Plasticity in Classical Hodgkin Composite Lymphomas: A Systematic Review

Abstract

The co-occurrence of several lymphomas in a patient defines composite/synchronous lymphoma. A common cellular origin has been reported for both contingents of such entities. In the present review, we aimed to gather the available data on composite lymphomas associating a classical Hodgkin lymphoma (cHL) with another lymphoma, to better understand the plasticity of mature B and T-cells. This review highlights that >70% of patients with a composite lymphoma are ≥55 years old, with a male predominance. The most reported associations are cHL with follicular lymphoma or diffuse large B-cell lymphoma, with over 130 cases reported. The cHL contingent is often of mixed cellularity type, with a more frequent focal/weak CD20 expression (30% to 55.6%) compared to de novo cHL, suggesting a particular pathophysiology. Moreover, Hodgkin cells may express specific markers of the associated lymphoma (e.g., BCL2/BCL6 for follicular lymphoma and Cyclin D1 for mantle cell lymphoma), sometimes combined with common BCL2/BCL6 or CCND1 rearrangements, respectively. In addition, both contingents may share similar IgH/IgK rearrangements and identical pathogenic variants, reinforcing the hypothesis of a common clonal origin. Finally, cHL appears to be endowed with a greater plasticity than previously thought, supporting a common clonal origin and a transdifferentiation process during lymphomagenesis of composite lymphomas.

Composite Lymphoma with Follicular Lymphoma Transformation to Clonally Related Epstein–Barr Virus (EBV) Positive Diffuse Large B-Cell Lymphoma and EBV-PositiveClassic Hodgkin Lymphoma

“…Te distinct components of composite lymphomas can include a wide spectrum of lymphoma entities which may or may not be clonally related on a case-by-case basis. While cHL has been reported as a composite lymphoma with either DLBCL or FL, occasionally in association with EBV [4,5], we believe that this case is the frst report of all three lymphomas arising in a single lymph node. Furthermore, we demonstrate a clonal relationship between the three lymphomas using B-cell receptor gene rearrangement studies.…”

A Rare Presentation of Collision Diffuse Large B-Cell Lymphoma and Hodgkin Lymphoma Treated with R-CHOP and Adjuvant Radiation Therapy

“…In a literature review by Trecourt et al, patients with a composite lymphoma of classic Hodgkin’s lymphoma and DLBCL are classically old or middle-aged, without a history of lymphoma at presentation [ 9 ]. Similarly, our patient had no past medical history of lymphoma.…”

Case report: Composite mantle cell lymphoma and classical Hodgkin lymphoma

“…Thus, it is challenging to differentiate HRS from HRS-like cells when diagnosing a CMLHL. The following reported criteria (23,24) could help in the recognition of HRSlike cells: 1) the HRS-like cells usually present as scattered single cells or small cluster distributions among NHL and 2) absence of a typical cHL background microenvironment (fibrosis and/or stromal inflammatory reaction). In the current case, the MCL and cHL components were roughly separated.…”