Hodgkin disease and cancer

ALSO KNOWN AS: Hodgkin’s disease, Hodgkin lymphoma, HD

Related condition: Mononucleosis

DEFINITION: Hodgkin disease is the malignant growth of abnormal immune cells called lymphocytes in the lymphatic system, a critical part of the body’s immune system. There are two main types of lymphocytes, B and T.

There are five types of Hodgkin disease: nodular lymphocyte-predominant Hodgkin lymphoma and four classic types:

• Nodular sclerosing Hodgkin lymphoma
• Mixed-cellularity Hodgkin lymphoma
• Lymphocyte-depleted Hodgkin lymphoma
• Lymphocyte-rich Hodgkin lymphoma

These five types differ mostly in how they look under a microscope. However, nodular lymphocyte-predominant Hodgkin lymphoma also behaves differently from the classic types.

Risk factors: The risk for Hodgkin disease depends on gender, age, race, medical condition, and family history. The disease is slightly more common in men, and the difference is particularly evident in children younger than age ten, with the number of boys with the disease up to four times the number of girls with the disease. Except for nodular lymphocyte-predominant Hodgkin lymphoma, the risk of developing the disease is highest in young adulthood (between ages fifteen and thirty-five years) and later life (over sixty years). The risk for nodular lymphocyte-predominant Hodgkin lymphoma is highest in a person’s thirties and forties. Hodgkin disease is more common in white patients, and infection with the Epstein-Barr virus (EBV), which causes infectious mononucleosis, increases a person’s risk of developing Hodgkin disease up to four times that of a person who has not had EBV. Having a first-degree relative with Hodgkin disease increases the risk of the disease. The identical twin of a Hodgkin patient has one hundred times the risk of developing this cancer compared with the general population.

Etiology and the disease process: The causes of Hodgkin disease are unclear. There are no known chemicals or environmental factors that increase the risk of Hodgkin. However, in some cases, a good argument can be made for a combination of genetics and infection with the EBV as causing the disease. EBV infects the majority of the world’s population. Estimates put the infection rates at 90 percent of adults, but most do not develop signs of EBV infection. The virus infects B lymphocytes and is thought to cause other types of cancer, including Burkitt lymphoma, another immune system cancer. Malignant cells of Hodgkin disease patients often carry EBV deoxyribonucleic acid (DNA).

At the heart of Hodgkin disease are two types of large, abnormal cells—the Reed-Sternberg and Hodgkin lymphoma cells. Hodgkin disease patients usually have tumors made up of these cells and inflammatory immune cells surrounding them. The exception is nodular lymphocyte-predominant Hodgkin lymphoma, in which there are hardly any Reed-Sternberg cells. Instead, this type of Hodgkin disease has typical abnormal cells known as “L and H” or “popcorn cells.”

The abnormal cells, surrounded by inflammatory cells, create tumors that usually start in lymph nodes in the chest or neck. These tumors cause swollen glands, usually the first signs of the disease.

Hodgkin disease spreads through the lymphatic system and, in advanced disease, blood vessels. It invades the lungs, bones, bone marrow, and liver. The presence of Hodgkin anywhere else usually means the patient has an HIV infection, which makes Hodgkin disease behave differently. Immunosuppressive conditions such as HIV infection and AIDS are risk factors for Hodgkin disease. Patients with HIV/AIDS are ten times as likely to develop Hodgkin lymphoma than the general population.

Incidence: New cases of Hodgkin disease occur in eight to nine thousand people each year in the United States. Globally, more than sixty thousand new cases of Hodgkin lymphoma are diagnosed annually. Hodgkin lymphoma accounts for 11 to 14 percent of all lymphomas in industrialized nations. Most diagnoses are in individuals between fifteen and thirty-five.

Symptoms: Swollen lymph nodes are often the first sign of Hodgkin disease. In most cases, the swollen nodes will be above the diaphragm, in the chest or neck. Sometimes, there are no symptoms, but people may feel pain in the affected nodes after drinking alcohol. The tumors in Hodgkin can get fairly large and may cause symptoms such as difficulty swallowing and breathing. Itching, sometimes severe, can precede the development of Hodgkin disease by several years.

