SESSION TITLE: Disorders of the Mediastinum 1 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 pm - 02:15 pm INTRODUCTION: In 2015, Le Loarer and colleagues retrospectively investigated nineteen previously unclassified sarcomas and reported a new type of aggressive thoracic malignancy, a SMARCA4-deficient thoracic sarcoma (SMARCA4-DTS).[1] An additional 12 cases were described in 2017 by Yoshida et al, with similar clinical features, immunohistochemistry, and gene expression profiles.[2] SMARCA4-DTS are readily recognizable in clinical practice as poorly differentiated, bulky thoracic malignant tumors, in predominantly middle-aged male smokers, with undifferentiated rhomboid morphology and abundant mitotic figures. Median overall survival is 7– 24 months, with mortality often due to local progression and mediastinal compression.[1] CASE PRESENTATION: A 55-year-old male with a history of tobacco and IV drug abuse presented with a two months history of progressive dyspnea, 100 lb weight loss, and new onset atrial fibrillation. Mediastinal and hilar masses were identified on CT, with encasement of broncho-vascular structures and mass effect on the SVC and aortic arch. Preliminary pathology reported a poorly differentiated necrotic neoplasm suggestive of carcinoma with neuroendocrine features. [Table 1] Considering the high level of suspicion for a SMARCA4 deficient tumor, no established standard of care, and rapidly deteriorating hemodynamic and respiratory status, the patient was not a chemotherapy candidate. Unfortunately, on the day of final pathology confirmation[Table 2], the patient had progressive respiratory failure and despite aggressive resuscitative measures continued to decline. Comfort measures were initiated on hospital day 16. DISCUSSION: Differential diagnosis of SMARCA4-DTS is wide and distinction from carcinomas can be difficult, as it requires extensive genomic profiling and immunohistochemical workup. In our case, the keys to the prospective diagnosis included 1) prior awareness of SMARCA4 deficiency, 2) an early high level of suspicion, 3) in-person collaboration between oncology and pathology services, and 4) established collaboration between our community medical center and an institution capable of extensive genetic testing. Per further literature review, CD34 is a useful, commonly available marker, as it is expressed in most SMARCA4-DTS but is not usually in lung carcinomas.[1,2] SMARCA4, SMARCA2 and SOX2 testing is important for confirmation of diagnosis. Imaging findings may also be helpful, as SMARCA4-DTS frequently arises in mediastinum and pleura, rather than in the lung. CONCLUSIONS: SMARCA4-DTS can be identified based on their unique presentation, distinctive rhabdoid morphology and immunohistochemistry. Awareness and prospective diagnosis of this rapidly progressive and rare malignancy, may provide opportunities for improved clinical management, prognostication, and identification of therapeutic or palliative options.Acknowledgement: Charles J. Nicely, MD. Dr. David Klimstra, MD. Reference #1: Le Loarer F, Watson S, Pierron G, et al. SMARCA4 inactivation defines a group of undifferentiated thoracic malignancies transcriptionally related to BAF-deficient sarcomas. Nat Genet 2015;47:1200-5. Reference #2: Yoshida A, Kobayashi E,Kubo T, et al. Clinicopathological and molecular characterization of SMARCA4-deficient thoracic sarcomas with comparison to potentially related entities. Mod Pathol 2017;30: 797-809. DISCLOSURES: No relevant relationships by Aliaksandr Ramaniuk, source=Web Response
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Oct 31, 2018
Kai Dong + 5
Open Access