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Published on: February 28, 2019
SMARCA4/BRG1-Deficient Sinonasal Carcinoma
Aanchal Kakkar1, Subiyathul Farah Ashraf1, Amber Rathor1
1From the Department of Pathology (Kakkar, Ashraf, Rathor, Jain), All India Institute of Medical Sciences, New Delhi, India.
Context.—:
Molecular analysis of poorly differentiated/undifferentiated sinonasal neoplasms has resulted in identification of a growing number of genetically defined tumors. SMARCA4-deficient sinonasal carcinoma is one such recently described entity that emerged from within sinonasal undifferentiated carcinoma (SNUC), neuroendocrine carcinoma (NEC), and teratocarcinosarcoma (TCS).
Objective.—:
To identify SMARCA4-deficient sinonasal carcinomas from a large institutional cohort of poorly differentiated/undifferentiated carcinomas and evaluate their clinicopathologic features.
Design.—:
SMARCA4/BRG1 immunohistochemistry was performed on all tumors diagnosed as SNUC, poorly differentiated carcinoma, NEC, and TCS during a 12-year period. SMARCA2/BRM and INSM1 immunostaining was performed in SMARCA4-deficient cases.
Results.—:
Twelve SMARCA4-deficient sinonasal carcinomas were identified among 299 cases. Morphologically, 5 cases were large cell NEC, 2 cases were small cell NEC, and 5 were TCS. SMARCA4 loss was diffuse and complete in 10 cases, while 2 cases showed focal retention. Most cases showed diffuse cytokeratin staining accompanied by weak, usually focal staining for chromogranin and synaptophysin. INSM-1 showed negativity in most cases. All cases showed retained SMARCA2 expression. IDH1/2 mutation was absent in all cases analyzed. Four of 7 patients died of disease, and aggressive multimodality treatment provided better outcome.
Conclusions.—:
SMARCA4-deficient sinonasal carcinomas are morphologically akin to sinonasal poorly differentiated NECs and TCS, display cytokeratin positivity and only focal staining for neuroendocrine markers, and have aggressive biological behavior. Inclusion of SMARCA4 in the immunohistochemical panel for diagnostic workup of all sinonasal NEC and TCS phenotypes will facilitate their early recognition. Comprehensive germline and somatic mutational analyses of these tumors are necessary for further insights into their molecular pathogenesis.
Insights
SMARCA4-deficient sinonasal carcinomas, a newly identified tumor type, exhibit aggressive behavior and resemble neuroendocrine carcinomas. Identifying these tumors aids in early diagnosis and treatment planning for better patient outcomes.
Area of Science:
- Oncology
- Pathology
- Genetics
Background:
- Molecular analysis is identifying new genetically defined sinonasal tumors.
- SMARCA4-deficient sinonasal carcinoma is a recently described entity.
- This tumor type emerged from sinonasal undifferentiated carcinoma (SNUC), neuroendocrine carcinoma (NEC), and teratocarcinosarcoma (TCS).
Purpose of the Study:
- Identify SMARCA4-deficient sinonasal carcinomas within a large institutional cohort.
- Evaluate the clinicopathologic features of these identified tumors.
Main Methods:
- SMARCA4/BRG1 immunohistochemistry on 299 poorly differentiated/undifferentiated sinonasal tumors.
- SMARCA2/BRM and INSM1 immunostaining in SMARCA4-deficient cases.
- Analysis of cytokeratin, chromogranin, synaptophysin, INSM-1, and IDH1/2 mutations.
Main Results:
- Twelve SMARCA4-deficient sinonasal carcinomas were identified.
- Morphologically, these included large cell NEC, small cell NEC, and TCS.
- SMARCA4 loss was observed, with retained SMARCA2 expression and absence of IDH1/2 mutations.
- Four of seven patients died of disease, with aggressive treatment improving outcomes.
Conclusions:
- SMARCA4-deficient sinonasal carcinomas resemble NECs and TCS, exhibiting aggressive behavior.
- Incorporating SMARCA4 immunohistochemistry aids in early recognition of these tumors.
- Further molecular analyses are needed to understand their pathogenesis.
