Refractory Malignant Pericardial Effusion as the Initial Presentation of Early T-Cell Precursor Acute Lymphoblastic Leukemia/Lymphoma.

Early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) is a rare, high-risk subtype of T-cell malignancy characterized by aggressive clinical behavior and poor outcomes. Pericardial effusion may occur in hematologic malignancies; however, presentation with cardiac tamponade as the initial manifestation of ETP-ALL/LBL is exceedingly uncommon. We report the case of a 55-year-old man with no significant past medical history who presented with progressive dyspnea, orthopnea, fatigue, and bilateral lower-extremity edema. Transthoracic echocardiography revealed a large circumferential pericardial effusion with tamponade physiology, necessitating urgent pericardiocentesis and drain placement. Cytopathologic evaluation and flow cytometric analysis of the pericardial fluid demonstrated immature T-lymphoblasts expressing terminal deoxynucleotidyl transferase (TdT), cluster of differentiation (CD)3, CD5, CD7, and CD34, findings highly suggestive of T-cell lymphoblastic leukemia/lymphoma. Peripheral blood flow cytometry and bone marrow biopsy showed no overt leukemic involvement, supporting a predominantly extramedullary disease process. Cross-sectional imaging subsequently identified a large infiltrative anterior mediastinal mass with extensive vascular encasement and bilateral malignant pleural effusions, consistent with ETP-ALL/LBL. The patient was treated with fractionated cyclophosphamide, vincristine, adriamycin, and dexamethasone (hyper-CVAD) chemotherapy and intrathecal methotrexate, with plans to incorporate venetoclax into subsequent treatment cycles. Despite therapy, he developed recurrent malignant pericardial effusions with persistent tamponade physiology, ultimately requiring repeat pericardiocentesis followed by video-assisted thoracoscopic pericardial window creation and bilateral PleurX catheter placement. This case highlights an unusual and diagnostically challenging presentation of ETP-ALL/LBL with isolated malignant pericardial involvement and cardiac tamponade in the absence of overt peripheral blood or bone marrow disease. It underscores the importance of considering aggressive hematologic malignancies in patients with unexplained malignant pericardial effusions and emphasizes the diagnostic value of pericardial fluid flow cytometry when conventional hematologic evaluation is unrevealing.