STUDIES OF GESTATIONAL TRAPHOBLASTIC DISEASES IN IBADAN, NIGERIA

Abstract

Gestational Trophallactic Diseases (MTD) embrace two main lesions of which is subdivided into two-hydatidiform mole, non-invasive and invasive (chorioadenoma destruens) and choriocarcinoma. These pregnancy-associated disease show a striking geographical variation (Joint Project, 1959) being relatively frequent in the far East and Asia but rare in Europe and America. There is a paucity of literature on their incidence in Africa where the disease have been suggested to be common (Hendrickse et al, 1964; Edington, 1978). The association of the disease with pregnancy and the knowledge that choriocarcinoma may play a part in its aetiology. Its peculiar distribution has also suggested that both genetic and environmental factors may be involved. This thesis was directed to defining the frequency and biological behavior of the lesions in Ibadan, and to determining what roles immunological mechanisms and common environmental infective agents may play in the pathogenesis of the tumour. Both retrospective and prospective studies were done and from the results obtained the following submissions were made. Frequency Hydatidiform mole and choriocarcinoma occur much more frequently in Ibadan than in Europe and America but whereas most patients come within and around Ibadan, the lesions are seen in most parts of Nigeria. Morbid Anatomy Both the Hydatidiform mole and choriocarcinoma are in their morphological expressions similar to similar lesions described from other parts of the world. Hydatidiform mole, abortion and full term pregnancy may precede choriocarcinoma. Histological grading of moles is not useful in predicting their subsequent clinical behavior. The invasion mole appears to be a different expression of behavior of moles in that it rarely results in choriocarcinoma or kills the patient. In contrast to reports from Western Europe, Nigerian patients show much less cellular reaction to both the invasive mole and choriocarcinoma. The cellular reaction is not related to the use of cytotoxic drugs. It does not appear to greatly influence the response to chemotherapy although late presentation and a poor clinical state may negate any advantage a good cellular response confers. Clinical Presentation Hydatidiform mole and choriocarcinoma are more common in the older multiparous Nigerian women and do not show the increase observed in teenage mothers in the U.S.A. and Israel (Matalon and Modan, 1978). Patients most frequently present with vaginal bleeding following varying periods amenorrhea. Hyperemia, gravidarum, preeclampsia and eclampsia are not unduly common in Nigerian patients with molar pregnancy. Uteri that are larger than the period of amenorrhoea and palpably enlarged cystic ovaries may indicate subsequent persistence of trophoblastic proliferation. Symptoms and signs in choriocarcinoma are protean and are essentially gynecological, respiratory, neurological and gastrointestinal. The tumor may mimic several other diseases and choriocarcinoma should be considered very highly in Nigerian women who presents with unrelated symptoms referable to more than one symptom. With cytotoxic drug therapy-methotrexate, 6 mercaptopurine and or Actinomycin D- a high salvage rate can be expected particularly if the diagnosis is made early. Ultrestructure Hydatidiform mole and choriocarcinoma show only minor differences from the trophoblast of normal placenta and resemble much that of the early placenta. No virus particles were seen in the cells examined. Large bodies measuring 1300-2240 in length and 650-920 in width were seen outside and within the trophoblastic cells of choriocarcinoma. The nature of these bodies is not known. Immunological reactivity The depression of cell mediated immune reaction in the normal pregnant women depends on an inhibitory factor present in normal pregnancy plasma. This factor does not appear to be human chorionic geneatrophin. A similar plasma factor was not demonstrated in the plasma and sera of patients with trophoblastic neoplastic. Patients with H.T.D. are not generally immune-suppressed. Immune-suppression in choriocarcinoma is associated with anaemia, disseminated disease and a poor prognosis. Augmented response to mitogen after chemotherapy suggests that immunological reactivity may respond to a decreased tumour load or play a part in elimination of tumour cells.

Aetiopathogenesis Blood groups and haemoglobin electrophroretic patterns play no part in the pathogenesis of trophoblastic neoplasia. In relation to its protection against malaria the sickle cell trait does not protect the pregnant woman from developing M.T.D. The herpes virus type-2, E-S virus, toxoplasmosis and hepatitis B associated antigen are not associated with M.T.D. Hepatic dysfunction is associated with a poor prognosis.

Tissue Culture Trophoblast of the normal placenta can be grown in tissue culture. Two patterns of growth are observed. The cells may grow nut as sheets within 24-46 hours or may be seen as single cells. Epithelioid, ovoid, spindle and multinucleated giant forms are seen. M.C.G. is produced in vitro. By the 3rd week, the predominant cells are spindle cells and in the fourth week they are the only cells and they do not appear to produce H.C.G. Normal trophoblast cultures die out in a month. Attempts to maintain choriocarcinoma cells in prolonged tissue culture were not successful. There is a non-specific cytotoxity of normal trophoblast growing in vitro by maternal and allogeneic lymphocytes.