A BAFfling liver aspirate: Metastatic high grade SMARCA4 deficient undifferentiated gastroesophageal junction carcinoma masquerading as a hematolymphoid malignancy

Abstract

Undifferentiated malignant SMARCA4-deficient neoplasms are rare, recently characterized, high grade, potentially lethal malignancies. Such tumors are characterized by the loss of BRG1 encoded by SMARCA4, a key component of the Switch/Sucrose Non-Fermenting (SWI/SNF) chromatin remodeling complex. As this complex, also referred as BAF (BRG1/BRM associated factors) complex, is involved in the epigenetic control of hundreds of genes, including those involved in lineage-specific differentiation, BAF-deficient tumors, show minimal or no differentiation and are difficult to classify. Their fine needle aspiration (FNA) cytologic features are still poorly defined. Here, we describe a 70-year-old man who presented with thickening of the wall of the distal esophagus and stomach and multiple liver and lung lesions. Liver FNA showed relatively uniform dispersed malignant cells with high nucleus: cytoplasm ratio, scant microvacuolated cytoplasm, eccentric nuclei and prominent nucleoli. Mitoses, necrotic debris, nuclear streak artifact, "ghost cells" and focal rhabdoid cytoplasmic inclusions were also present. The liver core biopsy and GI biopsies demonstrated sinusoidal and respectively submucosal involvement by a high grade undifferentiated malignant neoplasm. The tumor cells were negative for all applied markers on immunohistochemistry and flow cytometry, and only showed CD138 and weak PAX5 staining. After an initial diagnosis of hematolymphoid neoplasm, additional stains showed intact INI1 protein and loss of BRG1 protein immunoexpression, establishing the accurate diagnosis. This case highlights the difficulties and potential pitfalls encountered in the FNA diagnosis of BAF-deficient tumors, the accurate diagnosis of which is important due to their lack of response to conventional therapy and potential response to targeted therapy.

Keywords: SMARCA4; BRG1; fine needle aspiration; liver; undifferentiated malignant neoplasm.