate between ordinary and hydati-
 
form moles, but was misled by the old inclusive and confusing usage of the terms
 
mole and molar, still current at the present day.
 
  
Krueger (1909) also reported a case of hydatiform mole with a cyst as large as
+
That the case of Otto, with its pathetic history, really was one of hydatiform mole, can not be doubted in view of the careful description of the whole case — its clinical history, necropsy, and the histologic examination. This case is interesting also because the degeneration was in its early stages, the hydatids being only as large as a pinhead and the embryo still being present. Moreover, from Otto's description it is very likely that the specimen contained Hofbauer cells which I have discussed elsewhere (Meyer, 1919).
a "walnut." The pedicle was 4 cm. long and attached to the amnion near the
 
insertion of the cord. Krueger spoke of this as a i)lacental cyst but regarded it as a
 
hydatiform-mole-like structure wWch, microscoijically, was limited to a single
 
villus. If this were the only evidence presented liy Krueger one might well question
 
the nature of the cyst, but he added that microscopically the beginnings of hydati-
 
form formations could be recognized on other vilh also. Hence it would seem that  
 
Krueger's case must be added to the authenticated cases of hytlatiform degenera-
 
tion in the tubes.  
 
  
So far as I am able to learn, then, the literature contains reports of 9 cases of
 
hj'datiform mole occurring in the tube, but two or three of these cases are not well
 
authenticated. These 9 cases are formed by the 2 cases of Blasius or Hennig, that
 
of Otto, of von Recklinghausen and Freund, and of Wenzel, the 2 of Croom, that
 
of Matwejew and Sykow, and that of Krueger. A critical reading of Hennig's
 
book on diseases of the tubes and tubal pn^gnancy makes it ([uite clear, however,
 
vhcii, ilennig men^ly said that lilasius discovered "tubal moles" and that he observed
 
two, and Behm one case of abortion of tubal moles. From Llie context al.so it is
 
very clear that Hennig was not discus.sing hydatiform moles, although it is not
 
possible to say whether he meant that he himself or Blasius observed two cases.
 
I should judge that the latter is the idea it was meant to convey. To these 7
 
authenticated cases I would add that of Maxwell (1910). In reading Maxwell's
 
doscriiition one must feel that he himself regarded the case as one of hydatiform
 
mole, but deferred to the opinion of the "Committee." This is suggested also by
 
the title of his article. The illustration which accomjianies Maxwell's article is so
 
very suggestive, and his tloscrijjtion so characteristic of hydatiform mole, that it
 
seems very probable indeed that the specimen really was such. Maxwell states,
 
for example, that "sections of the viUi embedded in the wall of the tube have the
 
typical structureless, bloated appearance of such pathological vilU; and though
 
there is no central cavitation in the villi, their structure, associated with the active
 
proliferation of the Langhans layer, suggests that one is looking at a stage just
 
short of vesicle formation." Moreover, as I am about to show, hydatiform mole is
 
so verj^ common both in tubal pregnancies and in uterine abortions as to increase
 
still further the likelihood that Ma:. well's case actually was one of hydatiform mole.
 
This is merely an opinion, and only a completer description or an examination
 
of the specimen itself could decide the matter.
 
  
In connection with what was said before, it is interesting that Maxwell also
+
The history of the case observed by Wenzel in 1855 and reported in 1893 is equally complete and equally pathetic, as could be surmised by all familiar with the history of tubal pregnancy. In this case the mole was as large as a "hen egg," the hydatids varied in size from a dot to a "bird cherry'' (wild? cherry), and the degeneration was universal, although the menstrual cycle of this specimen was given as only 51 days. It is significant that Wenzel expresses surprise that even excellent handbooks of the day had nothing to say about hydatiform mole in cases of tubal pregnancy, except perhaps to refer to the case of Otto. Nor does the case of Wenzel seem to be the first one observed or that of Otto the first one reported, for Storch (1878), in truly epochal, though largely ignored, observations on hydatiform mole, cites Hennig (187G) as stating that two cases of moles in the tube were reported by Blasius (very likely E. Blasius, 1802-75). Since Storch wrote on hydatiform mole it is implied that Blasius saw one of these and not one of another type of mole, and since hydatiform mole is such a striking condition and has evoked much more interest than the other forms, an observation regarding it in the tubes well might travel down the decades, particularly since until recently the occurrence of hydatiform degeneration in the tubes was regarded as extremely rare. This is indicated also by the fact that Menu (1899) still referred to the case of Otto as a curiosity.
emphasized that epiblastic activity is increased in all abnormal sites of implantation,
 
and any one interested in the problems of tubal pregnancy and acquainted with
 
Mall's (1915) findings will be struck by Maxwell's statement that microscopical
 
examination of many cases of tubal gestation lends no weight to the view that chronic
 
inflammation of the tubes is at all a common causal factor of tubal pregnancy. Nor
 
can I refrain, in this connection, from quoting the uncontradicted o])inion of Doran,  
 
expressed in the discussion of [Maxwell's case, that tubal gestation "probably repre-
 
sents some general deterioration in the generative power among civiUzed women."
 
  
To the 8 cases contained in the literature I wish to add 48 found among the
 
first 1,187 accessions from the Mall Collection. Nor is it necessary to stop with
 
these, for this collection contains many more not here included. It is merely a
 
matter of recognizing the specimens by a routine examination, and since this paper
 
has been written a number of sjiecimens have been recognized among the daily
 
accessions of tubes received through the unselfish efforts and the scientific interest
 
of practitioners in all parts of the nation.
 
  
In addition to over 100 free specimens of uterine Iwdatiform degeneration,  
+
Pazzi (1908') states that two cases of extrauterine moles have been described each by Hennig (1872), Farell (1893), Donald (1902), and one case each by Otto, Freund, Theileher, Maret, Matwjew (Matwejew?) and Sycow (Sykow?), Bland Sutton, and one case of ovarian mole by Wenzel (1893). Wilkinson is said to have described a case of rupture of the tube with reduction of the mole to the size of a cherry, and Lob (1902) also gives a case of molar tubal pregnancy without cessation of menstruation. Since I am quoting Pazzi essentially verbatim, it is evident that he did not read the literature critically or discriminate between ordinary and hydatiform moles, but was misled by the old inclusive and confusing usage of the terms mole and molar, still current at the present day.
I have also seen more than a dozen fine specimens in large sections of uterine
 
implantation sites, and some entire specimens still embedded in pregnant uteri and  
 
tubes. Indeed, how many cases of hydatiform degeneration one can find in concep-
 
tuses in tubal or hysterectomy specimens will depend very much upon the care
 
with wliich the examination is made, for the condition undoubtedlj' is extremely
 
common, and not I'are, as heretofore supposed.  
 
  
Although the alleged menstrual age of these conceptuses ranged approximately
 
from 6 to 218 days, most of them were young empty chorionic vesicles or mere
 
remnants of such. Portions of quite a number still were implanted within the tubes, however, aiul among the(>c were two unusually line ones in a rare specimen of twin
 
pregnancy in the tube donated by Dr. Cecil E. Vest, of Baltimore. Since the ques-
 
tion of superfetation has been raised also in connection w4th twin tubal pregnancies,
 
I hasten to add thftt such a jihenomenon, even if it ever occurs (which seems exceed-
 
ingly doubtful) can be excluded alisolutely in this case. Both chorionic ve.sicles
 
were ai)proximately of the same size and lay in jiractieally the same cross-section
 
of the tube, the surfaces of contact being flattened.
 
  
Before proceeding with the statistical finthngs, I may say that the abortuses
+
Krueger (1909) also reported a case of hydatiform mole with a cyst as large as a "walnut." The pedicle was 4 cm. long and attached to the amnion near the insertion of the cord. Krueger spoke of this as a placental cyst but regarded it as a hydatiform-mole-like structure which, microscopically, was limited to a single villus. If this were the only evidence presented by Krueger one might well question the nature of the cyst, but he added that microscopically the beginnings of hydatiform formations could be recognized on other villi  also. Hence it would seem that Krueger's case must be added to the authenticated cases of hydatiform degeneration in the tubes.
in the Mall Collection regarded as pathological are grouped (1) as vilU only; (2) as
 
empty or partial chorionic vesicles; (3) as chorionic vesicles containing some or all
 
of the amnion; (4) all si^ecimens containing nodular, or (5) cylindrical embryos,
 
or (6) stunted, and (7) macerated and mummified fetuses. Any one interested in
 
this classification will find it discussed and exemphfied in an article by Mall (1917).  
 
  
There were 40 tubes containing villi only, and in 14 of these hydatiform
 
degeneration probably was present. In 10 specimens its presence was undoubted,
 
but in 4 it was probable only. I realize that this margin of probability is exceedingly
 
larg(>, but this is easily understood if it is recalled that often only a few degenerate
 
villi embedded in clot were contained in the cross-sections of many of the tubes,
 
and that only a few sections w'ere examined, not, of course, a comjilete series of
 
each tube. Had the entire tubes been examined, or if more villi had been present,
 
and if those present had been better preserved, the difficulty would have been
 
almost wholly obviated. However, it is idle to set forth these things, because such
 
conditions never will obtain, and the margin of probability becomes greatly reduced
 
if it is remembered that in a large series the specimens necessarily supplement each
 
other. Moreover, the changes in the vilU often are so typical that they are unmis-
 
takable, even if onlj^ a few villi are present. Besides, examination in complete
 
series undoubtedly would increase, not decrease the number found. In some of the
 
doubtful cases the existence of hydatiform degeneration became probable only
 
upon comparison with the many uterine specimens previously examined.
 
  
The evidence offered by the 36 tubal specimens in the second group, which is
+
So far as I am able to learn, then, the literature contains reports of 9 cases of hydatiform mole occurring in the tube, but two or three of these cases are not well authenticated. These 9 cases are formed by the 2 cases of Blasius or Hennig, that of Otto, of von Recklinghausen and Freund, and of Wenzel, the 2 of Croom, that of Matwejew and Sykow, and that of Krueger. A critical reading of Hennig's book on diseases of the tubes and tubal pregnancy makes it quite clear, however, vhcii, Hennig mainly said that Blasius discovered "tubal moles" and that he observed two, and Behm one case of abortion of tubal moles. From Llie context also it is very clear that Hennig was not discussing hydatiform moles, although it is not possible to say whether he meant that he himself or Blasius observed two cases. I should judge that the latter is the idea it was meant to convey. To these 7 authenticated cases I would add that of Maxwell (1910). In reading Maxwell's doscription one must feel that he himself regarded the case as one of hydatiform mole, but deferred to the opinion of the "Committee." This is suggested also by the title of his article. The illustration which accompanies Maxwell's article is so very suggestive, and his description so characteristic of hydatiform mole, that it seems very probable indeed that the specimen really was such. Maxwell states, for example, that "sections of the viUi embedded in the wall of the tube have the typical structureless, bloated appearance of such pathological villi; and though there is no central cavitation in the villi, their structure, associated with the active proliferation of the Langhans layer, suggests that one is looking at a stage just short of vesicle formation." Moreover, as I am about to show, hydatiform mole is so very common both in tubal pregnancies and in uterine abortions as to increase still further the likelihood that Ma:. well's case actually was one of hydatiform mole. This is merely an opinion, and only a completer description or an examination of the specimen itself could decide the matter.
composed of empty chorionic vesicles or parts thereof, was very conclusive, for the  
 
cut ])ortions of most of these tubes contained considerable jiortions or even sections
 
f)f whole chorionic vesicles, sometimes cjuite free from clot. Some of them were
 
implanted almost perfectly in the wall of the tube, and although many of them
 
were folded extremely and collapsed more or less, small areas of several were never-
 
theless implanted undisturbed within the tube. The villi in some of these implanted
 
specimens were so characteristic and the whole picture so exquisite, that the spec-
 
imens rightly belong among the very finest instances of hydatiform dogeiuM-ation
 
found anywhere so far. This is true in particular of the case of twin pregnancy  
 
received from Dr. Vest. In this specimen the two chorionic vesicles, the intervillous
 
.spaces of wliich were devoid of blood, lay in almost the same transverse diameter of
 
the tube and hence had distended the latter considerably. Both were implanted
 
(juite well over th(' entire area of contact, which included the whole j^erimeter of the  
 
tube. The ch(«ionic vesicles were; flattened at the region of mutual contact, which divided the tube somewhat unequallj^ as shown in figure 1. Although the embryo
 
and the amnicjn long had disintegrated completeh', and although the chorionic
 
membrane itself is thin, covered by degenerate epithelium and also disintegrating,  
 
the epithelium of the vilh not only is well preserved but is accompanied by large
 
masses of trophoblast and considerable syncytium. Syncytial buds are found on
 
the chorionic membrane also. The tubal mucosa is largeh' and the tubal wall partly
 
destroyed by the invading f rophoblast. Only a few small vestiges of the walls of the  
 
villous vessels remain, and the stroma of all the villi has undergone changes charac-
 
teristic of hydatiform degeneration represented in figure 2. One villus also contains
 
an epithehal cyst resulting from epithehal invagination with subsequent isolation of  
 
the distal extremity, a process to be referred to later in connection with uterine
 
specimens. Since most of the vilU of this and similar specimens still are implanted
 
in the tube, there can no longer be any question as to the time in which hydatiform  
 
changes in the stroma of the villi may be inaugurated. As illustrated in other
 
instances in which isolated and small groups of villi still were implanted, the advent
 
of degeneration of the stroma occurs, in part at least, before the villus is detached.  
 
Hence it is not merely a post-mortem or maceration change.  
 
  
Another verj* interesting specimen of tubal implantation is No. 1771, received
 
from Dr. H. M. N. Wynne, of the Johns Hopkins Hospital. The menstrual age of
 
this specimen is 49 days, but its anatomic age, as based upon length according to
 
Dr. Streeter's curve (unpubUshed), is 37 days, thus showing a discrepancy between
 
the menstrual and anatomic ages of 12 days. The embrj'onic length is only 12.5
 
mm., although with a menstrual age of 49 days it should be at least 18 mm. Upon
 
examination, Dr. Streeter found the chorionic vesicle to contain a good deal of
 
magma, some of which still was adherent to the embryo, as figure 3 shows. As has
 
been repeatedly emphasized in the hterature, the presence of this coagulum in
 
itself probablj' indicates that the embryo died some time previousl}'.
 
  
The wall of the tube is quite thin, as figure 4 shows, but the implantation is  
+
In connection with what was said before, it is interesting that Maxwell also emphasized that epiblastic activity is increased in all abnormal sites of implantation, and any one interested in the problems of tubal pregnancy and acquainted with Mall's (1915) findings will be struck by Maxwell's statement that microscopical examination of many cases of tubal gestation lends no weight to the view that chronic inflammation of the tubes is at all a common causal factor of tubal pregnancy. Nor can I refrain, in this connection, from quoting the uncontradicted opinion of Doran, expressed in the discussion of Maxwell's case, that tubal gestation "probably represents some general deterioration in the generative power among civilized women."
fairly well preserved around the whole perimeter of the specimen. The mucosa
 
is destroyed throughout the greater extent of the section and the trophoblast is
 
abundant, except in one rather degenerate and hemorrhagic area. The chorionic
 
membrane is thin but contains some vessels distended with blood. The stroma
 
of many of the villi also contains vessels filled with blood, but the vessels in many
 
others are very evidently in degeneration. The syncytium is scanty and many
 
of the villi are very plainly' hydatiform, as seen in figures 5 and 6.  
 
  
A tliird exceptionally fine specimen of tubal hydatiform mole is No. 2052,
 
donated by Dr. N. M. Davis, of Washington, D. C. Figure 7 shows a portion of
 
the tube containing the hydatiform mole, some hj'datiform x-iUi of which protrude
 
through an incision in the wall of the tube. The whole opening is filled with typical
 
hydatiform villi barelj' detected by the unaided eye but perfectly evident under
 
an enlargement of 4 diameters. The\' present an extremely fine picture when seen
 
with the binocular under a magnification of 10 to 20 diameters. Examination under
 
a higher magnification shows that the preservation of the specimen is unusually
 
good and that all the villi are markedly hydatiform. Trophoblastic proUferation
 
is so marked that in some places it gives the appearance of decidual formation.
 
  
 +
To the 8 cases contained in the literature I wish to add 48 found among the first 1,187 accessions from the Mall Collection. Nor is it necessary to stop with these, for this collection contains many more not here included. It is merely a matter of recognizing the specimens by a routine examination, and since this paper has been written a number of specimens have been recognized among the daily accessions of tubes received through the unselfish efforts and the scientific interest of practitioners in all parts of the nation.
  
  
Relatively little syncytium is present, but the trophoblast invades the muscularis
+
In addition to over 100 free specimens of uterine hydatiform degeneration, I have also seen more than a dozen fine specimens in large sections of uterine implantation sites, and some entire specimens still embedded in pregnant uteri and tubes. Indeed, how many cases of hydatiform degeneration one can find in conceptuses in tubal or hysterectomy specimens will depend very much upon the care with which the examination is made, for the condition undoubtedly is extremely common, and not I'are, as heretofore supposed.
in many places and a pood deal of coagulum is present, most of it ajjparently having
 
arisen from def>;eneration changes in the stroma of the mucosa and from similar
 
changes in the trophoblast and the muscularis. The latter is moderately invaded
 
by round cells. No remnant of the wall of the chorionic vesicle or of the amnion or
 
embryo could be detected in the sections examined, both evidently having been
 
absorbed completely, only some of the villi remaining behind; or, the chorionic
 
vesicle may have been aborted and these villi left imjilanted within the tube.  
 
  
Some exceedingly fine hydatiform villous trees wore found among the speci-
 
mens in this group. Scaffoldings or frameworks formed by proliferating syncytium
 
arising from the epithelium of the chorionic membrane also were seen. Since the
 
syncj^tial buds were found far out on proliferations of troi:)hoblast which capped the
 
viUi, and also in the center of trophoblastic nodules, the origin of the sync^-tium
 
from the Langhans layer would seem to be again and excei)tionally well confirmed.
 
In some cases a detached hydatiform villus was fastened by opposite extremities
 
to two portions of the tube wall. It is well to remember, however, that one of these
 
attachments probably was gained before the separation of the particular villus
 
from the chorionic vesicle.
 
  
 +
Although the alleged menstrual age of these conceptuses ranged approximately from 6 to 218 days, most of them were young empty chorionic vesicles or mere remnants of such. Portions of quite a number still were implanted within the tubes, however, and among these were two unusually line ones in a rare specimen of twin pregnancy in the tube donated by Dr. Cecil E. Vest, of Baltimore. Since the question of superfetation has been raised also in connection w4th twin tubal pregnancies, I hasten to add that such a phenomenon, even if it ever occurs (which seems exceedingly doubtful) can be excluded absolutely in this case. Both chorionic vesicles were approximately of the same size and lay in practically the same cross-section of the tube, the surfaces of contact being flattened.
  
Of the 36 cases remaining in this group of chorionic vesicles without amnion,
 
after deducting 8 (7 of which belong in group 1 and 1 in group 2), 50 per cent
 
showed the presence of undoubted hydatiform degeneration and in 1 additional
 
case its existence was doubtful.
 
  
 +
Before proceeding with the statistical findings, I may say that the abortuses in the Mall Collection regarded as pathological are grouped (1) as villi only; (2) as empty or partial chorionic vesicles; (3) as chorionic vesicles containing some or all of the amnion; (4) all specimens containing nodular, or (5) cylindrical embryos, or (6) stunted, and (7) macerated and mummified fetuses. Any one interested in this classification will find it discussed and exemplified in an article by Mall (1917).
  
Since only a few specimens are contained in each of the last five groups, I shall
 
treat them as one. Among 28 specimens remaining in these groups 12, or 43 per
 
cent, showed the presence of hydatiform degeneration and 4 others were doubtful.
 
From this percentage it is evident that the incidence of hydatiform degeneration
 
among tubal specimens seems to increase with advancing age of the conceptus
 
rather than decrease, as will be emphasized in connection with the uterine si)ecimens
 
to be considered later. This jirobably can be attributed to the fact that the speci-
 
mens in the first group are comjiosed of villi only, and that many of the emptj^
 
chorionic vesicles in group 2 were detached from the wall of the tube by hemorrhage
 
before hydatiform degeneration had developed sufficiently to enable me to recognize
 
it. Moreover, it must be remembered that all tubal specimens, no matter in what
 
group they are classified, are in fact young specimens, and since those falling in the
 
latter grou])s succeeded in maintaining a foothold in spite of re])eate(l hemorrhages,
 
a larger innnber of them might be expected rightly to show f h(> ])resence of a hydati-
 
form change.
 
  
The incidence of hydatiform degeneration in the 104 tubal pregnancies classed
+
There were 40 tubes containing villi only, and in 14 of these hydatiform degeneration probably was present. In 10 specimens its presence was undoubted, but in 4 it was probable only. I realize that this margin of probability is exceedingly largely, but this is easily understood if it is recalled that often only a few degenerate villi embedded in clot were contained in the cross-sections of many of the tubes, and that only a few sections were examined, not, of course, a complete series of each tube. Had the entire tubes been examined, or if more villi had been present, and if those present had been better preserved, the difficulty would have been almost wholly obviated. However, it is idle to set forth these things, because such conditions never will obtain, and the margin of probability becomes greatly reduced if it is remembered that in a large series the specimens necessarily supplement each other. Moreover, the changes in the villi often are so typical that they are unmistakable, even if only a few villi are present. Besides, examination in complete series undoubtedly would increase, not decrease the number found. In some of the doubtful cases the existence of hydatiform degeneration became probable only upon comparison with the many uterine specimens previously examined.
as pathologic is 44, or 42.3 per cent of the whole. This is a somewhat higher inci-  
 
dence than was obtained in the 348 uterine abortuses classed as jiathologic. and  
 
may be accounted for partly, or wholly even, by the greater incidence of young
 
specimens in th(> tubal series. That the tubal specimens undoubtedly were younger
 
follows from common knowledge regarding tubal pregnancies alone, but it also is
 
shown by the average menstrual ages, wliich were 43.4 days in 25 tubal, as compared with 66.6 days in 51 uterine specimens. Moreover, 32 of the 48 tubal specimens
 
of hydatiform defeneration, or 66.6 per cent, fall into the first two groups, thus
 
again showing that the majority' are small, young specimens.  
 
  
 +
[[File:Meyer1920_fig01.jpg|thumb|Fig. 1. Cross-section of twin hydatiform chorionic vesicles within the tube. (Specimen No. 825.)]]
 +
[[File:Meyer1920_fig02.jpg|thumb|Fig. 2. Hydatiform villi from same specimen in section.]]
  
Although the incidence of hydatiform degeneration among the pathologic
+
The evidence offered by the 36 tubal specimens in the second group, which is composed of empty chorionic vesicles or parts thereof, was very conclusive, for the cut portions of most of these tubes contained considerable portions or even sections of whole chorionic vesicles, sometimes quite free from clot. Some of them were implanted almost perfectly in the wall of the tube, and although many of them were folded extremely and collapsed more or less, small areas of several were nevertheless implanted undisturbed within the tube. The villi in some of these implanted specimens were so characteristic and the whole picture so exquisite, that the specimens rightly belong among the very finest instances of hydatiform degeneration found anywhere so far. This is true in particular of the case of twin pregnancy received from Dr. Vest. In this specimen the two chorionic vesicles, the intervillous spaces of which were devoid of blood, lay in almost the same transverse diameter of the tube and hence had distended the latter considerably. Both were implanted quite well over the entire area of contact, which included the whole perimeter of the tube. The chorionic vesicles were; flattened at the region of mutual contact, which divided the tube somewhat unequally as shown in figure 1. Although the embryo and the amnion long had disintegrated completely, and although the chorionic membrane itself is thin, covered by degenerate epithelium and also disintegrating, the epithelium of the villi  not only is well preserved but is accompanied by large masses of trophoblast and considerable syncytium. Syncytial buds are found on the chorionic membrane also. The tubal mucosa is larger and the tubal wall partly destroyed by the invading trophoblast. Only a few small vestiges of the walls of the villous vessels remain, and the stroma of all the villi has undergone changes characteristic of hydatiform degeneration represented in figure 2. One villus also contains an epithelial cyst resulting from epithelial invagination with subsequent isolation of the distal extremity, a process to be referred to later in connection with uterine specimens. Since most of the villi of this and similar specimens still are implanted in the tube, there can no longer be any question as to the time in which hydatiform changes in the stroma of the villi may be inaugurated. As illustrated in other instances in which isolated and small groups of villi still were implanted, the advent of degeneration of the stroma occurs, in part at least, before the villus is detached. Hence it is not merely a post-mortem or maceration change.
tubal specimens is but slightly higher than that among the pathologic uterine
 
specimens, the incidence of hydatiform degeneration in all tubal specimens con-
 
tained among both the normal and pathologic is twice as high as that among the  
 
same classes of uterine specimens. This can be explained only partlj' by the fact
 
that a larger proportion of the tubal specimens are young and pathologic. The  
 
pathologic tubal specimens form 69.2 per cent of 153 normal and pathologic tubal
 
specimens found among the first 1,187 accessions, but the pathologic uterine
 
specimens form only 33.6 per cent of the normal and pathologic uterine groujxs
 
among the same accessions. But the real question remains, for the incidence of  
 
hydatiform degeneration among the specimens classed as pathologic was essentially
 
the same in tube and uterus. Hence an increased incidence of 100 per cent in hj'dati-
 
form degeneration in the tubes may be due to the less favorable nidus found there.  
 
If so, it throws a very significant Ught upon the probable cause of hydatiform
 
degeneration, which would seem to he in the conditions surrounding the imjilanta-  
 
tion and early development rather than in the ova or spermatozoa themselves.  
 
  
 +
[[File:Meyer1920_fig03.jpg|thumb|Fig. 3. Embryo No. 1771, covered with magma.]]
 +
[[File:Meyer1920_fig04.jpg|thumb|Fig. 4.  Cross-section of tube No. 1771.]]
  
The conclusion reached in a study of uterine specimens that hydatiform
+
Another very interesting specimen of tubal implantation is No. 1771, received from Dr. H. M. N. Wynne, of the Johns Hopkins Hospital. The menstrual age of this specimen is 49 days, but its anatomic age, as based upon length according to Dr. Streeter's curve (unpublished), is 37 days, thus showing a discrepancy between the menstrual and anatomic ages of 12 days. The embryonic length is only 12.5 mm., although with a menstrual age of 49 days it should be at least 18 mm. Upon examination, Dr. Streeter found the chorionic vesicle to contain a good deal of magma, some of which still was adherent to the embryo, as figure 3 shows. As has been repeatedly emphasized in the hterature, the presence of this coagulum in itself probably indicates that the embryo died some time previously.
degeneration is absolutely less, not more frequent near the menopause, is confirmed
 
also by the study of the tubal specimens. The average age of 20 women in the
 
tubal series was 33.9 years, as opposed to an average of 31 years obtained from 36
 
women in the uterine grouj). This age difference offers a tempting opportunity
 
for generahzation, and did the statistics include thousands of cases one might be
 
willing to say that it points to a progressive change as cause, which begins in the  
 
uterus and finall)' reaches the tubes. But strangeh' enough, the average number of
 
years of married life of 15 women in the tubal series is exactlj^ the same as that of
 
29 women in the uterine series, or 7.1 years. This fact at once guards against a
 
venturesome hypothesis, for it allows no longer period for the supposed ascending
 
change to reach the tubes than the uterus.  
 
  
 +
[[File:Meyer1920_fig05.jpg|thumb|Fig. 5. Cross-section of tube from same case.]]
 +
[[File:Meyer1920_fig06.jpg|thumb|Fig. 6. Hydatiform villi from same case.]]
 +
The wall of the tube is quite thin, as figure 4 shows, but the implantation is fairly well preserved around the whole perimeter of the specimen. The mucosa is destroyed throughout the greater extent of the section and the trophoblast is abundant, except in one rather degenerate and hemorrhagic area. The chorionic membrane is thin but contains some vessels distended with blood. The stroma of many of the villi also contains vessels filled with blood, but the vessels in many others are very evidently in degeneration. The syncytium is scanty and many of the villi are very plainly hydatiform, as seen in figures 5 and 6.
  
Eight of 20 women from the tubal series had borne one child, 4 had borne two,  
+
[[File:Meyer1920_fig07.jpg|thumb|Fig. 7. Hydatiform chorionic vesicle in loco with the tube incised. No. 2052.]]
and 3 more than two; thus again more than confirming the statistical findings in
+
A third exceptionally fine specimen of tubal hydatiform mole is No. 2052, donated by Dr. N. M. Davis, of Washington, D. C. Figure 7 shows a portion of the tube containing the hydatiform mole, some hydatiform villi of which protrude through an incision in the wall of the tube. The whole opening is filled with typical hydatiform villi barely detected by the unaided eye but perfectly evident under an enlargement of 4 diameters. They present an extremely fine picture when seen with the binocular under a magnification of 10 to 20 diameters. Examination under a higher magnification shows that the preservation of the specimen is unusually good and that all the villi are markedly hydatiform. Trophoblastic proUferation is so marked that in some places it gives the appearance of decidual formation.
the uterine series, which show that 9 of 33 women had borne once and 18 but twice.  
 
The parallelism between these statistics is striking indeed, especially if the small
 
numbers be considered; 14 of 23 women, or 60.8 per cent, in the tubal series had
 
aborted but once, as compared to 19 out of 44, or 46.3 per cent in the uterine series,
 
a fact which again points to the middle rather than to the end of tlie reproductive
 
life of these women.  
 
  
  
I do not know whether or not hydatiform degeneration in the tube also is  
+
Relatively little syncytium is present, but the trophoblast invades the muscularis in many places and a good deal of coagulum is present, most of it apparently having arisen from degeneration changes in the stroma of the mucosa and from similar changes in the trophoblast and the muscularis. The latter is moderately invaded by round cells. No remnant of the wall of the chorionic vesicle or of the amnion or embryo could be detected in the sections examined, both evidently having been absorbed completely, only some of the villi remaining behind; or, the chorionic vesicle may have been aborted and these villi left implanted within the tube.
relatively more common near the menopause, as will be shown to be the case in the
 
uterus, for I have not been able to obtain data on the relative frequency of tubal
 
pregnancy in the different decades in the reproductive life of women. However,
 
smce by far the greater number of pregnancies usually occur early in this period, it probably would be safe to assume that most of the tubal pre}i;iia?icies occur also at
 
this time. Consequently, it might well follow that the ratio of tubal hydatiform
 
degeneration to the number of pregnancies occurring in the later actually might be
 
greater than that in the earlier decades.  
 
  
The structural changes in hydatiform degeneration will be considered more
 
fully in connection with the uterine cases. Suffice it to say that since I directed my
 
attention especially to hydatiform degeneration I have been able to recognize its
 
presence repeatedly at sight in relatively young vesicles (1 cm. large) not only from
 
uterine but also from tubal pregnancies. This is, of course, esi)ecially true in the
 
former, for the chorionic vesicles of these often are {}uite characteristic, and if
 
insjx'ction with the unaided eye or with a reading glass under a magnification of 2
 
diameters fails to reveal the true nature of the specimen, examination with a binocu-
 
lar under a magnification of 10 or 20 diameters often makes immediate identifica-
 
tion possible.
 
  
==UTERINE==
+
Some exceedingly fine hydatiform villous trees wore found among the specimens in this group. Scaffoldings or frameworks formed by proliferating syncytium arising from the epithelium of the chorionic membrane also were seen. Since the syncytial buds were found far out on proliferations of trophoblast which capped the viUi, and also in the center of trophoblastic nodules, the origin of the syncytium from the Langhans layer would seem to be again and exceptionally well confirmed. In some cases a detached hydatiform villus was fastened by opposite extremities to two portions of the tube wall. It is well to remember, however, that one of these attachments probably was gained before the separation of the particular villus from the chorionic vesicle.
  
To read the titles of articles on '"molar" pregnancies which have appeared
 
during the last few decades, even, is a rather wearisome task. By far the great
 
majority of the articles concern themselves merely with the report of "a case"
 
or (rarely) of "several cases" of hydatiform moles. The recent cancer hterature
 
stands in marked contrast to this, for not even the general practitioner would think
 
of reporting a routine case of cancer of the breast, let us say. The significance of
 
these facts is self-evident, and whatever else they may mean the\' do imply that
 
hydatiform mole still is regarded as a rare condition. Indeed, many of those
 
rei^orting "a case" frankly say so, and although the incidence of hydatiform degen-
 
eration is estimated variously by different authors and investigators, there seems
 
to be entire agreement that it is a rare, even if not an extremely rare condition.
 
Tliis opinion seems to be shared even by those general practitioners whose long
 
practice runs high up into the hundreds or even into the thousands of obstetrical
 
cases. Indeed, many general practitioners declare that they have not seen a single
 
case of hydatiform mole diunng the practice of a long life.
 
  
This j)revaihng opinion can not be attributed solely to the influence of the
+
Of the 36 cases remaining in this group of chorionic vesicles without amnion, after deducting 8 (7 of which belong in group 1 and 1 in group 2), 50 per cent showed the presence of undoubted hydatiform degeneration and in 1 additional case its existence was doubtful.
schools or to books, but is based upon the actual experience of the individual
 
practitioner and upon his conception of what constitutes hydaliform degeneration.
 
This is illustrated, for exam])le, by Menu, who said that a small hydatiform mole
 
weiglis 300 grams, a large one 8,000, with an average weight in his series of cases of
 
1,700 grams. But even specialists in charge of hospitals have reported experiences
 
similar to that of the general practitioner. Pazzi (1909), for example, stated that
 
although he had observed more than 6,000 cases of labor in liis private and hospital
 
I^ractice, he never met with a case of hydatiform mole. Moreover, it would seem
 
that only some specialists have come to regard the condition as somewhat l(>ss rare
 
than was hcretofon; supi)o.sed. This is well expressed by Williams (1917), who
 
wrote: "Hydatiform mole is a rare disease, occurring, according to Madam Hoivin,
 
once in 20,000 cases. On the other hand, the statistics of Williamson would indicate
 
that it may be found but once in 2,400 cases." Williams adds, however, that in his
 
own experience it occurred even more frequently than stated bj' Williamson; and
 
Essen-Moller (1912), on the basis of 6,000 cases treated between 1899-1908, gives
 
the incidence at the Frauen-Klinik at Lund as 3 per 1,000. My former colleague,
 
De Lee (1915), in commenting on hydatiform degeneration, also stated that he has
 
"frequently found in aborted ova one or more vilU degenerate and forming vesi-
 
cles"; and similar remarks were made also by others, notablj^ by Miiller (1847),
 
Marchand (1895), Veit (1899), van der Hoeven (1900), Hiess (and according to him
 
also by von Hecker), Langhans, Weber, and Frankel. Findlaj' (1917) also regards
 
"it as fair to conclude with Veit, Freund, and Dunger that abortive types of hj'dati-
 
form mole are commonly overlooked," and although he gave no evidence for his
 
opinion Weber (1892) insisted that hydatiform mole "occurs much oftener than we
 
are led to believe from books or other Uterature." Essen-IMoller saj's Konig gave
 
an incidence of 1 j^er 728 cases. Pazzi (1908^) stated that Dubisa}' and Jennin
 
found in 1903 that hydatiform degeneration occurs once in 2,000 pregnancies, and  
 
that Cortiguera in 1906 declared that the frequency' of hydatiform mole has a dis-
 
couraging variation of from 1 in 3,000 to 1 in 700 labors, but that in his personal
 
experience Cortiguera saw one case in every 300 labors. The latter incidence is
 
only shghtl}' higher than that given by Essen-Moller for the clinic at Lund, and
 
somewhat below that of Kroemer (1907), who found 15 hydatiform moles in 3,856
 
births, or one in every 257 cases. Maj^er (1911) reported 10 instances among 3,105
 
cases of labor, an incidence of 1 in 310 cases, and it is only necessary to add that
 
Donskoj (1911) stated that the incidence of hydatiform mole in 28,406 cases at the
 
Frauenkhnik at Miinchen, between the years 1884 and 1910, was onlj^ 1 for every
 
4,058 Jjirths, to emphasize the discouraging variation of which Cortiguera spoke.
 
Donskoj also stated that Engel gave the incidence as 1 in 800, and Korn as 1 in
 
1,250 births. Such a surprising fluctuation in the apparent incidence in adjacent
 
communities points to differences in conception of what constitutes a hydatiform
 
mole, and also to differences in character of the material upon which the calculations
 
are based.  
 
  
The existence of hj^datiform degeneration in far greater frequency than com-
 
monly supposed is indicated also by the records of the Department of Embrj-ologj^
 
of the Carnegie Institution of Washington. However, the material covered by
 
these records is not identical with that upon which the above opinions, or those of
 
other obstetricians are based. The opinion of the obstetrician is based upon
 
material belonging very largel}^ in the later months of pregnancy, while that in the
 
Mall Collection, on the other hand, belongs very largely in the earUer months.
 
Hence this material is not truly representative of the entire period of gestation, but
 
the same thing is true of the material upon which the general practitioner, the
 
obstetrician, and the gynecologists have based their opinions, for these are based
 
largely upon material from the last months of pregnancy. Hence mainly the cases
 
of hydatiform degeneration which survive come to their attention.
 
  
But unless we can assume that the incidence of hydatiform degeneration is
+
Since only a few specimens are contained in each of the last five groups, I shall treat them as one. Among 28 specimens remaining in these groups 12, or 43 per cent, showed the presence of hydatiform degeneration and 4 others were doubtful. From this percentage it is evident that the incidence of hydatiform degeneration among tubal specimens seems to increase with advancing age of the conceptus rather than decrease, as will be emphasized in connection with the uterine specimens to be considered later. This probably can be attributed to the fact that the specimens in the first group are composed of villi only, and that many of the empty chorionic vesicles in group 2 were detached from the wall of the tube by hemorrhage before hydatiform degeneration had developed sufficiently to enable me to recognize it. Moreover, it must be remembered that all tubal specimens, no matter in what group they are classified, are in fact young specimens, and since those falling in the latter grou])s succeeded in maintaining a foothold in spite of repeated hemorrhages, a larger number of them might be expected rightly to show the presence of a hydatiform change.
constant during the whole period of gestation, its incidence at any particular time
 
  
of this period may very incorrectly express that at any other time. This could fail
 
to be true only if the incidence of death of the conceptuses and their susceptibility
 
to hydatiform degeneration were exactly uniform throughout every period of
 
intrauterine life. But we know that neither is true, for it is common knowledge that
 
by far the great majority of the cases of uterine hydatiform degeneration, recorded
 
in the literature, are mature specimens of total or partial degeneration obtained
 
in the later months of pregnancy. Although such specimens may contjiin villi in
 
various stages of degeneration, they nevertheless represent end or near-end results.
 
Like the fetuses which rarely accompany them, they are full-term or near-term
 
products when regarded as hydatiform degenerations, and unless we are to assume
 
that conceptuses once affected by hydatiform degeneration always survive up to
 
this period, statistical deductions based ui)on the cases that do sur\'ive can give us
 
httle idea of the actual freciuency of the condition throughout the entire period
 
of antenatal life.
 
  
 +
The incidence of hydatiform degeneration in the 104 tubal pregnancies classed as pathologic is 44, or 42.3 per cent of the whole. This is a somewhat higher incidence than was obtained in the 348 uterine abortuses classed as pathologic. and may be accounted for partly, or wholly even, by the greater incidence of young specimens in the tubal series. That the tubal specimens undoubtedly were younger follows from common knowledge regarding tubal pregnancies alone, but it also is shown by the average menstrual ages, which were 43.4 days in 25 tubal, as compared with 66.6 days in 51 uterine specimens. Moreover, 32 of the 48 tubal specimens of hydatiform defeneration, or 66.6 per cent, fall into the first two groups, thus again showing that the majority' are small, young specimens.
  
That the specimens upon which past and also present opinion is based usually
 
were large, is confirmed by the belief in the prevailing clinical criterion of the
 
existence of a disproportionately large uterus in cases of hydatiform mole. The
 
emjihasis laid on this by clinicians is well illustrated by Seitz, who says that cases
 
in which the uterus is too small are the exception. Indeed, it seems that the validity
 
of this cUnical dictum has been questioned only very recently by Briggs (1912).
 
Since most early conceptuses showing hydatiform degeneration have been inhibited
 
in growth before being aborted, it probably is only the specimens which persist
 
that produce a uterine enlargement greater than could normally be expected.
 
However, since — as emphasized by Gierse (1847), Storch, Hicss, and others — most
 
hj'datiform moles are expelled early and spontaneously, it is evident that these can
 
not have been adherent — that is, have penetrated very deej^ly — or they would
 
not have been expelled early and spontaneously. Furthermore, maceration changes
 
so commonly present in aborted hydatiform moles indicate very clearly that a large
 
percentage of them, together with the decidua, had been more or less completely
 
detached from the uterine wall some time before abortion occurred.
 
  
 +
Although the incidence of hydatiform degeneration among the pathologic tubal specimens is but slightly higher than that among the pathologic uterine specimens, the incidence of hydatiform degeneration in all tubal specimens contained among both the normal and pathologic is twice as high as that among the same classes of uterine specimens. This can be explained only partlj' by the fact that a larger proportion of the tubal specimens are young and pathologic. The pathologic tubal specimens form 69.2 per cent of 153 normal and pathologic tubal specimens found among the first 1,187 accessions, but the pathologic uterine specimens form only 33.6 per cent of the normal and pathologic uterine groups among the same accessions. But the real question remains, for the incidence of hydatiform degeneration among the specimens classed as pathologic was essentially the same in tube and uterus. Hence an increased incidence of 100 per cent in hydatiform degeneration in the tubes may be due to the less favorable nidus found there. If so, it throws a very significant light upon the probable cause of hydatiform degeneration, which would seem to he in the conditions surrounding the implantation and early development rather than in the ova or spermatozoa themselves.
  
As far as one can gather from the literature, iiic present opinion regarding the
 
incidence of hydatiform degeneration would be i)arall(>ll(>d (luite correctly if, in the
 
case of measles, we assumed that it was as common in octogenarians as in children.
 
Measles, indeed, is an extremely rare disease in advanced age, but it nevertheless
 
is very common in infancy. This is exactly the mistake we have made regarding
 
hydatiform degeneration. It may be and undoubtedly is a rare disease at or near
 
term, as Clierse also stated, but it j^robably is the commonest of all diseases during
 
the earliest months of gestation. The typical large hydatiform mole is an end
 
result which it has taken long months to develop. No one seems to hav(» followed
 
its evolution, although hydatiform degeneration, whether total or jiartial, is, of
 
course, gradual in its advent.
 
  
 +
The conclusion reached in a study of uterine specimens that hydatiform degeneration is absolutely less, not more frequent near the menopause, is confirmed also by the study of the tubal specimens. The average age of 20 women in the tubal series was 33.9 years, as opposed to an average of 31 years obtained from 36 women in the uterine group. This age difference offers a tempting opportunity for generalization, and did the statistics include thousands of cases one might be willing to say that it points to a progressive change as cause, which begins in the uterus and finally reaches the tubes. But strangely enough, the average number of years of married life of 15 women in the tubal series is exactly the same as that of 29 women in the uterine series, or 7.1 years. This fact at once guards against a venturesome hypothesis, for it allows no longer period for the supposed ascending change to reach the tubes than the uterus.
  
