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

Abstract

Key Points• Accurate GZL diagnosis remains challenging, with .60% of patients with presumed GZL having the diagnosis reclassified on consensus review.• Treatment with DLBCLbased therapy appears most effective for GZL (including R-CHOP); however, new therapies are needed to improve outcomes.Gray zone lymphoma (GZL) is described as sharing features with 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 North American academic centers were 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 universal B-cell derivation, frequent CD30 expression, and rare Epstein-Barr virus (EBV) positivity (CD20 , 4%). Forty-two cases were reclassified: nodular sclerosis (NS) cHL, n 5 27 (including n 5 10 NS grade 2); lymphocyte predominant HL, n 5 4; DLBCL, n 5 4; EBV 1 DLBCL, n 5 3;primary mediastinal large BCL n 5 2; lymphocyte-rich cHL and BCL-not otherwise specified, n 5 1 each. GZL consensus-confirmed vs reclassified cases, respectively, more often had mediastinal disease (69% vs 41%; P 5 .038) and less likely more than 1 extranodal site (0% vs 25%; P 5 .019). With a 44-month median 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 5 .19 and P 5 .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 5 .01), whereas frontline cyclophosphamide, doxorubicin, vincristine, and prednisone 6 rituximab (CHOP6R) was associated with improved 3-year PFS (70% vs 20%; P 5 .03); both factors remained significant on multivariate analysis. Altogether, accurate diagnosis of GZL remains challenging, and improved therapeutic strategies are needed.

CD15, CD30, and PAX5 evaluation in Hodgkin's lymphoma on fine‐needle aspiration cytology samples

“…33 These cells express CD20 and B-cell markers other than CD15 or CD30 in a variable percentage of cases. 33 These cells express CD20 and B-cell markers other than CD15 or CD30 in a variable percentage of cases.…”

“…In this perspective, CD15 and CD30 expression in the so called "grey zone lymphoma" (GZL) is much more difficult to evaluate because neoplastic cells of GZL are generally described as pleomorphic with centroblastic or immunoblastic appearance. 33 These cells express CD20 and B-cell markers other than CD15 or CD30 in a variable percentage of cases. 33 In one case of mediastinal GZL observed on FNAC, 17 and support but allows assessing and identifying diagnostic cells to be tested by ICC.…”

“…33 These cells express CD20 and B-cell markers other than CD15 or CD30 in a variable percentage of cases. 33 In one case of mediastinal GZL observed on FNAC, 17 and support but allows assessing and identifying diagnostic cells to be tested by ICC. As reported above, in this study, CD30 resulted positive in 19/21 cases (90.5%; 11/11 smears and 8/10 CB); CD15 was positive in 14/21 cases (66.7%; 5/11 smears and 9/10 CB); and PAX5 was positive in 13/21 cases (61.9%; 9/11 smears and 4/10 CB).…”

Update on Lymphoma classification: The 2016 revised World Health Organization Classification of Hematopoietic and Lymphoid Neoplasms

“…The combination of MYC and BCL6 translocations also has been associated with a poor prognosis. These findings led to the concept of double (or triple) hit lymphoma . Most of these patients do not respond well to standard chemoimmunotherapy.…”

“… Histologically, most of these cases have morphologic features of DLBCL but others have features of so‐called Burkitt‐like lymphoma, blastoid B‐cell lymphoma, or cases referred to in the 2008 edition of the WHO classification as “B‐cell lymphoma unclassifiable, with features intermediate between diffuse large B‐cell lymphoma and Burkitt lymphoma.” For uncommon neoplasms with these highly aggressive morphologic features, but without MYC and BCL2 and/or BCL6 translocations, the diagnosis of HGBCL‐NOS is now proposed. The biologic and prognostic features of tumors in this category require more study.…”