Cytopathological Features of SMARCA4-Deficient Thoracic Sarcoma: Report of 2 Cases and Review of the Literature

Abstract

SMARCA4-deficient thoracic sarcoma (SMARCA4-DTS) is a recently described entity of thoracic sarcomas with an undifferentiated rhabdoid morphology and SMARCA4 inactivation. Regardless of some reports about the histopathological findings so far, there have been only a few reports about the cytological features. In this article, we present the pathological features of 2 SMARCA4-DTS cases, including the cytological findings. Histopathologically, the tumor cells showed atypical loosely cohesive large epithelioid cells focally with geographic necrosis. Some cells were characterized by rhabdoid cells. Both patients showed intrathoracic masses with a history of smoking, and loss of SMARCA4 expression was confirmed with histopathological specimens. Immunohistochemically, tumor cells of both cases were at least focally positive for cytokeratin, CD34, CD99, synaptophysin, SOX2, and SALL4. In addition, tumor cells demonstrated significantly reduced expression of BRG1/SMARCA4 and SMARCA2. In conclusion, SMARCA4-DTS should be taken into consideration in the differential diagnosis of tumors with undifferentiated rhabdoid morphology involving the thoracic region.

Cytology of SMARCA4-Deficient Thoracic Neoplasms: Comparative Analysis of SMARCA4-Deficient Non-Small Cell Lung Carcinomas and SMARCA4-Deficient Thoracic Sarcomas

“…Both our cases, including case 3 (Table 1) that showed a biphasic pattern of epithelioid and rhabdoid cells, showed cytomorphological features of a poorly differentiated malignant neoplasm, with morphological differential diagnoses encompassing a wide range of entities such as melanoma, high-grade lymphoma, germ cell tumour, undifferentiated carcinoma, and undifferentiated sarcomas, particularly malignant rhabdoid tumours and epithelioid sarcoma of the proximal type [10]. The cytomorphology observed was strikingly similar in both cases and matched previous descriptions of SMARCA4-dTS [10, 11], all showing poorly cohesive variably sized epithelioid to rhabdoid tumours cells with abundant cytoplasm, perinuclear cytoplasmic condensations, convoluted nuclei, and prominent nucleoli in a necrotic/inflammatory background. We also observed bi- and multinucleate tumour cells (Owl eye-/Reed-Sternberg-like cells) that have not been specifically highlighted in previous reports.…”

“…Case 3, in particular, showed 2 different tumour areas on small biopsy samples: most undifferentiated and some epithelioid in appearance, of which the epithelioid cells showed focal expression of cytokeratin-7 and TTF-1. However, there was also focal reactivity for stem cell markers: CD34 and SALL4, leading us to favour a SMARCA4-dTS over SMARCA4-dNSCLC [3, 11]. The absence of lung parenchymal involvement on reviewing the radiological films supported our diagnosis.…”

“…However, there is limited knowledge on the cytomorphological features of these neoplasms that would prompt cytopathologists to test for BRG1 loss. There are only 2 cytology descriptions of SMARCA4-dTS in the literature [10, 11], while there are none for SMARCA4-dNSCLC. The aim of our study was to shed light on the cytomorphological features of SMARCA4-dNSCLC; identify distinctive morphological clues, if any; and clarify whether differentiation from SMARCA4-dTS is possible by cytology alone.…”

SMARCA4-deficient thoracic sarcoma revealed by metastasis to the small intestine: a diagnostic dilemma

“…Presently, specific therapies combining the enhancer of zeste homolog (EZH2) inhibitors, used in patients with abnormalities in the SWI/SNF complex protein, and the topoisomerase II inhibitor are widely supported to treat SMARCA4-deficient malignancies [ 9 ]. A study published by Takeda K et al suggests that anti-PD-1 blockade may be effective for SMARCA4-DTC expressing PD-L1 [ 10 ]. These results remain to be validated.…”

Ipilimumab and Pembrolizumab Mixed Response in a 41-Year-Old Patient with SMARCA4-Deficient Thoracic Sarcoma: An Interdisciplinary Case Study

“…It predominantly affects males with a median age of 48 with a history of smoking. The prognosis is poor, with a median survival of 6-7 months; direct comparison with prognostic data of thymic carcinoma patients reveals a considerably shorter 2-year survival rate (12.5 vs. 64.4%) [1][2][3][4][5]. Since then several case studies reporting this entity have been described in the literature [1,[6][7][8][9].…”