Book - Contributions to Embryology Carnegie Institution No.1-4
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Mall FP. On the fate of the human embryo in tubal pregnancy. (1915) Contrib. Embryol., Carnegie Inst. Wash. Publ. 221, 1: 1-104.
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Pathological Embryos in Tubal Pregnancy
It is probable that a number of the normal embryos, in the specimens just described, are slightly deformed and at the beginning of pathological changes. Since the standard of normality had not been fully established, it is practically impossible at present to decide as to what is a slight abnormality. It is only when the change is very pronounced that we recognize embryos as pathological, and for this reason the two groups now under discussion are probably inaccurate. When we understand this subject better, no doubt a larger percentage of the normal group will be transferred to the pathological group, and the same is true regarding the group said to contain no embryos. The method of examination I employed is partly responsible for this. To cut a large number of greatly distended tubes into serial sections in order to determine this point is practically out of the question. However, when the pregnant tube is hardened in toto and cut into slabs about 5 mm. in thickness, it is quite easy to detect the remnant of an embryo in case it is lodged within a free amniotic cavity. If, however, the cavity of the chorion is filled with blood, the embryo may be so obscured as to be overlooked, and in several specimens falling under this group the embryo was found accidentally in the sections after it had been overlooked with the naked eye. Nevertheless, speaking from a somewhat wide experience, I think it unlikely that as large a percentage of specimens will have to be transferred from the group containing no embryos to that containing pathological embryos as from the group containing normal embryos.
Table 4. Group containing pathological embryos arranged chronologically
(table to be formatted)
|Template:CE567||55X30X25||5||3 weeks. (?)|
|Template:CE685||70X60X50||12||6 weeks. (?)|
|Template:CE697||55X30X30||3.5||4 weeks. (?)|
45X45X22 30X30X30 40X28X20
5 2 5
8 10 5 (') 25 days. 7 weeks. 30 days.
22.5 80 14(?) 1
8 3 8
3 weeks. (?)
4 weeks. 12 weeks.
As it can readily be seen that specimens can be picked out of this group and arranged according to the length of the embryos, we shall discuss them in this order, considering only those in which the material has been cut or in which the specimens have been worked up with a great deal of care. It follows, then, that the higher numbers are to receive more consideration than the lower numbers.
Four specimens contain embryos less than 5 mm. long. The'first of these (No. 324) contains a deformed embryo, 3.5 mm. long. The amniotic cavity is somewhat distended, the umbilical cord is short or lacking entirely, and the chorionic wall is well formed and contains a few long, slender villi ramifying in the blood clot. The trophoblast is scanty, but there are a few small knobs of syncytium upon the main wall of the chorion. It appears as though the ovum had become gradually detached and that its nourishment was gradually cut off, so that it ultimately resulted in a stunted embryo. We have here a repetition of what is often seen in ova expelled from the uterus. A stage less advanced than this, in fact intermediate between that in No. 808 and that in No. 324, is found in specimen No. 396. The tissue is unusually well preserved and the chorionic mass was cut into serial sections. According to the clinical history, the duration of pregnancy was 31 days. The relation of the chorion to the tube wall is practically identical with that in No. 808. The ovum is small, the villi are reaching out in tufts and radiating through an extensive freshly formed blood clot to implant themselves well in the tube wall. However, in one respect the two specimens are markedly different. In No. 396 the chorionic vesicle contains the remnant of a deformed umbilical vesicle and a small remnant of an embryo, as shown in plate 5, figure 1. Between the umbilical vesicle and the chorionic wall is a considerable amount of reticular magma with patches of maternal blood. The chorionic wall itself is fibrous, thickened, and contains numerous irregular blood vessels filled with blood. Some of the villi reaching out toward the chorion have likewise undergone fibrous degeneration. Although the trophoblast is very active, numerous long strands of cells radiate from it through the blood clot. In many instances these cells are undergoing degenerative changes. There also seems to be fresh hemorrhage encircling the trophoblast. It may be that the implantation was disturbed and the nourishment of the embryo was effected thereby. We have repeatedly observed that the most susceptible parts in young ova are the embryo and amnion, the umbilical vesicle being more resistant. This is emphasized again in this specimen, in which the embryo is more markedly affected than the umbilical vesicle. No doubt if this specimen had continued for some time, it would have become like the one containing the remnant of an ovum embedded in a large mass of organized blood; that is, if the tube had been removed at a later date the specimen would have fallen into group No. 3, which is to be discussed presently.
The two remaining specimens of this group, No. 554 and No. 697, may be considered together, as they exhibit practically the same changes. In the first the chorionic wall and its villi are very fibrous and completely separated from the uterine wall. Many of the villi are necrotic. The coelom contains granular magma and a remnant of an embryo measuring about 1 mm. in length. It is composed of round cells, but it is impossible to determine the outline of any of the organs.
In the second specimen (plate 7, fig. 5) the ovum is more fibrous, that is, the chorion is more fibrous and its cavity contains a nodule of round cells looking much like a section of lymph gland. Strands of trophoblast pass through a very large blood clot and some of it is still connected with the tube wall. At one point the syncytium is vacuolated and enters some of the venous sinuses.
This group taken together gives about the following story: If the ovum is detached early, the embryo first disintegrates and ultimately the umbilical vesicle is also destroyed, leaving only the wall of the chorion, which becomes strangulated and necrotic and is finally lost in the blood clot. If the ovum implants itself well, so that the embryo can get a start, we have a different story, as is shown by specimens Nos. 324 and 697. In the first the embryo is round and stunted, and in the second a later stage is represented; the embryo has almost entirely disappeared, repeating again conditions found in pathological ova in the uterus.
The first specimen of the next group is No. 567, which contains a dissociated embryo 5 mm. long. At first we believed this embryo to be normal, but serial sections soon showed that it had undergone decided changes, most of its tissues being dissociated. However, it was still possible to locate the organs in it. The chorionic wall is thin and contains numerous slender villi which radiate through the well organized clot, some of them reaching to the tube wall. Upon these are found occasional masses of active trophoblast containing vacuolated syncytium. These clusters are feeding upon fresh blood. They do not seem to be sufficiently numerous for the proper nourishment of the embryo. At any rate there are so many necrotic villi among the normal ones that one is led to believe that the nutrition of the ovum is impaired. There is also a marked infection in this case. A tuft of vacuolated syncytium, invaded by leucocytes, is shown in plate 2, figure 5. Either the faulty implantation or the infection would be sufficient to account for the death of the embryo.