The records of the Mall Collection contained 8 cases of hxdatiforni mole in
 
the first 2,400 accessions, showing a fretiuency 8 tim(\s as great as that gi\en by
 
WilUamson, or an excess of 700 per cent. Since the lirst 2,400 accessions contain 309 ctises of tubal and also 2 of ovarian pregnancy, only 2,089 uterine specimens
 
remain. Hence the recorded incidence in the uterine specimens really is 8 in 2,089,
 
or 1 in every 261 cases. This incidence is only slightly lower than that of Kroemer,
 
and somewhat higher per 1,000 than that given by Essen-Moller for the Frauen-
 
khnik at Lund, or the personal experience of Cortiguera.
 
  
 +
Eight of 20 women from the tubal series had borne one child, 4 had borne two, and 3 more than two; thus again more than confirming the statistical findings in the uterine series, which show that 9 of 33 women had borne once and 18 but twice. The parallelism between these statistics is striking indeed, especially if the small numbers be considered; 14 of 23 women, or 60.8 per cent, in the tubal series had aborted but once, as compared to 19 out of 44, or 46.3 per cent in the uterine series, a fact which again points to the middle rather than to the end of tlie reproductive life of these women.
  
The highest incidence of hydatiform degeneration previously reported is that
 
of .Storch, who estimated it as 50 per cent, but he unfortunately did not give a
 
record of his cases. However, Storch emphasized that the typical complete hydati-
 
form mole is a relatively rare form of the disease, and that all manner of transition
 
forms between the normal chorionic vesicle and the completely degenerated one can
 
be shown to exist. Storch further emphasized the commonness of hj^datiform
 
degeneration, especially in the early months of pregnancy, but as Veit (1899) well
 
said, Storch somehow has not received sufficient credit for his investigations.
 
Gierse was forgotten completelj'. This seems strange, especially in view of the fact
 
that Storch's work was done in Copenhagen, where Panum (1860) had done and
 
still was doing such fine and very suggestive, indeed epochal, work on the origin of
 
monsters. Although Storch devoted part of his paper to mj^oma fibrosum, and
 
reported only 5 cases of hydatiform mole, one of which, however, accompanied a
 
living fetus, his opinions on the whole were far ahead of his time. In order to make
 
this clear I shall quote a very significant passage, wliich indeed needs but slight
 
changes to serve as a conclusion for mj' own investigations:
 
  
 +
I do not know whether or not hydatiform degeneration in the tube also is relatively more common near the menopause, as will be shown to be the case in the uterus, for I have not been able to obtain data on the relative frequency of tubal pregnancy in the different decades in the reproductive life of women. However, since by far the greater number of pregnancies usually occur early in this period, it probably would be safe to assume that most of the tubal pregnancies occur also at this time. Consequently, it might well follow that the ratio of tubal hydatiform degeneration to the number of pregnancies occurring in the later actually might be greater than that in the earlier decades.
  
"Nun sind aber bekanntlich Eier mit blasiger Degeneration der Zotten und fehlerhaft
 
oder nicht entwickeltem Fotus ein sehr hiiufiger Befund bei Aborten aus den ersten Schwan-
 
gerschaftsmonaten. Mehrere solche Eier sind schon in den bekannten Arbeiten von Dohrn
 
und Hegar beschrieben worden. Ich habe im Laufe des letzten .Jahres eine grossere .\nzahl
 
von Aborten untersucht und derartige kranke Eier in mehr als der Halfte der Fiille gefunden.
 
Nicht selten ist die Amnionblase vollig leer und enthalt nur eine klare serose Fliissigkeit.
 
In anderen Fallen sitzt an der einen oder anderen Stelle der Innenfljiche des Amnion ein
 
kleiner rundlicher oder unregelmassig geformter, 5-I Mm. grosser Korper, welcher aus Nichts
 
als aus runden, schwach conturirten, zum Theil fettigentarteten Zellen und einer hellen, fast
 
homogenen Zwischensubstanz besteht, und der durch einen feinen, 1-3 Mm. langen Strang
 
von ahnlicher Natur mit dem Amnion verbunden ist. In noch anderen Eiern ist der Embryo
 
zwar etwas weiter entwickelt, aber von den verschiedensten Formen von Alissbildungen
 
befallen. Seltener ist der Embryo einigermaassen wohl gebildet und von bis zu 2 Cm. Lange,
 
wie dies auch Hohl nur einmal gefunden hat. Sehr gewohnlich ist fettige oder lipoide
 
Entartung des Embrj'o vorhanden; derselbe ist dann eine kiirzere oder langere Zeit vor
 
der Geburt abgestorben. Als die aussersten Glieder dieser Reihe von kranken Eiern
 
stehen endlich die sehr seltenen Falle, in welchen der Embryo seine Entwickelung ziemlich
 
ungestort fortgesetzt zu haben scheint, und von denen die Fiille von Martin und der oben
 
beschriebene dreimonatliche abort Beispiele sind.
 
  
"Die blasige Entartung der Chorionzotten kann demnach neben den verschiedensten
+
The structural changes in hydatiform degeneration will be considered more fully in connection with the uterine cases. Suffice it to say that since I directed my attention especially to hydatiform degeneration I have been able to recognize its presence repeatedly at sight in relatively young vesicles (1 cm. large) not only from uterine but also from tubal pregnancies. This is, of course, especially true in the former, for the chorionic vesicles of these often are {}uite characteristic, and if inspection with the unaided eye or with a reading glass under a magnification of 2 diameters fails to reveal the true nature of the specimen, examination with a binocular under a magnification of 10 or 20 diameters often makes immediate identification possible.
Zustanden des Embryo fegunden werden. Sehr hiiufig ist letzterer der Sitz von mehr oder
 
weniger eingreifenden Krankheitsprozessen gewesen, die in demselben verschiedene Aliss-
 
bildungen hervorgerufen und ihn in seiner Entwickelung gehemmt haben. Es sind diese
 
Krankheistprozesse wahrscheinlich immer sehr friih im Ei entstanden, und miissen mit
 
Panum zuniichst als entziindliche A'organge aufgefasst werden, welche nach ihrer Intensitat
 
und vielleicht nach dem Zeitpunkte, zu welchem sie im Keime auftreten, bald eine theil-
 
  
 +
==Uterine==
  
weiso N'crocliinp der KeinuinlaKPn dcr mcisten wiclitiKorcii Or^ano mit N'crkruppcUing
+
To read the titles of articles on '"molar" pregnancies which have appeared during the last few decades, even, is a rather wearisome task. By far the great majority of the articles concern themselves merely with the report of "a case" or (rarely) of "several cases" of hydatiform moles. The recent cancer hterature stands in marked contrast to this, for not even the general practitioner would think of reporting a routine case of cancer of the breast, let us say. The significance of these facts is self-evident, and whatever else they may mean they do imply that hydatiform mole still is regarded as a rare condition. Indeed, many of those reporting "a case" frankly say so, and although the incidence of hydatiform degeneration is estimated variously by different authors and investigators, there seems to be entire agreement that it is a rare, even if not an extremely rare condition. Tliis opinion seems to be shared even by those general practitioners whose long practice runs high up into the hundreds or even into the thousands of obstetrical cases. Indeed, many general practitioners declare that they have not seen a single case of hydatiform mole diunng the practice of a long life.  
des ganzcn embryonalon K()ri)ers, bald niehr locale I\lissl)il(hingeii oiiizi'lncr Korjier-
 
thcile horvorrufcn koiinen. Das Erstere ist in den hicr hosprochenen Aburteii sehr
 
hiiufig der Fall: der Embrj'o ist zu eineni unfDriiilichen Kluniiien umgewandelt, dein die
 
nieisten Organe deren Keiine dvirch Entziiiuhing zerstc'irt worden sind, giinzlich fehlen.  
 
^'oIl diescn verkriippelteii Aniorphi linden sieh in anderen Eiern alle Uebcrgiingsfornien zu
 
niehr oder weniger entwiekelten Missbildungen was auch Paniini an einigen Beispielen
 
nachgewiescn hat. Es Scheinen in der That die nicht zerstorten Keinizellen der verschiedenen
 
Organe, nach dem ablaiife des Krankheitsprozcsscs, ihren ursi)runglichen Entwickelungs-
 
j)lan mit einer oft merkwiirdigen Hartniickigkeit, so gut sie es kcinnen, festzuhalten. Von
 
dieseni \'erhaltnisse liefern die bekannten herzlosen Amorphi, die durch einen Zwillings-
 
bruder einhiirt werden und dadurch zu einer oft bedeutenden Cirosse heranwachsen konnen,
 
ein schlagendes Beispiel. In unseren Aborten sind zwar diese Amorphi, die keinen Zwillings-
 
bruder zur Erhaltung ihres Krcislaufes geliabt haben, fruhzeitig zu (Jrunde gegangen, und
 
ihre Clewebsteile sind einer fettigen (lipoiden) Entartung anheimgefallen ; sie haben jedoch
 
ihre Entwickehmg eine Zeit lang fortgesetzt.  
 
  
  
"Est is von den verschiedenen Verfassern vielfach von einer Auflosung der Embryonen
+
This prevailing opinion can not be attributed solely to the influence of the schools or to books, but is based upon the actual experience of the individual practitioner and upon his conception of what constitutes hydaliform degeneration. This is illustrated, for example, by Menu, who said that a small hydatiform mole weiglis 300 grams, a large one 8,000, with an average weight in his series of cases of 1,700 grams. But even specialists in charge of hospitals have reported experiences similar to that of the general practitioner. Pazzi (1909), for example, stated that although he had observed more than 6,000 cases of labor in liis private and hospital practice, he never met with a case of hydatiform mole. Moreover, it would seem that only some specialists have come to regard the condition as somewhat less rare than was hcretofon; supposed. This is well expressed by Williams (1917), who wrote: "Hydatiform mole is a rare disease, occurring, according to Madam Hoivin, once in 20,000 cases. On the other hand, the statistics of Williamson would indicate that it may be found but once in 2,400 cases." Williams adds, however, that in his own experience it occurred even more frequently than stated by Williamson; and Essen-Moller (1912), on the basis of 6,000 cases treated between 1899-1908, gives the incidence at the Frauen-Klinik at Lund as 3 per 1,000. My former colleague, De Lee (1915), in commenting on hydatiform degeneration, also stated that he has "frequently found in aborted ova one or more vilU degenerate and forming vesicles"; and similar remarks were made also by others, notablj^ by Miiller (1847), Marchand (1895), Veit (1899), van der Hoeven (1900), Hiess (and according to him also by von Hecker), Langhans, Weber, and Frankel. Findlaj' (1917) also regards "it as fair to conclude with Veit, Freund, and Dunger that abortive types of hydati- form mole are commonly overlooked," and although he gave no evidence for his opinion Weber (1892) insisted that hydatiform mole "occurs much oftener than we are led to believe from books or other literature." Essen-IMoller say's Konig gave an incidence of 1 j^er 728 cases. Pazzi (1908) stated that Dubisa}' and Jennin found in 1903 that hydatiform degeneration occurs once in 2,000 pregnancies, and that Cortiguera in 1906 declared that the frequency' of hydatiform mole has a discouraging variation of from 1 in 3,000 to 1 in 700 labors, but that in his personal experience Cortiguera saw one case in every 300 labors. The latter incidence is only slightly higher than that given by Essen-Moller for the clinic at Lund, and somewhat below that of Kroemer (1907), who found 15 hydatiform moles in 3,856 births, or one in every 257 cases. Mayer (1911) reported 10 instances among 3,105 cases of labor, an incidence of 1 in 310 cases, and it is only necessary to add that Donskoj (1911) stated that the incidence of hydatiform mole in 28,406 cases at the Frauenkhnik at Miinchen, between the years 1884 and 1910, was only 1 for every 4,058 births, to emphasize the discouraging variation of which Cortiguera spoke. Donskoj also stated that Engel gave the incidence as 1 in 800, and Korn as 1 in 1,250 births. Such a surprising fluctuation in the apparent incidence in adjacent communities points to differences in conception of what constitutes a hydatiform mole, and also to differences in character of the material upon which the calculations are based.  
in der Amnionfliissigkeit und von einer nachherigen Resorption derselben gesprochen
 
worden. Ich glaube indessen, dass die.sen Vorgiingen eine sehr geringe RoUe beizulegen ist.  
 
Man findet in der Tlmt gewohnlich Nichts, was auf eine solche Resorption deuten konne.  
 
Es scheinen vielniehr die abgestorbenen Embryonen auch lange nach ihrem Tode eine
 
v;rosse Wiederstandfiihigkeit gegen die Einwirkung, von .\mnionflussigkcit beizubehalten.  
 
Ich halie mehrmals ganz kleine, verkriippelte Embryonen zwar fetig entartet, in ihrer Form
 
aber v(")llig wt)hl erhalten, in Eiern gefunden, die bis zu 10 Monaten im Uterus zuriickge-  
 
hiilten worden sind. Zudem ist die Amnionfliissigkeit in diesen Eiern meist ganz klar, oder
 
sie enthalt nur losgestossene, hinfiillige Amnionejiithelzellen suspendii't. Wenn daher
 
die Eier ganz leer gefunden werden, so riihrt dies gewiss am Hiiufigsten tlaher, dass der
 
Primitivestreifen seiner Zeit vollig destruirt worden und somit gar kein Embryo zur Ent-
 
wickehmg gewommcn ist. * * * Im AUgemeinenerreichensiekienebedeutende (iriisse
 
und werden zudem oft fruhzeitig aus dem Uterus ausgestossen, in dem sie, wie oben
 
bcsprochen, ein sehr betriichtliches Contingent zu den Aborten iiberliaupt liefern. * * *
 
  
" Die Traubenmole und die verschiedenen Ucbergengsformen derselben, die an Aborten
 
sehr haufig vorgefunden werden, ist als Hyperplasie und secundiire cystoide Entartung des
 
(von AUantois nicht herstanuumenden) C'horionI)indegewebs vorzugsweise charactertisirt.
 
Die Krank^'eit wird von pathologischen Zustiuiden der i'lbrigen Eitheilc, Amnion und
 
Embryo (Missbildungen, ^'erkriipl)elungen und friihzeitigem .\bsterben des letzteren) sehr
 
haufig begleitet. Seltener ist der Embryo regelamasmig entwickelt, stirbt al)er meist auch
 
dann wegen mangelhafter Vascularisation der (Chorion) Placenta fruhzeitig ab. Sehr
 
selten scheint der P^mbryo ungestort bis zur Geburt sich fort entwickelt zu haben."
 
  
But the unregarded observations and illustrations of (Jierse arc still more
+
The existence of hydatiform degeneration in far greater frequency than commonly supposed is indicated also by the records of the Department of Embryology of the Carnegie Institution of Washington. However, the material covered by these records is not identical with that upon which the above opinions, or those of other obstetricians are based. The opinion of the obstetrician is based upon material belonging very largely in the later months of pregnancy, while that in the Mall Collection, on the other hand, belongs very largely in the earUer months. Hence this material is not truly representative of the entire period of gestation, but the same thing is true of the material upon which the general practitioner, the obstetrician, and the gynecologists have based their opinions, for these are based largely upon material from the last months of pregnancy. Hence mainly the cases of hydatiform degeneration which survive come to their attention.  
startling than these oi)inif)ns and observations by Storch, who knew of CJierse's
 
oliservations jiublished ])ostlunnously by Meckel. The latter {juite correctly stated
 
that such careful observations as those made by Clierse always introduce new i)oints
 
of view. If it be remembered that in these days, almost a century later, specimens
 
of hydatiform degeneration which are 4 cm. in diameter still are reported separately
 
as examples of early hydatiform degeneration, the great merit of Gierse's observa-
 
tions in this regard alone will l)e clearly evident, upon recalling that Giersc pictured
 
a hydatiform villus from a chorionic vesicle tlie size of a hazelnut (about 12 mm.),
 
the largest hydatiils on which were only one-tliird of a line large. Moreover, Gierse
 
added :
 
  
  
"Dcrlcichen geiinge krankhafte Veranderungen finden sich an au.serordentlichen vielcn
+
But unless we can assume that the incidence of hydatiform degeneration is constant during the whole period of gestation, its incidence at any particular time of this period may very incorrectly express that at any other time. This could fail to be true only if the incidence of death of the conceptuses and their susceptibility to hydatiform degeneration were exactly uniform throughout every period of intrauterine life. But we know that neither is true, for it is common knowledge that by far the great majority of the cases of uterine hydatiform degeneration, recorded in the literature, are mature specimens of total or partial degeneration obtained in the later months of pregnancy. Although such specimens may contjiin villi in various stages of degeneration, they nevertheless represent end or near-end results. Like the fetuses which rarely accompany them, they are full-term or near-term products when regarded as hydatiform degenerations, and unless we are to assume that conceptuses once affected by hydatiform degeneration always survive up to this period, statistical deductions based upon the cases that do survive can give us httle idea of the actual freciuency of the condition throughout the entire period of antenatal life.  
Abortus, und sie scheinen die hiiufigste Ursache des Abortus in den ersten Monaten zu
 
sein."
 
  
How such an epoch-making conclusion not only could be forgotten, but abso-
 
lutely overlooked or disregarded, by all but a few of the scores upon scores who have
 
written on hydatiform degeneration, it is thfficult indeed to understand. Gierse,
 
who took steps to ascertain what normal villi look like, stated that \-illi with mark(>d
 
irregularities as described by Desormaux, Breschet, Raspail, and Seller undoubtedly
 
were abnormal; surmised that vilh in abortuses seldom are normal, and added that
 
between the slight pathologic changes in the caUber of the vilh and the most evident
 
hydatiform moles the plainest transition can be found. Among other important
 
things Gierse also recognized the early fenestration of the stroma and pictured such
 
a villus under a magnification of 250 diameters, and although reported very briefly',
 
liis findings, wholly confirmed here, still wait for general recognition.
 
  
Just as the great majority of specimens described in the Uterature are large,  
+
That the specimens upon which past and also present opinion is based usually were large, is confirmed by the belief in the prevailing clinical criterion of the existence of a disproportionately large uterus in cases of hydatiform mole. The emjihasis laid on this by clinicians is well illustrated by Seitz, who says that cases in which the uterus is too small are the exception. Indeed, it seems that the validity of this cUnical dictum has been questioned only very recently by Briggs (1912). Since most early conceptuses showing hydatiform degeneration have been inhibited in growth before being aborted, it probably is only the specimens which persist that produce a uterine enlargement greater than could normally be expected. However, since — as emphasized by Gierse (1847), Storch, Hicss, and others — most hydatiform moles are expelled early and spontaneously, it is evident that these can not have been adherent — that is, have penetrated very deeply — or they would not have been expelled early and spontaneously. Furthermore, maceration changes so commonly present in aborted hydatiform moles indicate very clearly that a large percentage of them, together with the decidua, had been more or less completely detached from the uterine wall some time before abortion occurred.
so 4 of the 8 specimens originally classed as such in the Mall Collection also are  
 
large, and none of the 8 are very young, as the following protocols show:
 
  
No. 70 (Dr. Charles H. EUis) is a small, fimi, degenerate-looking, almost solid mass
 
40X30X28 mm., composed of small cysts, degenerate decidua, exudate and degeneration
 
products. As figure 8 shows, it is verj^ similar to a very much larger specimen. No. 323
 
(Dr. V. Van Williams). The latter is a large, firm, felt-fike mass 120X90X65 mm.,
 
represented in figure 9. The individual cysts, which vary from 1 to 20 mm., are packed
 
together rather firmly, though a few large ones are free. The exterior of the specimen is
 
formed by a thick layer of degenerate decidua and gives only a slight indication of its true
 
nature upon closer inspection or upon examination of the cut surface. No fetal remnants
 
were noticed, and microscopic examination shows tliat the specimen is composed merely of
 
a large hydatiform mass which was retained for a long tune and then aborted in toto with
 
the surrounding decidua and exudate.
 
  
No. 749 (Dr. G. G. McCormick), on the contrarj-, is a fresh, loose, typical hydatiform
+
As far as one can gather from the literature, iiic present opinion regarding the incidence of hydatiform degeneration would be parallelled quite correctly if, in the case of measles, we assumed that it was as common in octogenarians as in children. Measles, indeed, is an extremely rare disease in advanced age, but it nevertheless is very common in infancy. This is exactly the mistake we have made regarding hydatiform degeneration. It may be and undoubtedly is a rare disease at or near term, as Clierse also stated, but it probably is the commonest of all diseases during the earliest months of gestation. The typical large hydatiform mole is an end result which it has taken long months to develop. No one seems to have followed its evolution, although hydatiform degeneration, whether total or jiartial, is, of course, gradual in its advent.  
mass composed of loase hydatids of ^'a^ious sizes, as shown in figure 10. As the specimen
 
floats loosely in fluid, it fills a half-liter jar about two-thirds. A considerable portion of the  
 
hydatid cysts are glued into a solid mass by blood, exudate, and decidua, which form a
 
layer on the exterior.  
 
  
No. 1323 (Dr. J. W. SchUeder) also is a large mass very like the preceding, which
 
completely fills a liter jar. It is accompanied by much clot and composed mainly of a
 
large, thick-walled, hemorrhagic, necrotic mass 80X50X45 mm., containing a large,
 
thin- walled cavity 65X30X25 mm., which is broken at one end. This ca\'itj% which is
 
apparently that of the chorionic vesicle, is empty, smooth, and thin-walled, except where
 
it is composed of a characteristic hydatiform mass shown in figure 11.
 
  
No. 1325 (Dr. Fred R. Ford), shown in figure 12, is a small, irregular mass 40X33
+
The records of the Mall Collection contained 8 cases of hxdatiforni mole in the first 2,400 accessions, showing a fretiuency 8 times as great as that given by WilUamson, or an excess of 700 per cent. Since the lirst 2,400 accessions contain 309 ctises of tubal and also 2 of ovarian pregnancy, only 2,089 uterine specimens remain. Hence the recorded incidence in the uterine specimens really is 8 in 2,089, or 1 in every 261 cases. This incidence is only slightly lower than that of Kroemer, and somewhat higher per 1,000 than that given by Essen-Moller for the Frauenkhnik at Lund, or the personal experience of Cortiguera.  
X 20 mm. , the exterior of most of which is formed by a thin layer of decidua. Within this is
 
a small group of quite tj-pical hydatid cysts, the largest of which measures about 10X5 mm.
 
The appearance of the specimen suggests that it is merely a fragment, though the amount
 
of decidua present indicates that the entire specimen probably was not much larger. The
 
history of this specimen is especially interesting because of the diagnosis of tubal pregnancy,  
 
caused by the presence of a cornual myoma and the occurrence of repeated bleeding.  
 
  
By far the most interesting specimen, in some respects, of hydatiform degeneration
 
among those diagnosed as such upon gross examination in the Mall Collection is No. 1640.
 
  
 +
The highest incidence of hydatiform degeneration previously reported is that of Storch, who estimated it as 50 per cent, but he unfortunately did not give a record of his cases. However, Storch emphasized that the typical complete hydati- form mole is a relatively rare form of the disease, and that all manner of transition forms between the normal chorionic vesicle and the completely degenerated one can be shown to exist. Storch further emphasized the commonness of hydatiform degeneration, especially in the early months of pregnancy, but as Veit (1899) well said, Storch somehow has not received sufficient credit for his investigations. Gierse was forgotten completely. This seems strange, especially in view of the fact that Storch's work was done in Copenhagen, where Panum (1860) had done and still was doing such fine and very suggestive, indeed epochal, work on the origin of monsters. Although Storch devoted part of his paper to myoma fibrosum, and reported only 5 cases of hydatiform mole, one of which, however, accompanied a living fetus, his opinions on the whole were far ahead of his time. In order to make this clear I shall quote a very significant passage, which indeed needs but slight changes to serve as a conclusion for my own investigations:
  
This abortus, received tlirouKh the courtesy of Dr. J. W. Williams, measured 40X20
 
X15 mm. Upon examination Dr. G. L. Streeter found it to be composed of a flattened
 
decidual and chorionic mass which, upon section, showed "pearl-like vesicuhir enlarge-
 
ments which suggest hydatiform degeneration." The exterior of this specimen is com-
 
posed of a thin, hemorrhagic decidua which comi)letely surrounds the villi. The hydxitid
 
luiture of this clearly is recognizable upon close scrutiny with the imaided eye, and easily
 
becomes evident upon magnification of 12 diameters with the binocular microscope.
 
Examination of the histologic preparations reveals it to be a very fine specimen of
 
relatively early hydatiform degeneration.
 
  
No. 1914 (Dr. G. C. McGorniick) is a fine, very characteristic mass, part of which is
+
:"Nun sind aber bekanntlich Eier mit blasiger Degeneration der Zotten und fehlerhaft oder nicht entwickeltem Fotus ein sehr hiiufiger Befund bei Aborten aus den ersten Schwan- gerschaftsmonaten. Mehrere solche Eier sind schon in den bekannten Arbeiten von Dohrn und Hegar beschrieben worden. Ich habe im Laufe des letzten .Jahres eine grossere .\nzahl von Aborten untersucht und derartige kranke Eier in mehr als der Halfte der Fiille gefunden. Nicht selten ist die Amnionblase vollig leer und enthalt nur eine klare serose Fliissigkeit. In anderen Fallen sitzt an der einen oder anderen Stelle der Innenfljiche des Amnion ein kleiner rundlicher oder unregelmassig geformter, 5-I Mm. grosser Korper, welcher aus Nichts als aus runden, schwach conturirten, zum Theil fettigentarteten Zellen und einer hellen, fast homogenen Zwischensubstanz besteht, und der durch einen feinen, 1-3 Mm. langen Strang von ahnlicher Natur mit dem Amnion verbunden ist. In noch anderen Eiern ist der Embryo zwar etwas weiter entwickelt, aber von den verschiedensten Formen von Alissbildungen befallen. Seltener ist der Embryo einigermaassen wohl gebildet und von bis zu 2 Cm. Lange, wie dies auch Hohl nur einmal gefunden hat. Sehr gewohnlich ist fettige oder lipoide Entartung des Embryo vorhanden; derselbe ist dann eine kiirzere oder langere Zeit vor der Geburt abgestorben. Als die aussersten Glieder dieser Reihe von kranken Eiern stehen endlich die sehr seltenen Falle, in welchen der Embryo seine Entwickelung ziemlich ungestort fortgesetzt zu haben scheint, und von denen die Fiille von Martin und der oben beschriebene dreimonatliche abort Beispiele sind.  
shown in figure 18. It is like Nos. 749 and 132.3, but very much larger, for in fluid it com-
 
jiletely fills a 2-liter jar. This specimen was said to have accompanied a living, 7-months
 
fetus, having been expelled between the fetus and the placenta. Only a sniidl amount of
 
clot, and what seems to be a small portion of placenta and membranes, accomj)anied it.
 
Since the placenta was not saved it is impossible to say whether the mass resulted from
 
partial degeneration of the placenta belonging to the living child, or whether it represented
 
a degenerate twin placenta, which is rather unlikely but not imj)ossible, in view of the well-  
 
authenticated cases found in the literature. This specimen is of interest not only for the
 
numerous large, clear cysts, one of which measures 30X25 mm., w'hich it contains, but
 
because it accompanied the birth of a living child and becau.se of the relative rareness of
 
such a coincidence. In regard to the latter. Dr. McCormick added that in his experience
 
of over 1 ,000 labors he had never before met this coincidence. The rareness of the specimen
 
is emphasized still further by the statement of Professor Williams that such an instance has
 
not been observed in a series of over 17,930 obstetrical cases treated by the department of
 
obstetrics of the Johns Hopkins Medical School, as well as by the small series of such
 
cases recorded in the literature.  
 
  
No. 1926, a companion specimen to No. 1640, is composed of material from curettage
 
received through the courtesy of Dr. Karl Wilson, of the department of obstetrics of the
 
.Johns Hopkins Medical School. It was removed from the same patient about a year later
 
than specimen No. 1640. Upon gross examination the hydropic nature of some of the villi
 
is jilainly evident, as shown in figure 14, and upon microscopic examination the diagnosis of
 
hydatiform degeneration could be confirmed, although the villi were extremely degenerate.
 
The menstrual history of this case fortunately is known and is thoroughly reliable. The
 
last menstruation occurred January 24 and curettage was done August 4. Bleeding
 
occurred every two or three weeks during March and April and was repeated throughout
 
May. Since the uterus, which had reached the symphysis, liad not enlarged any for months,
 
in view of the long duration of pregnancy the ojjeration was ])erformed. The major por-
 
tion of the specimen is very small. The chorio-decidual ])ortion was felt-like in consistency
 
and extremely fibrous, due largely no doubt to the long retention. Most of the accom-
 
panying material looks like mucosa rather than decidua, although some of the larger pieces
 
very evidentlj' contained villi. Some of these were relatively thick and fibrous, and others
 
were vesicular. All of the material was extremely fibrous, making it difficult to get a satis-
 
factory tea.sed preparxition. Accomiianying this nmterial was a small body 5X7.5X
 
.30 mm., shown in figure 15. Both nodule and stalk contained some renuiants of the embryo.
 
Although the api)earance of the stalk suggests the umbilical cord, it contains fragments of
 
the body of the embryo, some of which evidently are composed of nerve tissue.
 
  
Microscopic examination of the jiedunculated mass further shows it to be comjiosed of
+
:"Die blasige Entartung der Chorionzotten kann demnach neben den verschiedensten Zustanden des Embryo fegunden werden. Sehr hiiufig ist letzterer der Sitz von mehr oder weniger eingreifenden Krankheitsprozessen gewesen, die in demselben verschiedene Aliss- bildungen hervorgerufen und ihn in seiner Entwickelung gehemmt haben. Es sind diese Krankheistprozesse wahrscheinlich immer sehr friih im Ei entstanden, und miissen mit Panum zuniichst als entziindliche A'organge aufgefasst werden, welche nach ihrer Intensitat und vielleicht nach dem Zeitpunkte, zu welchem sie im Keime auftreten, bald eine theilweiso N'crocliinp der KeinuinlaKPn dcr mcisten wiclitiKorcii Or^ano mit N'crkruppcUing des ganzcn embryonalon K()ri)ers, bald niehr locale I\lissl)il(hingeii oiiizi'lncr Korjier- thcile horvorrufcn koiinen. Das Erstere ist in den hicr hosprochenen Aburteii sehr hiiufig der Fall: der Embrj'o ist zu eineni unfDriiilichen Kluniiien umgewandelt, dein die nieisten Organe deren Keiine dvirch Entziiiuhing zerstc'irt worden sind, giinzlich fehlen. ^'oIl diescn verkriippelteii Aniorphi linden sieh in anderen Eiern alle Uebcrgiingsfornien zu niehr oder weniger entwiekelten Missbildungen was auch Paniini an einigen Beispielen nachgewiescn hat. Es Scheinen in der That die nicht zerstorten Keinizellen der verschiedenen Organe, nach dem ablaiife des Krankheitsprozcsscs, ihren ursi)runglichen Entwickelungs- j)lan mit einer oft merkwiirdigen Hartniickigkeit, so gut sie es kcinnen, festzuhalten. Von dieseni \'erhaltnisse liefern die bekannten herzlosen Amorphi, die durch einen Zwillingsbruder einhiirt werden und dadurch zu einer oft bedeutenden Cirosse heranwachsen konnen, ein schlagendes Beispiel. In unseren Aborten sind zwar diese Amorphi, die keinen Zwillings- bruder zur Erhaltung ihres Krcislaufes geliabt haben, fruhzeitig zu (Jrunde gegangen, und ihre Clewebsteile sind einer fettigen (lipoiden) Entartung anheimgefallen ; sie haben jedoch ihre Entwickehmg eine Zeit lang fortgesetzt.  
degenerate remnants of organs, tissues, and cells. It is j)artly denudeil and ])artly co\cred
 
by a layer of fibrous connective tissue which contains local thickenings. In other areas
 
this fibrous layer gives place to a single or more celled layer, or to polygonal epithelioid
 
cells. The interior of this specimen is composed of a degenerate jumble including fragments of the central nervous system, of the heart, liver, and cartilages. The entire body is
 
chaotic in its structure, and small fragments of the nervous system are scattered throughout
 
its entire extent. This would seem to indicate that the disruption of the tissues was  
 
mechanical. The material in which these remnants are contained is composed of coagulum,  
 
some mesenchyme, cellular detritus, blood and polymorphonuclear leucocytes, degenerated
 
cells, which appear to ha\'e been phagocytic, but which are more likely fusion products or
 
"symplasma" (as Bonnet called them). A few remnants of vessels are found only in the
 
fragments of cartilage.  
 
  
This short review of the gross appearance of the cases of hj'datiform degenera-
 
tion recognized by the unaided eye with the customary criteria, originally clas.sed
 
as such in the Mall Collection, shows that they vary decidedly in their gross, naked-
 
eye characteristics, both as to size and appearance. Xo. 1640 scarcel^^ is distin-
 
guishable as a case of hydatiform degeneration from gro.ss appearances alone,
 
unless one's attention is directed especiallj^ to the matter, but all the rest of the
 
specimens, both small and large, not only are easily recognizable, but are so char-
 
acteristic that the}' could not possibl^y be overlooked. As was indicated above, the
 
incidence of these specimens of hydatiform degeneration among the first 2,400
 
accessions in the Alall Collection w'as 1 in every 261 abortuses, or more than 8
 
times the incidence given by Williamson, and 1.3 times that given by E.ssen-Moller.
 
Although this incidence is so much higher, it does not necessarily contradict the
 
statements of Williamson, for it represents the incidence of hydatiform degenera-
 
tion in abortuses belonging very largely below 7 months. Nor does it tell the whole
 
story for these months, for since the incidence of hydatiform degeneration given
 
in the records of the ]\Iall Collection is based upon determinations made essentiallj^
 
in the usual way — that is, by unaided inspection of the gross specimen alone — we
 
must regard it also merelj' as an apparent, not as the actual incidence. For, as wiU
 
appear later, the actrual incidence can be revealed only by a careful gross and
 
microscopic study of all specimens, both normal and pathologic. Such a study has
 
not as yet been completed, but 348 uterine specimens classed as pathologic, and
 
105 pathologic tubal specimens, contained in the first 1,187 accessions, were care-
 
full}' examined.
 
  
The actual number of cases of hydatiform degeneration found among the 348
+
:"Est is von den verschiedenen Verfassern vielfach von einer Auflosung der Embryonen in der Amnionfliissigkeit und von einer nachherigen Resorption derselben gesprochen worden. Ich glaube indessen, dass die.sen Vorgiingen eine sehr geringe RoUe beizulegen ist. Man findet in der Tlmt gewohnlich Nichts, was auf eine solche Resorption deuten konne. Es scheinen vielniehr die abgestorbenen Embryonen auch lange nach ihrem Tode eine v;rosse Wiederstandfiihigkeit gegen die Einwirkung, von .\mnionflussigkcit beizubehalten. Ich halie mehrmals ganz kleine, verkriippelte Embryonen zwar fetig entartet, in ihrer Form aber v(")llig wt)hl erhalten, in Eiern gefunden, die bis zu 10 Monaten im Uterus zuriickge- hiilten worden sind. Zudem ist die Amnionfliissigkeit in diesen Eiern meist ganz klar, oder sie enthalt nur losgestossene, hinfiillige Amnionejiithelzellen suspendii't. Wenn daher die Eier ganz leer gefunden werden, so riihrt dies gewiss am Hiiufigsten tlaher, dass der Primitivestreifen seiner Zeit vollig destruirt worden und somit gar kein Embryo zur Ent- wickehmg gewommcn ist. * * * Im AUgemeinenerreichensiekienebedeutende (iriisse und werden zudem oft fruhzeitig aus dem Uterus ausgestossen, in dem sie, wie oben bcsprochen, ein sehr betriichtliches Contingent zu den Aborten iiberliaupt liefern. * * *
uterine abortuses classed as pathologic was 112, or 32.4 per cent of the whole. The
+
:" Die Traubenmole und die verschiedenen Ucbergengsformen derselben, die an Aborten sehr haufig vorgefunden werden, ist als Hyperplasie und secundiire cystoide Entartung des (von AUantois nicht herstanuumenden) C'horionI)indegewebs vorzugsweise charactertisirt. Die Krank^'eit wird von pathologischen Zustiuiden der i'lbrigen Eitheilc, Amnion und Embryo (Missbildungen, ^'erkriipl)elungen und friihzeitigem .\bsterben des letzteren) sehr haufig begleitet. Seltener ist der Embryo regelamasmig entwickelt, stirbt al)er meist auch dann wegen mangelhafter Vascularisation der (Chorion) Placenta fruhzeitig ab. Sehr selten scheint der P^mbryo ungestort bis zur Geburt sich fort entwickelt zu haben."
incidence of hydatiform degeneration in the pathologic tubal pregnancies was  
 
somewhat higher even — 44 specimens of undoubted hydatiform degeneration in
 
105, or 41.9 per cent. Since nearly all the tubal specimens are young, while the
 
uterine series contains many more relatively older ones, the effect of this fact upon
 
the determined relative incidence of hydatiform degeneration among the patho-  
 
logic tubal and uterine specimens must be borne in mind. For a reUable conclusion
 
regarding the relative incidence in the uterine and tubal pregnancies it W'ould be
 
necessary to select a series from each, composed of specimens of approximately
 
corresponding ages. "WTiat the incidence of hydatiform degeneration is among the
 
uterine and tubal specimens classed as normal I do not know^, but it undoubtedly
 
is far below that in those classed as pathologic. It is well to remember, how^ever, that many, if not most of the instances of beginning degeneration very likely will
 
be found among the specimens classed as normal. This is well illustrated by a
 
hysterectomy specimen, No. 83G.  
 
  
If we assvmie that the incidence of hydatiform degeneration amf)ng the ]):i11k)-
 
logic sj^ecimens in the rest of the Mall Collection is the same as that amf)ng those
 
in the first 1,1S7 accessions, then we get over 314 estimated instances of hydatiform
 
degeneration in ]iathologic tubal and uterine cases alone. Since I have found a
 
number of chorionic vesicles accompanying embryos classed as normal which also
 
show hydatiform degeneration, this number would be increased still further; but
 
unfortunately too few of the specimens classed as normal were examined to justify
 
an estimate. Yet these normal specimens form GO. 4 per cent of the first 1,000 and
 
40.7 per cent of th(> first 2,500 accessions. This supposed increase, due to inclusion
 
of specimens contained among the normal, would be offset somewhat, however, bj'
 
the fact that the first 1,000 accessions contain a somewhat larger proportion of
 
young conceptuses, each succeeding 1,000 probably becoming somewhat more
 
representative of actual life conditions. The difference between the composition
 
of the first 1,000 accessions and that of the 1.000 between 1,500 and 2,500 is not
 
very great, how'ever, for the former contains only an excess of 17.6 per cent of cases
 
falling in the first five groups of the IMall classification, which groujjs are comjiosed
 
largelj' of specimens below an embrj'onic length of 20 mm. Then, the relative
 
proportions of tubal and uterine specimens in the different thousands also must be
 
taken into consideration. But in any case the estimated incidence of hydatiform
 
degeneration in the Mall Collection, calculated without regard to those contained
 
among specimens classed as normal, is 7.5 per cent, and the actual incidence hence
 
probably is more than 1 in every 10 accessions. The incitlenc(> among the uterine
 
specimens alone would be 10.9 per cent, and among the tubal alone 20.8 per cent.
 
Tliis difference of 100 per cent between the tubal and uterine specimens maj' have
 
a probable significance in connection with the cause of hydatiform degeneration.
 
  
If, as alleged by various investigators, the great majority of abortions occur
+
But the unregarded observations and illustrations of (Jierse arc still more startling than these opinions and observations by Storch, who knew of CJierse's observations published posthumously by Meckel. The latter quite correctly stated that such careful observations as those made by Clierse always introduce new i)oints of view. If it be remembered that in these days, almost a century later, specimens of hydatiform degeneration which are 4 cm. in diameter still are reported separately as examples of early hydatiform degeneration, the great merit of Gierse's observa- tions in this regard alone will be clearly evident, upon recalling that Giersc pictured a hydatiform villus from a chorionic vesicle tlie size of a hazelnut (about 12 mm.), the largest hydatiils on which were only one-tliird of a line large. Moreover, Gierse added :
in the first 3 months, it is highly probable that many of these early conceptuses
 
are lost and never come to the attention of any one, and that therefore the pro-
 
jiortion of early specimens in this or any other collection is no doubt too small.  
 
Moreover, in quite a number of specimens of the first 1,000 accessions the chorionic
 
vesicles were too degenerate for examination, and in others they were absent, but
 
we have reason to believe that this is not true to the same extent in the material
 
beyond the first 1 ,000 accessions. Then, too, since only a few relatively large
 
sections from a single portion of the chorionic vesicles were examined, it is evident
 
that some cases in which the (k'generation may have been i)urely local i)r()])ably
 
were overlooked. Hence the actual incidence of hydatiform degeneration in this
 
collection is jjrobably not merely 8 times but 240 times as great as that givcMi by
 
Williamson (1900), and 33.3 times as great as that given by E.ssen-M()ller.  
 
  
Most persons will, I presume, be willing to regartl an increase of 700 per c(Mit
 
above that of William.son as jiossible, but one of 24,000 p(T cent above Williamson,
 
or even 3,333 per cent above that of Essen-Moller as wholly out of the ((uestion.
 
  
 +
:"Derlcichen geiinge krankhafte Veranderungen finden sich an au.serordentlichen vielcn Abortus, und sie scheinen die hiiufigste Ursache des Abortus in den ersten Monaten zu sein."
  
Yet, strange as it may seem at first sight, this is not a random guess Ijut an estimate
 
based upon (hi; actual incidence of iiydatiform degeneration as determined by a
 
careful gross and microscojjic examination of mounted and unmounted material
 
from over 400 abortuses. However, I lay no special emphasis on these percentages,
 
and am using them merely to emphasize the great frequency of hydatiform degenera-
 
tion. It matters little whether we shall ultimately determine an incidence of 10
 
or 5 per cent, but it does matter considerably whether we regard the frequency as
 
5 or 0.05 per cent, for this is a difTerence of 10, 000 per cent.
 
  
In view of the ])revailing opinion, I realize that these findings may .seem incom-
+
How such an epoch-making conclusion not only could be forgotten, but absolutely overlooked or disregarded, by all but a few of the scores upon scores who have written on hydatiform degeneration, it is difficult indeed to understand. Gierse, who took steps to ascertain what normal villi look like, stated that villi with marked irregularities as described by Desormaux, Breschet, Raspail, and Seller undoubtedly were abnormal; surmised that vilh in abortuses seldom are normal, and added that between the slight pathologic changes in the caliber of the vilh and the most evident hydatiform moles the plainest transition can be found. Among other important things Gierse also recognized the early fenestration of the stroma and pictured such a villus under a magnification of 250 diameters, and although reported very briefly, his findings, wholly confirmed here, still wait for general recognition.  
prehensible and perhaps incredible, unless it is distinctly borne in mind that it is
 
not stated that this incidence refers to the later months of pregnancy or to term.  
 
