Review articlePathology and diagnosis of SMARCB1-deficient tumors
Section snippets
Recognition of malignant rhabdoid tumors (kidney, soft tissue, and brain)
The first organ in which MRTs were recognized was the kidney. In 1978, Beckwith and Palmer described a subset of 24 patients treated on the first National Wilms Tumor Study. These renal tumors were distinctive both for their histology (anaplasia and sarcomatous features) and clinical characteristics (young age at presentation and strikingly worse prognosis) (11). The term “malignant rhabdoid tumor of the kidney” (RTK) was proposed in 1981 due to the cells' likeness to skeletal muscle myoblasts
SMARCB1
Although MRTs exhibit an extraordinary breadth of histologic and immunohistochemical diversity, nearly all are caused by mutation, deletion, loss of, or reduced RNA expression of the SMARCB1 gene found on chromosome 22q11.2 27, 28. First identified in 1999, SMARCB1 is a ubiquitously expressed nuclear protein, which is a component of the SWI/SNF chromatin remodeling complex. The SMARCB1 gene functions as a classic tumor suppressor in cases of MRT. Given that loss of SMARCB1 expression at the
Conclusion
MRTs are highly malignant tumors of infants and young children characterized by complex histopathology and polyphenotypic IHC staining.
The ubiquitous expression of SMARCB1 and its pathogenic loss in MRT make SMARCB1 IHC a powerful diagnostic tool. Widespread adoption of SMARCB1 IHC has lead to recognition of previously undiagnosed MRT at all sites. Additionally, it has led to the identification of loss of SMARCB1 expression in a wide variety of non-MRT neoplasms for which the biological
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2022, UrologyCitation Excerpt :Rhabdoid tumor cells are characteristically large with eccentric nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm with intracytoplasmic inclusions composed of intermediate filaments. However, the histologic features are often highly variable ranging from an absence of rhabdoid features to mesenchymal or epithelial differentiation, making histological diagnosis difficult, especially for partial excision or biopsy specimens.2 Therefore, immunostaining for INI1/BAF47 is critical when MRT is suspected.
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2021, Urologic Oncology: Seminars and Original InvestigationsCitation Excerpt :SMARCB1/INI1 functions as a tumor suppressor gene and is a core subunit of the ATP‐dependent SWI/SNF chromatin-remodeling complex [19]. Attempts to target SMARCB1/INI1 with targeting agents is currently in early stage clinical development [19, 17, 18]. Therapeutic approaches include the EZH2 inhibitor EPZ-6438 (E7438), hedgehog inhibitors, Cdk inhibitors, and/or Aurora kinase inhibitors [20-22].