Hodgkin's disease

Definition

Hodgkin's disease is a rare lymphoma, a cancer of the lymphatic system.

Description

Hodgkin's disease, or Hodgkin's lymphoma, was first described in 1832 by Thomas Hodgkin, a British physician. Hodgkin clearly differentiated between this disease and the much more common non-Hodgkin's lymphomas. Prior to 1970, few individuals survived Hodgkin's disease. Now, however, the majority of individuals with this cancer can be cured.

The lymphatic system is part of the body's immune system, for fighting disease, and a part of the blood-producing system. It includes the lymph vessels and nodes, and the spleen, bone marrow, and thymus. The narrow lymphatic vessels carry lymphatic fluid from throughout the body. The lymph nodes are small organs that filter the lymphatic fluid and trap foreign substances, including viruses, bacteria, and cancer cells. The spleen, in the upper left abdomen, removes old cells and debris from the blood. The bone marrow, the tissue inside the bones, produces new red and white blood cells.

Lymphocytes are white blood cells that recognize and destroy disease-causing organisms. Lymphocytes are produced in the lymph nodes, spleen, and bone marrow. They circulate throughout the body in the blood and lymphatic fluid. Clusters of immune cells also exist in major organs.

Hodgkin's disease is a type of lymphoma in which antibody-producing cells of the lymphatic system begin to grow abnormally. It usually begins in a lymph node and progresses slowly, in a fairly predictable way, spreading via the lymphatic vessels from one group of lymph nodes to the next. Sometimes it invades organs that are adjacent to the lymph nodes. If the cancer cells spread to the blood, the disease can reach almost any site in the body. Advanced cases of Hodgkin's disease may involve the spleen, liver, bone marrow, and lungs.

There are different subtypes of Hodgkin's disease:

• nodular sclerosis (30–60% of cases)
• mixed cellularity (20–40% of cases)
• lymphocyte predominant (5–10% of cases)
• lymphocyte depleted (less than 5% of cases)
• unclassified

— Rosalyn S. Carson-DeWitt, MD; Margaret Alic, Ph.D.

[After Thomas Hodgkin (1798-1866), British physician.]

For more information on Hodgkin disease, visit Britannica.com.

Key Terms: Antibody, Biopsy, Bone marrow, Chemotherapy, Epstein-Barr virus, Interferon, Interleukins, Laparotomy, Leukapheresis, Lymph nodes, Lymphatic system, Lymphocyte, PBSCT, Radiotherapy, Reed-Sternberg cells, Spleen, Splenectomy, Staging, Stem cells, Thymus.

Definition

Hodgkin's disease is a rare lymphoma, a cancer of the lymphatic system.

Description

Hodgkin's disease, or Hodgkin's lymphoma, was first described in 1832 by Thomas Hodgkin, a British physician. Hodgkin clearly differentiated between this disease and the much more common non-Hodgkin's lymphomas. Prior to 1970, few individuals survived Hodgkin's disease. Now, however, the majority of individuals with this cancer can be cured.

The Lymphatic System

The lymphatic system is part of the body's immune system, for fighting disease, and a part of the blood-producing system. It includes the lymph vessels and nodes, and the spleen, bone marrow, and thymus. The narrow lymphatic vessels carry lymphatic fluid from throughout the body. The lymph nodes are small organs that filter the lymphatic fluid and trap foreign substances, including viruses, bacteria, and cancer cells. The spleen, in the upper left abdomen, removes old cells and debris from the blood. The bone marrow, the tissue inside the bones, produces new red and white blood cells.

Lymphocytes are white blood cells that recognize and destroy disease-causing organisms. Lymphocytes are produced in the lymph nodes, spleen, and bone marrow. They circulate throughout the body in the blood and lymphatic fluid. Clusters of immune cells also exist in major organs.

Hodgkin's Lymphoma

Hodgkin's disease is a type of lymphoma in which antibody-producing cells of the lymphatic system begin to grow abnormally. It usually begins in a lymph node and progresses slowly, in a fairly predictable way, spreading via the lymphatic vessels from one group of lymph nodes to the next. Sometimes it invades organs that are adjacent to the lymph nodes. If the cancer cells spread to the blood, the disease can reach almost any site in the body. Advanced cases of Hodgkin's disease may involve the spleen, liver, bone marrow, and lungs.

There are different subtypes of Hodgkin's disease:

• nodular sclerosis (30–60% of cases)
• mixed cellularity (20–40% of cases)
• lymphocyte predominant (5–10% of cases)
• lymphocyte depleted (less than 5% of cases)
• unclassified

Demographics

Hodgkin's disease can occur at any age. However, the majority of cases develop in early adulthood (ages 15–40) and late adulthood (after age 55). Approximately 10–15% of cases are in children under age 17. It is more common in boys than in girls under the age of 10. The disease is very rare in children under five.

Causes and Symptoms

The cause of Hodgkin's disease is not known. It is suspected that some interaction between an individual's genetic makeup, environmental exposures, and infectious agents may be responsible. Immune system deficiencies also may be involved.

Early symptoms of Hodgkin's disease may be similar to those of the flu:

• fevers, night sweats, chills
• fatigue
• loss of appetite (anorexia)
• weight loss
• itching
• pain after drinking alcoholic beverages
• swelling of one or more lymph nodes

Sudden or emergency symptoms of Hodgkin's disease include:

• sudden high fever
• loss of bladder and/or bowel control
• numbness in the arms and legs and a loss of strength

As lymph nodes swell, they may push on other structures, causing a variety of symptoms:

• pain due to pressure on nerve roots
• loss of function in muscle groups served by compressed nerves
• coughing or shortness of breath due to compression of the windpipe and/or airways, by swollen lymph nodes in the chest
• kidney failure from compression of the ureters, the tubes that carry urine from the kidneys to the bladder
• swelling in the face, neck, or legs, due to pressure on veins
• paralysis in the legs due to pressure on the spinal cord

As Hodgkin's disease progresses, the immune system becomes less effective at fighting infection. Thus, patients with Hodgkin's lymphoma become more susceptible to both common infections caused by bacteria and unusual (opportunistic) infections. Later symptoms of Hodgkin's disease include the formation of tumors.

Significantly, as many as 75% of individuals with Hodgkin's disease do not have any typical symptoms.

Diagnosis

As with many forms of cancer, diagnosis of Hodgkin's disease has two major components.

• identification of Hodgkin's lymphoma as the cause of the patient's disease
• staging of the disease to determine how far the cancer has spread

The initial diagnosis of Hodgkin's disease often results from abnormalities in a chest x ray that was performed because of nonspecific symptoms. The physician then takes a medical history to check for the presence of symptoms and conducts a complete physical examination.

Lymph Node Biopsy

The size, tenderness, firmness, and location of swollen lymph nodes are determined and correlated with any signs of infection. In particular, lymph nodes that do not shrink after treatment with antibiotics may be a cause for concern. The lymph nodes that are most often affected by Hodgkin's disease include those of the neck, above the collarbone, under the arms, and in the chest above the diaphragm.

Diagnosis of Hodgkin's disease requires either the removal of an entire enlarged lymph node (an excisional biopsy) or an incisional biopsy, in which only a small part of a large tumor is removed. If the node is near the skin, the biopsy is performed with a local anesthetic. However, if it is inside the chest or abdomen, general anesthesia is required.

The sample of biopsied tissue is examined under a microscope. Giant cells called Reed-Sternberg cells must be present to confirm a diagnosis of Hodgkin's disease. These cells, which usually contain two or more nuclei, are named for the two pathologists who discovered them. Normal cells have only one nucleus (the organelle within the cell that contains the genetic material). Affected lymph nodes may contain only a few Reed-Sternberg cells and they may be difficult to recognize. Characteristics of other types of cells in the biopsied tissue help to diagnose the subtype of Hodgkin's disease.

A fine needle aspiration (FNA) biopsy, in which a thin needle and syringe are used to remove a small amount of fluid and bits of tissue from a tumor, has the advantage of not requiring surgery. An FNA may be performed prior to an excisional or incisional biopsy, to check for infection or for the spread of cancer from another organ. However an FNA biopsy does not provide enough tissue to diagnose Hodgkin's disease.

Occasionally, additional biopsies are required to diagnose Hodgkin's disease. In rare instances, other tests, that detect certain substances on the surfaces of cancer cells or changes in the DNA of cells, are used to distinguish Hodgkin's disease from non-Hodgkin's lymphoma.

