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

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

The American Cancer Society estimates that there will be 7,400 new cases of Hodgkin's disease in the United States in 2001—3, 500 in females and 3,900 in males. It is estimated that 700 men and 600 women in the United States will die of the disease in 2001.

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 can result in fatigue and easy bleeding and bruising. Damage to intestinal cells leads to a loss of appetite (anorexia ), 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 immuno-therapies, 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 diagnosedwith 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

As of 2001, 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.

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 mammo-grams 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.

See Also Amenorrhea; Bone marrow transplantation; Childhood cancers; Fertility and cancer; Imaging studies; Immune response

Resources

BOOKS

Dollinger, Malin, et al. Everyone's Guide to Cancer Therapy. Kansas City: Andrews McKeel 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.

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

Murphy, Gerald P., et al. Informed Decisions. New York:Viking, 1997.

Sutcliffe, Simon B., ed. Lymphoma and You: A Guide for Patients Living with Hodgkin's Disease and Non-Hodgkin's Lymphoma. Toronto: The Medicine Group Ltd., 1998.

PERIODICALS

Bhatia, S., L. L. Robison, O. Oberlin, M. Greenberg, G. Bunin, F. Fossati-Bellani, and A. T. Meadows. "Breast Cancer and Other Second Neoplasms after Childhood Hodgkin's Disease." New England Journal of Medicine 334, no. 12 (1996): 745-51.

Stoval, Ellen. "A Cancer Survivor Discusses Her Experiences."Washington Post 118 (February 14, 1995): WH15+.

ORGANIZATIONS

American Cancer Society. (800) ACS-2345. <http://www.cancer.org>. 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. <http://clinicaltrials.gov/ct/gui/c/a1b/screen/BrowseAny/action/GetStudy?JServSessionIdcs_current=mgdpq4z7pm>. 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. [email protected]. <http://www.cfl.org/home.html>. 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. <http://www.leukemia-lymphoma.org> Provides information, support, and guidance to patients and health care professionals.

The Lymphoma Research Foundation of America, Inc. 8800Venice Boulevard, Suite 207, Los Angeles, CA 90034. (310) 204-7040). <http://www.lymphoma.org>. 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. <http://www.nci.nih.gov/>. <http://cancernet.nci.nih.gov>. 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. 27 Mar. 2001. <http://www.leukemia-lymphoma.org>.

"Hodgkin's Disease." Cancer Resource Center. 10 Dec. 1999.American Cancer Society. 27 Mar. 2001. <http://www3.cancer.org>.

"Hodgkin's Disease." CancerNet. 12 Dec. 2000. National Cancer Institute. NIH Publication No. 99-1555. 27 Mar. 2001. >http://cancernet.nci.nih.gov/wyntk_pubs/hodgkins.htm>.

"Hodgkin's Lymphoma." Diseases & Conditions. 13 Mar.2001. MayoClinic.com. 27 Mar. 2001. <http://www.mayohealth.org>.

National Cancer Society. "NCI/PDQ Patient Statement: Adult Hodgkin's Disease." Oncolink. Nov. 2000.University of Pennsylvania Cancer Center. 27 Mar. 2001.<http://www.oncolink.upenn.edu/pdq_html/2/engl/200003.html>.

National Cancer Society. "NCI/PDQ Patient Statement: Childhood Hodgkin's Disease." Oncolink. Feb. 2001. University of Pennsylvania Cancer Center. 27 Mar. 2001 <http://www.oncolink.upenn.edu/pdq_html/2/engl/203043.html>.

"PET Scans Help Doctors Treat Hodgkin's Disease." ACS News Today. 13 Mar. 2001. American Cancer Society. 27 Mar. 2001 <http://www2.cancer.org>.

Rosalyn S. Carson-DeWitt, M.D.

Margaret Alic, Ph.D.

KEY TERMS

Antibody

—An immune system protein that recognizes a specific foreign molecule.

Biopsy

—The removal of a small sample of tissue for examination under a microscope; used for the diagnosis of cancer and to check for infection.

Bone marrow

—Tissue inside the bones that produce red and white blood cells.

Chemotherapy

—Treatment with various combinations of chemicals or drugs, particularly for the treatment of cancer.

Epstein-Barr virus (EBV)

—Very common virus that infects immune cells and can cause mononucleosis.

Interferon

—A potent immune-defense protein produced by viral-infected cells; used as an anti-cancer and anti-viral drug.

Interleukins

—A family of potent immune-defense molecules; used in various medical therapies.

Laparotomy

—A surgical incision of the abdomen.

Leukapheresis

—A technique that uses a machine to remove stem cells from the blood; the cells are frozen and then returned to the patient following treatment that has destroyed the bone marrow.

Lymph nodes

—Small round glands, located throughout the body and containing lymphocytes that remove foreign organisms and debris from the lymphatic fluid.

Lymphatic system

—The vessels, lymph nodes, and organs, including the bone marrow, spleen, and thymus, that produce and carry white blood cells to fight disease.

Lymphocyte

—hite blood cells that produce antibodies and other agents for fighting disease.

PBSCT

—Peripheral blood stem cell transplant; a method for replacing blood-forming cells that are destroyed by cancer treatment.

Radiotherapy

—Disease treatment involving exposure to x rays or other types of radiation.

Reed-Sternberg cells

—An abnormal lymphocyte that is characteristic of Hodgkin's disease.

Spleen

—An organ of the lymphatic system, on the left side of the abdomen near the stomach; it produces and stores lymphocytes, filters the blood, and destroys old blood cells.

Splenectomy

—Surgical removal of the spleen.

