SMARCA4-DEFICIENT UNDIFFERENTIATED TUMOR: A RARE THORACIC MALIGNANCY

ABSTRACT

SESSION TITLE Rare Malignancies SESSION TYPE Case Reports PRESENTED ON 10/17/2022 0315 pm - 0415 pm INTRODUCTION: SMARCA4 deficient undifferentiated tumors (SMARCA4-DUT) are rare and aggressive neoplasms that are most commonly encountered in young male smokers and portend a poor prognosis (1,2). They are characterized by loss of SMARCA4, a subunit of chromatin remodeling complexes, and loss of the tumor suppressor brahma-related gene 1 (BRG1). We present a case of an elderly female with an extensive smoking history who was diagnosed with SMARCA4-DUT. CASE PRESENTATION An 84 year old female with approximately 70 pack year smoking history, emphysema, ischemic cardiomyopathy, and coronary artery disease, presented to the emergency room with upper abdominal pain which started one day prior to admission. She endorsed an unintentional 10 pound weight loss in the past two months. The patient was admitted for an incarcerated ventral hernia for which she underwent repair. Of note, one and a half years ago, she was found to have a right lower lobe 7mm nodule but was unable to follow up due to the COVID pandemic. On this admission, a CT chest revealed a 4.2 x 3.8 x 3.7cm mediastinal mass and subcarincal lymphadenopathy. She underwent an EBUS with biopsy of the mediastinal mass and subcarinal lymph node. Cytology showed highly atypical epitheloid cells, concerning for a neoplasm with neuroendocrine differentiation and granulomas. Given the high suspicion for malignancy, she had a PET CT (figure 1) which showed FDG activity (SUV 11) in the mass with areas of necrosis and was referred to thoracic surgery. She underwent thoracoscopy with mediastinal mass resection and lymph node dissection and pathology showed diffuse sheets of epithelioid cells with large foci of necrosis. Neoplastic cells showed preserved INI (SMARCB1) expression, non-reactivity for NUT, and complete loss of BRG1 (SMARCA4) expression, consistent with a SMARCA4-DUT with positive margins (figure 2). She was referred to Radiation Oncology with plans to pursue further therapy thereafter. DISCUSSION: SMARCA4-DUT is a new and distinctive clinicopathological entity of aggressive thoracic tumors (1). The novelty of this class of tumors poses challenges in terms of treatment. Immune checkpoint inhibitors have shown compelling outcomes in case reports (3), however larger studies are needed to delineate optimal treatment regimens. CONCLUSIONS: SMARCA4-DUT are are rare but highly aggressive thoracic neoplasms. They present as large tumors and are smoking related. Prompt recognition may aid in early diagnosis. No definitive therapy exists but immunotherapy has shown promising results. Reference #1 Chatzopoulos, K., Boland, J.M. Update on genetically defined lung neoplasms NUT carcinoma and thoracic SMARCA4-deficient undifferentiated tumors. Virchows Arch 478, 21–30 (2021). Reference #2 Roden AC. Thoracic SMARCA4-deficient undifferentiated tumor-a case of an aggressive neoplasm-case report. Mediastinum. 2021;539. Published 2021 Dec 25. Reference #3 Henon C, Blay JY, Massard C, Mir O, Bahleda R, Dumont S, Postel-Vinay S, Adam J, Soria JC, Le Cesne A. Long lasting major response to pembrolizumab in a thoracic malignant rhabdoid-like SMARCA4-deficient tumor. Ann Oncol. 2019 Aug 1;30(8)1401-1403. DISCLOSURES No relevant relationships by Sathya Alekhya Bukkuri No relevant relationships by Erin Meier No relevant relationships by Mangalore Amith Shenoy No relevant relationships by Alexandra Zavin