Clinical Staging

Staging is very important in Hodgkin's disease. This is because the cancer usually spreads in a predictable pattern, without skipping sets of lymph nodes until late in the progression of the disease.

Imaging

Imaging of the abdomen, chest, and pelvis is used to identify areas of enlarged lymph nodes and abnormalities in the spleen or other organs. Computed tomography (CT or CAT) scans use a rotating x-ray beam to obtain pictures. Magnetic resonance imaging (MRI) uses magnetic fields and radio waves to produce images of the body. Chest x rays also may be taken. These images will reveal rounded lumps called nodules in the affected lymph nodes and other organs.

Another imaging technique for Hodgkin's disease is a gallium scan, in which the radioactive element gallium is injected into a vein. The cancer cells take up the gallium and a special camera that detects the gallium is used to determine the location and size of tumors. Gallium scans are used when Hodgkin's disease is in the chest and may be hard to detect by other methods. Gallium scans also are used to monitor progress during treatment.

A lymphangiogram, a radiograph of the lymphatic vessels, involves injecting a dye into a lymphatic vessel in the foot. Tracking of the dye locates the disease in the abdomen and pelvis. This method is used less frequently and is usually not used with children.

Positron emission tomography (PET) scans are an extremely accurate method for staging Hodgkin's disease. A very low dose of radioactive glucose, a sugar, is injected into the body. The glucose travels to metabolically active sites, including cancerous regions that require large amounts of glucose. The PET scan detects the radioactivity and produces images of the entire body that distinguish between cancerous and non-cancerous tissues.

BONE MARROW Anemia (a low red-blood-cell count), fevers, or night sweats are indications that Hodgkin's disease may be in the bone marrow. In these cases, a bone marrow aspiration and biopsy may be ordered. In biopsy, a large needle is used to remove a narrow, cylindrical piece of bone. Alternatively, an aspiration, in which a needle is used to remove small bits of bone marrow, may be used. The marrow usually is removed from the back of the hip or other large bone. This procedure may help to determine cancer spread.

Pathological Staging

Sometimes further staging, called pathological staging or a staging laparotomy, is used for Hodgkin's disease. In this operation, a surgeon checks the abdominal lymph nodes and other organs for cancer and removes small pieces of tissue. A pathologist examines the tissue samples for Hodgkin's disease cells. Usually the spleen is removed (a splenectomy) during the laparotomy. The splenectomy helps with staging Hodgkin's disease, as well as removing a disease site.

Treatment Team

The cancer care team for Hodgkin's disease includes a medical oncologist (a physician specializing in cancer), oncology nurses, technicians, and social workers. A surgeon performs the biopsies, as well as the laparotomy and splenectomy if required. Pathologists examine the biopsy specimens for the presence of Reed-Sternberg and other abnormal cells.

In the United States, most children with Hodgkin's disease are treated at children's cancer centers. Here, the treatment team includes psychologists, child life specialists, nutritionists, and educators, as well as a pediatric oncologist.

Clinical Staging, Treatments, and Prognosis

The Stages

All of the available treatments for Hodgkin's disease have serious side effects, both short and long-term. However, with accurate staging, physicians and patients often can choose the minimum treatment that will cure the disease. The staging system for Hodgkin's disease is the Ann Arbor Staging Classification, also called the Cotswold System or the Revised Ann Arbor System.

Hodgkin's disease is divided into four stages, with additional substages:

• Stage I: The disease is confined to one lymph node area
• Stage IE: The disease extends from the one lymph node area to adjacent regions
• Stage II: The disease is in two or more lymph node areas on one side of the diaphragm (the muscle below the lungs)
• Stage IIE: The disease extends to adjacent regions of at least one of these nodes
• Stage III: The disease is in lymph node areas on both sides of the diaphragm
• Stage IIIE/IIISE: The disease extends into adjacent areas or organs (IIIE) and/or the spleen (IIISE)
• Stage IV: The disease has spread from the lymphatic system to one or more other organs, such as the bone marrow or liver

Treatment for Hodgkin's disease depends both on the stage of the disease and whether or not symptoms are present. Stages are labeled with an A if no symptoms are present. If symptoms are present, the stage is labeled with a B. These symptoms include:

• loss of more than 10% of body weight over the previous six months
• fevers above 100 degrees F
• drenching night sweats

Treatments

RADIATION THERAPY Radiation therapy and/or chemotherapy (drug therapy) are the standard treatments for Hodgkin's disease. If the disease is confined to one area of the body, radiotherapy is usually used. This treatment, with x rays or other high-energy rays, also is used when the disease is in bulky areas such as the chest, where chemotherapeutic drugs cannot reach all of the cancer. External-beam radiation, a focused beam from an external machine, is used to irradiate only the affected lymph nodes. This procedure is called involved field radiation.

More advanced stages of Hodgkin's disease may be treated with mantle field radiation, in which the lymph nodes of the neck, chest, and underarms are irradiated. Inverted Y field radiation is used to irradiate the spleen and the lymph nodes in the upper abdomen and pelvis. Total nodal irradiation includes both mantle field and inverted Y field radiation.

Since external-beam radiation damages healthy tissue near the cancer cells, the temporary side effects of radiotherapy can include sunburn-like skin damage, fatigue, nausea, and diarrhea. Other temporary side effects may include a sore throat and difficulty swallowing. Long-term side effects depend on the dose and the location of the radiation and the age of the patient. Since radiation of the ovaries causes permanent sterility (the inability to have offspring), the ovaries of girls and young women are protected during radiotherapy. Sometimes the ovaries are surgically moved from the region to be irradiated.

CHEMOTHERAPY If the Hodgkin's disease has progressed to additional lymph nodes or other organs, or if there is a recurrence of the disease within two years of radiation treatment, chemotherapy is used.

Chemotherapy utilizes a combination of drugs, each of which kills cancer cells in a different way. The most common chemotherapy regimens for Hodgkin's disease are MOPP (either mechlorethamine or methotrexate with Oncovin, procarbazine, prednisone) and ABVD (Adriamycin or doxorubicin, bleomycin, vincristine, dacarbazine). Each of these consists of four different drugs. ABVD is used more frequently than MOPP because it has fewer severe side effects. However MOPP is used for individuals who are at risk for heart failure. The chemotherapeutic drugs may be injected into a vein or muscle, or taken orally, as a pill or liquid.

Children who are sexually mature when they develop Hodgkin's disease, and whose muscle and bone mass are almost completely developed, usually receive the same treatment as adults. Younger children usually are treated with chemotherapy, since radiation will adversely affect bone and muscle growth. However, radiation may be used in low dosages, in combination with chemotherapy. The chemotherapy for children with Hodgkin's disease usually includes more drugs than ABVD and MOPP.

The side effects of chemotherapy for Hodgkin's disease depend on the dose of drugs and the length of time they are taken. Since these drugs target rapidly dividing cancer cells, they also affect normal cells that grow rapidly. These include the cells of the bone marrow, the linings of the mouth and intestines, and hair follicles. Damage to bone marrow leads to lower white blood cell counts and lower resistance to infection. It also leads to lower red blood cell counts that can result in fatigue and easy bleeding and bruising. Damage to intestinal cells leads to a loss of appetite (anorexia), and nausea and vomiting. Mouth sores and hair loss (alopecia) also are common side effects of chemotherapy. These side effects disappear when the chemotherapy is discontinued. Some drugs can reduce or prevent the nausea and vomiting.

Chemotherapy for Hodgkin's disease may lead to long-term complications. The drugs may damage the heart, lungs, kidneys, and liver. In children, growth may be impeded. Some chemotherapy can cause sterility, so men may choose to have their sperm frozen prior to treatment. Women may stop ovulating and menstruating during chemotherapy. This may or may not be permanent.

Treatment for higher-stage Hodgkin's disease often involves a combination of radiotherapy and chemotherapy. Following three or four chemotherapy regimens, involved field radiation may be directed at the most affected areas of the body. The long-term side effects often are more severe when radiation and chemotherapy are used in combination.

The development of a second type of cancer is the most serious risk from radiation and chemotherapy treatment for Hodgkin's disease. In particular, there is a risk of developing leukemia, breast cancer, bone cancer, or thyroid cancer. Chemotherapy, particularly MOPP, or chemotherapy in conjunction with radiotherapy, significantly increases the risk for leukemia.

