Thoracic SMARCA4‐deficient undifferentiated tumor with associated granulomatous reaction and response to pembrolizumab

Abstract

Thoracic SMARCA4‐deficient undifferentiated tumor (SMARCA4‐UT) is a rare entity that was recently described in the current World Health Organization Classification of Tumors. These lesions are highly aggressive with dismal prognosis, and most patients present with metastasis at the time of diagnosis. While there are about 100 cases of SMARCA4‐UT described in the literature, there are only few existing reports that describe the cytomorphology of these lesions. We present a patient with masses involving the mediastinum, right lung, right supraclavicular lymph node and right adrenal gland. Subsequent core‐needle biopsy of the right supraclavicular lymph node showed epithelioid to pleomorphic tumor cells with prominent nucleoli and associated granulomatous inflammation. The tumor cells were positive for CD34 and synaptophysin, and were negative for cytokeratins. SMARCA4 and SMARCA2 both showed loss of expression, which led to the diagnosis of SMARCA4‐UT. The patient underwent treatment with pembrolizumab (PD‐1 blocker), carboplatin, etoposide, and radiotherapy, resulting in an almost 55% reduction in the size of the primary tumor. Our case illustrates that an associated granulomatous inflammation might be an uncommon presentation of an already rare malignancy, and awareness of this phenomenon would prevent from mistaking SMARCA4‐UT for other more well‐known entities that can present with granulomas.

Treatment of Thoracic SMARCA4-Deficient Undifferentiated Tumors: Where We Are and Where We Will Go

“…While one study concerning SMARCA4-deficient NSCLC showed higher chemosensitivity to platinum-based chemotherapy in an adjuvant setting, no study has reported the efficacy of chemotherapy alone in SMARCA4-UT [ 75 ]. In the last few years, many studies have demonstrated the efficacy of immunotherapy in SMARCA4-UT patients both as a monotherapy and in combination with chemotherapy [ 6 , 7 , 8 , 9 , 63 , 76 ].…”

Three shades of an unusual mediastinal tumour

“…Thoracic SMARCA4-deficient undifferentiated tumour (SMARCA4-UT) is an unusual and aggressive tumour. While there are approximately 100 cases of this tumour reported in the literature, 1 there are very few detailed descriptions of its cytomorphologic characteristics (Table 2), and only rare cases in which primary diagnosis was made on cytologic material. Herein we present a case with a detailed description of the appearance on three specimen types: transbronchial needle aspiration (TBNA) cytology, transbronchial needle biopsy (TBNB) and effusion cytology.…”