Hodgkin's Disease

Localized or disseminated malignant proliferation of tumor cells arising from the lymphoreticular system, primarily involving lymph node tissue and the bone marrow.

The annual incidence of Hodgkin's disease is 2/100,000 in the USA. There is a bimodal age distribution, with an initial peak between ages 15 and 35 and a second peak between ages 50 and 80. At age 75, incidence is 7/100,000 annually, slightly higher in men. Hodgkin's disease is more common in people at higher socioeconomic levels. Geographic, occupational (woodworkers), and family clusters of Hodgkin's disease have been noted.

Etiology and Pathophysiology

The cause of Hodgkin's disease is unknown. However, seroepidemiologic studies suggest that the Epstein-Barr virus may be involved. Patients with immunodeficiencies and autoimmune disease are at increased risk (suggesting that the immune system plays a role), as are those taking hydantoin drugs, such as phenytoin.

Histologically, Hodgkin's disease is subdivided into four major types: lymphocyte-predominant (mainly lymphocytes with few Reed-Sternberg cells); mixed cellularity (a cellular response of mature lymphoid cells, plasma cells, eosinophils, and Reed-Sternberg cells); lymphocyte-depleted (few lymphoid cells with a majority of histiocytes, fibrotic reaction, and Reed-Sternberg cells); and nodular sclerosis (effacement of lymphoid structure by nodular aggregates of mature lymphoid cells and lacunar variants of Reed-Sternberg cells separated by bands of birefringent collagen).

In all types, normal lymphoid tissue is replaced by the malignant lymphoma, resulting in immunodeficiency and infections. The bone marrow may be replaced, resulting in pancytopenia and subsequent bleeding and infection. Tumor bulk may obstruct or invade vital organs, ultimately causing death.

Symptoms and Signs

Patients with Hodgkin's disease usually present with enlarged lymph nodes in the neck. The lymph nodes may be painful or tender, and drinking alcohol may make them more so. Although any nodal group can be involved, the central or axial lymph nodes are most commonly affected. The patient may be asymptomatic (when the disease is clinically staged as A) or may have fever, night sweats, or loss of >= 10% of body weight (stage B). These systemic symptoms are often associated with extensive disease. Patients with extensive disease may also present with diffuse adenopathy and involvement of the spleen, liver, bone marrow, or lungs.

Diagnosis

The diagnosis is made when biopsy of a lymph node reveals the histologic picture of Hodgkin's disease. Fundamental to the diagnosis is the histologic finding in the lymph node of the giant Reed-Sternberg cell, which usually has twin nuclei and nucleoli that give it the appearance of owl's eyes. The Reed-Sternberg cell is probably the malignant cell, and the surrounding cells probably represent tissue reaction.

Clinical staging in Hodgkin's disease is extremely important in determining treatment. The currently accepted stages are listed in Table 74-1. Clinical staging is based on a complete physical examination with special attention to all lymph node areas. Laboratory studies include a routine blood chemistry profile and CBC count and CT scans of the abdomen, pelvis, and, in some cases, the chest. Lymphangiograms via the pedal lymphatics to outline the femoral, inguinal, pelvic, and paraaortic nodes are being replaced by positron emission tomography, spiral CT scans, and MRI. In cases in which the clinical stage may change the treatment modality, laparotomy including splenectomy, liver biopsies, and biopsies of grossly suspicious lymph nodes are performed as needed. A bone marrow biopsy is required only if the findings will affect treatment. A staging laparotomy, by providing additional findings, results in a change in clinical and pathologic stages in up to 30% of patients. In the elderly, Hodgkin's disease is more likely to present as advanced disease (stage III or IV). Some authorities believe that patients > 40, particularly those with mixed cellularity or lymphocyte depletion, may not benefit from the findings gained by laparotomy.

Prognosis

Hodgkin's disease is often curable, even though older age is an unfavorable prognostic factor because the elderly cannot tolerate as much chemotherapy and have more concomitant illnesses. The 5-year survival rate for patients < 40 is about 80%; for those 40 to 60, 60%; and for those > 60, about 30%. Other unfavorable prognostic signs are bulky disease, high serum lactic dehydrogenase (LDH) levels, and extranodal involvement. However, the stage at the time of treatment is by far the most predictive of outcome. Hodgkin's disease in the elderly may have a different etiology than that occurring in the young, since elderly patients often present with stage IV disease and a greater number of unfavorable prognostic signs. Alternatively, aging might alter the presentation.

Before the introduction of potentially curative treatment, the lymphocyte-predominant and nodular sclerosis types carried better prognoses than the other types.

Treatment

Elderly persons in advanced stages do not do as well as younger persons because they are usually unable to tolerate maximum doses of radiation and chemotherapy.

Recommendations for treatment depend on stage (see Table 74-2). However, the regeneration of bone marrow after radiation therapy or chemotherapy is markedly diminished in patients > 40, and the gastrointestinal (GI) side effects are much more severe. Thus, consideration should be given to limiting the usual field of radiation in elderly patients with early-stage disease. Similarly, administering the optimum dose of chemotherapy may be impossible in elderly patients, even though the benefit of aggressive therapy generally outweighs the risk. Many elderly patients can tolerate only 30 to 50% of the optimum doses of chemotherapy, although the survival rate of patients given less than the optimum doses is dramatically lower.

The most frequently used regimens in the elderly are MOPP, British MOPP, and ABVD, each of which consists of four drugs (see Table 74-3). The duration of chemotherapy is 6 to 8 months or for at least 2 months after complete remission. The incidence of a second malignancy (usually acute leukemia or non-Hodgkin's lymphoma) increases in patients who have Hodgkin's disease and who are receiving or have received chemotherapy, especially when combined with total nodal irradiation.

Hemolymphopoietic growth factors can sometimes be used to help overcome loss of normal lymphatic cells, which occurs through destruction of lymphoid tissue by lymphoma. Fifteen of these factors have been characterized; three of them--erythropoietin, granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF)--are commercially available. Human G-CSF is also used in patients who are receiving myelosuppressive anticancer drugs, which can cause severe neutropenia. The recommended starting dose is 5 µg/kg/day sc or IV. The use of G-CSF varies with different chemotherapeutic regimens. Human GM-CSF has been used mainly after bone marrow transplantation and, therefore, no data exist in the elderly. The use of other growth factors (including all the interleukins) is still experimental.