What the incidence in the later months of pregnancy may be I do not know, but I
 
have called attention to an apj^arently well-founded belief that it is a relatively
 
rare condition, the estimates ranging from 1 in 2,000 to 1 in 728 or 300 cases.  
 
  
In regard to the incidence of hydatiform degeneration in uterine specimens,
 
it should also be remembered that the life, in contrast to the laboratory incidence
 
for the entire period of gestation is higher, not only because the chorionic vesicles
 
were not included in many of the accessions and because others were too degenerate,
 
but because I have not as yet been able to recognize the very earhest stages with
 
entire certainty. Furthermore, many instances of hydatiform degeneration from
 
the early months of pregnancy, especially the first and second, are inevitably lost.
 
The increase due to these things would be offset somewhat, however, by the lower
 
incidence of hydatiform degeneration in specimens from the last months of preg-
 
nancy, relatively few abortuses from these months being contained in the Mall
 
Collection.
 
  
To what extent the material in this Collection is truly representative of actual
+
Just as the great majority of specimens described in the literature are large, so 4 of the 8 specimens originally classed as such in the Mall Collection also are large, and none of the 8 are very young, as the following protocols show:
life conditions is difficult, if not impossible, to determine. This question could
 
be answered only if all the abortuses and material from abortions actually reached
 
physicians, and if the latter sent all of them to the laboratory. I\Iy own impression
 
so far is that the material representative of a sufficientl}' large community probably
 
would have a somewhat lower incidence, notwithstanding the fact that many
 
specimens not only of hydatiform degeneration, but of abortuses in general, espe-
 
cially from the first month of pregnancy, are lost. However, since the presence of
 
hydatiform degeneration is especially common among early specimens, the inclusion
 
of these might raise the incidence for the whole period of gestation more than the
 
inclusion of all specimens (not excepting those of the last three months) would
 
lower it. But the result obtained would represent the incidence of hydatiform
 
degeneration in abortuses alone, and not that in all pregnancies. The latter could
 
be obtained only by including all gestations which end normally. If we accept
 
Pearson's (1897) estimate that approximately 40 per cent of all pregnancies end
 
prematurely, then the incidence of hydatiform degeneration among abortuses would
 
represent very nearly twice that in all pregnancies. Mall's estimate of 20 per cent
 
prenatal mortahty, on the other hand, would give us an incidence only one-fifth
 
as great as that among abortuses. Hence, the actual life incidence of hydatiform degeneration in all gestations would t lien be 1 in 10, as based upon Pearson's, and 1 in
 
25. as based upon Mall's estimated i)renatal mortality. But even if, as estimated
 
upon this basis, 4 or 10 per cent of all conceptions end in hydatiform degeneration,
 
this does not necessarily contradict the current opinion regarding its rareness at or
 
near term.
 
  
A careful examination witli the binocular microscope of all specimens has shown
+
[[File:Meyer1920_fig08.jpg|thumb|Fig. 8. Gross appearance of specimen No. 70.]]
that hydatiform degeneration as a rule is sufficiently general even in young vesicles,
+
[[File:Meyer1920_fig09.jpg|thumb|Fig. 9. Gross appearance of specimen No. 323.]]
so that sections of a single portion about 10 mm. scjuare, would enable one to make
 
a fairly rehable diagnosis. Now and then, however, the process seems to be rather
 
irregularly developed, especially in the larger specimens.  
 
  
In order to determine accurately the question of distribution of hydatiform
+
:'''No. 70''' (Dr. Charles H. Ellis) is a small, fimi, degenerate-looking, almost solid mass 40X30X28 mm., composed of small cysts, degenerate decidua, exudate and degeneration products. As figure 8 shows, it is very similar to a very much larger specimen. No. 323 (Dr. V. Van Williams). The latter is a large, firm, felt-fike mass 120X90X65 mm., represented in figure 9. The individual cysts, which vary from 1 to 20 mm., are packed together rather firmly, though a few large ones are free. The exterior of the specimen is formed by a thick layer of degenerate decidua and gives only a slight indication of its true nature upon closer inspection or upon examination of the cut surface. No fetal remnants were noticed, and microscopic examination shows tliat the specimen is composed merely of a large hydatiform mass which was retained for a long tune and then aborted in toto with the surrounding decidua and exudate.  
degeneration over various j^ortions of the chorionic vesicle, it will be necessary to
 
examine a series of sections of i)ortions of the chorionic vesicle for each small  
 
specimen. This has not yet been done, but since the portions used for microscopic
 
examination had been taken at random without previous knowledge of the existence
 
of hydatiform degeneration in any but the 8 specimens above described, and since
 
a series of 453 vesicles was examined, I can not beUeve that it can often be limited
 
to any particular area on relatively young vesicles. In these it usually is universal
 
even if not complete. It is of special interest in tliis connection that Muggia (1915),  
 
after reviewing the small Ust of cases of alleged hydatiform degeneration of the
 
chorion laeve in connection with a study of a case of liis own, came to the conclusion
 
that these cases are not really degenerations of the chorion laeve, but merely jiartial
 
degenerations of the placenta. Although I have given no thorough attention to
 
the normal changes in the chorion la?ve, I am (luite certain that they are not the
 
cause of confusion in the series of hydatiform degenerations from the Mall Collec-
 
tion. Cases in which whole chorionic vesicles excjuisitely hydatiform in character
 
were contained in the tubes, and a number of others which still were implanted
 
within the uteri showed equally exquisite hydatiform changes around the whole
 
])erimeter. Such cases as these ultimately confirm the oi)inion that in young vesicles
 
as a rule the condition is general except at its very inception. This is true
 
particularly by the time the degeneration has reached a stage which can be con-
 
sidered at all tyijical in its gro.ss development, as determin(>d liy can^ful examina-
 
tion of numerous specimens with the binocular.  
 
  
It is especially interesting that, just as soon as tyj)it'al hydatitl elliptical villi,  
+
[[File:Meyer1920_fig10.jpg|thumb|Fig. 10. Gross appearance of specimen No. 749.]]
or portions of the same begin to appear, the condition can be recognized with some
+
:'''No. 749''' (Dr. G. G. McCormick), on the contrary, is a fresh, loose, typical hydatiform mass composed of loase hydatids of various sizes, as shown in figure 10. As the specimen floats loosely in fluid, it fills a half-liter jar about two-thirds. A considerable portion of the hydatid cysts are glued into a solid mass by blood, exudate, and decidua, which form a layer on the exterior.  
certainty under a magnification of 12 to 20 diameters with the binocular micro-
 
scope. It often was surprising how relatively early stages could thus be detected
 
and th(! diagnosis confirmed later l)v histologic examination. Indeed, C(>ll()idin
 
blocks of tissue from which sections had been cut gave spk^ndid testimony when
 
examined in Huid with the binocular. One of the not very early stages contained in
 
utero and rei»-esented in figure 10 could be recognizetl with the unaided eye; and
 
when examined with the binocular, under a magnification of about 12 diameters,  
 
the picture was unusually fine and wholly uiiinistakable, as shown in figure 17.  
 
  
 +
[[File:Meyer1920_fig11.jpg|thumb|Fig. 11. Gross appearance of specimen No. 1323.]]
 +
:'''No. 1323''' (Dr. J. W. SchUeder) also is a large mass very like the preceding, which completely fills a liter jar. It is accompanied by much clot and composed mainly of a large, thick-walled, hemorrhagic, necrotic mass 80X50X45 mm, containing a large, thin-walled cavity 65X30X25 mm, which is broken at one end. This cavity which is apparently that of the chorionic vesicle, is empty, smooth, and thin-walled, except where it is composed of a characteristic hydatiform mass shown in figure 11.
  
That hydatiform degeneration is incomparably more common in the earUer
+
[[File:Meyer1920_fig12.jpg|thumb|Fig. 12. Gross appearance of specimen No. 1325.]]
than in the hiter months of pregnancy, thus justifying the comparison made with
+
:'''No. 1325''' (Dr. Fred R. Ford), shown in figure 12, is a small, irregular mass 40X33 X 20 mm. , the exterior of most of which is formed by a thin layer of decidua. Within this is a small group of quite tj-pical hydatid cysts, the largest of which measures about 10X5 mm. The appearance of the specimen suggests that it is merely a fragment, though the amount of decidua present indicates that the entire specimen probably was not much larger. The history of this specimen is especially interesting because of the diagnosis of tubal pregnancy, caused by the presence of a cornual myoma and the occurrence of repeated bleeding.  
measles, is substantiated by statistics covering the material examined. From these
 
it is evident that, excepting cases of large hydatiform ma.sses originally classed as
 
hydatiform degeneration from inspection of the gross specimens alone, practically
 
all the specimens are relatively young. This is true especially of those from tubal
 
pregnancies, and we may henc(> regard it as established that hydatiform degenera-
 
tion is a change which is exceedingly common in the earlier months of pregnancy,
 
just as measles is common in childhood, and that it becomes progres.sively less
 
common as the end of pregnancy is approached, just as does measles as senility is
 
approached. The obstetrician does not see most of the cases of hydatiform degen-
 
eration, for they merely are reported as miscarriages and the specimens often are
 
destroyed or retained unrecognized by the general practitioner or the midwife.
 
They often are alwrted spontaneously and completely with the decidua and rarely
 
are still contained in a closed decidual cast when they reach the laboratory.  
 
  
The spontaneity of the abortion, especially in early cases, was emi^hasized also
+
By far the most interesting specimen, in some respects, of hydatiform degeneration among those diagnosed as such upon gross examination in the Mall Collection is No. 1640.  
by Storch in the above quotation. Cortiguera (1906) is reported by Pazzi (1908^)
 
also to have declared that many moles disappear wholly without leaving a remnant,
 
even if occurring rejieatedly in the same woman, and Donskoj also stated that many
 
of those aborted do not come to the attention of physicians because of their harm-
 
lessness. This, however, does not imply that those which persist and develop into
 
large masses are equally harmless, and it must be remembered that it is upon these
 
that the current opinion regarding the tendencies to malignancy of the hydatiform
 
mole is based.  
 
  
The conclusion regarding the greater incidence of hydatiform degeneration in
 
the early months of pregnancy is conclusively confirmed by the occurrence of 32
 
of the 48 tubal specimens within the first two clas.ses of the pathologic division of
 
Mall, and 104 of the 112 uterine specimens in the first six classes of this division.
 
Most of the specimens in these classes are composed of villi, of empty chorionic
 
vesicles, or of vesicles with embryos most of which have a length of less than 20
 
to 30 mm. That hydatiform degeneration is more common in the early months of
 
pregnancy is indicated also by the well-known reports of Kehrer (1894) on 50 cases,
 
and of Borland and Gerson (1896), who found that 63 per cent of 100 cases had
 
aborted in the fourth and fifth months of pregnancy. According to Seitz, Hirtz-
 
man (1874) also found that 62.8 per cent of 35 cases had aborted between the third
 
and sixth month. Only 4 per cent of Kehrer's 50 cases and only 3 per cent of
 
the cases of Borland and Gerson aborted at the tenth month. Bonskoj stated that
 
7 of the 10 cases reported by him aborted in the fourth month and none after the
 
sixth month. He stated further that 56 per cent of Bloch's 50 cases aborted before
 
the sixth month, 44 per cent later than this, one being retained until the fourteenth
 
month. The latter case is especially interesting because retention not only beyond
 
term but after the death of the mole seems to be regarded as relatively rare. This,
 
however, does not imply that retention beyond the period of growth of the hydatid
 
mole does not occur, although Sternberg (1910), who also emphasized the great rarity of this condition, erroneously stated that the (Jerman Hterature reveals onl}-
 
a single instance of missed abortion in case of hydatiform mole, viz., that of Poten
 
(1901). In this case a hydatiform mole of the size of a duck egg; was said to have
 
been aborted ai^proximately one month beyond term. Hence growth must have
 
ceased long before and the mole have remained in ulcro as a "harmless body." To
 
this case of Poten, Sternberg adds a case in which a hydatiform mole of 14X9.6
 
X4.3 mm. was aborted in the twelfth month after the cessation of menstruation.
 
Although Sternberg included 4 cases from other countries among these missed-
 
abortion moles, inz., those of Shell (undated), Ferguson (also undated), Colorni
 
(190S), and Gaifani (1908), one can hardly doubt that more cases could be added.
 
Since the case of Shell was one of twin pregnancy in which one conceptus l)ecame
 
hydatiform, it is not at all unlikely that some other cases among this rather small
 
series of twin pregnancies accompanied by hydatiform degeneration may belong
 
in this category.
 
  
Maj'er also emphasized the fact that, although instances of retention of fetuses
+
:'''No. 1640''' This abortus, received through the courtesy of Dr. J. W. Williams, measured 40X20 X15 mm. Upon examination Dr. G. L. Streeter found it to be composed of a flattened decidual and chorionic mass which, upon section, showed "pearl-like vesicuhir enlargements which suggest hydatiform degeneration." The exterior of this specimen is composed of a thin, hemorrhagic decidua which completely surrounds the villi. The hydxitid luiture of this clearly is recognizable upon close scrutiny with the imaided eye, and easily becomes evident upon magnification of 12 diameters with the binocular microscope. Examination of the histologic preparations reveals it to be a very fine specimen of relatively early hydatiform degeneration.  
are verj'^ common, instances of retention of hydatiform mole are very rare, onlj' a
+
[[File:Meyer1920_fig13.jpg|thumb|Fig. 13. Grass appearance of specimen No. 1914.]]
few cases having been recorded. Maj^er refers to 2 cases by Kehrer, 3 of Borland
 
and Gerson, and to 1 case of Lange, and reports 4 of his own. These 4 were found
 
among 10 cases of hydatiform mole, an incidence of retention of 40 per cent. Thej^
 
are interesting, especially in connection with the observation of Briggs that, con-
 
trary to current beUef, uterine enlargement often is not beyond the normal. Mayer
 
says that this enlargement was too great in but 1 of the 4 cases, and that retention
 
lasted as long as 4 to 5 months.  
 
  
At least 3 of the cases of hydatiform mole originally recorded as such in the  
+
:'''No. 1914''' (Dr. G. C. McGorniick) is a fine, very characteristic mass, part of which is shown in figure 13. It is like Nos. 749 and 132.3, but very much larger, for in fluid it completely fills a 2-liter jar. This specimen was said to have accompanied a living, 7-months fetus, having been expelled between the fetus and the placenta. Only a sniidl amount of clot, and what seems to be a small portion of placenta and membranes, accompanied it. Since the placenta was not saved it is impossible to say whether the mass resulted from partial degeneration of the placenta belonging to the living child, or whether it represented a degenerate twin placenta, which is rather unlikely but not imj)ossible, in view of the well- authenticated cases found in the literature. This specimen is of interest not only for the numerous large, clear cysts, one of which measures 30X25 mm., which it contains, but because it accompanied the birth of a living child and because of the relative rareness of such a coincidence. In regard to the latter. Dr. McCormick added that in his experience of over 1 ,000 labors he had never before met this coincidence. The rareness of the specimen is emphasized still further by the statement of Professor Williams that such an instance has not been observed in a series of over 17,930 obstetrical cases treated by the department of obstetrics of the Johns Hopkins Medical School, as well as by the small series of such cases recorded in the literature.  
Mall Collection belong among retained specimens, as the illustrations alone suggest.
 
But a fair percentage of detached chorionic vesicles included in the Ust of cases
 
here reported undoubtedly also was retained after the cessation of growth, and it is  
 
for this reason that I further emphasize the fact that the uterine volume in a con-
 
siderable percentage of these cases also, instead of having been too great for the
 
duration of the pregnancy unfiuestionably was too small. This is well illustrated
 
by the histories of specimens Nos. 70, 323, 1G40 and 1926, and by the sjiecimens
 
themselves.  
 
  
The average menstrual age of 51 of 112 uterine specimens of this series of  
+
[[File:Meyer1920_fig14.jpg|thumb|Fig. 14.]]
hydatiform degeneration — in which the data were available — was 66.6 days, or  
+
[[File:Meyer1920_fig15.jpg|thumb|Fig. 15.]]
2\ months. As will be seen, this is a far lower average age than heretofore reported,  
+
:'''No. 1926''', a companion specimen to No. 1640, is composed of material from curettage received through the courtesy of Dr. Karl Wilson, of the department of obstetrics of the Johns Hopkins Medical School. It was removed from the same patient about a year later than specimen No. 1640. Upon gross examination the hydropic nature of some of the villi is plainly evident, as shown in figure 14, and upon microscopic examination the diagnosis of hydatiform degeneration could be confirmed, although the villi were extremely degenerate. The menstrual history of this case fortunately is known and is thoroughly reliable. The last menstruation occurred January 24 and curettage was done August 4. Bleeding occurred every two or three weeks during March and April and was repeated throughout May. Since the uterus, which had reached the symphysis, had not enlarged any for months, in view of the long duration of pregnancy the operation was performed. The major portion of the specimen is very small. The chorio-decidual portion was felt-like in consistency and extremely fibrous, due largely no doubt to the long retention. Most of the accompanying material looks like mucosa rather than decidua, although some of the larger pieces very evidently contained villi. Some of these were relatively thick and fibrous, and others were vesicular. All of the material was extremely fibrous, making it difficult to get a satisfactory teased preparation. Accompanying this material was a small body 5X7.5X .30 mm., shown in figure 15. Both nodule and stalk contained some remnants of the embryo. Although the appearance of the stalk suggests the umbilical cord, it contains fragments of the body of the embryo, some of which evidently are composed of nerve tissue.  
a difference which exjilains itself from what has lieen said already. It is interesting
 
that the average menstrual age of 5 of the 8 specimens in the Mall Collection
 
originally classed as hydatiform degenerations is 168.2 days, or 2.^, times as great,
 
thus being in substantial agreement with the usual results. Three of these 5 are
 
large specimens, the fourth measures 40X20X15 mm., and the other is composed
 
of small fragments contained in material from curettage. I<>om this alone it follows
 
that the menstrual age is a very uncertain guide, es])ecially as to the size of a hydati-
 
form mole.  
 
  
  
It seems superfluous to add any tiling to the good description of the gross
+
Microscopic examination of the jiedunculated mass further shows it to be composed of degenerate remnants of organs, tissues, and cells. It is partly denuded and partly covered by a layer of fibrous connective tissue which contains local thickenings. In other areas this fibrous layer gives place to a single or more celled layer, or to polygonal epithelioid cells. The interior of this specimen is composed of a degenerate jumble including fragments of the central nervous system, of the heart, liver, and cartilages. The entire body is chaotic in its structure, and small fragments of the nervous system are scattered throughout its entire extent. This would seem to indicate that the disruption of the tissues was mechanical. The material in which these remnants are contained is composed of coagulum, some mesenchyme, cellular detritus, blood and polymorphonuclear leucocytes, degenerated cells, which appear to have been phagocytic, but which are more likely fusion products or "symplasma" (as Bonnet called them). A few remnants of vessels are found only in the fragments of cartilage.  
appearance of the typical h3'datiform mole currently reported in the literature.
 
Such cases are so characteristic that even a novice can recognize them at sight.
 
Yet if the findings reported here are reliable, or even approximately so, it never-
 
theless must be evident that, in the past, the great majority of specimens of true
 
hydatiform mole have remained unrecognized mer(!ly because they did not happen
 
to present the customary, well-known picture to ike unaided eye. Small chorionic
 
vesicles, such as No. 2077 shown in natural size in figure 18, which attract no atten-
 
tion upon cursory inspection may, and often do, present the most exquisite picture
 
of hydatiform degeneration when seen under a magnification of 3 to 20 diameters,  
 
as illustrated in figure 19. This is true especially if the examination is made with
 
the binocular microscope. Since I have adopted tliis method of examination it has
 
been possible to recognize instances of decidedly general and typical hydatiform
 
degeneration in chorionic vesicles less than 2 cm. in size, with later confirmation of  
 
the diagnosis by a histologic examination. However, I have not been able to rec-
 
ognize YQvy early stages merely by examination of the gross specimens, for gross
 
recognition is possible only when portions of at least some of the villi have  
 
become sufficiently elliptical or globular to attract attention. Histologic recognition
 
is possible far earlier than this, as shown in figure 20.  
 
  
The general appearance of the whole chorionic vesicle sometimes is an aid in
 
gross identification, for the villi not infrequently are smooth, slightly branched,
 
and unusually long, so that the vosicle looks shaggy, as illustrated in figure 21.
 
The typical gross, hydatid or watery, translucent nature of the vilU can not be relied
 
upon in early stages, for normally shaped villi, which have undergone considerable
 
lysis, may be almost transparent and also somewhat more than normally bulbous.
 
However, save in the case of some specimens of tubal pregnancy, the swelling of the
 
villi, due to maceration or to luetic changes, is quite different in character from
 
that characteristic of hydatiform degeneration, and usually quite easily distinguish-
 
able from it. Judging from several specimens of villi which were macerated in
 
distilled water during a period of weeks, post partum maceration never could cause
 
confusion and the same thing undoubtedly is true of intra-uterine maceration.
 
  
Since numerous trophoblastic nodules are present also in other conditions,  
+
This short review of the gross appearance of the cases of hydatiform degeneration recognized by the unaided eye with the customary criteria, originally classed as such in the Mall Collection, shows that they vary decidedly in their gross, naked-eye characteristics, both as to size and appearance. Xo. 1640 scarcely is distinguishable as a case of hydatiform degeneration from gross appearances alone, unless one's attention is directed especially to the matter, but all the rest of the specimens, both small and large, not only are easily recognizable, but are so characteristic that they could not possibly be overlooked. As was indicated above, the incidence of these specimens of hydatiform degeneration among the first 2,400 accessions in the Mall Collection was 1 in every 261 abortuses, or more than 8 times the incidence given by Williamson, and 1.3 times that given by Essen-Moller. Although this incidence is so much higher, it does not necessarily contradict the statements of Williamson, for it represents the incidence of hydatiform degeneration in abortuses belonging very largely below 7 months. Nor does it tell the whole story for these months, for since the incidence of hydatiform degeneration given in the records of the Mall Collection is based upon determinations made essentially in the usual way — that is, by unaided inspection of the gross specimen alone — we must regard it also merely as an apparent, not as the actual incidence. For, as will appear later, the actual incidence can be revealed only by a careful gross and microscopic study of all specimens, both normal and pathologic. Such a study has not as yet been completed, but 348 uterine specimens classed as pathologic, and 105 pathologic tubal specimens, contained in the first 1,187 accessions, were carefully examined.  
notably in retained placentae as found by Aschoff and others. I have not been able
 
to regard their presence in unusual numbers, in some cases of hydatiform degenera-
 
tion, as of crucial value, but the absence of placental differentiation at a time when
 
it should be present, with a uniform and unusual development of the villi over the
 
whole exterior of relatively large chorionic vesicles, is decidedlj'^ significant and has
 
often been found to imply the ]:)rcsence of hydatiform degeneration. The same
 
thing is true of a very irregular distribution of the villi, or of uniformly distributed
 
fusiform enlargements on the villi and of the loss of the dull appearance of their
 
cut surfaces, as seen under the binocular. As soon as the stroma becomes hydati-
 
form, and even before Uquefaction is present, the cut surfaces of hydatiform villi
 
look somewhat shiny and waxy or, j^erhaps better still, parafiine-like, as in the speci-
 
men in situ shown in figure 21. A bluish tinge always is present, and this appear-
 
ance is verv characteristic. However, how easih' a specimen of hydatiform mole can be recognized by examination with the binocular alone necessarily will depend
 
also upon the condition of the specimen. If the villi are matted, glued, or macerated,  
 
not only the early hydatiform changes but even fairly advanced ones often are
 
masked so completely that recognition is difficult or impo-ssibie without histologic
 
examination.  
 
  
In many early specimens the diagnosis could be made at sight from a histologic
 
preparation under low magnification, even when it was impossible to make a diag-
 
nosis by examination with the binocular microscope alone. What makes this
 
possible is not, as has been generally assumed since Marchand's epochal work on
 
chorio-epithlioma, the ajipearance of the syncytium or that of the Langhans laj^er
 
or of the tropho])last, but the changes in the stroma which precede those in the
 
epithehum. The evidence in regard to this matter is overwhelming, and in the
 
early stages when the stroma already has been altered, it often is impossible to tell
 
whether the epithehal development is normally or abnormally active. Moreover,
 
in spite of Marchant's statement to the contrary, extremely large cysts often have
 
but a single smooth layer of epithelium. This has been asserted repeatedly by other
 
investigators also. The two layers of epithelium are not by any means always
 
present and, while there is no agreement in the matter, the opinion seems to be
 
that the grade of epithelial proliferation can not be used as a criterion for the deter-
 
mination of the presence of hydatiform degeneration. Menu said that the presence
 
of marked epithelial proliferation was emphasized early by Miiller (1847), Ercolani
 
(1876), Franque (1896), and Owry (1897); and according to Pazzi (1908'^), Ercolani
 
and Polano altogether denied the existence of connective tissue in the hydatiform
 
mole. The same thing was asserted by Sfameni (1903), who claimed to have found
 
further evidence of the exclusively epithelial nature of the hydatiform mole in 1905.
 
According to Sfameni the hydatiform mole does not result from a modification of
 
existing chorionic villi, but from an entirely new growth which is wholly epithehal
 
in character! But this opinion, which was accepted also by Niosi (1906), seems to
 
exist among Italian writers only.
 
  
Although Durante (1898) represented extremely long syncytial buds, he never-
+
The actual number of cases of hydatiform degeneration found among the 348 uterine abortuses classed as pathologic was 112, or 32.4 per cent of the whole. The incidence of hydatiform degeneration in the pathologic tubal pregnancies was somewhat higher even — 44 specimens of undoubted hydatiform degeneration in 105, or 41.9 per cent. Since nearly all the tubal specimens are young, while the uterine series contains many more relatively older ones, the effect of this fact upon the determined relative incidence of hydatiform degeneration among the pathologic tubal and uterine specimens must be borne in mind. For a reliable conclusion regarding the relative incidence in the uterine and tubal pregnancies it would be necessary to select a series from each, composed of specimens of approximately corresponding ages. "What the incidence of hydatiform degeneration is among the uterine and tubal specimens classed as normal I do not know, but it undoubtedly is far below that in those classed as pathologic. It is well to remember, however, that many, if not most of the instances of beginning degeneration very likely will be found among the specimens classed as normal. This is well illustrated by a hysterectomy specimen, No. 83G.  
theless found (1909) ci)ithelial proliferation present only where certain vascular
 
changes were present. Winter (1907) stated that the condition of the epithelium
 
varies greatly, and Falgowski (1911) emphasized that he could not demonstrate
 
the presence of an increased epithelial proliferation or of vacuolation of the syn-
 
cytium. Aman (1916) also found that ei:)ithelial proliferation may be wholly absent.  
 
Ballantyne (1913), on the contrary, found epithelial jn-oliferation "so well develo])ed
 
that it suggested that it is an essential proce.s.s in the formation of the mole."  
 
liallantyne further likened hydatiform degeneration to edematous growths and  
 
emi)hasized that both really are epithelial new growths. This opinion is accepted
 
also by de Hnoo (1914), who regarded the hydatiform mole as a neoplasm of the
 
trophoblast with secondary changes in the stroma.  
 
  
There is no agreement at present as to whether the epithelial changes are
 
primary or secondary. As is well known, Marchand (1895) — und Miiller, l*]rco!aiii,
 
and Langhans long before that — regarded the epithelial changes as primary, but most investigators seem to have come to the opposite conclusion. Some share the
 
opinion of Schrocder that hydatiform degeneration jioints to a stimuhis resulting
 
in hypcri)lasia of the entire chorionic villus. Nor is there agreement as to what the
 
initial changes are. Durante (1909) regarded the presence of vessels with an imper-
 
fect endotheUal lining and with thick infiltrated walls as the initial lesion in hydati-
 
form degeneration. These changes were noted by him, especially in trunk villi,
 
and epitheUal proliferation was most evident where the vascular le.sions were most
 
pronounced. Durante further stated that the chain form of the hydatids is due to
 
the fact that the vascular lesions occur at intervals along the villus. Unfortunately,
 
the structure of long hydatiform villi does not confirm such an explanation nor
 
Durante's conclusion that the hydatid cavities within the viUi result from dilatation
 
of the capillaries. Many investigators report the early disappearance of the blood-
 
vessels, a phenomenon which some regard as secondary and others as primary to
 
the death of the embryo.
 
  
In the course of this investigation a villus with a normal stroma and normal
+
If we assume that the incidence of hydatiform degeneration among the pathologic specimens in the rest of the Mall Collection is the same as that among those in the first 1,1S7 accessions, then we get over 314 estimated instances of hydatiform degeneration in pathologic tubal and uterine cases alone. Since I have found a number of chorionic vesicles accompanying embryos classed as normal which also show hydatiform degeneration, this number would be increased still further; but unfortunately too few of the specimens classed as normal were examined to justify an estimate. Yet these normal specimens form GO. 4 per cent of the first 1,000 and 40.7 per cent of the first 2,500 accessions. This supposed increase, due to inclusion of specimens contained among the normal, would be offset somewhat, however, by the fact that the first 1,000 accessions contain a somewhat larger proportion of young conceptuses, each succeeding 1,000 probably becoming somewhat more representative of actual life conditions. The difference between the composition of the first 1,000 accessions and that of the 1,000 between 1,500 and 2,500 is not very great, however, for the former contains only an excess of 17.6 per cent of cases falling in the first five groups of the Mall classification, which groups are composed largely of specimens below an embryonic length of 20 mm. Then, the relative proportions of tubal and uterine specimens in the different thousands also must be taken into consideration. But in any case the estimated incidence of hydatiform degeneration in the Mall Collection, calculated without regard to those contained among specimens classed as normal, is 7.5 per cent, and the actual incidence hence probably is more than 1 in every 10 accessions. The incitlency among the uterine specimens alone would be 10.9 per cent, and among the tubal alone 20.8 per cent. This difference of 100 per cent between the tubal and uterine specimens may have a probable significance in connection with the cause of hydatiform degeneration.  
vascularization never was found to have undergone true hydatiform degeneration,
 
but one with a normally active epitheUum — both Langhans layer and syncj-tium —
 
often was truly hj^datiform. That is, it not only was watery in appearance, but also
 
fusiform or globular even in external form. In fact, Marchand (1895) himself found  
 
that "Das Epithel welches die Zotten und ihre Anschwellungen bekleidet zeigt
 
ein sehr verschiedenes Verhalten." Yet even to-day, the feeling on the part of many
 
seems to be that unless a marked hyperplasia of the Langhans layer and of the  
 
syncytium is present the condition is not one of hydatiform mole. This position
 
seems to me to be untenable for, as Marchand himself said, the change in epitheUum
 
usually is least in the young viUi, and he should have added it is unrecognizable
 
in the early stages and in young conceptuses. A perusal of the Uterature descrip-
 
tive of the actual cases leaves little doubt upon this point, and a careful study of  
 
the advent of the earliest recognizable changes in hydatiform mole is absolutely
 
convincing. The earliest recognizable, even if not the incipient, changes occur in  
 
the stroma and in the vessels — and not in the epitheUum. In passing, it may be
 
noted that although Marchand stated that the change in the epitheUum is primary,  
 
he nevertheless somewhat contradictorily added that the most important fact is
 
the degenerative change in the stroma of the villi.  
 
  
Although not applicable to what I have come to regard as the incipient changes
 
in hydatiform degeneration, it nevertheless is true that the stroma often, if not
 
always, quite early becomes hydatiform — that is, glassy or clear, though not
 
necessarily watery. Moreover, the villous vessels often degenerate or disappear
 
completely at a very early stage. It is exceedingly difficult to make any definite
 
statement as to what is typical regarding the ejiithelium. This has been said by
 
others also. Indeed, this necessarily foUows from the fact agreed to by every one,
 
that histologically there is no true line of demarcation between the ordinary benign
 
hydatiform mole, the so-called destructive benign (?) hydatiform mole — whatever
 
its status may be — and the maUgnant hydatiform mole, or chorio-epitheUoma.
 
Such a conclusion alone presupposes the existence of the widest differences in the condition of the t'pitlu'lium in the these cases, and that such differences actually exist is bcj'ond (juestion.
 
  
Marchand's revolutionary investigation on chorio-ei)ithelioma notwithstanding,  
+
If, as alleged by various investigators, the great majority of abortions occur in the first 3 months, it is highly probable that many of these early conceptuses are lost and never come to the attention of any one, and that therefore the proportion of early specimens in this or any other collection is no doubt too small. Moreover, in quite a number of specimens of the first 1,000 accessions the chorionic vesicles were too degenerate for examination, and in others they were absent, but we have reason to believe that this is not true to the same extent in the material beyond the first 1 ,000 accessions. Then, too, since only a few relatively large sections from a single portion of the chorionic vesicles were examined, it is evident that some cases in which the degeneration may have been purely local probably were overlooked. Hence the actual incidence of hydatiform degeneration in this collection is probably not merely 8 times but 240 times as great as that givcMi by Williamson (1900), and 33.3 times as great as that given by Essen-Moller.  
the epithelium is not always two-layered, nor is it always thickened, in hydatiform
 
mole. That the epithelium can not always be active beyond the normal follows also
 
from the fact that the proliferative changes in it are subsecjuent to, even if not
 
necessarily conseciuent upon, changes in the stroma. Furthermore, like the latter
 
they are gradual in their evolution and may stop or be stopped at any stage of their
 
development. Then, too, the condition of the epithelium depends very largely upon
 
the preservation of the abortus, and this, as is well known, varies greatly. The
 
most striking thing about the epithelium usually is not its thickness, the; presence
 
of large masses of trophoblast, or of numerous syncytial buds, but its si)leiidid state
 
of preservation, especially as contrasted with that of the stroma. This is true of all
 
except macerated or degenerate specimens, for the hfe of the ei)ithelium seems
 
assured as long as there are periodic accessions of fresh blood, which, as the clinical
 
histories illustrate, usually is the case. The stroma, on the other hand, probably not
 
being wholly independent of the contained capillaries, is deprived verj^ largely of its
 
sustenance during, even if not in consequence of, their degeneration. According to
 
some, hydatiform degeneration of the stroma is the result of an accumulation of
 
nutritive j^roducts in consequence of the absence of the vessels. Degeneration of
 
stroma and vessels, however, may result from malnutrition due to poor implantation.  
 
  
The epithelium of the villi often was found single-layered without any syn-
 
cytium whatever, or with at most a few syncytial buds. Nevertheless, both the
 
syncytium and trophoblast very often show evidences of a marked activity which is
 
not confined to implanted vilh or to the epithelium of the villi as a whole, but wliich
 
may extend to that of the chorionic membrane as well. Sur])risingly long, com])lex
 
syncytial buds, whorls and festoons, as shown in figures 22, 23, and 24, and as said
 
to have been observed by Frankel, often are present, especially on the villi, although
 
in a few instances fine buds and frameworks of syncytium also were seen arising
 
from the epithelium of the chorionic membrane. This feature (shown in figure 23)
 
has, I believe, not been specially emphasized heretofore, though ol)served by
 
Clivio (1908).
 
  
Mounds formed by the Langhans layer were common, especially on the tips
+
Most persons will, I presume, be willing to regard an increase of 700 per cent above that of Williamson as possible, but one of 24,000 percent above Williamson, or even 3,333 per cent above that of Essen-Moller as wholly out of the question.  
of the viUi where they frequently formed irregular masses of small nodules — the
 
"appendici durate" of Crosti (1895). These gave the villous tree the appearance
 
of a leafless orange loaded with fruit, only that the trophoblastic nodules are mainly
 
apical, iis shown in figure 25. In several instances syncytial buds were found
 
far out on thc-sc; trophoblastic ma.s.ses, a fact wliich is of special, if not of crucial
 
significance in connection with the old (luestion of the origin of the syncytium, for
 
these buds undoubtedly had not been transported tluMc. But however one may
 
regard these things, such appearances as represented in figure 24 are unmistakable,  
 
for they show thickenings composed of Langhans cells aiul garlands of considerable
 
length, portions of which are composed of absolutely distinct cells of the Langhans
 
type, as well iis other portions composed of syncytium with e\erv gradation between the two. Nor do I believe that the assumption that syncytium can resolve itself
 
into indi^•iduaI cells can be used to deny the implication of these facts.  
 
  
Although hydatiform villi covered by a single layer of rather small cells of the
 
nature of Langhans cells, sometimes without visible cell boundaries, frequently
 
were seen, viUi covered by typical syncytium only never were seen. The single
 
layer present, although syncytial in places, suggested Langhans cells rather than
 
the real syncytium. IMoreover, since the cells of the Langhans layer usually were
 
smaller rather than larger than normal, it follows from this alone that their jiro-
 
liferation must have been marked, in order to completely cover the enlarged villus,
 
in spite of the fact that the layer remained single-celled. Were tliis not the case,
 
the extraordinary increase in size which accomi)anies the formation of large hydatid
 
cysts could not possibly occur without rupture of the covering layer.
 
  
Not infrequenth' proliferation of the epithelium without increase in thickness
+
Yet, strange as it may seem at first sight, this is not a random guess but an estimate based upon (hi; actual incidence of hydatiform degeneration as determined by a careful gross and microscopic examination of mounted and unmounted material from over 400 abortuses. However, I lay no special emphasis on these percentages, and am using them merely to emphasize the great frequency of hydatiform degeneration. It matters little whether we shall ultimately determine an incidence of 10 or 5 per cent, but it does matter considerably whether we regard the frequency as 5 or 0.05 per cent, for this is a diference of 10, 000 per cent.  
may manifest itself in another way. The cahber of the villi in the earUcr stages of  
 
hydatiform degeneration sometimes does not increase much, no thickening of the
 
proliferating ejjithelium is noticeable, and yet the latter shows marked proliferation.  
 
Under these circumstances, the borders of the vilU and of the chorionic epitheUum
 
may appear extraordinarily sinuous as illustrated in figure 26, and epithelial invagi-
 
nations from opposite sides rarely meet in the center, as indicated in figure 27, and
 
by fusion completely isolate a portion of the stroma. It usually is in these cases of
 
verj^ sinuous epithelium that the epithelial invaginations sometimes become con-
 
stricted, leaving a closed epithehal vesicle or a nodule of epithelium attached to a
 
stalk or wholly isolated within the stroma, as shown in figures 28 and 29. All
 
stages in this process of vesicle formation were found, and rarely also extensions of
 
epithelial sprouts as described by Neumann (1897) and others were seen, portions
 
of which had become isolated in the stroma to appear later as typical sync3i:ial
 
giant cells. These facts, too, would seem to throw a sidelight upon the origin of the
 
syncytium for those to whom this question is still an open one.  
 
  
All these tilings abundantly testify to the activity on the part of the epitheUum
 
in many hydatiform moles, even when thickening of it is absent, but they are of
 
diagnostic value only if present, and I wish to emphasize again that thej^ may be
 
wholly absent or at least unrecognizable in the earlj^ stages. Moreover, the degree
 
of epithehal prohferation varies greatly, as illustrated in figures 30, 31, and 32.
 
  
Until I am able to learn more about the structure of normal villi in various
+
In view of the prevailing opinion, I realize that these findings may seem incomprehensible and perhaps incredible, unless it is distinctly borne in mind that it is not stated that this incidence refers to the later months of pregnancy or to term. What the incidence in the later months of pregnancy may be I do not know, but I have called attention to an apparently well-founded belief that it is a relatively rare condition, the estimates ranging from 1 in 2,000 to 1 in 728 or 300 cases.  
stages of development, I am not willing to commit nwself regarding the incipient
 
changes in hydatiform degeneration. These may be unrecognizable with present
 
methods. However, it is possible to saj^ that in young conceptuses the disappear-
 
ance of the capillaries, which was regarded as a possible cause for the development
 
of hydatiform mole by Hewitt (1860 and 1861), and also emphasized later by Hahn
 
(1865), Maslowsky (1882), and bj^ others, undoubtedly is a very early and possibly
 
the very earliest noticeable change in some cases. Of course, I do not imply that  
 
death of the embryo is the cause of this disappearance, as Hewitt held, and I am not
 
ready to say that the vascular change is the very earliest one in all cases. This
 
would imply that hydatiform degeneration under no circumstances can begin before the capillaries have ai)i)carocl in the villi. Tlicrc is some cvidcMice which suggests
 
that it possibly may appear before this time. If so, it would be incorrect to si)eak
 
of a disajipearance of the vessels in such chorionic vesicles, for if the advent of hydat-  
 
iform degeneration can precede the appearance of the villous capillaries, vasculari-
 
zation of the villi ma.v never occur. In older conceptuses, however, in which vascu-
 
larization of the villi has sujiervened, the hrst recognizable change is the disappear-
 
ance of these capillaries. Many si)ecimens in which the latter were in \'arious
 
stages of degeneration were examined carefully, and the opinion of Hewitt (1860),
 
that hydatiform degeneration can not arise in villi which have been vascularized,  
 
can be regarded as of historical interest only. Different stages in the process of
 
vascular degeneration are represented in figures 33 to 35 inclusive.  
 
  
Coincident with the disappearance of the vessels, changes in the stroma also
 
are noticeable. Usually it tends to become glassy, the individual nuclei becoming
 
separated farther. The stroma, though apparently solid, is uniformly slightly
 
bluish and vitreous, with well-defined, rather small, pycnotic, pointed nuclei, but
 
with not a vestige of a vessel, though the epithelium is splendidly preserved. The
 
latter may be one-layered or two-layered, and may be accompanied by syncytial
 
buds and trophoblastic masses and nodules. In such specimens the entire picture
 
really is exquisite, and a mere glance through the comjiound microscope reveals
 
the lack of vessels in the vitreous stroma and the marked differences in size of the
 
sections of the villi.
 
  
After these early changes, licjuefaction of the stroma usually follows. As is
+
In regard to the incidence of hydatiform degeneration in uterine specimens, it should also be remembered that the life, in contrast to the laboratory incidence for the entire period of gestation is higher, not only because the chorionic vesicles were not included in many of the accessions and because others were too degenerate, but because I have not as yet been able to recognize the very earliest stages with entire certainty. Furthermore, many instances of hydatiform degeneration from the early months of pregnancy, especially the first and second, are inevitably lost. The increase due to these things would be offset somewhat, however, by the lower incidence of hydatiform degeneration in specimens from the last months of pregnancy, relatively few abortuses from these months being contained in the Mall Collection.  
well known, liquefaction generally begins in the interior and first appears in the
 
form of vacuolation; but this vacuolation (which I can not regard merely as an
 
edema) is not intra-cellular but intercellular, and as it becomes more pronounced
 
it really takes on the nature of fenestration. Hections of the whole cross-section
 
of the villi, even though large, may be composed of a series of fenestrse (see fig. 36)
 
separated by exceedingly fine strands of the remaining stroma which may contain
 
remnants of the nuclei. But finally, even the fine trabecular separating the fenes-
 
tras disappear, and the stage of the watery, old, hydatid condition has been reached.
 
