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Clinicopathologic and Molecular Characterization of SMARCB1-Deificient Sinonasal Carcinomas -A Systematic Study from
Qinyuan Li1, Tarek Abi-Saab1, Andrey Prilutskiy1
1Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI, 53705, USA.
Abstract:
BACKGROUND: SMARCB1-deficient and SMARCA4-deficient sinonasal carcinomas are rare, with only a few systematic studies available in the literature. Secondary EWSR1 gene abnormalities have been reported in SMARCB1-deficient tumors. This study aimed to systematically investigate SWI/SNF complex-deficient sinonasal carcinomas in a single-institution cohort, perform clinicopathologic characterization, and explore the underlying molecular mechanisms. METHOD: Immunohistochemistry (IHC) of INI1 and BRG1 was performed on tissue microarrays containing tumor tissue from 149 consecutive sinonasal carcinomas. Single nucleotide polymorphism (SNP) array and EWSR1 gene fluorescence in situ hybridization (FISH) analyses were conducted on SMARCB1-deficient sinonasal carcinomas. Clinicopathologic characterization was studied. RESULT: Of the 149 sinonasal carcinomas, 7 (4.7%) showed SMARCB1 loss, while none demonstrated SMARCA4 loss. All patients were male and presented with advanced-stage tumors. Four SMARCB1-deficient sinonasal carcinomas exhibited basaloid morphology, two displayed eosinophilic tumor morphology, and one had mixed morphology. Homozygous and heterozygous SMARCB1 deletions were identified in 4/6 and 2/6 cases respectively. Heterozygous loss involving genes neighboring SMARCB1 gene, including EWSR1, was observed in four cases. One tumor showed a heterozygous loss of the entire chromosome 22q. EWSR1 FISH assay revealed concordant heterozygous EWSR1 loss in these five cases. CONCLUSION: SMARCB1-deficient carcinomas account for 4.7% of sinonasal carcinomas in this single-institution cohort, while SMARCA4-deficient tumors are even rarer, with none identified. SMARCB1-deficient sinonasal carcinomas exhibit a broad spectrum of morphologic and immunohistochemical features. These carcinomas show complex genetic alterations, with homozygous SMARCB1 deletions present in the majority of cases.
Insights
SMARCB1-deficient sinonasal carcinomas, identified in 4.7% of cases, show diverse morphology and complex genetic alterations, including homozygous deletions. SMARCA4-deficient tumors were not found in this cohort.
Area of Science:
- Oncology
- Genetics
- Pathology
Background:
- Sinonasal carcinomas with SMARCB1 or SMARCA4 deficiency are rare, with limited systematic research.
- Previous studies suggest EWSR1 gene abnormalities in SMARCB1-deficient tumors.
Purpose of the Study:
- To systematically investigate SWI/SNF complex-deficient sinonasal carcinomas.
- To characterize the clinicopathologic features and molecular mechanisms of these rare tumors.
Main Methods:
- Immunohistochemistry (INI1, BRG1) on 149 sinonasal carcinomas.
- SNP array and EWSR1 FISH analysis on SMARCB1-deficient tumors.
Main Results:
- SMARCB1 loss observed in 4.7% (7/149) of cases; no SMARCA4 loss detected.
- SMARCB1-deficient tumors presented in advanced stages, with varied morphology (basaloid, eosinophilic, mixed).
- Complex genetic alterations including homozygous SMARCB1 deletions and heterozygous EWSR1 loss were identified.
Conclusions:
- SMARCB1-deficient carcinomas represent 4.7% of sinonasal carcinomas in this cohort; SMARCA4-deficient tumors are rarer.
- These carcinomas display diverse morphologic and immunohistochemical features.
- Complex genetic alterations, particularly homozygous SMARCB1 deletions, are characteristic.
