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Precision Molecular Pathology of Hodgkin Lymphoma pp 127–155Cite as

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

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Part of the book series: Molecular Pathology Library ((MPLB))

Abstract

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.

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Abbreviations

ALCL:

Anaplastic large cell lymphoma

BCR:

B-cell receptor

cHL:

Classical Hodgkin lymphoma

CLL:

Chronic lymphocytic leukemia

DLBCL:

Diffuse large B-cell lymphoma

EBV:

Epstein-Barr virus

FISH:

Fluorescence in situ hybridization

FL:

Follicular lymphoma

GC:

Germinal center

HL:

Hodgkin lymphoma

HRS:

Hodgkin and Reed/Sternberg

IgV:

Immunoglobulin variable

LMP1:

Latent membrane protein 1

LP:

Lymphocyte predominant

MCL:

Mantle cell lymphoma

MZL:

Marginal zone lymphoma

NHL:

Non-Hodgkin lymphoma

NLPHL:

Nodular lymphocyte predominant Hodgkin lymphoma

PCR:

Polymerase chain reaction

PMBL:

Primary mediastinal B-cell lymphoma

SLL:

Small lymphocytic lymphoma

TCR:

T-cell receptor

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Acknowledgments

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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  1. Institute of Cell Biology (Cancer Research), Medical Faculty, University of Duisburg-Essen, Virchowstr. 173, 45122, Essen, Germany

    Marc A. Weniger & Ralf Küppers

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Correspondence to Ralf Küppers .

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  1. Department of Pathology and Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut, USA

    S. David Hudnall

  2. Universität Duisburg-Essen, Institute for Cell Biology, Essen, Nordrhein-Westfalen, Germany

    Ralf Küppers

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Weniger, M.A., Küppers, R. (2018). Composite Lymphomas and the Relationship of Hodgkin Lymphoma to Non-Hodgkin Lymphomas. In: Hudnall, S., Küppers, R. (eds) Precision Molecular Pathology of Hodgkin Lymphoma . Molecular Pathology Library. Springer, Cham. https://doi.org/10.1007/978-3-319-68094-1_7

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