Clinicopathological and molecular characteristics of small cell carcinoma of the ovary, hypercalcemic type: three case reports

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), is a rare and aggressive ovarian cancer that affects populations ranging from children to young adults. It is usually associated with germline and somatic variants of SMARCA4, which encodes the SMARCA4 protein (BRG1), as well as SMARCA2 (BRM) deficiency, both subunits of the switch/sucrose-nonfermenting (SWI/SNF) chromatin remodeling complex. Here, we report the clinical, morphological, immunohistochemical, and molecular characteristics of three cases. All three patients showed abnormally elevated preoperative CA-125 levels and hypercalcemia during disease progression. Two patients were initially misdiagnosed with adult granulosa cell tumor (AGCT) in local hospitals. These tumors typically exhibit a diffuse sheet growth pattern characterized by small cells with follicle-like spaces and contain variable numbers of larger cells with a rhabdoid appearance. Immunohistochemistry reveals an absence of SMARCA4 (BRG1) and SMARCA2 (BRM) in these tumors, along with diffuse expression of WT1-N terminus, vimentin, and variable expression of keratins and EMA. Next-generation sequencing (NGS) identified SMARCA4 mutations. Integrated clinical, morphological, immunohistochemical, and molecular analyses enhance diagnostic accuracy, despite the condition often being misdiagnosed.