Chorion

CHORION, see Pregnancy, Embryo, Placenta. Chorionic epithelioma, malignant (chorionepithelioma malignum), is a malignant neoplasm of embryonic ectoderm, histogenetically developing from the syncytium and cells of Langhans' layer ('typical forms' according to Marchand) or, which is more commonly observed, from the syncytium alone ('atypical forms' according to Marchand). Older names—deciduoma malignum (R. Maier), sarcoma deciduo-cellulare (Sanger), carcinoma serotinale, blastoma deci-duo-chorio-cellulare—should be considered incorrect, since after the capital research of Marchand no one any longer doubts that chorionic epitheliomas develop only from fetal, not from maternal tissue elements. In the overwhelming majority of cases, chorionic epitheliomas develop in connection with a past pregnancy—full-term, interrupted, ectopic, especially complicated by hydatidiform mole. Some classify as chorionic epitheliomas similar teratoid tumors with chorionic epitheliomatous inclusions (teratomas 'with unidifferentiation'), which occur in the ovaries of non-pregnant women and even in men (in the testicles). The starting material for such teratomas can apparently serve as isolated blastomeres capable of forming the indicated chorionic epitheliomatous structures. If these tumors are excluded, then the position remains valid: without pregnancy there cannot be chorionic epithelioma. Women who have had a hydatidiform mole are especially predisposed to chorionic epithelioma (see). After hydatidiform mole, chorionic epithelioma occurs on average in 6-7% (according to some authors in 15%, even in 33%—Kroemer). Veit believes that every chorionic epithelioma develops on the basis of hydatidiform mole, only the latter, due to the rudimentary development of the vesicles, cannot always be detected. Nevertheless, chorionic epithelioma can undoubtedly develop after a normal pregnancy, especially after a miscarriage. According to Burdzinski's data, in 42% of all cases collected by him, the starting point for chorionic epithelioma was hydatidiform mole, in 33% the tumor developed after miscarriages and interrupted ectopic pregnancy, and in 25%—after full-term and premature births. Primarily, chorionic epithelioma more often develops in the uterus (in the area of the placental site), less frequently in the fallopian tubes and even less frequently in the ovaries. Macroscopically, the tumor appears as isolated, small-sized (up to a walnut, to a chicken egg) nodes, blue-red (dark red) in color, soft-spongy in consistency, abundantly impregnated with blood, with an exceptional tendency to disintegrate (Fig. 1). Such a form of chorionic epithelioma ('typical' according to Burdzinski) is more common (Fig. 2). Less frequently, an atypical form is observed, in the form of diffuse growths in the thickness of the uterine wall itself (Fig. 3 and 4). The tumor nodes are usually quite clearly demarcated from the uterine muscle. The soft, spongy, necrotically disintegrating tumor mass often looks like a polypoid tumor hanging into the uterine cavity. At the same time, similar characteristic nodes can be found in the vagina, in the area of the vulva, in the ovaries. In this respect, the external appearance of metastatic vaginal nodes is especially typical: dark red-blue in color, well demarcated from the surrounding tissue, they by their appearance resemble subepithelial

Figure 1. Primary chorionic epithelioma of the vagina.

Figure 2. Typical malignant chorionic epithelioma.

Figure 3. Malignant chorionic epithelioma.

hemorrhage (hematoma), on section giving the complete impression of crushed placental tissue. Under the microscope, the tumor is morphologically (and biologically) identical to normal trophoblast (Hitschmann). It consists of elements of normal chorion (syncytium and Langhans' cells), only arranged atypically in the most diverse quantitative ratios. Unlike hydatidiform mole, in which we also have atypical proliferation of villous epithelium, in chorionic epithelioma the mesodermal stroma, separating the tumor cellular formations into individual complexes, is as a rule completely absent (in hydatidiform mole all three elements of the villi are present). A more detailed pathohistological picture of chorionic epithelioma is as follows—„_w ««*™ (Fig. 2 and 4). The main and predominant mass of the neoplasm consists of darkly stained, rich in nuclei (often giant), without cell boundaries, protoplasmic accumulations in the form of strands of various shapes or isolated masses. Bizarre syncytial proliferations are richly vacuolated, the protoplasm itself is homogeneous or weakly granular, on the free edge it often bears cilia; large, densely stained numerous nuclei lie to

Figure 4. Atypical form of malignant chorionic epithelioma; diffuse infiltration of the uterine mucous membrane.

