Comprehensive characterization of nodal peripheral T-cell lymphoma, not otherwise specified A report of the 2023 SH/EA4HP lymphoma workshop

Objective: To summarize the conclusions of the 2023 Society for Hematopathology/ European Association for Hematopathology Workshop in peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). Methods: There were 36 cases with a submitted diagnosis of PTCL reviewed in Session 2. Results: The cases were classified based on submitted data and additional studies conducted during the workshop, including nodal PTCL with YS immunophenotype (n = 5), PTCL-NOS subclassified into PTCL-TBX21 (n = 8) and PTCL-GATA3 (n = 8) molecular subtypes, PTCL-NOS expressing CD30 (n = 2), PTCL arising from an underlying low-grade T-cell lymphoproliferative disorder (n = 2), and nodal involvement by primary cutaneous T-cell lymphoma (n = 5). Additionally, we reviewed 5 cases of T-cell lymphoma with lymphoepithelioid features, including 2 cases that do not meet the current criteria for PTCL-NOS, with 1 included in PTCL-TBX21 and 1 in PTCL YS described above. Three cases remain unclassified. We highlight the diagnostic challenges of PTCL-NOS, emphasizing the importance of performing a comprehensive panel of immunomarkers and molecular studies to establish the diagnosis and address the heterogeneity of these lymphomas. We identify rare cases of nodal YS PTCL-NOS with a unique immunophenotype and TP53 mutations. We also discuss the features of PTCL-GATA3 and PTCL-TBX21, including enrichment for cytotoxic markers in PTCL-TBX21 and aberrant B-cell marker expression in a subset of PTCL-GATA3 cases. The differential diagnosis of PTCL-NOS cases expressing, as well as those with lymphoepithelioid features, is briefly discussed. The importance of access to clinical history and staging is emphasized, as demonstrated by cases of nodal involvement by primary cutaneous T-cell lymphomas and cases that have progressed from low-grade lymphoproliferative disorders. Conclusions: Peripheral T-cell lymphoma, not otherwise specified is heterogeneous with distinct emerging subgroups. The diagnosis is complex and requires a comprehensive approach.