Isolated Pleural Effusion as Presentation of a Large B‐Cell Lymphoma: A Case Report and Diagnostic Considerations

BACKGROUND: Fluid Overload-associated Large B-Cell Lymphoma (FO-LBCL) is one of the newly added entities in the WHO classification of Haematolymphoid Tumors 5th edition [1]. Formerly, these cases were classified as primary effusion lymphoma-like (effusion) lymphoma (PEL-like (effusion) lymphoma) or HHV8-unrelated PEL-like lymphoma. As knowledge grew regarding the differences in clinical presentation and prognosis of these entities, the need for a distinct classification became apparent. METHOD: We describe a case of a 79-year-old man with acute dyspnea and cough due to massive pleural effusion, revealed by CT scan of the thorax. Further diagnostic evaluation with PET-CT showed no detectable tumor mass apart from the pleural fluid. Pleural fluid cytology revealed numerous large atypical lymphoid cells. Flow cytometric immunophenotyping showed a predominant monoclonal CD19+/CD20+ B-cell population with light chain restriction and CD5 expression. Molecular analysis demonstrated partial clonality, and cytogenetics revealed a complex hyperdiploid karyotype. EBV in situ hybridization and testing for HHV8 and HIV were negative. No underlying immunodeficiency or systemic disease was identified. RESULTS AND CONCLUSION: Based on these findings, diagnosis was most consistent with FO-LBCL, but distinction from other HHV8-negative effusion-based large B-cell lymphomas remains challenging due to overlapping features. The patient received R-CHOP-based immunochemotherapy and remains clinically stable without systemic progression. This case highlights the critical role of integrated cytologic, immunophenotypic, molecular, and virological analyses in establishing the correct classification of effusion-based large B-cell lymphomas and underscores the diagnostic challenges posed by this emerging entity. Accurate recognition of FO-LBCL is essential, as its clinical behavior and therapeutic implications differ from other effusion-based lymphomas.