Unusual Aspects of Small Cell Carcinoma of the Ovary of Hypercalcaemic Type: Retained SMARCA4 Immunohistochemical Staining and Positive Staining With TLE1

Small cell carcinoma of the ovary of hypercalcaemic type (SCCOHT) is a rare and aggressive ovarian neoplasm that is most common in the second and third decades. Molecular studies have established inactivating SMARCA4 alterations as the driver of SCCOHT, these being present in over 95% of these neoplasms. SMARCA4 alterations almost always result in loss of immunoreactivity with SMARCA4 (BRG1) antibody, and this is an extremely useful adjunct in the diagnosis of SCCOHT. Herein, we report 7 cases of SCCOHT (2 from the same patient) with retention of nuclear immunoreactivity with SMARCA4, but with SMARCA4 alterations identified on molecular testing. All cases exhibited loss of SMARCA2 (BRM) immunoreactivity. In addition, following the identification of diffuse TLE1 immunoreactivity in one of these cases (which did not exhibit an SS18 gene rearrangement characteristic of synovial sarcoma), we stained a total of 63 cases of SCCOHT (14 on whole tissue sections: 49 on tissue microarray) with this marker and 7 of 14 (50%) and 22 of 49 (45%) were positive on whole sections and tissue microarray, respectively. Most cases were focally positive but occasional cases exhibited diffuse immunoreactivity. Our observations highlight the importance of SMARCA2 immunohistochemical staining and molecular testing in suspected cases of SCCOHT that exhibit retained SMARCA4 immunoreactivity. Th common expression of TLE1 in these neoplasms represents a potential diagnostic pitfall since synovial sarcoma may be considered in the differential, especially in cases with retained SMARCA4 immunohistochemistry.