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Original Article
- SMARCA4/BRG1 protein-deficient thoracic tumors dictate re-examination of small biopsy reporting in non–small cell lung cancer
- Anurag Mehta, Divya Bansal, Rupal Tripathi, Ankush Jajodia
- J Pathol Transl Med. 2021;55(5):307-316. Published online June 21, 2021
- DOI: https://doi.org/10.4132/jptm.2021.05.11
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- 6 Web of Science
- 7 Crossref
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Abstract
PDF - Background
SMARCA4/BRG1 protein–deficient lung adenocarcinomas and thoracic sarcoma are recently described entities that lack distinctive histological features, transcription termination factor 1 (TTF1) reactivity, and actionable driver mutations. The current diagnostic path for small lung biopsies as recommended by the World Health Organization (WHO, 2015) is likely to categorize these as non– small cell carcinoma–not otherwise specified (NSCC-NOS). The present study attempts to define the subtle but distinctive clinicopathologic features of SMARCA4/BRG1 protein-deficient thoracic tumors; highlight their unique biology; and addresses the unmet need to segregate these using a new, tissue-proficient diagnostic pathway.
Methods
All lung biopsies and those from metastatic sites in patients with suspected advanced lung cancer and classified as NSCC-NOS as per WHO (2015) guidelines were subjected to BRG1 testing by immunohistochemistry. SMARCA4/BRG1 protein–deficient thoracic tumors were evaluated by an extended immunohistochemistry panel. Predictive biomarker and programmed death–ligand 1 testing was conducted in all cases.
Results
Of 110 cases, nine were found to be SMARCA4/BRG1 protein-deficient; six were identified as SMARCA4/BRG1 protein–deficient lung adenocarcinomas, and three were SMARCA4/BRG1 protein-deficient thoracic sarcomas. The histology ranged from poorly differentiated to undifferentiated to rhabdoid. None of the cases showed significant expression of TTF1 or p40, and no actionable mutation was identified.
Conclusions
It is difficult to separate BRG1-deficient lung adenocarcinomas and thoracic sarcomas based on morphology alone. We propose a diagnostic pathway for small biopsies of thoracic tumors to segregate these distinct entities so that they can be studied more efficaciously for new biomarkers and therapeutic options. -
Citations
Citations to this article as recorded by
- Unravelling switch/sucrose non-fermentable (SWI-SNF) complex-deficient thoracic tumours: a clinicopathological comparative on undifferentiated tumours and non-small cell lung carcinomas with BRG1 and BRM deficiency
Ridhi Sood, Arshi Tandon, Warisa Khatoon, Jayashimman Vasanthraman, Aruna Nambirajan, Anant Mohan, Prabhat Singh Malik, Deepali Jain
Journal of Clinical Pathology.2024; : jcp-2024-209619. CrossRef - Case report: The first account of undifferentiated sarcoma with epithelioid features originating in the pleura
Ling-Xi Xiao, Li Liu, Wang Deng
Frontiers in Medicine.2024;[Epub] CrossRef - SMARCA4-deficient central nervous system metastases: A case series and systematic review
Meaghan Morris, Kerime Ararat, Hannah Cutshall, Murat Gokden, Analiz Rodriguez, Lisa Rooper, Matthew Lindberg, James Stephen Nix
Journal of Neuropathology & Experimental Neurology.2024; 83(8): 638. CrossRef - Chemotherapy and Immune Checkpoint Inhibitors in a Case of SMARCA4-dUT: A Case Report and Review of Literature
Akriti Pokhrel, Ruchi Yadav, Kapil Kumar Manvar, Richard Wu, Vijay Jaswani, Carrie Brooke Wasserman, Jen C. Wang
Journal of Investigative Medicine High Impact Case Reports.2023;[Epub] CrossRef - TTF1-positive SMARCA4/BRG1 deficient lung adenocarcinoma
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Lei Zhang, Ting Sun, Xiao-Ye Wu, Fa-Ming Fei, Zhen-Zhen Gao
World Journal of Clinical Cases.2022; 10(29): 10501. CrossRef - Artificial intelligence platform, RADR®, aids in the discovery of DNA damaging agent for the ultra-rare cancer Atypical Teratoid Rhabdoid Tumors
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Frontiers in Drug Discovery.2022;[Epub] CrossRef
- Unravelling switch/sucrose non-fermentable (SWI-SNF) complex-deficient thoracic tumours: a clinicopathological comparative on undifferentiated tumours and non-small cell lung carcinomas with BRG1 and BRM deficiency
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