More generally, however, the vacuoles or small fenestra' lying in the middle ])ecome
 
confiuent at the center of the cross-section of the villus, which then is licjuefied
 
completely. As is well known, this liquefaction gradually extends to the ijeriphery
 
as the zone of the surrounding stroma is narrowed in the process. Not infreciuently,
 
however, liquefaction of the stroma occurs quite generally throughout the cross-
 
section of the villus and is accompanied by the formation of numerous large cells,  
 
the wandering or migrating cells of earlier writers. A f(>w of these cells almost
 
always can be found, and rarely the whole section of the villus is studded with  
 
(fig. 37) or even formed by these large, erratic cells which usually lie in fenestra? in
 
the stroma. In other instances a large portion of the sections of the villi may be
 
occupied by them, as shown in figure 38. The presence of these cells in viUi regarded
 
as normal has long been known. Their presence in hydatiform moles was not(>d by
 
Otto, Marchand (1S9S), Essen-Miiller, and by many others. Tlieir occurrence in
 
normal and pathological chorionic vesicles, and their significance are considered more fully bj- Meyer (1919). No matter what the condition of the epitheUum, or
 
more specifically that of the Langhans lajer, the syncytium and trophoblast may
 
be, the above-noted changes in the stroma always are quite typical. They are not
 
the only changes noted, however, and their advent may differ somewhat.  
 
  
Not infrequentl}', changes quite comparable to those in the villi occur also in  
+
[[File:Meyer1920_fig16.jpg|thumb|Fig. 16.]]
the stroma of the chorionic membrane itself, a fact which has not heretofore
+
To what extent the material in this Collection is truly representative of actual life conditions is difficult, if not impossible, to determine. This question could be answered only if all the abortuses and material from abortions actually reached physicians, and if the latter sent all of them to the laboratory. My own impression so far is that the material representative of a sufficiently large community probably would have a somewhat lower incidence, notwithstanding the fact that many specimens not only of hydatiform degeneration, but of abortuses in general, especially from the first month of pregnancy, are lost. However, since the presence of hydatiform degeneration is especially common among early specimens, the inclusion of these might raise the incidence for the whole period of gestation more than the inclusion of all specimens (not excepting those of the last three months) would lower it. But the result obtained would represent the incidence of hydatiform degeneration in abortuses alone, and not that in all pregnancies. The latter could be obtained only by including all gestations which end normally. If we accept Pearson's (1897) estimate that approximately 40 per cent of all pregnancies end prematurely, then the incidence of hydatiform degeneration among abortuses would represent very nearly twice that in all pregnancies. Mall's estimate of 20 per cent prenatal mortality, on the other hand, would give us an incidence only one-fifth as great as that among abortuses. Hence, the actual life incidence of hydatiform degeneration in all gestations would then be 1 in 10, as based upon Pearson's, and 1 in 25. as based upon Mall's estimated prenatal mortality. But even if, as estimated upon this basis, 4 or 10 per cent of all conceptions end in hydatiform degeneration, this does not necessarily contradict the current opinion regarding its rareness at or near term.  
been emphasized. Also, it is frecjuently decidedly glassy; liquefaction may occur
 
here and there and may become complete in the course of time. Hofbauer cells
 
not uncommonly also are present. Among the changes noted in this membrane
 
the disappearance of the vessels is most common and constant, although epitheUal
 
proliferation is not rare, as already stated. Moreover, when (as in one of Storch's
 
cases) a hydatiform villus is 15 cm. long, one scarcely can doubt that the stroma
 
also must have proliferated — not merely degenerated. Some of the strings of  
 
hydatid cysts in a specimen in the Mall Collection have a length of over 10 to 12
 
cm., and in these cases also one can hardly assume that this increased length in  
 
the vilU was unaccompanied by prohferation of the stroma. From these things alone
 
it follows that the stroma can not remain passive always, although Gromadzki
 
(1913) concluded that the stroma never proliferates. Vecchi (1906), however,  
 
reported an increase in the stroma of the vilU, and it will be recalled that Marchand
 
also implied the presence of proliferative changes in the connective tissue when he
 
wrote that they depend on those in the epithelium.  
 
  
I have never been able to find mitotic figures, a fact which ma}^ be accounted
 
for, however, by the presence of degenerative changes due to intrauterine separa-
 
tion and retention of most specimens. Indeed, the failure to find mitoses speaks
 
against proliferation in the stroma no more than in case of the epitheUum, in which
 
the presence of karyokinetic figures has been reported by a few investigators only.
 
Yet pronounced proliferation of the epitheUum often is present. The failure to
 
find mitotic figures is very Ukely due to the condition of the material.
 
  
Careful scrutiny of a large series of specimens has revealed the fact that the
+
A careful examination witli the binocular microscope of all specimens has shown that hydatiform degeneration as a rule is sufficiently general even in young vesicles, so that sections of a single portion about 10 mm. square, would enable one to make a fairly reliable diagnosis. Now and then, however, the process seems to be rather irregularly developed, especially in the larger specimens.  
disappearance of the vessels in the vilU, in the chorionic membrane, and also in the
 
umbiUcal cord is centripetal as a rule. However, in many specimens the vessels
 
not only may be present in the chorionic membrane although absent in the villi,  
 
but may be very numerous and even engorged with blood. It is difficult to say to
 
what extent the engorged condition of these vessels and of those in the body of the
 
abnormal embryos sometimes contained in these hydatiform moles is due to the
 
propulsion of the embryonic blood before the advancing vascular constriction and
 
degeneration, but I am inclined to beUeve that the centripetal movement of the
 
process is not a negligible factor.  
 
  
Although only a few instances of the birth of a living fetus or of a fetus wliich
 
had reached the later months of pregnancy are recorded in the Uterature, it now
 
is quite generaUy recognized that the fetus, though dead and too smaU for its
 
menstrual age, usually is present. This stands in contradiction to the earlier beUef
 
iUustrated by the statement of Gierse (1847), that the fetus usually was reported as
 
absent, and that when present (as in the cases of Meckel, Gregorini, Otto, Cruveilhier, and his own) it usually was less tluui 1 inch lonjj;, oven when retained for a period of
 
from 3 to 10 months.
 
  
This apparent contradiction regarding the presence of the fetus in hydatiforin
+
In order to determine accurately the question of distribution of hydatiform degeneration over various portions of the chorionic vesicle, it will be necessary to examine a series of sections of portions of the chorionic vesicle for each small specimen. This has not yet been done, but since the portions used for microscopic examination had been taken at random without previous knowledge of the existence of hydatiform degeneration in any but the 8 specimens above described, and since a series of 453 vesicles was examined, I can not believe that it can often be limited to any particular area on relatively young vesicles. In these it usually is universal even if not complete. It is of special interest in this connection that Muggia (1915), after reviewing the small list of cases of alleged hydatiform degeneration of the chorion laeve in connection with a study of a case of his own, came to the conclusion that these cases are not really degenerations of the chorion laeve, but merely partial degenerations of the placenta. Although I have given no thorough attention to the normal changes in the chorion laeve, I am (quite certain that they are not the cause of confusion in the series of hydatiform degenerations from the Mall Collection. Cases in which whole chorionic vesicles exclusively hydatiform in character were contained in the tubes, and a number of others which still were implanted within the uteri showed equally exquisite hydatiform changes around the whole perimeter. Such cases as these ultimately confirm the oi)inion that in young vesicles as a rule the condition is general except at its very inception. This is true particularly by the time the degeneration has reached a stage which can be considered at all typical in its gross development, as determined by careful examination of numerous specimens with the binocular.
moles is explained easily by the fact that the cases in the earlier Uterature are old,  
 
far advanced in degeneration, while the more recent literature contains manj^ more
 
in the earlier stages of degeneration. Yet in spite of this fact the earlier opinion
 
survives to the i«-escnt day, for Graves (1909-10) spoke of "the very unusual
 
presence of a normal fetus inside a mole," and Vineberg (1911) still more strangely
 
held that the presence of a fetus excludes the specimen from the class of true hj'dati-
 
form moles!
 
  
Among the specimens concerned in this report many contained a fetus. Tliis
+
[[File:Meyer1920_fig17.jpg|thumb|Fig. 17.]]
was true of 24.5 per cent of 49 tubal and 64.4 per cent of 121 uterine specimens,  
+
It is especially interesting that, just as soon as syncitial hydatitl elliptical villi, or portions of the same begin to appear, the condition can be recognized with some certainty under a magnification of 12 to 20 diameters with the binocular microscope. It often was surprising how relatively early stages could thus be detected and the diagnosis confirmed later by histologic examination. Indeed, Colloidin blocks of tissue from which sections had been cut gave splendid testimony when examined in Huid with the binocular. One of the not very early stages contained in utero and represented in figure 10 could be recognized with the unaided eye; and when examined with the binocular, under a magnification of about 12 diameters, the picture was unusually fine and wholly unmistakable, as shown in figure 17.  
including some (9) doubtful cases. In some earlj' specimens the fetus is in a state
 
of excell(>nt jjreservation. This is what one might expect, for the on.set of hydati-
 
form degeneration is gradual and often partial. The condition of the fetus in many
 
of them alone also suggests that its death was secondary to the degeneration.  
 
  
The fetal length ranges from 1 to 90 mm. in the uterine and from 1 to 80 mm.
 
in the tubal series. Although the average length of the embryo in the tubal series
 
is 12.3 mm., and that of the uterine only 10.1 mm., 58 per cent of the tuljal speci-
 
mens nevertheless were below 7 mm. in length as contrasted with 52.5 per cent of
 
the uterine.
 
  
The presence of a fetus with a frequency almost three times as great in the  
+
That hydatiform degeneration is incomparably more common in the earlier than in the later months of pregnancy, thus justifying the comparison made with measles, is substantiated by statistics covering the material examined. From these it is evident that, excepting cases of large hydatiform masses originally classed as hydatiform degeneration from inspection of the gross specimens alone, practically all the specimens are relatively young. This is true especially of those from tubal pregnancies, and we may hence regard it as established that hydatiform degeneration is a change which is exceedingly common in the earlier months of pregnancy, just as measles is common in childhood, and that it becomes progres.sively less common as the end of pregnancy is approached, just as does measles as senility is approached. The obstetrician does not see most of the cases of hydatiform degeneration, for they merely are reported as miscarriages and the specimens often are destroyed or retained unrecognized by the general practitioner or the midwife. They often are aborted spontaneously and completely with the decidua and rarely are still contained in a closed decidual cast when they reach the laboratory.  
uterine series again indicates that the abnormal conditions within the tubes lead
 
to early death, digestion, and absorption, or at least to dissolution, of the embryo.  
 
This fact again points directly to a faulty nidus as causative agent, for if the absence
 
of a fetus is to be laid to primary ovular defects, then one must admit that relatively
 
far more of such diseased ova become implanted within the tube than within the  
 
uterus.  
 
  
Of the many explanations which have been offered for the advent of hydati-
 
form degeneration, none seems to be better established than that of endometritis.
 
Tliis was first emphasized by Virchow (1863), and Lwow (1892) also reported 4
 
cases in i)atients under liis care in whom lues could be excluded l^ut in whom he
 
held endometritis responsible. Emanuel (1895) was the first, it seems, to demon-
 
strate the presence of cocci in inflammatory foci of round cells in the decidua
 
accompanying a case of hydatiform mole. Veit (1899) also believed that disease
 
of the decidua is the cause of hydatiform degeneration. Veit further stated that
 
W'aldeyer, Jarotzky, and Storch also believed that an irritative condition of the
 
decidua is responsible. Stoffel (1905) also found cocci other than gonococci present
 
and says he can not avoid holding endometritis resi)oiisible in hi.s ca.se. The asso-
 
ciation of hydatiform degeneration and endometritis was noted also l)y INIarchand
 
(1895), Oster (1904), and Sternberg; also by Essen-Mollor, who reported the phe-
 
nomenal case of a woman with endometritis, who had aborted a hydatiform mole
 
18 times in 9 years. Falgf)wski, on the contrary, concluded that the ova themselves
 
were diseased and argued that hydatiform degeneration should be much more common if it were due to endometritis. Taussig (1911) also stated that leucocytic
 
infiltration of the decidua is frequently present in hydatiform moles, but iasistcd
 
that "leucocytic infiltration in the placenta then should not be interpreted as
 
infection. * * * Inflammation and infection should be kept apart." I presume
 
Taussig really meant infiltration and infection should be kept apart, and the ques-
 
tion then turns upon the structure of the normal decidua and the significance of
 
infiltration for the development of the ovum.
 
  
It may be recalled that Marchand (1904) reported the presence of isolated
+
The spontaneity of the abortion, especially in early cases, was emphasized also by Storch in the above quotation. Cortiguera (1906) is reported by Pazzi (1908) also to have declared that many moles disappear wholly without leaving a remnant, even if occurring repeatedly in the same woman, and Donskoj also stated that many of those aborted do not come to the attention of physicians because of their harmlessness. This, however, does not imply that those which persist and develop into large masses are equally harmless, and it must be remembered that it is upon these that the current opinion regarding the tendencies to malignancy of the hydatiform mole is based.  
groups of small cells in the normal decidua wliich looked hke mononuclears under
 
low magnification, and which he beUeved often have been confused with them.
 
But even granting this, and the further facts that the exact histologic changes in  
 
the decidua are not fully known, and that it is rather difficult to ascertain just what
 
decidual changes are regarded as evidence of the existence of an endometritis, any
 
one examining a large series of cases of hj'datiform degeneration aborted ^^•ith the
 
decidua can not doubt the presence of marked decidual changes in a very large
 
percentage of them. These changes are not hmited to infiltration with scattered
 
round cells or erythrocytes, or to focal accumulation of the same, but often extend
 
to almost complete fibrosis, as shown in figure 39, so that experienced investigators
 
have mistaken the thin, fibrous decidua for a part of the chorionic membrane.  
 
  
It is true that the existence of these changes in the deciduae themselves does
 
not necessarily imply that they were antecedent to the implantation of the ovum,
 
but fortunatch' the clinical histories and material from curettage often supply
 
crucial evidence. From such cases and from the cumulative weight of evidence
 
from the large series of cases here reported, the great majority of which showed
 
decidual infiltration or other changes suggestive of endometritis, the frequent
 
association of abnormal deciduae with hydatiform degenerations is evident. The
 
fact that the incidence of hj^datiform degeneration in the tubal was somewhat higher
 
than that in the uterine series might be regarded as contradicting this relationship,
 
but such is not the case. The mucosa of the tubes at best is an unfavorable nidus
 
for implantation because of the absence of decidual formation alone. Hence, even
 
if salpingitis were somewhat less frequent than endometritis, proper nidification in
 
the tube could easily more than account for the existing differences. Hence the
 
higher incidence of hydatiform degeneration in the tubal series in fact becomes
 
confirmatory of the conclusion that abnormal nidification really may be responsible
 
for the advent of hydatiform degeneration.
 
  
The only fact wliich might be interpreted as indicating that germinal defects
+
The conclusion regarding the greater incidence of hydatiform degeneration in the early months of pregnancy is conclusively confirmed by the occurrence of 32 of the 48 tubal specimens within the first two classes of the pathologic division of Mall, and 104 of the 112 uterine specimens in the first six classes of this division. Most of the specimens in these classes are composed of villi, of empty chorionic vesicles, or of vesicles with embryos most of which have a length of less than 20 to 30 mm. That hydatiform degeneration is more common in the early months of pregnancy is indicated also by the well-known reports of Kehrer (1894) on 50 cases, and of Borland and Gerson (1896), who found that 63 per cent of 100 cases had aborted in the fourth and fifth months of pregnancy. According to Seitz, Hirtzman (1874) also found that 62.8 per cent of 35 cases had aborted between the third and sixth month. Only 4 per cent of Kehrer's 50 cases and only 3 per cent of the cases of Borland and Gerson aborted at the tenth month. Bonskoj stated that 7 of the 10 cases reported by him aborted in the fourth month and none after the sixth month. He stated further that 56 per cent of Bloch's 50 cases aborted before the sixth month, 44 per cent later than this, one being retained until the fourteenth month. The latter case is especially interesting because retention not only beyond term but after the death of the mole seems to be regarded as relatively rare. This, however, does not imply that retention beyond the period of growth of the hydatid mole does not occur, although Sternberg (1910), who also emphasized the great rarity of this condition, erroneously stated that the (Jerman literature reveals only a single instance of missed abortion in case of hydatiform mole, viz., that of Poten (1901). In this case a hydatiform mole of the size of a duck egg; was said to have been aborted approximately one month beyond term. Hence growth must have ceased long before and the mole have remained in ulcro as a "harmless body." To this case of Poten, Sternberg adds a case in which a hydatiform mole of 14X9.6 X4.3 mm. was aborted in the twelfth month after the cessation of menstruation. Although Sternberg included 4 cases from other countries among these missed- abortion moles, inz., those of Shell (undated), Ferguson (also undated), Colorni (190S), and Gaifani (1908), one can hardly doubt that more cases could be added. Since the case of Shell was one of twin pregnancy in which one conceptus became hydatiform, it is not at all unlikely that some other cases among this rather small series of twin pregnancies accompanied by hydatiform degeneration may belong in this category.  
primarily are responsible for the development of hydatiform degeneration is the  
 
relatively higher incidence of the condition in older women. Against this, however,  
 
stands the other fact that such women also show the cumulative effects upon the  
 
endometrium of age, endometritis and pregnane}'. Furthermore, since hydatiform  
 
degeneration so often follows one or two normal births or abortions, it would be
 
impossible to find an adequate explanation for the release of the defective ova so
 
often after and not before these events.  
 
  
I am reminded also in this connection of a case the detailed history of which
 
is fully known. It is that of a robust young woman who successively gave birth to two moles and then to a normal full-term cliilcl and sccundincs. In this case
 
curettage was done in connection with each mole. Apparently the new endo-
 
metrium, which had formed after the second abortion and curettage, permitted
 
normal implantation and normal development to ])rogre8s to term. To ignore the
 
condition of the endometrium in tliis case and attribute the develojmient of hydati-
 
form degeneration to the successive release of abnormal ova would seem to cUs-
 
regard important facts — especially so since no one has estabU.shed the occurrence
 
of abnormal ova within the Graafian foUicle, a possibility which I do not wish to
 
deny, although Donskoj 's report of a case of hereditary mole must surely be taken
 
cum (jrano salis.
 
  
That an abnormal nidus may be responsible for the advent of hydatiform
+
Mayer also emphasized the fact that, although instances of retention of fetuses are very common, instances of retention of hydatiform mole are very rare, only a few cases having been recorded. Mayer refers to 2 cases by Kehrer, 3 of Borland and Gerson, and to 1 case of Lange, and reports 4 of his own. These 4 were found among 10 cases of hydatiform mole, an incidence of retention of 40 per cent. They are interesting, especially in connection with the observation of Briggs that, contrary to current belief, uterine enlargement often is not beyond the normal. Mayer says that this enlargement was too great in but 1 of the 4 cases, and that retention lasted as long as 4 to 5 months.  
degeneration would seem to be indicated also by the fact that the i:)rocess usually
 
was better developed and more general in the tubal than in the uterine cases. That
 
both endometrium and decidua show astonishing differences in structure under
 
pathological conditions is well known. The entire tubal mucosa, on the other hand,  
 
even when normal, forms an abnormal nidus which would affect all portions of early
 
chorionic vesicles somewhat alike, and since, as found by Mall, inflammatory
 
conditions in the tubes predispose to tubal imjilantation, the higher incidence of  
 
hydatiform degeneration in the tubes is easily explained. Nor does the existence
 
of partial hydatiform degeneration argue against such an explanation.  
 
  
Although Kehrer reported not a single fatality in 50 cases of hydatiform mole,
 
Hirtzman (according to von Winckel) gave the fataUty as 13 per cent, Borland and
 
Gerson as 18, and ^^'illiamson as 20 to 30 per cent. Von Winckel (1904) regarded
 
these i)ercentages as entirely too high, however, although Oster reported 2 cases of
 
malignancy out of 15 among cases in which the late results were ascertainable —
 
an incidence of 13.3 per cent. Kroemer (1907) found that chorio-epithelioma
 
developed in 5 out of 15 cases of hydatiform moles, or in 33.3 per cent, but only
 
twice in 3,841 "normal implantations." Daels (1908) says La Torre claimed a
 
malignancy of 64 per cent; de 8enarcleus one of 28.7 per cent, or 14 out of 49 cases.
 
Frjienkel (1910) emphasized that the estimates of the number of cases in wliich
 
hydatiform degeneration is followed by malignant disease vary greatly, while
 
Robertson (1915) quoted Findley as finding that IG per cent of 250 hydatiform
 
moles collected from the literature were followed by malignant disease. Briggs,
 
who reported 21 cases of hydatiform degeneration with 2 of chorio-epithelioma or
 
an incidence of malignancy of 9.5 per cent, called attention to the "diminishing
 
ratio in the; tendency to malignancy shown by his series."
 
  
Findley stated that ch()rio-e])ithehoma develoiH'd in 131 out of 500 cases  
+
At least 3 of the cases of hydatiform mole originally recorded as such in the Mall Collection belong among retained specimens, as the illustrations alone suggest. But a fair percentage of detached chorionic vesicles included in the list of cases here reported undoubtedly also was retained after the cessation of growth, and it is for this reason that I further emphasize the fact that the uterine volume in a considerable percentage of these cases also, instead of having been too great for the duration of the pregnancy unquestionably was too small. This is well illustrated by the histories of specimens Nos. 70, 323, 1G40 and 1926, and by the specimens themselves.  
gathered by him from the literature, which is an incidence of 26.2 per cent; but, as
 
already stated, most of these cases from the hterature are old, advanced degen-
 
erations, many of which have been retained for a long time. The tendency to
 
malignancy in these probably can in no way be compared to that in smaller and
 
younger specimens, many of which are aborted entire with the surrounding decidua.  
 
Con.sefjuentlj', it need not surpri.sc us that out of 19 cases of this .series, in which
 
later reports were obtainable, none were reported as having developed chorio-
 
epithelioma.  
 
  
  
Perhaps I may here add a word of caution, however, in regard to a possible
+
The average menstrual age of 51 of 112 uterine specimens of this series of hydatiform degeneration — in which the data were available — was 66.6 days, or 2\ months. As will be seen, this is a far lower average age than heretofore reported, a difference which explains itself from what has been said already. It is interesting that the average menstrual age of 5 of the 8 specimens in the Mall Collection originally classed as hydatiform degenerations is 168.2 days, or 2.^, times as great, thus being in substantial agreement with the usual results. Three of these 5 are large specimens, the fourth measures 40X20X15 mm., and the other is composed of small fragments contained in material from curettage. From this alone it follows that the menstrual age is a very uncertain guide, especially as to the size of a hydatiform mole.  
change in attitude toward the question of malignancy with a consequent relaxation
 
of vigilance. It is true that out of the 21 cases of Briggs only 2 developed chorio-
 
epithelioma, but it must not be forgotten that Briggs in part was, and I to a far  
 
larger extent, am dealing with a different class of hydatiform moles than those
 
upon a study of which the prevailing conception of malignancy is ba.sed. Hydati-
 
form moles wliich continue to grow and which survive for months after the death
 
of the embryo evidently are more vigorous, and hence no doubt also more dangerous
 
than those which are aborted early and spontaneously. Since the latter formed the
 
great majority of all moles here considered, opinions regarding malignancy formed on
 
this basis probably would lead to disaster if apphed in practice. Such conceptions
 
would be based upon a totally different incidence than the current one of 1 hj^dat-
 
iform mole in every 2,000 cases. Instead of relaxing our vigilance it would seem
 
wise to increase it, particularly in the cases of so-called spontaneous abortions —
 
the cases in which no ascertainable cause for the termination of [jregnancy can
 
be found, especially if the chorionic vesicle is empty or if the embr^^o belongs in
 
one of the early groups of Mall's classification.  
 
  
The average age of 36 women aborting hydatiform moles was 31 j-ears.  
+
[[File:Meyer1920_fig18.jpg|thumb|Fig. 18.]]
Although I do not regard the alleged ages as necessarily^ the actual ones, this average
+
[[File:Meyer1920_fig19.jpg|thumb|Fig. 19.]]
age agrees very well with that of 6 cases reported by Poten, 10 by Donskoj, 23 by
+
[[File:Meyer1920_fig20.jpg|thumb|Fig. 20.]]
Briggs, 6 by Gromadski, and 8 by Robertson. The average age of Poten's cases
+
It seems superfluous to add any tiling to the good description of the gross appearance of the typical h3'datiform mole currently reported in the literature. Such cases are so characteristic that even a novice can recognize them at sight. Yet if the findings reported here are reliable, or even approximately so, it nevertheless must be evident that, in the past, the great majority of specimens of true hydatiform mole have remained unrecognized merely because they did not happen to present the customary, well-known picture to ike unaided eye. Small chorionic vesicles, such as No. 2077 shown in natural size in figure 18, which attract no attention upon cursory inspection may, and often do, present the most exquisite picture of hydatiform degeneration when seen under a magnification of 3 to 20 diameters, as illustrated in figure 19. This is true especially if the examination is made with the binocular microscope. Since I have adopted this method of examination it has been possible to recognize instances of decidedly general and typical hydatiform degeneration in chorionic vesicles less than 2 cm. in size, with later confirmation of the diagnosis by a histologic examination. However, I have not been able to recognize very early stages merely by examination of the gross specimens, for gross recognition is possible only when portions of at least some of the villi have become sufficiently elliptical or globular to attract attention. Histologic recognition is possible far earlier than this, as shown in figure 20.  
was 32 years, of Donskoj 's 25 j-ears, of Briggs's 28 j-ears, of Gromadski's 29.6 years,
 
and of Robertson's 28.4 years. Pazzi (1908'') , on the other hand, stated that Briquel
 
placed the greatest frequency of hj^datiform degeneration between 20 and 30 years.  
 
These averages are so far on the near side of the menopause that one can make
 
liberal allowances for the proverbial disinclination of women to state their exact
 
age, even to physicians, and nevertheless regard the prevailing opinion undoubtedly
 
as ill-founded. If, as Le\\is (1906) stated, it is necessary to add onh^ half a year to
 
the average age of a large group of women in order to ascertain the actual average
 
age when considering general social statistics, then everyone will admit that stiU
 
less allowance than this need be made in the case of women who are speaking to  
 
their physicians, knowing that whatever they may say will be regarded as strictly
 
confidential. That it is unncessary to make large allowances for under-statement
 
of their age on the part of these women is indicated also bj' the average duration of  
 
their married life before aborting moles. This in the case of 29 women was 7.1
 
j'-ears. Hence, if one bears in mind that the average age of first marriages according
 
to Webb (1911) is 25.1 years, one can easily see that the average age of the women
 
aborting hydatiform moles, which was given as 29.6 years, is probably not too low
 
at all, thus confirming the findings of Williamson, who denied that hydatiform mole
 
was especially common near the menopause.  
 
  
The conclusion that the average age of 29.6 years undoubtedly is near the  
+
[[File:Meyer1920_fig21.jpg|thumb|Fig. 21.]]
actual is confirmed also by the fact that a hydatiform mole was the first abortion
+
The general appearance of the whole chorionic vesicle sometimes is an aid in gross identification, for the villi not infrequently are smooth, slightly branched, and unusually long, so that the vesicle looks shaggy, as illustrated in figure 21. The typical gross, hydatid or watery, translucent nature of the vilU can not be relied upon in early stages, for normally shaped villi, which have undergone considerable lysis, may be almost transparent and also somewhat more than normally bulbous. However, save in the case of some specimens of tubal pregnancy, the swelling of the villi, due to maceration or to luetic changes, is quite different in character from that characteristic of hydatiform degeneration, and usually quite easily distinguishable from it. Judging from several specimens of villi which were macerated in distilled water during a period of weeks, post partum maceration never could cause confusion and the same thing undoubtedly is true of intra-uterine maceration.  
in 19 out of 41 women, or almost hah the niunber; 12, or almost one-third, had
 
aborted twice, and only 10 had aborted more than twice. But what is still more confirmatory is the existence of a surprising parallelism between the data on abor-
 
tion and those on births; 9 of 33 women had given birth to but 1 child, and an eriual
 
number had given birth to but 2. Hence over 50 per cent of the 33 women had
 
borne children twice, or less than twice, and only 15, or less than half, had borne
 
oftener than this.  
 
  
This undoubted evidence of the youth of these women is confirmed still further
 
by the statement of Lewis who, from an analysis of 16,325 first births, found that
 
nearly one-half of them occur between the ages of 20 and 24, almost three-fourths
 
between 20 and 29 years, and that first births are more frequent between 30 and 40
 
than between 15 and 19 years. I realize, to be sure, that social statistics can not
 
be translated from one country to another without mocUfication, but in such a
 
mixed population as ours this modification probably need be less (rather than
 
greater) than in case of some countries.
 
  
The conclusion that the occurrence of but a single birth before the advent of
+
Since numerous trophoblastic nodules are present also in other conditions, notably in retained placentae as found by Aschoff and others. I have not been able to regard their presence in unusual numbers, in some cases of hydatiform degeneration, as of crucial value, but the absence of placental differentiation at a time when it should be present, with a uniform and unusual development of the villi over the whole exterior of relatively large chorionic vesicles, is decidedly significant and has often been found to imply the presence of hydatiform degeneration. The same thing is true of a very irregular distribution of the villi, or of uniformly distributed fusiform enlargements on the villi and of the loss of the dull appearance of their cut surfaces, as seen under the binocular. As soon as the stroma becomes hydatiform, and even before liquefaction is present, the cut surfaces of hydatiform villi look somewhat shiny and waxy or, perhaps better still, parafiine-like, as in the specimen in situ shown in figure 21. A bluish tinge always is present, and this appearance is very characteristic. However, how easily a specimen of hydatiform mole can be recognized by examination with the binocular alone necessarily will depend also upon the condition of the specimen. If the villi are matted, glued, or macerated, not only the early hydatiform changes but even fairly advanced ones often are masked so completely that recognition is difficult or impossibie without histologic examination.  
hydatiform degeneration probably impUes that such women are relatively young
 
is emphasized still further by the statement of Lewis that in one-third of the mar-
 
riages in Scotland "the bride had a child when unmarried or was pregnant at the
 
time of marriage," and that 50 per cent of the first births in Scotland occur within
 
9 to 24 months after marriage. Lewis also gives the average intcr^•al between
 
marriage and the first birth in 16,176 first births as 13.54 months, but little more
 
than one year. Since Lewis stated that the interval between the birth of the first
 
and that of the second child is but little longer than that between marriage and the  
 
birth of the first child, being only 3.07 years, it is evident that not even those women
 
who had borne two children before the advent of hydatiform degeneration could
 
have been near the menopause. This conclusion is emphasized still further by the  
 
fact that in 96.12 per cent of 16,176 fruitful marriages fertility was demonstrated
 
within three years after marriage.  
 
  
Nevertheless, in spite of the clear implication of all these facts, I wish to empha-
 
size again that since what have been heretofore regarded as hydatiform degenera-
 
tions were large specimens mainly, it well may be, and according to certain authors
 
it is true, that such cases occur later in the reproductive life of women. Yet it
 
certainly is significant that Findley in tabulating 500 of such cases from the litera-
 
ture found that 275, or 55 per cent, occurred before the thirty-fifth year, and of 36
 
specimens from the Mall Collection 23, or 63.6 per cent, came from women below
 
this age. It may also be recalled that 78 per cent of Kehrer's 50 cases and 90 per
 
cent of Bloch's occurred before the fourth decade.
 
  
Fourteen out of 23 cases, or 61.3 per cent of the uterine series, in which the age
+
In many early specimens the diagnosis could be made at sight from a histologic preparation under low magnification, even when it was impossible to make a diagnosis by examination with the binocular microscope alone. What makes this possible is not, as has been generally assumed since Marchand's epochal work on chorio-epithlioma, the ajipearance of the syncytium or that of the Langhans layer or of the trophoblast, but the changes in the stroma which precede those in the epithelium. The evidence in regard to this matter is overwhelming, and in the early stages when the stroma already has been altered, it often is impossible to tell whether the epithehal development is normally or abnormally active. Moreover, in spite of Marchant's statement to the contrary, extremely large cysts often have but a single smooth layer of epithelium. This has been asserted repeatedly by other investigators also. The two layers of epithelium are not by any means always present and, while there is no agreement in the matter, the opinion seems to be that the grade of epithelial proliferation can not be used as a criterion for the deter- mination of the presence of hydatiform degeneration. Menu said that the presence of marked epithelial proliferation was emphasized early by Miiller (1847), Ercolani (1876), Franque (1896), and Owry (1897); and according to Pazzi (1908), Ercolani and Polano altogether denied the existence of connective tissue in the hydatiform mole. The same thing was asserted by Sfameni (1903), who claimed to have found further evidence of the exclusively epithelial nature of the hydatiform mole in 1905. According to Sfameni the hydatiform mole does not result from a modification of existing chorionic villi, but from an entirely new growth which is wholly epithehal in character! But this opinion, which was accepted also by Niosi (1906), seems to exist among Italian writers only.  
was given, occurred at or before the thirtieth year, and 18 out of 23, or approxi-
 
mately 80 per cent, at or before the thirty-fifth year. These things abundantly
 
emphasize the conclusion reached by some investigators that hydatiform mole is
 
not absolutely more common at or near the menopause. But it nevertheless may be
 
relatively more common. That is, the number of hydatiform moles aborted after
 
40 com.pared with the total number of pregnancies or births after 40, actually may
 
be greater than this ratio before 40 years.  
 
  
  
 +
Although Durante (1898) represented extremely long syncytial buds, he nevertheless found (1909) epithelial proliferation present only where certain vascular changes were present. Winter (1907) stated that the condition of the epithelium varies greatly, and Falgowski (1911) emphasized that he could not demonstrate the presence of an increased epithelial proliferation or of vacuolation of the syncytium. Aman (1916) also found that epithelial proliferation may be wholly absent. Ballantyne (1913), on the contrary, found epithelial proliferation "so well developed that it suggested that it is an essential process in the formation of the mole." liallantyne further likened hydatiform degeneration to edematous growths and emphasized that both really are epithelial new growths. This opinion is accepted also by de Hnoo (1914), who regarded the hydatiform mole as a neoplasm of the trophoblast with secondary changes in the stroma.
  
HYDATIFORM DEGENERATION IN TUBAL AND UTERINE PREGNANCY. 361
 
  
From calculations based on data given by Lewis the average number of births
+
There is no agreement at present as to whether the epithelial changes are primary or secondary. As is well known, Marchand (1895) — und Miiller, l*]rco!aiii, and Langhans long before that — regarded the epithelial changes as primary, but most investigators seem to have come to the opposite conclusion. Some share the opinion of Schrocder that hydatiform degeneration points to a stimuhis resulting in hypoplasia of the entire chorionic villus. Nor is there agreement as to what the initial changes are. Durante (1909) regarded the presence of vessels with an imperfect endothelial lining and with thick infiltrated walls as the initial lesion in hydatiform degeneration. These changes were noted by him, especially in trunk villi, and epithelial proliferation was most evident where the vascular lesions were most pronounced. Durante further stated that the chain form of the hydatids is due to the fact that the vascular lesions occur at intervals along the villus. Unfortunately, the structure of long hydatiform villi does not confirm such an explanation nor Durante's conclusion that the hydatid cavities within the viUi result from dilatation of the capillaries. Many investigators report the early disappearance of the blood-vessels, a phenomenon which some regard as secondary and others as primary to the death of the embryo.  
occurring after 40 years in Sweden, Norway, Denmark, Brunswick, Berlin, Buda
 
Pesth, France, and Scotland is 9.9 per cent. This agrees remarkably well with
 
Bloch's estimate of 10 per cent. But if 77.2 per cent of the cases of hydatiform  
 
mole occur below 40, and 22.8 per cent after that year, then it is evident that  
 
hydatiform mole nevertheless is relatively more common after than before 40
 
years, for approximately one-fourth of the cases of hydatiform degeneration would
 
be associated with one-tenth of the births. This would be an increased frequency
 
of 300 per cent above that before 40 years. A similar result would be obtained
 
by comparing Findley's or Williamson's series. Hence, hydatiform degeneration
 
though absolutely loss is relatively more frequent in later Ufe. This fact, however,
 
does not necessarily imply that age in itself is responsible for the increased incidence
 
after 40. A comparison of the incidences of hydatiform degeneration in young and  
 
old primiparse, of good health, might elucidate this question.  
 
  
These statistics are not in agreement with the prevailing opinion that hydati-
 
form moles are more common in multipara; than in primiparfe. Indeed, as I under-
 
stand, they suggest rather that after the first conception, which was normal in a
 
large percentage of these young women, something happened which interfered with
 
the normal development of succeeding conceptions. That, it seems to me, is
 
extremely significant and very suggestive. Here is a group of relatively young
 
women, over 50 per cent of whom had borne but twice and some only once, and then
 
gave birth to a hydatiform mole. Wliile I reahze the necessitj^ for circumspection,
 
especially in these matters, these facts seem to me to suggest that something hap-
 
pened to a normal endometrium. Other facts also point in the same direction.
 
  
Even if it is not wholly correct, as Findley states, that more cases of hydatiform  
+
In the course of this investigation a villus with a normal stroma and normal vascularization never was found to have undergone true hydatiform degeneration, but one with a normally active epithelium — both Langhans layer and syncytium — often was truly hydatiform. That is, it not only was watery in appearance, but also fusiform or globular even in external form. In fact, Marchand (1895) himself found that "Das Epithel welches die Zotten und ihre Anschwellungen bekleidet zeigt ein sehr verschiedenes Verhalten." Yet even to-day, the feeling on the part of many seems to be that unless a marked hyperplasia of the Langhans layer and of the syncytium is present the condition is not one of hydatiform mole. This position seems to me to be untenable for, as Marchand himself said, the change in epithelium usually is least in the young viUi, and he should have added it is unrecognizable in the early stages and in young conceptuses. A perusal of the literature descriptive of the actual cases leaves little doubt upon this point, and a careful study of the advent of the earliest recognizable changes in hydatiform mole is absolutely convincing. The earliest recognizable, even if not the incipient, changes occur in the stroma and in the vessels — and not in the epithelium. In passing, it may be noted that although Marchand stated that the change in the epithelium is primary, he nevertheless somewhat contradictorily added that the most important fact is the degenerative change in the stroma of the villi.  
mole were reported in the last decade than in the previous 14 centuries, it is not
 
unhkely that approximately as many specimens of this condition are contained in  
 
the Mall Collection as have been reported heretofore. Moreover, upon the basis
 
of the present rate of accession, a large number of formerly unrecognized cases of  
 
hydatiform moles both tubal and uterine — are donated to this collection annually.  
 
This fact, together with others to wliich attention has been called, ought to stimulate
 
our interest in this problem.  
 
  
  
==BIBLIOGRAPHY==
+
Although not applicable to what I have come to regard as the incipient changes in hydatiform degeneration, it nevertheless is true that the stroma often, if not always, quite early becomes hydatiform — that is, glassy or clear, though not necessarily watery. Moreover, the villous vessels often degenerate or disappear completely at a very early stage. It is exceedingly difficult to make any definite statement as to what is typical regarding the epiithelium. This has been said by others also. Indeed, this necessarily foUows from the fact agreed to by every one, that histologically there is no true line of demarcation between the ordinary benign hydatiform mole, the so-called destructive benign (?) hydatiform mole — whatever its status may be — and the malignant hydatiform mole, or chorio-epitheUoma. Such a conclusion alone presupposes the existence of the widest differences in the condition of the t'pitlu'lium in the these cases, and that such differences actually exist is beyond question.
  
  
 +
Marchand's revolutionary investigation on chorio-epithelioma notwithstanding, the epithelium is not always two-layered, nor is it always thickened, in hydatiform mole. That the epithelium can not always be active beyond the normal follows also from the fact that the proliferative changes in it are subsequent to, even if not necessarily conseciuent upon, changes in the stroma. Furthermore, like the latter they are gradual in their evolution and may stop or be stopped at any stage of their development. Then, too, the condition of the epithelium depends very largely upon the preservation of the abortus, and this, as is well known, varies greatly. The most striking thing about the epithelium usually is not its thickness, the presence of large masses of trophoblast, or of numerous syncytial buds, but its splendid state of preservation, especially as contrasted with that of the stroma. This is true of all except macerated or degenerate specimens, for the life of the epithelium seems assured as long as there are periodic accessions of fresh blood, which, as the clinical histories illustrate, usually is the case. The stroma, on the other hand, probably not being wholly independent of the contained capillaries, is deprived very largely of its sustenance during, even if not in consequence of, their degeneration. According to some, hydatiform degeneration of the stroma is the result of an accumulation of nutritive products in consequence of the absence of the vessels. Degeneration of stroma and vessels, however, may result from malnutrition due to poor implantation.
  
Aman, J. A., 1916. VhcT (lestruirende Blasenmolc.  
+
[[File:Meyer1920_fig22.jpg|thumb|Fig. 22.]]
 +
[[File:Meyer1920_fig23.jpg|thumb|Fig. 23.]]
 +
The epithelium of the villi often was found single-layered without any syncytium whatever, or with at most a few syncytial buds. Nevertheless, both the syncytium and trophoblast very often show evidences of a marked activity which is not confined to implanted vilh or to the epithelium of the villi as a whole, but which may extend to that of the chorionic membrane as well. Surprisingly long, complex syncytial buds, whorls and festoons, as shown in figures 22, 23, and 24, and as said to have been observed by Frankel, often are present, especially on the villi, although in a few instances fine buds and frameworks of syncytium also were seen arising from the epithelium of the chorionic membrane. This feature (shown in figure 23) has, I believe, not been specially emphasized heretofore, though observed by Clivio (1908).  
  
Monatschr. f. Geb. u. Gyn., Bd. 34.  
+
[[File:Meyer1920_fig24.jpg|thumb|Fig. 24.]]
Ballantyn'e, J. W., and James Young, 1913. Fatal case
+
[[File:Meyer1920_fig20.jpg|thumb|Fig. 25.]]
 +
Mounds formed by the Langhans layer were common, especially on the tips of the villi where they frequently formed irregular masses of small nodules — the "appendici durate" of Crosti (1895). These gave the villous tree the appearance of a leafless orange loaded with fruit, only that the trophoblastic nodules are mainly apical, as shown in figure 25. In several instances syncytial buds were found far out on these; trophoblastic masses, a fact which is of special, if not of crucial significance in connection with the old question of the origin of the syncytium, for these buds undoubtedly had not been transported tluMc. But however one may regard these things, such appearances as represented in figure 24 are unmistakable, for they show thickenings composed of Langhans cells aiul garlands of considerable length, portions of which are composed of absolutely distinct cells of the Langhans type, as well iis other portions composed of syncytium with every gradation between the two. Nor do I believe that the assumption that syncytium can resolve itself into indiviiduaI cells can be used to deny the implication of these facts.  
  
of hydatiform mole. Obst. Trans. Edin., 38.
 
