From Hodgkin’s Disease to Hodgkin Lymphoma

Hodgkin lymphoma was described by Thomas Hodgkin in 1932. It was referred to as Hodgkin’s disease till the WHO classification proposed the use of the term Hodgkin Lymphoma. The journey from Hodgkin’s disease to Hodgkin Lymphoma was possible because of breakthroughs immunophonotyping, molecular biology and microdissection.

The difference between Hodgkin’s disease and Hodgkin lymphoma is not about semantics. The term lymphoma recognises the disorder to be malignant whereas the term “disease” was ambiguous. Unlike any other malignancy the bulk the tumour in patients with Hodgkin lymphoma is made of normal reactive cells, lymphocytes, neutrophils, eosinophils and plasma cells. Reed-Sternberg (RS) is the malignant cell of classical Hodgkin lymphoma (cHL) and the LP cell is the malignant cell of nodular lymphocytic predominant Hodgkin lymphoma (NLPHL). Both cells form a small minority of the tumour mass. The combination of a bizarre looking cell that are sparsely distributed in what looked like a chronic inflammatory infiltrate was unlike any other malignancy and was the cause of uncertainty about the malignant nature of Hodgkin lymphoma. The term Hodgkin’s diseases reflected this uncertainty.

Malignancy is driven by mutations in genes regulating growth and differentiation. Many mutations result from chromosomal defects that can be demonstrated by karyotyping. The RS cell and the LP cell from a small proportion of the tumour mass. A pure population of malignant cells was needed for karyotyping. Today it is possible to separate out these cells from tissue by laser micro dissection. Before this technology became available the only way to get a pure population of RS cells was by establishing cell lines from patients suffering from Hodgkin’s disease. Study of cell lines as well as laser dissected RS cells showed the cells to have karyotype anomalies confirming the disease was a malignancy.

Another area of confusion was the cell of origin of Hodgkin lymphoma. The cells that had been suggested to be giving rise to RS cell included B-lymphocyte, T-lymphocyte, reticulum cell, dendritic cell and histiocyte/macrophage. Molecular studies have shown that the RS cell originates from the pre-apoptotic germinal centre B cell and the LP cell originates from the antigen selected germinal centre B cell. The former does not express the classical B cell markers the latter does. There are multiple reasons for the lack of expression of B cell markers and these include expression of inhibitors of B-cell molecules, down-regulation of B-cell transcription factors and the epigenetic silencing of B-cell genes.

Hodgkin lymphoma is a malignancy of germinal B cell origin and the term lymphoma describes the disease more accurately than the word disease. WHO classification of lymphoid malignancies refers to the disorder as Hodgkin Lymphoma in recognition of this fact.

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