Resistant, Progressive, and Recurrent Hodgkin's Disease

Following treatment, the original diagnostic tests for Hodgkin's disease are repeated, to determine whether all traces of the cancer have been eliminated and to check for long-term side effects of treatment. In resistant Hodgkin's disease, some cancer cells remain following treatment. If the cancer continues to spread during treatment, it is called progressive Hodgkin's disease. If the disease returns after treatment, it is known as recurrent Hodgkin's disease. It may recur in the area where it first started or elsewhere in the body. It may recur immediately after treatment or many years later.

Additional treatment is necessary with these types of Hodgkin's disease. If the initial treatment was radiation therapy alone, chemotherapy may be used, or vice versa. Chemotherapy with different drugs, or higher doses, may be used to treat recurrent Hodgkin's. However, radiation to the same area is never repeated.

Bone Marrow and Peripheral Blood Stem Cell Transplantations

An autologous bone marrow and/or a peripheral blood stem cell transplantation (PBSCT) often is recommended for treating resistant or recurrent Hodgkin's disease, particularly if the disease recurs within a few months of a chemotherapy-induced remission. These transplants are autologous because they utilize the individual's own cells. The patient's bone marrow cells or peripheral blood stem cells (immature bone marrow cells found in the blood) are collected and frozen prior to high-dosage chemotherapy, which destroys bone marrow cells. A procedure called leukapheresis is used to collect the stem cells. Following the high-dosage chemotherapy, and possibly radiation, the bone marrow cells or stem cells are reinjected into the individual.

Alternative and Complementary Therapies

Most complementary therapies for Hodgkin's disease are designed to stimulate the immune system to destroy cancer cells and repair normal cells that have been damaged by treatment. These therapies are used in conjunction with standard treatment.

Immunologic therapies, also known as immunotherapies, biological therapies, or biological response modifier therapies, utilize substances that are produced by the immune system. These include interferon (an immune system protein), monoclonal antibodies (specially engineered antibodies), colony-stimulating (growth) factors (such as filgrastim), and vaccines. Many immunotherapies for Hodgkin's disease are experimental and available only through clinical trials. These biological agents may have side effects.

Coenzyme Q10 (CoQ10) and polysaccharide K (PSK) are being evaluated for their ability to stimulate the immune system and protect healthy tissue, as well as possible anti-cancer activities. Camphor, also known as 714-X, green tea, and hoxsey (which is a mixture of a number of substances), have been promoted as immune system enhancers. However there is no evidence that they are effective against Hodgkin's disease. Hoxsey, in particular, can produce serious side effects.

Prognosis

Hodgkin's disease, particularly in children, is one of the most curable forms of cancer. Approximately 90% of individuals are cured of the disease with chemotherapy and/or radiation.

The one-year relative survival rate following treatment for Hodgkin's disease is 93%. Relative survival rates do not include individuals who die of causes other than Hodgkin's disease. The percentage of individuals who have not died of Hodgkin's disease within five years of diagnosis is 90–95% for those with stage I or stage II disease. The figure is 85–90% for those diagnosed with stage III Hodgkin's and approximately 80% for those diagnosed with stage IV disease. The 15-year relative survival rate is 63%. Approximately 75% of children are alive and cancer free 20 years after the original diagnosis of Hodgkin's.

Acute myelocytic leukemia, a very serious cancer, may develop in as many as 2–6% of individuals receiving certain types of treatment for Hodgkin's disease. Women under the age of 30 who are treated with radiation to the chest have a much higher risk for developing breast cancer. Both men and women are at higher risk for developing lung or thyroid cancers as a result of chest irradiation.

Individuals with the type of Hodgkin's disease known as nodular lymphocytic predominance have a 2% chance of developing non-Hodgkin's lymphoma. Apparently, this is a result of the Hodgkin's disease itself and not the treatment.

Coping With Cancer Treatment

Sufficient rest and good nutrition are important for relieving the side effects of treatment for Hodgkin's disease. As strength returns, a weekly exercise routine should be initiated. Support groups can be beneficial for helping with emotional problems that may arise during treatment.

Clinical Trials

At least 115 clinical trials for the treatment of Hodgkin's disease were recruiting or planning to recruit participants. A number of these studies are directed at treating resistant (refractory) or recurrent (relapsed) Hodgkin's disease in both children and adults. Some are aimed at specific stages or subtypes of Hodgkin's disease. Some trials are for previously treated individuals and others are for those who have not yet received treatment.

Questions to Ask the Doctor

• What type of Hodgkin's disease do I have?
• What is the stage of my disease?
• What are the choices for treatment and what do you recommend?
• Should I obtain a second opinion?
• What are the short-term side effects of the treatment and what can be done about them?
• What are the possible long-term side effects of the treatment?
• Are there other risks from the treatment?
• How should I prepare for the treatment?
• How long will the treatment continue?
• What is the recovery time following the treatment?
• What are the chances of success?
• Are there clinical trials which may be appropriate for me?
• Are there complementary or alternative therapies that may be helpful?
• What is the likelihood that the cancer will return? How will a recurrence be diagnosed?
• Is a recurrence more likely with one treatment than with another?

Clinical trials of new treatments for Hodgkin's disease include:

• new drugs
• new chemotherapies
• monoclonal antibody therapy
• interferon, interleukin-2, and interleukin-12
• a vaccine made from cancer cells that contain the Epstein-Barr virus
• bone marrow and umbilical cord blood transplantations
• PBSCT
• various combinations of treatments

There also are ongoing genetic studies of children and adults with Hodgkin's disease and quality-of-life studies of children who are undergoing treatment.

Prevention

There are very few known risk factors for Hodgkin's disease. A family history of the disease and the presence of the Epstein-Barr virus are associated with an increased risk. Individuals with acquired immunodeficiency syndrome (AIDS) are particularly susceptible to Hodgkin's disease.

Special Concerns

Follow-up examinations continue for many years following treatment for Hodgkin's disease. Women who have had chest irradiation must have frequent mammograms and clinical and breast self examinations for early detection of breast cancer. Frequent physical exams and chest x rays may help to detect lung or thyroid cancer. Treatment with mantle field radiation causes hyperthyroidism, which requires thyroid medication and annual thyroid function tests.

Individuals with Hodgkin's disease do not have normal immune system function, a problem that can be intensified by chemotherapy, radiation, and removal of the spleen. Therefore, vaccinations and prompt treatment of infections are very important.

Resources

Books

Mauch, Peter M., et al., editors. Hodgkin's Disease. Philadelphia: Lippincott Williams & Wilkins, 1999.

Organizations

American Cancer Society. (800) ACS-2345. . Provides information, funds for cancer research, prevention programs, and patient services, including education and support programs for patients and families, temporary accommodations for patients, and camps for children with cancer.

ClinicalTrials.gov. U. S. National Library of Medicine. National Institutes of Health. 8600 Rockville Pike, Bethesda, MD 20894. . Information about clinical trials involving Hodgkin's disease.

Cure for Lymphoma Foundation. 215 Lexington Avenue, New York, NY 10016. (212) 213-9595. (800)-CFL-6848. infocfl@cfl.org. . An advocacy organization that provides education and support programs, research grants, and information on clinical trials for Hodgkin's and non-Hodgkin's lymphomas.

The Leukemia and Lymphoma Society. 600 Third Avenue, New York, NY 10016. (800) 955-4572. (914) 949-5213. Provides information, support, and guidance to patients and health care professionals.

The Lymphoma Research Foundation of America, Inc. 8800 Venice Boulevard, Suite 207, Los Angeles, CA 90034. (310) 204-7040). . Supports research into treatments for lymphoma and provides educational and emotional support programs for patients and families.

National Cancer Institute. Public Inquiries Office, Building 31, Room 10A31, 31 Center Drive, MSC 2580, Bethesda, MD 20892-2580. (800)-4-CANCER. . . Provides information on cancer and on clinical trials; conducts cancer research.

Other

FS-8-Complementary and Alternative Therapies for Leukemia, Lymphoma, Hodgkin's Disease, and Myeloma. The Leukemia and Lymphoma Society. [cited Mar.27, 2005]. .

"Hodgkin's Disease." CancerNet. National Cancer Institute. NIH Publication No. 99-1555. [cited Mar.27, 2005]. >http://cancernet.nci.nih.gov/wyntk_pubs/hodgkins.htm>.

"Hodgkin's Disease." Cancer Resource Center. 10 Dec. 1999. American Cancer Society. [cited Mar. 27, 2005]. .

"Hodgkin's Lymphoma." Diseases & Conditions. MayoClinic.com. [cited Mar. 27, 2005]. .

National Cancer Society. "NCI/PDQ Patient Statement: Adult Hodgkin's Disease." Oncolink. Nov. 2000. University of Pennsylvania Cancer Center. [cited Mar. 27, 2005]. .

