Thoracic SMARCA4-deficient undifferentiated tumor: A clinicopathologic study.

Abstract

e14642 Background: 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 clinicopathologic features of this rare tumor in a series of 5 patients, diagnosed and treated at our institution. Methods: After approval from institutional review board, pathology department archive was searched for the patients with diagnosis of Thoracic SMARCA4-deficient undifferentiated tumor from January 2020 to December 2022. Data such as patient demographics, pathologic features including immunohistochemical stains, treatment and clinical outcome were collected. Results: Among 5 patients, 3 were male and 2 were female. Median age was 62 years (range 49 to 77 years). In three patients the primary site of the tumor was lung. One patient had tumor of the gastroesophageal junction while one patient had epicenter of the tumor in the paraspinous muscle. Diagnosis was made on biopsy specimen in all cases. All tumor showed undifferentiated histologic appearance. Rare cells with keratin positivity were observed in 2 specimens while 3 were completely negative for keratin stains. Focal TTF1 positivity was observed in one specimen while 4 were negative. Among neuroendocrine markers performed on variable number of cases, synaptophysin was positive in 4/4 cases while chromogranin was negative in 2/2 cases and INSM1 was negative in 1/1 case. PD-L1 (Dako 22C3) was performed on two specimens and showed less than 1% tumor cells to be positive. Next generation sequencing was performed on one specimen and showed pathogenic variants in TP53, CDKN2A, and APC genes and likely pathogenic variants in ATR, SMARCA4, and BCOR genes. Two patients received carbotaxol and radiation, one patient received FOLFOX, nivolumab and radiation, 1 patient pursued hospice care and 1 patient lost follow up. Two patients died 2 and 7 months after diagnosis. One patient is alive with metastatic disease 4 months after initial diagnosis. Conclusions: SMARCA4-deficient undifferentiated tumor is an aggressive malignancy that shows undifferentiated histology with synaptophysin positivity. From a diagnosis standpoint, Pathologists need to keep this entity in mind while working up tumors showing poorly differentiated to undifferentiated histology that are negative for most immunohistochemical markers. From clinical standpoint there is need to develop targeted therapy for this aggressive tumor.