Pathobiology of hodgkin lymphoma

Abstract

Hodgkin's lymphoma is a lymphoid tumour that represents about 1% of all de novo neoplasms occurring every year worldwide. Its diagnosis is based on the identification of characteristic neoplastic cells within an inflammatory milieu. Molecular studies have shown that most, if not all cases, belong to the same clonal population, which is derived from peripheral B-cells. The relevance of Epstein-Barr virus infection at least in a proportion of patients was also demonstrated. The REAL/WHO classification recognizes a basic distinction between nodular lymphocyte predominance HL (NLPHL) and classic HL (CHL), reflecting the differences in clinical presentation, behavior, morphology, phenotype, molecular features as well as in the composition of their cellular background. CHL has been classified into four subtypes: lymphocyte rich, nodular sclerosing, mixed cellularity and lymphocyte depleted. Despite its well known histological and clinical features, Hodgkin's lymphoma (HL) has recently been the object of intense research activity, leading to a better understanding of its phenotype, molecular characteristics and possible mechanisms of lymphomagenesis.

Figure 1

a) Lymphocyte Predominant (LP) cells in NLPHL with typical popcorn morphology indicated by the two arrows (×400 Giemsa stain); b) LP cell expressing CD20 (arrow) (×400); c) LP cells EMA⁺ (×400); d) BCL6 positivity in LP cell (×400); e) CD30 negativity in LP cells; note the mononuclear non neoplastic CD30+ blasts (×400); f) LP cells IgD⁺; g) the arrow highlight a rosette of CD3⁺ small T lymphocytes around LP cells (×200); h) rosettes of PD1⁺ small lymphocytes around LP cells (×400).

Figure 2

a) Nodular growth pattern in a typical case of NS-CHL; one of the nodules is indicated by the arrow (×20, Hematoxylin-Eosin); b) Hodgkin Reed-Sternberg (HRS) and Hodgkin (H) cells in a CHL (×400, Hematoxylin-Eosin); c) lacunar cell in a NS-CHL case (×400, Hematoxylin-Eosin); d) mummified cell showed by arrow in a MC-CHL case (×400, Hematoxylin-Eosin); e) HRS and H cells CD30⁺; note the typical membranous and dot-like (in Golgi area) staining pattern (×400); f) HRS and H cells CD30⁺ in a case of NS-CHL syncytial variant (×200) ; g) H cell showing dot-like CD15 positivity (×400); h) the arrows indicate two H cells CD45⁻ in a background of CD45⁺ reactive lymphocytes (×400); i) H cells CD20⁻ highlighted by the arrows (×400); j) irregular expression of CD20 in HRS cells (×400); k) H cell PAX5/BSAP⁺; note the weaker expression in comparison with small reactive B lymphocytes (×400); l) EBV viral integration in the genome of HRS cells, revealed by in situ hybridization reaction using anti-EBER1/2 probes (×400).