Paper - A case of early ectopic gestation

Robinson AL. A case of early ectopic gestation. (1934) BJOGA

A Case of Early Ectopic Gestation

By

A. Leyland Robinson, M.D., Lond., F.R.C.S., Eng., F.C.O.G.

Professor of Midwifery and Gynaecology, The University of Liverpool,

and M. M. DATNOW, M.D., Liverpool, F.R.C.S., Edin., M.C.O.G.

Hon. Assistant Surgeon, The Hospital for Women, Liverpool.

46

The definitive diagnosis of ectopic gestation generally devolves upon the discovery of an extra—uterine foetus in the abdominal cavity, or the demonstration of typical lchorionic villi in the sections derived from pathological material removed at operation. Proof of the conceptional origin of tubal haematomata is occasionally furnished by the presence of an early ovum, but such evidence is very rarely obtainable at a stage of embryonic development which is antecedent to the appearance of fullyformed chorionic villi.

In our opinion, the case now to be described belongs to this exceptional group, and we believe that the morbid anatomy of any very early example of tubal gestation is worthy of record.

Clinical Historyu

The specimen was removed from a woman 36 years of age, the mother of two children, the younger of whom was two years of age.

The patient had never had any serious illnesses or operations, and there was no history of miscarriage. The menstrual cycle, three to four days every 26 days, had always been regular and painless until the onset of the illness for which she was admitted to hospital on June 13th, 1932.

The patient stated on admission that her last ordinary period had commenced on May 6th and terminated four days later, and that she had not noticed anything unusual until the beginning of June, when her period, due on the 2nd, did not come on at the expected time.

Bleeding of a menstrual type began on June Ioth, and this was followed, two days later, by severe pain in the abdomen.

No further information was elicited by cross-examination, and it was evident that the patient looked upon her symptoms as due to menstruation, and only remarkable because the period was delayed and painful.

Ordinary clinical examination failed to reveal any definite physical signs but, in view of the history, a tentative diagnosis of ectopic gestation was made and the patient prepared for operation.

In the first place careful local examination was carried out, but in spite of the complete relaxation induced by the anaesthetic, a gross abnormality could not be detected. The uterus did not appear to be enlarged, or softened, and did not give any impression of pregnancy; both ovaries were palpable and mobile, and no adventitious lump could be felt in either of the appendage.

To complete the investigation, an exploratory incision was made into the peritoneal cavity through the posterior fornix, and this procedure disclosed the presence of two small pieces of clot in the floor of the pouch of Douglas. Liquid blood was not present, and the whole of the clot did not exceed the size of a threepenny piece, but these findings, in conjunction with the clinical history, were considered to justify immediate laparotomy.

The pelvic organs were approached through a small median sub-umbilical incision, and on inspection of the pelvis, the left Fallopian tube was found to be swollen at the junction of its middle and outer thirds, at which point it exhibited a cone-shaped swelling of approximately the same size as the terminal phalanx of the little finger. There was no structure corresponding to a ripe follicle, or a corpus luteum of pregnancy, present in either ovary, and careful investigation of the uterus, appendages and surrounding structures generally did not reveal any gross abnormality apart from the swelling of the left Fallopian tube.

The absence of adhesions was specially noted, and there was not any clinical evidence of recent or old infection of the appendix or neighbouring viscera. There was no free blood clot near the left Fallopian tube, or elsewhere in the abdominal cavity.

Operative interference was restricted to the removal of the distal three-quarters of the Fallopian tube, and the subsequent recovery of the patient was uneventful.

PREPARATION or SPECIMEN. The bulging portion of the specimen (see Fig I) measured I3 millimetres on cross section at its point of maximal distension. Apart from this abnormality of shape, and an associated increase in consistence affecting the bulging area, there was little obvious departure from the normal appearance of the Fallopian tube. There was not any vascular engorgement of the peritoneal surface, and the serous coat was everywhere intact: the abdominal ostium was patent and surrounded by healthy-looking fimbriae, and we were unable to discover any external evidence of gross congenital maldevelopment in this or any other part of the Miillerian system.

A transverse section of the specimen after fixation at once revealed two features of pathological interest: (I) an area of blood clot, localized in position and circular in shape, and (2) the presence of more than one lumen (Fig. 2).

In order to make a closer study of the histological changes associated with these findings and to determine, if possible, the source of the blood-clot, the whole specimen was subjected to serial section.

Careful examination of the slides has enabled us to reconstruct the morbid anatomy of the Fallopian tube, and the details of the longitudinal sections are indicated in a diagrammatic form in the drawing (Fig. 3).

INTRATUBAL HAEMATOMA.

