Approach to nodal-based T-cell lymphomas

Abstract

Peripheral T-cell lymphomas (PTCLs) represent a heterogeneous group of uncommon malignancies derived from mature T cells and usually characterised by an aggressive clinical course. Their clinical presentation, localisation and pattern of dissemination are highly variable, but the majority of cases present as nodal diseases. The recently revised classification of lymphomas has incorporated many new molecular genetic data derived from gene expression profiling and next generation sequencing studies, which refine the definition and diagnostic criteria of several entities. Nevertheless, the distinction of PTCL from various reactive conditions, and the diagnosis of PTCL subtypes remains notably challenging. Here, an updated summary of the clinicopathological and molecular features of the most common nodal-based PTCLs (angioimmunoblastic T-cell lymphoma and other nodal lymphomas derived from follicular T helper cells, anaplastic large cell lymphomas and peripheral T-cell lymphoma, not otherwise specified) is presented. Practical recommendations in the diagnostic approach to nodal T-cell lymphoproliferations are presented, including indications for the appropriate use and interpretation of ancillary studies. Finally, we discuss commonly encountered diagnostic problems, including pitfalls and mimics in the differential diagnosis with various reactive conditions, and the criteria that allow proper identification of distinct PTCL entities.

Advances in understanding of angioimmunoblastic T-cell lymphoma

“…Typical AITL lymph nodes (pattern III, roughly 80% of AITL) [17,47] show complete structural effacement. Infiltrating cellular components include clear cells, blastic cells, and arborizing vessels composed of high endothelial venules (HEVs), which have been identified morphologically in 69%, 94%, and 98% of AITL, respectively, based on hematoxylin-eosin staining [40].…”

“…Immunostaining reveals the presence of increased FDCs in 93% [40] of cases. Quantity and distribution of all of these cells can differ, resulting in highly significant variation [47,50]. In addition, there are two nonclassical types of AITL: AITL with hyperplastic follicles (pattern I) and AITL with depleted follicles (pattern II) [17,47,50].…”

“…Quantity and distribution of all of these cells can differ, resulting in highly significant variation [47,50]. In addition, there are two nonclassical types of AITL: AITL with hyperplastic follicles (pattern I) and AITL with depleted follicles (pattern II) [17,47,50]. Immunohistochemically, CD3, CD4, and CD5 are positive in most cases (100%, 90-95%, and 85-95%, respectively) [41,42].…”

“…DCs and macrophages are among infiltrating myeloid cells in AITL [47]. Tet2 activity resolves inflammation by actively and selectively repressing Il-6 expression in innate myeloid cells, including DCs and macrophages [105].…”

“…VEGF overproduction is likely associated with the increase in HEVs, although how HEVs impact AITL establishment is obscure. Typically, HEVs, FDCs, and neoplastic Tfh cells localize near each other [47,50]. Thus, cell-cell contact among them may be important for AITL establishment and development.…”