National Cancer Society. "NCI/PDQ Patient Statement: Childhood Hodgkin's Disease." Oncolink. Feb. 2001. University of Pennsylvania Cancer Center. [cited Mar. 27, 2005]. .

"PET Scans Help Doctors Treat Hodgkin's Disease." ACS News Today. American Cancer Society. [cited Mar. 27, 2005]. .

—Rosalyn S. Carson-DeWitt, M.D.; Margaret Alic, Ph.D.

A malignant lymphoid neoplasm, usually arising in lymph nodes characterized by morphological heterogeneity and bizarre giant tumor cells referred to as Reed-Sternberg cells. The etiology of Hodgkin's disease is unknown, although current epidemiological data suggest an infectious (viral) etiology.

Persons with Hodgkin's disease usually seek medical advice because of enlarged painless lymph nodes. They may also have fever, weight loss, anorexia, pruritus, and anemia. The clinical extent of the disease is determined by a process of staging based on physical examination, various biopsies, and usually a laparotomy for examination of the spleen and liver.

Hodgkin's disease more commonly affects males than females, except for the nodular sclerosing variety, which occurs with equal frequency in both sexes. It generally is a disease of persons between the ages of 20 and 40, but it may affect the very young and the very old. Characteristically, persons with Hodgkin's disease exhibit a loss of cell-mediated immunity and become susceptible hosts for infection with a variety of microorganisms such as tubercle bacilli.

The treatment of Hodgkin's disease is dependent on its clinical stage and microscopic appearance. A combination of chemotherapy and radiation therapy is commonly used. See also Lymphatic system.

A generally fatal lymphomatous disorder of unknown etiology that has neoplastic and granulomatous characteristics. Chiefly involves the lymph nodes, but sometimes the spleen, liver, bone marrow, and other organs are involved as well. Three variants include Hodgkin’s paragranuloma, Hodgkin’s granuloma (classical or common type), and Hodgkin’s sarcoma. All have in common the presence of Sternberg-Reed, or Dorothy Reed, cells and lymph node enlargement. Cervical lymph nodes are often the first to be affected. See also cell, Sternberg-Reed.

Hodgkin’s disease. (Seidel/Ball/Dains/Bene-dict, 2003)

Definition

Hodgkin's disease, also called Hodgkin's lymphoma, is a type of cancer involving tissues of the lymphatic system, or lymph nodes. Its cause is unknown, although some interaction between individual genetic makeup, family history, environmental exposures, and infectious agents is suspected.

Description

Hodgkin's lymphoma can occur at any age, although the majority of these lymphomas occur in people aged 15–34, and over the age of 60. Lymphoma is a cancer of the lymphatic system. Depending on the specific type, a lymphoma can have any or all of the characteristics of cancer: rapid multiplication of cells, abnormal cell types, loss of normal arrangement of cells with respect to one another, and invasive ability.

Causes & Symptoms

Hodgkin's lymphoma usually begins in a lymph node. The node enlarges and—similar to enlarged lymph nodes due to infectious causes—may or may not cause any pain. Hodgkin's lymphoma progresses in a fairly predictable way, traveling from one group of lymph nodes to another unless it is treated. More advanced cases of Hodgkin's involve the spleen, liver, and bone marrow.

The features and prognosis of patients with Hodgkin's disease and non-Hodgkin's lymphoma (NHL) differ significantly. However, research in 2001 found that among patients with human immunodeficiency virus (HIV), Hodgkin's disease appears very similar to HIV-related non-Hodgkin's lymphoma. NHL occurs much more often in patients with HIV, but in recent years, a small but significant increase in Hodgkin's disease has been seen in HIV-infected patients.

Constitutional symptoms—symptoms that affect the whole body—are common. They include fever, weight loss, heavy sweating at night, and itching. Some patients note pain after drinking alcoholic beverages.

As the lymph nodes swell, they may push against nearby structures, resulting in other local symptoms. These symptoms include pain from pressure on nerve roots as well as loss of function of specific muscle groups served by the compressed nerves. Kidney failure may result from compression of the ureters, the tubes which carry urine from the kidneys to the bladder. The face, neck, or arms may swell due to pressure slowing the flow in veins that should drain blood from those regions (superior vena cava syndrome). Pressure on the spinal cord can result in leg paralysis. Compression of the trachea and/or bronchi (airways) can cause wheezing and shortness of breath. Masses in the liver can cause the accumulation of certain chemicals in the blood, resulting in jaundice—a yellowish discoloration of the skin and the whites of the eyes.

As Hodgkin's lymphoma progresses, a patient's immune system becomes less and less effective at fighting infection. Thus, patients with Hodgkin's lymphoma become increasingly more susceptible to both common infections caused by bacteria and unusual (opportunistic) infections caused by viruses, fungi, and protozoa.

Diagnosis

Diagnosis of Hodgkin's lymphoma requires the removal of a sample of a suspicious lymph node (biopsy) and careful examination of the tissue under a microscope. In Hodgkin's lymphoma, certain characteristic cells—Reed-Sternberg cells—must be present in order to confirm the diagnosis. These cells usually contain two or more nuclei—oval centrally-located structures within cells that house their genetic material. In addition to the identification of these Reed-Sternberg cells, other cells in the affected tissue sample are examined. The characteristics of these other cells help to classify the specific subtype of Hodgkin's lymphoma.

Once Hodgkin's disease has been diagnosed, staging is the next important step. Staging involves computed tomography (CT) scans of the abdomen, chest, and pelvis, to identify areas of lymph node involvement. In rare cases, a patient must undergo abdominal surgery so that lymph nodes in the abdominal area can be biopsied (staging laparotomy). Some patients have their spleens removed during this surgery, both to help with staging and to remove a focus of the disease. Bone marrow biopsy is also required unless there is obvious evidence of vital organ involvement. Some physicians also order a lymphangiogram—a radiograph of the lymphatic vessels.

Staging is important because it helps to determine what kind of treatment a patient should receive. On one hand, it is important to understand the stage of the disease so that the treatment chosen is sufficiently strong to provide the patient with a cure. On the other hand, all the available treatments have serious side effects, so staging allows the patient to have the type of treatment necessary to achieve a cure, and to minimize the severity of short and long-term side effects from which the patient may suffer.

Treatment

Hodgkin's disease is a life-threatening disease. A correct diagnosis and appropriate treatment with surgery, chemotherapy, and/or radiation therapy are critical to controlling the illness.

Acupuncture, ypnotherapy, and guided imagery may be useful tools in treating pain symptoms associated with Hodgkin's. Acupuncture involves the placement of a series of thin needles into the skin at targeted locations on the body known as acupoints in order to harmonize the energy flow within the human body.

In guided imagery, the patient creates pleasant and comfortable mental images that promote relaxation and improve a patient's ability to cope with discomfort and pain symptoms. Other guided imagery techniques involve creating a visual mental image of the pain. Once the pain can be visualized, the patient can adjust the image to make it more pleasing and thus more manageable.

A number of herbal remedies are also available to lessen pain symptoms and promote relaxation and healing. However, individuals should consult with their healthcare professionals before taking them. Depending on the preparation and the type of herb, these remedies may interact with or enhance the effects of other prescribed medications.

Allopathic Treatment

Treatment of Hodgkin's lymphoma has become increasingly effective over the years. The type of treatment used for Hodgkin's depends on the information obtained by staging, and may include chemotherapy (treatment with a combination of drugs), and/or radiotherapy (treatment with radiation to kill cancer cells).

Both chemotherapy and radiation therapy have unfortunate side effects. Chemotherapy can result in nausea, vomiting,

hair loss, and increased susceptibility to infection. Radiation therapy can cause sore throat, difficulty in swallowing, diarrhea, and growth abnormalities in children. Both forms of treatment, especially in combination, can result in sterility (the permanent inability to have offspring), as well as heart and lung damage. A 2003 study showed a link between radiation therapy for Hodgkin's disease and increased risk for later breast cancer. However, adding chemotherapy to the regimen decreased the chance for breast cancer, perhaps by inducing premature menopause.

Expected Results

Hodgkin's is one of the most curable forms of cancer. Current treatments are quite effective, especially with early diagnosis. Children have a particularly high rate of cure from the disease, with about 75% still living cancer-free 20 years after their original diagnosis. Adults with the most severe form of the disease have about a 50% cure rate. In 2003, new research noted that even after complete remission, some patients showed signs of thyroid dysfunction, most likely from the immune problems caused by Hodgkin's disease. The researchers recommended thyroid examinations every year during follow-up of the disease.

