Abstract
BACKGROUND: Malignant pericardial mesothelioma (MPM) is a rare, aggressive neoplasm with nonspecific clinical presentations. Although BAP1 loss and CDKN2A deletion are common in pleural mesothelioma, they are not universally present in MPM, complicating diagnosis. CASE SUMMARY: A 73-year-old man presented with recurrent fever and chest pain from pericarditis. Positron emission tomography-computed tomography and transthoracic echocardiography revealed pericardial thickening and aortitis, concerning for inflammatory or infectious etiology. Initial histopathology was inconclusive. Diagnosis of MPM was confirmed via lymph node biopsy and molecular profiling, which revealed TAZ amplification. The patient was treated with IL-1 blockage and chemotherapy, with symptom improvement. DISCUSSION: In BAP1/CDKN2A-negative mesothelial proliferations, molecular testing for additional mutations, including TAZ amplification, may guide diagnostic certainty and novel therapeutic treatment. TAKE-HOME MESSAGES: MPM can closely mimic chronic inflammatory disease, and accurate diagnosis with comprehensive profiling is essential to guide targeted therapy. TAZ amplification suggests Hippo pathway as a driver of BAP-intact tumors and may serve as a predictive biomarker of mesothelial immunogenicity.