Diagnostic Challenges in Small Cell Carcinoma of The Ovary, Hypercalcemic Type: A Case Report With Histopathological and Molecular Correlation

Abstract

Background: Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and highly aggressive ovarian malignancy affecting predominantly young women. Owing to its overlapping histomorphological features with other ovarian small round cell tumors, diagnosis remains challenging and increasingly relies on integration of histopathology, immunohistochemistry, and molecular testing.

Case Presentation: We report the case of a 24-year-old woman presenting with abdominal pain, vomiting, weight loss, and paraneoplastic hypercalcemia. Imaging revealed a large right ovarian mass with metastatic para-aortic and supraclavicular lymphadenopathy. Histopathological examination demonstrated a highly cellular malignant neoplasm composed predominantly of small round to oval cells arranged in sheets, nests, and trabeculae with brisk mitotic activity, extensive necrosis, admixed rhabdoid cells, and characteristic follicle-like spaces. An extensive immunohistochemical panel excluded the principal differential diagnoses but was not entirely specific. Comprehensive next-generation sequencing identified two pathogenic truncating SMARCA4 frameshift mutations, confirming biallelic SMARCA4 inactivation and establishing the diagnosis of SCCOHT. The tumor was staged as FIGO IIIA2 (pT3aN1b). The patient underwent surgical resection followed by platinum-based chemotherapy with etoposide and cisplatin and remained disease-free at early follow-up.

Conclusion: This case highlights the diagnostic challenges posed by SCCOHT and emphasizes the importance of integrating morphology, immunophenotyping, and molecular analysis for accurate diagnosis. Identification of biallelic SMARCA4 inactivation provides definitive diagnostic confirmation and supports the evolving role of molecular pathology in distinguishing SCCOHT from its numerous histological mimics. Early recognition and multidisciplinary management are essential to optimize patient care.