Systemic symptoms that indicate a more serious disease include:

• Persistent fever higher than 38 degrees Celsius (100.4 degrees Fahrenheit)
• Weight loss of more than 10 percent of the total body weight in six months
• Drenching night sweats

Screening and diagnosis: Diagnosing Hodgkin disease requires a complete medical history and several tests. These tests include a complete blood count (CBC) to look at the different cells in the blood and their levels; an erythrocyte sedimentation rate (ESR) test to see how fast blood cells settle to the bottom of a test tube and thereby detect possible infection, cancer, or a bone marrow problem; an open lymph node biopsy; plus X-ray, computed tomography (CT), and positron emission tomography (PET) scans. Though surgery to determine the stage of the cancer is no longer standard, some patients may still need it if the affected areas are hard to reach or hard to see or sample with nonsurgical techniques.

Staging of Hodgkin disease is commonly accomplished using the Lugano classification system, which is based on the older Ann Arbor or the Cotswolds classification system established in Ann Arbor, Michigan, and modified in Cotswolds, England.

Treatment and therapy: Oncologists decide on treatment for Hodgkin disease according to the stage and prognostic factors. The prognosis depends not only on the stage of the cancer but also on several risk factors. The presence of these risk factors usually means the disease will be harder to control, and patients are likely to relapse unless they receive more intense or longer treatment. Therefore, even in early-stage Hodgkin, some patients may require treatments similar to those given to patients with advanced disease.

Risk factors for early-stage (Stages I and II) adult Hodgkin disease include the following:

• The presence of a tumor larger than 10 centimeters (cm; 3.9 inches) in size
• The presence of systemic symptoms
• An ESR value greater than 50
• Cancer outside the lymph nodes
• Cancer in three or more lymph nodes

For advanced disease in adults (Stage III and IV), the risk factors are as follows:

• Age older than forty-five years
• Male gender
• Serum albumin levels lower than 4 grams/deciliter (this is a measure of the levels of the most important protein in the blood)
• Hemoglobin levels below 10.5 grams/deciliter
• High white cell count
• Low lymphocyte count
• Stage IV disease

Four categories determine treatment:

• Early-stage favorable: Stage I or II disease with no risk factors
• Early-stage unfavorable: Stage I or II with one or more early-stage risk factors
• Advanced favorable: Stage III or IV with up to three advanced-stage risk factors
• Advanced unfavorable: Stage III or IV with four or more advanced-stage risk factors

Treatment for early-stage favorable disease consists of short-duration chemotherapy followed by radiation to the affected areas. The current standard chemotherapy regimen, known as ABVD, uses a combination of four drugs: doxorubicin (adriamycin), bleomycin, vinblastine, and dacarbazine. Another regimen, though less effective, is COPP—cyclophosphamide, vincristine (Oncovin), procarbazine, and prednisone. Other combinations of chemotherapy drugs are also available.

Treatment of early-stage unfavorable disease consists of radiation to the affected site and two to eight cycles of chemotherapy.

Advanced disease is treated with chemotherapy combinations. Patients who do not respond to treatment or respond but relapse can benefit from high-dose chemotherapy followed by a transplant of their own stem cells. Stem cells are harvested before beginning the high-dose chemotherapy and transplanted back to produce healthy red and white blood cells.

Risk factors in children are the same as those of the adult early-stage risk factors. Treatments in children are different in intensity of radiation and the drug combinations used in chemotherapy. For example, in drug protocols for boys, etoposide is substituted for procarbazine because procarbazine induces sterility.

Because Hodgkin disease often strikes during the childbearing years, the question of treatment during pregnancy may arise. Treatment decisions for pregnant patients are individualized and depend on the stage of the disease, the stage of the pregnancy, and the mother’s preferences. In many cases, treatment can be delayed until the end of the pregnancy unless life-threatening symptoms occur. Labor might be induced early to allow for an earlier start of treatments. Case reports also show that women receiving radiation treatments to the upper body, with heavy shielding of the fetus, deliver healthy babies with no apparent abnormalities. However, there is possibly a danger of future cancer in the child, resulting from stray radiation that may have penetrated the shield. Chemotherapy treatments with vinblastine during the second part of the pregnancy are safe and effective, as is the ABVD combination treatment. The ABVD regimen during the first trimester may harm the fetus.

Prognosis, prevention, and outcomes: Hodgkin disease has a high cure rate. The cure rate is approximately 75 percent in adults and nearly 95 percent in children. More than 75 percent of patients survive for ten years, and 90 percent are alive one year after diagnosis.

Because Hodgkin disease is highly curable, more and more patients find themselves facing late complications of treatment years after their disease has disappeared. Late complications include infertility, hypothyroidism, and lowered immunity. A particularly problematic late complication is the development of secondary cancers, including leukemia, as well as breast, skin, and lung cancers.

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