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Cytomorphologic features of SMARCA4-deficient non-small cell lung carcinoma and correlation with immunohistochemical
Tong Sun1, Syed M Gilani1, Peter Podany1
1Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA.
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.
Insights
SMARCA4/BRG1-deficient non-small cell lung carcinoma (NSCLC) exhibits diverse cytomorphologic features, from well-differentiated adenocarcinoma to poorly differentiated carcinoma. This study details these features and common molecular alterations in SMARCA4-deficient NSCLC.
Area of Science:
- Cytopathology
- Oncology
- Molecular Pathology
Background:
- SMARCA4/BRG1-deficient tumors are aggressive carcinomas and sarcomas.
- A subset of non-small cell lung carcinoma (NSCLC) exhibits SMARCA4/BRG1 deficiency.
- Cytomorphologic features of SMARCA4-deficient NSCLC are not well-described.
Purpose of the Study:
- To evaluate the cytomorphologic features of SMARCA4/BRG1-deficient NSCLC.
- To analyze the immunohistochemical and molecular profiles of these tumors.
- To characterize SMARCA4-deficient NSCLC (SMARCA4-dNSCLC).
Main Methods:
- Retrospective search for cases with SMARCA4/BRG1 functional loss.
- Confirmation of BRG1 loss via immunocytochemistry.
- Review of cytomorphologic features, immunohistochemistry, and molecular profiling.
Main Results:
- 12 cytopathology cases of SMARCA4-dNSCLC were analyzed.
- Variable cytokeratin expression and diverse morphologic features (glandular, squamoid, poorly differentiated) were observed.
- Common cytologic findings included sheets/papillary architecture, nuclear enlargement, pleomorphism, coarse chromatin, and frequent TP53 co-mutation.
Conclusions:
- SMARCA4-dNSCLC presents a wide spectrum of cytomorphologic appearances.
- Features range from well-differentiated adenocarcinoma to poorly differentiated/undifferentiated carcinoma.
- Most cases display high-grade features like mitosis, apoptosis, necrosis, and marked pleomorphism.
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