P2.06-41 Differentiating Sarcomatoid Mesothelioma from Pleomorphic Carcinoma and Chest Wall Sarcoma Using GATA-3/MUC4/BAP1 IHC

Current immunohistochemistry (IHC) biomarkers, or so-called “mesothelial markers”, lack sensitivity and specificity in differentiating sarcomatoid mesothelioma from pleomorphic carcinoma of the lung, and poorly differentiated chest wall sarcoma. Hence it frequently poses a diagnostic challenge for pulmonary pathologists. In this pilot study we evaluated the diagnostic performance of two recently proposed IHC biomarkers, GATA-3 and MUC4, in conjunction with BAP1. Sarcomatoid mesothelioma or sarcomatoid- predominant biphasic mesothelioma (10 cases), pleomorphic carcinoma of the lung (10 cases) and poorly differentiated primary or metastatic chest wall or pleural sarcoma (10 cases) were retrieved from our diagnostic archive. Resections or large biopsies were selected over small biopsies whenever possible. All the cases were diagnosed between 2009 and 2017 by a specialist pulmonary pathologist and discussed at the local multi-disciplinary team meeting in relation to final diagnosis. Whole slide GATA-3 (L50-823, pre-diluted), MUC4 (8G7, 1:50) and BAP1 (C-4, 1:50) immunohistochemistry was performed using Ventana Benchmark ULTRA system. Lymphocytes (GATA-3/BAP1) and bronchiolar epithelium (MUC4) were used as internal positive controls. Loss of GATA-3/BAP1 and MUC4 staining was defined as complete loss of nuclear or membrane and cytoplasmic signals, respectively. Any staining intensity above the external negative controls was accepted as positive. Extent of positive staining was grouped as <1%, 1-50% and >50%. GATA-3 was positive in 8/10 sarcomatoid mesothelioma, 6/10 chest wall/pleural sarcoma and 2/10 pleomorphic carcinoma of the lung. MUC4 positivity was observed exclusively in pleomorphic carcinoma of the lung (6/10), but only focally. BAP1 loss was infrequently observed in all three types of tumours. The combination of GATA-3 and MUC4 immunohistochemistry show promise as markers that would help in distinguishing these three tumours. The role of BAP1 is uncertain. These pilot results warrant an extended study that consists of a larger cohort to evaluate the utility of these biomarkers.