SMARCA4-Deficient Undifferentiated Tumor of Lung Mass—A Rare Tumor With the Rarer Occurrence of Brain Metastasis: A Case Report and Review of the Literature

Abstract

Among thoracic tumors, these include subsets of a relatively newly described and yet to be fully characterized tumor entity: SMARCA4-deficient Undifferentiated Tumor (SMARCA4-dUT). Mutations of SMARCA4 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4) gene and loss of BRG1 (Brahma-related gene-1) is the underlying molecular hallmark of SMARCA4-dUT. They mostly involved the mediastinum, lung, and/or pleura showing undifferentiated round cell or rhabdoid morphology associated with aggressive clinical behavior. The pathogenesis of these tumors is still not clear. Morphologically, SMARAC4-dUT is differentiated from SMARCA4-dNSCLC by the presence of squamous and solid components in the latter. Immunohistochemically SMARC4-dUT has characteristic loss of SMARCA4 and SMARCA2 and strong expression of SOX2, CD34, and SALL4. Common sites of metastasis include lymph nodes, bones, and adrenal glands but rarely brain metastasis. We present a unique and rare case of a 76-year-old male with a right lung mass with documented pathology of SMARCA4-dUT and was found to have multiple brain metastases.

Chemotherapy and Immune Checkpoint Inhibitors in a Case of SMARCA4-dUT: A Case Report and Review of Literature

“…SMARCA4-dUT, as historically reported, are rare aggressive tumors, typically affecting patients in the age group of 30-59 years with a male:female ratio of 9:1. 2 , 10 , 17 The characteristic of this tumor is loss of Brahma (BRM) that is encoded by SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 2 (SMARCA2) or Brahma-related gene 1 (BRG1) encoded by SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (SMARCA4), respectively. 2 , 4 , 13 The most common sites of involvement in descending order are anterior mediastinum (61%), pleura (29%), and lung.…”

“… 2 , 10 , 17 The characteristic of this tumor is loss of Brahma (BRM) that is encoded by SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 2 (SMARCA2) or Brahma-related gene 1 (BRG1) encoded by SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (SMARCA4), respectively. 2 , 4 , 13 The most common sites of involvement in descending order are anterior mediastinum (61%), pleura (29%), and lung. Often, the tumors are larger at presentation, extending from the mediastinum to the lungs, pleura, neck, and ribs, as in our case.…”

“…They were dubbed as SMARCA4-deficient thoracic sarcoma (SMARCA4-dTS). 2 These tumors have a loss of the SMARCA4 gene and the Brahma-related gene-1 (BRG1) gene and are seen in up to 5% of non–small cell lung carcinomas (NSCLCs). 2 , 3 The patients are mostly young male smokers.…”

“… 2 These tumors have a loss of the SMARCA4 gene and the Brahma-related gene-1 (BRG1) gene and are seen in up to 5% of non–small cell lung carcinomas (NSCLCs). 2 , 3 The patients are mostly young male smokers. Recently, in addition to sarcomas, there is another entity of poorly differentiated carcinoma, predominantly occurring in lungs, that is associated with the loss of SMARCA4/BRG1.…”

SMARCA4-deficient undifferentiated thoracic tumor: A case report

“…Associated symptoms include dyspnea, pain, weight loss, and symptoms based on the involved organs. Common sites of metastasis include the lymph nodes, bones, and adrenal glands and rarely the brain[ 4 , 5 ].…”