Prevention

While Hodgkin's disease cannot be prevented, researchers continue to study risk factors for the disease. In 2003, a study showed a possible link between exposure to the measles virus around the time of pregnancy or birth. As research continues, these and other discoveries may help people control certain risk factors for Hodgkin's disease and other cancers.

Resources

Books

Dollinger, Malin, et al. Everyone's Guide to Cancer Therapy. Kansas City, MO: Andrews McMeel Publishing, 1997.

Freedman, Arnold S. and Lee M. Nadler. "Hodgkin's Disease." In Harrison's Principles of Internal Medicine, edited by Anthony S. Fauci, et al. New York: McGraw-Hill, 1998.

Periodicals

"Chemotherapy May Suppress Breast Cancer Risk in Hodgkin Disease Survivors." Women's Health Weekly (July 31, 2003): 52.

"HIV-Positive Hodgkin Patients' Disease Looks Like NHL." Cancer Weekly (December 18, 2001):22.

"The Risk of Hodgkin Disease May be Association with Exposure to Infections." Blood Weekly (June 12, 2003):10.

"Thyroid Should be Examined Once a Year During Follow-up for Hodgkin Disease." Clinical Trials Week (March 24, 2003): 70.

Organizations

The Lymphoma Research Foundation of America, Inc. 8800 Venice Boulevard, Suite 207, Los Angeles, CA 90034. (310) 204-7040. http://www.lymphoma.org.

[Article by: Paula Ford-Martin; Teresa G. Odle]

A chronic disease in which the lymph nodes, spleen, and liver become enlarged. The disease, whose cause is still unknown, can spread throughout other tissues and organs of the body and cause death if not treated at an early stage. Many view Hodgkin's disease as a form of cancer affecting the lymphatic system; for this reason, radiation and chemotherapy are often used in treating it.

A primary lymph node neoplastic disease of humans. Rarely in animals, mainly dogs, do lymphoid neoplasms satisfy the criteria, e.g. Reed–Sternberg cells, for diagnosis as Hodgkin's lymphoma.

Hodgkin lymphoma
Classification and external resources
Lymph node biopsy showing Hodgkin's lymphoma.
ICD-10	C81.
ICD-9	201
ICD-O:	9650/3-9667/3
DiseasesDB	5973
MedlinePlus	000580
eMedicine	med/1022
MeSH	D006689

Hodgkin's lymphoma, previously known as Hodgkin's disease, is a type of lymphoma, which is a type of cancer originating from white blood cells called lymphocytes. It was named after Thomas Hodgkin, who first described abnormalities in the lymph system in 1832.^[1][2] Hodgkin's lymphoma is characterized by the orderly spread of disease from one lymph node group to another, and by the development of systemic symptoms with advanced disease. The disease is characterized by the presence of Reed-Sternberg cells (RS cells) on microscopic examination. Hodgkin's lymphoma was one of the first cancers which could be treated using radiation therapy and, later, it was one of the first to be treated by combination chemotherapy.

The disease occurrence shows two peaks: the first in young adulthood (age 15–35) and the second in those over 55 years old.^[3]

The survival rate is generally 90% or higher when the disease is detected during early stages, making it one of the more curable forms of cancer.^[4] Hodgkin's lymphoma is one of the handful of cancers that, even in its later stages, has a very high cure rate, in the 90's.^[5] Most patients who are able to be successfully treated and thus enter remission generally go on and live long lives.

Contents 1 Classification 1.1 Types 1.2 Staging 2 Signs and symptoms 3 Cause 4 Pathogenesis 5 Diagnosis 5.1 Pathology 6 Management 7 Prognosis 8 Epidemiology 9 History 10 Society and culture 10.1 Notable cases 10.2 Cultural references 11 See also 12 References 13 External links

Classification

Types

Classical Hodgkin's lymphoma (excluding nodular lymphocyte predominant Hodgkin's lymphoma) can be subclassified into 4 pathologic subtypes based upon Reed-Sternberg cell morphology and the composition of the reactive cell infiltrate seen in the lymph node biopsy specimen (the cell composition around the Reed-Stenberg cell(s)).

Name	Description	ICD-10	ICD-O
Nodular sclerosing CHL	Is the most common subtype and is composed of large tumor nodules showing scattered lacunar classical RS cells set in a background of reactive lymphocytes, eosinophils and plasma cells with varying degress of collagen fibrosis/sclerosis.	C81.1	M9663/3
Mixed-cellularity subtype	Is a common subtype and is composed of numerous classic RS cells admixed with numerous inflammatory cells including lymphocytes, histiocytes, eosinophils, and plasma cells. without sclerosis. This type is most often associated with EBV infection and may be confused with the early, so-called 'cellular' phase of nodular sclerosing CHL.	C81.2	M9652/3.
Lymphocyte-rich	Is a rare subtype, show many features which may cause diagnostic confusion with nodular lymphocyte predominant B-cell Non-Hodgkin's Lymphoma (B-NHL).	C81.0	M9651/3
Lymphocyte depleted	Is a rare subtype, composed of large numbers of often pleomorphic RS cells with only few reactive lymphocytes which may easily be confused with diffuse large cell lymphoma. Many cases previously classified within this category would now be reclassified under anaplastic large cell lymphoma.[6]	C81.3	M9653/3
Unspecified		C81.9	M9650/3

Nodular lymphocyte predominant Hodgkin's lymphoma expresses CD20, and is not currently considered a form of classical Hodgkin's.

For the other forms, although the traditional B cell markers (such as CD20) are not expressed on all cells,^[6] Reed-Sternberg cells are usually of B cell origin.^[7][8] Although Hodgkin's is now frequently grouped with other B cell malignancies, some T cell markers (such as CD2 and CD4) are occasionally expressed.^[9] However, this may be an artifact of the ambiguity inherent in the diagnosis.

Hodgkin's cells produce Interleukin-21 (IL-21), which was once thought to be exclusive to T cells. This feature may explain the behavior of classical Hodgkin's lymphoma, including clusters of other immune cells gathered around HL cells (infiltrate) in cultures.^[10]

Staging

The staging is the same for both Hodgkin as well as non-Hodgkin lymphoma.

After Hodgkin's lymphoma is diagnosed, a patient will be staged: that is, they will undergo a series of tests and procedures that will determine what areas of the body are affected. These procedures will include documentation of their histology, a physical examination, blood tests, chest X-ray radiographs, computed tomography (CT) scans or magnetic resonance imaging (MRI) scans of the chest, abdomen and pelvis, and a bone marrow biopsy. Positron emission tomography (PET) scan is now used instead of the gallium scan for staging. In the past, a lymphangiogram or surgical laparotomy (which involves opening the abdominal cavity and visually inspecting for tumors) were performed. Lymphangiograms or laparotomies are very rarely performed, having been supplanted by improvements in imaging with the CT scan and PET scan.

On the basis of this staging, the patient will be classified according to a staging classification (the Ann Arbor staging classification scheme is a common one):

• Stage I is involvement of a single lymph node region (I) or single extralymphatic site (Ie);
• Stage II is involvement of two or more lymph node regions on the same side of the diaphragm (II) or of one lymph node region and a contiguous extralymphatic site (IIe);
• Stage III is involvement of lymph node regions on both sides of the diaphragm, which may include the spleen (IIIs) and/or limited contiguous extralymphatic organ or site (IIIe, IIIes);
• Stage IV is disseminated involvement of one or more extralymphatic organs.

The absence of systemic symptoms is signified by adding 'A' to the stage; the presence of systemic symptoms is signified by adding 'B' to the stage. For localized extranodal extension from mass of nodes that does not advance the stage, subscript 'E' is added.

Signs and symptoms

Patients with Hodgkin lymphoma may present with the following symptoms:

• Night Sweats

• Unexplained weight loss

• Lymph nodes: the most common symptom of Hodgkin's is the painless enlargement of one or more lymph nodes. The nodes may also feel rubbery and swollen when examined. The nodes of the neck and shoulders (cervical and supraclavicular) are most frequently involved (80–90% of the time, on average). The lymph nodes of the chest are often affected, and these may be noticed on a chest radiograph.

