Elsevier

Cancer Genetics

Volume 207, Issue 9, September 2014, Pages 358-364
Cancer Genetics

Review article
Pathology and diagnosis of SMARCB1-deficient tumors

https://doi.org/10.1016/j.cancergen.2014.07.004Get rights and content

Malignant rhabdoid tumor (MRT) can occur in the kidney, central nervous system, or extracranial/extrarenal locations and is characterized by alterations in the SMARCB1 gene. The tumors occur in infants and young children and confer a poor prognosis requiring aggressive therapeutic interventions to improve the chances for survival. MRTs pose a diagnostic challenge, as they display heterogeneous histopathologic features and differentiate along multiple lineages. The identification of alterations in the SMARCB1 gene in MRT using immunohistochemical (IHC) staining has lead to improved diagnosis of MRT as well as the discovery of the loss of SMARCB1 expression in some non-MRTs. Whether loss of SMARCB1 plays a pathogenic role in nonrhabdoid tumors remains to be determined; however, most of these tumors lack the clinical and other molecular features of MRT. We review the histopathologic features of MRT and the importance and significance of loss of expression of SMARCB1 in both MRT and nonrhabdoid 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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