Discussion

Choriocarcinoma is a highly malignant trophoblastic neoplasm arising from neoplastic syncytiotrophoblast, intermediate trophoblast, and cytotrophoblast. It usually occurs in the uterus but may occasionally present at an ectopic or metastatic site. Abnormal uterine bleeding is a common clinical presentation, and serum human chorionic gonadotropin (hCG) is typically markedly elevated. Most cases occur in women of reproductive age; however, rare cases have been reported in postmenopausal women, as in the present patient.

Histologically, it is an infiltrative and destructive tumor characterized by an intimate admixture of mononuclear trophoblastic cells and multinucleated syncytiotrophoblasts. The mononuclear component consists of cytotrophoblasts and variable numbers of intermediate trophoblasts. The relative proportions of these trophoblastic cell types may vary considerably from case to case. In tumors containing predominantly mononuclear trophoblasts, careful examination of deeper sections may be necessary to identify diagnostic syncytiotrophoblasts.

The tumor is characteristically associated with extensive hemorrhage and necrosis, and viable tumor cells may be present predominantly at the periphery of hemorrhagic and necrotic areas. Mitotic activity is usually brisk. Chorionic villi are characteristically absent; their presence should raise consideration of an invasive hydatidiform mole or another gestational trophoblastic lesion.

An unusual feature of gestational choriocarcinoma is its vascular architecture. Unlike most malignant tumors, the central portions of choriocarcinoma generally lack conventional endothelial-lined neovascularization. Instead, blood-filled spaces may be lined directly by neoplastic trophoblastic cells, particularly syncytiotrophoblasts, a phenomenon termed “trophoblastic vasculogenic mimicry.” At the tumor periphery, neoplastic trophoblasts invade and replace the endothelium of pre-existing maternal vessels. This distinctive vascular arrangement probably contributes to the prominent hemorrhage characteristic of the tumor.

Immunohistochemistry may be helpful in morphologically difficult cases. Syncytiotrophoblasts show strong cytoplasmic expression of β-hCG, while mononuclear trophoblastic cells may show more variable staining. The Ki-67 proliferation index is usually high.

The principal differential diagnoses among gestational trophoblastic neoplasms are placental site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor (ETT). Their major distinguishing features are summarized below.

In an unusual clinical setting, particularly in a postmenopausal patient or when distinction between gestational and nongestational choriocarcinoma is clinically important, molecular genotyping may be useful. Demonstration of paternal alleles supports gestational origin, whereas their absence may suggest a nongestational tumor or a somatic malignancy showing trophoblastic differentiation.

Despite its highly malignant histologic appearance and propensity for hematogenous metastasis, choriocarcinoma is highly sensitive to chemotherapy, and modern treatment achieves excellent outcomes in most patients.

References

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