Atypical lymphoid proliferations associated with therapeutic intervention: a report of the 2024 EA4HP/SH lymphoma workshop.

The challenging boundaries between neoplastic and reactive lymphoproliferations were discussed during the 2024 European Association for Haematopathology/Society for Hematopathology workshop in Dubrovnik, Croatia. Session 3 focussed on the atypical lymphoid proliferations associated with therapeutic interventions. Forty-four cases were submitted representing a broad spectrum of lymphoproliferative disorders (LPDs) encountered in the settings of immunosuppressive and immunomodulatory therapies, various interventions for solid tumor treatment, drug reaction with eosinophilia and systemic symptoms (DRESS), CAR T-cell therapy for B-cell lymphomas, Bruton tyrosine kinase inhibitors (BTKI) for SLL/CLL treatment, ABL-kinase inhibitor dasatinib, and COVID-19 vaccination. The cases of this session highlighted the importance of having sufficient clinical information including drug history and distribution of disease in order to achieve reliable diagnosis. Among LPDs associated with immunosuppressive and immunomodulatory therapies, the most challenging were T- and NK-derived infiltrates as they ranged from non-clonal to clonal. DRESS-associated lymphadenopathy exhibited variable histologic patterns with the most difficult differential diagnosis being with a T-cell lymphoma. LPDs observed after CAR T-cell therapy for B-cell neoplasms exhibited unexpected phenotypes resulting either from lineage switching/transdifferentiation, or from harvested T-cells already harbouring cancer-associated variants. Temporary interruption of BTKI treatment for CLL/SLL due to surgical procedures led to a "Pseudo-Richter transformation" that disappeared after reintroduction of therapy. Dasatinib led to a lymphadenopathy with a peculiar florid follicular hyperplasia that regressed after discontinuation of therapy. The findings of the few thoroughly studied COVID-19 vaccination associated lymphadenopathy cases reflected a disordered immune response. This report describes the most important features for diagnosis of these challenging cases.