The blood clot extends continuously throughout 800 sections, or 5.6 millimetres of the specimen. By working out the anatomical relation of this haematoma to the other structures found within the walls of the Fallopian tube, it appears that the suffusion has begun in close contact with the blind end of a diverticulum and extended forwards into the tissues between the lumen of the latter and the mesosalpinx (Fig. 3).

The pathogenesis of this condition was obscure until a partially disintegrated ovum was discovered in the midst of the blood clot. The evidence upon which the identity of this ovum is based will be furnished later, but, assuming that an ovum has been implanted in this situation, it is probable that the haemorrhage has been induced by the invasive action of the trophoblast.

The blood set free in this way has crumpled up the ovum and tracked forwards in and along the outer wall of the second diverticulum: it has raised the general intratubal tension and produced some distortion of the plicae of the neighbouring lumen.

In spite of this compression, the epithelial lining of the diverticulum remains intact except over one area where it has disappeared with the formation of a fistulous communication between the lumen of the Fallopian tube and the blood space containing the embryo.

48 FIG. 1.

FIG. 2.

FIG. 4.

FIG. 5A.

The presence of this fistulous communication forms a connecting link between the blood composing the haematoma and the clot found in the pouch of Douglas, and so makes it possible for the one to be the source of the other.

The serial sections clearly show that intratubal leakage has occurred at this point, and that the escaping blood has passed along the main lumen and through the patent abdominal ostium into the abdominal cavity.

Leakage appears to be the correct term for the process that established continuity between the haematoma and the peritoneal cavity; the fact that the remains of the ovum have not been dislodged from their position in the wall of the Fallopian tube seems to preclude the possibility of rupture, implying as this does, a sudden accident with much destruction of tissue and a relatively considerable loss of blood.

The position of the ovum still in situ and the associated changes are more in accordance with the intermittent escape of a trifling amount of blood and the sequential formation of a small channel of communication between the blood cyst and the tubal lumen.

Diverticulosis.

The naked-eye examination of the section shows an abnormal type of canalization, and further investigation discloses a condition of diverticulosis. This condition is clearly shown in the photographs and in the drawing (see Figs. 2 and 3).

There appears to be one main lumen with at least three offshoots of which one is in close relation with the haematoma already described.

A fourth diverticulum, which has no demonstrable connexion with the main lumen, or any of its subsidiaries, is found in the later sections obtained from the uterine end of the specimen (see Fig. 2).

Each diverticulum has a complete epithelial lining and an independent muscle coat which separate it from the main lumen and its fellow diverticula. We have been unable to find any fibrosis, adhesion of plicae, or other evidence of an inflammatory process which might have preceded the formation of these diverticula.

The condition of the Fallopian tube, in our opinion, is not an artifact, but a congenital diverticulosis, the result of faulty canalization at an early stage of embryonic development.

According to some authorities, the abdominal ostium arises as a separate structure independent of the Miillerian duct proper, with which it fuses later in foetal life, and if this be so, it is not difficult to understand how divcrticulosis may arise during the process of fusion.

Buchanan and F raser' state that in embryos of 8.5 millimetres in length, the abdominal ostium consists of several subsidiary ingrowths which do not merge until later into one large opening. At this stage of development there is more than one canal in association with the abdominal ostium, and the persistence of this foetal condition would afford a ready explanation of the presence of diverticulosis in the adult.

Reference to the drawing (Fig. 3) will show that the first diverticulum arises near the fimbriated end and has a wide connexion with the main lumen. It is a short outgrowth which runs inwards and terminates blindly in a number of processes like the fingers of a glove. In close proximity to the blind end of this diverticulum, and intervening between it and the outer pole of the haematoma, there is a hyaline area in the muscle wall of the Fallopian tube. This hyaline area is separate from the main lumen, but it is continuous with the terminal finger-like processes of the diverticulum, and we suggest that it may represent the site of implantation of an ovum trapped in the first diverticulum. A few blood-sinuses can be seen around the periphery and some round-celled infiltration.

The other diverticula are similar to No. I and do not require any further description, with. the exception of No. 4. The latter arises as an island of tissue outside the tubal wall, but soon fuses with the peritoneal coat and becomes absorbed in the tube proper, although its lumen remains a distinct and independent structure throughout the remaining available sections. This diverticulum may be regarded as an accessory Fallopian tube, or ostium of a rudimentary type, and its morphological characters lend support to the view that all the diverticula are congenital in origin. It is interesting to note that the main lumen, or what appears to be the main lumen, shows faulty canalization in the later sections derived from the uterine end of the specimen, where the epithelial lining has failed to develop, and the canal is represented by a solid and symmetrical column of cells (Figs. 3 and 4).

The absence of fibrosis and distortion rules out the possibility of infection as an aetiological factor and indicates that this obliteration is simply another phase of congenital maldevelop-ment.