loosely clumped. The described structural material of Ch. corresponds to the syncytium in a normal placenta. The second morphological element of the new formation consists of cells with well-defined boundaries, spindle-shaped, with finely vacuolated protoplasm, with a relatively large bubble-like nucleus, giving a clear reaction to glycogen. Figures of karyomitosis are often found in the cells. These are elements of the normal Langhans layer. In addition to this, a third cellular ingredient is also found in Ch. - the so-called mononuclear giants, round, resembling sarcomatous cells, with a large nucleus dividing mainly by budding. They are considered derivatives of the maternal tissue. These polymorphous cells ('wandering syncytial elements', 'decidual sarcomatous cells') should more correctly be considered transitional elements, which can originate partly from the syncytium (by detachment from syncytial masses) and partly from the cells of the Langhans layer. When examining microscopic preparations of Ch., the abundant hemorrhages into the tumor tissue and the widespread necrosis of tissues are striking. The hemorrhages are undoubtedly connected with the destructive effect that the tumor cells have on the adjacent tissues - a property, as is known, also inherent in the elements of the villous covering in normal conditions ('plasmodial trophoblast'). The tumor elements infiltrate the surrounding tissue, and the latter, as always and everywhere, responds to irritation with a sharply expressed inflammatory infiltration. It should be noted that the breakthrough of cellular elements of Ch. into blood vessels does not cause blood clotting. The histogenesis of Ch. (formal genesis) can at present be considered sufficiently clarified. The villous epithelium (differentiated trophoblast), morphologically and biologically identical to the tumor elements of Ch., and in normal pregnancy enters the maternal circulation (the so-called deportation of villi-Veit, Schmorl). Usually, the chorionic elements that remain in the mother's body (in the myometrium, in the lungs and other organs) undergo reverse development, degenerate and disappear. Under other conditions, they acquire the ability to unlimited proliferation and lead to the formation of Ch. The main cause of Ch. is still not known. In this respect, there are only assumptions and guesses that have not yet been confirmed and generally accepted. In the clinical picture of the disease, the main symptom is atypical, often accompanied by colicky pains, hemorrhages, extremely strong, not yielding to therapeutic measures (abrasio). A rapidly progressing anemia is striking, along with it and cachexia. In the intervals between hemorrhages, patients show serosanguineous discharge with a putrefactive odor (decay of the tumor). In later stages of the disease, feverish conditions are observed, often with chills (addition of septic infection), and albuminuria. Metastases occur extremely early in Ch.: in the vagina, lungs, kidneys, liver, gastro-intestinal tract, bladder, brain, bones, etc. According to the material of Burdzhinsky (107 cases), at autopsy, metastases of Ch. in the lungs were found in 82.2%, in the vagina - in 46%, in the liver - in 2.5%, in the kidneys - in 2.4%, in the brain - in 2.1%. Metastases in Ch. occur through the bloodstream. Lymphogenous metastases also occur, but, in contrast to cancer, they are extremely rare in Ch. In connection with the metastases, secondary signs begin to appear in the clinical picture: cough with bloody sputum, pulmonary hemorrhages, gastric pains, nausea, vomiting, apoplexy cerebri, paralysis; in the urine - syncytial cells, etc. In the ovaries in Ch., cystic formations are observed (in 50% they occur in mola hydatidosa), usually bilateral, filled with light gelatinous, sometimes bloody contents (the so-called lutein cysts). There is undoubtedly a close etiological connection between hydatidiform mole, Ch., and lutein cysts. After hydatidiform mole, they quickly regress and after some time disappear completely. Hyperluteinization of ovarian tissue occurs in Ch. due to the formation of corpora lutea atretica. Ch. develops during the period of a woman's reproductive life (the average age for Ch. is 33 years), although the possibility of tumor formation in later years of life is not excluded (the oldest patient with Ch. was 55 years old). The frequency of the disease increases with the number of pregnancies suffered. On average, the course of Ch. continues (from the beginning to the fatal outcome) no more than 8 months. Patients die from sepsis or from general cachexia due to metastases. Recognition of Ch. in some cases does not present difficulties. The suspicious coincidence in time of the first signs of the appearance of the tumor with a past pregnancy (normal or premature labor, abortion, hydatidiform mole), an enlarged, soft consistency, sometimes with poorly defined protrusions of the uterus, slightly opened external os, abundant hemorrhages and serosanguineous discharge with odor, and finally the presence of spongy masses hanging into the vagina in the form of placental polyps - all this makes recognition sufficiently easy. The microscope only confirms the diagnosis. In other cases, recognition is quite difficult. In suspected Ch. (in the uterus), the most reliable means is diagnostic curettage (carefully! tumor elements, when the integrity of blood vessels is violated, can enter the bloodstream). Sometimes it really has a decisive significance, but in some cases, even microscopic examination of the material obtained at exploratory abrasio does not clarify the diagnosis (necrotic masses without a definite structure are obtained, sometimes it is difficult to decide whether there is a benign placental polyp or malignant Ch.). When interpreting the microscopic picture of Ch., all authors point to the absence of connective tissue (and its own blood vessels) in the tumor - the latter consists only of elements of the exochorion, although again cases of Ch. with endochorionic elements have been described. The presence of characteristic metastatic nodes in the vagina helps in recognition. In the very recent time, for the diagnosis of Ch., the pregnancy test of Zondek-Aschheim is used. This reaction makes it possible to say with sufficient accuracy whether fetal elements remain after hydatidiform mole (the Zondek-Aschheim reaction should be negative 8-10 days after the operation), whether Ch. was radically removed during the operation or whether its metastases remained somewhere, whether the given tumor is suspicious for Ch., etc. The prognosis in Ch. is always serious, the prognosis should be made cautiously (rapidity of course, early metastases). Ch. from an anat.-histological point of view is definitely a malignant new formation. If one can sometimes speak of benign Ch., it is only from a clinical point of view. In this respect, the literature contains clinically established and verified observations of a benign course of Ch. (spontaneous self-healing, healing after non-radical operations, even without any surgical intervention). Metastases and the primary tumor can disappear spontaneously. Hermann described a case of healing of inoperable Ch. with metastases in the lungs. From a practical point of view, the attempts of a number of authors to give the physician more or less reliable signs for judging whether a given case (mola hydatidosa, resp. chorionepithelioma) is suspicious in the sense of the transition of hydatidiform mole into Ch. and whether Ch. is malignant in its course are of great interest. Thus Neumann considered the penetration of syncytial elements into the stroma of villi as a sign of malignancy. Others saw unmistakable signs of malignancy in the deep penetration of the exochorion into the muscular tissue of the uterus. Meyer considers suspicious those cases where chorionic elements, in the absence of villi and their remnants, remain and are microscopically revealed after the 3rd week of the postpartum period (normally they should disappear by 7 days post partum). The same Meyer recommends paying attention to the presence of leukocytic infiltration, necrosis and thrombi around the exochorial proliferations. Bauer considers suspicious in the sense of malignancy the invasion of proliferating villous epithelium through intact vascular walls into the blood vessels. Brenner considers the pictures of the decay of syncytial masses into separate cellular elements ('wandering syncytial cells') as a sign of malignancy. Finally, some try to establish the benign or malignant character of the tumor proliferations in Ch. according to the predominance in them of Langhans cells or syncytial elements. However, all these attempts should be considered as not having justified themselves in practice. Therapy: radical extirpation of the uterus with appendages (according to the Wertheim operation type or extended vaginal extirpation according to Schauta-Stoeckel) with subsequent properly conducted radiotherapy. The prognosis after the operation is not bad. The percentage of stable recoveries after radical operation is determined by the figure of 40-60%. A period of 2 years without recurrence after the operation can be considered a guarantee of the firmness of the cure. In advanced cases - radiotherapy.

