Epithelioid Trophoblastic Tumor Presenting as a Large Cystic Mass: Diagnostic Clue From Foreign DNA Sequences Detected by Comprehensive Genomic Profiling

Epithelioid trophoblastic tumor (ETT) is an extremely rare gestational trophoblastic neoplasm typically presenting as solid nodular lesions. We report an unusual case of ETT in a postmenopausal woman in her 50s that occurred 20 years after her last pregnancy. The tumor presented as a 19-cm multilocular cystic mass protruding from the cervix and was suspected to be infected. Initial histopathological examination revealed a solid proliferation of epithelioid to spindle cells expressing cytokeratins and p40, leading to a provisional diagnosis of sarcomatoid carcinoma. Comprehensive genomic profiling (CGP) was performed because of uncertainty regarding the primary site. Unexpectedly, CGP revealed DNA sequences of foreign origin, which prompted consideration of gestational trophoblastic disease rather than contamination. Additional immunohistochemical staining demonstrated positivity for HSD3B1, a specific marker of trophoblastic differentiation, confirming a diagnosis of ETT. Complete surgical resection was achieved, with no recurrence during 18 months of follow-up. This case has 2 important teaching points. First, ETT can present as a large cystic lesion rather than as a classical solid mass, likely as a result of extensive necrosis and superimposed infection. Second, detection of foreign DNA sequences during genomic profiling of a uterine tumor should alert pathologists to the possibility of gestational trophoblastic disease, given that these tumors are of fetal origin with a distinct genetic profile differing from that of maternal tissue. Recognition of these features is crucial for accurate diagnosis and appropriate management of this rare neoplasm.