Clinicopathologic consensus study of gray zone lymphoma with features intermediate between DLBCL and classical HL

Monika Pilichowska, Stefania Pittaluga, Judith A. Ferry, Jessica Hemminger, Hong Chang, Jennifer A. Kanakry, Laurie H. Sehn, Tatyana Feldman, Jeremy S. Abramson, Athena Kritharis, Francisco J. Hernandez-Ilizaliturri, Izidore S. Lossos, Oliver W. Press, Timothy S. Fenske, Jonathan W. Friedberg, Julie M. Vose, Kristie A. Blum, Deepa Jagadeesh, Bruce Woda, Gaurav K. GuptaRandy D. Gascoyne, Elaine S. Jaffe, Andrew M. Evens

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2600-2609
Number of pages10
JournalBlood Advances
Issue number26
StatePublished - Dec 12 2017

ASJC Scopus subject areas

  • Hematology


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