03/07/2026
ISGYP 170.1: 53 year old female with right ovarian mass.
Diagnosis: Grade 3 endometrioid adenocarcinoma with choriocarcinoma.
Comment: Gestational choriocarcinoma and non-gestational choriocarcinoma are distinct entities, with significant differences in their etiology, pathogenesis, clinical presentation, management, and prognosis. A clinical history of pregnancy, amenorrhea, or antecedent gestational trophoblastic disease helps to establish the gestational or non-gestational nature of choriocarcinoma. In difficult cases, tissue genotyping should be employed to confirm the diagnosis and to tailor apt management strategies, since both gestational and non-gestational choriocarcinoma exhibit identical clinical and radiological features, serum biochemical markers, histology, and immunohistochemical characteristics.
Histomorphologically, both gestational choriocarcinoma and non-gestational choriocarcinoma are composed of mono-nucleate and multi-nucleate trophoblastic cells in varying proportions. The cytotrophoblasts and intermediate trophoblasts display centrally placed small, round hyperchromatic nuclei, with clear-to-eosinophilic cytoplasm and distinct cell borders. The multi-nucleated cells are larger with irregular outlines, and correspond to syncytiotrophoblasts. These tumors often show extensive areas of hemorrhage and necrosis. The degree of trophoblastic differentiation may vary from well differentiated to poorly differentiated, and villous structure is absent. If choriocarcinoma is found in combination with other germ cell tumors in a pre-menarchal girl, then it can be ascertained to be of the non-gestational type. Non-gestational choriocarcinoma arising in association with somatic carcinoma will display adjacent areas of squamous-, transitional-, or adeno-carcinoma like above case.
The intermediate trophoblastic cells exhibit strong and diffuse cytoplasmic positivity for MUC-4, HLA-G, Mel-CAM, hPL (human placental lactogen), p63, and inhibin. In contrast, the cytotrophoblasts are immune-negative for the above markers, and show nuclear positivity for beta-catenin. Syncytiotrophoblasts cells are strongly reactive to beta-hCG, hPL. These immunohistochemical markers or cytokeratin 18 are usually used to confirm trophoblastic differentiation in poorly differentiated adenocarcinomas (ie, non-gestational choriocarcinoma arising in association with somatic malignancies) or mixed germ cell tumors. All types of trophoblastic cells show membranous positivity for cytokeratin 18 and AE1/AE3.
SALL4 (spalt-like transcription factor 4 and sal-like protein 4) has shown up to 100% specificity and sensitivity in detecting seminoma, dysgerminoma, embryonal carcinoma, and yolk sac tumor. In contrast, SALL4 is only focally or weakly expressed in choriocarcinoma. However, according to some experts, if SALL4 positivity is present, it almost certainly rules out gestational choriocarcinoma, and confirms the diagnosis of non-gestational choriocarcinoma in tumors exhibiting trophoblastic differentiation.
