Académie royale de Médecine de Belgique


Résumé de Laurence de Leval, membre étranger


par Laurence de LEVAL (Institut Universitaire de Pathologie – Lausanne), membre étranger.

Peripheral T-cell lymphomas (PTCLs) comprise a heterogeneous group of predominantly aggressive malignancies representing overall less than 15% of all non-Hodgkin lymphomas. PTCLs of the adaptive immune system constitute the majority of cases with a nodal presentation while those (less frequent) derived from the innate immune system are predominantly extranodal and cytotoxic.

Angioimmunoblastic T-cell lymphoma (AITL) is a clinico-pathological entity characterized by lymphadenopathies, systemic symptoms, various biological abnormalities and a polymorphous lymphoproliferation. We demonstrated the origin of AITL from follicular helper T (TFH) cells, and this important determinant of the biology of the disease is now incorporated as a defining feature of this lymphoma. It was subsequently recognized that the spectrum of TFH-derived neoplasms also encompasses follicular T-cell lymphoma and other nodal lymphomas with a TFH phenotype. In addition to a shared immunophenotype, nodal TFH lymphomas feature similar patterns of genetic aberrations including often multiple mutations in epigenetic modifiers (TET2, DNMT3A, IDH2), RHOA G17V mutations and gain-of-function mutations in various genes related to in T-cell receptor signaling pathway (CD28, FYN, PLCG1, CARD11, …).

Among extranodal PTCLs, primary intestinal T-cell lymphomas (enteropathy-associated (EATL) and moinomorphic epitheliotropic (MEITL)) are derived from intestinal intraepithelial lymphocytes, the former complicating overt or incipient celiac disease, and the latter being unassociated to enteropathy. Mutation-induced activation of the JAK-STAT pathway (usually mutually exclusive JAK1, JAK3, STAT3, STAT5B mutations) is a pathogenic mechanism also found in extranodal PTCL entities. Inactivation of the methytransferase SETD2 gene is observed in a high proportion of MEITL and is a recurrent feature of hepatosplenic T-cell lymphoma, a very rare and highly aggressive disease involving the spleen and liver in young individuals.

The various PTCL entities encompass diverse clinical presentations and natural history, and heterogeneous pathology, biology and genetics. In addition to their biological relevance and diagnostic value, some of the newly recognized PTCL-associated mutations potentially potentially open novel avenues for the development of targeted therapies.