Proximal-type Epithelioid Sarcoma of the Head and Neck (HN): A Study with Immunohistochemical and Molecular Analysis of SMARCB1

Proximal-type epithelioid sarcoma is an aggressive variant of epithelioid sarcoma most often occurring in soft tissues of the proximal limbs, characterized by polygonal cells, marked nuclear atypia, and varied rhabdoid features. Malignant rhabdoid tumor is an aggressive, well characterized entity typically with rhabdoid morphology and involving the kidney of pediatric patients. Rarely, tumors with morphologic and biologic features identical to those in kidney occur in extra-renal sites and are regarded as an extrarenal presentation of the same entity in kidney, named malignant extra-renal rhabdoid tumor. Morphologic and immunophenotypical similarities between proximal-type epithelioid sarcoma and malignant rhabdoid tumor pose a diagnostic challenge and may suggest a relationship between the two. Both tumors are characterized by loss of SMARCB1 (INI1/BAF47/SNF5) expression; however, the molecular events involved differ. Here we describe the immunohistochemical and molecular analysis of three head and neck tumors with morphologic features shared by proximal-type epithelioid sarcoma and malignant rhabdoid tumor. All tumors showed loss of SMARCB1expression. Direct sequencing of the promoter and nine coding exons of SMARCB1, multiplex ligation-dependent probe amplification, and whole genome single nucleotide polymorphism array were performed on the two adult cases and showed only a heterozygous deletion of chromosome 22 in a minority of cells in one of the cases. Though rare, proximal-type epithelioid sarcoma could occur in the head and neck and should be differentiated from other epithelioid tumors by the loss of SMARCB1 expression. The lack of detectable genetic alteration in the SMARCB1 locus in head and neck proximal-type epithelioid sarcoma warrants further investigation into the molecular mechanism underlying loss of SMARCB1 expression.