Grey zone lymphoma with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma: a clinicopathological study of 14 Epstein-Barr virus-positive cases

Histopathology. 2017 Mar;70(4):579-594. doi: 10.1111/his.13100. Epub 2016 Dec 16.

Abstract

Aims: To investigate the clinicopathological features of Epstein-Barr virus (EBV)-positive grey zone lymphoma (GZL) with features intermediate between diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin lymphoma (CHL).

Methods and results: We investigated the clinicopathological features of 14 cases of EBV-positive GZL in Japan. The control group included 173 cases of EBV-positive CHL and 64 cases of EBV-positive DLBCL of the elderly (polymorphous type). The patients were 10 men and four women with a median age of 62 years. Twelve patients (86%) had advanced clinical stage, 11 (79%) had B-symptoms, eight (57%) had mediastinal disease, 10 (71%) had elevated serum lactate dehydrogenase (LDH) levels, and five (36%) had thrombocytopenia. All cases had CHL-like morphology but strongly expressed at least one B-cell marker. The neoplastic cells were Hodgkin and Reed-Sternberg-like cells, but with a large number of mononuclear variants. EBV-positive GZL patients were more significantly more likely than EBV-positive CHL patients to have advanced clinical stage (P = 0.023), presence of B-symptoms (P = 0.011), elevated serum LDH levels (P = 0.047), thrombocytopenia (P = 0.042), and mediastinal involvement (P = 0.023). The progression-free survival (PFS) of EBV-positive GZL patients was significantly poorer than that of EBV-positive CHL patients (P = 0.043) but no difference from EBV-positive DLBCL patients was observed (P = 0.367).

Conclusions: EBV-positive GZL patients have significantly worse PFS than EBV-positive CHL patients, and are significantly more likely to have adverse clinical parameters such as advanced clinical stage, presence of B-symptoms, and thrombocytopenia. Further studies are needed to better characterize this entity, which may require the development of innovative therapeutic strategies.

Keywords: Epstein-Barr virus; classical Hodgkin lymphoma; diffuse large B-cell lymphoma; grey zone lymphoma.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Disease-Free Survival
  • Epstein-Barr Virus Infections / complications*
  • Female
  • Hodgkin Disease / pathology
  • Humans
  • Immunohistochemistry
  • Immunophenotyping
  • In Situ Hybridization
  • Japan
  • Kaplan-Meier Estimate
  • Lymphoma / mortality
  • Lymphoma / pathology*
  • Lymphoma / virology
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Male
  • Middle Aged

Substances

  • Biomarkers, Tumor