Hodgkin lymphoma was first described by Thomas Hodgkin in an 1832 series of tumors of the absorbent (lymph) glands. The characteristic Reed-Sternberg cell was decribed by Carl Sternberg (l898) and Dorothy Reed (l902).

Hodgkin lymphoma generally presents as regional enlargement of a single group of peripheral lymph nodes, as opposed to non-Hodgkin lymphoma in which nodal involvement is more widely disseminated.

In addition, Hodgkin lymphoma is rarely extranodal whereas extranodal involvement is frequent in non-Hodgkin lymphomas. At presentation, bone marrow involvement by HD is highly unusual (< 5%).

When Hodgkin lymphoma involves the spleen or liver it generally presents as a mass lesion rather than as diffuse involvement.

The etiology of HD is unknown. Possible etiologic factors associated with the development of Hodgkin lymphoma (no conclusive evidence supporting any factor) include: prior EBV infection and frequent bcl-2 translocations. Epstein-Barr virus has been detected in approximately 40% of the cases of classical HL, and it is clonal; suggesting that EBV might play a role in the pathogenesis of at least some types of HL.

Rearrangements of immunoglobulin genes are found in Hodgkin lymphoma. Most cases are B-cell derived and the Hodgkin cells are clonal.

Abnormal cellular immunity is a feature of HD. Combined with chemotherapy it may lead to infectious complications. Further evidence of an immune defect is the lymphopenia seen in 40-50% of people with HD and which is more common in late stages.

Classic Reed-Sternberg cells are large (15-45 m) with abundant pale cytoplasm and two or more oval lobulated nuclei containing prominent "owl-eye" eosinophilic (H&E) nucleoli.

In some R-S cell variants the cytoplasm shrinks during formalin fixation and processing of tissue, leaving an empty space around the nucleus. Such R-S variants are known as "lacunar cells".

Another R-S variant is the "L&H" or "popcorn" cell with a fluffy, lobulated nucleus having fine chromatin and small nucleoli.

Other common R-S variants are mononuclear Hodgkin cells and "mummified" cells.

The frequency and character of the Reed-Sternberg cells ie., mononuclear R-S variants (Hodgkin cells), lacunar cells or so-called "popcorn" cells are features contributing to the histopathologic classification.

The accompanying cellular background of lymphocytes, plasma cells, eosinophils, histiocytes, and stromal cells is variable and is reactive to the neoplastic R-S cells.

The relative frequency of lymphocytes, eosinophils, and plasma cells and the character and amount of fibrosis in lymph nodes, are further clues as to the diagnosis and classification of Hodgkin lymphoma.

The primary diagnosis of Hodgkin lymphoma from the histopathologic examination of a lymph node requires the identification of Reed-Sternberg cells in an appropriate, reactive cellular background.

If a diagnosis of HD has been established on lymph node biopsy, the criteria for diagnosis of extranodal sites can be relaxed - requiring only mononuclear R-S cells and their variants in an appropriate background- not classic bilobed R-S cells.

Of course, benign reactive disorders must be ruled out by an experienced hematopathologist (see Reactive Lymphadenopathy).