Expanding the Immunophenotype Spectrum of SMARCA4-Deficient Non-Small Cell Lung Carcinomas: A Case Series with Neuroendocrine Markers Expression

Aims. In recent years, SMARCA4-deficient nonsmall cell lung cancer (NSCLC) has been recognized as a distinct new subtype of lung cancer, which is characterized by loss of SMARCA4 (Brahma-related gene-1 [BRG1]) protein expression. Only a limited number of SMARCA4-deficient NSCLC case series have been reported, and their clinicopathological features have not yet been fully elucidated. Our main aim was to analyze the clinical history, histology, immunohistochemistry, and molecular pathology of 5 SMARCA4-deficient NSCLC patients with poorly differentiated or undifferentiated histology and neuroendocrine markers expression. Methods and results. Five patients with complete loss of nuclear BRG1 immunostaining were identified among 53 patients of poorly differentiated/undifferentiated NSCLC. We then performed immunohistochemical staining and gene mutation analysis using a real-time polymerase chain reaction. All patients were male aged between 58 and 82 years (average 67.6 years), with smoking exposure. Histologically, the tumors had a relatively monotonous morphology and showed solid nest-like, sheet-like growth, and geographic necrosis. Thyroid transcription factor 1, cytokeratin 7, and Napsin A were all negative (5 of 5). Moreover, all tumors showed a variable expression of neuroendocrine markers, including synaptophysin, chromogranin A and CD56. Hot spot epidermal growth factor receptor/anaplastic large-cell lymphoma kinase/c-ros oncogene 1 mutations were not detected in any of the 5 tumors. Conclusions. To the best of our knowledge, this is the first study that has reported the poorly differentiated morphology with a frequent expression of neuroendocrine markers. Our results have expanded the immunophenotype spectrum of SMARCA4-deficient NSCLC. However, the clinicopathological significance of this subset of SMARCA4-deficient NSCLC should be further clarified in larger series studies.