In the three following specimens, Nos. 477, 784, and 838, the embryos are markedly deformed, so that the process must be regarded as being further advanced than in the one just described. No. 784 contains an embryo that is markedly deformed, but can hardly be considered normal. The chorion is completely separated from the tube wall, but within this mass of blood is considerable active trophoblast, together with a large number of necrotic villi. The tube has been practically eaten through and there is a very active inflammation in its wall and lumen. In No. 838 it appears as though the chorion has become entirely detached by a sudden hemorrhage; the blood clot around it is more uniform than usual, as a tuft of villi was protruding from the clot when it arrived at the laboratory. Much of the trophoblast is active, but a great many of the villi are degenerated. It appears as if the villi are being compressed into a single mass. The embryo within (plate 11, fig. 2) is very much deformed. The tissues are markedly dissociated, so much so that the central nervous system and many of the organs can hardly be recognized.
In the last specimen of this group, No. 342, the chorion is fibrous and contains a thickened amnion. The umbilical cord is of the normal size for an embryo about 10 mm. long, and upon its tip rests a small nodule containing a cavity. No doubt this is all that is left of the embryo (plate 5, fig. 2).
After the embryo attains a length of about 5 mm., affections of the ovum in the tube seem to influence it much as in the case of pathological ova from the uterus. The embryo does not disintegrate so rapidly as is the case in younger specimens, but its tissues become dissociated, finally run together, and in this way produce atrophy of the embryo. The beginning of this change is beautifully illustrated in No. 567 and the end of it in No. 342.
The specimens containing embryos from 8 to 14 mm. are easily brought together into a single group, with the exception of No. 729 (plate 10). The tube wall and the chorion of this specimen have every appearance of being normal. The embryo was not found, but judging by the degree of development of the cord, it is estimated that the escaped embryo must have been about 8 mm. long. The remaining specimens of this group usually show markedly hemorrhagic chorionic walls. The first specimen of this group (No. 524) contains an embryo 14 mm. long. The ovum contains a cavity about 25 mm. in diameter, which is encircled by a wall 15 mm. thick. The wall is composed of an organized clot ramified by numerous necrotic villi. There is some irregular or active trophoblast upon the villi, but in general it does reach to the tube wall. There are also signs of extensive inflammation. The chorionic wall is fibrous, the amnion is well developed, and the umbilical cord appears as though the specimen might contain a normal embryo. In many respects the chorionic wall appears much like that of No. 535, which contains a normal embryo.
In the next case (No. 685) the amniotic cavity is practically obliterated, but it contains within a dissociated and macerated embryo. In general the chorion is entirely separated from the tube wall. It contains no active villi. A similar process is seen in No. 766, but the wall of the chorion seems more fibrous, and in general the chorion is detached from the tube wall. An earlier stage of reaction, like the one just given, is found in No. 846. The dissociation of the embryo is not quite so marked and the hemorrhage around it seems fresher. Practically all of the villi are necrotic and the wall of the ovum is fibrous and has a single active mass of trophoblast upon it. Complete destruction of the embryo is well illustrated in No. 804. The chorion here is destroyed entirely, only a faint outline of the villi remaining. The cavity of the ovum is entirely filled with a homogeneous mass of cells representing the embryo. In other words, the dissociation is complete.
We have in this group all stages of the destruction of the embryo, beginning with what appears to be the normal embryos (Nos. 729 and 724) and ending with complete destruction, as in No. 804. It is quite clear that this destruction is due to extensive hemorrhage between the villi, which ultimately detaches the ovum and causes its strangulation.
There are four specimens in the collection containing pathological embryos over 20 mm. long. In two (Nos. 307 and 314) marked changes have taken place in the embryo. The first is thoroughly dissociated and the second, in addition to this dissociation, is small and atrophic. It resembles the embryo in No. 478, although it is not quite normal in form. It is one of those border-line cases in which it is difficult to determine whether the embryo is normal or pathological. The examination of the chorion in this case was not extensive, but it was sufficient to show that most of the villi were necrotic. There are 3 normal embryos between 20 and 28 mm., and an equal number of pathological ones in our collection, showing that about half of the embryos succumb after they reach this size. Beyond this are 8 normal embryos ranging from 35 to 96 mm. and 1 specimen (No. 479) which contains a pathological embryo 80 mm. long. This remarkable specimen consists of a ruptured tubal pregnancy with a protruding fetus, whose tissues are edematous, one foot being swollen more than the rest of the body. Evidently the fetus had been dead for some time. The secondary changes observed in this specimen are best accounted for by an impairment of circulation. The fetus is adherent to the chorion by a band of tissue, which reaches from the chorion to the neck. It is one of those secondary bands occasionally observed in pathological embryos. The tissues of the chorion are also edematous, the mesoderm of the villi being more or less destroyed. Remnants of blood-vessels are left, but contain no blood. There is some hemorrhage between the villi, but in its neighborhood the trophoblast is not active.
Pathological Ova in Tubal Pregnancy
Under the two previous headings, ova with normal and pathological embryos were considered; the first in order to make comparison with normal uterine implantation; the second, in order to describe the preliminary destructive changes after the ovum has been normally implanted in the tube. In this way only has it been possible for me to consider, in any sort of a connected fashion, tubal pregnancy containing pathological ova. Were it possible to describe the very earliest stages in the tube, it would not be necessary to resort to the cumbersome and inverse method employed in the present description. With the pictures of normal and pathological ova in the tube and uterus clearly before us, we can make something of the earlier specimens, in which implantation was not properly effected or, when it had occurred, detachment from the tube wall speedily followed. Usually in such cases the ovum is thrown into the lumen of the tube, where it undergoes degeneration before it is aborted into the abdominal cavity. At the same time, there is every indication that a specimen may be completely destroyed and absorbed in case it fails to be aborted. The other possibility regarding the fate of the ovum is that it may eat through the tube wall quickly and by this direct path enter the abdominal cavity. This is usually the case when the ovum becomes lodged at the uterine end of the tube. When implantation is opposite the attachment of the broad ligament, the ovum may perforate the tube on the broad ligament side and then burrow for itself a large cavity. This is usually the fate of an ovum in which the embryo undergoes normal development.
In most of the specimens in which the ovum becomes detached and enters the tube lumen, or possibly may never have been well implanted, we hardly expect a normal development of the embryo. It is this group which I wish to consider first. We have one very good specimen (No. 754) belonging to this group. It came with a history that rupture had occurred, but careful examination did not show the point of the rupture. The patient had given birth to a normal child 5 years before, and was operated upon for tubal pregnancy a week after the beginning of the last menstrual period. Clinically, there was no indication of disease at the time of the operation.
