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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.

Follicular lymphoma and classic Hodgkin lymphoma can be associated in composite and/or sequential lymphomas. Common IGH and BCL2 rearrangements have already been identified between both contingents of these entities, but mutation profiles have not yet been investigated. The main objective of this study was to analyze the transdifferentiation process that may occur between Hodgkin and follicular contingents in sequential and composite lymphomas to better characterize these entities. From 2004 to 2020, a retrospective multicentric study was performed, including 9 composite and 13 sequential lymphomas. Clinical data were retrospectively collected. Fluorescent in situ hybridization of BCL2 and BCL6 rearrangements, polymerase chain reaction of IGH and IGK rearrangements, next-generation sequencing of IGK rearrangement, and targeted next-generation sequencing (TNGS) on a panel of genes frequently mutated in lymphomas were performed on each contingent of composite and sequential lymphomas. For TNGS, each contingent was isolated by laser capture microdissection. Clinical presentation and evolution were more aggressive in sequential than composite lymphomas. By fluorescent in situ hybridization, common rearrangements of BCL6 and BCL2 were identified between both contingents. Similarly, a common clonal relationship was established by evaluating IGH and IGK rearrangement by polymerase chain reaction or next-generation sequencing. By TNGS, the same pathogenic variants were identified in both contingents in the following genes: CREBBP, KMT2D, BCL2, EP300, SF3B1, SOCS1, ARID1A, and BCOR. Specific pathogenic variants for each contingent were also identified: XPO1 for Hodgkin lymphoma contingent and FOXO1, TNFRSF14 for follicular lymphoma contingent. This study reinforces the hypothesis of a transdifferentiation process between Hodgkin and follicular contingent of sequential/composite lymphomas.

T cell prolymphocytic leukemia (T-PLL) is a rare, aggressive neoplasm derived from post-thymic T cells. Patients are typically middle-aged with a slight male predominance who present with a high white blood cell count, hepatosplenomegaly, lymphadenopathy, and other symptoms typically associated with leukemia. Although cutaneous involvement has been reported in up to 30% of cases of T-PLL, to our knowledge, none have presented with a presentation resembling livedoid vasculopathy. In the correct clinical context, an underlying hematolymphoid neoplasm should be included in the differential diagnosis of a patient presenting with livedoid vasculopathy.

Rosai-Dorfman-Destombes disease is a rare non-Langerhansian cell histiocytosis characterized by the accumulation of large activated histiocytes in the affected tissues with images of emperipolesis. The diagnosis is not really problematic in the classical forms, with a lymph node presentation, whose histology is very suggestive. However, it can be much more difficult in the extra-nodal forms, which are misleading in both their clinical and histological presentation. We report here a case illustrating this diagnostic difficulty. Firstly, clinically, the disease was revealed by an unusual laryngeal location, responsible for acute obstructive respiratory distress and requiring urgent surgical management. Secondly, histologically, the diagnosis was not evoked in the first instance by analysis of the laryngeal lesion. Indeed, there was a not specific appearing polymorphic infiltrate, associating small lymphocytes, plasma cells and numerous histiocytes, without evidence for a lymphoma after immunohistochemistry and lymphocyte clonality analysis. However, after re-examination of the slides, the histiocytes sometimes appeared large or xanthomised and have a PS100+, CD1a-, langerhine- phenotype, with rare images of emperipolesis. These aspects finally suggested the diagnosis of Rosai-Dorfman-Destombes disease, then confirmed by a cervical lymph node biopsy showing characteristic histological features. Simultaneously, NGS analysis of the laryngeal lesion showed a mutation in the MAP2K1 gene, in accordance with the diagnosis. The patient was treated with revlimid and dexamethasone for 6 months, with complete remission, and is currently undergoing maintenance treatment with revlimid.