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Cytomorphologic and immunophenotypical analysis of SMARCA4 (BRG1)-deficient non-small cell lung carcinoma
Oluwaseun B Ogunbona1, Xiaoqi Lin2, Jason L Hornick3
1Department of Pathology and Laboratory Medicine, Emory University Hospital Midtown, Emory University School of Medicine, Atlanta, Georgia; Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas.
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.
Insights
SMARCA4-deficient non-small cell lung cancers (NSCLCs) show high-grade cytologic features like marked pleomorphism and multinucleation. Awareness of these features aids diagnosis of SMARCA4-deficient NSCLC.
Area of Science:
- Oncology
- Cytopathology
- Molecular Pathology
Background:
- SMARCA4 (BRG1) inactivation occurs in a subset of non-small cell lung carcinomas (NSCLCs).
- Cytomorphologic features of SMARCA4-deficient NSCLCs (SMARCA4-dNSCLC) are rarely reported.
- SMARCA4 is a key component of the switch/sucrose nonfermentable chromatin remodeling complex.
Purpose of the Study:
- To compare the cytomorphologic and immunophenotypic features of SMARCA4-deficient NSCLCs (SMARCA4-dNSCLC) with SMARCA4-retained NSCLCs (SMARCA4-rNSCLC).
- To highlight diagnostic clues for SMARCA4-dNSCLC on fine needle aspiration cytology.
Main Methods:
- Retrospective review of 8 SMARCA4-dNSCLC and 8 SMARCA4-rNSCLC cytology cases.
- Cytologic evaluation included cell cohesion, nuclear pleomorphism, nucleoli, multinucleation, plasmacytoid morphology, and necrosis.
- Immunophenotypic analysis included markers for AE1/AE3, thyroid transcription factor-1, Napsin A, p40, p63, and BRG1 expression.
Main Results:
- SMARCA4-dNSCLC cases predominantly featured loosely cohesive, high-grade epithelioid cells with marked nuclear pleomorphism and prominent nucleoli.
- Multinucleation (5/8), focal plasmacytoid morphology (6/8), and necrosis (2/8) were observed in SMARCA4-dNSCLC.
- SMARCA4-rNSCLC cases typically showed cohesive cells with mild to moderate pleomorphism and lacked necrosis; multinucleation was rare (1/8).
- Both groups lacked thyroid transcription factor-1/Napsin A and p40/p63 expression, but SMARCA4-dNSCLC showed a loss of BRG1 expression.
Conclusions:
- SMARCA4-dNSCLCs exhibit high-grade cytologic features, including marked pleomorphism, multinucleation, and plasmacytoid morphology.
- SMARCA4-rNSCLCs generally present with mild to moderate pleomorphism and round to polygonal shapes.
- Both tumor types characteristically lack expression of common lung adenocarcinoma and squamous cell carcinoma markers.
- Recognizing these cytomorphologic distinctions is crucial for diagnosing SMARCA4-dNSCLC on fine needle aspiration.