Microscopic sections show that the tube wall is infiltrated with round cells, but is otherwise normal. The ovum, which measures 1 by 2 mm., was lying free upon the folds of the fimbriie without entering the adjacent blood clot. For the most part the walls of the chorion have degenerated, showing all stages of necrosis. It appears as though the nutrition of the ovum had been cut off. At no point is it directly attached to the wall of the tube, though the villi are intermingled with its folds, as shown in plate 9, figure 3. The villi are also undergoing fibrous degeneration and the coelom is filled with a mottled magma, into which there radiate strands of mesenchyme cells from the chorionic membrane, as shown in plate 3, figure 2.
It is necessary at this point to discuss briefly the nature of the magma as well as the various kinds of degeneration that the villi may undergo. The nature of the magma has been a puzzle to embryologists ever since it was first described by Valpeau. In the course of time it was shown that magma is present in all normal ova, and according to Retzius it first fills the entire exocoelom. As the amnion distends the magma is swept along ahead of it and ultimately comes to lie as a delicate layer between the amnion and the chorion. This observation has been confirmed many times in the study of the normal human ova and the magma has been described by Keibel in the ova of ape embryos. Giacomini first pointed out that an increase of magma indicates that the ovum is pathological and that it does not contain a normal embryo. In fact, whenever we have an embryo which is obscured by an excessive amount of magma, we are sure that no normal embryo will be found. In my various papers on pathological embryos I have emphasized this point and have also called attention to two kinds of magma, a fresh reticular and an older granular variety. It appears that as the magma increases in quantity a granular mass is deposited between the fibrillae.
I have also called attention to the fact that the amnion, especially when it is greatly distended, often contains a granular mass, but in general this substance is gelatinous when the specimen has been fixed in formalin. I was formerly inclined to believe that when this became inspissated we then had granular magma in its purest state and that reticular magma belonged to the coelom and granular magma to the amniotic cavity. Further investigation, however, seems to demonstrate that both kinds of magma belong to the coelom, and the substance so frequently found within the amnion is not to be confused with them. At any rate, it seems better at present to speak of this as a third kind of magma, possibly as amniotic magma or gelatinous magma. Until we have further information upon this point it may be better to ignore the amniotic magma. A careful study of very young ova, like those of Bryce and Teacher and of Peters, shows that the entire coelom is at first filled with dense reticular fibrils, with which are intermingled some mesoderm cells. This is especially well brought out by Grosser in his study of Peters's specimen. He is inclined to believe that two small spaces form within the magma on either side of the embryo. These spaces form the primitive exocoelom. The magma fibrils encircle these and radiate to blend with the chorionic wall. An interpretation of this specimen is shown in Grosser's figure 97 in the Handbook of Embryology. It is quite proper to conclude from this figure, as well as from Peters's own figure, that the magma is only a portion of the chorionic wall detached to fill the coelom of the older embryologists in fact, this is Grosser's view. Stating it somewhat differently, we might say that as the ovum is expanding to pass from the Bryce and Teacher stage to the Peters stage, its center becomes filled with more fluid and separates the fibrillar connective tissue, leaving them as magma fibrils, so that we must look upon the coelom of the older embryologists, identical in structure with the center of the villi, as the true coelom, which this substance with its cells is pushing aside, as described by Retains. In pathological specimens, however, the true coelom does not develop normally, but the magma simply becomes thickened, making it appear as though the coelom were filled with the magma. This conception of the magma allows one to interpret properly a section of the chorion and the coelom as shown in my figure 169 in the Handbook of Embryology. It is quite clear, upon second consideration, that the magma fibrils are simply prolongations of the mesoderm cells of the chorion. We can see in this arrangement a repetition of the ordinary development of the connective tissue fibrils, as illustrated by a section through any part of the embryo. In fact, this is well brought out in the human chorion, if it is well stained by the Van Gieson method. I have taken the trouble to make a careful examination, by this method, of a chorion containing a normal embryo and one containing a pathological embryo.
Specimen No. 808 contained a practically normal embryo with a dense reticular magma filling one portion of its cavity. Sections were stained with the Van Gieson stain and drawn in black, as given in plate 11, figure 3. At the point from which the illustration is taken the chorionic wall is not very compact. It is composed of loose fibrils intermingled with cells. The fibrils, which are stained intensely red, radiate from the cells, forming a dense connective-tissue framework, as may be seen in sections of the umbilical cord or villi. Just surrounding the cells, or rather the nuclei, the fibrils are more marked, having a tendency to grow in parallel lines; in other words, they are more highly developed, and as the chorion becomes older we find that all the fibrils of the chorionic wall undergo similar changes. As long as the magma fibrils fill the cavity of the ovum a condition is maintained like that shown in the figure, but as the amnion pushes the magma fibrils up against the chorion, they form a layer which blends with it. This is the ordinary development of this process.
When the cavity of a pathological ovum is filled with a dense magma, or, as it is usually put, when the coelom is filled with a dense reticular magma, it also becomes fibrillar, and this is well shown in No. 402, which is a typical pathological specimen. Here the fibrils radiate from the chorionic wall and are also sharp and wavy, having a tendency to run parallel with one another. We have here a thickening of the magma in its normal position, without a development of the amnion. There is an excessive growth of the magma fibrils, which in this specimen radiate from the chorionic wall to the center of the ovum. As specimens like this continue to grow, the delicate connective tissue fibrils of the magma become intermingled with flakes of a peculiar tissue which take on an intense stain in hsematoxylin. Sometimes a few of these flakes are found in specimens containing normal embryos, but in numerous pathological specimens large areas of these flakes are seen. In tubal pregnancy they are often present, and at first were described as large plaques of mucin, "possibly representing a degenerate yolk sac," but upon further study it was soon found that these plaques first arise within the magma fibrils of the ovum quite independently of the yolk sac. They grow in large masses, and with the destruction of the ovum they are also spilled out into the tube lumen. The plaques are stratified, forming layers that alternatingly take on the haematoxylin more intensely. When cut transversely they resemble sections from an onion with a central nucleus, as shown in plate 11, figure 4. The central point is generally intensely stained. When a section is not cut transversely, the markings are more or less parallel, as shown in the other portion of this same figure. Gradually, in the later development, these plaques run together and form a spongy substance which stains intensely with haematoxylin; the individual portions of the plaques, however, always show stratification. Whether the last word has been said about granular magma it is difficult to determine at present. It may be that only a portion of granular magma takes on this stain, while the other portion does not. At any rate, it is established that the reticular magma is formed of connective tissue fibrils which belong to the cells of the chorionic wall. They are not elastic nor white fibrils, but practically identical with the connective-tissue syncytium of the embryo and the chorion. The granular magma is a peculiar substance composed of individual particles that are stratified and stain intensely with hsematoxylin.