• Splenomegaly: enlargement of the spleen occurs in about 30% of people with Hodgkin's lymphoma. The enlargement, however, is seldom massive and the size of the spleen may fluctuate during the course of treatment.
• Hepatomegaly: enlargement of the liver, due to liver involvement, is present in about 5% of cases.
• Hepatosplenomegaly: the enlargement of both the liver and spleen caused by the same disease.
• Pain:
• Pain following alcohol consumption: classically, involved nodes are painful after alcohol consumption, though this phenomenon is very uncommon.^[11]
• Back pain: nonspecific back pain (pain that cannot be localized or its cause determined by examination or scanning techniques) has been reported in some cases of Hodgkin lymphoma. The lower back is most often affected.^{[citation needed]}
• Red-coloured patches on the skin, easy bleeding and petechiae due to low platelet count (as a result of bone marrow infiltration, increased trapping in the spleen etc – ie decreased production, increased removal)

• Systemic symptoms: about one-third of patients with Hodgkin's disease may also present with systemic symptoms, including low-grade fever; night sweats; unexplained weight loss of at least 10% of the patient's total body mass in six months or less, itchy skin (pruritus) due to increased levels of eosinophils in the bloodstream; or fatigue (lassitude). Systemic symptoms such as fever, night sweats, and weight loss are known as B symptoms; thus, presence of fever, weight loss, and night sweats indicate that the patient's stage is, for example, 2B instead of 2A.^[12]

• Cyclical fever: patients may also present with a cyclical high-grade fever known as the Pel-Ebstein fever,^[13] or more simply "P-E fever". However, there is debate as to whether or not the P-E fever truly exists^[14].

Cause

There are no guidelines for preventing Hodgkin lymphoma because the cause is unknown. A risk factor is something that statistically increases your chance of getting a disease or condition.

Risk factors include:^[15]

• Sex: male
• Ages: 15–40 and over 55
• Family history
• History of infectious mononucleosis or infection with Epstein-Barr virus, a causative agent of mononucleosis
• Weakened immune system, including infection with HIV or the presence of AIDS
• Prolonged use of human growth hormone

Pathogenesis

Diagnosis

Hodgkin lymphoma must be distinguished from non-cancerous causes of lymph node swelling (such as various infections) and from other types of cancer. Definitive diagnosis is by lymph node biopsy (Usually excisional biopsy with microscopic examination). Blood tests are also performed to assess function of major organs and to assess safety for chemotherapy. Positron emission tomography (PET) is used to detect small deposits that do not show on CT scanning. PET scans are also useful in functional imaging (by using a radiolabeled glucose to image tissues of high metabolism). In some cases a Gallium Scan may be used instead of a PET scan.^{[citation needed]}

Pathology

Macroscopy

Affected lymph nodes (most often, laterocervical lymph nodes) are enlarged, but their shape is preserved because the capsule is not invaded. Usually, the cut surface is white-grey and uniform; in some histological subtypes (e.g. nodular sclerosis) a nodular aspect may appear.

Microscopy

Microscopic examination of the lymph node biopsy reveals complete or partial effacement of the lymph node architecture by scattered large malignant cells known as Reed-Sternberg cells (RSC) (typical and variants) admixed within a reactive cell infiltrate composed of variable proportions of lymphocytes, histiocytes, eosinophils, and plasma cells. The Reed-Sternberg cells are identified as large often bi-nucleated cells with prominent nucleoli and an unusual CD45-, CD30+, CD15+/- immunophenotype. In approximately 50% of cases, the Reed-Sternberg cells are infected by the Epstein-Barr virus.

Characteristics of classic Reed-Sternberg cells include large size (20–50 micrometres), abundant, amphophilic, finely granular/homogeneous cytoplasm; two mirror-image nuclei (owl eyes) each with an eosinophilic nucleolus and a thick nuclear membrane (chromatin is distributed at the cell periphery).

Variants:

• Hodgkin cell (atypical mononuclear RSC) is a variant of RS cell, which has the same characteristics, but is mononucleated.
• Lacunar RSC is large, with a single hyperlobated nucleus, multiple, small nucleoli and eosinophilic cytoplasm which is retracted around the nucleus, creating an empty space ("lacunae").
• Pleomorphic RSC has multiple irregular nuclei.
• "Popcorn" RSC (lympho-histiocytic variant) is a small cell, with a very lobulated nucleus, small nucleoli.
• "Mummy" RSC has a compact nucleus, no nucleolus and basophilic cytoplasm.

Hodgkin's lymphoma can be sub-classified by histological type. The cell histology in Hodgkin's lymphoma is not as important as it is in non-Hodgkin's lymphoma: the treatment and prognosis in classic Hodgkin's lymphoma usually depends on the stage of disease rather than the histotype.

Management

Patients with early stage disease (IA or IIA) are effectively treated with radiation therapy or chemotherapy. The choice of treatment depends on the age, sex, bulk and the histological subtype of the disease. Patients with later disease (III, IVA, or IVB) are treated with combination chemotherapy alone. Patients of any stage with a large mass in the chest are usually treated with combined chemotherapy and radiation therapy.

ABVD	Stanford V	BEACOPP
Currently, the ABVD chemotherapy regimen is the gold standard for treatment of Hodgkin's disease. The abbreviation stands for the four drugs Adriamycin, bleomycin, vinblastine, and dacarbazine. Developed in Italy in the 1970s, the ABVD treatment typically takes between six and eight months, although longer treatments may be required.	Another form of treatment is the newer Stanford V regimen, which is typically only half as long as the ABVD but which involves a more intensive chemotherapy schedule and incorporates radiation therapy. However, in a randomized controlled study, Stanford V was inferior.[16]	Another form of treatment, mainly in Europe for stages > II is BEACOPP. The cure rate with the BEACOPP esc. regimen is approximately 10–15% higher than with standard ABVD in advanced stages. Although this was shown in a landmark paper in The New England Journal of Medicine (Diehl et al.), the US physicians still favor ABVD, which may be because some physicians think that BEACOPP induces more secondary leukemia. However, this seems negligible compared to the higher cure rates. Also, BEACOPP is more expensive because of the requirement for concurrent treatment with GCSF to increase production of white blood cells. Currently, the German Hodgkin Study Group tests 8 cycles (8x) BEACOPP esc vs. 6x BEACOPP esc vs. 8x BEACOPP-14 baseline (HD15-trial).[17]
Doxorubicin	Doxorubicin	Doxorubicin
Bleomycin	Bleomycin	Bleomycin
Vinblastine	Vinblastine, Vincristine	Vincristine
Dacarbazine	Mechlorethamine	Cyclophosphamide, Procarbazine
	Etoposide	Etoposide
	Prednisone	Prednisone

It should be noted that the common non-Hodgkin's treatment, rituximab (which targets CD-20) is not used to treat Hodgkin's due to the lack of CD-20 surface antigens in Hodgkin's.

Although increased age is an adverse risk factor for Hodgkin's lymphoma, in general elderly patients without major comorbidities are sufficiently fit to tolerate standard therapy, and have a treatment outcome comparable to that of younger patients. However, the disease is a different entity in older patients and different considerations enter into treatment decisions. ^[18]

The high cure rates and long survival of many patients with Hodgkin's lymphoma has led to a high concern with late adverse effects of treatment, including cardiovascular disease and second malignancies such as acute leukemias, lymphomas, and solid tumors within the radiation therapy field. Most patients with early stage disease are now treated with abbreviated chemotherapy and involved-field radiation therapy rather than with radiation therapy alone. Clinical research strategies are exploring reduction of the duration of chemotherapy and dose and volume of radiation therapy in an attempt to reduce late morbidity and mortality of treatment while maintaining high cure rates. Hospitals are also treating those who respond quickly to chemotherapy with no radiation.

Prognosis

Treatment of Hodgkin's disease has been improving over the past few decades. Recent trials that have made use of new types of chemotherapy have indicated higher survival rates than have previously been seen. In one recent European trial, the 5-year survival rate for those patients with a favorable prognosis was 98%, while that for patients with worse outlooks was at least 85%.^[4]

In 1998, an international effort^[19] identified seven prognostic factors that accurately predict the success rate of conventional treatment in patients with locally extensive or advanced stage Hodgkin's lymphoma. Freedom from progression (FFP) at 5 years was directly related to the number of factors present in a patient. The 5-year FFP for patients with zero factors is 84%. Each additional factor lowers the 5-year FFP rate by 7%, such that the 5-year FFP for a patient with 5 or more factors is 42%.

