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SWI/SNF-deficient head and neck neoplasms: An overview.

With wide-spread use of next generation sequencing tools in surgical pathology, a variety of neoplasms have been increasingly recognized to be associated with specific recurrent defining genetic abnormalities. This has led to recognition of new genetically defined entities and refinements of preexisting heterogeneous neoplastic categories. Among these, neoplasms associated with inactivating mutations involving different subunits of the SWI/SNF chromatin remodeling complex have received special attention. In the head and neck area, SMARCB1 (INI1) and SMARCA4 (BRG1) are the main two SWI/SNF components responsible for several recently described highly aggressive undifferentiated malignancies with predilection for the soft tissue of the neck (SMARCB1-deficient malignant rhabdoid tumors in children and rare epithelioid sarcoma cases in adults) and the sinonasal tract (SMARCB1-deficient sinonasal carcinoma including a small subset of adenocarcinomas, SMARCA4-deficient sinonasal undifferentiated carcinoma and SMARCA4-deficient sinonasal teratocarcinosarcoma). Molecular studies confirmed paucity of additional genetic abnormalities in these diseases underlining the central role of SWI/SNF deficiency as the primary and frequently sole genetic driver of these lethal diseases. Initiation of clinical trials using drugs that target the SWI/SNF collapse encourages recognition and correct classification of these morphologically frequently overlapping malignancies and underpins the role of SWI/SNF immunohistochemistry as emerging powerful adjunct tool in surgical pathology of the head and neck.