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SMARCB1-deficient carcinomas of the head and neck region: a cytopathologic characterization
Brie E Kezlarian1, Oscar Lin1, Snjezana Dogan1
1Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
Introduction:
SMARCB1 encodes for a component of the SWI/SNF complex and is widely implicated in carcinogenesis. In the head and neck, SMARCB1-deficient carcinomas typically arise in the sinonasal tract but can be found at other sites. EZH2 inhibitors have emerged as potential targeted therapy against SWI/SNF-deficient tumors. We sought to characterize the cytomorphology of head and neck carcinomas with SMARCB1 deficiencies to identify potential candidates for targeted therapy.
Materials And Methods:
Head and neck carcinomas with SMARCB1 mutations were retrospectively identified and confirmed to be SMARCB1-deficient by both molecular (fluorescent in-situ hybridization or next generation sequencing) and immunohistochemical means. Cases with positive cytology were reviewed and their cytologic features cataloged.
Results:
A total of 19 specimens from 13 patients were reviewed, including 8 specimens from 7 sinonasal carcinomas, 4 specimens from 3 thyroid carcinomas, 3 specimens from 2 skin carcinomas, and 4 specimens from 1 carcinoma of unknown primary origin. High-grade features were common, including mitoses (11 of 19) necrosis (13 of 19) and multinucleation (16 of 19). Tumors showed either dense cytoplasm with distinct cell borders (10 of 19) or delicate cytoplasm with indistinct cell borders (9 of 19). Most tumors showed no distinct epithelial differentiation (12 of 19), while some (7 of 19) showed glandular or signet ring features. A minor cohort demonstrated rhabdoid cells (4 of 19).
Conclusions:
Head and neck carcinomas with SMARCB1 deficiencies have a wide array of morphologies and tend to demonstrate high-grade features. Only a minor cohort demonstrate rhabdoid-type cells. Evaluation of SMARCB1 deficiency for potential targeted therapy should not be limited to tumors with rhabdoid morphology.
Insights
SMARCB1-deficient head and neck cancers show diverse cell appearances, often with aggressive traits. This suggests that targeted therapy evaluation should include non-rhabdoid tumors.
Area of Science:
- Oncology
- Genetics
- Pathology
Background:
- SMARCB1 gene mutations are linked to various cancers, including head and neck carcinomas.
- SWI/SNF complex deficiencies are implicated in tumorigenesis.
- EZH2 inhibitors show promise for treating SWI/SNF-deficient tumors.
Purpose of the Study:
- To characterize the cytomorphology of head and neck carcinomas with SMARCB1 deficiencies.
- To identify potential candidates for targeted therapy based on cytologic features.
Main Methods:
- Retrospective identification of head and neck carcinomas with SMARCB1 mutations.
- Confirmation of SMARCB1 deficiency using molecular (FISH, NGS) and immunohistochemical methods.
- Review and cataloging of cytologic features from positive cytology specimens.
Main Results:
- Nineteen specimens from 13 patients were analyzed, including sinonasal, thyroid, and skin carcinomas.
- High-grade features such as mitoses, necrosis, and multinucleation were common.
- Tumor morphologies varied, with some showing rhabdoid cells, but this was not a universal feature.
Conclusions:
- Head and neck carcinomas with SMARCB1 deficiencies exhibit diverse morphologies and high-grade features.
- Rhabdoid morphology is present in only a minority of these tumors.
- Targeted therapy evaluation for SMARCB1-deficient tumors should not be restricted to those with rhabdoid features.
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