Hodgkin's disease is a clonal lymphoid malignancy mainly confined to lymph nodes and lymphoid organs. For the period 1960–1963, 5-year survival from Hodgkin's disease was 40%; for the period from 1989 to 1993, 5-year survival had increased to 86%.
About 7500 new cases are diagnosed in the United States each year (roughly 2.9 per 100,000 population) (1). Males are affected somewhat more often than females (M:F 1.4:1). Hodgkin's disease accounts for about 11% of all lymphomas and is about half as common as multiple myeloma. It has a bimodal age distribution with the first peak in the late twenties and a second peak in late life. The etiology is unknown. Farmers, wood workers, and meat workers are at somewhat increased risk. A minor increased risk is associated with an HLA-linkage disequilibrium. Hodgkin's disease can complicate the genetic disease and ataxia telangiectasia, and occurs at increased frequency in patients with AIDS. An identical twin of an affected person is at 99-fold increased risk of developing the disease. Some geographic clusters have been noted and molecular studies have implicated Epstein–Barr virus (EBV) in the pathogenesis of some cases, particularly cases in Central and South America and patients with mixed cellularity histology (2) (see below).
Two major forms of Hodgkin's disease are recognized: classical Hodgkin's disease accounts for 95% of cases and nodular lymphocyte predominant Hodgkin's disease accounts for 5% (3). Classical Hodgkin's disease is divided into four histologic subtypes: nodular sclerosis (70% of cases), mixed cellularity (20% of cases), lymphocyte rich (3%–5% of cases), and lymphocyte depleted (<2% of cases). As diagnostic methods have improved, cases of lymphocyte depleted Hodgkin's disease have declined both because some cases were actually other lymphoma entities and because earlier diagnosis has made the entity more rare.
The malignant cell of Hodgkin's disease is the Reed–Sternberg cell; it has different forms in distinct histologic subtypes. In classical Hodgkin's disease, it is usually derived from a follicular center B cell that has clonally rearranged its immunoglobulin genes but does not transcribe them. Thus, no tumor immunoglobulin molecules are detected. From a clinical perspective, the distinction between classical Hodgkin's disease and nodular lymphocyte predominant Hodgkin's disease is critical because the entities differ in natural history and in standard approach to treatment. The distinction between subsets of classical Hodgkin's disease is not technically difficult, but carries little impact as the natural history and management are not affected by the subset diagnosis.
Immunophenotypic studies define differences between classic and nodular lymphocyte predominant Hodgkin's disease (see Table 32-1). All forms of Hodgkin's disease share three histologic features: effacement of the normal lymph node architecture; infiltration with a broad range of normal-appearing cells including reactive T cells, plasma cells, histiocytes, neutrophils, eosinophils, and stromal cells (the malignant cells are usually 3% or less of the total cells in an enlarged node); and presence of the characteristic neoplastic cells.
TABLE 32-1IMMUNOPHENOTYPE OF MALIGNANT CELLS IN HODGKIN'S DISEASE