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.

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.…”

Composite Lymphoma’s Ability to Adapt and Change Through Plasticity: A Case Report and Literature Review

“…Reviews showcase that over 70% of patients who have composite lymphomas are aged 55 or older, which indicates that advanced age and host immune status could be potential factors that increase the risk of developing synchronous lymphomas [ 8 ]. Nonetheless, instances of cHL/NLPHL [ 9 ], cHL/DLBCL [ 10 ], and cHL/T-cell lymphoma [ 11 ] in individuals below the age of 35 have also been documented, attesting to the fact that this pathogenesis can arise at any stage of life. Histopathology analysis of published data often reveals that the cHL group predominantly consists of mixed cellularity (MC-type), which could imply a specific underlying pathophysiology linked to these subtypes.…”

“…First-degree relatives of affected individuals have a cumulative risk of developing Hodgkin lymphoma of 0.6% [ 19 ]. Reported familial syndromes linked to Hodgkin lymphomas include conditions such as DICER1 syndrome, association with human leucocyte antigen (HLA) abnormalities, NPAT germinal mutation, germinal homozygote CD27 deficiency, KLHDC8B gene translocation, and familial KDR mutations associated syndrome [ 9 ]. Due to the lack of understanding regarding the precise development of this type of tumor, it is essential to undertake further research investigations to enhance our comprehension of lymphomagenesis.…”