Primary pure large cell neuroendocrine carcinoma of the ovary: histopathologic and immunohistochemical analysis with review of the literature

Background: Primary ovarian large cell neuroendocrine carcinoma (POLNEC) is an extremely rare and highly aggressive malignancy. Establishing a definite diagnosis requires histopathologic examination with immunohistochemical demonstration of neuroendocrine differentiation in the tumor cells. The histopathology may overlap with a variety of other ovarian malignancies; however, rendering an accurate diagnosis is essential, owing to the therapeutic and prognostic implications. Case: A 62-year-old, post-menopausal woman presented with complaints of abdominal fullness and dull-aching abdominal pain for the last three months. A pelvic ultrasound revealed the presence of a complex adnexal mass. Serum levels of tumor markers, CA125, carcinoembryonic antigen, alpha-fetoprotein, and beta-human chorionic gonadotropin, were within normal limits. Pelvic magnetic resonance imaging showed a heterogeneous lobulated right adnexal mass measuring 6.7×5.8×5.6 cm, which was T2-hyperintense and T1-hypointense. A provisional diagnosis of ovarian carcinoma was made, and a total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. Results: Histopathology showed an organoid and nesting pattern with a focal perivascular arrangement of the tumor cells with large, moderately pleomorphic, round to oval nuclei, granular chromatin, conspicuous nucleoli, and a moderate amount of pale-eosinophilic cytoplasm. Brisk mitosis and lymphovascular space involvement were noted. On immunohistochemistry, the tumor cells showed positivity for chromogranin, synaptophysin, and neuron-specific enolase and were negative for PAX8, WT1, vimentin, and epithelial membrane antigen. p53 showed wild-type, and SMARCB1/INI-1 showed retained nuclear expression. Based on the histopathologic and immunohistochemical features, a final diagnosis of POLNEC was rendered. The patient received 4 cycles of adjuvant chemotherapy and is disease-free, 28 months post-treatment. Conclusions: The present report highlights the characteristic histopathologic and immunohistochemical features of POLCNEC to distinguish it from other clinicopathologic mimics and present a comprehensive review of the published literature of all such cases.