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Our knowledge regarding the role of genes encoding the chromatin remodeling switch/sucrose non-fermenting (SWI/SNF) complex in the initiation and progression of gynecologic malignancies continues to evolve. This review focuses on gynecologic tumors in which the sole or primary genetic alteration is in SMARCA4 or SMARCB1, two members of the SWI/SNF chromatin remodeling complex. In this review, we present a brief overview of the classical example of such tumors, ovarian small cell carcinoma of hypercalcemic type, and then a detailed review and update of SMARCB1-deficient and SMARCA4-deficient tumors of the uterus and vulva., (© 2020 Wiley Periodicals LLC.)

Evolution of poorly differentiated chordoma from conventional chordoma has not been previously reported. We encountered a case of a poorly differentiated chordoma with evidence of whole-genome doubling arising from a SMARCB1-deficient conventional chordoma. The tumor presented as a destructive sacral mass in a 43-year-old man and was comprised of a highly cellular poorly differentiated chordoma with small, morphologically distinct nodules of conventional chordoma accounting for <5% of the total tumor volume. Immunohistochemistry (IHC) revealed both components were strongly reactive for brachyury and lacked normal staining for INI1. Single nucleotide polymorphism (SNP) array analysis identified multiple genomic imbalances in the conventional component, including deletions of 1p, 3p, and 22q (involving SMARCB1) and loss of chromosomes 5 and 15, while the poorly differentiated component exhibited the same aberrations at a more profound level with additional loss of chromosome 4, low level focal deletion of 17p (involving TP53), and tetraploidy. Homozygous deletion of SMARCB1 was present in both components. Fluorescence in situ hybridization (FISH) analysis confirmed the relevant deletions in both components as well as genome doubling in the poorly differentiated tumor. This case suggests that SMARCB1 loss is an early event in rare conventional chordomas that could potentially evolve into poorly differentiated chordoma through additional genomic aberrations such as genome doubling. Further studies with additional patients will be needed to determine if genome doubling is a consistent pathway for evolution of poorly differentiated chordoma., (© 2020 Wiley Periodicals LLC.)

Tumors of the head and neck are extremely diverse and a subset are poorly differentiated and difficult to classify. Recently, a new entity has been described with rhabdoid and/or plasmacytoid cytologic features and a characteristic genetic signature-inactivation of the SMARCB1 (INI-1) tumor suppressor gene. To date, only 16 cases of SMARCB1 (INI-1) deficient sinonasal carcinoma have been described, and there are currently no reports of the cytopathologic features by fine needle aspiration (FNA) cytology. A case of a 77-year-old man who presented with a posterior ethmoid sinus lesion with invasion into the skull base and bone was reported. FNA cytology of a right retropharyngeal lymph node revealed relatively monomorphic, loosely cohesive clusters of plasmacytoid cells with occasional nucleoli, rare intranuclear cytoplasmic inclusions, and mitotic figures in a background of necrosis and absence of overt squamous or glandular differentiation. A diagnosis of metastatic myoepithelial carcinoma was made; however, retrospectively, the surgical excision showed loss of the SMARCB1 (INI-1) tumor suppressor gene by immunohistochemistry. In summary, the cytomorphologic features of SMARCB1 (INI-1) deficient sinonasal carcinoma are relatively nonspecific and overlap with other regional tumors, including myoepithelial neoplasms. As a result, this entity should be considered in the differential diagnosis for a plasmacytoid tumor arising in the sinonasal tract by FNA cytology. Diagn. Cytopathol. 2016;44:700-703. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)