Background: T cell lymphoblastic leukemia/lymphoma with the initial symptom of effusion is an uncommon condition. It may present a diagnostic challenge as lymphoblastic cells mimic normal lymphocytes under a low-power microscopic view. Cases: Two cases are presented, both male, with the first aged 31 years and the second aged 54 years. Both initially presented with chest pain and shortness of breath, and CT scans found an anterior mediastinal mass and left pleural effusion in both subjects. Cytological smears of pleural fluid in each case showed monotonous small-to-medium-sized lymphoid cells with moderate chromatin condensation and round-to-convoluted nuclei. There were prominent apoptotic bodies and mitosis in both cases. Immunohistochemistry of cell blocks demonstrated their T cell lineage and lymphoblastic nature. Diagnosis of T cell lymphoblastic leukemia/lymphoma was determined by a 3-step algorithmic approach using complete panels of immunohistochemical markers (CD3, CD20, Ki-67, CD10, CD5, CD99, CD1a, CD34, CD4, CD8, TDT, CD7, CD2 and CD68). Conclusion: An algorithmic approach based on cytological morphology and immunophenotyping is an effective way to diagnose T cell lymphoblastic leukemia/lymphoma in patients with an initial symptom of pleural effusion and insidious cytological morphology.

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