Mediastinal gray zone lymphoma: clinico-pathological characteristics and outcomes of 99 patients from the Lymphoma Study Association

Abstract

Mediastinal gray zone lymphoma, B-cell lymphomas with intermediate features between classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma, have not been well described in the literature. We report the clinical characteristics and outcomes of a large retrospective series of 99 cases centrally reviewed by a panel of hematopathologists, with a consensus established for the diagnosis. Cases were defined as classical Hodgkin lymphoma-like morphology (64.6%) with primary mediastinal B-cell lymphoma immunophenotype, primary mediastinal B-cell lymphoma-like morphology (30.3%) with classical Hodgkin lymphoma or composite (5.1%) (synchronous occurrence of classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma). The median age was 32 years (13-83 years); 55% were women. Thirteen of 81 evaluable cases (16%) were Epstein-Barr virus-positive. Twenty-eight percent of patients presented primary refractory disease (progression under first-line treatment or relapse within one year). The 3-year event-free and overall survival rates were 63% and 80%, respectively. Patients treated with a standard regimen (RCHOP/ABVD) had worse event-free survival (P=0.003) and overall survival (P=0.02) than those treated with a dose-intensive chemotherapy (high-dose RCHOP/escalated BEACOPP). Rituximab added to chemotherapy was not associated with better event-free survival (P=0.55) or overall survival (P=0.88). Radiotherapy for patients in complete remission had no impact on event-free survival. In multivariate prognostic analysis, ECOG-PS and anemia were the strongest factors associated with a shorter event-free survival and overall survival, respectively. In conclusion, this report describes the largest series of mediastinal gray zone lymphoma. Our data suggest that a dose-intensive treatment might improve the outcome of this rare and aggressive disease.

Figure 1.

Pathological features of cases included in this series. (A) Classical Hodgkin lymphoma (CHL)-like morphology with tumoral cells resembling Hodgkin lymphoma cells but with less inflammatory background, and a frequent sheet of large cells associated with a phenotype of primary mediastinal B-cell lymphoma (PMBCL) (growth X10). (B) Strong and diffuse CD20 expression in all CHL-like lymphoma cells (growth X10). (C) CD30 expression in lymphoma cells (growth X10). (D) Mediastinal gray zone lymphoma (MGZL) with a primary mediastinal B-cell lymphoma-like morphology (growth X20) with an intermediate morphology with larger and more pleomorphic cells than in typical PMBCL and some cells resemble bi- or multinucleated Reed Sternberg cells (not shown) and sometimes inflammatory background with numerous eosinophils in association with a CHL phenotype. (E and F) High CD30 and CD15 expression in all lymphoma cells (growth X5).

Figure 2.

Event-free survival (EFS) and overall survival (OS) in the global population of mediastinal gray zone lymphoma (MGZL). After a median follow up of 34 months (range 0.4–198.5 months) according to reverse Kaplan-Meier method, the estimated EFS at three years was 63% (95%CI: 52%–72%) and OS was 80% (95%CI: 68–87%). NA: not available.

Figure 3.

(A and B) Event-free survival (EFS) and overall survival (OS) in the population of patients under 60 years of age according to whether a dose-intensive chemotherapy regimen was administered. To avoid age-related biases, only patients under 60 years of age for whom a dose-intensive regimen could be proposed were included in this analysis. The dose-intensive regimen consisted of escalated (esc)BEACOPP (n=31), R-ACVBP (n=27) or DA-EPOCH-R (n=1). The standard regimen consisted of R-CHOP (n=19), ABVD (n=10) and R-CEOP (n=1). The 3-year estimated EFS was 74% (95%CI: 60%–84%) for patients treated with a dose-intensive regimen versus 46% (95%CI: 28%–63%) for those treated with a standard regimen, with a statistically significant difference [P=0.003, HR=0.37, (95%CI: 018–0.74)]. The 3-year estimated OS was 90% (95%CI: 78%–96%) for patients treated with a dose-intensive regimen, which was higher than for patients treated with a standard regimen [72% (95%CI: 49%–86%)], although the difference was not statistically significant; P=0.06, Hazard Ratio 0.39, (95%CI: 0.14–1.1). ABVD: doxorubicin, vinblastine, bleomycin, dacarbazine; escBEACOPP, escalated BEACOPP: methylprednisolone, doxorubicin, cyclophosphamide, procarbazine, etoposide, bleomycin, vincristine; CHOP: doxorubicin, methylprednisolone, cyclophosphamide, vincristine; ACBVP: doxorubicin, methylprednisolone, cyclophosphamide, bleomycin, vindesine; CEOP: etoposide, methylprednisolone, cyclophosphamide, vincristine; DA-EPOCH: dose-adapted etoposide, prednisolone, oncovin, cyclophosphamide, doxorubicin; R: rituximab; NA: not available.