igk and Hodgkin-Disease

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.

Topics: Aged; Aged, 80 and over; B-Lymphocytes; Biomarkers, Tumor; Cell Plasticity; DNA Mutational Analysis; Female; France; Gene Rearrangement, B-Lymphocyte, Heavy Chain; High-Throughput Nucleotide Sequencing; Hodgkin Disease; Humans; Immunoglobulin Heavy Chains; Immunoglobulins; Immunohistochemistry; In Situ Hybridization, Fluorescence; Lymphoma, Follicular; Male; Middle Aged; Mutation; Phenotype; Polymerase Chain Reaction; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogene Proteins c-bcl-6; Retrospective Studies

Topics: Adolescent; Genetic Predisposition to Disease; High-Throughput Nucleotide Sequencing; Hodgkin Disease; Humans; Immunoglobulin kappa-Chains; Immunoglobulins; Immunohistochemistry; Lymph Nodes; Lymphocytes; Lymphoma, Large B-Cell, Diffuse; Male

Although the analysis of molecular clonality rearrangements of the immunoglobulin light chains (IGK and IGL) is an alternative approach for diagnosis of B cell non-Hodgkin lymphomas (NHLs) using BIOMED-2 protocols, NHLs have not been extensively confirmed for Hodgkin lymphoma (HL) cases. We evaluated BIOMED-2 protocols in HL cases, which have been suggested previously as gold standard method for molecular clonality analysis on formalin fixed, paraffin-embedded (FFPE) tissue in NHL patients.. We recruited 50 consecutive FFPE tissues of HL samples to evaluate IGK and IGL clonality gene rearrangements using BIOMED-2 and Heteroduplex methods.. Our findings revealed a total of 94% (47/50) positive clonality, which consisted of 70% (35/50) for IGK and 44% (22/50) for IGL. In three cases, clonality was not detected in any of the immunoglobulin gene segments.. Analysis of clonality gene rearrangements in IGK and IGL genes using BIOMED-2 protocols could be implemented as a valuable method for improving clonality detection rate in HL cases and sensitivity (94%) and accuracy of HL diagnosis similar to that of the NHL samples will be increased.

Topics: Adolescent; Adult; Aged; Female; Gene Rearrangement; Hodgkin Disease; Humans; Immunoglobulins; Male; Middle Aged; Sensitivity and Specificity

A 35-year-old man suffered simultaneously from nodular sclerosis Hodgkin's disease (HD), Langerhans' cell histiocytosis and multiple myeloma (MM). There was no prior history of irradiation or chemotherapy, and clinically the lymphoma was confined to cervical lymph nodes. Immunohistochemically, neoplastic lymphoma cells reacted with CD15 and CD30 markers. The patient's bone marrow exhibited a diffuse infiltration by rather atypical plasma cells showing kappa immunoglobulin light-chain restriction. At 14 months after the diagnosis, after autologous bone marrow transplantation, the clinical evolution is favourable with complete remission of the diseases. This is the first time that the coexistence of these three haematological disorders has been discussed, and only the fourth documented case of simultaneous HD and MM. Speculations about the significance of this finding are discussed.

Topics: Adult; Histiocytosis, Langerhans-Cell; Hodgkin Disease; Humans; Immunoglobulins; Lymph Nodes; Male; Multiple Myeloma; Plasma Cells