Cytomorphologic features of SMARCA4-deficient non–small cell lung carcinoma and correlation with immunohistochemical and molecular features

Tong Sun, Syed M. Gilani, Peter Podany, Malini Harigopal, Minghao Zhong, He Wang

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


BACKGROUND: SMARCA4/BRG1-deficient tumors and those that have loss of SMARCA/BRG1 have been described as various aggressive carcinomas and sarcomas, including a subset of non–small cell lung carcinoma (NSCLC). Cytomorphologic features of NSCLCs are yet to be described. The objective of this study was to evaluate the cytomorphologic features, immunohistochemical profile, and molecular profile of SMARCA4/BRG1-deficient NSCLC (SMARCA4-dNSCLC). METHODS: The authors retrospectively searched for cases with SMARCA4/BRG1 functional loss alterations, which were identified in molecular studies and further confirmed by immunocytochemistry, and they reviewed the cytomorphologic features. Tumors with BRG1 loss were also stained with an extensive antibody panel. Molecular profiling and clinical information of the identified cases were scrutinized. RESULTS: In total, 12 cytopathology cases from different anatomic sites were included. All cases showed variable expression of cytokeratin irrespective of type. One-half of cases had glandular features, followed by squamoid features, and poorly differentiated features. The most common cytologic features included sheets or papillary architecture, round or oval cell shapes, nuclear enlargement, moderate-to-marked pleomorphism, and coarse chromatin. Two cases with poorly differentiated cytomorphology had a predominance of single cells, scant cytoplasm, and macronucleoli. Variable expression of epithelial markers was noted in all cases. TP53 was the most frequently co-mutated gene in SMARCA4-dNSLCs. CONCLUSIONS: This study demonstrates that SMARCA4-dNSCLCs can have a wide spectrum of cytomorphologic features, ranging from a relatively well differentiated adenocarcinoma to a poorly differentiated/undifferentiated carcinoma, with the majority of cases exhibiting some high-grade features, such as mitosis, apoptosis, necrosis, and marked pleomorphism.

Original languageEnglish (US)
Pages (from-to)620-629
Number of pages10
JournalCancer Cytopathology
Issue number8
StatePublished - Aug 2022
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2022 American Cancer Society.


  • Switch/sucrose nonfermenting complex–related
  • actin-dependent regulator of chromatin
  • cytomorphology
  • immunohistochemistry
  • matrix-associated
  • member 4 (SMARCA4)
  • molecular alterations
  • non–small cell lung carcinoma
  • subfamily A

PubMed: MeSH publication types

  • Journal Article


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