Acta Cytologica
Nongynecologic Cytopathology
Cytology of SMARCA4-Deficient Thoracic Neoplasms: Comparative Analysis of SMARCA4-Deficient Non-Small Cell Lung Carcinomas and SMARCA4-Deficient Thoracic SarcomasNambirajan A.a · Dutta R.a · Malik P.S.b · Bubendorf L.c · Jain D.aaDepartment of Pathology, All India Institute of Medical Sciences, New Delhi, India
bDepartment of Medical Oncology, Dr. B. R. Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India cInstitute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland |
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Article / Publication Details
Received: June 23, 2020
Accepted: July 15, 2020
Published online: August 27, 2020
Issue release date: January - February
Number of Print Pages: 8
Number of Figures: 4
Number of Tables: 1
ISSN: 0001-5547 (Print)
eISSN: 1938-2650 (Online)
For additional information: https://www.karger.com/ACY
Abstract
Introduction: Inactivating mutations of the SMARCA4 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4) gene and/or loss of the BRG1 (brahma-related gene 1) protein defines SMARCA4-deficient thoracic sarcoma (SMARCA4-dTS), an aggressive neoplasm with a usually fatal outcome. Similar SMARCA4 mutations/BRG1 loss is also seen in a subset of non-small cell lung carcinomas (NSCLCs; SMARCA4-dNSCLCs) that lack alterations in currently targetable oncogenic drivers, that is, EGFR, ALK, and ROS1. There is limited knowledge on the cytomorphological features of these SMARCA4-deficient thoracic neoplasms. Methods: We retrospectively analysed the cytology of 2 cases each of SMARCA4-dNSCLC and SMARCA4-dTS to understand their cytomorphological overlap, if any, and identify features that would prompt testing for BRG1 loss. Results: All 4 patients were males presenting with advanced disease, with a mean age of 41.5 years (SMARCA4-dTS) and 58.5 years (SMARCA4-dNSCLC) at presentation. The cytology of the 2 SMARCA4-dTSs was strikingly similar, showing predominantly singly dispersed rhabdoid phenotype tumour cells with perinuclear cytoplasmic condensations in an inflammatory or necrotic background. The cytology raised suspicion for a wide range of differentials, including melanoma, high-grade lymphoma, germ cell tumour, undifferentiated carcinoma, and undifferentiated sarcoma. SMARCA4-dNSCLCs, on the other hand, were recognizable as poorly differentiated (adeno)carcinomas and were easily distinguished from SMARCA4-dTSs, with both cases showing cohesive clusters of frequently large tumour cells with abundant pale cytoplasm. Conclusion: A diagnosis of SMARCA4-dTS is possible on cytology with appropriate ancillary testing and a high index of suspicion. The cytology of SMARCA4-dNSCLCs does not overlap with SMARCA4-dTS; rather, it resembles that of any poorly differentiated (adeno)carcinoma in the limited numbers analysed in this study.
© 2020 S. Karger AG, Basel
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Article / Publication Details
Received: June 23, 2020
Accepted: July 15, 2020
Published online: August 27, 2020
Issue release date: January - February
Number of Print Pages: 8
Number of Figures: 4
Number of Tables: 1
ISSN: 0001-5547 (Print)
eISSN: 1938-2650 (Online)
For additional information: https://www.karger.com/ACY
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