The adverse prognostic factors identified in the international study are:

• Age >= 45 years
• Stage IV disease
• Hemoglobin < 10.5 g/dl
• Lymphocyte count < 600/µl or < 8%
• Male
• Albumin < 4.0 g/dl
• White blood count >= 15,000/µl

Other studies have reported the following to be the most important adverse prognostic factors: mixed-cellularity or lymphocyte-depleted histologies, male sex, large number of involved nodal sites, advanced stage, age of 40 years or more, the presence of B symptoms, high erythrocyte sedimentation rate, and bulky disease (widening of the mediastinum by more than one third, or the presence of a nodal mass measuring more than 10 cm in any dimension.)

Epidemiology

Age-standardized death from lymphomas and multiple myeloma per 100,000 inhabitants in 2004.^[20]

     no data      less than 1.8      1.8-3.6      3.6-5.4      5.4-7.2      7.2-9      9-10.8      10.8-12.6      12.6-14.4      14.4-16.2      16.2-18      18-19.8      more than 19.8

Unlike some other lymphomas, whose incidence increases with age, Hodgkin lymphoma has a bimodal incidence curve; that is, it occurs most frequently in two separate age groups, the first being young adulthood (age 15–35) and the second being in those over 55 years old although these peaks may vary slightly with nationality.^[21] Overall, it is more common in males, except for the nodular sclerosis variant, which is slightly more common in females. The annual incidence of Hodgkin's lymphoma is about 1 in 25,000 people, and the disease accounts for slightly less than 1% of all cancers worldwide.

The incidence of Hodgkin lymphoma is increased in patients with HIV infection.^[22] In contrast to many other lymphomas associated with HIV infection it occurs most commonly in patients with higher CD4 T cell counts.

History

Hodgkin lymphoma was first described in an 1832 report by Thomas Hodgkin, although Hodgkin noted that perhaps the earliest reference to the condition was provided by Marcello Malpighi in 1666.^[1][2] While occupied as museum curator at Guy's Hospital, Hodgkin studied seven patients with painless lymph node enlargement. Of the seven cases, two were patients of Richard Bright, one was of Thomas Addison, and one was of Robert Carswell.^[1] Carswell's report of this seventh patient was accompanied by numerous illustrations that aided early descriptions of the disease.^[23]

Hodgkin's report on these seven patients, entitled "On some morbid appearances of the absorbent glands and spleen", was presented to the Medical and Chirurgical Society in London in January of 1832 and was subsequently published in the society's journal, Medical-Chirurgical Society Transactions.^[1] Hodgkin's paper went largely unnoticed, however, even despite Bright highlighting it in an 1838 publication.^[1] Indeed, Hodgkin himself did not view his contribution as particularly significant.^[24]

In 1856, Samuel Wilks independently reported on a series of patients with the same disease that Hodgkin had previously described.^[24] Wilks, a successor to Hodgkin at Guy's Hospital, was unaware of Hodgkin's prior work on the subject. Bright made Wilks aware of Hodgkin's contribution and in 1865, Wilks published a second paper, entitled "Cases of enlargement of the lymphatic glands and spleen", in which he called the disease "Hodgkin's disease" in honor of his predecessor.^[24]

Theodor Langhans and WS Greenfield first described the microscopic characteristics of Hodgkin lymphoma in 1872 and 1878, respectively.^[1] In 1898 and 1902, respectively, Carl Sternberg and Dorothy Reed independently described the cytogenetic features of the malignant cells of Hodgkin lymphoma, now called Reed-Sternberg cells.^[1]

Tissue specimens from Hodgkin's seven patients remained at Guy's Hospital for a number of years. Nearly 100 years after Hodgkin's initial publication, histopathologic reexamination confirmed Hodgkin lymphoma in only three of seven of these patients.^[24] The remaining cases included non-Hodgkin lymphoma, tuberculosis, and syphilis.^[24]

Society and culture

Notable cases

Wikinews has related news: Mother and son disappear after court orders cancer treatment Court rules teen must take chemotherapy

• Arlen Specter, US Senator from Pennsylvania, was first diagnosed with Stage 4 Hodgkin's disease in 2005 when he was 75 years old. He underwent chemotherapy treatments without missing a day of work in the US Senate, and subsequently wrote a book, "Never Give In" which chronicled his battle with Hodgkins. The cancer recurred in April, 2008, and he underwent 12 more chemotherapy treatments. In August, 2009, he continues to thrive at age 79.
• Howard Carter, Egyptologist and discoverer of the Tomb of Tutankhamum, died in 1939 from Hodgkin's disease^[25]

• Nancy Mitford, English writer, died of Hodgkin's disease in 1973
• Freida Riley, American school teacher, written about in Homer Hickam's Rocket Boys/October Sky, played by Laura Dern in film October Sky, died of Hodgkin's disease in 1969.
• Paul Allen, Microsoft co-founder, was diagnosed and treated for Hodgkin's lymphoma in 1983.^[26] He subsequently developed non-Hodgkin's lymphoma in November 2009^[27]
• Lynden David Hall died of Hodgkin's lymphoma in 2006.^[28]
• Martin Fry, UK frontman of the pop group ABC, treated for Hodgkin's in 1987.
• Delta Goodrem, Australian singer, was diagnosed with Hodgkin's lymphoma in July 2003^[29]
• Richard Harris, Irish actor, died from the condition in 2002
• Dinu Lipatti, the Romanian pianist, died of Hodgkin's disease in 1950, aged 33^[30]
• Mario Lemieux, National Hockey League superstar, was diagnosed with Hodgkin's lymphoma in 1993^[31]
• Luke Menard, a finalist on the seventh season of American Idol, was diagnosed with the disease after being voted off the show^{[citation needed]}
• Starchild Abraham Cherrix, a teenager whose refusal to finish his chemotherapy regimen resulted in a court battle^[32]
• Simon Poynton- Australian business man and cricket player, diagnosed October 2000. Cancer free for 9 years.
• Big John Studd, Wrestler John William Minton, died from the disease in 1995^[33]
• Brandon Tartikoff, American television executive, died from the disease in 1997
• Ethan Zohn, Won "Survivor: Africa"^[34]
• Daniel Hauser, whose mother fled with him in order to prevent him from undergoing chemotherapy.^[35]
• Roger Maris, hall of fame baseball player, died of this disease in 1984.

Cultural references

• A main character in the movie October Sky (and the book Rocket Boys), Miss Riley, was diagnosed with Hodgkin's lymphoma.
• In the film Erin Brockovich, Hodgkin's is mentioned as a malaise afflicting one of her clients.
• In the HBO movie 61*, Hodgkin's is mentioned as familial cause of early death.
• The documentary film Crazy Sexy Cancer mentions Hodgkin's.
• In the novel Don't Die, My Love, by Lurlene McDaniel, one of the main characters, Luke, is diagnosed with Hodgkin's and dies after about a year and a half.
• In the latter part of the television series Party of Five, Charlie Salinger (played by Matthew Fox), was diagnosed with Hodgkin's and, through rigorous regimens and treatments, went into remission.
• In the television show Curb your Enthusiasm episode "The Five Wood", Larry David believes his friend's father suffered from "the good Hodgkin's," and that he learned about it from the aforementioned Party Five series.
• In the movie Sweet November, the character of Charlize Theron is in a terminal stage of non-Hodgkin's lymphoma.
• In Desperate Housewives, the character of Lynette Scavo, (played by Felicity Huffman) is diagnosed with Hodgkin's lymphoma, which she tries to keep a secret.
• Bang the Drum Slowly by Mark Harris is a novel about a baseball player's last season when only he and his best friend know he is dying of Hodgkin's disease. It was later made into a film of the same name.
• In Jeffrey Archer's "Kane and Abel", Matthew Lester is diagnosed with Hodgkin's, but does not disclose his discovery to anyone. His best friend, William Kane, is told by Doctor MacKenzie abut the illness shortly before Matthew's death.
• Constable Deirdre 'Dash' McKinley in Australian police drama Blue Heelers was diagnosed with Hodgkins and shaved her head to save herself the trauma of going through hair loss. Barry Watson of 7th heaven was also diagnosed with Hodgkin's lymphoma.
• Nuclear Physicist, Nobel Prize Laureate, Richard P. Feynman's beloved first wife might have died of this lymphoma disease after all being accidentally, correctly though, diagnosed by a physician in the hospital where she was hospitalized at the time Feynman was working on the Manhattan Project. The featuring doctor curiously matches the "infamous" character moves of Dr. House in the popular TV show going by the same name. (look also for the story in: Surely You're Joking, Mr. Feynman!)
• In the movie No Escape. the character of The Father, (played by Lance Henriksen) is diagnosed with Hodgkin's lymphoma.

