Mediastinal grey zone lymphomas: Results of the expert pathological review analysis of a case series enrolled in the multicentre BIOGZL-2020 study in Italy

Mediastinal grey zone lymphoma (MGZL) is a rare disease with overlapping features between classical Hodgkin lymphoma (CHL) and primary mediastinal large B-cell lymphoma (PMBL). The recent classifications limit the disease to mediastinal cases. Epstein–Barr virus (EBV) is negative in most instances. Predominant resemblance to CHL (MGZL-HL) or primary mediastinal B-cell lymphoma (MGZL-PMBL) can commonly be defined, although mixed features do occur. The morpho-phenotypic heterogeneity of MGZL has significantly affected diagnostic reproducibility also among experts and the proposed diagnostic criteria turned out less concrete than for other lymphomas. Seventy GZL cases were collected from 14 Italian centres and slides reviewed by expert haematopathologists: 17 samples were confirmed according to current classification criteria, the residual being reclassified, mostly as CHL and PMBL, which well reflects the diagnostic challenge. By applying six B-cell markers, MGZL-HL commonly expressed ≥4 B-antigens in ≥50% neoplastic cells at moderate–strong intensity; MGZL-PMBL expressed less B-cell markers than expected (average 3.4 per case, in ≥50% neoplastic cells) at variable intensity. Overall, morphology, number of positive B-cell markers, staining intensity and percentage of positive neoplastic cells are features that must be considered collectively, case by case, trying to adhere to the recent classification criteria, being aware that not all cases may easily be included.