Angioimmunoblastic T-cell lymphoma with lymphomatous effusion: Diagnostic challenges and cytology-based approaches

Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive peripheral T-cell lymphoma with a poor prognosis. Lymphomatous serous effusion, defined as the presence of malignant lymphoma cells in the pleural, pericardial, or peritoneal fluid, is a rare but clinically important manifestation, particularly when a lymph node biopsy is difficult or delayed. We performed a narrative review of case reports and a small series of AITL cases with lymphomatous effusion, focusing on the clinical presentation, cytologic features, ancillary studies, and outcomes. Reported patients are typically older adults with advanced-stage disease; effusions are usually exudative, of low volume, and cytologically tumor-cell-poor but inflammation-rich; therefore, atypical T follicular helper (TFH)-type T cells are easily overlooked or misclassified. Immunocytochemistry (ICC) on cell block or cell-transfer preparations, flow cytometry, and EBER in situ hybridization improve the recognition of the AITL phenotype, whereas next-generation sequencing (NGS) can detect hallmark mutations such as RHOA G17V, TET2, DNMT3A, and IDH2 directly from effusion samples, enabling a less invasive diagnostic approach when tissue is not readily available. According to previous reports, lymphomatous effusion, which is frequently measured in months, is associated with a short survival. Based on these data and current World Health Organization (WHO) and National Comprehensive Cancer Network (NCCN) guidance, we propose a practical fluid-based diagnostic algorithm that integrates cytology, ancillary tools, and lymph node biopsy when feasible, and we highlight the need for standardized effusion-based workflows, multicenter registries, and the integration of liquid biopsies, multiomics, and artificial intelligence-assisted cytology to refine risk stratification and guide therapy in this distinct subgroup.