Gray Zone Lymphomas: Clinical and Histological Characteristics and Treatment with Dose-Adjusted-EPOCH-R

Gray zone lymphomas (GZL) are diseases with transitional morphology and immunophenotypic features between Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Their pathological and clinical characteristics are not well studied and the best treatment strategy (using HL or DLBCL regimens) has not been defined. Small previous series of HL-like ALCL, which would include GZL, suggest they have a poor outcome with HL treatments. We present GZL’s treated on studies of DA-EPOCH-R at the National Cancer Institute and describe their clinical and histological features and outcome. Overall, 14 patients with GZL were identified. Characteristics included median (range) age 30 (12–51) years; male sex 10 (71%); stage III/IV 2 (14%) and; elevated LDH 7 (50%). These cases could be divided into three Gray zone groups:

1. classical HL (cHL) and primary mediastinal B-cell lymphoma (PMBL) in 9 (64%) patients;

2. cHL and DLBCL in 2 (14%) and;

3. lymphocyte predominant HL (LPHL) and T-cell histiocyte-rich large cell lymphoma (TCRBCL) in 2 (14%).

Pathological characteristics are shown below. All but one case was CD 10 negative. Markers of cHL included CD15 in 33–50% and CD30 in 66–100% of cases. Morphologically, Reed-Sternberg like cells were typically seen in GZL with cHL features. Thirteen newly diagnosed patients received DA-EPOCH-R. Of 11 patients evaluable for response (2TE), 10 (91%) achieved CR and 1 PR. At a median follow-up time of 4 years, OS and PFS are is 86% and 57%, respectively. Of 9 patients with GZL between cHL and PMBL, 4 (44%) also required radiation therapy compared to only 3/31 (10%) patients with PMBL to achieve durable remissions. Gray zone lymphomas represent a biological and clinical continuum between HL and B-cell lymphomas. Clinically, they appear to be more resistant to treatment than either HL or DLBCL and may require aggressive treatment strategies including radiation. Accrual continues.