Clinical, pathological and genetic features of primary mediastinal large B-cell lymphomas and mediastinal gray zone lymphomas in children

Abstract

Background Primary mediastinal large B-cell lymphoma is a rare lymphoma accounting for no more than 3% of all B-cell lymphomas in children and adolescents. However, patients in this young age group with this lymphoma have the shortest event-free survival of patients with any B-cell lymphoma under current standard chemotherapy protocols. Lymphomas with features intermediate between primary mediastinal large B-cell lymphoma and classical Hodgkin's lymphoma (mediastinal gray zone lymphomas) have been acknowledged in the latest World Health Organization classification. Recent studies suggest that mediastinal gray zone lymphomas have an aggressive clinical course whereas patients, at least adult ones, with primary mediastinal large B-cell lymphoma might respond very well to chemotherapy in combination with anti-CD20 antibody.

Design and methods: We aimed to evaluate whether biological differences or so far unrecognized admixed mediastinal gray zone lymphomas might explain the relatively poor outcome of pediatric patients with apparent primary mediastinal large B-cell lymphoma. We, therefore, performed a retrospective histopathological, immunohistochemical and interphase cytogenetic analysis of 52 pediatric lymphomas.

Results: The childhood primary mediastinal large B-cell lymphomas (n=44) showed a similar pattern of histology, immunophenotype and gains at 9p (59%) and 2p (41%) as adult cases, as determined from published data. We identified only four so far unrecognized cases of mediastinal gray zone lymphoma among 52 lymphomas registered in previous trials. Conclusions Mediastinal gray zone lymphoma is very rare in children and adolescents. It does, therefore, seem unlikely that these lymphomas account for the unsatisfactory clinical results with current therapy protocols in pediatric patients. These data have major implications for the design of future treatment protocols for mediastinal lymphomas in children and adolescents.

Figure 1.

Representative example of MGZL (corresponding to case 34 in Online Supplementary Table S2) displaying areas with typical PMBCL morphology with sheets of medium to large blasts (A) and areas with a morphology reminiscent of cHL with single blasts in a T-cell-rich background in the same tumor specimen (B) (H&E, inserts CD20).

Figure 2.

MGZL positive for EBV-encoded RNA (EBER) corresponding to case 49 in Online Supplementary Table S2 (A) = H&E, (B) = CD20, (C) = CD30, (D) = EBER.

Figure 3.

H&E morphology (A) and FISH for breaks in the MYC gene (B) in a case of a PMBCL (case 26 from Online Supplementary Table S2). Split signals are indicated by red and green arrows.