Causes
Gestational choriocarcinoma (GC) is the most aggressive form of trophoblastic tumor; it most commonly arises from certain fertilization defects, such as molar pregnancy, which results in increased level of growth factors and uncontrolled proliferation of trophoblasts in the uterus. Statistics from clinical cases have shown that GC is associated with any pregnancy events, with 50% of GC arise from hydatidiform moles, 25% from gestation, and 25% from abortion or tubal pregnancy. Risk factors
The exact underlying causes for this disease are still not fully elucidated, part of the reasons being that this condition is very rare and it is clinically hard to distinguish it from invasive mole, which are other type of trophoblastic tumor  that present some similarities as GC. But several risk factors have been reported to have association with gestational choriocarcinoma. Maternal age. This is one of the two well-established risk factors for GC. Many studies have shown that the risk of developing GC increased very rapidly in gestational women older than 40 years old. Prior history of complete hydatidiform mole. This is another well-established risk factor for GC. It has been showed that the risk of having GC after a complete hydatidiform mole is significantly higher than after a live birth. Others risk factors such as reproductive factors, use of oral contraceptives, diet and environmental factors were also reported. But because of data inconsistency, such associations are still questionable. For example, there is a case-control study showed that theres a significant association of GC in women having more than 5 births.
But other studies had showed no association when corrected for age. Pathogenesis
At the cellular level, any abnormalities in the placental trophoblastic proliferation could potentially contribute to molar pregnancy and tumor development. There are three different types of trophoblasts: cytotrophoblasts, syncytiotrophoblasts, and intermediate trophoblasts. Each of them possesses distinct specialized functions to support a developing embryo. Cytotrophoblasts are the germinating cells that forms the chorion villi and can be differentiated into syncytiotrophoblasts which produce hCG and can intrude to the inner muscle layer of the uterus to help embed the developing embryo, and intermediate trophoblasts which spread throughout the chorion villi to support maternal-fetal circulation. Malignant cellular transformation of all of these three trophoblastic cells contribute to the development of gestational choriocarcinoma. Common pathological features of GC include abnormal trophoblastic enlargement, loss of trophoblastic specialized features and functions, absence of villi in the placenta, abnormal bleeding, and necrosis.Many efforts have been made to try to understand the mechanism of how non-malignant mole could become invasive. It is suspected that activation of certain oncogenes (such as up-regulations of MDM2, c-ERB2, and BLC2) and inactivation of tumor suppressor genes (such as up-regulations of p53, p21) were involved in the processes of genetic changes in this malignant transformation. But trophoblastic cells, by nature, are highly active in cell division, the increased activities of those genes are also necessary to maintain their normal cell function. Therefore, it is still unclear how significantly these genetic changes are in the pathogenesis of gestational choriocarcinoma.