Pregnancy-Associated Small Cell Carcinoma of the Ovary, Hypercalcaemic Type Initially Misdiagnosed as Granulosa Cell Tumour: Diagnostic Pitfalls, Treatment Challenges, and Molecular Confirmation by Next-Generation Sequencing.

BACKGROUND

Small cell carcinoma of the ovary, hypercalcaemic type (SCCOHT), is an exceptionally rare and highly aggressive ovarian malignancy affecting predominantly young women. Its overlapping morphology with other poorly differentiated ovarian tumours and lack of specific early markers frequently lead to diagnostic delay. Universal loss of SMARCA4 expression defines the disease and has critical diagnostic and therapeutic implications.

CASE PRESENTATION: We describe a young woman diagnosed with an ovarian malignancy during pregnancy (12.6 weeks), initially interpreted as a granulosa cell tumour based on histomorphology. She underwent surgical management (initial surgery during pregnancy at 16.2 weeks, hysterectomy at 39 weeks) followed by platinum-based chemotherapy and achieved an initial complete radiologic response. However, the disease recurred rapidly with extensive peritoneal, visceral, skeletal, and cutaneous metastases, including scar-site involvement. Recurrent tumour histology showed an undifferentiated phenotype with a non-contributory immunohistochemical profile, resulting in significant diagnostic ambiguity. A definitive diagnosis was established by next-generation sequencing, which identified a pathogenic SMARCA4 alteration, confirming SCCOHT. Despite aggressive multimodal therapy, the disease progressed relentlessly with rapid clinical deterioration.

CONCLUSION

This case underscores the profound diagnostic challenges posed by SCCOHT, particularly when presenting during pregnancy and mimicking sex cord-stromal tumours. It highlights the limitations of morphology and immunohistochemistry alone in poorly differentiated ovarian neoplasms and reinforces the indispensable role of SMARCA4 testing and molecular profiling for accurate diagnosis. Early recognition is essential to guide aggressive multimodal therapy, genetic counselling, and consideration of emerging targeted strategies. This report adds to the limited literature on SCCOHT and emphasises the need for heightened clinical suspicion and precision diagnostics in young women with rapidly progressive ovarian malignancies.