Gray zone lymphoma (GZL) is described as sharing featureswith classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL). However, there remains complexity in establishing diagnosis, delineating prognosis, and determining optimum therapy. Sixty-eight cases diagnosed as GZL across 15 NorthAmerican academic centerswere evaluated by central pathology review to achieve consensus. Of these, only 26 (38%) were confirmed as GZL. Morphology was critical to GZL consensus diagnosis (eg, tumor cell richness); immunohistochemistry showed universalB-cellderivation, frequent CD30 expression, and rare Epstein-Barr virus (EBV) positivity (CD20+, 83%; PAX5+, 100%; BCL6+, 20%; MUM1+, 100%; CD30+, 92%; EBV+, 4%). Forty-two cases were reclassified: nodular sclerosis (NS) cHL, n = 27 (including n = 10 NS grade 2); lymphocyte predominant HL, n = 4; DLBCL, n = 4; EBV1 DLBCL, n=3; primary mediastinal large BCL n = 2; lymphocyte-rich cHL and BCL-not otherwise specified, n=1 each. GZL consensus-confirmed vs reclassified cases, respectively, more often had mediastinal disease (69% vs 41%; P=.038) and less likely more than 1 extranodal site (0%vs 25%; P5.019).With a 44-monthmedian follow-up, 3-year progression-free survival (PFS) and overall survival for patients with confirmed GZL were 39% and 95%, respectively, vs 58% and 85%, respectively, for reclassified cases (P=.19 and P=.15, respectively). Interestingly, NS grade 2 reclassified patients had similar PFS as GZL consensus-confirmed cases. For prognostication of GZL cases, hypoalbuminemia was a negative factor (3-year PFS, 12% vs 64%; P=.01), whereas frontline cyclophosphamide, doxorubicin, vincristine, and prednisone ± rituximab (CHOP6R) was associated with improved 3-year PFS (70% vs 20%; P=.03); both factors remained significant on multivariate analysis. Altogether, accurate diagnosis of GZL remains challenging, and improved therapeutic strategies are needed.
ASJC Scopus subject areas