Bloch, 1S69. Die Blasenmole. Inaug. Dis.s., Freiburg.
 
Brioos, H., 1912. On the relative ahe of the uterus in
 
  
civses of hydatid mole with illustrative eases and
+
Although hydatiform villi covered by a single layer of rather small cells of the nature of Langhans cells, sometimes without visible cell boundaries, frequently were seen, villi covered by typical syncytium only never were seen. The single layer present, although syncytial in places, suggested Langhans cells rather than the real syncytium. Moreover, since the cells of the Langhans layer usually were smaller rather than larger than normal, it follows from this alone that their proliferation must have been marked, in order to completely cover the enlarged villus, in spite of the fact that the layer remained single-celled. Were this not the case, the extraordinary increase in size which accompanies the formation of large hydatid cysts could not possibly occur without rupture of the covering layer.
 +
[[File:Meyer1920_fig26.jpg|thumb|Fig. 26.]]
 +
[[File:Meyer1920_fig27.jpg|thumb|Fig. 27.]]
  
specimens. Jour. Obst. and Gyn., British Emp.,  
+
Not infrequently proliferation of the epithelium without increase in thickness may manifest itself in another way. The caliber of the villi in the earlier stages of hydatiform degeneration sometimes does not increase much, no thickening of the proliferating epithelium is noticeable, and yet the latter shows marked proliferation. Under these circumstances, the borders of the villi and of the chorionic epithelium may appear extraordinarily sinuous as illustrated in figure 26, and epithelial invaginations from opposite sides rarely meet in the center, as indicated in figure 27, and by fusion completely isolate a portion of the stroma. It usually is in these cases of very sinuous epithelium that the epithelial invaginations sometimes become constricted, leaving a closed epithelial vesicle or a nodule of epithelium attached to a stalk or wholly isolated within the stroma, as shown in figures 28 and 29. All stages in this process of vesicle formation were found, and rarely also extensions of epithelial sprouts as described by Neumann (1897) and others were seen, portions of which had become isolated in the stroma to appear later as typical syncytial giant cells. These facts, too, would seem to throw a sidelight upon the origin of the syncytium for those to whom this question is still an open one.
  
London, 21.
 
Clivio, I., 1908. A proposito di un cjiso di mola vesci-
 
  
colare iniziale. Folia Ginaecologia, i, Fasc. Primo.
+
All these tilings abundantly testify to the activity on the part of the epithelium in many hydatiform moles, even when thickening of it is absent, but they are of diagnostic value only if present, and I wish to emphasize again that they may be wholly absent or at least unrecognizable in the early stages. Moreover, the degree of epithelial proliferation varies greatly, as illustrated in figures 30, 31, and 32.  
Croom, J. IIalliday, 1895. Two cases of extra-uterine
 
  
gestation operated ujion at the fourth month.
 
  
Edin. Med. Jour., 40, part 2.  
+
Until I am able to learn more about the structure of normal villi in various stages of development, I am not willing to commit myself regarding the incipient changes in hydatiform degeneration. These may be unrecognizable with present methods. However, it is possible to say that in young conceptuses the disappearance of the capillaries, which was regarded as a possible cause for the development of hydatiform mole by Hewitt (1860 and 1861), and also emphasized later by Hahn (1865), Maslowsky (1882), and by others, undoubtedly is a very early and possibly the very earliest noticeable change in some cases. Of course, I do not imply that death of the embryo is the cause of this disappearance, as Hewitt held, and I am not ready to say that the vascular change is the very earliest one in all cases. This would imply that hydatiform degeneration under no circumstances can begin before the capillaries have ai)i)carocl in the villi. There is some evidence which suggests that it possibly may appear before this time. If so, it would be incorrect to speak of a disappearance of the vessels in such chorionic vesicles, for if the advent of hydatiform degeneration can precede the appearance of the villous capillaries, vascularization of the villi ma.v never occur. In older conceptuses, however, in which vascularization of the villi has sujiervened, the first recognizable change is the disappearance of these capillaries. Many specimens in which the latter were in various stages of degeneration were examined carefully, and the opinion of Hewitt (1860), that hydatiform degeneration can not arise in villi which have been vascularized, can be regarded as of historical interest only. Different stages in the process of vascular degeneration are represented in figures 33 to 35 inclusive.  
Crosti, G., 1895. Contribuzione alio studio dell' aborto
 
  
di origine ovulaire. Atti dall assoziazione medica
 
  
Lombardo, No. 3. Rev. in Centralbl. f. Gyn.,
+
Coincident with the disappearance of the vessels, changes in the stroma also are noticeable. Usually it tends to become glassy, the individual nuclei becoming separated farther. The stroma, though apparently solid, is uniformly slightly bluish and vitreous, with well-defined, rather small, pycnotic, pointed nuclei, but with not a vestige of a vessel, though the epithelium is splendidly preserved. The latter may be one-layered or two-layered, and may be accompanied by syncytial buds and trophoblastic masses and nodules. In such specimens the entire picture really is exquisite, and a mere glance through the compound microscope reveals the lack of vessels in the vitreous stroma and the marked differences in size of the sections of the villi.  
  
Bd. 20, 1896.
 
Daels, F., 1908. Au sujet de I'^tiologic do la mole
 
  
hydatique. Ann. Soe. de med. de Gand.  
+
After these early changes, licjuefaction of the stroma usually follows. As is well known, liquefaction generally begins in the interior and first appears in the form of vacuolation; but this vacuolation (which I can not regard merely as an edema) is not intra-cellular but intercellular, and as it becomes more pronounced it really takes on the nature of fenestration. Sections of the whole cross-section of the villi, even though large, may be composed of a series of fenestrse (see fig. 36) separated by exceedingly fine strands of the remaining stroma which may contain remnants of the nuclei. But finally, even the fine trabecular separating the fenestras disappear, and the stage of the watery, old, hydatid condition has been reached. More generally, however, the vacuoles or small fenestra lying in the middle become confluent at the center of the cross-section of the villus, which then is liquefied completely. As is well known, this liquefaction gradually extends to the periphery as the zone of the surrounding stroma is narrowed in the process. Not infrequently, however, liquefaction of the stroma occurs quite generally throughout the cross- section of the villus and is accompanied by the formation of numerous large cells, the wandering or migrating cells of earlier writers. A few of these cells almost always can be found, and rarely the whole section of the villus is studded with (fig. 37) or even formed by these large, erratic cells which usually lie in fenestra? in the stroma. In other instances a large portion of the sections of the villi may be occupied by them, as shown in figure 38. The presence of these cells in viUi regarded as normal has long been known. Their presence in hydatiform moles was noted by Otto, Marchand (1895), Essen-Miiller, and by many others. Their occurrence in normal and pathological chorionic vesicles, and their significance are considered more fully by Meyer (1919). No matter what the condition of the epithelium, or more specifically that of the Langhans lajer, the syncytium and trophoblast may be, the above-noted changes in the stroma always are quite typical. They are not the only changes noted, however, and their advent may differ somewhat.
De Lee, J. B., 1915. The principles and practice of  
 
  
obstetrics. Philadelphia.
 
DoN-SKOJ, DiMiTRY, 1911. Beitrage zur Kenntniss der
 
  
Blasenmole. I. D., Miinchen.  
+
Not infrequently, changes quite comparable to those in the villi occur also in the stroma of the chorionic membrane itself, a fact which has not heretofore been emphasized. Also, it is frequently decidedly glassy; liquefaction may occur here and there and may become complete in the course of time. Hofbauer cells not uncommonly also are present. Among the changes noted in this membrane the disappearance of the vessels is most common and constant, although epithelial proliferation is not rare, as already stated. Moreover, when (as in one of Storch's cases) a hydatiform villus is 15 cm. long, one scarcely can doubt that the stroma also must have proliferated — not merely degenerated. Some of the strings of hydatid cysts in a specimen in the Mall Collection have a length of over 10 to 12 cm., and in these cases also one can hardly assume that this increased length in the villi was unaccompanied by prohferation of the stroma. From these things alone it follows that the stroma can not remain passive always, although Gromadzki (1913) concluded that the stroma never proliferates. Vecchi (1906), however, reported an increase in the stroma of the vilU, and it will be recalled that Marchand also implied the presence of proliferative changes in the connective tissue when he wrote that they depend on those in the epithelium.
DoRLAND and Gerson, 1896. Cystic disease of the  
 
  
chorion, with a tabulation of one hundred cases.
 
  
Unvi. Med. Mag., vol. 8.  
+
I have never been able to find mitotic figures, a fact which may be accounted for, however, by the presence of degenerative changes due to intrauterine separation and retention of most specimens. Indeed, the failure to find mitoses speaks against proliferation in the stroma no more than in case of the epithelium, in which the presence of karyokinetic figures has been reported by a few investigators only. Yet pronounced proliferation of the epithelium often is present. The failure to find mitotic figures is very likely due to the condition of the material.  
Durante, G., 1898. Varietes, histologic et nature de
 
  
la mole hydatid. Arch, de med. exper.
 
, 1909. Lesions des vaisseaux fa>taux dans le
 
  
mole hydatiforme (nature et pathologic de la
+
Careful scrutiny of a large series of specimens has revealed the fact that the disappearance of the vessels in the villi, in the chorionic membrane, and also in the umbiUcal cord is centripetal as a rule. However, in many specimens the vessels not only may be present in the chorionic membrane although absent in the villi, but may be very numerous and even engorged with blood. It is difficult to say to what extent the engorged condition of these vessels and of those in the body of the abnormal embryos sometimes contained in these hydatiform moles is due to the propulsion of the embryonic blood before the advancing vascular constriction and degeneration, but I am inclined to beUeve that the centripetal movement of the process is not a negligible factor.
  
mole). Gynec, Par. I, 13.
 
Emanuel, R., 1895. Demonstration zur Lehre von der
 
  
Endometritis in der Schwangerschaft. Zeitschr.  
+
Although only a few instances of the birth of a living fetus or of a fetus which had reached the later months of pregnancy are recorded in the literature, it now is quite generaUy recognized that the fetus, though dead and too small for its menstrual age, usually is present. This stands in contradiction to the earlier belief iUustrated by the statement of Gierse (1847), that the fetus usually was reported as absent, and that when present (as in the cases of Meckel, Gregorini, Otto, Cruveilhier, and his own) it usually was less tihan 1 inch long, even when retained for a period of from 3 to 10 months.  
  
f. Geb, u. Gyn., Bd. 31.
 
EssEN-MoLLER, Elis, 1912. Studien iiber die Bla.sen-
 
  
mole. Wiesbaden.
+
This apparent contradiction regarding the presence of the fetus in hydatiform moles is explained easily by the fact that the cases in the earlier literature are old, far advanced in degeneration, while the more recent literature contains many more in the earlier stages of degeneration. Yet in spite of this fact the earlier opinion survives to the present day, for Graves (1909-10) spoke of "the very unusual presence of a normal fetus inside a mole," and Vineberg (1911) still more strangely held that the presence of a fetus excludes the specimen from the class of true hydatiform moles!
Falgow.ski, W., 1911. Kritische Wiirdigung eines
 
  
Falles von Blasenmole bei ZvvilUngsschwanger-
 
  
schaft mit einem ausgetragenen Kind. Monat-
+
Among the specimens concerned in this report many contained a fetus. Tliis was true of 24.5 per cent of 49 tubal and 64.4 per cent of 121 uterine specimens, including some (9) doubtful cases. In some early specimens the fetus is in a state of excellent preservation. This is what one might expect, for the onset of hydatiform degeneration is gradual and often partial. The condition of the fetus in many of them alone also suggests that its death was secondary to the degeneration.  
  
schr. f. Geb. u. Gyn., Bd., 34.
 
Fellner, O. O., 1903. Ueber periphere Langhanszellen,
 
  
zugleioh eine Erwiederung auf den Aufsatz von
+
The fetal length ranges from 1 to 90 mm. in the uterine and from 1 to 80 mm. in the tubal series. Although the average length of the embryo in the tubal series is 12.3 mm., and that of the uterine only 10.1 mm., 58 per cent of the tuljal speci- mens nevertheless were below 7 mm. in length as contrasted with 52.5 per cent of the uterine.
  
R. Meyer: "Zur Kenntniss der benignen Chorio-
 
  
epithelialen Zellinvasion." Zeitschr. f. Geb. u.  
+
The presence of a fetus with a frequency almost three times as great in the uterine series again indicates that the abnormal conditions within the tubes lead to early death, digestion, and absorption, or at least to dissolution, of the embryo. This fact again points directly to a faulty nidus as causative agent, for if the absence of a fetus is to be laid to primary ovular defects, then one must admit that relatively far more of such diseased ova become implanted within the tube than within the uterus.  
  
Gyn., Bd. 21.
 
FiNDLEY, P., 1917. Hydatiform mole; an analysis of 500
 
  
cases. Amer. Jour. Obst., 75.  
+
Of the many explanations which have been offered for the advent of hydatiform degeneration, none seems to be better established than that of endometritis. Tliis was first emphasized by Virchow (1863), and Lwow (1892) also reported 4 cases in patients under his care in whom lues could be excluded but in whom he held endometritis responsible. Emanuel (1895) was the first, it seems, to demonstrate the presence of cocci in inflammatory foci of round cells in the decidua accompanying a case of hydatiform mole. Veit (1899) also believed that disease of the decidua is the cause of hydatiform degeneration. Veit further stated that Waldeyer, Jarotzky, and Storch also believed that an irritative condition of the decidua is responsible. Stoffel (1905) also found cocci other than gonococci present and says he can not avoid holding endometritis responsible in his case. The association of hydatiform degeneration and endometritis was noted also l)y INIarchand (1895), Oster (1904), and Sternberg; also by Essen-Mollor, who reported the phenomenal case of a woman with endometritis, who had aborted a hydatiform mole 18 times in 9 years. Falgf)wski, on the contrary, concluded that the ova themselves were diseased and argued that hydatiform degeneration should be much more common if it were due to endometritis. Taussig (1911) also stated that leucocytic infiltration of the decidua is frequently present in hydatiform moles, but iasistcd that "leucocytic infiltration in the placenta then should not be interpreted as infection.  
Fraenkel, L., 1910. Ruckbildung von Ovarialtumoren
 
  
nach Blasenmole. Monatschr. f. Geb. u. Gyn.,
+
:Inflammation and infection should be kept apart." I presume Taussig really meant infiltration and infection should be kept apart, and the question then turns upon the structure of the normal decidua and the significance of infiltration for the development of the ovum.  
  
Bd. 32.
 
Freund, W. a., 1889. (No title.) See "Berichte uber
 
  
die Verhandlungen der gynakologischen Sektion
+
It may be recalled that Marchand (1904) reported the presence of isolated groups of small cells in the normal decidua which looked hke mononuclears under low magnification, and which he believed often have been confused with them. But even granting this, and the further facts that the exact histologic changes in the decidua are not fully known, and that it is rather difficult to ascertain just what decidual changes are regarded as evidence of the existence of an endometritis, any one examining a large series of cases of hydatiform degeneration aborted with the decidua can not doubt the presence of marked decidual changes in a very large percentage of them. These changes are not limited to infiltration with scattered round cells or erythrocytes, or to focal accumulation of the same, but often extend to almost complete fibrosis, as shown in figure 39, so that experienced investigators have mistaken the thin, fibrous decidua for a part of the chorionic membrane.
  
der 62 Versammlung deutscher Naturforschcr
 
  
und Arzte zu Heidelberg," 1889. (A reference to
+
It is true that the existence of these changes in the deciduae themselves does not necessarily imply that they were antecedent to the implantation of the ovum, but fortunately' the clinical histories and material from curettage often supply crucial evidence. From such cases and from the cumulative weight of evidence from the large series of cases here reported, the great majority of which showed decidual infiltration or other changes suggestive of endometritis, the frequent association of abnormal deciduae with hydatiform degenerations is evident. The fact that the incidence of hydatiform degeneration in the tubal was somewhat higher than that in the uterine series might be regarded as contradicting this relationship, but such is not the case. The mucosa of the tubes at best is an unfavorable nidus for implantation because of the absence of decidual formation alone. Hence, even if salpingitis were somewhat less frequent than endometritis, proper nidification in the tube could easily more than account for the existing differences. Hence the higher incidence of hydatiform degeneration in the tubal series in fact becomes confirmatory of the conclusion that abnormal nidification really may be responsible for the advent of hydatiform degeneration.  
  
the case only.) Centralbl. f. Gyn., Jahr. 13,
 
  
p. 690.  
+
The only fact which might be interpreted as indicating that germinal defects primarily are responsible for the development of hydatiform degeneration is the relatively higher incidence of the condition in older women. Against this, however, stands the other fact that such women also show the cumulative effects upon the endometrium of age, endometritis and pregnancy. Furthermore, since hydatiform degeneration so often follows one or two normal births or abortions, it would be impossible to find an adequate explanation for the release of the defective ova so often after and not before these events.  
Gierse, Aucju.st, 1847. Ueber die Krankheiten des
 
  
Eies und der Placenta. Verhandlung der Gcsell-
 
  
Bch. f. Gebh., Berlin, Bd. 2.
+
I am reminded also in this connection of a case the detailed history of which is fully known. It is that of a robust young woman who successively gave birth to two moles and then to a normal full-term child and secundincs. In this case curettage was done in connection with each mole. Apparently the new endometrium, which had formed after the second abortion and curettage, permitted normal implantation and normal development to progress to term. To ignore the condition of the endometrium in this case and attribute the development of hydatiform degeneration to the successive release of abnormal ova would seem to disregard important facts — especially so since no one has established the occurrence of abnormal ova within the Graafian foUicle, a possibility which I do not wish to deny, although Donskoj 's report of a case of hereditary mole must surely be taken cum grano sails (with a grain of salt).  
Chaves, E. W. IL, 1909-10. A specimen of tubal mole.  
 
  
Proc. Roy. Soc. Med., London, 3, Obst. and
 
  
Gyn. sec. 1.  
+
That an abnormal nidus may be responsible for the advent of hydatiform degeneration would seem to be indicated also by the fact that the process usually was better developed and more general in the tubal than in the uterine cases. That both endometrium and decidua show astonishing differences in structure under pathological conditions is well known. The entire tubal mucosa, on the other hand, even when normal, forms an abnormal nidus which would affect all portions of early chorionic vesicles somewhat alike, and since, as found by Mall, inflammatory conditions in the tubes predispose to tubal imjilantation, the higher incidence of hydatiform degeneration in the tubes is easily explained. Nor does the existence of partial hydatiform degeneration argue against such an explanation.  
  
  
 +
Although Kehrer reported not a single fatality in 50 cases of hydatiform mole, Hirtzman (according to von Winckel) gave the fataUty as 13 per cent, Borland and Gerson as 18, and Williamson as 20 to 30 per cent. Von Winckel (1904) regarded these i)ercentages as entirely too high, however, although Oster reported 2 cases of malignancy out of 15 among cases in which the late results were ascertainable — an incidence of 13.3 per cent. Kroemer (1907) found that chorio-epithelioma developed in 5 out of 15 cases of hydatiform moles, or in 33.3 per cent, but only twice in 3,841 "normal implantations." Daels (1908) says La Torre claimed a malignancy of 64 per cent; de 8enarcleus one of 28.7 per cent, or 14 out of 49 cases. Frjienkel (1910) emphasized that the estimates of the number of cases in which hydatiform degeneration is followed by malignant disease vary greatly, while Robertson (1915) quoted Findley as finding that IG per cent of 250 hydatiform moles collected from the literature were followed by malignant disease. Briggs, who reported 21 cases of hydatiform degeneration with 2 of chorio-epithelioma or an incidence of malignancy of 9.5 per cent, called attention to the "diminishing ratio in the; tendency to malignancy shown by his series."
  
V. Gromadzki, IIrinhich, 1913. Ein Beitrag zur Lehn'
 
  
von der Blasenmole mit besonderer Beriick-  
+
Findley stated that chorio-epithehoma develoiH'd in 131 out of 500 cases gathered by him from the literature, which is an incidence of 26.2 per cent; but, as already stated, most of these cases from the hterature are old, advanced degenerations, many of which have been retained for a long time. The tendency to malignancy in these probably can in no way be compared to that in smaller and younger specimens, many of which are aborted entire with the surrounding decidua. Consequently, it need not surprise us that out of 19 cases of this series, in which later reports were obtainable, none were reported as having developed chorio- epithelioma.
sichtigung deren Pathogenese. Inaug. Diss.,  
 
  
Halle.
 
Hahn, C. F. O., 1865. Ueber ein cystcnnrtiges Gebilde
 
  
im NabelstrangeinerTraubcnmole Monatschr. f.  
+
Perhaps I may here add a word of caution, however, in regard to a possible change in attitude toward the question of malignancy with a consequent relaxation of vigilance. It is true that out of the 21 cases of Briggs only 2 developed chorio- epithelioma, but it must not be forgotten that Briggs in part was, and I to a far larger extent, am dealing with a different class of hydatiform moles than those upon a study of which the prevailing conception of malignancy is based. Hydatiform moles which continue to grow and which survive for months after the death of the embryo evidently are more vigorous, and hence no doubt also more dangerous than those which are aborted early and spontaneously. Since the latter formed the great majority of all moles here considered, opinions regarding malignancy formed on this basis probably would lead to disaster if applied in practice. Such conceptions would be based upon a totally different incidence than the current one of 1 hydatiform mole in every 2,000 cases. Instead of relaxing our vigilance it would seem wise to increase it, particularly in the cases of so-called spontaneous abortions — the cases in which no ascertainable cause for the termination of pregnancy can be found, especially if the chorionic vesicle is empty or if the embr^^o belongs in one of the early groups of Mall's classification.  
  
Gebk. u. Frauenkrankh., Bd. 26.
 
Hennig, Carl, 1876. Die Krankheiten der Eileiter und
 
  
die Tubenschwangerschaft. Stuttgart.  
+
The average age of 36 women aborting hydatiform moles was 31 years. Although I do not regard the alleged ages as necessarily the actual ones, this average age agrees very well with that of 6 cases reported by Poten, 10 by Donskoj, 23 by Briggs, 6 by Gromadski, and 8 by Robertson. The average age of Poten's cases was 32 years, of Donskoj 's 25 years, of Briggs's 28 years, of Gromadski's 29.6 years, and of Robertson's 28.4 years. Pazzi (1908'') , on the other hand, stated that Briquel placed the greatest frequency of hydatiform degeneration between 20 and 30 years. These averages are so far on the near side of the menopause that one can make liberal allowances for the proverbial disinclination of women to state their exact age, even to physicians, and nevertheless regard the prevailing opinion undoubtedly as ill-founded. If, as Lewis (1906) stated, it is necessary to add only half a year to the average age of a large group of women in order to ascertain the actual average age when considering general social statistics, then everyone will admit that still less allowance than this need be made in the case of women who are speaking to their physicians, knowing that whatever they may say will be regarded as strictly confidential. That it is unncessary to make large allowances for under-statement of their age on the part of these women is indicated also by the average duration of their married life before aborting moles. This in the case of 29 women was 7.1 j'-ears. Hence, if one bears in mind that the average age of first marriages according to Webb (1911) is 25.1 years, one can easily see that the average age of the women aborting hydatiform moles, which was given as 29.6 years, is probably not too low at all, thus confirming the findings of Williamson, who denied that hydatiform mole was especially common near the menopause.
Hewitt, Graily, 1860. On the hydatiform or vesicular
 
  
mole; its nature and mode of origin. Obst. Trans.,
 
  
1, London.
 
, 1861. Hydatiform degeneration of the ovum.
 
  
Obst. Trans. London, 2.  
+
The conclusion that the average age of 29.6 years undoubtedly is near the actual is confirmed also by the fact that a hydatiform mole was the first abortion in 19 out of 41 women, or almost half the number; 12, or almost one-third, had aborted twice, and only 10 had aborted more than twice. But what is still more confirmatory is the existence of a surprising parallelism between the data on abortion and those on births; 9 of 33 women had given birth to but 1 child, and an eriual number had given birth to but 2. Hence over 50 per cent of the 33 women had borne children twice, or less than twice, and only 15, or less than half, had borne oftener than this.  
HiEss, Viktor, 1914. Ein Beitrag zur Pathologie und
 
  
Klinik der Blasenmole. Gynak. Rundschau, Ber-
 
lin u. Wien, Jalu-. 8.
 
Hirtzman, 1874. Mentioned by Seitz, 1904. Thfese,
 
  
Paris.  
+
This undoubted evidence of the youth of these women is confirmed still further by the statement of Lewis who, from an analysis of 16,325 first births, found that nearly one-half of them occur between the ages of 20 and 24, almost three-fourths between 20 and 29 years, and that first births are more frequent between 30 and 40 than between 15 and 19 years. I realize, to be sure, that social statistics can not be translated from one country to another without modification, but in such a mixed population as ours this modification probably need be less (rather than greater) than in case of some countries.  
Kehrer, F. a., 1894. Ueber Traubenmole. Arch. f.  
 
  
Gyn., Bd. 45.
 
Kroemer, p., 1907. Klinische Beobachtungen iiber
 
  
Etiologie und Therapie des ChorionepitheUom
+
The conclusion that the occurrence of but a single birth before the advent of hydatiform degeneration probably implies that such women are relatively young is emphasized still further by the statement of Lewis that in one-third of the marriages in Scotland "the bride had a child when unmarried or was pregnant at the time of marriage," and that 50 per cent of the first births in Scotland occur within 9 to 24 months after marriage. Lewis also gives the average interval between marriage and the first birth in 16,176 first births as 13.54 months, but little more than one year. Since Lewis stated that the interval between the birth of the first and that of the second child is but little longer than that between marriage and the birth of the first child, being only 3.07 years, it is evident that not even those women who had borne two children before the advent of hydatiform degeneration could have been near the menopause. This conclusion is emphasized still further by the fact that in 96.12 per cent of 16,176 fruitful marriages fertility was demonstrated within three years after marriage.
  
insbesondere uber die Behandlung der Blasenmole.
 
  
Deutsche med. Wochenschr., Jahr. 33, 2.  
+
Nevertheless, in spite of the clear implication of all these facts, I wish to emphasize again that since what have been heretofore regarded as hydatiform degenerations were large specimens mainly, it well may be, and according to certain authors it is true, that such cases occur later in the reproductive life of women. Yet it certainly is significant that Findley in tabulating 500 of such cases from the literature found that 275, or 55 per cent, occurred before the thirty-fifth year, and of 36 specimens from the Mall Collection 23, or 63.6 per cent, came from women below this age. It may also be recalled that 78 per cent of Kehrer's 50 cases and 90 per cent of Bloch's occurred before the fourth decade.  
Krueger, M., 1909. Eine seltene Form der Placen-
 
  
tarcy.ste; ein Beitrag zur Lehre von der Blasen-
 
mole. Zeitschr. f. Geb. u. Gyn., Bd. 64, H. 2.
 
Lewis, C. J. and J. N., 1906. NataUty and fecundity.
 
  
London.  
+
Fourteen out of 23 cases, or 61.3 per cent of the uterine series, in which the age was given, occurred at or before the thirtieth year, and 18 out of 23, or approximately 80 per cent, at or before the thirty-fifth year. These things abundantly emphasize the conclusion reached by some investigators that hydatiform mole is not absolutely more common at or near the menopause. But it nevertheless may be relatively more common. That is, the number of hydatiform moles aborted after 40 com.pared with the total number of pregnancies or births after 40, actually may be greater than this ratio before 40 years.  
Lwow, J. M., 1892. Mola vesiculosa. Centralbl. f. Gyn.,
 
  
Jahr. 16.
 
Mall, F. P., 1915. On the fate of the human embryo in
 
  
tubal pregnancy. Contributions to Embryology,  
+
From calculations based on data given by Lewis the average number of births occurring after 40 years in Sweden, Norway, Denmark, Brunswick, Berlin, Buda Pesth, France, and Scotland is 9.9 per cent. This agrees remarkably well with Bloch's estimate of 10 per cent. But if 77.2 per cent of the cases of hydatiform mole occur below 40, and 22.8 per cent after that year, then it is evident that hydatiform mole nevertheless is relatively more common after than before 40 years, for approximately one-fourth of the cases of hydatiform degeneration would be associated with one-tenth of the births. This would be an increased frequency of 300 per cent above that before 40 years. A similar result would be obtained by comparing Findley's or Williamson's series. Hence, hydatiform degeneration though absolutely loss is relatively more frequent in later life. This fact, however, does not necessarily imply that age in itself is responsible for the increased incidence after 40. A comparison of the incidences of hydatiform degeneration in young and old primiparse, of good health, might elucidate this question.
  
I, Carnegie Institution of Washington.
 
— , 1917. On the frequency of localized anom.alies in
 
  
human embryos and infants at birth. Amer.  
+
These statistics are not in agreement with the prevailing opinion that hydatiform moles are more common in multipara; than in primiparfe. Indeed, as I under- stand, they suggest rather that after the first conception, which was normal in a large percentage of these young women, something happened which interfered with the normal development of succeeding conceptions. That, it seems to me, is extremely significant and very suggestive. Here is a group of relatively young women, over 50 per cent of whom had borne but twice and some only once, and then gave birth to a hydatiform mole. While I realize the necessity for circumspection, especially in these matters, these facts seem to me to suggest that something hap- pened to a normal endometrium. Other facts also point in the same direction.  
  
Jour. Anat., 22.
 
Marchand, Franz, 1895. Ueber den Bau der Bhisen-
 
  
molen. Monatschr. for Geb. u. Gyn., Bd. 32.
+
Even if it is not wholly correct, as Findley states, that more cases of hydatiform mole were reported in the last decade than in the previous 14 centuries, it is not unlikely that approximately as many specimens of this condition are contained in the Mall Collection as have been reported heretofore. Moreover, upon the basis of the present rate of accession, a large number of formerly unrecognized cases of hydatiform moles — both tubal and uterine — are donated to this collection annually. This fact, together with others to which attention has been called, ought to stimulate our interest in this problem.
, 1898. Ueber diis maligne Chorio-epitheUom.  
 
  
Zeitschr. for Geb. u. Gyn., Bd. 39.
+
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, 1904. Beitrag zur Kenntniss der normalen und
 
  
pathologischen Histologic der Decidua. Arch. f.
 
  
Gyn., Bd. 72.
 
Maslowski, 1882. Zur pathologischen Anatomie der
 
  
Traubenmole. Centralbl. f. Gyn., No. 10.  
+
Aman, J. A., 1916. VhcT (lestruirende Blasenmolc. Monatschr. f. Geb. u. Gyn., Bd. 34.  
Matwejew, G. F., and W. M. Sykow, 1901. Blasen-
 
mole in <ler Tuba Fallopii und cystische Degenera-
 
tion des Ovariums. .Sitzngsb. der Mosk. gj'n.  
 
  
GeselLsch. \\'iatseh., No. 24. (Rev. in Zentralbl.  
+
Ballantyn'e, J. W., and James Young, 1913. Fatal case of hydatiform mole. Obst. Trans. Edin., 38.  
  
f. Gyn., Bd. 26, 1901.)
+
Bloch, 1S69. Die Blasenmole. Inaug. Dis.s., Freiburg.  
Maxwell, R. D., 1910. Tubal mole with edema of the
 
  
connective tissue of the villi. Proc. Roj-al Soc.  
+
Brioos, H., 1912. On the relative ahe of the uterus in cases of hydatid mole with illustrative cases and specimens. Jour. Obst. and Gyn., British Emp., London, 21.  
  
Med., London, 3, Sect. Obst. and Gyn.
+
Clivio, I., 1908. A proposito di un cjiso di mola vescicolare iniziale. Folia Ginaecologia, i, Fasc. Primo.  
Mayer, Karl, 1911. Retention von Blasenmolen. Med.  
 
  
klin. lierlin Jahr. 7, Th. 2.  
+
Croom, J. IIalliday, 1895. Two cases of extra-uterine gestation operated ujion at the fourth month. Edin. Med. Jour., 40, part 2.  
Menu, Adolphe, 1S99. La mole vfisiculairc. Tumeur
 
  
maligne. Thfee, Paris.  
+
Crosti, G., 1895. Contribuzione alio studio dell' aborto di origine ovulaire. Atti dall assoziazione medica Lombardo, No. 3. Rev. in Centralbl. f. Gyn., Bd. 20, 1896.
Meyer, A. W., 1919. On the nature, occurrence and
 
  
identity of the plasma cells of Hofbauer. Jr.  
+
Daels, F., 1908. Au sujet de I'^tiologic do la mole hydatique. Ann. Soe. de med. de Gand.  
  
Morph., vol. 32.  
+
De Lee, J. B., 1915. The principles and practice of obstetrics. Philadelphia.
MucGiA, ViRoiNio, 1915. Contributo alio studio della
 
  
parziale degenerazione vesicolare partiale della
+
DoN-SKOJ, DiMiTRY, 1911. Beitrage zur Kenntniss der Blasenmole. I. D., Miinchen.
  
placenta Folia gynec, Pavia, T. 2.  
+
DoRLAND and Gerson, 1896. Cystic disease of the chorion, with a tabulation of one hundred cases. Unvi. Med. Mag., vol. 8.  
  
 +
Durante, G., 1898. Varietes, histologic et nature de la mole hydatid. Arch, de med. exper. , 1909. Lesions des vaisseaux fa>taux dans le mole hydatiforme (nature et pathologic de la mole). Gynec, Par. I, 13.
  
MfTLLER, H., 1847. Bau der Molen. Wurzburg.  
+
Emanuel, R., 1895. Demonstration zur Lehre von der Endometritis in der Schwangerschaft. Zeitschr. f. Geb, u. Gyn., Bd. 31.  
Neumann, Julius, 1897. Ueber Blasenmole und
 
  
maligne Deciduom. Monatschr. f. Geb. u. Gyn.,
+
EssEN-MoLLER, Elis, 1912. Studien iiber die Bla.senmole. Wiesbaden.  
  
Bd. 6.  
+
Falgow.ski, W., 1911. Kritische Wiirdigung eines
Niosi, Francesco, 1905. Corioncpitelioma maligno,
 
  
primitivo, bilaterale dell' ovaia, non embrio-
+
Falles von Blasenmole bei ZvvilUngsschwangerschaft mit einem ausgetragenen Kind. Monatschr. f. Geb. u. Gyn., Bd., 34.
  
matoso, indipendente da gravidanza e con incip-  
+
Fellner, O. O., 1903. Ueber periphere Langhanszellen, zugleioh eine Erwiederung auf den Aufsatz von R. Meyer: "Zur Kenntniss der benignen Chorio-epithelialen Zellinvasion." Zeitschr. f. Geb. u. Gyn., Bd. 21.
  
iente formazione di vescicole raolari. Atti della
+
FiNDLEY, P., 1917. Hydatiform mole; an analysis of 500 cases. Amer. Jour. Obst., 75.  
  
Societa Italiana di Ostetricia e Ginecologia, 11.  
+
Fraenkel, L., 1910. Ruckbildung von Ovarialtumoren nach Blasenmole. Monatschr. f. Geb. u. Gyn., Bd. 32.  
  
Roma, 1900.  
+
Freund, W. a., 1889. (No title.) See "Berichte uber die Verhandlungen der gynakologischen Sektion der 62 Versammlung deutscher Naturforschcr und Arzte zu Heidelberg," 1889. (A reference to the case only.) Centralbl. f. Gyn., Jahr. 13, p. 690.  
OsTEB, Karl R., 1904. Uber das spiitere Befinden der
 
  
Frauen nach Gebiirt einer Blasenmole. H.  
+
Gierse, Aucju.st, 1847. Ueber die Krankheiten des Eies und der Placenta. Verhandlung der Gcsell-Bch. f. Gebh., Berlin, Bd. 2.  
  
Fiencke, Kiel.  
+
Chaves, E. W. IL, 1909-10. A specimen of tubal mole. Proc. Roy. Soc. Med., London, 3, Obst. and Gyn. sec. 1.  
Otto, Heinrich, 1871. Ueber Tubcnschwangerschaft
 
  
mit Beriicksichtigung eines Falles von Graviditas
+
V. Gromadzki, IIrinhich, 1913. Ein Beitrag zur Lehn' von der Blasenmole mit besonderer Beriicksichtigung deren Pathogenese. Inaug. Diss., Halle.
  
tubaria molaris hydatidosa. Inaug. Dissert,  
+
Hahn, C. F. O., 1865. Ueber ein cystcnnrtiges Gebilde im NabelstrangeinerTraubcnmole Monatschr. f. Gebk. u. Frauenkrankh., Bd. 26. Hennig, Carl, 1876. Die Krankheiten der Eileiter und die Tubenschwangerschaft. Stuttgart.
  
Greifswald.  
+
Hewitt, Graily, 1860. On the hydatiform or vesicular mole; its nature and mode of origin. Obst. Trans., 1, London.  
Panttm, p. L., 18G0. Untersuchungen uber die Entste-
+
, 1861. Hydatiform degeneration of the ovum. Obst. Trans. London, 2.  
  
hung der Missbildungen zunachst in den Eiern
 
  
der Vogel. Berlin.  
+
HiEss, Viktor, 1914. Ein Beitrag zur Pathologie und Klinik der Blasenmole. Gynak. Rundschau, Berlin u. Wien, Jalu-. 8.  
Pazzi, M., 1908'. Vescicole molari iniziali. Folia Gine-  
 
cologia, 1, Fasc. Terzo.  
 
, 1908'. Vescicole molari iniziali e nouva orienta-
 
  
zione della teoria patogenetica della mole vesci-
+
Hirtzman, 1874. Mentioned by Seitz, 1904. Thfese, Paris.
  
colare e del corionepitelioma. Folia Gynaecolo-
+
Kehrer, F. a., 1894. Ueber Traubenmole. Arch. f. Gyn., Bd. 45.  
  
gia, 1, Fasc. 3.  
+
Kroemer, p., 1907. Klinische Beobachtungen iiber Etiologie und Therapie des ChorionepitheUom insbesondere uber die Behandlung der Blasenmole. Deutsche med. Wochenschr., Jahr. 33, 2.  
, 1908^. La Nostre cognizioni intorno alia mola
 
  
vescicolare ed alia nidificazione del-l'uovo. Ras-
+
Krueger, M., 1909. Eine seltene Form der Placentarcy.ste; ein Beitrag zur Lehre von der Blasen-mole. Zeitschr. f. Geb. u. Gyn., Bd. 64, H. 2.  
  
segna D'Ostetricia e Ginecologia, 17.  
+
Lewis, C. J. and J. N., 1906. NataUty and fecundity. London.  
, 1909. Note di patologia sperimentale e di
+
Lwow, J. M., 1892. Mola vesiculosa. Centralbl. f. Gyn., Jahr. 16.  
  
istologica patologiea intorno alia mola vescicolare
 
  
e considerazioni relative. La Ginecologia Mo-
+
Mall, F. P., 1915. On the fate of the human embryo in tubal pregnancy. Contributions to Embryology, I, Carnegie Institution of Washington.
 +
— , 1917. On the frequency of localized anom.alies in human embryos and infants at birth. Amer. Jour. Anat., 22.  
  
derna, 2, Fasc. 2.  
+
Marchand, Franz, 1895. Ueber den Bau der Bhisenmolen. Monatschr. for Geb. u. Gyn., Bd. 32. , 1898. Ueber diis maligne Chorio-epithelium. Zeitschr. for Geb. u. Gyn., Bd. 39. , 1904. Beitrag zur Kenntniss der normalen und pathologischen Histologic der Decidua. Arch. f. Gyn., Bd. 72.  
Pearson, K., 1897. The chances of death and other
 
  
studies in evolution. London.  
+
Maslowski, 1882. Zur pathologischen Anatomie der Traubenmole. Centralbl. f. Gyn., No. 10.  
PoTEN, W., 1901. Beitrag zur Diagnose der Blasen-
 
  
molen Schwangerschaft. Monatschr. f. Geb. u.  
+
Matwejew, G. F., and W. M. Sykow, 1901. Blasen-mole in <ler Tuba Fallopii und cystische Degeneration des Ovariums. .Sitzngsb. der Mosk. gj'n. GeselLsch. \\'iatseh., No. 24. (Rev. in Zentralbl. f. Gyn., Bd. 26, 1901.)
  
Gyn., Bd. 14.
 
V. Recklinghausen, 1889. Perforierende Blasenmole
 
  
bei fiinfwochentUcher Tubenschwangerschaft.  
+
Maxwell, R. D., 1910. Tubal mole with edema of the connective tissue of the villi. Proc. Roj-al Soc. Med., London, 3, Sect. Obst. and Gyn.  
  
Deutsch med. Wochenschr. (Merely a society
 
  
minute.)
+
Mayer, Karl, 1911. Retention von Blasenmolen. Med. klin. lierlin Jahr. 7, Th. 2. Menu, Adolphe, 1S99. La mole vfisiculairc. Tumeur maligne. Thfee, Paris.  
RiSEL, W., 1895. Demonstration von frischen Prapara-
 
  
ten nebst Bemerkungen. Gesellsch. f. Geb. zu
+
Meyer, A. W., 1919. On the nature, occurrence and identity of the plasma cells of Hofbauer. Jr. Morph., vol. 32.  
  
Leipzig, June 17. (As reported in Zentralbl. f.  
+
MucGiA, ViRoiNio, 1915. Contributo alio studio della parziale degenerazione vesicolare partiale della placenta Folia gynec, Pavia, T. 2.  
  
Gyn. 1896.)
 
Robertson, J. F., 1915. Hydatiform mole; a report of
 
  
eight cases. N. Y. Med. Jour., 102.  
+
MfTLLER, H., 1847. Bau der Molen. Wurzburg. Neumann, Julius, 1897. Ueber Blasenmole und maligne Deciduom. Monatschr. f. Geb. u. Gyn., Bd. 6.
Seitz, L. 1904. Erkrankungen der Placenta. Kap. iii,  
 
  
Handb. der Geb. F. von Winckel, Bd. 2, Wies-  
+
Niosi, Francesco, 1905. Corioncpitelioma maligno, primitivo, bilaterale dell' ovaia, non embrio- matoso, indipendente da gravidanza e con incipiente formazione di vescicole raolari. Atti della Societa Italiana di Ostetricia e Ginecologia, 11. Roma, 1900.  
baden.  
 
Sfameni, p., 1905. Sulla natura esclusivamente epithe-
 
  
liale delle vescicole nella mola idatigena. Ann. di
+
OsTEB, Karl R., 1904. Uber das spiitere Befinden der Frauen nach Gebiirt einer Blasenmole. H. Fiencke, Kiel.  
  
ostet., Milano, T. 27.  
+
Otto, Heinrich, 1871. Ueber Tubcnschwangerschaft mit Beriicksichtigung eines Falles von Graviditas tubaria molaris hydatidosa. Inaug. Dissert, Greifswald.  
Sternberg, Martin, 1910. Ueber sogennante Fleisch-
 
  
Blasen-Molen mit lingerer Verhaltung im Uterus.  
+
Panttm, p. L., 18G0. Untersuchungen uber die Entstehung der Missbildungen zunachst in den Eiern der Vogel. Berlin.  
  
