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

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.

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.

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.