Degeneration of Villi and Chorion
We have repeatedly alluded to the various kinds of degeneration of villi and their covering. It remains now to consider this question in a somewhat connected way, as it is perfectly well known that villi are constantly undergoing degeneration in normal development. The trophoblast becomes active in regions where it receives nutrition, but when this nutrition is cut off it degenerates. In general, the stroma of the villi responds in a similar way. After the trophoblast has become necrotic, the body of the villus degenerates. When the trophoblast is active the villi sprout and grow. We have a condition which is frequently seen in organic nature and is well illustrated by the growth of the vine over the lattice- work; the favored twigs grow and the rest fail.
Trophoblast. When the larger villi are detached from the decidua in normal development, they contract and form small nodules composed mostly of trophoblast cells. These soon become white and necrotic, and can readily be observed with the naked eye, as they measure about 1 mm. in diameter. In the course of time these necrotic masses are invaded by new trophoblast cells, usually from neighboring villi, and we have here an interesting phenomenon, the dead cells being eaten up by the living. This may be seen in the normally developed ovum. A modification of this process is observed at the point of juncture of the villi with the decidua. Here also the necrotic masses, often spoken of as fibrinoid substance, are invaded by new trophoblast cells, giving in transverse section the appearance of cartilage. Fibrinoid substance is probably derived from a variety of sources, trophoblast, epithelial cells, blood, and also fibrin. This is well shown in plate 2, figure 3, which is from an ovum containing a normal embryo. The figure pictures the tips of the villi reaching through a blood clot, the normal trophoblast surmounting the villus and clot, and at the border the cells are undergoing hyaline degeneration, which grades over into strands forming the fibrinoid substance. In the course of time the degenerate cells coalesce to form either a stratified mass or irregular plaques. This is all shown in the figure. The larger plaques are now often invaded by fresh trophoblast cells, and so the process continues. Such a condition is found just as frequently in tubal as in uterine pregnancy. Another type of degeneration of the trophoblast is well shown in specimens which have become suddenly detached from the tube wall. Here large masses of cells become necrotic suddenly, and this condition I have usually spoken of in my notes as an indication of strangulation of the ovum. Such a specimen is well illustrated in plate 2, figure 4. Here we have a villus, the core of which is almost entirely destroyed, surmounted by an irregular layer of trophoblast from which the nuclei have largely vanished. From this degenerate covering fibrils run out in all directions, becoming continuous with the adjacent fibrinoid substance. In this specimen there has been a secondary invasion of the dead villus by maternal leucocytes which are polymorphonuclear and also show fragmentation. A more intense reaction in the sudden death of the trophoblast is seen in plate 2, figure 6. Here also there is no inflammatory reaction, so that the process of histolysis is not complicated by it, but the protoplasm of the trophoblast, forming an irregular hyaline mass, also continues to surround the fibrinoid substance. In this specimen the arrangement of the nuclear granulars is especially interesting; they have run together, forming large masses, which stain intensely in hsematoxylin. In some portions of the specimen these masses may be so large as to be seen with the naked eye. In general the mass of nuclear substance grades off into fine particles, as shown in plate 2, figure 3. Sometimes these particles are arranged in streaks or they are scattered irregularly and may then be spoken of as nuclear dust. This is often seen in specimens which have become detached suddenly from the tube wall. A similar condition, but not so intense, is shown in plate 4, figure 1. In this we have all stages of destruction of the stroma of the villus. On account of its peculiar appearance, as well as on account of the fact that it often takes up the hsematoxylin stain, I have termed this kind of degeneration "mucoid." At any rate, whether it be mucoid or not, the core of the villus gradually breaks down and disintegrates. While this process is taking place, we often see scattered through the stroma of the villus large protoplasmic cells, first observed by Hofbauer (plate 2, fig. 7) . These cells, which I have repeatedly seen in the villi of pathological ova, may be a type of wandering cells; at any rate, when the villus is being invaded by the leucocytes and trophoblast, it might be thought that they arise from the latter, but this is improbable. Plate 2, figure 4, and plate 11, figure 2, are taken from the same specimen and represent two stages of "mucoid" degeneration. In both stages the villi are being attacked by the leucocytes. In plate 7, figure 2, there is a large area of blood around the villus which contains no strands of fibrin or fibrinoid substance. The leucocytes are scattered throughout this area as well as the adjacent area containing the fibrils. This picture is seen very frequently in sections from tubal pregnancies. Immediately around the villi there is no fibrin whenever the section is mottled, that is, when it contains both old and fresh blood; the latter nearly always encircles the villi. This would indicate that when the ovum is lodged in a clot fresh blood can reach the chorion only along the line of its villi. As this small layer encircling the villi contains no fibrin and as the small mass of blood which enters the intervillous spaces has not coagulated, it seems allowable to conclude that the trophoblast produces a ferment which prevents coagulation of blood. In fact, this idea seems to be acceptable to all authors who have written upon this subject. So when we have relatively large ova covered with tufts of villi, the fresh blood produces large patches around them, while the older blood, somewhat distant, is forming the well-organized clot. This condition is shown in plate 8, figure 4; plate 9, figure 3; and plate 10, figure 1. It can also be demonstrated in practically any distended tube containing a pathological embryo. On a smaller scale the condition is well shown in plate 7, figure 2.
Nevertheless, we frequently find large independent clots in a normal implantation, both within the tube and uterus, showing that the anti-clotting property of the trophoblast does not extend far beyond its own border. It prevents clotting of the blood in its immediate neighborhood. When the trophoblast taps the blood vessels the escaping blood does not coagulate until it has formed a larger mass within the intervillous spaces, but it then forms a large rigid clot.
