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Hodgkin lymphoma: a review of pathological features and recent advances in pathogenesis.

Abstract：

:Hodgkin lymphoma (HL) is composed of two distinct pathological entities, nodular lymphocyte predominant HL and classic HL, the latter with four subtypes. In contrast with most other human lymphomas, in which the neoplastic cells are a major population of the tumour constituents, the neoplastic 'Hodgkin (H) and Reed-Sternberg (RS)' cells usually account for less than 10% of tumour bulk against an inflammatory background. The neoplastic cells of HL are of B-cell lineage (PAX5+) in virtually all cases. HL usually affects young patients with a localised nodal disease and its clinical behaviour is typically indolent. Patients respond well to chemotherapy with cure rates of 80-90% and the recent finding of PD-L1 expression, an immune checkpoint, warrants the use of immunotherapy for some patients with recurrent and/or refractory HL. The enigmatic RS cells of HL are unique in their abundant cytoplasm and characteristic bilobed nuclei with eosinophilic prominent nucleoli, imparting an 'owl-eye' appearance. H cells are mononuclear variants. The viral inclusion-like morphology was a clue on the way to discovering an association between classic HL and Epstein-Barr virus (EBV). However, this association is variable in different geographic regions and in pathological subtypes, and correlates with older age (>60 years) and socioeconomic status, indicating that environmental factors are likely involved in HL pathogenesis. Virus-associated endoplasmic reticulum (ER) stress also may contribute to mechanisms underlying the characteristic morphological features of HRS cells. ER stress has been found to induce aberrant, cytoplasmic cyclin A expression, leading to nuclear hyperdiploidy. Aberrant expression of cyclin A is commonly associated with HRS cell morphology in HL, probably through EBV-latent membrane protein-1 (LMP1) signalling. Shelterin also may play a role in the morphogenesis of multinucleated RS cells. In addition, EBV-positive and -negative HL cases express survival, but not death signals of ER stress at similar levels and EBV-LMP1 transfection increases expression of survival signals in HL cell lines. These data suggest that surviving ER stress may be involved in HL pathogenesis.

journal_name

Pathology

journal_title

Pathology

authors

Piris MA,Medeiros LJ,Chang KC

doi

10.1016/j.pathol.2019.09.005

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

154-165

issue

eissn

0031-3025

issn

1465-3931

pii

S0031-3025(19)30395-2

journal_volume

pub_type

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Hodgkin lymphoma: a review of pathological features and recent advances in pathogenesis.