Cytomorphologic and immunophenotypical analysis of SMARCA4 (BRG1)-deficient non-small cell lung carcinoma

Oluwaseun B. Ogunbona, Xiaoqi Lin, Jason L. Hornick, Daniel J. Lubin, Qun Wang, Michelle D. Reid, Frank Schneider, Dehong Li, Dong M. Shin, Qiuying Shi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Introduction: Inactivation of SMARCA4/BRG1 (Brahma-related gene 1), a member of the switch/sucrose nonfermentable subfamily of adenosine triphosphate-dependent chromatin remodeling complexes, has been demonstrated in a subset of non–small cell lung carcinomas (NSCLCs). However, the cytomorphologic features of SMARCA4-deficient NSCLCs (SMARCA4-dNSCLC) have only rarely been reported. Materials and methods: Eight cytology cases of SMARCA4-dNSCLC and eight SMARCA4-retained NSCLC (SMARCA4-rNSCLC) cases were retrieved from our institution's database. These were compared cytologically and immunophenotypically. Results: All 8 patients with SMARCA4-dNSCLC had a smoking history, and 4 of 8 cases had a prior cancer history. Cytologically, the tumors demonstrated predominantly loosely cohesive and high-grade epithelioid cells with markedly pleomorphic nuclei and prominent nucleoli. Binucleated/multinucleated cells were seen in 5 cases. Six cases showed focal plasmacytoid morphology, and 2 cases showed necrosis. In contrast, in all 8 cases of SMARCA4-rNSCLC, the aspirates were predominantly cohesive with focal, loosely cohesive epithelioid cells showing mild to moderate pleomorphism and lacked necrosis. Only 1 case showed multinucleated cells. All 8 cases of SMARCA4-dNSCLC showed an immunoprofile similar to that of the SMARCA4-rNSCLC cases, including immunoreactivity for AE1/AE3, a lack of immunoreactivity for thyroid transcription factor-1/Napsin A, and p40/p63 but with a loss of BRG1 expression. Conclusions: SMARCA4-dNSCLCs exhibited high-grade cytologic features with marked pleomorphism and might show multinucleation and plasmacytoid morphology. In contrast, SMARCA4-rNSCLCs often show mild to moderate pleomorphism with round to polygonal shapes. Both characteristically lack expression of lung adenocarcinoma/squamous markers. Increased awareness of their cytomorphologic features on fine needle aspiration can ensure consideration of the diagnosis.

Original languageEnglish (US)
Pages (from-to)183-193
Number of pages11
JournalJournal of the American Society of Cytopathology
Volume11
Issue number4
DOIs
StatePublished - Jul 1 2022

Keywords

  • BRG1
  • Clinicopathology correlation
  • Cytology
  • Immunohistochemistry
  • Non–small cell lung carcinoma
  • SMARCA4

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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