Theron, M.Goedhals, Jacqueline2022-04-042022-04-042020-02http://hdl.handle.net/11660/11564Gestational trophoblastic disease (GTD) is a group of disorders derived from the placenta and includes hydatidiform mole, choriocarcinoma, placental site trophoblastic tumour (PSTT) and epithelioid trophoblastic tumour (ETT). As they are related to pregnancy, they predominantly occur in the reproductive years. These disorders are uncommon and choriocarcinoma, PSTT and ETT are very rare. Choriocarcinoma, PSTT and ETT can arise many years after a previous pregnancy and can therefore be difficult to diagnose. Rapid and accurate diagnosis is important as patients have a very good prognosis if appropriate treatment is provided timeously. Data from South Africa (SA) are lacking, and the aim of this study was therefore to evaluate the local demographic and genetic features of patients with GTD seen in public health care facilities in the Free State Province to determine whether they conform to the available African and international literature. The demographic features were evaluated by performing a retrospective review of all cases of GTD diagnosed by the Department of Anatomical Pathology, National Health Laboratory Service and University of the Free State over a 10-year period. The department provides Anatomical Pathology services to all public sector health care facilities in the Free State Province of South Africa. In addition, all patients with GTD referred to the Department of Oncology, National District Hospital for clinical management were evaluated to determine whether a human immunodeficiency virus (HIV) positive status is a poor prognostic factor. Two hundred and twenty-six patients were diagnosed in the 10 year period, 200 with hydatidiform moles (88.5%) and 26 with choriocarcinomas (11.5%). No PSTT or ETT were identified. The age of the patients and the presenting features were similar to that reported in available literature. The incidence of hydatidiform mole and choriocarcinoma was 0.4/1000 deliveries and 0.05/1000 deliveries respectively. This is extremely low and additional studies are required to determine whether this is a true reflection of the incidence or whether it may be due to non-referral of products of conception for histopathological confirmation. This study confirmed that HIV positive patients with a CD4 count of less than 200 cells/μl have a statistically significantly worse prognosis than HIV positive patients with a CD4 count of more than 200 cells/μl and HIV negative patients (p=0.03). This is of clinical significance as the Free State Province has the second highest HIV prevalence in SA and 25.5% of adults between the ages of 15 and 49 years are HIV positive. To evaluate the genetic features of GTD, next generation sequencing for NLRP7 and KHDC3L was performed on patients with a history of a previous hydatidiform mole and one or more additional episodes of reproductive wastage. These genes are maternal-effect genes and are associated with recurrent hydatidiform moles. One novel pathogenic NLRP7 variant and two novel NLRP7 variants of unknown clinical significance were identified. This is the first report of a pathogenic NLRP7 variant in a South African patient. In the second part of the study, microsatellite genotyping was performed on 20 patients with choriocarcinoma as was successful in 18 cases. Microsatellite genotyping indicated the majority to be gestational choriocarcinomas (17/18), with only a single case being non-gestational (1/18). Sixteen of the gestational choriocarcinomas were secondary to a prior complete hydatidiform mole (CHM) while one was due to a previous normal pregnancy. Their origin proved to be critical as choriocarcinomas secondary to a prior CHM have the best prognosis and primary choriocarcinoma requires different chemotherapy. The data obtained from this study will improve patient care for women with GTD and both the molecular techniques will be implemented onto the diagnostic platform after validation.enThesis (Ph.D. (Anatomical Pathology))--University of the Free State, 2020Gestational trophoblastic disease (GTD)Placental site trophoblastic tumor (PSTT)Epithelioid trophoblastic tumor (ETT)ChoriocarcinomaThesisUniversity of the Free State