[Diagnostic approach to non-cutaneous T-cell lymphomas in 2025: What pitfalls and how should they be classified?]

Peripheral T-cell lymphomas are a heterogeneous group of neoplasms derived from mature T or NK lymphocytes. With the exception of primary cutaneous T-cell lymphomas, these lymphomas are rare (<7% of lymphomas in France). Peripheral T-cell lymphomas derived from follicular helper T cells (TFH) account for more than 40% of cases. TFH lymphoma has numerous diagnostic pitfalls, including classical Hodgkin lymphoma, diffuse large B-cell lymphoma, and marginal zone lymphoma, which are attributable to the "follicular T helper" function of the tumor cells. Anaplastic large cell lymphomas (ALCL) are classified according to the presence or absence of an ALK gene fusion (ALCL-ALK+) and, for ALCL ALK-, according to their clinical presentation as nodal, cutaneous, or breast implant-associated disease. Among intestinal peripheral T-cell lymphomas, classifications distinguish enteropathy-associated T-cell lymphoma and monomorphic epitheliotropic intestinal T-cell lymphoma, two diseases derived from intraepithelial intestinal T lymphocytes that differ in their clinical context, immunomorphological features, and distinct mutational profiles. Assessment of Epstein-Barr virus (EBV) status is a fundamental prerequisite in peripheral T-cell lymphomas. Among extranodal peripheral T-cell lymphomas, EBV association defines extranodal NK/T-cell lymphoma. This review will address the diagnostic approach to a T-cell infiltrate, the various T cell lymphoma entities according to nodal, extranodal, or leukemic presentation, the main differential diagnoses, and the diagnosis of exclusion, peripheral T-cell lymphoma, not otherwise specified. With a few exceptions, peripheral T-cell lymphomas are aggressive diseases for which conventional chemotherapies are of limited efficacy.