Pathobiology and molecular profiling of peripheral T-cell lymphomas.

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.