BACKGROUND: GZL (B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and cHL) was described in 2005 and included in the 2008 WHO classification. Most cases present with mediastinal disease and share features with cHL and primary mediastinal large B-cell lymphoma (PMBCL). Non-mediastinal lymphomas with similar pathologic features have also been reported. Because of rarity and diagnostic complexity, data on GZL are limited and further study of this entity is desired.
METHODS: Clinical data from cases originally diagnosed as GZL were collected from 19 academic centers across the US and Canada (Evens AM et al. Am J Hematol 90:778-83, 2015). To further characterize the diagnostic features and correlations, 73 cases (majority from the above series and n=4 subsequent cases) were submitted for central pathology review using criteria of the 2016 revised WHO classification. Initial diagnostic samples were evaluated with a panel comprising CD20, CD79a, PAX5, OCT2, BCL6, MUM1, CD30, CD15, CD3 and EBV by in situ hybridization (EBER). Beyond the tumor cell immunoprofile, diagnostic criteria included tumor cell density and morphology, necrosis, and the microenvironment. cHL nodular sclerosis grade 2 (cHL-NS2) were classified according to prior criteria (MacLennan K. et al Cancer 64: 1686-93, 1989). 5 cases were rejected for insufficient material/technical issues; 68 cases were evaluated by 5 hematopathologists and consensus diagnosis was reached at multiheaded scope review.
RESULTS: Of 68 cases submitted with an original diagnosis of GZL, only 26 cases were confirmed as GZL on consensus review (14M/12F, median age 38 years, range 19-69). 11/26 biopsies were mediastinal in origin, and in an additional 4 cases, a mediastinal mass was present clinically; 11 had only peripheral lymphadenopathy (ie, non-mediastinal). 42 cases were re-classified as follows: NS cHL, n=27 (n=10 of which were cHL-NS2); DLBCL NOS, n=4; nodular lymphocyte predominant HL (NLPHL), n=3; EBV positive LBCL, n=3; PMBCL, n=2; lymphocyte-rich cHL, n=1; and B-cell lymphoproliferative disorder, n=1. Most cases of cHL diagnosed as GZL had strong CD20 expression. Furthermore, cHL-NS2 was frequently misdiagnosed as GZL typically due to confluent growth of lacunar cells.
CONCLUSIONS: Diagnosis of GZL remains a challenge. Rarity of the cases, and overlap with cHL-NS2, contribute to the difficulty. Further biologic and clinical analyses may contribute to improved understanding.