Composite Lymphomas and the Relationship of Hodgkin Lymphoma to Non-Hodgkin Lymphomas

Part of the Molecular Pathology Library book series (MPLB)


Composite lymphomas are rare combinations of two distinct types of lymphomas occurring simultaneously in one patient, often a Hodgkin lymphoma (HL) and a non-Hodgkin lymphoma (NHL). In other instances, a HL and a NHL may occur subsequently in a patient. Some composite lymphomas likely represent chance occurrences of two independent tumors. However, in a large fraction of combined HL and NHL, the two lymphomas are clonally related and hence have a common origin. Detailed analysis of the rearranged immunoglobulin V region genes of such related lymphomas provided strong evidence that in many cases, the two lymphomas in composite as well as consecutive HL and B-cell NHL developed from distinct daughter cells of a mutating germinal center (GC) B-cell clone. Clonally related composite lymphomas carry both shared early genetic lesions as well as later separate transforming events, supporting a multi-step transformation process in such cases. The pattern of clonally related immunoglobulin V region genes and shared genetic lesions points to a close relationship of HL to B-cell NHL.

Nodular lymphocyte predominant HL shows numerous histological and phenotypic similarities to follicular lymphoma. The tumor cells of both lymphomas represent transformed GC B cells, but the two lymphomas differ in their patterns of mutated oncogenes and tumor suppressor genes. The lymphomas most closely related to classical HL are primary mediastinal B-cell lymphoma (PMBL) and anaplastic large cell lymphoma (ALCL). Classical HL and PMBL share many constitutively activated signaling pathways and show a large overlap in their patterns of genetic lesions, but the lymphoma cells seem to derive from two distinct subsets of GC B cells. The lymphoma cells in cHL and ALCL also share a number of deregulated signaling pathways, as well as morphological and phenotypical features, but a major distinction is the B-cell derivation of classical HL and the T-cell origin of ALCL.


Anaplastic large cell lymphoma Composite lymphoma Germinal center Hodgkin lymphoma Immunoglobulin genes Non-Hodgkin lymphoma Primary mediastinal B-cell lymphoma Reed-Sternberg cell Somatic mutations 



Anaplastic large cell lymphoma


B-cell receptor


Classical Hodgkin lymphoma


Chronic lymphocytic leukemia


Diffuse large B-cell lymphoma


Epstein-Barr virus


Fluorescence in situ hybridization


Follicular lymphoma


Germinal center


Hodgkin lymphoma


Hodgkin and Reed/Sternberg


Immunoglobulin variable


Latent membrane protein 1


Lymphocyte predominant


Mantle cell lymphoma


Marginal zone lymphoma


Non-Hodgkin lymphoma


Nodular lymphocyte predominant Hodgkin lymphoma


Polymerase chain reaction


Primary mediastinal B-cell lymphoma


Small lymphocytic lymphoma


T-cell receptor



We thank Martin-Leo Hansmann for many stimulating discussions. Own work discussed in this chapter was supported by the Wilhelm Sander Stiftung (No. 2014.136.1), the Deutsche Forschungsgemeinschaft (KU1315/10-1), and the Deutsche Krebshilfe (70112112).


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© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Institute of Cell Biology (Cancer Research), Medical FacultyUniversity of Duisburg-EssenEssenGermany

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