Exploring the boundaries between neoplastic and reactive lymphoproliferations: lymphoid neoplasms with indolent behavior and clonal lymphoproliferations-a report of the 2024 EA4HP/SH lymphoma workshop.

The boundaries between neoplastic and reactive lymphoproliferations were discussed during the 2024 European Association for Haematopathology/Society for Hematopathology workshop in Dubrovnik, Croatia. Session 5 focused on indolent lymphoid neoplasms and clonal lymphoproliferations. Seventy-two cases were submitted, representing good examples of indolent lymphomas and lymphoproliferative disorders (LPD) and their diagnostic challenges. The morphologic spectrum of primary cutaneous marginal zone lymphoma/lymphoproliferation (PC-MZL/PC-MZLPD) was discussed. PC-MZL/PC-MZLPD is divided in the immunoglobulin heavy chain switched-type and non-switched-type with some clinicopathological differences. The overlapping features between PC-MZL/PC-MZLPD and PC-CD4 + T-cell LPD were highlighted. The criteria for the diagnosis of indolent T-lymphoblastic proliferation (iT-LBP) were reviewed. Indolent T-cell lymphoproliferation of the gastrointestinal tract (iT-LPD-GI) is a rare clonal, non-destructive, and non-epitheliotropic T-cell LPD occurring in adults with a male predominance. The cases submitted to the workshop revealed clinicopathological heterogeneity. Unusual features like infiltration of the complete intestinal wall, mesenteric lymph node involvement, and splenomegaly were observed. A novel group of PD1 + /CD4 + indolent cases with intestinal tropism and dissemination to blood, bone marrow, lymph node, and skin was identified. Other indolent clonal B- and T-cell LPDs were discussed including transient, clonal CD8 + T-cell proliferations, usually the result of immune-mediated cytotoxic T-cell response to virus or neoantigens, and the recently described follicle center lymphoma (FLC) of the lower female genital tract. The increasing awareness of the existence of indolent LPDs should avoid unnecessary treatments. In this report, novel findings, recommendations for diagnosis, open questions, and diagnostic challenges raised by the cases submitted to the workshop will be discussed.