Pathobiology and Molecular Profiling of Peripheral T-Cell Lymphomas

Abstract

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of rare diseases, usually manifesting clinical aggressiveness. Although important novel insights into the pathobiology of nodal PTCL have been gained recently from molecular profiling studies and clinico-pathological analyses, the pathogenetic molecular lesions remain to be deciphered for most entities. Angioimmunoblastic T-cell lymphoma (AITL) comprises CD4+ CXCL13+ neoplastic cells displaying overlapping immunophenotypical and molecular features with normal follicular helper T cells. This derivation might account for the presence of a prominent non-neoplastic component in AITL tissues and the clinical manifestations of the disease reflective of an immunological dysfunction. ALK+ anaplastic large cell lymphoma (ALCL), defined by ALK gene translocation with various gene partners, is composed of CD30+ ALK+ cells with a cytotoxic phenotype and usually carries a good prognosis. ALK– ALCL, now considered as a distinct disease entity, is morphologically and immunophenotypically similar to ALK+ ALCL, except for ALK expression, but has distinctive molecular features. PTCL, not otherwise specified (PTCL, NOS), the largest PTCL category, which is derived from activated CD4+ (or CD8+) T cells, is markedly heterogeneous, including at the molecular level. Gene expression profiling approaches have identified novel biomarkers of potential therapeutic interest, and suggest the existence of molecularly distinct PTCL, NOS subgroups.

Peripheral T‐cell lymphoma gene expression profiling and potential therapeutic exploitations

“…disseminated, nodal or extranodal/cutaneous disease. In sharp contrast with B‐cell lymphomas, which are assigned to a normal cellular counterpart, the cellular origin of PTCLs remains difficult to determine, although molecular profiling has recently allowed significant progress (de Leval et al , 2007; de Leval & Gaulard, 2008). The recent development of gene expression profiling (GEP) technology may contribute to better classification, pathophysiological understanding and treatment approach in PTCLs, together with the identification of normal cellular counterparts.…”

The pathological features of angioimmunoblastic T-cell lymphomas with IDH2 mutations

“…Angioimmunoblastic T-cell lymphoma is a peripheral T-cell lymphoma derived from follicular T-helper cells [1,2]. The 2016 revised World Health Organization (WHO) classification of lymphomas recognizes, in addition to angioimmunoblastic T-cell lymphoma, two provisional lymphoma entities derived from follicular T-helper cells, namely follicular peripheral T-cell lymphoma and nodal peripheral Tcell lymphoma with a follicular T-helper phenotype [3,4].…”

New biomarkers in T-cell lymphomas

“…This is likely due to the complexity of normal T-cell differentiation, characterized by marked functional diversity but also evidence of functional overlap and plasticity between T-and NK-cell subsets. These features might in turn account for frequent aberrations and a pronounced variability in the phenotype within distinct PTCL categories (reviewed in [24][25][26]). Over the past years it has become clear that cell lineage or differentiation traits represent major determinants of the biology of these neoplasms, relevant to their classification and prognosis, and significant progresses have been achieved in the identification of the cellular derivation of several PTCL entities.…”