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

Chapter
Part of the Molecular Pathology Library book series (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.

Keywords

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 

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

Notes

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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© 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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