The most unusual kind of degeneration of villi is fibrous. We recognize in this variety an advanced stage of development; that is, a fibrous degeneration of a young villus makes the stroma appear like that of an older one. Undoubtedly this process may take place very rapidly. This statement is adduced from a condition found in specimen No. 874. Here the ovum was divided, part of it lying near the point of implantation in the uterine end of the tube and the other part somewhat distant in the fimbriated end. In the second portion practically all of the villi have undergone marked fibrous degeneration. Three stages of this process are shown in plate 2, figures 1 and 2, and plate 3, figure 1. The main wall of the chorion of the specimen No. 694 appears to be quite normal. The mesenchyme is delicate and transparent, with active strands reaching into the cavity of the ovum; but the chorion is well encircled by a clot, which in turn is perforated by a number of villi containing an active trophoblast upon their tips. Many of the villi have undergone mucoid degeneration and there is much nuclear dust. A few, however, are undergoing fibrous degeneration, as illustrated by this figure, which shows a villus lying free within the fresh clot. It is also surrounded with numerous leucocytes not shown in the picture. Plate 2, figure 2, is taken from a specimen is which only a few villi are found within the tube lumen. Most of them are more fibrous than the one from which the figure was drawn. Here the stroma is denser than in the previous specimen, and there is no regular trophoblast lying upon the villus. At one point it forms a necrotic fibrinoid mass. It is interesting to note that where a villus comes in contact with the tube wall it also is undergoing a hyaline degeneration. The extent of this process is shown in the coloring in the figure.
Plate 3, figure 1, shows a most advanced stage of fibrous degeneration. The ovum has reduced itself to a single fibrous strand and the coelom is obliterated.
From this strand, which is a collapsed ovum, delicate fibrous strands reach to the surface of the clot. One of these is shown in the figure. It can be seen that the epithelial covering is separated from the body of the villus. The space between the villus and its covering is filled with a coagulated fluid which takes on the eosin stain. In different portions of the specimen this fluid contains numerous red blood corpuscles, indicating that the surrounding villus is composed of red coagulated plasma. As the epithelial covering lies free in this fluid and was undoubtedly fixed when the specimen was preserved, we must view this relation as being normal for this stage of degeneration. According to the history of this specimen this ovum was 46 days old, while a normal specimen of this size would not be more than half as old. This shows the probable duration of degeneration in the specimen. The clot itself is highly organized and permeated with stratified fibrils, which form a very dense network on the outside of the specimen. There is no hemorrhage in it and not much infiltration of leucocytes. We have here an example of a tubal pregnancy with almost complete destruction of the ovum through fibrous degeneration.
Specimen No. 754. Now that I have given a somewhat detailed account of the magma and the various kinds of degeneration of villi, I can take up the description of small pathological ova without repeating too often the description of the various kinds of degeneration found in them. This specimen seems to have been dead some time before the operation, as most of the trophoblast is necrotic and there is also a great deal of nuclear dust. Outside of the chorion there has been quite an extensive invasion of leucocytes. There are a few small masses of syncytium, which still appear to be alive, but some of them are vacuolated. The magma is mottled and at its periphery some delicate fibrils are seen. Otherwise, each of the two types of granular magma is quite homogeneous in structure. Occasionally they are mixed, that is, the particles of darker magma invade the lighter, and vice versa. All this is shown in plate 3, figure 2. The relation of the chorion to the tube wall is shown in the outline of plate 9, figure 3. Most of the chorion and its villi are lodged between the blood clot and the folds of the tube wall, but nowhere is the chorion attached to the surrounding structure through the trophoblast. The conclusion is that the ovum was attached high in the tube; it is now being aborted into the peritoneal cavity.
Specimen No. 4$S. This specimen, which was discussed at some length when speaking of the etiology of tubal pregnancy, is also of especial value at this time, as it shows the structure of a small ovum in process of abortion. The ovum had attached to it numerous small, slender villi, which are outlined in text-figure 9. These were embedded in a fresh blood-clot, as is indicated in text-figure 8. On account of the great interest of this specimen, we also give a drawing of the tube with part of it cut open (text-figure 7). The tissues of the ovum are pale and do not stain very well. The villi are partly necrotic, partly granular, and partly fibrous. The trophoblast is scanty. The coelom is filled with granular magma, through which radiate some mesoderm cells and in which is lodged a crumpled membrane, as shown in plate 5, figure 4. This mass has also scattered through it a good deal of maternal blood. No doubt some of this blood was dragged in as a result of the manipulations which were required to free the specimen from the tube wall, but since so many cells are embedded within the mass of magma, it can not be admitted that all of them were introduced by mechanical processes. It may be that the crumpled membrane represents the amnion, but this could not be established with certainty, although the specimen was cut into serial sections. We have in this specimen a repetition of the condition found in No. 754.
Specimen No. 367. In this, the third specimen in this group, the process of degeneration is not so far advanced as in the other two. The coelom is filled with reticular magma, as shown in the figure. The villi are fairly well developed and there is some trophoblast, most of which is necrotic. This specimen has entirely separated itself from the tube wall and lies free within the lumen. It was removed from the tube wall by Mr. Brodel, who made a sketch of the clot and the ovum. He peeled the ovum out of the clot and found on one side a small tuft of villi. This was cut into serial sections. Some of the villi are undergoing mucoid degeneration, and one of these is shown in text-figure 5, and plate 4, figure 2.
Another specimen which belongs to this group is No. 520. It was found on the side of a tubal clot which measured 35 mm. in diameter. The ovum itself is 5 mm. in diameter and is filled with a reticular mass. Most of the chorionic wall is necrotic, but there are a few slender fibrous villi, one of which penetrates the clot to its middle. There are loose villi within this clot. This specimen has become entirely separated from the tube wall and is surrounded by a large highly organized clot, indicating that the tubal pregnancy is of considerable duration. In many respects the fibrin within the clot corresponds with that of the next specimen.
Specimen No. 570. In this the most advanced stage of degeneration is shown. It is possible that when degeneration began this specimen was somewhat older than the ones just described. The ovum has been reduced to a single mass of fibrous tissue without a coelom, and from this central mass several long, slender villi arise, which reach to the periphery of the highly organized clot containing the ovum. The tip of one of these villi is shown in plate 3, figure 1. The trophoblast is entirely degenerated, and the clot is composed of a dense network of fibrils which stain intensely with haBmatoxylin. Here we have a detached ovum which has undergone complete fibrous degeneration within a highly organized clot.
There are a number of other small specimens which belong to this group, and which, therefore, can be treated collectively. In No. 154 considerable activity is apparent. The villi are somewhat fibrous, and have upon them a considerable amount of trophoblast, which at points is quite active, especially where it comes in contact with the blood. No. 367 was found free in the abdominal cavity. The ovum is 10 mm. in diameter and is well developed. The villi appear normal. The coelom was filled with a dense reticular magma, but no embryo could be found. Specimen No. 378 has an appearance somewhat similar to that of No. 754. It is dumbbell-shaped, and is 12 mm. in length. This specimen had parthy eroded the tube wall, and one end of the dumbbell was projecting into the peritoneal cavity, while the other extended back to the middle of the clot. The coelom contained a considerable amount of granular magma. The syncytium was necrotic, showing that the ovum was partly strangulated. The other portion of the syncytium seemed quite normal, a number of tufts being vacuolated. No embryo was found in this specimen.
