SMARCB1/INI1-deficient carcinoma with yolk sac tumor-like features in the inguinal region of a young man: a case of a deceptive and emerging entity.

SMARCB1 (INI1) is a tumor suppressor gene essential for chromatin remodeling and transcriptional regulation. Loss of SMARCB1 expression defines a heterogeneous group of mostly aggressive neoplasms collectively termed SMARCB1/INI1-deficient tumors. A rare subset of these tumors exhibits yolk sac tumor (YST)-like morphology, causing significant diagnostic challenges as they can be misclassified as true germ cell tumors. We report a case of SMARCB1-deficient carcinoma with YST-like differentiation arising in the inguinal region of a 40-year-old man. The patient presented with an inguinal mass and elevated serum alpha-fetoprotein. Needle biopsy and excision specimens at an outside facility were considered consistent with a germ cell tumor, specifically a YST. He was initially treated with standard chemotherapy and had a suboptimal response. Our review of the histopathologic and immunophenotype studies verified YST-like features except for complete loss of SMARCB1 expression. Fluorescence in situ hybridization failed to identify isochromosome 12p or 12p amplification, further supporting a somatic origin. Next generation sequencing (NGS) by a commercial laboratory showed SMARCB1 deletion, microsatellite stable status, low tumor mutation burden, and an NGS-based algorithm predictive of a germ cell tumor with 99% probability, a result we consider inaccurate. This case highlights the need to consider SMARCB1-deficient carcinoma in the differential diagnosis of extra-gonadal tumors with YST-like features, especially in cases with atypical clinical presentation or resistance to standard germ cell tumor regimens. The inguinal region of young males appears to be one of the favored sites for these tumors. Furthermore, NGS-based algorithms may fail to accurately classify such tumors.