Gray-zone Lymphoma Between cHL and Large B-Cell Lymphoma

Abstract

Gray-zone lymphoma (GZL) with features intermediate between classic Hodgkin lymphoma (cHL) and large B-cell lymphoma (LBCL) was introduced as a provisional entity into the World Health Organization classification in 2008. However, as diagnostic criteria are imprecise, reliable identification of GZL cases remains challenging. Here, we describe the histopathologic features of 139 GZL cases from a retrospective Lymphoma Study Association (LYSA) study with the goal to improve classification accuracy. Inclusion criteria were based on literature review and an expert consensus opinion of the LYSA hematopathologist panel. We observed 86 cases with a morphology more closely related to cHL, but with an LBCL immunophenotype based on strong and homogenous B-cell marker expression (CD20 and/or CD79a, OCT2, BOB1, PAX5) on all tumor cells (cHL-like GZL). Fifty-three cases were morphologically more closely related to LBCL but harbored a cHL immunophenotype (LBCL-like GZL). Importantly, we observed a continuous morphologic and immunophenotypic spectrum within these 2 GZL categories. The majority of cases presented genetic immune escape features with CD274/PDCD1LG2 and/or CIITA structural variants by fluorescence in situ hybridization. Patients without mediastinal involvement at diagnosis (17%) were older than those with mediastinal tumors (median: 56 vs. 39 y). Cases associated with Epstein-Barr virus (24%) presented with similar patient characteristics and outcome as Epstein-Barr virus negative cases. In summary, we provide refined diagnostic criteria that contribute to a more precise pathologic and clinical characterization of GZL within a broad spectrum from cHL-like to LBCL-like disease.

Composite and sequential lymphoma between classical Hodgkin lymphoma and primary mediastinal lymphoma/diffuse large B‐cell lymphoma, a clinico‐pathological series of 25 cases

“…Among the 233 cases centrally reviewed for the GZ study (Sarkozy et al , , ), 139 were diagnosed as GZL, 28 were diagnosed as composite or sequential lymphoma and 66 were not included. Among the 28 composite or sequential lymphoma cases, two sequential cases were finally classified as GZL (at diagnosis and at relapse), and one sequential case was excluded due to EBV positivity at relapse 10 years after the initial diagnosis of an EBV‐negative CHL, making the differential diagnosis of EBV‐associated lymphoproliferation in an immunocompromised patient more likely (see Figure S1).…”

“…All cases were centrally reviewed by expert haematopathologists involved in the GZ LYSA studies (Sarkozy et al , ; Sarkozy et al , ). CHL, DLBCL and PMBCL diagnoses were made based on tumour cell morphology, architecture, growth pattern and immunophenotype according to WHO classification (Swerdlow et al , ).…”

“…For each biopsy, the existence of a GZ or transitional area between both components was carefully assessed and reported. When present, a GZ component was further classified according to our previous report as group 0, 1, 2 or 3 GZL (Sarkozy et al , ). Group 0 corresponds to cases with a more typical morphology of CHL but with strong and diffuse CD20 expression on all tumour cells and the expression of other B‐cell markers, whereas group 3 includes cases with a more typical morphology of LBCL but with intense and diffuse CD30 (and/or CD15) expression.…”

Management of children and adolescents with gray zone lymphoma: A case series

“…In all patients, diagnosis of GZL had been made in the course of their disease, including one patient with initial diagnosis before 2009, described as unclassifiable B‐cell lymphoma with features of both DLBCL and cHL. All cases were reevaluated and retrospectively further classified into one of four subgroups (cHL‐like, LBCL‐like, composite, and sequential GZL), as previously proposed 14 . Patient data collected included demographics and information on disease (lymphoma subtype, immunohistochemistry, age, gender, sites of involvement, stage of disease, and pretherapeutic leukocyte count and lactate dehydrogenase level), treatment (chemotherapy, radiotherapy, autologous HSCT), and outcome (date of progression/relapse, last follow‐up, and death).…”

Into the gray-zone: update on the diagnosis and classification of a rare lymphoma

“…Currently, composite and sequential cases of CHL/PMBL are viewed as biologically related; however, these are not strictly accepted as GZL [1]. Furthermore, non-mediastinal presentations of gray-zone lymphoma (non-MGZL) are recognized, occurring more frequently in older patients [8].…”