Thoracic SMARCA4-deficient undifferentiated tumor: A rare entity and challenging diagnosis

Abstract

Abstract Introduction/Objective Thoracic SMARCA4-deficient undifferentiated tumor is a high-grade malignant neoplasm that frequently shows undifferentiated morphology and deficiency of SMARCA4. There is limited data in literature for this entity. The purpose of this report is to describe a case of this entity and to emphasize the importance of keep this entity in mind when dealing with poorly differentiated thoracic / lung tumors. Methods/Case Report A 49-year-old female with 7.5 pack years smoking history presented with a right shoulder pain. A chest x-ray showed rounded density in the right lung apex. This was followed by a CT chest which revealed a 5.6 cm mass with local destruction of the adjacent right third rib suggestive of a chest wall invasion. Also, hilar and paratracheal lymphadenopathy were noted. Subsequently the patient underwent a right upper lobe biopsy which showed diffuse discohesive sheets of moderately pleomorphic large epithelioid cells with vesicular chromatin, focal rhabdoid morphology, frequent mitoses, and extensive necrosis. Immunochemical staining showed the tumor cells to be positive for Cam 5.2, pancytokeratin (focal, weak), synaptophysin, p53 and TTF-1 (focal, weak) and negative for Napsin, SOX-10, CD45, chromogranin, INSM1, p40, CK7, and CK20. Ki-67 proliferation index was 40-50%. Tumor cells had intact expression of RB and were negative BRG1 (SMARCA4). Therefore, diagnosis of thoracic SMARCA4- deficient undifferentiated tumor was rendered. Next generation sequencing showed pathogenic variants in TP53, CDKN2A, and APC genes and likely pathogenic variants in ATR, SMARCA4, and BCOR genes. The patient received carbotaxol and radiation therapy and is alive with metastatic disease 4 months after initial diagnosis. Results (if a Case Study enter NA) NA Conclusion SMARCA4-deficient undifferentiated tumor is an aggressive malignancy that shows undifferentiated histology with frequent synaptophysin positivity and negativity for other neuroendocrine markers. Pathologists need to keep this entity in their differential when dealing with poorly to undifferentiated thoracic / lung tumors and appropriate immunohistochemical staining can clinch the diagnosis.