It having been shown that the ovum must gradually disintegrate and be absorbed, we have looked with special care to find remnants of specimens after the small ovum has fallen to pieces. A good specimen of this kind is No. 472. There is little to be said about it, as only a few villi were found scattered within the tube lumen. A larger group of villi, shown in plate 2, figure 2, was found in the lumen near the fimbriated end, lying within a cleft which no doubt had held them there for some time. The degree of fibrous degeneration and reaction of the villus with its trophoblast upon the tissue of the tube wall have already been described. In other parts of the section are other smaller groups of villi which have undergone a greater degree of degeneration. Some of the trophoblast is found well embedded within the smaller clefts of the tube wall, and, wherever it is present, we find signs of a reaction upon the tissue of the tube wall. In the immediate vicinity of the villi there is fibrinoid degeneration, surrounded by extensive leucocytic infiltration.
The specimen which fits in with No. 472 is No. 787. It is much like it except that the few scattered villi are encircled with a great deal of fresh blood. The specimen consists of four blood-clots, which with the distended right tube, measure 11 mm. in diameter, the distention being near the fimbriated end. The blood clots were produced by blood which had leaked into the peritoneal cavity. The tube was examined with great care and it was found that its uterine end and folds were matted together, almost obliterating its lumen. There are also numerous outpocketings of the epithelial lining. In the middle of the tube the adherent folds form a plexiform mass, encircling the organized clot. There are also numerous fresh hemorrhages. At one point a small group of fibrous vilh' was found lodged between the clot and the mucosa, which in this region was infiltrated with fresh blood. This shows clearly that the hemorrhage in these cases arises from the tube opposite a small mass of fibrous villi. No doubt in the course of time this bleeding would flush away the loose villi and thus bring these cases of tubal pregnancy to a happy conclusion.
Another specimen in which there is a large blood clot and few villi is shown in the sections from No. 514. The blood clot here appears to be quite fresh and scattered through it are a few fibrous villi. At points surrounding the villi are small tufts of vacuolated syncytium, showing that there is some activity left when the trophoblast comes in contact with fresh blood. It appears as if the few villi have been engulfed by a fresh mass of blood, which will ultimately be discharged into the peritoneal cavity, carrying these villi with it. A different fate is shown in specimen No. 539. This shows a highly organized clot full of fibrin, which is especially marked [at its periphery. The clot is also markedly infiltrated with leucocytes at its periphery. It peels out easily, measuring 1 cm. in length and 5 mm. in diameter. After it had been cut into serial sections, a few degenerate villi were found scattered through the middle of the clot. Some of these had undergone mucoid changes and others were fibrous. Many of the villi were filled with polymorphonuclear leucocytes, which were very numerous throughout the clot. In the course of time this clot might have been extruded into the peritoneal cavity, or it might have undergone further organization, ending ultimately in absorption. It is difficult to find fewer villi than have just been described in these specimens, except when they are held together with a large clot. It is simply a matter of chance that only a single villus is found attached to the tube, but quite frequently only a few villi appear in the larger clots. Good specimens of this sort are No. 298 and No. 659, in which 3 or 4 villi were found. They were small, irregular bodies, giving no evidence that they had been detached from the chorion that is, they were rounded off on all sides. The same is the case in specimen No. 519. At this point a specimen which is especially interesting is No. 794, in which the tube was well distended and the clot was not adherent to the tube wall at any place. After repeated examinations no villi could be found with certainty. At a few points small groups of necrotic cells were seen, which may represent the last remnants of degenerated villi; yet it remains a matter of opinion whether or not this tube contains any villi, though it can be considered as a specimen from which the villi have nearly or entirely disappeared (plate 5, fig. 3, and plate 6, fig. 7).
In all the specimens just described, excepting No. 378, the ova are not attached to the tube wall. In all cases they seem to have gained nutrition directly from the epithelial surface of the tube, or from hemorrhages, or from blood which comes from the folds to which the ova begin to attach themselves. They were speedily separated and moved around free within the tube lumen. Ultimately they were engulfed in a fibrous clot or were aborted into the abdominal cavity. No. 378 represents the transition stage; here the ovum had become well attached to the tube and was then promptly torn loose. In order to make this point clear a third set of specimens will be described.
Specimen No. 540 shows the coelom well filled with magma and its chorionic wall partly fibrous and partly necrotic. Some slender villi arise from this wall and reach through the blood clot to the folds of the tube, which shows a very pronounced follicular salpingitis. At one point several villi are entering one of these follicles and coming in contact with fresh blood. On these villi the trophoblast is active, so this specimen may be looked upon as being still attached to a fold of the tube, but in which, on account of the extensive hemorrhage, the ovum has collapsed and been strangled (plate 6, fig. 6).
Specimen No. 673 shows the process less advanced than in No. 540. Here the chorionic wall is sharply defined, the coelom contains maternal blood, and the villi are very irregular, but some of them reach to the tube wall, where they are fairly well attached and show an active trophoblast. At one point the trophoblast is puncturing a blood vessel. On one side of the hemorrhage there is a crescentshaped space which represents the tube lumen. In this case the implantation has been interstitial and abortion has taken place into the tube lumen. At any rate, the ovum has been partly attached to the tube wall and is at the beginning of strangulation.
Specimen No. 772 is the last specimen of this group. The clot lies free within the tube lumen; the chorion is collapsed and fibrous, and some of the villi are still reaching to the periphery of the clot, where they come in contact with fresh blood. Here the trophoblast is active, but there is no ovum to nourish. It appears as if the independent villi possess a considerable power to grow even after they are separated from the ovum. Several specimens, to be described presently, will bring out this point.
I have separated the last 3 specimens from the rest for the reason that in these cases it is practically impossible to eliminate implantation within the tube wall. In the small specimens it seems quite clear that at most the ovum attaches itself only to the folds of the tube and never becomes well implanted within the muscular wall. As soon as hemorrhage starts up it is naturally detached and encircled by the clot, but in the last 3 specimens it is not clear whether the ovum had only attached itself to the tube wall or had actually become implanted within it. This point can not be determined definitely by the technical methods I have employed. Serial sections are here required. For the present this question remains open.