1. D., BerUn.  
+
Pazzi, M., 1908'. Vescicole molari iniziali. Folia Ginecologia, 1, Fasc. Terzo. , 1908'. Vescicole molari iniziali e nouva orientazione della teoria patogenetica della mole vescicolare e del corionepitelioma. Folia Gynaecologia, 1, Fasc. 3.
 +
• , 1908^. La Nostre cognizioni intorno alia mola vescicolare ed alia nidificazione del-l'uovo. Rassegna D'Ostetricia e Ginecologia, 17. , 1909. Note di patologia sperimentale e di istologica patologiea intorno alia mola vescicolare e considerazioni relative. La Ginecologia Moderna, 2, Fasc. 2.  
  
  
 +
Pearson, K., 1897. The chances of death and other studies in evolution. London.
  
DE Snoo, K., 1914. Bijdrage tot de anatomic en de
+
PoTEN, W., 1901. Beitrag zur Diagnose der Blasenmolen Schwangerschaft. Monatschr. f. Geb. u. Gyn., Bd. 14. V. Recklinghausen, 1889. Perforierende Blasenmole bei fiinfwochentUcher Tubenschwangerschaft. Deutsch med. Wochenschr. (Merely a society minute.)
aetiologie der blaasmola. Nederlandsch Tijd-
 
schrift voor Verloskunde en Gynaecologie, 23,  
 
p. 56.  
 
  
Stoffel, A., 1905. Untersuchungsergebnisse eincs
 
Friistadium von Blasenmole; zugleieh ein Beitrag
 
7ur Aetiologie derselben. Monatschr. f. Gyn. u.
 
Gebh., Bd. 21.
 
  
Storch, E. D., 1878. Beitrag zur pathologic des Eies.  
+
RiSEL, W., 1895. Demonstration von frischen Praparaten nebst Bemerkungen. Gesellsch. f. Geb. zu Leipzig, June 17. (As reported in Zentralbl. f. Gyn. 1896.)
Falle von sogenannter partiellem Myom der
 
Placenta. Arch. f. path. Anat., Bd. 72.  
 
  
Taussig, F. J., 1911. Hydatiform mole of unusual type.  
+
Robertson, J. F., 1915. Hydatiform mole; a report of eight cases. N. Y. Med. Jour., 102.  
Weekly Bull. St. Louis Med. Soc, 5.  
 
  
Teacher, J. IL, 190.3. On chorioepithelioma (the so-
+
Seitz, L. 1904. Erkrankungen der Placenta. Kap. iii, Handb. der Geb. F. von Winckel, Bd. 2, Wiesbaden.  
called deciduoma malignum), and the occurrence
 
of chorioepithelioma and hydatiform-mole-like
 
structures in tumors of the testes. London Obst.  
 
Trans., 45.  
 
  
Van der Hoeven, 1900. Ueber die Etiologie der Mole
+
Sfameni, p., 1905. Sulla natura esclusivamente epitheliale delle vescicole nella mola idatigena. Ann. di ostet., Milano, T. 27.  
hydatidosa. Arch. f. Gyn., Bd. 62.  
 
  
Vecchi, Mario, 1906. Di una particolare alterazione di
+
Sternberg, Martin, 1910. Ueber sogennante Fleisch- Blasen-Molen mit lingerer Verhaltung im Uterus. 1. D., BerUn.  
sviluppo die viUi coriaU. Note anatomiche per
 
lo studio della mola vescicolare. Raccolta di
 
scritti ostelrico-ginecologici pel Giubileo Didat-  
 
tico del Prof. Senatore Luigi Mangialh. Pavia.  
 
  
Veit, J., 1899. Das Deciduom malignum. Bla.semnole
 
und ihr Verhiiltnis zum Deciduom. Handb. der
 
Gynak., Bd. Ill', Wiesbaden.
 
  
, 1908. Das maligne chorioepitheliom. Handb.  
+
DE Snoo, K., 1914. Bijdrage tot de anatomic en de aetiologie der blaasmola. Nederlandsch Tijdschrift voor Verloskunde en Gynaecologie, 23, p. 56.  
  
der Gyn., Bd. 3, Zweite Hiilfte, Wiesbaden.  
+
Stoffel, A., 1905. Untersuchungsergebnisse eincs Friistadium von Blasenmole; zugleieh ein Beitrag 7ur Aetiologie derselben. Monatschr. f. Gyn. u. Gebh., Bd. 21.  
  
Vineberg, Hiram V., 1911. Hj'datid mole. Amer.  
+
Storch, E. D., 1878. Beitrag zur pathologic des Eies. Falle von sogenannter partiellem Myom der Placenta. Arch. f. path. Anat., Bd. 72.  
Jour. Obst., 64.  
 
  
Virchow, R., 1863. Die krankhaften Geschiilste,  
+
Taussig, F. J., 1911. Hydatiform mole of unusual type. Weekly Bull. St. Louis Med. Soc, 5.  
Berlin.  
 
  
Webb, A. D., 1911. New dictionary of statistics, London.  
+
Teacher, J. IL, 190.3. On chorioepithelioma (the so-called deciduoma malignum), and the occurrence of chorioepithelioma and hydatiform-mole-like structures in tumors of the testes. London Obst. Trans., 45.  
  
Weber, Samuel L. 1892. Remarks on the differential
+
Van der Hoeven, 1900. Ueber die Etiologie der Mole hydatidosa. Arch. f. Gyn., Bd. 62.  
diagnosis and treatment of cystic degeneration
 
of the chorion. Amer. Jour. Obst.  
 
  
Wenzel, Carl, 1893. Alte Erfahrungen im Lichte der
+
Vecchi, Mario, 1906. Di una particolare alterazione di sviluppo die viUi coriaU. Note anatomiche per lo studio della mola vescicolare. Raccolta di
neuen Zeit und ihre Anschauungen iiber die  
+
scritti ostelrico-ginecologici pel Giubileo Didattico del Prof. Senatore Luigi Mangialh. Pavia.  
Entstehung von Krankheiten. 1 Blasenmole
 
Eileiter, Wiesbaden.  
 
  
Werth, R., 1904. Die Extrauterineschwangerschaft.  
+
Veit, J., 1899. Das Deciduom malignum. Blasemnole und ihr Verhiiltnis zum Deciduom. Handb. der Gynak., Bd. Ill', Wiesbaden.  
Kap. I, Handb. der Geb. F. von Winckel, Bd.  
 
II, Wiesbaden.  
 
  
Williams, J. W., 1917. Obstetrics. New York and
+
, 1908. Das maligne chorioepitheliom. Handb. der Gyn., Bd. 3, Zweite Hiilfte, Wiesbaden.  
London.  
 
  
Williamson, 1900. The pathology and sjTnptoms of
+
Vineberg, Hiram V., 1911. Hj'datid mole. Amer. Jour. Obst., 64.  
hydatiform degeneration of the chorion. Trans.  
 
London Obst. Soc, 41.  
 
  
voN Winckel, 1904. Handbuch der Geburtshilfe, Wies-
+
Virchow, R., 1863. Die krankhaften Geschiilste, Berlin.  
baden.  
 
 
 
Winter, George, 1907. Lehrbuch der gynakologischen
 
Diagnostik. Leipzig Dritte Auflage.
 
 
 
 
 
 
 
==LIST OF ILLUSTRATIONS==
 
 
 
 
 
Fig. 1. Cross-soot ion of twin hydatiform chorionic vesicles within the tube. (Specimen No. 825.)
 
X3.
 
 
 
Fig. 2. Ilydatiform viUi from same specimen in section. X 45.
 
 
 
Embryo No. 1771, covered with magma. X 4.
 
 
 
Cross-section of tube No. 1771. X 2.
 
 
 
Cross-section of tube from same case. X 4.
 
 
 
Hydatiform villi from same case. X 45.
 
 
 
Hydatiform chorionic vesicle in loco with the tube incised. No. 2052. X 2.
 
 
 
Gross appearance of specimen No. 70. X1.6.
 
 
 
Gross appearance of specimen No. 323. X 1.75.
 
 
 
Gross appearance of specimen No. 749. X 1.1.
 
 
 
Gross appearance of specimen No. 1323. X 1.2.
 
 
 
Gross appearance of specimen No. 1325. X 12.
 
 
 
Grass appearance of specimen No. 1914. X i-
 
 
 
External appearance of the larger part of the
 
small mass of specimen No. 1926. X 4.
 
 
 
Embryonic (cyemic) mass accompanying No.
 
1926. X 4.
 
 
 
A small portion of specimen No. 1189 still in
 
Inco. X 6.
 
 
 
Another portion of the same specimen. X 30.
 
 
 
No. 2077, an apparently normal specimen,
 
partly surrounded by decidua. Natural size.
 
Fia. 19. A portion of the above clearly showing numer-
 
ous typical hydatid cysts in area in focus.
 
X 3.
 
Fig. 20. Sections of vilU from specimen No. 690. X 50.
 
Fia. 21. A portion of specimen No. 865 still embedded
 
 
 
within the uteras. X 4, reduced J.
 
Fig. 22. A portion of specimen No. 435", showing a
 
small villus in mid-portion of the figure,
 
which has an exceptionally long syncytial
 
bud. X 50.
 
Fio. 23. A small portion of specimen No. 962", showing
 
a framework of epitheUum arising from the
 
chorionic membrane. X 50.  
 
  
 +
Webb, A. D., 1911. New dictionary of statistics, London.
  
 +
Weber, Samuel L. 1892. Remarks on the differential diagnosis and treatment of cystic degeneration of the chorion. Amer. Jour. Obst.
  
Fig.  
+
Wenzel, Carl, 1893. Alte Erfahrungen im Lichte der neuen Zeit und ihre Anschauungen iiber die Entstehung von Krankheiten. 1 Blasenmole Eileiter, Wiesbaden.  
  
 +
Werth, R., 1904. Die Extrauterineschwangerschaft. Kap. I, Handb. der Geb. F. von Winckel, Bd. II, Wiesbaden.
  
3.  
+
Williams, J. W., 1917. Obstetrics. New York and London.  
  
 +
Williamson, 1900. The pathology and symptoms of hydatiform degeneration of the chorion. Trans. London Obst. Soc, 41.
  
Fig.  
+
voN Winckel, 1904. Handbuch der Geburtshilfe, Wiesbaden.  
  
 +
Winter, George, 1907. Lehrbuch der gynakologischen Diagnostik. Leipzig Dritte Auflage.
  
4.
+
==List of Illustrations==
  
 +
[[Book_-_Contributions_to_Embryology_Carnegie_Institution_No.40|'''Links''']]: [[:File:Meyer1920_Plate_1.jpg|Plate 1]] | [[:File:Meyer1920_Plate_2.jpg|Plate 2]] | [[:File:Meyer1920_Plate_3.jpg|Plate 3]] | [[:File:Meyer1920_Plate_4.jpg|Plate 4]] | [[:File:Meyer1920_Plate_5.jpg|Plate 5]] | [[:File:Meyer1920_Plate_6.jpg|Plate 6]] | [[Book_-_Contributions_to_Embryology_Carnegie_Institution_No.40|Contribution No.40]] | [[Book_-_Contributions_to_Embryology#Volume_IX|Volume IX]] | [[Book_-_Contributions_to_Embryology|Contributions to Embryology]]
  
Fig.  
+
===Plate 1===
 +
:[[:File:Meyer1920_Plate_1.jpg|Plate 1]]: [[:File:Meyer1920_fig01.jpg|Fig. 1]] | [[:File:Meyer1920_fig02.jpg|Fig. 2]] | [[:File:Meyer1920_fig03.jpg|Fig. 3]] | [[:File:Meyer1920_fig04.jpg|Fig. 4]] | [[:File:Meyer1920_fig05.jpg|Fig. 5]] | [[:File:Meyer1920_fig06.jpg|Fig. 6]] | [[:File:Meyer1920_fig07.jpg|Fig. 7]]
  
  
5.  
+
[[File:Meyer1920_Plate_1.jpg|600px]]
  
  
Fig.  
+
:[[:File:Meyer1920_Plate_1.jpg|Plate 1]]: [[:File:Meyer1920_fig01.jpg|Fig. 1]] | [[:File:Meyer1920_fig02.jpg|Fig. 2]] | [[:File:Meyer1920_fig03.jpg|Fig. 3]] | [[:File:Meyer1920_fig04.jpg|Fig. 4]] | [[:File:Meyer1920_fig05.jpg|Fig. 5]] | [[:File:Meyer1920_fig06.jpg|Fig. 6]] | [[:File:Meyer1920_fig07.jpg|Fig. 7]]
  
 +
<gallery>
 +
File:Meyer1920_fig01.jpg|Fig. 1. Cross-section of twin hydatiform chorionic vesicles within the tube. (Specimen No. 825.) X3.
 +
File:Meyer1920_fig02.jpg|Fig. 2. Hydatiform villi from same specimen in section. X 45.
 +
File:Meyer1920_fig03.jpg|Fig. 3. Embryo No. 1771, covered with magma. X 4.
 +
File:Meyer1920_fig04.jpg|Fig. 4.  Cross-section of tube No. 1771. X 2.
 +
File:Meyer1920_fig05.jpg|Fig. 5. Cross-section of tube from same case. X 4.
 +
File:Meyer1920_fig06.jpg|Fig. 6. Hydatiform villi from same case. X 45.
 +
File:Meyer1920_fig07.jpg|Fig. 7. Hydatiform chorionic vesicle in loco with the tube incised. No. 2052. X 2.
 +
</gallery>
  
6.
 
  
 +
===Plate 2===
 +
:[[:File:Meyer1920_Plate_2.jpg|Plate 2]]: [[:File:Meyer1920_fig08.jpg|Fig. 8]] | [[:File:Meyer1920_fig09.jpg|Fig. 9]] | [[:File:Meyer1920_fig10.jpg|Fig. 10]] | [[:File:Meyer1920_fig11.jpg|Fig. 11]] | [[:File:Meyer1920_fig12.jpg|Fig. 12]] | [[:File:Meyer1920_fig13.jpg|Fig. 13]]
  
Fig.  
+
[[File:Meyer1920_Plate_2.jpg|600px]]
  
  
7.  
+
:[[:File:Meyer1920_Plate_2.jpg|Plate 2]]: [[:File:Meyer1920_fig08.jpg|Fig. 8]] | [[:File:Meyer1920_fig09.jpg|Fig. 9]] | [[:File:Meyer1920_fig10.jpg|Fig. 10]] | [[:File:Meyer1920_fig11.jpg|Fig. 11]] | [[:File:Meyer1920_fig12.jpg|Fig. 12]] | [[:File:Meyer1920_fig13.jpg|Fig. 13]]
 +
  
 +
<gallery>
 +
File:Meyer1920_fig08.jpg|Fig. 8. Gross appearance of specimen No. 70.
 +
File:Meyer1920_fig09.jpg|Fig. 9. Gross appearance of specimen No. 323.
 +
File:Meyer1920_fig10.jpg|Fig. 10. Gross appearance of specimen No. 749. X 1.1.
 +
File:Meyer1920_fig11.jpg|Fig. 11. Gross appearance of specimen No. 1323. X 1.2.
 +
File:Meyer1920_fig12.jpg|Fig. 12. Gross appearance of specimen No. 1325. X 12.
 +
File:Meyer1920_fig13.jpg|Fig. 13. Grass appearance of specimen No. 1914. X i
 +
</gallery>
  
Fig.  
+
===Plate 3===
 +
:[[:File:Meyer1920_Plate_3.jpg|Plate 3]]: [[:File:Meyer1920_fig14.jpg|Fig. 14]] | [[:File:Meyer1920_fig15.jpg|Fig. 15]] | [[:File:Meyer1920_fig16.jpg|Fig. 16]] | [[:File:Meyer1920_fig17.jpg|Fig. 17]] | [[:File:Meyer1920_fig18.jpg|Fig. 18]] | [[:File:Meyer1920_fig19.jpg|Fig. 19]] | [[:File:Meyer1920_fig20.jpg|Fig. 20]]
  
  
8.  
+
[[File:Meyer1920_Plate_3.jpg|600px]]
  
  
Fig.  
+
:[[:File:Meyer1920_Plate_3.jpg|Plate 3]]: [[:File:Meyer1920_fig14.jpg|Fig. 14]] | [[:File:Meyer1920_fig15.jpg|Fig. 15]] | [[:File:Meyer1920_fig16.jpg|Fig. 16]] | [[:File:Meyer1920_fig17.jpg|Fig. 17]] | [[:File:Meyer1920_fig18.jpg|Fig. 18]] | [[:File:Meyer1920_fig19.jpg|Fig. 19]] | [[:File:Meyer1920_fig20.jpg|Fig. 20]]
  
 +
<gallery>
 +
File:Meyer1920_fig14.jpg|Fig. 14
 +
File:Meyer1920_fig15.jpg|Fig. 15
 +
File:Meyer1920_fig16.jpg|Fig. 16
 +
File:Meyer1920_fig17.jpg|Fig. 17
 +
File:Meyer1920_fig18.jpg|Fig. 18
 +
File:Meyer1920_fig19.jpg|Fig. 19
 +
File:Meyer1920_fig20.jpg|Fig. 20
 +
</gallery>
  
9.  
+
===Plate 4===
 +
:[[:File:Meyer1920_Plate_4.jpg|Plate 4]]: [[:File:Meyer1920_fig21.jpg|Fig. 21]] | [[:File:Meyer1920_fig22.jpg|Fig. 22]] | [[:File:Meyer1920_fig23.jpg|Fig. 23]] | [[:File:Meyer1920_fig24.jpg|Fig. 24]] | [[:File:Meyer1920_fig25.jpg|Fig. 25]] | [[:File:Meyer1920_fig26.jpg|Fig. 26]] | [[:File:Meyer1920_fig27.jpg|Fig. 27]]
  
  
Fig.  
+
[[File:Meyer1920_Plate_4.jpg|600px]]
  
 +
:[[:File:Meyer1920_Plate_4.jpg|Plate 4]]: [[:File:Meyer1920_fig21.jpg|Fig. 21]] | [[:File:Meyer1920_fig22.jpg|Fig. 22]] | [[:File:Meyer1920_fig23.jpg|Fig. 23]] | [[:File:Meyer1920_fig24.jpg|Fig. 24]] | [[:File:Meyer1920_fig25.jpg|Fig. 25]] | [[:File:Meyer1920_fig26.jpg|Fig. 26]] | [[:File:Meyer1920_fig27.jpg|Fig. 27]]
  
10.  
+
<gallery>
 +
File:Meyer1920_fig21.jpg|Fig. 21
 +
File:Meyer1920_fig22.jpg|Fig. 22
 +
File:Meyer1920_fig23.jpg|Fig. 23
 +
File:Meyer1920_fig24.jpg|Fig. 24
 +
File:Meyer1920_fig25.jpg|Fig. 25
 +
File:Meyer1920_fig26.jpg|Fig. 26
 +
File:Meyer1920_fig27.jpg|Fig. 27
 +
</gallery>
  
 +
===Plate 5===
  
Fig.  
+
:[[:File:Meyer1920_Plate_5.jpg|Plate 5]]: [[:File:Meyer1920_fig28.jpg|Fig. 28]] | [[:File:Meyer1920_fig29.jpg|Fig. 29]] | [[:File:Meyer1920_fig30.jpg|Fig. 30]] | [[:File:Meyer1920_fig31.jpg|Fig. 31]] | [[:File:Meyer1920_fig32.jpg|Fig. 32]] | [[:File:Meyer1920_fig33.jpg|Fig. 33]]
  
 +
[[File:Meyer1920_Plate_5.jpg|600px]]
  
11.  
+
:[[:File:Meyer1920_Plate_5.jpg|Plate 5]]: [[:File:Meyer1920_fig28.jpg|Fig. 28]] | [[:File:Meyer1920_fig29.jpg|Fig. 29]] | [[:File:Meyer1920_fig30.jpg|Fig. 30]] | [[:File:Meyer1920_fig31.jpg|Fig. 31]] | [[:File:Meyer1920_fig32.jpg|Fig. 32]] | [[:File:Meyer1920_fig33.jpg|Fig. 33]]
  
 +
<gallery>
 +
File:Meyer1920_fig28.jpg|Fig. 28
 +
File:Meyer1920_fig29.jpg|Fig. 29
 +
File:Meyer1920_fig30.jpg|Fig. 30
 +
File:Meyer1920_fig31.jpg|Fig. 31
 +
File:Meyer1920_fig32.jpg|Fig. 32
 +
File:Meyer1920_fig33.jpg|Fig. 33
 +
</gallery>
  
Fig.
+
===Plate 6===
  
 +
[[File:Meyer1920_Plate_6.jpg|600px]]
  
12.
 
  
 +
Fig. 1. Cross-section of twin hydatiform chorionic vesicles within the tube. (Specimen No. 825.) X3.
  
Fig.  
+
Fig. 2. Hydatiform villi from same specimen in section. X 45.  
  
 +
Fig. 3. Embryo No. 1771, covered with magma. X 4.
  
13.  
+
Fig. 4.  Cross-section of tube No. 1771. X 2.  
  
 +
Fig. 5. Cross-section of tube from same case. X 4.
  
Fig.  
+
Fig. 6. Hydatiform villi from same case. X 45.  
  
 +
Fig. 7. Hydatiform chorionic vesicle in loco with the tube incised. No. 2052. X 2.
  
14.  
+
Fig. 8. Gross appearance of specimen No. 70. X1.6.  
  
 +
Fig. 9. Gross appearance of specimen No. 323. X 1.75.
  
Fig.  
+
Fig. 10. Gross appearance of specimen No. 749. X 1.1.  
  
 +
Fig. 11. Gross appearance of specimen No. 1323. X 1.2.
  
15.  
+
Fig. 12. Gross appearance of specimen No. 1325. X 12.  
  
 +
Fig. 13. Grass appearance of specimen No. 1914. X i
  
Fig.  
+
Fig. 14. External appearance of the larger part of the small mass of specimen No. 1926. X 4.  
  
 +
Fig. 15. Embryonic (cyemic) mass accompanying No. 1926. X 4.
  
16.  
+
Fig. 16. A small portion of specimen No. 1189 still in Inco. X 6.  
  
 +
Fig. 17. Another portion of the same specimen. X 30.
  
Fig.  
+
Fig. 18. No. 2077, an apparently normal specimen, partly surrounded by decidua. Natural size.  
  
 +
Fig. 19. A portion of the above clearly showing numerous typical hydatid cysts in area in focus. X 3.
  
17.  
+
Fig. 20. Sections of villi from specimen No. 690. X 50.  
  
 +
Fig. 21. A portion of specimen No. 865 still embedded within the uteras. X 4, reduced J.
  
Fig.  
+
Fig. 22. A portion of specimen No. 435", showing a small villus in mid-portion of the figure, which has an exceptionally long syncytial bud. X 50.  
  
 +
Fig. 23. A small portion of specimen No. 962", showing a framework of epitheUum arising from the chorionic membrane. X 50.
  
18.  
+
Fig. 24. Vacuolated masses of syncytium, nodules of trophoblast, and especially garlands com- posed in part of distinct cells of the Langhans type. Specimen No. 1324. X 300.  
  
 +
Fig. 25. An apical trophoblastic nodule from specimen No. 516. X 6.
  
 +
Fig. 26. A portion of the chorionic membrane from No. 714, showing corrugation of the proliferating epithelium. X 50.
  
Fig. 24. Vacuolated masses of syncytium, nodules of
+
Fig. 27. A hydatid villus illustrating epithelial constrictions between successive portions. Specimen No. 714. X 50.  
trophoblast, and especially garlands com-
 
posed in part of distinct cells of the Lang-
 
hans type. Specimen No. 1324. X 300.  
 
  
Fig. 25. An apical trophoblastic nodule from specimen
+
Fig. 28. Epithelial vesicles within the stroma. Specimen No. 872. X ISO.  
No. 516. X 6.  
 
  
Fig. 26. A portion of the chorionic membrane from No.  
+
Fig. 29. Extremity of an epithelial vesicle. Specimen No. 872. X 300.  
714, showing corrugation of the proliferating
 
epithelium. X 50.  
 
  
FiQ. 27. A hydatid villus illustrating epithelial con-
+
Fig. 30. Marked syncytial budding and epithelial proliferation in specimen No. 874*. X 50.  
strictions between successive portions.
 
Specimen No. 714. X 50.  
 
  
Fig. 28. Epithelial vesicles within the stroma. Speci-
+
Fig. 31. Very slight epithelial proliferation in specimen No. 134. X 50.  
men No. 872. X ISO.  
 
  
Fig. 29. Extremity of an epithelial vesicle. Specimen
+
Fig. 32. Extremely marked epithelial proliferation on a small, glassy villus from specimen No. 415. X 95
No. 872. X 300.
 
  
Fig. 30. Marked syncytial budding and epithelial pro-
+
Fig. 33. Disappearing capillaries represented by large, incomplete curved outlines. Specimen No. 749. X 50  
liferation in specimen No. 874*. X 50.
 
  
Fig. 31. Very slight epithelial proliferation in specimen
+
Fig. 34. Collapsed capillaries in process of degeneration. Specimen No. 712. X 95.  
No. 134. X 50.  
 
  
Fig. 32. Extremely marked epithelial proliferation on
+
Fig. 35. The degenerating capillaries show as faint lines only. Specimen No. 651g. X 50.
a small, glassy villus from specimen No. 415.  
 
X 95
 
  
Fig. 33. Disappearing capillaries represented by large,
+
Fig. 36. Fenestrated hydatiform villi among others that are quite fibrous. Specimen No. 651d. X 50.
incomplete curved outlines. Specimen No.  
 
749. X 50  
 
  
Fig. 34. Collapsed capillaries in process of degeneration.
+
Fic. 37. A section of villus from No. 510, showing scattered Hofbauer cells. X 300.  
Specimen No. 712. X 95.  
 
  
Fig. 35. The degenerating capillaries show as faint lines
+
Fig. 38. A small portion of a villus from No. 749, showing an accumulation of Hofbauer cells. X 300.  
only. Specimen No. 651g. X 50.  
 
  
Fig. 36. Fenestrated hydatiform villi among others that
+
Fig. 39. A portion of a rather fibrous decidua. Specimen No. 874". X 300.  
are quite fibrous. Specimen No. 651d. X 50.  
 
  
Fic. 37. A section of villus from No. 510, showing scat-
 
tered Hofbauer cells. X 300.
 
  
Fig. 38. A small portion of a villus from No. 749, showing
 
an accumulation of Hofbauer cells. X 300.
 
  
Fig. 39. A portion of a rather fibrous decidua. Speci-
 
men No. 874". X 300.
 
  
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[[Category:Historic Embryology]] [[Category:Human]] [[Category:Abnormal Development]][[Category:Hydatidiform Mole]][[Category:1920's]]

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Meyer AW. Hydatiform degeneration in tubal and uterine pregnancy. (1920) Carnegie Instn. Wash. Publ., Contrib. Embryol., 40: 327- 364.

Online Editor 
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This historic 1920 paper by Arthur William Meyer represents an early description of hydatiform moles (hydatiform mole, hydatid mole, molar pregnancy, gestational trophoblastic disease) using embryos from the Carnegie Collection. Some of these concepts are historic and have been updated with a better understanding of the genetics of this abnormal development.


See also: 1921 Hydatiform Degeneration in Uterine Pregnancy | 1921 Hydatiform Degeneration in Tubal Pregnancy

Franklin Mall Links: Franklin Mall | 1891 26 Day Human Embryo | 1905 Blood-Vessels of the Brain | 1906 Human Ossification | 1910 Manual of Human Embryology 1 | 1912 Manual of Human Embryology 2 | 1911 Mall Human Embryo Collection | 1912 Heart Development | 1915 Tubal Pregnancy | 1916 Human Magma in Normal and Pathological Development | 1917 Frequency Human Abnormalities | 1917 Human Embryo Cyclopia | 1918 Embryo Age | 1918 Appreciation | 1934 Franklin Mall biography PDF | Mall photograph | Mall painting | Mall painting | Carnegie Stages | Carnegie Embryos | Carnegie Collection | Category:Franklin Mall


Modern Pages:

Links: Hydatidiform_Mole | Carnegie Collection

A type of fertilisation abnormality, when only the conceptus trophoblast layers proliferates and not the embryoblast, no embryo develops, this is called a "hydatidiform mole". Due to the continuing presence of the trophoblastic layer, this abnormal conceptus can also implant in the uterus or ectopically. The trophoblast cells will secrete human chorionic gonadotropin (hCG), as in a normal pregnancy, and may appear maternally and by pregnancy test to be "normal". Prenatal diagnosis by ultrasound analysis demonstrates the absence of a embryo.

  • Complete Mole - Only paternal chromosomes.
  • Partial Mole - 3 sets of chromosomes ( (triploidy) instead of the usual 2.
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Pages where the terms "Historic" (textbooks, papers, people, recommendations) appear on this site, and sections within pages where this disclaimer appears, indicate that the content and scientific understanding are specific to the time of publication. This means that while some scientific descriptions are still accurate, the terminology and interpretation of the developmental mechanisms reflect the understanding at the time of original publication and those of the preceding periods, these terms, interpretations and recommendations may not reflect our current scientific understanding.     (More? Embryology History | Historic Embryology Papers)

Hydatiform Degeneration In Tubal And Uterine Pregnancy

Arthur William Meyer (1873 – 1966)
Arthur William Meyer (1873 – 1966)

By Arthur William Meyer.

Professor of Anatomy in the Lelaiul Stanford Jr. University.

Volume IX (1920) pp 327- 364 With six plates.


Links: Plate 1 | Plate 2 | Plate 3 | Plate 4 | Plate 5 | Plate 6 | Contribution No.40 | Volume IX | Contributions to Embryology | Hydatidiform Mole | Tubal Pregnancy

Introduction

The following study is an outgrowth of a survey (planned by Mall) of the embryological collection of the Carnegie Institution of Washington. It was my privilege to share in this undertaking and to be permitted to follow any matters of special interest to me. The following report concerns itself especially with the occurrence of hydatiform degeneration in abortuses and specimens in the Mall Collection which were obtained through operation and were classed as pathological. My attention was attracted to the subject while engaged in an examination of the Hofbauer cells, begun at the suggestion of Mall. For the purpose of convenience I shall discuss the tubal and uterine cases separately, including what is common to both with the latter.

Tubal

Strangely enough, the occurrence of chorio-epithelioma arising from tuba pregnancy seems to be better known and also better established than the occurrence of hydatiform mole within the tube. This is especially surprising in view of the stress laid by Marchand (1898) upon epithelial proliferation in cases of hydatiform mole and in view of the fact that trophoblast formation and epithelial proliferation in general have been regarded as being greater in tubal than in cases of uterine implantation. This is illustrated well by such cases as that of Fellner (1903), in which it was impossible to distinguish by histologic examination between the epithelial proliferation present in a case of tubal pregnancy and that from a chorio-epithelioma. From these circumstances alone it seems to me that one might expect hydatiform degeneration to be relatively more common in the tubes. Moreover, when it is recalled that experts still regard it as impossible to decide upon the question of malignancy or benignity in cases of suspected uterine chorio-epithelioma from histologic preparations alone, this surmise gains more in probability. The presence of hyperactivity in the trophoblast in many cases of tubal pregnancy as compared with the uterine was confirmed also by personal observation, and if, as stated by Teacher (1903), chorio-epithelioma arose in hydatiform moles in approximately 40 per cent of 287 cases, and according to Seitz (1904) and Fraenkel (1910) even in 50 per cent, the occurrence of hydatiform degeneration in tubal pregnancy can hardly be doubted because of this fact alone. Nevertheless, of the 7 cases of tubal hydatiform moles cited by him, Werth (1904) regards only the case reported separately by von ReckUnghausen (1889) and by Freund (1889) as well authenticated. Werth reserves judgment, however, on the case of Matwejew and Sykow (1901), a report upon which was accessible to him, and to me, in a short review only. Seitz, however, accepted the short review of this case as convincing, nor did he question the case of Otto (1871), or that of Wenzel (1893), and he incorrectly credited Wenzel with two cases. Werth, on the contrary, regarded these last two cases, and also that of Croom (1895), which is accepted also by Veit (1899), as undoubted instances of "simple hydropic degeneration of the connective tissue of the villi so connnon in aborted chorionic vesicles, both from the tubes and from the uterus." Werth unfortunately does not state just what he means by simple hydropic degeneration, but since he speaks of it as common in aborted ova, one may conclude that he refers to changes in the chorionic vesicle which have followed its isolation within the uterus after complete detachment from its implantation site. For want of a better term, such changes may, I presume, be spoken of as maceration changes, although usually they occur under non-putrefactive conditions. However, I do not thereby imply that these changes are similar under sterile and under putrefactive conditions.


Since Werth speaks of simple hydropic degeneration in aborted ova he does not, I take it, refer to a dropsical condition of the villi possibly due to an obstruction of the venous return, for such a condition necessarily would be rare and not common. Moreover, this condition of necessity would have to arise before and not after the death of the embryo and detachment of the chorionic vesicle. As in one of the cases of Hiess (1914), such a specimen also should contain blood-vessels — for, as emphasized also by Ballantyne (1913), the hydatiform villus is not merely an edematous villus.


That any one at all familiar with hydatiform degeneration, in its earlier as well as its later forms, upon gross and microscopic examination, could confuse it with maceration changes in a fairly well-preserved specimen in any but its very earliest stages does not seem possible to me. Normal villi contain capillaries, not to mention other things characteristic of them. Hydatiform villi, on the contrary, do not contain them, or only very rarely so, and in the early stages. When a villus becomes hydatiform — that is, when hquefaction of the stroma occurs — this liquefaction appears in more or less restricted portions of the villus, thus giving rise to the long fusiform and later spherical vesicles so characteristic of hydatiform mole. But when a villus becomes macerated the change is general, and usually also is noticeable in the embryonic and chorionic membrane itself, or at least within the epithelium. The latter usually is lifted from the stroma here and there, the caliber of the entire villus is increased, and the cai)illaries and the stroma show maceration changes as the villus becomes more translucent. This increase in cahber of the entire villus is not due to local liquefaction of the stroma, but to the pseudo-edema occurring in a villus of normal structure and form. In hydatiform moles, on the contrary, the epithelium not only is firmly attached but usually hyperactive. The changes characteristic of hydatiform degeneration may and often do appear in the villi wliile they still are imjilanted, and not only after the chorionic vesicles are detached. This docs not imply, however, that the villi of a detached hydatiform mole can not also undergo maceration changes. They, of course, frequently do so, and it is in such cases as the.se that differentiation may be difficult or impossible, esjjecially if it is to be made from an examination of ill-preserved fragments only. The same thing is true also of the villi in the early stages of hydatiform degeneration and maceration, especially when the latter masks the former. The difficulty would be still greater in case of whole chorionic vesicles which are almost completely dissolved, leaving only a shadow picture formed by a coagulum without nuclei, which nevertheless may retain almost perfectly the form of the chorionic vesicle and of the individual villi. It may long be impossible to differentiate such cases as these, but they form only a relatively small proportion of the whole. The many cases both of uterine and tubal chorionic vesicles which still were implanted and show exceedingly fine instances of hydatiform degeneration, as well as the many splendid examples of groups of villi which were still implanted in the tube or in the decidua, and which were eciually good examples of hydatiform degeneration, leave no room for doubt as to the frequency of occurrence of this condition, even after due allowance is made for the doubtful cases.


Werth further concluded that not one of the 7 cases of chorio-epithelioma regarded as having arisen from tubal pregnancies recorded before 1904 was sufficiently authenticated. Nevertheless, by 1910 Veit felt justified in saying that a considerable number of cases of chorio-epithelioma arising from tubal pregnancies had been described. He added that Risel (1895) gathered 11 cases from the literature and that the second case had been reported since Risel's paper. Since my interest in the subject is largely incidental, I have not taken the trouble to gather from the literature cases of chorio-epithelioma alleged to have arisen from tubal pregnancies which may have been reported since Veit wrote. Moreover, I could not presume to judge these cases critically. Hence I will accept the fact that chorio-epithelioma arising from tubal pregnancy is regarded as established by a number of investigators. If the conception regarding the relation of chorio-epithelioma to hydatiform mole is justified, then the occurrence of hydatiform degeneration in tubal pregnancy must follow on a priori grounds alone. Moreover, whatever the causes of hydatiform degeneration may be, one possibly is safe in assuming that the condition is not restricted to the uterus, and when I noticed that hydatiform degeneration was so very common in young uterine abortuses the surmise that it might he still more common in cases of tubal pregnancy seemed justified. Since over 100 specimens of tubal pregnancies from the Mall Collection were included in the survey originally planned by him, a study of these specimens formed an excellent opportunity for observations on this subject.


That the case of Otto, with its pathetic history, really was one of hydatiform mole, can not be doubted in view of the careful description of the whole case — its clinical history, necropsy, and the histologic examination. This case is interesting also because the degeneration was in its early stages, the hydatids being only as large as a pinhead and the embryo still being present. Moreover, from Otto's description it is very likely that the specimen contained Hofbauer cells which I have discussed elsewhere (Meyer, 1919).


The history of the case observed by Wenzel in 1855 and reported in 1893 is equally complete and equally pathetic, as could be surmised by all familiar with the history of tubal pregnancy. In this case the mole was as large as a "hen egg," the hydatids varied in size from a dot to a "bird cherry (wild? cherry), and the degeneration was universal, although the menstrual cycle of this specimen was given as only 51 days. It is significant that Wenzel expresses surprise that even excellent handbooks of the day had nothing to say about hydatiform mole in cases of tubal pregnancy, except perhaps to refer to the case of Otto. Nor does the case of Wenzel seem to be the first one observed or that of Otto the first one reported, for Storch (1878), in truly epochal, though largely ignored, observations on hydatiform mole, cites Hennig (187G) as stating that two cases of moles in the tube were reported by Blasius (very likely E. Blasius, 1802-75). Since Storch wrote on hydatiform mole it is implied that Blasius saw one of these and not one of another type of mole, and since hydatiform mole is such a striking condition and has evoked much more interest than the other forms, an observation regarding it in the tubes well might travel down the decades, particularly since until recently the occurrence of hydatiform degeneration in the tubes was regarded as extremely rare. This is indicated also by the fact that Menu (1899) still referred to the case of Otto as a curiosity.


Pazzi (1908') states that two cases of extrauterine moles have been described each by Hennig (1872), Farell (1893), Donald (1902), and one case each by Otto, Freund, Theileher, Maret, Matwjew (Matwejew?) and Sycow (Sykow?), Bland Sutton, and one case of ovarian mole by Wenzel (1893). Wilkinson is said to have described a case of rupture of the tube with reduction of the mole to the size of a cherry, and Lob (1902) also gives a case of molar tubal pregnancy without cessation of menstruation. Since I am quoting Pazzi essentially verbatim, it is evident that he did not read the literature critically or discriminate between ordinary and hydatiform moles, but was misled by the old inclusive and confusing usage of the terms mole and molar, still current at the present day.


Krueger (1909) also reported a case of hydatiform mole with a cyst as large as a "walnut." The pedicle was 4 cm. long and attached to the amnion near the insertion of the cord. Krueger spoke of this as a placental cyst but regarded it as a hydatiform-mole-like structure which, microscopically, was limited to a single villus. If this were the only evidence presented by Krueger one might well question the nature of the cyst, but he added that microscopically the beginnings of hydatiform formations could be recognized on other villi also. Hence it would seem that Krueger's case must be added to the authenticated cases of hydatiform degeneration in the tubes.


So far as I am able to learn, then, the literature contains reports of 9 cases of hydatiform mole occurring in the tube, but two or three of these cases are not well authenticated. These 9 cases are formed by the 2 cases of Blasius or Hennig, that of Otto, of von Recklinghausen and Freund, and of Wenzel, the 2 of Croom, that of Matwejew and Sykow, and that of Krueger. A critical reading of Hennig's book on diseases of the tubes and tubal pregnancy makes it quite clear, however, vhcii, Hennig mainly said that Blasius discovered "tubal moles" and that he observed two, and Behm one case of abortion of tubal moles. From Llie context also it is very clear that Hennig was not discussing hydatiform moles, although it is not possible to say whether he meant that he himself or Blasius observed two cases. I should judge that the latter is the idea it was meant to convey. To these 7 authenticated cases I would add that of Maxwell (1910). In reading Maxwell's doscription one must feel that he himself regarded the case as one of hydatiform mole, but deferred to the opinion of the "Committee." This is suggested also by the title of his article. The illustration which accompanies Maxwell's article is so very suggestive, and his description so characteristic of hydatiform mole, that it seems very probable indeed that the specimen really was such. Maxwell states, for example, that "sections of the viUi embedded in the wall of the tube have the typical structureless, bloated appearance of such pathological villi; and though there is no central cavitation in the villi, their structure, associated with the active proliferation of the Langhans layer, suggests that one is looking at a stage just short of vesicle formation." Moreover, as I am about to show, hydatiform mole is so very common both in tubal pregnancies and in uterine abortions as to increase still further the likelihood that Ma:. well's case actually was one of hydatiform mole. This is merely an opinion, and only a completer description or an examination of the specimen itself could decide the matter.


In connection with what was said before, it is interesting that Maxwell also emphasized that epiblastic activity is increased in all abnormal sites of implantation, and any one interested in the problems of tubal pregnancy and acquainted with Mall's (1915) findings will be struck by Maxwell's statement that microscopical examination of many cases of tubal gestation lends no weight to the view that chronic inflammation of the tubes is at all a common causal factor of tubal pregnancy. Nor can I refrain, in this connection, from quoting the uncontradicted opinion of Doran, expressed in the discussion of Maxwell's case, that tubal gestation "probably represents some general deterioration in the generative power among civilized women."


To the 8 cases contained in the literature I wish to add 48 found among the first 1,187 accessions from the Mall Collection. Nor is it necessary to stop with these, for this collection contains many more not here included. It is merely a matter of recognizing the specimens by a routine examination, and since this paper has been written a number of specimens have been recognized among the daily accessions of tubes received through the unselfish efforts and the scientific interest of practitioners in all parts of the nation.


In addition to over 100 free specimens of uterine hydatiform degeneration, I have also seen more than a dozen fine specimens in large sections of uterine implantation sites, and some entire specimens still embedded in pregnant uteri and tubes. Indeed, how many cases of hydatiform degeneration one can find in conceptuses in tubal or hysterectomy specimens will depend very much upon the care with which the examination is made, for the condition undoubtedly is extremely common, and not I'are, as heretofore supposed.