See also

• ABVD
• Ann Arbor staging
• Stanford V
• Non-Hodgkin lymphoma

References

1. ^ ^{a b c d e f g} Hellman S (2007). "Brief Consideration of Thomas Hodgkin and His Times". in Hoppe RT, Mauch PT, Armitage JO, Diehl V, Weiss LM. Hodgkin Lymphoma (2nd ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. pp. 3–6. ISBN 0-7817-6422-X. 
2. ^ ^{a b} Hodgkin T (1832). "On some morbid experiences of the absorbent glands and spleen". Med Chir Trans 17: 69–97. 
3. ^ Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) http://canques.seer.cancer.gov/cgi-bin/cq_submit?dir=seer2006&db=4&rpt=LINE&sel=1^0^79^0^^^&x=Age%20at%20diagnosis^6,7,8,9,10,11,12,13,14,15,16,17,18,19,20&y=Race^0,1,2^Sex^0,1,2&dec=1&template=null
4. ^ ^{a b} Fermé C, Eghbali H, Meerwaldt JH, et al. (November 2007). "Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease". The New England Journal of Medicine 357 (19): 1916–27. doi:10.1056/NEJMoa064601. PMID 17989384. http://content.nejm.org/cgi/pmidlookup?view=short&pmid=17989384&promo=ONFLNS19. 
5. ^ Stein RS, Morgan D (2003). Handbook of cancer chemotherapy (6th ed.). Hagerstown, MD: Lippincott Williams & Wilkins. pp. 493. ISBN 0-7817-3629-3. 
6. ^ ^{a b} "HMDS: Hodgkin's Lymphoma". http://www.hmds.org.uk/hl.html. Retrieved 2009-02-01. 
7. ^ Küppers R, Schwering I, Bräuninger A, Rajewsky K, Hansmann ML (2002). "Biology of Hodgkin's lymphoma". Ann. Oncol. 13 Suppl 1: 11–8. PMID 12078890. http://annonc.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=12078890. 
8. ^ Bräuninger A, Schmitz R, Bechtel D, Renné C, Hansmann ML, Küppers R (April 2006). "Molecular biology of Hodgkin's and Reed/Sternberg cells in Hodgkin's lymphoma". Int. J. Cancer 118 (8): 1853–61. doi:10.1002/ijc.21716. PMID 16385563. 
9. ^ Tzankov A, Bourgau C, Kaiser A, et al. (December 2005). "Rare expression of T-cell markers in classical Hodgkin's lymphoma". Mod. Pathol. 18 (12): 1542–9. doi:10.1038/modpathol.3800473. PMID 16056244. 
10. ^ Lamprecht B, Kreher S, Anagnostopoulos, I, Johrens k, Monteleone G, Junt F, Stein H, Janz M, Dorken B, Mathas S (2008). "Aberrant expression of the Th2 cytokine IL-21 in Hodgkin lymphoma cells regulates STAT3 signaling and attracts Treg cells via regulation of MIP-3a". Blood 112 (Oct 2008): 3339–3347. doi:10.1182/blood-2008-01-134783. PMID 18684866. http://bloodjournal.hematologylibrary.org/cgi/content/abstract/112/8/3339. 
11. ^ Bobrove AM (June 1983). "Alcohol-related pain and Hodgkin's disease". The Western Journal of Medicine 138 (6): 874–5. PMID 6613116. 
12. ^ Portlock CS (July 2008). "Hodgkin Lymphoma". Merck Manual Professional. http://www.merck.com/mmpe/sec11/ch143/ch143b.html. Retrieved 2009-06-18. 
13. ^ {Hodgon DC, Gospodarowicz MK (2007). "Clinical Evaluation and Staging of Hodgkin Lymphoma". in Hoppe RT, Mauch PT, Armitage JO, Diehl V, Weiss LM. Hodgkin’s disease. Lippincott Williams & Wilkins. pp. 123–132. ISBN 978-0-7817-6422-3. 
14. ^ Asher, Richard (July 6, 1995). "Making Sense". The New England Journal of Medicine 333 (1): 66–67. doi:10.1056/NEJM199507063330118. PMID 7777006. 
15. ^ Hodgkin's disease (Hodgkin's lymphoma) at Mount Sinai Hospital
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External links

• Hodgkin Disease at American Cancer Society
• Hodgkin's Lymphoma at the American National Cancer Institute
• Information from the German Hodgkin Studygroup (English version)
• Timeline of discovery and treatment of Hodgkin's Lymphoma at hodgkinshistory.com
• Video and information booklet on Hodgkins Lymphoma
• Information on Hodgkins Lymphoma from Lymphoma Research Foundation

v • d • e Hematological malignancy/leukemia histology (ICD-O 9590-9989, C81-C96, 200-208) Lymphoid/Lymphoproliferative, Lymphomas/Lymphoid leukemias (9590-9739, 9800-9839) B cell (lymphoma, leukemia) (most CD19, CD20) By development/ marker TdT+ ALL (Precursor B acute lymphoblastic leukemia/lymphoma) CD5+ naive B cell (CLL/SLL) mantle zone (Mantle cell) CD22+ Prolymphocytic · CD11c (Hairy cell leukemia) CD79a+ germinal center/follicular B cell (Follicular, Burkitt's, GCB-DLBCL) marginal zone/marginal-zone B cell (Splenic marginal zone, MALT, Nodal marginal zone) RS (CD15+,CD30+) Classic Hodgkin's lymphoma (Nodular sclerosis) · CD20 (Nodular lymphocyte predominant Hodgkin's lymphoma) PCDs/PP (CD38+/CD138+) see immunoproliferative immunoglobulin disorders By infection KSHV (Primary effusion) · EBV (Lymphomatoid granulomatosis, Post-transplant lymphoproliferative disorder) · HIV (AIDS-related lymphoma) · Helicobacter pylori (MALT lymphoma) T/NK T cell (lymphoma, leukemia) (most CD3, CD4, CD8) By development/ marker TdT+: ALL (Precursor T acute lymphoblastic leukemia/lymphoma) prolymphocyte (Prolymphocytic) CD30+ (Anaplastic large cell, Lymphomatoid papulosis) By location/peripheral Cutaneous (Mycosis fungoides, Sézary's disease) · Hepatosplenic · Angioimmunoblastic · Enteropathy-associated T-cell lymphoma By infection HTLV-1 (Adult T-cell leukemia/lymphoma) NK cell/ (most CD56) Aggressive NK-cell leukemia · Blastic NK cell lymphoma T or NK EBV (Extranodal NK-T-cell lymphoma) · Large granular lymphocytic leukemia Lymphoid+myeloid Acute biphenotypic leukaemia Lymphocytosis Lymphoproliferative disorders (X-linked lymphoproliferative disease, Autoimmune lymphoproliferative syndrome) · Leukemoid reaction · Pseudolymphoma lymphocyte navs: cells/physio, immunodeficiency/immunoproliferative immunoglobulin/neoplasia, proc

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Dansk (Danish)
n. - Hodgkin

idioms:

• hodgkin's disease    Hodgkins sygdom

Français (French)
idioms:

• hodgkin's disease    maladie de Hodgkin

Deutsch (German)
idioms:

• hodgkin's disease    (Med.) Hodgkin-Krankheit, (Lymphogranulomatose)

Ελληνική (Greek)
idioms:

• hodgkin's disease    νόσος του Χόντγκιν, λεμφαδένωμα

Italiano (Italian)
idioms:

• hodgkin's disease    morbo di Hodgkin

Português (Portuguese)
n. - doença (f) de Hodgkin (Patol.)

idioms:

• hodgkin's disease    doença (f) de Hodgkin (neoplásica) (Patol.)

Русский (Russian)
Ходжкин

idioms:

• hodgkin's disease    лимфогрануломатоз

Español (Spanish)
idioms:

• hodgkin's disease    linfoma, cáncer linfático

Svenska (Swedish)
(h`id╔kin) - hodgkin's disease

中文（简体）(Chinese (Simplified))
霍奇金, 霍奇金病, 淋巴肉芽肿病

idioms:

• hodgkin's disease    霍奇金氏病, 恶性肉芽肿

中文（繁體）(Chinese (Traditional))
n. - 霍奇金, 霍奇金病, 淋巴肉芽腫病

idioms:

• hodgkin's disease    霍奇金氏病, 惡性肉牙腫

한국어 (Korean)
n. - 호지킨

日本語 (Japanese)
n. - ホジキン

עברית (Hebrew)
n. - ‮הודג'קין (הרופא שגילה את מחלת הודג'קין)‬

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