Oedematous Plicae and Decidual Reaction.

A conspicuous feature of the histological field is the appearance of localized oedema of the epithelium lining a portion of each lumen (Fig. 5).

In the affected area the plicae are swollen to three or four times their normal size, and it is noticeable that in each case they are localized to that part of the circumference of the Fallopian tube which is nearest to the peritoneal coat and farthest away from the blood-supply.

It is easy to demonstrate these findings, for the changes are uniform and constant, but we have been unable to find an entirely satisfactory explanation of them. It is possible that the condition of the cells may be decidual in origin, although it seems unlikely that a decidual reaction would be restricted in this remarkable way: it is, however, well known that decidual changes are very imperfectly carried out in the Fallopian tube and that in the early stages of gestation they are limited to the area surrounding the ovum.

The enlargement of the plicae is certainly d11e to oedema and, if it is not decidual in origin, it must be the result of vascular changes associated with the implantation of the ovum, or the increased tension set up by the development of the haematoma.

The decidual view is supported by a study of the changes found in the rabbit's uterus in which three different zones can be clearly demarcated from each other.

The features peculiar to the so-called placental and obplacental regions are not so well marked in late pregnancy, but they are characteristic in the early stages. They demonstrate that in the primitive uterus and morphologically the human Fallopian tube is comparable to a primitive uterus such as the rabbit’s, very marked differences may be found in the character of the cells lining the same section of the cavity. Moreover, the so-called decidual reaction in the-rabbit is limited to that part of the lining of the uterus which corresponds to the anti—mesometric border, and it is at least noteworthy that in the human Fallopian tube now under discussion, the oedema of the plicae is restricted in an exactly comparable way to the same region.

This selective relation may be correlated with the fact that the anti—mesometric border is farthest away from the main vessels, since the tissues in this distal situation must be exceedingly sensitive to changes in their blood-supply and unduly prone to develop oedema.

For this reason the raised intratubal pressure produced by the haematoma cannot be excluded as one of the possible aetiological factors in the production of the remarkable changes found in the plicae.

The Embryo.

In the midst of the blood forming the haematoma and present continuously throughout I20 sections, an organoid structure may be seen consisting of large cells containing active deeply staining nuclei (Fig. 6).

These cells bear a relation to each other which is constant and unmistakable throughout the whole of the sections in which they appear. The details of their morphology have been destroyed by the suffused blood, but their main features are readily discernible, and they constitute an entity that cannot be explained as the result of injury, inflammation or neoplasia.

The appearances of the cells are those of embryonic tissue, and their general arrangements, in our opinion, is susceptible of only one explanation, i.e. the presence of an embryo. This view receives additional support from the histological changes that accompany and surround this structure, and notably from the peripheral cells which are displaying an invasive action characteristic of the trophoblast. Associated with this embroynic tissue and scattered throughout the haeinatoma are collections of cells that have a syncytial appearance. These cells are formed of darkly staining protoplasmic masses of various shapes in which there are a varying number of nuclei. There is a tendency for these masses to surround large spaces which appear to be young blood-sinuses, since in most cases they contain blood-corpuscles.

The tendency for young syncytium to become vacuolated and to surround spaces has been frequently described by authors who have investigated the morphology of the trophoblast, and these appearances are sufficient in themselves to establish the embryonic origin of cells that exhibit such behaviour.

This View is supported in the present instance by the fact that the syncytium-like masses are well preserved and actively growing in spite of their detachment from the surrounding maternal tissues: their survival is probably another expression of the parasitic habits which distinguish the behaviour of the syncytium during implantation of the ovum.

The trophoblastic layers of cells have been ploughed up by intratubal haemorrhage, but a very careful search has failed to reveal the presence of villi. The absence of the latter is a point of great interest in conjunction with the age of the embryo.

No good purpose would be served by any further description of an ovum so badly mutilated with extravasated blood, but we believe the main features are sufficiently definite to establish its identity: there still remains, however, something to be said concerning its probable age.

An estimation of the age of an ovum can be arrived at by a consideration of three factors:

I. Dates of coitus. 2. Size of embryo. 3. Stage of development of chorion.

I. Dates of Coitus. The dates of the last normal period were May 6th—Ioth and ovulation probably occurred between May 19th and the 22nd. Coitus took place twice, namely on May 21st and 22nd: bleeding began on June Ioth, or about 18 days after ovulation, which probably coincided with one of the acts of coitus. These figures suggest that the ovum may have been fertilized 17-18 days before the date of operation, but they do not throw

any light upon the age of the embryo at the time of intratubal death.

2. Size of the Ovum.

Embryonic elements were found continuously in I20 sections and none elsewhere, so that the embryonic sac in our specimen measures 0.6 millimetres in length. The maximum width on any slide did not exceed 0.48 millimetres.

