SMARCA4 as a support for the differential diagnosis of poorly differentiated lung carcinomas

Abstract

Among non-small cell lung cancers (NSCLCs), sarcomatoid carcinomas account for 3%. They are rare tumours with a poor prognosis, classified into three subgroups, namely pleomorphic carcinoma, pulmonary blastoma and carcinosarcoma. In the 5th edition of WHO Classification of Thoracic Tumours more space is given to SMARC4-deficient lung cancers. Although studies on SMARCA4-deficient lung tumours are limited, a small percentage of SMARCA4 loss is present within NSCLCs. This finding is clinically relevant, as the loss of the SMARCA4 gene is associated with a worse prognosis. In our study, we analysed the presence of the main catalytic subunit of the SMARCA4 gene, the BRG1 protein, in 60 sarcomatoid lung tumours. The results of our study show that 5.3% of sarcomatoid carcinomas have BRG1-loss in tumour cells, proving that a non-negligible amount of lung sarcomatoid carcinomas are SMARCA4-deficient. These data open the debate on the necessity of including the detection of SMARCA4 within a standardised immunohistochemical panel.

Keywords: BRG1; NSCLC; SMARCA4; pleomorphic lung cancer; sarcomatoid lung cancer.

Figure 1.

Histomorphologic features of BRG1-positive sarcomatoid carcinoma. A-B, Pulmonary blastoma (hematoxylin and eosin stain) (A), immunostained sections showing retained BRG1 nuclear expression both in tumour cells and in the background cells (B). C-D, Carcinosarcoma (hematoxylin and eosin stain) (C), BRG1 stain both in tumour cells and in the background cells (D). E-F, Pleomorphic carcinoma (haematoxylin and eosin stain) (E), BRG1 stain both in tumour cells and in the background cells (F).

Figure 2.

Histomorphologic features of SMARCA4-deficient pleomorphic carcinoma. A-C, Pleomorphic carcinoma (haematoxylin and eosin stain): spindle cells and poorly differentiated areas of adenocarcinoma (A); spindle cells, epithelioid cells with glandular formations and eosinophilic, vacuolated and clear cytoplasm giant cells (B); tumour composed only by giant cells (C). D-F, Immunostained sections showing loss of BRG1 expression in tumour cells and retained nuclear staining in the background cells in the pleomorphic carcinoma in A (D), B (E) and C (F). G-I, positive nuclear staining for CK7 in the pleomorphic carcinoma in A (G), B (H) and C (I).