Although the alleged menstrual age of these conceptuses ranged approximately from 6 to 218 days, most of them were young empty chorionic vesicles or mere remnants of such. Portions of quite a number still were implanted within the tubes, however, and among these were two unusually line ones in a rare specimen of twin pregnancy in the tube donated by Dr. Cecil E. Vest, of Baltimore. Since the question of superfetation has been raised also in connection w4th twin tubal pregnancies, I hasten to add that such a phenomenon, even if it ever occurs (which seems exceedingly doubtful) can be excluded absolutely in this case. Both chorionic vesicles were approximately of the same size and lay in practically the same cross-section of the tube, the surfaces of contact being flattened.


Before proceeding with the statistical findings, I may say that the abortuses in the Mall Collection regarded as pathological are grouped (1) as villi only; (2) as empty or partial chorionic vesicles; (3) as chorionic vesicles containing some or all of the amnion; (4) all specimens containing nodular, or (5) cylindrical embryos, or (6) stunted, and (7) macerated and mummified fetuses. Any one interested in this classification will find it discussed and exemplified in an article by Mall (1917).


There were 40 tubes containing villi only, and in 14 of these hydatiform degeneration probably was present. In 10 specimens its presence was undoubted, but in 4 it was probable only. I realize that this margin of probability is exceedingly largely, but this is easily understood if it is recalled that often only a few degenerate villi embedded in clot were contained in the cross-sections of many of the tubes, and that only a few sections were examined, not, of course, a complete series of each tube. Had the entire tubes been examined, or if more villi had been present, and if those present had been better preserved, the difficulty would have been almost wholly obviated. However, it is idle to set forth these things, because such conditions never will obtain, and the margin of probability becomes greatly reduced if it is remembered that in a large series the specimens necessarily supplement each other. Moreover, the changes in the villi often are so typical that they are unmistakable, even if only a few villi are present. Besides, examination in complete series undoubtedly would increase, not decrease the number found. In some of the doubtful cases the existence of hydatiform degeneration became probable only upon comparison with the many uterine specimens previously examined.

Fig. 1. Cross-section of twin hydatiform chorionic vesicles within the tube. (Specimen No. 825.)
Fig. 2. Hydatiform villi from same specimen in section.

The evidence offered by the 36 tubal specimens in the second group, which is composed of empty chorionic vesicles or parts thereof, was very conclusive, for the cut portions of most of these tubes contained considerable portions or even sections of whole chorionic vesicles, sometimes quite free from clot. Some of them were implanted almost perfectly in the wall of the tube, and although many of them were folded extremely and collapsed more or less, small areas of several were nevertheless implanted undisturbed within the tube. The villi in some of these implanted specimens were so characteristic and the whole picture so exquisite, that the specimens rightly belong among the very finest instances of hydatiform degeneration found anywhere so far. This is true in particular of the case of twin pregnancy received from Dr. Vest. In this specimen the two chorionic vesicles, the intervillous spaces of which were devoid of blood, lay in almost the same transverse diameter of the tube and hence had distended the latter considerably. Both were implanted quite well over the entire area of contact, which included the whole perimeter of the tube. The chorionic vesicles were; flattened at the region of mutual contact, which divided the tube somewhat unequally as shown in figure 1. Although the embryo and the amnion long had disintegrated completely, and although the chorionic membrane itself is thin, covered by degenerate epithelium and also disintegrating, the epithelium of the villi not only is well preserved but is accompanied by large masses of trophoblast and considerable syncytium. Syncytial buds are found on the chorionic membrane also. The tubal mucosa is larger and the tubal wall partly destroyed by the invading trophoblast. Only a few small vestiges of the walls of the villous vessels remain, and the stroma of all the villi has undergone changes characteristic of hydatiform degeneration represented in figure 2. One villus also contains an epithelial cyst resulting from epithelial invagination with subsequent isolation of the distal extremity, a process to be referred to later in connection with uterine specimens. Since most of the villi of this and similar specimens still are implanted in the tube, there can no longer be any question as to the time in which hydatiform changes in the stroma of the villi may be inaugurated. As illustrated in other instances in which isolated and small groups of villi still were implanted, the advent of degeneration of the stroma occurs, in part at least, before the villus is detached. Hence it is not merely a post-mortem or maceration change.

Fig. 3. Embryo No. 1771, covered with magma.
Fig. 4. Cross-section of tube No. 1771.

Another very interesting specimen of tubal implantation is No. 1771, received from Dr. H. M. N. Wynne, of the Johns Hopkins Hospital. The menstrual age of this specimen is 49 days, but its anatomic age, as based upon length according to Dr. Streeter's curve (unpublished), is 37 days, thus showing a discrepancy between the menstrual and anatomic ages of 12 days. The embryonic length is only 12.5 mm., although with a menstrual age of 49 days it should be at least 18 mm. Upon examination, Dr. Streeter found the chorionic vesicle to contain a good deal of magma, some of which still was adherent to the embryo, as figure 3 shows. As has been repeatedly emphasized in the hterature, the presence of this coagulum in itself probably indicates that the embryo died some time previously.

Fig. 5. Cross-section of tube from same case.
Fig. 6. Hydatiform villi from same case.

The wall of the tube is quite thin, as figure 4 shows, but the implantation is fairly well preserved around the whole perimeter of the specimen. The mucosa is destroyed throughout the greater extent of the section and the trophoblast is abundant, except in one rather degenerate and hemorrhagic area. The chorionic membrane is thin but contains some vessels distended with blood. The stroma of many of the villi also contains vessels filled with blood, but the vessels in many others are very evidently in degeneration. The syncytium is scanty and many of the villi are very plainly hydatiform, as seen in figures 5 and 6.

Fig. 7. Hydatiform chorionic vesicle in loco with the tube incised. No. 2052.

A third exceptionally fine specimen of tubal hydatiform mole is No. 2052, donated by Dr. N. M. Davis, of Washington, D. C. Figure 7 shows a portion of the tube containing the hydatiform mole, some hydatiform villi of which protrude through an incision in the wall of the tube. The whole opening is filled with typical hydatiform villi barely detected by the unaided eye but perfectly evident under an enlargement of 4 diameters. They present an extremely fine picture when seen with the binocular under a magnification of 10 to 20 diameters. Examination under a higher magnification shows that the preservation of the specimen is unusually good and that all the villi are markedly hydatiform. Trophoblastic proUferation is so marked that in some places it gives the appearance of decidual formation.


Relatively little syncytium is present, but the trophoblast invades the muscularis in many places and a good deal of coagulum is present, most of it apparently having arisen from degeneration changes in the stroma of the mucosa and from similar changes in the trophoblast and the muscularis. The latter is moderately invaded by round cells. No remnant of the wall of the chorionic vesicle or of the amnion or embryo could be detected in the sections examined, both evidently having been absorbed completely, only some of the villi remaining behind; or, the chorionic vesicle may have been aborted and these villi left implanted within the tube.


Some exceedingly fine hydatiform villous trees wore found among the specimens in this group. Scaffoldings or frameworks formed by proliferating syncytium arising from the epithelium of the chorionic membrane also were seen. Since the syncytial buds were found far out on proliferations of trophoblast which capped the viUi, and also in the center of trophoblastic nodules, the origin of the syncytium from the Langhans layer would seem to be again and exceptionally well confirmed. In some cases a detached hydatiform villus was fastened by opposite extremities to two portions of the tube wall. It is well to remember, however, that one of these attachments probably was gained before the separation of the particular villus from the chorionic vesicle.


Of the 36 cases remaining in this group of chorionic vesicles without amnion, after deducting 8 (7 of which belong in group 1 and 1 in group 2), 50 per cent showed the presence of undoubted hydatiform degeneration and in 1 additional case its existence was doubtful.


Since only a few specimens are contained in each of the last five groups, I shall treat them as one. Among 28 specimens remaining in these groups 12, or 43 per cent, showed the presence of hydatiform degeneration and 4 others were doubtful. From this percentage it is evident that the incidence of hydatiform degeneration among tubal specimens seems to increase with advancing age of the conceptus rather than decrease, as will be emphasized in connection with the uterine specimens to be considered later. This probably can be attributed to the fact that the specimens in the first group are composed of villi only, and that many of the empty chorionic vesicles in group 2 were detached from the wall of the tube by hemorrhage before hydatiform degeneration had developed sufficiently to enable me to recognize it. Moreover, it must be remembered that all tubal specimens, no matter in what group they are classified, are in fact young specimens, and since those falling in the latter grou])s succeeded in maintaining a foothold in spite of repeated hemorrhages, a larger number of them might be expected rightly to show the presence of a hydatiform change.


The incidence of hydatiform degeneration in the 104 tubal pregnancies classed as pathologic is 44, or 42.3 per cent of the whole. This is a somewhat higher incidence than was obtained in the 348 uterine abortuses classed as pathologic. and may be accounted for partly, or wholly even, by the greater incidence of young specimens in the tubal series. That the tubal specimens undoubtedly were younger follows from common knowledge regarding tubal pregnancies alone, but it also is shown by the average menstrual ages, which were 43.4 days in 25 tubal, as compared with 66.6 days in 51 uterine specimens. Moreover, 32 of the 48 tubal specimens of hydatiform defeneration, or 66.6 per cent, fall into the first two groups, thus again showing that the majority' are small, young specimens.


Although the incidence of hydatiform degeneration among the pathologic tubal specimens is but slightly higher than that among the pathologic uterine specimens, the incidence of hydatiform degeneration in all tubal specimens contained among both the normal and pathologic is twice as high as that among the same classes of uterine specimens. This can be explained only partlj' by the fact that a larger proportion of the tubal specimens are young and pathologic. The pathologic tubal specimens form 69.2 per cent of 153 normal and pathologic tubal specimens found among the first 1,187 accessions, but the pathologic uterine specimens form only 33.6 per cent of the normal and pathologic uterine groups among the same accessions. But the real question remains, for the incidence of hydatiform degeneration among the specimens classed as pathologic was essentially the same in tube and uterus. Hence an increased incidence of 100 per cent in hydatiform degeneration in the tubes may be due to the less favorable nidus found there. If so, it throws a very significant light upon the probable cause of hydatiform degeneration, which would seem to he in the conditions surrounding the implantation and early development rather than in the ova or spermatozoa themselves.


The conclusion reached in a study of uterine specimens that hydatiform degeneration is absolutely less, not more frequent near the menopause, is confirmed also by the study of the tubal specimens. The average age of 20 women in the tubal series was 33.9 years, as opposed to an average of 31 years obtained from 36 women in the uterine group. This age difference offers a tempting opportunity for generalization, and did the statistics include thousands of cases one might be willing to say that it points to a progressive change as cause, which begins in the uterus and finally reaches the tubes. But strangely enough, the average number of years of married life of 15 women in the tubal series is exactly the same as that of 29 women in the uterine series, or 7.1 years. This fact at once guards against a venturesome hypothesis, for it allows no longer period for the supposed ascending change to reach the tubes than the uterus.


Eight of 20 women from the tubal series had borne one child, 4 had borne two, and 3 more than two; thus again more than confirming the statistical findings in the uterine series, which show that 9 of 33 women had borne once and 18 but twice. The parallelism between these statistics is striking indeed, especially if the small numbers be considered; 14 of 23 women, or 60.8 per cent, in the tubal series had aborted but once, as compared to 19 out of 44, or 46.3 per cent in the uterine series, a fact which again points to the middle rather than to the end of tlie reproductive life of these women.


I do not know whether or not hydatiform degeneration in the tube also is relatively more common near the menopause, as will be shown to be the case in the uterus, for I have not been able to obtain data on the relative frequency of tubal pregnancy in the different decades in the reproductive life of women. However, since by far the greater number of pregnancies usually occur early in this period, it probably would be safe to assume that most of the tubal pregnancies occur also at this time. Consequently, it might well follow that the ratio of tubal hydatiform degeneration to the number of pregnancies occurring in the later actually might be greater than that in the earlier decades.


The structural changes in hydatiform degeneration will be considered more fully in connection with the uterine cases. Suffice it to say that since I directed my attention especially to hydatiform degeneration I have been able to recognize its presence repeatedly at sight in relatively young vesicles (1 cm. large) not only from uterine but also from tubal pregnancies. This is, of course, especially true in the former, for the chorionic vesicles of these often are {}uite characteristic, and if inspection with the unaided eye or with a reading glass under a magnification of 2 diameters fails to reveal the true nature of the specimen, examination with a binocular under a magnification of 10 or 20 diameters often makes immediate identification possible.

Uterine

To read the titles of articles on '"molar" pregnancies which have appeared during the last few decades, even, is a rather wearisome task. By far the great majority of the articles concern themselves merely with the report of "a case" or (rarely) of "several cases" of hydatiform moles. The recent cancer hterature stands in marked contrast to this, for not even the general practitioner would think of reporting a routine case of cancer of the breast, let us say. The significance of these facts is self-evident, and whatever else they may mean they do imply that hydatiform mole still is regarded as a rare condition. Indeed, many of those reporting "a case" frankly say so, and although the incidence of hydatiform degeneration is estimated variously by different authors and investigators, there seems to be entire agreement that it is a rare, even if not an extremely rare condition. Tliis opinion seems to be shared even by those general practitioners whose long practice runs high up into the hundreds or even into the thousands of obstetrical cases. Indeed, many general practitioners declare that they have not seen a single case of hydatiform mole diunng the practice of a long life.


This prevailing opinion can not be attributed solely to the influence of the schools or to books, but is based upon the actual experience of the individual practitioner and upon his conception of what constitutes hydaliform degeneration. This is illustrated, for example, by Menu, who said that a small hydatiform mole weiglis 300 grams, a large one 8,000, with an average weight in his series of cases of 1,700 grams. But even specialists in charge of hospitals have reported experiences similar to that of the general practitioner. Pazzi (1909), for example, stated that although he had observed more than 6,000 cases of labor in liis private and hospital practice, he never met with a case of hydatiform mole. Moreover, it would seem that only some specialists have come to regard the condition as somewhat less rare than was hcretofon; supposed. This is well expressed by Williams (1917), who wrote: "Hydatiform mole is a rare disease, occurring, according to Madam Hoivin, once in 20,000 cases. On the other hand, the statistics of Williamson would indicate that it may be found but once in 2,400 cases." Williams adds, however, that in his own experience it occurred even more frequently than stated by Williamson; and Essen-Moller (1912), on the basis of 6,000 cases treated between 1899-1908, gives the incidence at the Frauen-Klinik at Lund as 3 per 1,000. My former colleague, De Lee (1915), in commenting on hydatiform degeneration, also stated that he has "frequently found in aborted ova one or more vilU degenerate and forming vesicles"; and similar remarks were made also by others, notablj^ by Miiller (1847), Marchand (1895), Veit (1899), van der Hoeven (1900), Hiess (and according to him also by von Hecker), Langhans, Weber, and Frankel. Findlaj' (1917) also regards "it as fair to conclude with Veit, Freund, and Dunger that abortive types of hydati- form mole are commonly overlooked," and although he gave no evidence for his opinion Weber (1892) insisted that hydatiform mole "occurs much oftener than we are led to believe from books or other literature." Essen-IMoller say's Konig gave an incidence of 1 j^er 728 cases. Pazzi (1908) stated that Dubisa}' and Jennin found in 1903 that hydatiform degeneration occurs once in 2,000 pregnancies, and that Cortiguera in 1906 declared that the frequency' of hydatiform mole has a discouraging variation of from 1 in 3,000 to 1 in 700 labors, but that in his personal experience Cortiguera saw one case in every 300 labors. The latter incidence is only slightly higher than that given by Essen-Moller for the clinic at Lund, and somewhat below that of Kroemer (1907), who found 15 hydatiform moles in 3,856 births, or one in every 257 cases. Mayer (1911) reported 10 instances among 3,105 cases of labor, an incidence of 1 in 310 cases, and it is only necessary to add that Donskoj (1911) stated that the incidence of hydatiform mole in 28,406 cases at the Frauenkhnik at Miinchen, between the years 1884 and 1910, was only 1 for every 4,058 births, to emphasize the discouraging variation of which Cortiguera spoke. Donskoj also stated that Engel gave the incidence as 1 in 800, and Korn as 1 in 1,250 births. Such a surprising fluctuation in the apparent incidence in adjacent communities points to differences in conception of what constitutes a hydatiform mole, and also to differences in character of the material upon which the calculations are based.


The existence of hydatiform degeneration in far greater frequency than commonly supposed is indicated also by the records of the Department of Embryology of the Carnegie Institution of Washington. However, the material covered by these records is not identical with that upon which the above opinions, or those of other obstetricians are based. The opinion of the obstetrician is based upon material belonging very largely in the later months of pregnancy, while that in the Mall Collection, on the other hand, belongs very largely in the earUer months. Hence this material is not truly representative of the entire period of gestation, but the same thing is true of the material upon which the general practitioner, the obstetrician, and the gynecologists have based their opinions, for these are based largely upon material from the last months of pregnancy. Hence mainly the cases of hydatiform degeneration which survive come to their attention.


But unless we can assume that the incidence of hydatiform degeneration is constant during the whole period of gestation, its incidence at any particular time of this period may very incorrectly express that at any other time. This could fail to be true only if the incidence of death of the conceptuses and their susceptibility to hydatiform degeneration were exactly uniform throughout every period of intrauterine life. But we know that neither is true, for it is common knowledge that by far the great majority of the cases of uterine hydatiform degeneration, recorded in the literature, are mature specimens of total or partial degeneration obtained in the later months of pregnancy. Although such specimens may contjiin villi in various stages of degeneration, they nevertheless represent end or near-end results. Like the fetuses which rarely accompany them, they are full-term or near-term products when regarded as hydatiform degenerations, and unless we are to assume that conceptuses once affected by hydatiform degeneration always survive up to this period, statistical deductions based upon the cases that do survive can give us httle idea of the actual freciuency of the condition throughout the entire period of antenatal life.


That the specimens upon which past and also present opinion is based usually were large, is confirmed by the belief in the prevailing clinical criterion of the existence of a disproportionately large uterus in cases of hydatiform mole. The emjihasis laid on this by clinicians is well illustrated by Seitz, who says that cases in which the uterus is too small are the exception. Indeed, it seems that the validity of this cUnical dictum has been questioned only very recently by Briggs (1912). Since most early conceptuses showing hydatiform degeneration have been inhibited in growth before being aborted, it probably is only the specimens which persist that produce a uterine enlargement greater than could normally be expected. However, since — as emphasized by Gierse (1847), Storch, Hicss, and others — most hydatiform moles are expelled early and spontaneously, it is evident that these can not have been adherent — that is, have penetrated very deeply — or they would not have been expelled early and spontaneously. Furthermore, maceration changes so commonly present in aborted hydatiform moles indicate very clearly that a large percentage of them, together with the decidua, had been more or less completely detached from the uterine wall some time before abortion occurred.


As far as one can gather from the literature, iiic present opinion regarding the incidence of hydatiform degeneration would be parallelled quite correctly if, in the case of measles, we assumed that it was as common in octogenarians as in children. Measles, indeed, is an extremely rare disease in advanced age, but it nevertheless is very common in infancy. This is exactly the mistake we have made regarding hydatiform degeneration. It may be and undoubtedly is a rare disease at or near term, as Clierse also stated, but it probably is the commonest of all diseases during the earliest months of gestation. The typical large hydatiform mole is an end result which it has taken long months to develop. No one seems to have followed its evolution, although hydatiform degeneration, whether total or jiartial, is, of course, gradual in its advent.


The records of the Mall Collection contained 8 cases of hxdatiforni mole in the first 2,400 accessions, showing a fretiuency 8 times as great as that given by WilUamson, or an excess of 700 per cent. Since the lirst 2,400 accessions contain 309 ctises of tubal and also 2 of ovarian pregnancy, only 2,089 uterine specimens remain. Hence the recorded incidence in the uterine specimens really is 8 in 2,089, or 1 in every 261 cases. This incidence is only slightly lower than that of Kroemer, and somewhat higher per 1,000 than that given by Essen-Moller for the Frauenkhnik at Lund, or the personal experience of Cortiguera.


The highest incidence of hydatiform degeneration previously reported is that of Storch, who estimated it as 50 per cent, but he unfortunately did not give a record of his cases. However, Storch emphasized that the typical complete hydati- form mole is a relatively rare form of the disease, and that all manner of transition forms between the normal chorionic vesicle and the completely degenerated one can be shown to exist. Storch further emphasized the commonness of hydatiform degeneration, especially in the early months of pregnancy, but as Veit (1899) well said, Storch somehow has not received sufficient credit for his investigations. Gierse was forgotten completely. This seems strange, especially in view of the fact that Storch's work was done in Copenhagen, where Panum (1860) had done and still was doing such fine and very suggestive, indeed epochal, work on the origin of monsters. Although Storch devoted part of his paper to myoma fibrosum, and reported only 5 cases of hydatiform mole, one of which, however, accompanied a living fetus, his opinions on the whole were far ahead of his time. In order to make this clear I shall quote a very significant passage, which indeed needs but slight changes to serve as a conclusion for my own investigations:


"Nun sind aber bekanntlich Eier mit blasiger Degeneration der Zotten und fehlerhaft oder nicht entwickeltem Fotus ein sehr hiiufiger Befund bei Aborten aus den ersten Schwan- gerschaftsmonaten. Mehrere solche Eier sind schon in den bekannten Arbeiten von Dohrn und Hegar beschrieben worden. Ich habe im Laufe des letzten .Jahres eine grossere .\nzahl von Aborten untersucht und derartige kranke Eier in mehr als der Halfte der Fiille gefunden. Nicht selten ist die Amnionblase vollig leer und enthalt nur eine klare serose Fliissigkeit. In anderen Fallen sitzt an der einen oder anderen Stelle der Innenfljiche des Amnion ein kleiner rundlicher oder unregelmassig geformter, 5-I Mm. grosser Korper, welcher aus Nichts als aus runden, schwach conturirten, zum Theil fettigentarteten Zellen und einer hellen, fast homogenen Zwischensubstanz besteht, und der durch einen feinen, 1-3 Mm. langen Strang von ahnlicher Natur mit dem Amnion verbunden ist. In noch anderen Eiern ist der Embryo zwar etwas weiter entwickelt, aber von den verschiedensten Formen von Alissbildungen befallen. Seltener ist der Embryo einigermaassen wohl gebildet und von bis zu 2 Cm. Lange, wie dies auch Hohl nur einmal gefunden hat. Sehr gewohnlich ist fettige oder lipoide Entartung des Embryo vorhanden; derselbe ist dann eine kiirzere oder langere Zeit vor der Geburt abgestorben. Als die aussersten Glieder dieser Reihe von kranken Eiern stehen endlich die sehr seltenen Falle, in welchen der Embryo seine Entwickelung ziemlich ungestort fortgesetzt zu haben scheint, und von denen die Fiille von Martin und der oben beschriebene dreimonatliche abort Beispiele sind.


"Die blasige Entartung der Chorionzotten kann demnach neben den verschiedensten Zustanden des Embryo fegunden werden. Sehr hiiufig ist letzterer der Sitz von mehr oder weniger eingreifenden Krankheitsprozessen gewesen, die in demselben verschiedene Aliss- bildungen hervorgerufen und ihn in seiner Entwickelung gehemmt haben. Es sind diese Krankheistprozesse wahrscheinlich immer sehr friih im Ei entstanden, und miissen mit Panum zuniichst als entziindliche A'organge aufgefasst werden, welche nach ihrer Intensitat und vielleicht nach dem Zeitpunkte, zu welchem sie im Keime auftreten, bald eine theilweiso N'crocliinp der KeinuinlaKPn dcr mcisten wiclitiKorcii Or^ano mit N'crkruppcUing des ganzcn embryonalon K()ri)ers, bald niehr locale I\lissl)il(hingeii oiiizi'lncr Korjier- thcile horvorrufcn koiinen. Das Erstere ist in den hicr hosprochenen Aburteii sehr hiiufig der Fall: der Embrj'o ist zu eineni unfDriiilichen Kluniiien umgewandelt, dein die nieisten Organe deren Keiine dvirch Entziiiuhing zerstc'irt worden sind, giinzlich fehlen. ^'oIl diescn verkriippelteii Aniorphi linden sieh in anderen Eiern alle Uebcrgiingsfornien zu niehr oder weniger entwiekelten Missbildungen was auch Paniini an einigen Beispielen nachgewiescn hat. Es Scheinen in der That die nicht zerstorten Keinizellen der verschiedenen Organe, nach dem ablaiife des Krankheitsprozcsscs, ihren ursi)runglichen Entwickelungs- j)lan mit einer oft merkwiirdigen Hartniickigkeit, so gut sie es kcinnen, festzuhalten. Von dieseni \'erhaltnisse liefern die bekannten herzlosen Amorphi, die durch einen Zwillingsbruder einhiirt werden und dadurch zu einer oft bedeutenden Cirosse heranwachsen konnen, ein schlagendes Beispiel. In unseren Aborten sind zwar diese Amorphi, die keinen Zwillings- bruder zur Erhaltung ihres Krcislaufes geliabt haben, fruhzeitig zu (Jrunde gegangen, und ihre Clewebsteile sind einer fettigen (lipoiden) Entartung anheimgefallen ; sie haben jedoch ihre Entwickehmg eine Zeit lang fortgesetzt.


"Est is von den verschiedenen Verfassern vielfach von einer Auflosung der Embryonen in der Amnionfliissigkeit und von einer nachherigen Resorption derselben gesprochen worden. Ich glaube indessen, dass die.sen Vorgiingen eine sehr geringe RoUe beizulegen ist. Man findet in der Tlmt gewohnlich Nichts, was auf eine solche Resorption deuten konne. Es scheinen vielniehr die abgestorbenen Embryonen auch lange nach ihrem Tode eine v;rosse Wiederstandfiihigkeit gegen die Einwirkung, von .\mnionflussigkcit beizubehalten. Ich halie mehrmals ganz kleine, verkriippelte Embryonen zwar fetig entartet, in ihrer Form aber v(")llig wt)hl erhalten, in Eiern gefunden, die bis zu 10 Monaten im Uterus zuriickge- hiilten worden sind. Zudem ist die Amnionfliissigkeit in diesen Eiern meist ganz klar, oder sie enthalt nur losgestossene, hinfiillige Amnionejiithelzellen suspendii't. Wenn daher die Eier ganz leer gefunden werden, so riihrt dies gewiss am Hiiufigsten tlaher, dass der Primitivestreifen seiner Zeit vollig destruirt worden und somit gar kein Embryo zur Ent- wickehmg gewommcn ist. * * * Im AUgemeinenerreichensiekienebedeutende (iriisse und werden zudem oft fruhzeitig aus dem Uterus ausgestossen, in dem sie, wie oben bcsprochen, ein sehr betriichtliches Contingent zu den Aborten iiberliaupt liefern. * * *
" Die Traubenmole und die verschiedenen Ucbergengsformen derselben, die an Aborten sehr haufig vorgefunden werden, ist als Hyperplasie und secundiire cystoide Entartung des (von AUantois nicht herstanuumenden) C'horionI)indegewebs vorzugsweise charactertisirt. Die Krank^'eit wird von pathologischen Zustiuiden der i'lbrigen Eitheilc, Amnion und Embryo (Missbildungen, ^'erkriipl)elungen und friihzeitigem .\bsterben des letzteren) sehr haufig begleitet. Seltener ist der Embryo regelamasmig entwickelt, stirbt al)er meist auch dann wegen mangelhafter Vascularisation der (Chorion) Placenta fruhzeitig ab. Sehr selten scheint der P^mbryo ungestort bis zur Geburt sich fort entwickelt zu haben."


But the unregarded observations and illustrations of (Jierse arc still more startling than these opinions and observations by Storch, who knew of CJierse's observations published posthumously by Meckel. The latter quite correctly stated that such careful observations as those made by Clierse always introduce new i)oints of view. If it be remembered that in these days, almost a century later, specimens of hydatiform degeneration which are 4 cm. in diameter still are reported separately as examples of early hydatiform degeneration, the great merit of Gierse's observa- tions in this regard alone will be clearly evident, upon recalling that Giersc pictured a hydatiform villus from a chorionic vesicle tlie size of a hazelnut (about 12 mm.), the largest hydatiils on which were only one-tliird of a line large. Moreover, Gierse added :


"Derlcichen geiinge krankhafte Veranderungen finden sich an au.serordentlichen vielcn Abortus, und sie scheinen die hiiufigste Ursache des Abortus in den ersten Monaten zu sein."


How such an epoch-making conclusion not only could be forgotten, but absolutely overlooked or disregarded, by all but a few of the scores upon scores who have written on hydatiform degeneration, it is difficult indeed to understand. Gierse, who took steps to ascertain what normal villi look like, stated that villi with marked irregularities as described by Desormaux, Breschet, Raspail, and Seller undoubtedly were abnormal; surmised that vilh in abortuses seldom are normal, and added that between the slight pathologic changes in the caliber of the vilh and the most evident hydatiform moles the plainest transition can be found. Among other important things Gierse also recognized the early fenestration of the stroma and pictured such a villus under a magnification of 250 diameters, and although reported very briefly, his findings, wholly confirmed here, still wait for general recognition.


Just as the great majority of specimens described in the literature are large, so 4 of the 8 specimens originally classed as such in the Mall Collection also are large, and none of the 8 are very young, as the following protocols show:

Fig. 8. Gross appearance of specimen No. 70.
Fig. 9. Gross appearance of specimen No. 323.
No. 70 (Dr. Charles H. Ellis) is a small, fimi, degenerate-looking, almost solid mass 40X30X28 mm., composed of small cysts, degenerate decidua, exudate and degeneration products. As figure 8 shows, it is very similar to a very much larger specimen. No. 323 (Dr. V. Van Williams). The latter is a large, firm, felt-fike mass 120X90X65 mm., represented in figure 9. The individual cysts, which vary from 1 to 20 mm., are packed together rather firmly, though a few large ones are free. The exterior of the specimen is formed by a thick layer of degenerate decidua and gives only a slight indication of its true nature upon closer inspection or upon examination of the cut surface. No fetal remnants were noticed, and microscopic examination shows tliat the specimen is composed merely of a large hydatiform mass which was retained for a long tune and then aborted in toto with the surrounding decidua and exudate.
Fig. 10. Gross appearance of specimen No. 749.
No. 749 (Dr. G. G. McCormick), on the contrary, is a fresh, loose, typical hydatiform mass composed of loase hydatids of various sizes, as shown in figure 10. As the specimen floats loosely in fluid, it fills a half-liter jar about two-thirds. A considerable portion of the hydatid cysts are glued into a solid mass by blood, exudate, and decidua, which form a layer on the exterior.
Fig. 11. Gross appearance of specimen No. 1323.
No. 1323 (Dr. J. W. SchUeder) also is a large mass very like the preceding, which completely fills a liter jar. It is accompanied by much clot and composed mainly of a large, thick-walled, hemorrhagic, necrotic mass 80X50X45 mm, containing a large, thin-walled cavity 65X30X25 mm, which is broken at one end. This cavity which is apparently that of the chorionic vesicle, is empty, smooth, and thin-walled, except where it is composed of a characteristic hydatiform mass shown in figure 11.
Fig. 12. Gross appearance of specimen No. 1325.
No. 1325 (Dr. Fred R. Ford), shown in figure 12, is a small, irregular mass 40X33 X 20 mm. , the exterior of most of which is formed by a thin layer of decidua. Within this is a small group of quite tj-pical hydatid cysts, the largest of which measures about 10X5 mm. The appearance of the specimen suggests that it is merely a fragment, though the amount of decidua present indicates that the entire specimen probably was not much larger. The history of this specimen is especially interesting because of the diagnosis of tubal pregnancy, caused by the presence of a cornual myoma and the occurrence of repeated bleeding.

By far the most interesting specimen, in some respects, of hydatiform degeneration among those diagnosed as such upon gross examination in the Mall Collection is No. 1640.


No. 1640 This abortus, received through the courtesy of Dr. J. W. Williams, measured 40X20 X15 mm. Upon examination Dr. G. L. Streeter found it to be composed of a flattened decidual and chorionic mass which, upon section, showed "pearl-like vesicuhir enlargements which suggest hydatiform degeneration." The exterior of this specimen is composed of a thin, hemorrhagic decidua which completely surrounds the villi. The hydxitid luiture of this clearly is recognizable upon close scrutiny with the imaided eye, and easily becomes evident upon magnification of 12 diameters with the binocular microscope. Examination of the histologic preparations reveals it to be a very fine specimen of relatively early hydatiform degeneration.
Fig. 13. Grass appearance of specimen No. 1914.
No. 1914 (Dr. G. C. McGorniick) is a fine, very characteristic mass, part of which is shown in figure 13. It is like Nos. 749 and 132.3, but very much larger, for in fluid it completely fills a 2-liter jar. This specimen was said to have accompanied a living, 7-months fetus, having been expelled between the fetus and the placenta. Only a sniidl amount of clot, and what seems to be a small portion of placenta and membranes, accompanied it. Since the placenta was not saved it is impossible to say whether the mass resulted from partial degeneration of the placenta belonging to the living child, or whether it represented a degenerate twin placenta, which is rather unlikely but not imj)ossible, in view of the well- authenticated cases found in the literature. This specimen is of interest not only for the numerous large, clear cysts, one of which measures 30X25 mm., which it contains, but because it accompanied the birth of a living child and because of the relative rareness of such a coincidence. In regard to the latter. Dr. McCormick added that in his experience of over 1 ,000 labors he had never before met this coincidence. The rareness of the specimen is emphasized still further by the statement of Professor Williams that such an instance has not been observed in a series of over 17,930 obstetrical cases treated by the department of obstetrics of the Johns Hopkins Medical School, as well as by the small series of such cases recorded in the literature.
Fig. 14.
Fig. 15.
No. 1926, a companion specimen to No. 1640, is composed of material from curettage received through the courtesy of Dr. Karl Wilson, of the department of obstetrics of the Johns Hopkins Medical School. It was removed from the same patient about a year later than specimen No. 1640. Upon gross examination the hydropic nature of some of the villi is plainly evident, as shown in figure 14, and upon microscopic examination the diagnosis of hydatiform degeneration could be confirmed, although the villi were extremely degenerate. The menstrual history of this case fortunately is known and is thoroughly reliable. The last menstruation occurred January 24 and curettage was done August 4. Bleeding occurred every two or three weeks during March and April and was repeated throughout May. Since the uterus, which had reached the symphysis, had not enlarged any for months, in view of the long duration of pregnancy the operation was performed. The major portion of the specimen is very small. The chorio-decidual portion was felt-like in consistency and extremely fibrous, due largely no doubt to the long retention. Most of the accompanying material looks like mucosa rather than decidua, although some of the larger pieces very evidently contained villi. Some of these were relatively thick and fibrous, and others were vesicular. All of the material was extremely fibrous, making it difficult to get a satisfactory teased preparation. Accompanying this material was a small body 5X7.5X .30 mm., shown in figure 15. Both nodule and stalk contained some remnants of the embryo. Although the appearance of the stalk suggests the umbilical cord, it contains fragments of the body of the embryo, some of which evidently are composed of nerve tissue.


Microscopic examination of the jiedunculated mass further shows it to be composed of degenerate remnants of organs, tissues, and cells. It is partly denuded and partly covered by a layer of fibrous connective tissue which contains local thickenings. In other areas this fibrous layer gives place to a single or more celled layer, or to polygonal epithelioid cells. The interior of this specimen is composed of a degenerate jumble including fragments of the central nervous system, of the heart, liver, and cartilages. The entire body is chaotic in its structure, and small fragments of the nervous system are scattered throughout its entire extent. This would seem to indicate that the disruption of the tissues was mechanical. The material in which these remnants are contained is composed of coagulum, some mesenchyme, cellular detritus, blood and polymorphonuclear leucocytes, degenerated cells, which appear to have been phagocytic, but which are more likely fusion products or "symplasma" (as Bonnet called them). A few remnants of vessels are found only in the fragments of cartilage.


This short review of the gross appearance of the cases of hydatiform degeneration recognized by the unaided eye with the customary criteria, originally classed as such in the Mall Collection, shows that they vary decidedly in their gross, naked-eye characteristics, both as to size and appearance. Xo. 1640 scarcely is distinguishable as a case of hydatiform degeneration from gross appearances alone, unless one's attention is directed especially to the matter, but all the rest of the specimens, both small and large, not only are easily recognizable, but are so characteristic that they could not possibly be overlooked. As was indicated above, the incidence of these specimens of hydatiform degeneration among the first 2,400 accessions in the Mall Collection was 1 in every 261 abortuses, or more than 8 times the incidence given by Williamson, and 1.3 times that given by Essen-Moller. Although this incidence is so much higher, it does not necessarily contradict the statements of Williamson, for it represents the incidence of hydatiform degeneration in abortuses belonging very largely below 7 months. Nor does it tell the whole story for these months, for since the incidence of hydatiform degeneration given in the records of the Mall Collection is based upon determinations made essentially in the usual way — that is, by unaided inspection of the gross specimen alone — we must regard it also merely as an apparent, not as the actual incidence. For, as will appear later, the actual incidence can be revealed only by a careful gross and microscopic study of all specimens, both normal and pathologic. Such a study has not as yet been completed, but 348 uterine specimens classed as pathologic, and 105 pathologic tubal specimens, contained in the first 1,187 accessions, were carefully examined.


The actual number of cases of hydatiform degeneration found among the 348 uterine abortuses classed as pathologic was 112, or 32.4 per cent of the whole. The incidence of hydatiform degeneration in the pathologic tubal pregnancies was somewhat higher even — 44 specimens of undoubted hydatiform degeneration in 105, or 41.9 per cent. Since nearly all the tubal specimens are young, while the uterine series contains many more relatively older ones, the effect of this fact upon the determined relative incidence of hydatiform degeneration among the pathologic tubal and uterine specimens must be borne in mind. For a reliable conclusion regarding the relative incidence in the uterine and tubal pregnancies it would be necessary to select a series from each, composed of specimens of approximately corresponding ages. "What the incidence of hydatiform degeneration is among the uterine and tubal specimens classed as normal I do not know, but it undoubtedly is far below that in those classed as pathologic. It is well to remember, however, that many, if not most of the instances of beginning degeneration very likely will be found among the specimens classed as normal. This is well illustrated by a hysterectomy specimen, No. 83G.


If we assume that the incidence of hydatiform degeneration among the pathologic specimens in the rest of the Mall Collection is the same as that among those in the first 1,1S7 accessions, then we get over 314 estimated instances of hydatiform degeneration in pathologic tubal and uterine cases alone. Since I have found a number of chorionic vesicles accompanying embryos classed as normal which also show hydatiform degeneration, this number would be increased still further; but unfortunately too few of the specimens classed as normal were examined to justify an estimate. Yet these normal specimens form GO. 4 per cent of the first 1,000 and 40.7 per cent of the first 2,500 accessions. This supposed increase, due to inclusion of specimens contained among the normal, would be offset somewhat, however, by the fact that the first 1,000 accessions contain a somewhat larger proportion of young conceptuses, each succeeding 1,000 probably becoming somewhat more representative of actual life conditions. The difference between the composition of the first 1,000 accessions and that of the 1,000 between 1,500 and 2,500 is not very great, however, for the former contains only an excess of 17.6 per cent of cases falling in the first five groups of the Mall classification, which groups are composed largely of specimens below an embryonic length of 20 mm. Then, the relative proportions of tubal and uterine specimens in the different thousands also must be taken into consideration. But in any case the estimated incidence of hydatiform degeneration in the Mall Collection, calculated without regard to those contained among specimens classed as normal, is 7.5 per cent, and the actual incidence hence probably is more than 1 in every 10 accessions. The incitlency among the uterine specimens alone would be 10.9 per cent, and among the tubal alone 20.8 per cent. This difference of 100 per cent between the tubal and uterine specimens may have a probable significance in connection with the cause of hydatiform degeneration.


If, as alleged by various investigators, the great majority of abortions occur in the first 3 months, it is highly probable that many of these early conceptuses are lost and never come to the attention of any one, and that therefore the proportion of early specimens in this or any other collection is no doubt too small. Moreover, in quite a number of specimens of the first 1,000 accessions the chorionic vesicles were too degenerate for examination, and in others they were absent, but we have reason to believe that this is not true to the same extent in the material beyond the first 1 ,000 accessions. Then, too, since only a few relatively large sections from a single portion of the chorionic vesicles were examined, it is evident that some cases in which the degeneration may have been purely local probably were overlooked. Hence the actual incidence of hydatiform degeneration in this collection is probably not merely 8 times but 240 times as great as that givcMi by Williamson (1900), and 33.3 times as great as that given by Essen-Moller.


Most persons will, I presume, be willing to regard an increase of 700 per cent above that of Williamson as possible, but one of 24,000 percent above Williamson, or even 3,333 per cent above that of Essen-Moller as wholly out of the question.


Yet, strange as it may seem at first sight, this is not a random guess but an estimate based upon (hi; actual incidence of hydatiform degeneration as determined by a careful gross and microscopic examination of mounted and unmounted material from over 400 abortuses. However, I lay no special emphasis on these percentages, and am using them merely to emphasize the great frequency of hydatiform degeneration. It matters little whether we shall ultimately determine an incidence of 10 or 5 per cent, but it does matter considerably whether we regard the frequency as 5 or 0.05 per cent, for this is a diference of 10, 000 per cent.


In view of the prevailing opinion, I realize that these findings may seem incomprehensible and perhaps incredible, unless it is distinctly borne in mind that it is not stated that this incidence refers to the later months of pregnancy or to term. What the incidence in the later months of pregnancy may be I do not know, but I have called attention to an apparently well-founded belief that it is a relatively rare condition, the estimates ranging from 1 in 2,000 to 1 in 728 or 300 cases.


In regard to the incidence of hydatiform degeneration in uterine specimens, it should also be remembered that the life, in contrast to the laboratory incidence for the entire period of gestation is higher, not only because the chorionic vesicles were not included in many of the accessions and because others were too degenerate, but because I have not as yet been able to recognize the very earliest stages with entire certainty. Furthermore, many instances of hydatiform degeneration from the early months of pregnancy, especially the first and second, are inevitably lost. The increase due to these things would be offset somewhat, however, by the lower incidence of hydatiform degeneration in specimens from the last months of pregnancy, relatively few abortuses from these months being contained in the Mall Collection.

Fig. 16.

To what extent the material in this Collection is truly representative of actual life conditions is difficult, if not impossible, to determine. This question could be answered only if all the abortuses and material from abortions actually reached physicians, and if the latter sent all of them to the laboratory. My own impression so far is that the material representative of a sufficiently large community probably would have a somewhat lower incidence, notwithstanding the fact that many specimens not only of hydatiform degeneration, but of abortuses in general, especially from the first month of pregnancy, are lost. However, since the presence of hydatiform degeneration is especially common among early specimens, the inclusion of these might raise the incidence for the whole period of gestation more than the inclusion of all specimens (not excepting those of the last three months) would lower it. But the result obtained would represent the incidence of hydatiform degeneration in abortuses alone, and not that in all pregnancies. The latter could be obtained only by including all gestations which end normally. If we accept Pearson's (1897) estimate that approximately 40 per cent of all pregnancies end prematurely, then the incidence of hydatiform degeneration among abortuses would represent very nearly twice that in all pregnancies. Mall's estimate of 20 per cent prenatal mortality, on the other hand, would give us an incidence only one-fifth as great as that among abortuses. Hence, the actual life incidence of hydatiform degeneration in all gestations would then be 1 in 10, as based upon Pearson's, and 1 in 25. as based upon Mall's estimated prenatal mortality. But even if, as estimated upon this basis, 4 or 10 per cent of all conceptions end in hydatiform degeneration, this does not necessarily contradict the current opinion regarding its rareness at or near term.


