54 – Classical Hodgkin Lymphoma

Hodgkin's lymphoma was first described in 1832. The aetiology of this lymphoma, however, remained enigmatic for a long time. Only within the past 10 years has the B-cell nature of the pathognomonic Hodgkin and Reed-Sternberg (HRS) cells been revealed, along with several recurrent genetic lesions. The pathogenetic role for Epstein-Barr virus infection has also been substantiated. HRS cells in classical Hodgkin's lymphoma have several characteristics that are unusual for lymphoid tumour cells, and the Hodgkin's lymphoma microenvironment is dominated by an extensive mixed, potentially inflammatory cellular infiltrate. Understanding the contribution of all of these changes to the pathogenesis of this disease is essential for the development of novel therapies.

The biology of Hodgkin's lymphoma.

Hodgkin's lymphoma (HL) represents the most common subtype of malignant lymphoma in young people in the Western world. Most patients can be cured with modern treatment strategies, although approximately 20% will die after relapse or progressive disease. The histologic hallmark of the disease is the presence of the characteristic Hodgkin Reed-Sternberg (HRS) cells in classical HL and so-called lymphocyte-predominant (LP) cells in nodular lymphocyte-predominant HL. HL is unique among all cancers because malignant cells are greatly outnumbered by reactive cells in the tumor microenvironment and make up only approximately 1% of the tumor. Expression of a variety of cytokines and chemokines by the HRS and LP cells is believed to be the driving force for an abnormal immune response, perpetuated by additional factors secreted by reactive cells in the microenvironment that help maintain the inflammatory milieu. The malignant HRS and LP cells manipulate the microenvironment, permitting them to develop their malign...

Molecular Pathogenesis of Hodgkin's Lymphoma: Increasing Evidence of the Importance of the Microenvironment

Genome-wide copy number analysis of Hodgkin Reed-Sternberg cells identifies recurrent imbalances with correlations to treatment outcome.

In the past few years, there has been a greater understanding of the spectrum and biology of Hodgkin lymphoma (HL). In standard texts, HL is classified as 2 distinct entities, namely nodular lymphocyte-predominant HL and classical HL (CHL). However, recent evidence suggests that CHL is not a single disease. Although the mixed cellularity and lymphocyte-depleted subtypes might be part of a biologic continuum, the nodular sclerosis subtype has a distinct epidemiology, clinical presentation, and histology. Nodular sclerosis HL might also be related to primary mediastinal B-cell lymphoma and mediastinal gray-zone lymphomas. We present an update on the pathobiology of HL and discuss these biologic and clinical differences in this review.

/pdf/hodgkin-lymphoma-an-update-on-its-biology-with-new-insights-5a8h7u977y.pdf

Hodgkin Lymphoma: An Update on its Biology with New Insights into Classification

Hodgkin lymphoma (HL) is an unusual malignancy in that the tumour cells, the Hodgkin and Reed-Sternberg (HRS) cells, are a minor component of the tumour mass, the bulk of which is a mixed cellular infiltrate. There is compelling evidence that HRS cells are clonal B cells that have lost their B cell phenotype. Mature B cells lacking B cell receptors would normally die by apoptosis, and therefore HRS cells must have developed mechanisms to facilitate survival. The escape from apoptosis and transcriptional reprogramming of HRS cells are interlinked and appear central to disease pathogenesis. Epstein-Barr virus (EBV) is present in the HRS cells of a proportion of cases and expresses genes with a plausible oncogenic function. It is likely that EBV plays a role in reprogramming and survival through dysregulation of several signalling networks and transcription factors, including nuclear factor (NF)-κB. Activation of NF-κB is a feature of all HRS cells and gene mutations affecting this pathway appear common in EBV-negative HL. The HRS cell furthers its own survival by attracting a supportive microenvironment of immune and stromal cells, and suppressing local immune responsiveness. Although many questions remain unanswered, the last two decades have witnessed a considerable increase in our knowledge of this complex disease.

/pdf/the-molecular-pathogenesis-of-hodgkin-lymphoma-296ydfs079.pdf

54 – Classical Hodgkin Lymphoma

References

The biology of Hodgkin's lymphoma.

Molecular Pathogenesis of Hodgkin's Lymphoma: Increasing Evidence of the Importance of the Microenvironment

Genome-wide copy number analysis of Hodgkin Reed-Sternberg cells identifies recurrent imbalances with correlations to treatment outcome.

Hodgkin Lymphoma: An Update on its Biology with New Insights into Classification

The molecular pathogenesis of Hodgkin lymphoma.

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