The measurements of the present specimen are compared with those of three other early ectopic ova in the following table:

NAME OF AUTHOR. AGE or OVUM. MEASUREMENTS.

Young2 - - ~ -» I3%—I4}{_; days 1.12 ><0.67 m.m. Ivens-3 — - - - I4 days 0. 8x0. 6x0. 8 m.m. VVade and Watson4 14-21 days T. 9 xo.87 xo.64 m.m. Robinson and Datnow 9 Less than 10 days 0.48 x0. 6><o.48 m.m.

It is obvious that but little reliance can be placed upon dates and measurements in connexion with the age of an ovum that has been dead for an unknown length of time; it is necessary in such cases to fall back upon the general morphology of the embryo and in particular to rely upon the stage of development reached by the trophoblast.

3. Development of Trophoblast.

The primitive trophoblast consists of small cuboidal cells which are packed closely together and undifferentiated: next, buds spring from the outer layer of these cells: later still, these buds are invaded by a core of mesothelial tissue and assume the characters and appearance of villi: finally these villi become branched.

A careful search throughout the whole series of sections cut from our specimen has failed to reveal any villi, and we feel justified in assuming that the ovum must have perished before the trophoblast had reached the stage of fully formed villi.

According to Streeterf writing in 1926, only four ova of this very early age had been described up to date, namely those of Kleinhans (Grosser), von Mollendorff Sch., Teacher—Bryce and Miller.

To these four must be added the beautiful specimen described by F alkiner° in 1932.

Conclusions

I. We believe our case to be an ectopic gestation in the early stage of intratubal abortion.

2. The diagnosis rests upon the clinical history obtained from the patient and the morbid anatomy and histology of the specimen.

3. The Fallopian tube displays a condition of congenital diverticulosis

4. A localized oedema, selective in distribution and probably decidual in origin, affects a portion of the epithelial lining of the main lumen and the diverticula.

5. A haematoma containing an organoid structure has arisen from the invasive action of cells resembling trophoblast.

6. This organoid structure consists of specialized cells of

embryonic type which represent in our opinion the remains of a fertilized ovum.

7. Consideration of the factors that determine age suggests that the embryo has undergone development for about a week

or I0 days before succumbing to the effects of intratubal haemorrhage.

Bibliography

r. Buchanan, G. and E. A. Fraser. four. of Anatomy, 1918-19, liii, 82. 2. Young, J. “Reproduction in the Human Female.” Wm. Green and Sons, 1911, Edin. and London. 3. Ivens,.F. Proc. Royal Soc., 1911, iv. (Obstet. Section 313). 4. Wade, H., and B. P. Watson. Transactions Obstet. Soc. Edin., 1907-8 xxxiii, 229. 5. Streeter, G. L. “The ‘ Miller ’ Ovum—the youngest normal human embryo thus far known." Contributions to Embryology, I926, xviii, 33. 6. Falkiner, M. Mc. ]our. of Obstet. and Gynaecol. Brit. Emp., 1932. xxxix, 441. ILLUSTRATIONS. FIG. 1. Photograph of specimen. FIG. 2. Cross section of the Fallopian tube showing the condition of diverticulosis at the junction of the second diverticulum and the main lumen. Note the presence of free blood in the main lumen and the associated diverticula, and the absence of blood from the two remaining diverticula. 1. Third diverticulum. 2. Second diverticulum joining main lumen. 3. Main lumen. 4. Fourth diverticulum. FIG. 3. Reconstruction of the morbid anatomy of the specimen based upon an examination of 1,500 serial sections.

. Patent abdominal ostium. 2. First diverticulum.

. Hyaline area—? site of implantation.

. Area in which the embryonic rudiments are found. Extravasated blood. 6. Site of intratubal leakage.

. Second diverticulum. 8. Third diverticulum.

. Non-canalized portion of Fallopian tube.

10. Main lumen. 11. Fourth diverticulum. FIG. 4. Section taken from the uterine end of the specimen to show the faulty canalization of this part of the Fallopian tube. The main lumen (M.L.) is represented by a remanent of epithelial tissue embedded in a cylindrical mass of muscle. FIG. 5. A and B. Oedematous and normal plicae.

The two photographs have been taken from different parts of the same section and submitted to the same magnification: the appearances of each are, therefore, exactly comparable.

FIG. 6.

Muscle wall of Fallopian tube showing the localized haematoma containing at A the remains of a broken up ovum (x 15).

FIG. 7.

Embryonic tissue taken from area marked A in Fig. 6 (x 100).

FIG. 8.

Embryonic tissue taken from area marked A in Fig. 6 (x2oo).

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