A careful examination witli the binocular microscope of all specimens has shown that hydatiform degeneration as a rule is sufficiently general even in young vesicles, so that sections of a single portion about 10 mm. square, would enable one to make a fairly reliable diagnosis. Now and then, however, the process seems to be rather irregularly developed, especially in the larger specimens.


In order to determine accurately the question of distribution of hydatiform degeneration over various portions of the chorionic vesicle, it will be necessary to examine a series of sections of portions of the chorionic vesicle for each small specimen. This has not yet been done, but since the portions used for microscopic examination had been taken at random without previous knowledge of the existence of hydatiform degeneration in any but the 8 specimens above described, and since a series of 453 vesicles was examined, I can not believe that it can often be limited to any particular area on relatively young vesicles. In these it usually is universal even if not complete. It is of special interest in this connection that Muggia (1915), after reviewing the small list of cases of alleged hydatiform degeneration of the chorion laeve in connection with a study of a case of his own, came to the conclusion that these cases are not really degenerations of the chorion laeve, but merely partial degenerations of the placenta. Although I have given no thorough attention to the normal changes in the chorion laeve, I am (quite certain that they are not the cause of confusion in the series of hydatiform degenerations from the Mall Collection. Cases in which whole chorionic vesicles exclusively hydatiform in character were contained in the tubes, and a number of others which still were implanted within the uteri showed equally exquisite hydatiform changes around the whole perimeter. Such cases as these ultimately confirm the oi)inion that in young vesicles as a rule the condition is general except at its very inception. This is true particularly by the time the degeneration has reached a stage which can be considered at all typical in its gross development, as determined by careful examination of numerous specimens with the binocular.

Fig. 17.

It is especially interesting that, just as soon as syncitial hydatitl elliptical villi, or portions of the same begin to appear, the condition can be recognized with some certainty under a magnification of 12 to 20 diameters with the binocular microscope. It often was surprising how relatively early stages could thus be detected and the diagnosis confirmed later by histologic examination. Indeed, Colloidin blocks of tissue from which sections had been cut gave splendid testimony when examined in Huid with the binocular. One of the not very early stages contained in utero and represented in figure 10 could be recognized with the unaided eye; and when examined with the binocular, under a magnification of about 12 diameters, the picture was unusually fine and wholly unmistakable, as shown in figure 17.


That hydatiform degeneration is incomparably more common in the earlier than in the later months of pregnancy, thus justifying the comparison made with measles, is substantiated by statistics covering the material examined. From these it is evident that, excepting cases of large hydatiform masses originally classed as hydatiform degeneration from inspection of the gross specimens alone, practically all the specimens are relatively young. This is true especially of those from tubal pregnancies, and we may hence regard it as established that hydatiform degeneration is a change which is exceedingly common in the earlier months of pregnancy, just as measles is common in childhood, and that it becomes progres.sively less common as the end of pregnancy is approached, just as does measles as senility is approached. The obstetrician does not see most of the cases of hydatiform degeneration, for they merely are reported as miscarriages and the specimens often are destroyed or retained unrecognized by the general practitioner or the midwife. They often are aborted spontaneously and completely with the decidua and rarely are still contained in a closed decidual cast when they reach the laboratory.


The spontaneity of the abortion, especially in early cases, was emphasized also by Storch in the above quotation. Cortiguera (1906) is reported by Pazzi (1908) also to have declared that many moles disappear wholly without leaving a remnant, even if occurring repeatedly in the same woman, and Donskoj also stated that many of those aborted do not come to the attention of physicians because of their harmlessness. This, however, does not imply that those which persist and develop into large masses are equally harmless, and it must be remembered that it is upon these that the current opinion regarding the tendencies to malignancy of the hydatiform mole is based.


The conclusion regarding the greater incidence of hydatiform degeneration in the early months of pregnancy is conclusively confirmed by the occurrence of 32 of the 48 tubal specimens within the first two classes of the pathologic division of Mall, and 104 of the 112 uterine specimens in the first six classes of this division. Most of the specimens in these classes are composed of villi, of empty chorionic vesicles, or of vesicles with embryos most of which have a length of less than 20 to 30 mm. That hydatiform degeneration is more common in the early months of pregnancy is indicated also by the well-known reports of Kehrer (1894) on 50 cases, and of Borland and Gerson (1896), who found that 63 per cent of 100 cases had aborted in the fourth and fifth months of pregnancy. According to Seitz, Hirtzman (1874) also found that 62.8 per cent of 35 cases had aborted between the third and sixth month. Only 4 per cent of Kehrer's 50 cases and only 3 per cent of the cases of Borland and Gerson aborted at the tenth month. Bonskoj stated that 7 of the 10 cases reported by him aborted in the fourth month and none after the sixth month. He stated further that 56 per cent of Bloch's 50 cases aborted before the sixth month, 44 per cent later than this, one being retained until the fourteenth month. The latter case is especially interesting because retention not only beyond term but after the death of the mole seems to be regarded as relatively rare. This, however, does not imply that retention beyond the period of growth of the hydatid mole does not occur, although Sternberg (1910), who also emphasized the great rarity of this condition, erroneously stated that the (Jerman literature reveals only a single instance of missed abortion in case of hydatiform mole, viz., that of Poten (1901). In this case a hydatiform mole of the size of a duck egg; was said to have been aborted approximately one month beyond term. Hence growth must have ceased long before and the mole have remained in ulcro as a "harmless body." To this case of Poten, Sternberg adds a case in which a hydatiform mole of 14X9.6 X4.3 mm. was aborted in the twelfth month after the cessation of menstruation. Although Sternberg included 4 cases from other countries among these missed- abortion moles, inz., those of Shell (undated), Ferguson (also undated), Colorni (190S), and Gaifani (1908), one can hardly doubt that more cases could be added. Since the case of Shell was one of twin pregnancy in which one conceptus became hydatiform, it is not at all unlikely that some other cases among this rather small series of twin pregnancies accompanied by hydatiform degeneration may belong in this category.


Mayer also emphasized the fact that, although instances of retention of fetuses are very common, instances of retention of hydatiform mole are very rare, only a few cases having been recorded. Mayer refers to 2 cases by Kehrer, 3 of Borland and Gerson, and to 1 case of Lange, and reports 4 of his own. These 4 were found among 10 cases of hydatiform mole, an incidence of retention of 40 per cent. They are interesting, especially in connection with the observation of Briggs that, contrary to current belief, uterine enlargement often is not beyond the normal. Mayer says that this enlargement was too great in but 1 of the 4 cases, and that retention lasted as long as 4 to 5 months.


At least 3 of the cases of hydatiform mole originally recorded as such in the Mall Collection belong among retained specimens, as the illustrations alone suggest. But a fair percentage of detached chorionic vesicles included in the list of cases here reported undoubtedly also was retained after the cessation of growth, and it is for this reason that I further emphasize the fact that the uterine volume in a considerable percentage of these cases also, instead of having been too great for the duration of the pregnancy unquestionably was too small. This is well illustrated by the histories of specimens Nos. 70, 323, 1G40 and 1926, and by the specimens themselves.


The average menstrual age of 51 of 112 uterine specimens of this series of hydatiform degeneration — in which the data were available — was 66.6 days, or 2\ months. As will be seen, this is a far lower average age than heretofore reported, a difference which explains itself from what has been said already. It is interesting that the average menstrual age of 5 of the 8 specimens in the Mall Collection originally classed as hydatiform degenerations is 168.2 days, or 2.^, times as great, thus being in substantial agreement with the usual results. Three of these 5 are large specimens, the fourth measures 40X20X15 mm., and the other is composed of small fragments contained in material from curettage. From this alone it follows that the menstrual age is a very uncertain guide, especially as to the size of a hydatiform mole.

Fig. 18.
Fig. 19.
Fig. 20.

It seems superfluous to add any tiling to the good description of the gross appearance of the typical h3'datiform mole currently reported in the literature. Such cases are so characteristic that even a novice can recognize them at sight. Yet if the findings reported here are reliable, or even approximately so, it nevertheless must be evident that, in the past, the great majority of specimens of true hydatiform mole have remained unrecognized merely because they did not happen to present the customary, well-known picture to ike unaided eye. Small chorionic vesicles, such as No. 2077 shown in natural size in figure 18, which attract no attention upon cursory inspection may, and often do, present the most exquisite picture of hydatiform degeneration when seen under a magnification of 3 to 20 diameters, as illustrated in figure 19. This is true especially if the examination is made with the binocular microscope. Since I have adopted this method of examination it has been possible to recognize instances of decidedly general and typical hydatiform degeneration in chorionic vesicles less than 2 cm. in size, with later confirmation of the diagnosis by a histologic examination. However, I have not been able to recognize very early stages merely by examination of the gross specimens, for gross recognition is possible only when portions of at least some of the villi have become sufficiently elliptical or globular to attract attention. Histologic recognition is possible far earlier than this, as shown in figure 20.

Fig. 21.

The general appearance of the whole chorionic vesicle sometimes is an aid in gross identification, for the villi not infrequently are smooth, slightly branched, and unusually long, so that the vesicle looks shaggy, as illustrated in figure 21. The typical gross, hydatid or watery, translucent nature of the vilU can not be relied upon in early stages, for normally shaped villi, which have undergone considerable lysis, may be almost transparent and also somewhat more than normally bulbous. However, save in the case of some specimens of tubal pregnancy, the swelling of the villi, due to maceration or to luetic changes, is quite different in character from that characteristic of hydatiform degeneration, and usually quite easily distinguishable from it. Judging from several specimens of villi which were macerated in distilled water during a period of weeks, post partum maceration never could cause confusion and the same thing undoubtedly is true of intra-uterine maceration.


Since numerous trophoblastic nodules are present also in other conditions, notably in retained placentae as found by Aschoff and others. I have not been able to regard their presence in unusual numbers, in some cases of hydatiform degeneration, as of crucial value, but the absence of placental differentiation at a time when it should be present, with a uniform and unusual development of the villi over the whole exterior of relatively large chorionic vesicles, is decidedly significant and has often been found to imply the presence of hydatiform degeneration. The same thing is true of a very irregular distribution of the villi, or of uniformly distributed fusiform enlargements on the villi and of the loss of the dull appearance of their cut surfaces, as seen under the binocular. As soon as the stroma becomes hydatiform, and even before liquefaction is present, the cut surfaces of hydatiform villi look somewhat shiny and waxy or, perhaps better still, parafiine-like, as in the specimen in situ shown in figure 21. A bluish tinge always is present, and this appearance is very characteristic. However, how easily a specimen of hydatiform mole can be recognized by examination with the binocular alone necessarily will depend also upon the condition of the specimen. If the villi are matted, glued, or macerated, not only the early hydatiform changes but even fairly advanced ones often are masked so completely that recognition is difficult or impossibie without histologic examination.


In many early specimens the diagnosis could be made at sight from a histologic preparation under low magnification, even when it was impossible to make a diagnosis by examination with the binocular microscope alone. What makes this possible is not, as has been generally assumed since Marchand's epochal work on chorio-epithlioma, the ajipearance of the syncytium or that of the Langhans layer or of the trophoblast, but the changes in the stroma which precede those in the epithelium. The evidence in regard to this matter is overwhelming, and in the early stages when the stroma already has been altered, it often is impossible to tell whether the epithehal development is normally or abnormally active. Moreover, in spite of Marchant's statement to the contrary, extremely large cysts often have but a single smooth layer of epithelium. This has been asserted repeatedly by other investigators also. The two layers of epithelium are not by any means always present and, while there is no agreement in the matter, the opinion seems to be that the grade of epithelial proliferation can not be used as a criterion for the deter- mination of the presence of hydatiform degeneration. Menu said that the presence of marked epithelial proliferation was emphasized early by Miiller (1847), Ercolani (1876), Franque (1896), and Owry (1897); and according to Pazzi (1908), Ercolani and Polano altogether denied the existence of connective tissue in the hydatiform mole. The same thing was asserted by Sfameni (1903), who claimed to have found further evidence of the exclusively epithelial nature of the hydatiform mole in 1905. According to Sfameni the hydatiform mole does not result from a modification of existing chorionic villi, but from an entirely new growth which is wholly epithehal in character! But this opinion, which was accepted also by Niosi (1906), seems to exist among Italian writers only.


Although Durante (1898) represented extremely long syncytial buds, he nevertheless found (1909) epithelial proliferation present only where certain vascular changes were present. Winter (1907) stated that the condition of the epithelium varies greatly, and Falgowski (1911) emphasized that he could not demonstrate the presence of an increased epithelial proliferation or of vacuolation of the syncytium. Aman (1916) also found that epithelial proliferation may be wholly absent. Ballantyne (1913), on the contrary, found epithelial proliferation "so well developed that it suggested that it is an essential process in the formation of the mole." liallantyne further likened hydatiform degeneration to edematous growths and emphasized that both really are epithelial new growths. This opinion is accepted also by de Hnoo (1914), who regarded the hydatiform mole as a neoplasm of the trophoblast with secondary changes in the stroma.


There is no agreement at present as to whether the epithelial changes are primary or secondary. As is well known, Marchand (1895) — und Miiller, l*]rco!aiii, and Langhans long before that — regarded the epithelial changes as primary, but most investigators seem to have come to the opposite conclusion. Some share the opinion of Schrocder that hydatiform degeneration points to a stimuhis resulting in hypoplasia of the entire chorionic villus. Nor is there agreement as to what the initial changes are. Durante (1909) regarded the presence of vessels with an imperfect endothelial lining and with thick infiltrated walls as the initial lesion in hydatiform degeneration. These changes were noted by him, especially in trunk villi, and epithelial proliferation was most evident where the vascular lesions were most pronounced. Durante further stated that the chain form of the hydatids is due to the fact that the vascular lesions occur at intervals along the villus. Unfortunately, the structure of long hydatiform villi does not confirm such an explanation nor Durante's conclusion that the hydatid cavities within the viUi result from dilatation of the capillaries. Many investigators report the early disappearance of the blood-vessels, a phenomenon which some regard as secondary and others as primary to the death of the embryo.


In the course of this investigation a villus with a normal stroma and normal vascularization never was found to have undergone true hydatiform degeneration, but one with a normally active epithelium — both Langhans layer and syncytium — often was truly hydatiform. That is, it not only was watery in appearance, but also fusiform or globular even in external form. In fact, Marchand (1895) himself found that "Das Epithel welches die Zotten und ihre Anschwellungen bekleidet zeigt ein sehr verschiedenes Verhalten." Yet even to-day, the feeling on the part of many seems to be that unless a marked hyperplasia of the Langhans layer and of the syncytium is present the condition is not one of hydatiform mole. This position seems to me to be untenable for, as Marchand himself said, the change in epithelium usually is least in the young viUi, and he should have added it is unrecognizable in the early stages and in young conceptuses. A perusal of the literature descriptive of the actual cases leaves little doubt upon this point, and a careful study of the advent of the earliest recognizable changes in hydatiform mole is absolutely convincing. The earliest recognizable, even if not the incipient, changes occur in the stroma and in the vessels — and not in the epithelium. In passing, it may be noted that although Marchand stated that the change in the epithelium is primary, he nevertheless somewhat contradictorily added that the most important fact is the degenerative change in the stroma of the villi.


Although not applicable to what I have come to regard as the incipient changes in hydatiform degeneration, it nevertheless is true that the stroma often, if not always, quite early becomes hydatiform — that is, glassy or clear, though not necessarily watery. Moreover, the villous vessels often degenerate or disappear completely at a very early stage. It is exceedingly difficult to make any definite statement as to what is typical regarding the epiithelium. This has been said by others also. Indeed, this necessarily foUows from the fact agreed to by every one, that histologically there is no true line of demarcation between the ordinary benign hydatiform mole, the so-called destructive benign (?) hydatiform mole — whatever its status may be — and the malignant hydatiform mole, or chorio-epitheUoma. Such a conclusion alone presupposes the existence of the widest differences in the condition of the t'pitlu'lium in the these cases, and that such differences actually exist is beyond question.


Marchand's revolutionary investigation on chorio-epithelioma notwithstanding, the epithelium is not always two-layered, nor is it always thickened, in hydatiform mole. That the epithelium can not always be active beyond the normal follows also from the fact that the proliferative changes in it are subsequent to, even if not necessarily conseciuent upon, changes in the stroma. Furthermore, like the latter they are gradual in their evolution and may stop or be stopped at any stage of their development. Then, too, the condition of the epithelium depends very largely upon the preservation of the abortus, and this, as is well known, varies greatly. The most striking thing about the epithelium usually is not its thickness, the presence of large masses of trophoblast, or of numerous syncytial buds, but its splendid state of preservation, especially as contrasted with that of the stroma. This is true of all except macerated or degenerate specimens, for the life of the epithelium seems assured as long as there are periodic accessions of fresh blood, which, as the clinical histories illustrate, usually is the case. The stroma, on the other hand, probably not being wholly independent of the contained capillaries, is deprived very largely of its sustenance during, even if not in consequence of, their degeneration. According to some, hydatiform degeneration of the stroma is the result of an accumulation of nutritive products in consequence of the absence of the vessels. Degeneration of stroma and vessels, however, may result from malnutrition due to poor implantation.

Fig. 22.
Fig. 23.

The epithelium of the villi often was found single-layered without any syncytium whatever, or with at most a few syncytial buds. Nevertheless, both the syncytium and trophoblast very often show evidences of a marked activity which is not confined to implanted vilh or to the epithelium of the villi as a whole, but which may extend to that of the chorionic membrane as well. Surprisingly long, complex syncytial buds, whorls and festoons, as shown in figures 22, 23, and 24, and as said to have been observed by Frankel, often are present, especially on the villi, although in a few instances fine buds and frameworks of syncytium also were seen arising from the epithelium of the chorionic membrane. This feature (shown in figure 23) has, I believe, not been specially emphasized heretofore, though observed by Clivio (1908).

Fig. 24.
Fig. 25.

Mounds formed by the Langhans layer were common, especially on the tips of the villi where they frequently formed irregular masses of small nodules — the "appendici durate" of Crosti (1895). These gave the villous tree the appearance of a leafless orange loaded with fruit, only that the trophoblastic nodules are mainly apical, as shown in figure 25. In several instances syncytial buds were found far out on these; trophoblastic masses, a fact which is of special, if not of crucial significance in connection with the old question of the origin of the syncytium, for these buds undoubtedly had not been transported tluMc. But however one may regard these things, such appearances as represented in figure 24 are unmistakable, for they show thickenings composed of Langhans cells aiul garlands of considerable length, portions of which are composed of absolutely distinct cells of the Langhans type, as well iis other portions composed of syncytium with every gradation between the two. Nor do I believe that the assumption that syncytium can resolve itself into indiviiduaI cells can be used to deny the implication of these facts.


Although hydatiform villi covered by a single layer of rather small cells of the nature of Langhans cells, sometimes without visible cell boundaries, frequently were seen, villi covered by typical syncytium only never were seen. The single layer present, although syncytial in places, suggested Langhans cells rather than the real syncytium. Moreover, since the cells of the Langhans layer usually were smaller rather than larger than normal, it follows from this alone that their proliferation must have been marked, in order to completely cover the enlarged villus, in spite of the fact that the layer remained single-celled. Were this not the case, the extraordinary increase in size which accompanies the formation of large hydatid cysts could not possibly occur without rupture of the covering layer.

Fig. 26.
Fig. 27.

Not infrequently proliferation of the epithelium without increase in thickness may manifest itself in another way. The caliber of the villi in the earlier stages of hydatiform degeneration sometimes does not increase much, no thickening of the proliferating epithelium is noticeable, and yet the latter shows marked proliferation. Under these circumstances, the borders of the villi and of the chorionic epithelium may appear extraordinarily sinuous as illustrated in figure 26, and epithelial invaginations from opposite sides rarely meet in the center, as indicated in figure 27, and by fusion completely isolate a portion of the stroma. It usually is in these cases of very sinuous epithelium that the epithelial invaginations sometimes become constricted, leaving a closed epithelial vesicle or a nodule of epithelium attached to a stalk or wholly isolated within the stroma, as shown in figures 28 and 29. All stages in this process of vesicle formation were found, and rarely also extensions of epithelial sprouts as described by Neumann (1897) and others were seen, portions of which had become isolated in the stroma to appear later as typical syncytial giant cells. These facts, too, would seem to throw a sidelight upon the origin of the syncytium for those to whom this question is still an open one.


All these tilings abundantly testify to the activity on the part of the epithelium in many hydatiform moles, even when thickening of it is absent, but they are of diagnostic value only if present, and I wish to emphasize again that they may be wholly absent or at least unrecognizable in the early stages. Moreover, the degree of epithelial proliferation varies greatly, as illustrated in figures 30, 31, and 32.


Until I am able to learn more about the structure of normal villi in various stages of development, I am not willing to commit myself regarding the incipient changes in hydatiform degeneration. These may be unrecognizable with present methods. However, it is possible to say that in young conceptuses the disappearance of the capillaries, which was regarded as a possible cause for the development of hydatiform mole by Hewitt (1860 and 1861), and also emphasized later by Hahn (1865), Maslowsky (1882), and by others, undoubtedly is a very early and possibly the very earliest noticeable change in some cases. Of course, I do not imply that death of the embryo is the cause of this disappearance, as Hewitt held, and I am not ready to say that the vascular change is the very earliest one in all cases. This would imply that hydatiform degeneration under no circumstances can begin before the capillaries have ai)i)carocl in the villi. There is some evidence which suggests that it possibly may appear before this time. If so, it would be incorrect to speak of a disappearance of the vessels in such chorionic vesicles, for if the advent of hydatiform degeneration can precede the appearance of the villous capillaries, vascularization of the villi ma.v never occur. In older conceptuses, however, in which vascularization of the villi has sujiervened, the first recognizable change is the disappearance of these capillaries. Many specimens in which the latter were in various stages of degeneration were examined carefully, and the opinion of Hewitt (1860), that hydatiform degeneration can not arise in villi which have been vascularized, can be regarded as of historical interest only. Different stages in the process of vascular degeneration are represented in figures 33 to 35 inclusive.


Coincident with the disappearance of the vessels, changes in the stroma also are noticeable. Usually it tends to become glassy, the individual nuclei becoming separated farther. The stroma, though apparently solid, is uniformly slightly bluish and vitreous, with well-defined, rather small, pycnotic, pointed nuclei, but with not a vestige of a vessel, though the epithelium is splendidly preserved. The latter may be one-layered or two-layered, and may be accompanied by syncytial buds and trophoblastic masses and nodules. In such specimens the entire picture really is exquisite, and a mere glance through the compound microscope reveals the lack of vessels in the vitreous stroma and the marked differences in size of the sections of the villi.


After these early changes, licjuefaction of the stroma usually follows. As is well known, liquefaction generally begins in the interior and first appears in the form of vacuolation; but this vacuolation (which I can not regard merely as an edema) is not intra-cellular but intercellular, and as it becomes more pronounced it really takes on the nature of fenestration. Sections of the whole cross-section of the villi, even though large, may be composed of a series of fenestrse (see fig. 36) separated by exceedingly fine strands of the remaining stroma which may contain remnants of the nuclei. But finally, even the fine trabecular separating the fenestras disappear, and the stage of the watery, old, hydatid condition has been reached. More generally, however, the vacuoles or small fenestra lying in the middle become confluent at the center of the cross-section of the villus, which then is liquefied completely. As is well known, this liquefaction gradually extends to the periphery as the zone of the surrounding stroma is narrowed in the process. Not infrequently, however, liquefaction of the stroma occurs quite generally throughout the cross- section of the villus and is accompanied by the formation of numerous large cells, the wandering or migrating cells of earlier writers. A few of these cells almost always can be found, and rarely the whole section of the villus is studded with (fig. 37) or even formed by these large, erratic cells which usually lie in fenestra? in the stroma. In other instances a large portion of the sections of the villi may be occupied by them, as shown in figure 38. The presence of these cells in viUi regarded as normal has long been known. Their presence in hydatiform moles was noted by Otto, Marchand (1895), Essen-Miiller, and by many others. Their occurrence in normal and pathological chorionic vesicles, and their significance are considered more fully by Meyer (1919). No matter what the condition of the epithelium, or more specifically that of the Langhans lajer, the syncytium and trophoblast may be, the above-noted changes in the stroma always are quite typical. They are not the only changes noted, however, and their advent may differ somewhat.


Not infrequently, changes quite comparable to those in the villi occur also in the stroma of the chorionic membrane itself, a fact which has not heretofore been emphasized. Also, it is frequently decidedly glassy; liquefaction may occur here and there and may become complete in the course of time. Hofbauer cells not uncommonly also are present. Among the changes noted in this membrane the disappearance of the vessels is most common and constant, although epithelial proliferation is not rare, as already stated. Moreover, when (as in one of Storch's cases) a hydatiform villus is 15 cm. long, one scarcely can doubt that the stroma also must have proliferated — not merely degenerated. Some of the strings of hydatid cysts in a specimen in the Mall Collection have a length of over 10 to 12 cm., and in these cases also one can hardly assume that this increased length in the villi was unaccompanied by prohferation of the stroma. From these things alone it follows that the stroma can not remain passive always, although Gromadzki (1913) concluded that the stroma never proliferates. Vecchi (1906), however, reported an increase in the stroma of the vilU, and it will be recalled that Marchand also implied the presence of proliferative changes in the connective tissue when he wrote that they depend on those in the epithelium.


I have never been able to find mitotic figures, a fact which may be accounted for, however, by the presence of degenerative changes due to intrauterine separation and retention of most specimens. Indeed, the failure to find mitoses speaks against proliferation in the stroma no more than in case of the epithelium, in which the presence of karyokinetic figures has been reported by a few investigators only. Yet pronounced proliferation of the epithelium often is present. The failure to find mitotic figures is very likely due to the condition of the material.


Careful scrutiny of a large series of specimens has revealed the fact that the disappearance of the vessels in the villi, in the chorionic membrane, and also in the umbiUcal cord is centripetal as a rule. However, in many specimens the vessels not only may be present in the chorionic membrane although absent in the villi, but may be very numerous and even engorged with blood. It is difficult to say to what extent the engorged condition of these vessels and of those in the body of the abnormal embryos sometimes contained in these hydatiform moles is due to the propulsion of the embryonic blood before the advancing vascular constriction and degeneration, but I am inclined to beUeve that the centripetal movement of the process is not a negligible factor.


Although only a few instances of the birth of a living fetus or of a fetus which had reached the later months of pregnancy are recorded in the literature, it now is quite generaUy recognized that the fetus, though dead and too small for its menstrual age, usually is present. This stands in contradiction to the earlier belief iUustrated by the statement of Gierse (1847), that the fetus usually was reported as absent, and that when present (as in the cases of Meckel, Gregorini, Otto, Cruveilhier, and his own) it usually was less tihan 1 inch long, even when retained for a period of from 3 to 10 months.


This apparent contradiction regarding the presence of the fetus in hydatiform moles is explained easily by the fact that the cases in the earlier literature are old, far advanced in degeneration, while the more recent literature contains many more in the earlier stages of degeneration. Yet in spite of this fact the earlier opinion survives to the present day, for Graves (1909-10) spoke of "the very unusual presence of a normal fetus inside a mole," and Vineberg (1911) still more strangely held that the presence of a fetus excludes the specimen from the class of true hydatiform moles!


Among the specimens concerned in this report many contained a fetus. Tliis was true of 24.5 per cent of 49 tubal and 64.4 per cent of 121 uterine specimens, including some (9) doubtful cases. In some early specimens the fetus is in a state of excellent preservation. This is what one might expect, for the onset of hydatiform degeneration is gradual and often partial. The condition of the fetus in many of them alone also suggests that its death was secondary to the degeneration.


The fetal length ranges from 1 to 90 mm. in the uterine and from 1 to 80 mm. in the tubal series. Although the average length of the embryo in the tubal series is 12.3 mm., and that of the uterine only 10.1 mm., 58 per cent of the tuljal speci- mens nevertheless were below 7 mm. in length as contrasted with 52.5 per cent of the uterine.


The presence of a fetus with a frequency almost three times as great in the uterine series again indicates that the abnormal conditions within the tubes lead to early death, digestion, and absorption, or at least to dissolution, of the embryo. This fact again points directly to a faulty nidus as causative agent, for if the absence of a fetus is to be laid to primary ovular defects, then one must admit that relatively far more of such diseased ova become implanted within the tube than within the uterus.


Of the many explanations which have been offered for the advent of hydatiform degeneration, none seems to be better established than that of endometritis. Tliis was first emphasized by Virchow (1863), and Lwow (1892) also reported 4 cases in patients under his care in whom lues could be excluded but in whom he held endometritis responsible. Emanuel (1895) was the first, it seems, to demonstrate the presence of cocci in inflammatory foci of round cells in the decidua accompanying a case of hydatiform mole. Veit (1899) also believed that disease of the decidua is the cause of hydatiform degeneration. Veit further stated that Waldeyer, Jarotzky, and Storch also believed that an irritative condition of the decidua is responsible. Stoffel (1905) also found cocci other than gonococci present and says he can not avoid holding endometritis responsible in his case. The association of hydatiform degeneration and endometritis was noted also l)y INIarchand (1895), Oster (1904), and Sternberg; also by Essen-Mollor, who reported the phenomenal case of a woman with endometritis, who had aborted a hydatiform mole 18 times in 9 years. Falgf)wski, on the contrary, concluded that the ova themselves were diseased and argued that hydatiform degeneration should be much more common if it were due to endometritis. Taussig (1911) also stated that leucocytic infiltration of the decidua is frequently present in hydatiform moles, but iasistcd that "leucocytic infiltration in the placenta then should not be interpreted as infection.

Inflammation and infection should be kept apart." I presume Taussig really meant infiltration and infection should be kept apart, and the question then turns upon the structure of the normal decidua and the significance of infiltration for the development of the ovum.


It may be recalled that Marchand (1904) reported the presence of isolated groups of small cells in the normal decidua which looked hke mononuclears under low magnification, and which he believed often have been confused with them. But even granting this, and the further facts that the exact histologic changes in the decidua are not fully known, and that it is rather difficult to ascertain just what decidual changes are regarded as evidence of the existence of an endometritis, any one examining a large series of cases of hydatiform degeneration aborted with the decidua can not doubt the presence of marked decidual changes in a very large percentage of them. These changes are not limited to infiltration with scattered round cells or erythrocytes, or to focal accumulation of the same, but often extend to almost complete fibrosis, as shown in figure 39, so that experienced investigators have mistaken the thin, fibrous decidua for a part of the chorionic membrane.


It is true that the existence of these changes in the deciduae themselves does not necessarily imply that they were antecedent to the implantation of the ovum, but fortunately' the clinical histories and material from curettage often supply crucial evidence. From such cases and from the cumulative weight of evidence from the large series of cases here reported, the great majority of which showed decidual infiltration or other changes suggestive of endometritis, the frequent association of abnormal deciduae with hydatiform degenerations is evident. The fact that the incidence of hydatiform degeneration in the tubal was somewhat higher than that in the uterine series might be regarded as contradicting this relationship, but such is not the case. The mucosa of the tubes at best is an unfavorable nidus for implantation because of the absence of decidual formation alone. Hence, even if salpingitis were somewhat less frequent than endometritis, proper nidification in the tube could easily more than account for the existing differences. Hence the higher incidence of hydatiform degeneration in the tubal series in fact becomes confirmatory of the conclusion that abnormal nidification really may be responsible for the advent of hydatiform degeneration.


The only fact which might be interpreted as indicating that germinal defects primarily are responsible for the development of hydatiform degeneration is the relatively higher incidence of the condition in older women. Against this, however, stands the other fact that such women also show the cumulative effects upon the endometrium of age, endometritis and pregnancy. Furthermore, since hydatiform degeneration so often follows one or two normal births or abortions, it would be impossible to find an adequate explanation for the release of the defective ova so often after and not before these events.


I am reminded also in this connection of a case the detailed history of which is fully known. It is that of a robust young woman who successively gave birth to two moles and then to a normal full-term child and secundincs. In this case curettage was done in connection with each mole. Apparently the new endometrium, which had formed after the second abortion and curettage, permitted normal implantation and normal development to progress to term. To ignore the condition of the endometrium in this case and attribute the development of hydatiform degeneration to the successive release of abnormal ova would seem to disregard important facts — especially so since no one has established the occurrence of abnormal ova within the Graafian foUicle, a possibility which I do not wish to deny, although Donskoj 's report of a case of hereditary mole must surely be taken cum grano sails (with a grain of salt).


That an abnormal nidus may be responsible for the advent of hydatiform degeneration would seem to be indicated also by the fact that the process usually was better developed and more general in the tubal than in the uterine cases. That both endometrium and decidua show astonishing differences in structure under pathological conditions is well known. The entire tubal mucosa, on the other hand, even when normal, forms an abnormal nidus which would affect all portions of early chorionic vesicles somewhat alike, and since, as found by Mall, inflammatory conditions in the tubes predispose to tubal imjilantation, the higher incidence of hydatiform degeneration in the tubes is easily explained. Nor does the existence of partial hydatiform degeneration argue against such an explanation.


Although Kehrer reported not a single fatality in 50 cases of hydatiform mole, Hirtzman (according to von Winckel) gave the fataUty as 13 per cent, Borland and Gerson as 18, and Williamson as 20 to 30 per cent. Von Winckel (1904) regarded these i)ercentages as entirely too high, however, although Oster reported 2 cases of malignancy out of 15 among cases in which the late results were ascertainable — an incidence of 13.3 per cent. Kroemer (1907) found that chorio-epithelioma developed in 5 out of 15 cases of hydatiform moles, or in 33.3 per cent, but only twice in 3,841 "normal implantations." Daels (1908) says La Torre claimed a malignancy of 64 per cent; de 8enarcleus one of 28.7 per cent, or 14 out of 49 cases. Frjienkel (1910) emphasized that the estimates of the number of cases in which hydatiform degeneration is followed by malignant disease vary greatly, while Robertson (1915) quoted Findley as finding that IG per cent of 250 hydatiform moles collected from the literature were followed by malignant disease. Briggs, who reported 21 cases of hydatiform degeneration with 2 of chorio-epithelioma or an incidence of malignancy of 9.5 per cent, called attention to the "diminishing ratio in the; tendency to malignancy shown by his series."


Findley stated that chorio-epithehoma develoiH'd in 131 out of 500 cases gathered by him from the literature, which is an incidence of 26.2 per cent; but, as already stated, most of these cases from the hterature are old, advanced degenerations, many of which have been retained for a long time. The tendency to malignancy in these probably can in no way be compared to that in smaller and younger specimens, many of which are aborted entire with the surrounding decidua. Consequently, it need not surprise us that out of 19 cases of this series, in which later reports were obtainable, none were reported as having developed chorio- epithelioma.


Perhaps I may here add a word of caution, however, in regard to a possible change in attitude toward the question of malignancy with a consequent relaxation of vigilance. It is true that out of the 21 cases of Briggs only 2 developed chorio- epithelioma, but it must not be forgotten that Briggs in part was, and I to a far larger extent, am dealing with a different class of hydatiform moles than those upon a study of which the prevailing conception of malignancy is based. Hydatiform moles which continue to grow and which survive for months after the death of the embryo evidently are more vigorous, and hence no doubt also more dangerous than those which are aborted early and spontaneously. Since the latter formed the great majority of all moles here considered, opinions regarding malignancy formed on this basis probably would lead to disaster if applied in practice. Such conceptions would be based upon a totally different incidence than the current one of 1 hydatiform mole in every 2,000 cases. Instead of relaxing our vigilance it would seem wise to increase it, particularly in the cases of so-called spontaneous abortions — the cases in which no ascertainable cause for the termination of pregnancy can be found, especially if the chorionic vesicle is empty or if the embr^^o belongs in one of the early groups of Mall's classification.


The average age of 36 women aborting hydatiform moles was 31 years. Although I do not regard the alleged ages as necessarily the actual ones, this average age agrees very well with that of 6 cases reported by Poten, 10 by Donskoj, 23 by Briggs, 6 by Gromadski, and 8 by Robertson. The average age of Poten's cases was 32 years, of Donskoj 's 25 years, of Briggs's 28 years, of Gromadski's 29.6 years, and of Robertson's 28.4 years. Pazzi (1908) , on the other hand, stated that Briquel placed the greatest frequency of hydatiform degeneration between 20 and 30 years. These averages are so far on the near side of the menopause that one can make liberal allowances for the proverbial disinclination of women to state their exact age, even to physicians, and nevertheless regard the prevailing opinion undoubtedly as ill-founded. If, as Lewis (1906) stated, it is necessary to add only half a year to the average age of a large group of women in order to ascertain the actual average age when considering general social statistics, then everyone will admit that still less allowance than this need be made in the case of women who are speaking to their physicians, knowing that whatever they may say will be regarded as strictly confidential. That it is unncessary to make large allowances for under-statement of their age on the part of these women is indicated also by the average duration of their married life before aborting moles. This in the case of 29 women was 7.1 j'-ears. Hence, if one bears in mind that the average age of first marriages according to Webb (1911) is 25.1 years, one can easily see that the average age of the women aborting hydatiform moles, which was given as 29.6 years, is probably not too low at all, thus confirming the findings of Williamson, who denied that hydatiform mole was especially common near the menopause.


The conclusion that the average age of 29.6 years undoubtedly is near the actual is confirmed also by the fact that a hydatiform mole was the first abortion in 19 out of 41 women, or almost half the number; 12, or almost one-third, had aborted twice, and only 10 had aborted more than twice. But what is still more confirmatory is the existence of a surprising parallelism between the data on abortion and those on births; 9 of 33 women had given birth to but 1 child, and an eriual number had given birth to but 2. Hence over 50 per cent of the 33 women had borne children twice, or less than twice, and only 15, or less than half, had borne oftener than this.


This undoubted evidence of the youth of these women is confirmed still further by the statement of Lewis who, from an analysis of 16,325 first births, found that nearly one-half of them occur between the ages of 20 and 24, almost three-fourths between 20 and 29 years, and that first births are more frequent between 30 and 40 than between 15 and 19 years. I realize, to be sure, that social statistics can not be translated from one country to another without modification, but in such a mixed population as ours this modification probably need be less (rather than greater) than in case of some countries.


The conclusion that the occurrence of but a single birth before the advent of hydatiform degeneration probably implies that such women are relatively young is emphasized still further by the statement of Lewis that in one-third of the marriages in Scotland "the bride had a child when unmarried or was pregnant at the time of marriage," and that 50 per cent of the first births in Scotland occur within 9 to 24 months after marriage. Lewis also gives the average interval between marriage and the first birth in 16,176 first births as 13.54 months, but little more than one year. Since Lewis stated that the interval between the birth of the first and that of the second child is but little longer than that between marriage and the birth of the first child, being only 3.07 years, it is evident that not even those women who had borne two children before the advent of hydatiform degeneration could have been near the menopause. This conclusion is emphasized still further by the fact that in 96.12 per cent of 16,176 fruitful marriages fertility was demonstrated within three years after marriage.


Nevertheless, in spite of the clear implication of all these facts, I wish to emphasize again that since what have been heretofore regarded as hydatiform degenerations were large specimens mainly, it well may be, and according to certain authors it is true, that such cases occur later in the reproductive life of women. Yet it certainly is significant that Findley in tabulating 500 of such cases from the literature found that 275, or 55 per cent, occurred before the thirty-fifth year, and of 36 specimens from the Mall Collection 23, or 63.6 per cent, came from women below this age. It may also be recalled that 78 per cent of Kehrer's 50 cases and 90 per cent of Bloch's occurred before the fourth decade.


Fourteen out of 23 cases, or 61.3 per cent of the uterine series, in which the age was given, occurred at or before the thirtieth year, and 18 out of 23, or approximately 80 per cent, at or before the thirty-fifth year. These things abundantly emphasize the conclusion reached by some investigators that hydatiform mole is not absolutely more common at or near the menopause. But it nevertheless may be relatively more common. That is, the number of hydatiform moles aborted after 40 com.pared with the total number of pregnancies or births after 40, actually may be greater than this ratio before 40 years.


From calculations based on data given by Lewis the average number of births occurring after 40 years in Sweden, Norway, Denmark, Brunswick, Berlin, Buda Pesth, France, and Scotland is 9.9 per cent. This agrees remarkably well with Bloch's estimate of 10 per cent. But if 77.2 per cent of the cases of hydatiform mole occur below 40, and 22.8 per cent after that year, then it is evident that hydatiform mole nevertheless is relatively more common after than before 40 years, for approximately one-fourth of the cases of hydatiform degeneration would be associated with one-tenth of the births. This would be an increased frequency of 300 per cent above that before 40 years. A similar result would be obtained by comparing Findley's or Williamson's series. Hence, hydatiform degeneration though absolutely loss is relatively more frequent in later life. This fact, however, does not necessarily imply that age in itself is responsible for the increased incidence after 40. A comparison of the incidences of hydatiform degeneration in young and old primiparse, of good health, might elucidate this question.


These statistics are not in agreement with the prevailing opinion that hydatiform moles are more common in multipara; than in primiparfe. Indeed, as I under- stand, they suggest rather that after the first conception, which was normal in a large percentage of these young women, something happened which interfered with the normal development of succeeding conceptions. That, it seems to me, is extremely significant and very suggestive. Here is a group of relatively young women, over 50 per cent of whom had borne but twice and some only once, and then gave birth to a hydatiform mole. While I realize the necessity for circumspection, especially in these matters, these facts seem to me to suggest that something hap- pened to a normal endometrium. Other facts also point in the same direction.


Even if it is not wholly correct, as Findley states, that more cases of hydatiform mole were reported in the last decade than in the previous 14 centuries, it is not unlikely that approximately as many specimens of this condition are contained in the Mall Collection as have been reported heretofore. Moreover, upon the basis of the present rate of accession, a large number of formerly unrecognized cases of hydatiform moles — both tubal and uterine — are donated to this collection annually. This fact, together with others to which attention has been called, ought to stimulate our interest in this problem.

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List of Illustrations

Links: Plate 1 | Plate 2 | Plate 3 | Plate 4 | Plate 5 | Plate 6 | Contribution No.40 | Volume IX | Contributions to Embryology

Plate 1

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Plate 1: Fig. 1 | Fig. 2 | Fig. 3 | Fig. 4 | Fig. 5 | Fig. 6 | Fig. 7


Plate 2

Plate 2: Fig. 8 | Fig. 9 | Fig. 10 | Fig. 11 | Fig. 12 | Fig. 13

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Plate 2: Fig. 8 | Fig. 9 | Fig. 10 | Fig. 11 | Fig. 12 | Fig. 13