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Background <p>SMARCB1-deficient and SMARCA4-deficient sinonasal carcinomas are rare, with only a few systematic studies available in the literature. Secondary <i>EWSR1</i> 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.</p> Method <p>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 <i>EWSR1</i> gene fluorescence in situ hybridization (FISH) analyses were conducted on SMARCB1-deficient sinonasal carcinomas. Clinicopathologic characterization was studied.</p> Result <p>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 <i>SMARCB1</i> deletions were identified in 4/6 and 2/6 cases respectively. Heterozygous loss involving genes neighboring <i>SMARCB1 gene</i>, including <i>EWSR1</i>, was observed in four cases. One tumor showed a heterozygous loss of the entire chromosome 22q. <i>EWSR1</i> FISH assay revealed concordant heterozygous <i>EWSR1</i> loss in these five cases.</p> Conclusion <p>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 <i>SMARCB1</i> deletions present in the majority of cases.</p>

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Clinicopathologic and Molecular Characterization of SMARCB1-Deficient Sinonasal Carcinomas – A Systematic Study from a Single Institution Cohort

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月14日

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  • Qinyuan Li,
  • Tarek Abi-Saab,
  • Andrey Prilutskiy,
  • Vanessa Horner,
  • Leah Frater-Rubsam,
  • Yajing Peng,
  • Wei Huang,
  • Randall J. Kimple,
  • Paul M. Harari,
  • Ricardo V. Lloyd,
  • Rong Hu

摘要

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.