Hodgkin Lymphoma

Hodgkin lymphoma is a malignancy of the lymphatic system distinguished from other lymphomas by the presence of characteristic giant cells — Reed-Sternberg cells in the classical type — set within a reactive inflammatory background. It accounts for a minority of lymphomas but is notable for its frequently young patients and its high curability with modern therapy. Hodgkin lymphoma is divided into classical Hodgkin lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma.

Definition

Hodgkin lymphoma is a B-cell-derived lymphoid malignancy defined by a small population of neoplastic Reed-Sternberg cells (in classical Hodgkin lymphoma) or lymphocyte-predominant cells (in the nodular lymphocyte-predominant type) embedded in an abundant reactive inflammatory infiltrate.

Scope

This entry covers the defining pathology of Hodgkin lymphoma, its principal subtypes, the cell of origin of the neoplastic cells, the role of staging in describing disease extent, and its place within the World Health Organization classification of lymphoid neoplasms. It is a reference description of the disease entity and not clinical management guidance.

Core questions

• What pathological features distinguish Hodgkin lymphoma from non-Hodgkin lymphoma?
• What is the cell of origin of the Reed-Sternberg cell?
• How are classical and nodular lymphocyte-predominant subtypes defined?
• How is the anatomical extent of disease described and staged?

Key concepts

• Reed-Sternberg cell
• Classical Hodgkin lymphoma
• Nodular lymphocyte-predominant Hodgkin lymphoma
• Reactive inflammatory microenvironment
• Germinal-centre B-cell origin
• Ann Arbor and Lugano staging
• CD30 and CD15 immunophenotype

Mechanisms

In classical Hodgkin lymphoma the malignant Reed-Sternberg cells are derived from germinal-centre B cells that have lost much of their B-cell gene expression programme yet survive through deregulated signalling pathways. These scarce neoplastic cells recruit and depend upon an extensive reactive infiltrate of lymphocytes, eosinophils, and other cells, which is why involved tissue is dominated by inflammatory rather than tumour cells. Classical Hodgkin lymphoma cells characteristically express CD30 and CD15, whereas nodular lymphocyte-predominant Hodgkin lymphoma is composed of lymphocyte-predominant cells that retain B-cell markers; these features anchor the entity within the World Health Organization classification.

Clinical relevance

Hodgkin lymphoma is a reference example of a highly curable lymphoid malignancy and of how the tumour microenvironment shapes a cancer. Recognising its distinct pathology and subtypes clarifies why it is classified and behaves differently from the non-Hodgkin lymphomas. This entry describes the disease conceptually and is not a basis for individual diagnosis or treatment.

Epidemiology

Hodgkin lymphoma is less common than non-Hodgkin lymphoma and shows a characteristic age pattern, with a prominent incidence peak in young adults and a second rise in older age. Classical Hodgkin lymphoma comprises the large majority of cases; nodular lymphocyte-predominant Hodgkin lymphoma is uncommon. Epstein-Barr virus is associated with a proportion of classical cases.

History

The disease was first described by Thomas Hodgkin in the nineteenth century, and the characteristic giant cells were later detailed by Dorothy Reed and Carl Sternberg. Twentieth-century work established its staging and, ultimately, its curability, while immunophenotyping and molecular studies clarified the B-cell origin of the Reed-Sternberg cell. Successive World Health Organization classifications refined the distinction between classical and nodular lymphocyte-predominant forms.

Debates

Boundary between nodular lymphocyte-predominant Hodgkin lymphoma and B-cell lymphomas

Nodular lymphocyte-predominant Hodgkin lymphoma retains B-cell features and can overlap morphologically and biologically with certain B-cell lymphomas, prompting ongoing refinement of how it is defined and named in successive classifications.

Key figures

• Stephen M. Ansell
• Steven H. Swerdlow
• Bruce D. Cheson

Seminal works

• swerdlow-2016
• ansell-2022
• cheson-2014

Frequently asked questions

What is a Reed-Sternberg cell?

It is the characteristic large, often binucleate neoplastic cell of classical Hodgkin lymphoma. It derives from a germinal-centre B cell and is greatly outnumbered by the surrounding reactive inflammatory cells in affected tissue.

How does Hodgkin lymphoma differ from non-Hodgkin lymphoma?

Hodgkin lymphoma is defined by its characteristic Reed-Sternberg or lymphocyte-predominant cells within a reactive background and tends to spread in a contiguous nodal pattern, whereas non-Hodgkin lymphoma encompasses a large and biologically diverse set of lymphoid neoplasms classified mainly by cell of origin.