Other specimens. In cases in which the ovum remains attached to the side of the tube wall for some time, it is quite clear that the method of its degeneration would differ from that which occurs when the ovum is entirely detached and free in the tube lumen. It certainly seems probable that the ovum receives its nutrition best in case it comes in contact both with the tube wall and with fresh blood. It appears as though both these, elements are required to produce the most perfect pabulum, so that the ovum free in the tube lumen must feed upon maternal blood, while that still attached to its wall receives its nutrition also from the maternal tissues.
An interesting specimen in this connection is No. 415. It came from an operation which took place 6 weeks after the last menstrual period. The tube was hardened in Mo, and then cut into blocks and the region in which the villi were seen was cut in serial sections. In these was found a small clump of villi attached to the folds in the tube and undergoing mucoid degeneration. At one point there was a single villus within the tissues of the fold encircled by an extensive trophoblast which radiated in all directions. Here, then, we have a small mass of necrotic villi and a single one which is active.
A more advanced stage is shown in No. 773. A single fold of the tube has the ovum implanted within it. This fold is distended and looks much like a cherry about 8 mm. in diameter, hanging into the tube lumen, which is about 18 mm. in diameter. Within the center of this nodule are a few villi covered with a certain amount of trophoblast and encircled by fresh blood. From this central mass the blood forms layers which are more successfully organized as the wall of the fold is reached. The principal mass of blood within the tube lumen is of uniform consistency, but contains no remnants of the ovum. It appears that this ovum had attached itself within the tissue of the folds and there gradually undergone degeneration. A similar condition is seen in specimen No. 772. In this trophoblast and villi are more active and some necrotic villi are scattered through the blood clot within the lumen of the tube.
A far more active picture is supplied by No. 720. Here the trophoblast is attached around for nearly two-thirds of the circumference of the tube. In all probability this was a case of interstitial implantation with the crescent-shaped lumen of the tube on one side. In many respects the attachment to the tube wall and active trophoblast is much like that seen in No. 808, which contained an almost normal embryo. The villi are partly normal in appearance and partly edematous. The trophoblast over the villi is very active, especially where these come in contact with the tube wall. At these points they might pass for normal villi and trophoblast.
About 6 specimens remain, which show the fate of an attached ovum extending into the organized clot within the tube lumen. In all of these specimens the lumen encircles more than one-half of the clot, so that it is impossible to determine, with any degree of certainty, whether we are here dealing with a true interstitial implantation or whether the ovum was attached only to a fold in the tube wall, as is well illustrated in specimens Nos. 415, 473, and 418. The first specimen of this group (No. 659) contains a well-formed clot, having in the center a few small fibrous villi. Some of these, in turn, are encircled with a narrow zone of fresh blood. Another specimen belonging to this group (No. 575) contains a coelom 5 mm. in diameter; that is, the ovum did not collapse. Between the coelom and the tube wall is a mass of radiating fibrinoid tissue with scattered villi covered with necrotic trophoblast, containing much nuclear dust. Some of the villi are also necrotic, some are undergoing mucoid degeneration, and others are fibrous. A few of them are encircled with a zone of fresh blood. Curiously enough, these are undergoing mucoid degeneration. No. 726 gives an appearance similar to that in No. 659, excepting that the distention of the tube is greater. Here the description of No. 575 could also be applied to this specimen. There are a few fibrous villi and a few which have undergone mucoid degeneration. These latter are also encircled by a zone of fresh blood.
Nos. 762 and 809 can be taken up together, as in many respects they are alike. In both the tube wall contains an extensive hemorrhage, which has not become organized to any great degree. Both contain scattered fibrous villi, a ramified system of fibrinoid substance, and a great marked invasion of leucocytes. These pass along the line of the fibrinoid substance. At some points the villi are being destroyed by the leucocytes.
The group of specimens in which the ovum has become fairly well implanted in a fold of tube wall differs in several respects from a group in which the ovum lies free within the tube lumen. In the former the ovum grows to a larger size before it begins to degenerate, there is a more marked hemorrhage, and the degeneration of the ovum is delayed; in other words, there is a greater mass of necrotic tissue to undergo destruction.
The remaining group to be considered consists of ova which have become well implanted in the tube wall and contain practically no remnants of the embryo. Such a specimen usually contains a well-defined coelom, and occasionally a very small remnant of an embryo may be detected. It is probable that the embryo was present in more of the cases, but was overlooked. This group is to be viewed as a continuation of the one containing pathological embryos. In the further course of destruction the embryos gradually disintegrate and finally the chorion is left attached to the tube wall. In the first specimen of this group (No. 825) the chorion appears to be normal and the coelom well defined. This specimen is described in the protocols and is accompanied with two good illustrations. Plate 9, figure 5, shows a section through the middle of the most distended portion of the tube. One can see, at once, that the ovum contains two cavities, and further examination shows definitely that we have a double ovum; but in neither was there an amnion, and only one showed any trace of an embryo. This consisted of a very small, delicate nodule representing probably the last remnant of the attachment of the embryo to the chorion. This specimen might be classed with those containing pathological embryos, but since the embryo has been practically destroyed, it is of special value when placed at the head of the present group. The villi of the chorion are very active and their trophoblast is firmly attached to the tube wall. The implantation seems to be normal; but for some unknown reason the embryo has been destroyed.
Another specimen which naturally follows this is No. 874. Here we have also a double ovum, one part of which lies within the uterine end of the tube and the other is somewhat distant and in process of abortion. Between the two divisions of the ovum the tube is constricted and contains no chorion within its lumen. Near the uterine end the chorion is well implanted within the tube wall. The lumen of the tube is on one side of the specimen, but the chorionic mass has broken into it. Beyond this the tube lumen is filled with a very much disintegrated ovum, the trophoblast of which, however, shows marked activity. The villi are matted together with fresh blood and the trophoblast is extremely active. At only one point is there a remnant of the embryo, which is being invaded by leucocytes and is undergoing histolysis. In many respects the picture suggests a tissue culture. At any rate, this specimen shows that if the fresh ovum is crushed and intermingled with fresh blood, it may undergo a further growth. The portion of the ovum, which is in process of abortion, has undergone some fibrous degeneration, but the trophoblast is still very active. This portion of the specimen is markedly infiltrated with leucocytes, which have also invaded some of the fibrous and necrotic villi. This specimen differs greatly from No. 835, which seems to show simply a double ovum.
In No. 874 the ovum is double, owing to some injury, whereby the normally implanted ovum has been crushed, partly destroyed, and pushed into the lumen of the tube, and a portion of it is being discharged into the abdominal cavity. There is no history to account for this condition, but examination of the section certainly suggests that the distribution of this crushed specimen was due to some mechanical injury. Another point worthy of notice is that the ovum which is being aborted contains a remnant of a chorion in a somewhat advanced stage of degeneration, whereas the portion near the point of implantation seems to be quite normal. In other words, as this ovum left its point of attachment to move out into the tube, it began to undergo necrosis and fibrous degeneration (plate 11, fig. 1).