In the very recent literature, there are indications of the remarkable successes of actinotherapy in chorionepithelioma. Wintz reports 77.7% absolute cure with the use of radiotherapy. If these data are confirmed, then the mentioned therapeutic method will be the method of choice in the treatment of chorionepithelioma. In a preventive aspect, it is important that each patient after hydatidiform mole remains under the vigilant supervision of a physician for at least a year (the latent period in chorionepithelioma in 70%, according to Burdzinsky, lasts 2 months and in 87% - a year). In the presence of suspicious symptoms, a diagnostic curettage is mandatory (only a positive result of the material obtained during curettage is significant). As a preventive measure, Stöckel insists on the complete removal of the uterus along with the hydatidiform mole in women who are close to the climacteric period in age. As a reliable control in the observation of patients after hydatidiform mole, one should remember the use of the Zondek-Aschheim reaction. Chorionepitheliomas of the Fallopian tubes. Primary malignant chorionepithelioma of the Fallopian tubes, developing on the basis of ectopic pregnancy, is a rather rare disease: in the world literature by 1930 (according to Georgii), 23 such cases had been described (among them, one case each was described in our country by Snegirev, Nikiforov, and Ushkov; in 1933, one such case was described by Grudzev and Ruzsky). The pathological-anatomical picture of the disease does not differ from that of uterine chorionepithelioma; typical forms are encountered much more frequently than atypical ones. Clinically, primary chorionepithelioma of the tubes proceeds under the guise of ectopic pregnancy (at this time, the extremely rapid growth of the tumor at the site of former resistance attracts attention). Recognition of tubal chorionepithelioma is impossible: to this day, there has not been a single case of correct diagnosis before surgery or autopsy. Therapy: radical operation followed by vigorous use of X-ray irradiation. However, with such therapy, sustained recovery was achieved in only one case of primary chorionepithelioma of the tube, described by Klein. Chorionepithelioma of the ovary is an extremely rare malignant neoplasm (8 cases of primary chorionepithelioma). In the ovary, it is customary to distinguish: 1) true chorionepitheliomas from placental epithelium, 2) chorionepitheliomas as a variety of teratoid tumors, and 3) false chorionepitheliomas. Among true chorionepitheliomas, three forms are distinguished: metastatic chorionepithelioma (developing as a result of the implantation of villous epithelium from an existing primary focus - in the uterus or tubes), ectopic (the development of chorionic cells occurs without a primary focus, at the site of egg attachment), and heterotopic (development of chorionepithelioma after a preceding ovarian pregnancy). - Teratoid tumors with the structure of chorionepithelioma ("teratomas with unidifferentiation") by some authors are included in the group of true chorionepitheliomas on the grounds that they have the same macro- and microscopic structure; it is still more correct to single them out into a separate group. Under the name of false chorionepitheliomas, syncytium-like formations in carcinomas (more often) and in sarcomas are known. True chorionepitheliomas, genetically associated with pregnancy, do not differ in their macro- and microscopic structure from ordinary uterine chorionepitheliomas. Clinically, these are malignant tumors requiring radical surgery, although cases of complete spontaneous healing have been described.