There is a small group which follows closely upon the two just described. In these specimens there is a sharply defined cavity which has not collapsed, and some of them contain an amnion. In each the ovum is fairly well implanted within the tube wall and to all appearances the cavity should contain a normal or certainly a pathological embryo. In general they represent a stage of degeneration in advance of that seen in No. 825. The first specimen belonging to this group is No. 430. The chorionic wall is well infiltrated with blood, the villi are mostly necrotic, and there is a great deal of nuclear dust, which also indicates that a large mass of trophoblast has undergone rapid destruction. Even the chorionic membrane itself is fibrous. No. 495 shows appearances very similar to those just described, except that the degeneration is not so far advanced. There is still some active trophoblast left, but large masses of it are necrotic. At certain points the chorionic wall and villi are being invaded by the syncytium. No. 507 also belongs to this class. In the following two specimens the degeneration seems to be less advanced than in those just described. No. 515 had been examined before it was fixed, and was found to contain a smooth internal surface without amnion. The villi appeared to be fibrous, and some of the trophoblast had undergone hyaline degeneration. No. 517 contained an amnion and possibly the remnants of an embryo. It appeared as though the embryo had been removed through mechanical means. The chorionic wall and the amnion were normal in appearance, but the trophoblast was beginning to undergo complete hyaline degeneration. The specimen suggests that the whole ovum had become detached sometime before the operation, since most of the trophoblast and villi are necrotic and large clumps of nuclear dust are present. The specimens that have just been considered show degrees of degeneration in a reverse order. In none was there any marked effort towards further growth, but it appears as if the ovum had become strangulated and had undergone necrosis promptly. There are, however, other specimens (e. g., Nos. 561, 602, and 694) which show an attempt at further growth after the embryo had been destroyed. In all three there is still great activity of the trophoblast, although much of it is necrotic. We have in these specimens, side by side, some villi that are very active and well implanted and others that are necrotic. A pregnancy of this sort may continue for a considerable time and form a large tubal mole. It all depends on how long the mass receives nourishment from the tube wall. If the trophoblast continues to erode the tube wall, new blood sinuses are punctured, and if this blood in turn comes in contact with the ovum, the specimen may continue to grow. In fact, we see every indication of such a growth when the tubal mass is large. The specimen becomes mottled, that is, between the long fibrous strands larger areas of fresh fluid blood appear, which can be seen through the tube wall and become very apparent when sections are made. Hence the further growth of this type of tubal pregnancy can continue along two paths; first, we may have the generally slow growth throughout the chorion, and secondly, when the strangulation is nearly complete, development may continue, owing to the advent of large quantities of new blood. Illustrative of the former type we have several good specimens. In the first (No. 418) the ovum was still attached to the tube wall, although the chorion had undergone almost complete fibrous degeneration. In many respects the arrangement of the chorion to surround the clot is similar to that shown in plate 10, figure 1. A less advanced stage of degeneration is shown in No. 513. The ovum has collapsed and the villi are long and fibrous. Some are long and slender. The strangulation here is also nearly complete, and the ovum is pretty well inclosed within an organized clot. A stage intermediate to those just described is found in No. 553. The ovum here is also partly collapsed. It is hourglass-shaped, showing that it is in a process of division. The chorion and its few irregular processes have undergone marked fibrous degeneration. In No. 686 the condition is similar, but the ovum is encircled by a larger clot.
We have represented here, on a larger scale, what was found to take place in the case of the small ova found free within the tube lumen. There occurs a rapid destruction of the main wall of the chorion, leaving the villi free; they then become rounded and atrophic as a result of fibrous degeneration. These small remnants then become surrounded by a well-organized fibrous clot. In larger specimens (e. g., No. 418) the main wall itself not only disappears, but also undergoes fibrous degeneration. Such an ovum then becomes encircled by an organized clot. In order to bring out this point more clearly, we have illustrated three stages by means of diagrams, which have been made from the entire section of the tube containing the degenerated ovum. Plate 8, figure 4, is taken from a case in which there was a pus tube on one side of the uterus and a pregnancy in the other tube. The tube had gradually become distended and contained within it a collapsed and fibrous ovum, as indicated in the figure. From this body a few slender villi reach to the wall of the tube. On one side there is a small lumen of the tube, showing undoubtedly that these sections were taken from the beginning of an interstitial implantation. Radiating through the clot from side to side are large fibrous strands, and immediately surrounding the ovum and elsewhere are large masses of fresh blood.
A different type of specimen is shown in plate 10, figure 1. Here there is a large crescent-shaped tube lumen; otherwise the arrangement is somewhat similar to that in plate 8, figure 4. The coelom is entirely obliterated and from the collapsed ovum are radiating numerous slender fibrous villi. In this specimen fresh hemorrhages are neither so numerous nor so pronounced. A combination of these two specimens is shown in plate 9, figure 1. The coelom is very small and filled with a dense reticular magma, and the villi are numerous and radiate in all directions throughout the specimen. The clot is only slightly attached to the tube wall, and is almost entirely encircled by the tube lumen. The hemorrhages have probably occurred successively, as the fresher blood is of two different colors. It has gradually leaked in, no doubt through the point of attachment of the fibrous ovum to the folds of the tube wall. The following specimens are very similar. No. 765 has within it a fibrous chorion with a considerable amount of reticular and granular magma within the coelom. The villi are mostly necrotic, partly fibrous, and radiate through the large clot. About the same condition prevails in No. 815, but the main wall of the chorion is not necrotic and some villi reach to the tube wall. Most of the villi are necrotic, some are fibrous. In No. 809 there is a general destruction of the ovum. The main wall is fibrous and contains within it a stellate cavity. The villi are large and necrotic and there has been a very extensive invasion of leucocytes.
A hemorrhage forms an unusually large clot in No. 777. It lies mostly free within the tube and contains within it some necrotic villi and several detached folds in the tube wall; otherwise the ovum has vanished. A similar condition prevails in No. 835. Here also are a few scattered villi, some of which are long and fibrous and permeate the clot. The trophoblast is scanty, but on one side it shows slight activity; here it comes in contact with the tube wall and there is marked leucocytic infiltration. The next step would be a complete destruction of the scattered villi and the gradual absorption of the blood clot. Possibly such a specimen would result in a pure hemato-salpinx, but my material does not carry me into a discussion of this subject.
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