Staging

—The use of various diagnostic methods to accurately determine the extent of disease; used to select the appropriate type and amount of treatment and to predict the outcome of treatment.

Stem cells

—The cells from which all blood cells are derived.

Thymus

—An organ of the lymphatic system, located behind the breast bone, that produces the T lymphocytes of the immune system.

Thyroid

—A gland in the throat that produces hormones that regulate growth and metabolism.

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?

Hodgkin's Disease

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

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

The American Cancer Society estimates that there will be 7,400 new cases of Hodgkin's disease in the United States in 2001—3,500 in females and 3,900 in males. It is estimated that 700 men and 600 women in the United States will die of the disease in 2001.

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.

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
• 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.

DOROTHY MENDENHALL (1874–1964)

Dorothy Reed Mendenhall, the last of three children, was born September 22, 1874, in Columbus, Ohio, to William Pratt Reed, a shoe manufacturer, and Grace Kimball Reed, both of whom had descended from English settlers who came to America in the seventeenth century. Mendenhall attended Smith College and obtained a baccalaureate degree. Although she initially contemplated a career in journalism, Mendenhall's interest in medicine was inspired by a biology course she attended.

Dorothy Reed Mendenhall was a well-respected researcher, obstetrician, and pioneer in methods of childbirth. She was the first to discover that Hodgkin's disease was not a form of tuberculosis, as had been thought. This finding received international acclaim. As a result of her work, the cell type characteristic of Hodgkin's disease bears her name. The loss of her first child due to poor obstetrics changed her research career to a lifelong effort to reduce infant mortality rates. Mendenhall's efforts paid off with standards being set for weight and height for children ages birth to six and also in programs that stressed the health of both the mother and child in the birthing process.

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.

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.

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 of the abdomen, chest, and pelvis is used to identify areas of enlarged lymph nodes and abnormalities in the spleen or other organs. Computerized axial 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.

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 biopsy, in which a large needle is used to remove a narrow, cylindrical piece of bone, may be necessary to determine the spread of the cancer. 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.

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.

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 (37.70 C) degrees F
• drenching night sweats

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.

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, which can result in fatigue and easy bleeding and bruising. Damage to intestinal cells leads to a loss of appetite, nausea, and vomiting. Mouth sores and hair loss 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.

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.

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.

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.

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.

KEY TERMS

Antibody— An immune system protein that recognizes a specific foreign molecule.

Biopsy— The removal of a small sample of tissue for examination under a microscope; used for the diagnosis of cancer and to check for infection.

Bone marrow— Tissue inside the bones that produce red and white blood cells.

Chemotherapy— Treatment with various combinations of chemicals or drugs, particularly for the treatment of cancer.

Epstein-Barr virus (EBV)— Very common virus that infects immune cells and can cause mononucleosis.

Interferon— A potent immune-defense protein produced by viral-infected cells; used as an anti-cancer and anti-viral drug.

Interleukins— A family of potent immune-defense molecules; used in various medical therapies.

Laparotomy— A surgical incision of the abdomen.

Leukapheresis— A technique that uses a machine to remove stem cells from the blood; the cells are frozen and then returned to the patient following treatment that has destroyed the bone marrow.

Lymph nodes— Small round glands, located throughout the body and containing lymphocytes that remove foreign organisms and debris from the lymphatic fluid.

Lymphatic system— The vessels, lymph nodes, and organs, including the bone marrow, spleen, and thymus, that produce and carry white blood cells to fight disease.

Lymphocyte— White blood cells that produce antibodies and other agents for fighting disease.

PBSCT— Peripheral blood stem cell transplant; a method for replacing blood-forming cells that are destroyed by cancer treatment.

Radiotherapy— Disease treatment involving exposure to x rays or other types of radiation.

Reed-Sternberg cells— An abnormal lymphocyte that is characteristic of Hodgkin's disease.

Spleen— An organ of the lymphatic system, on the left side of the abdomen near the stomach; it produces and stores lymphocytes, filters the blood, and destroys old blood cells.

Splenectomy— Surgical removal of the spleen.

Staging— The use of various diagnostic methods to accurately determine the extent of disease; used to select the appropriate type and amount of treatment and to predict the outcome of treatment.

Stem cells— The cells from which all blood cells are derived.

Thymus— An organ of the lymphatic system, located behind the breast bone, that produces the T lymphocytes of the immune system.

Thyroid— A gland in the throat that produces hormones that regulate growth and metabolism.

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.

Hodgkin's disease

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.

Paula Ford-Martin

Teresa G. Odle

Hodgkin's disease

Hodgkin's disease is a type of cancer involving tissues of the lymphatic system . The lymphatic system is a network of organs, tissues, and ducts in the human body. The lymphatic system maintains the fluid balance in the body by coordinating the draining of fluid from cells and tissues back into the bloodstream. Also, the lymphatic system aids in fighting infections caused by microorganisms , by supplying the body with white blood cells.

A variety of cancers called lymphomas affect the lymph tissues. Hodgkin's disease represents a specific type of lymphoma. Its cause is unknown, although some interaction between individual genetic makeup, environmental exposures, and infectious agents is suspected.

Hodgkin's lymphoma can occur at any age. The majority of all cases of Hodgkin's lymphoma occur in people between the ages of 15 and 34, and those who are older than 60 years of age.

The lymphatic system

The lymphatic system is part of the body's immune system . It consists of a number of elements. First, there is a network of vessels. The vessels drain tissue fluid from all the major organs of the body, including the skin, and from all four limbs. These vessels pass through lymph nodes on their way to empty their contents into major veins at the base of the neck and within the abdomen.

The lymph nodes are clusters of specialized cells that serve to filter the lymph fluid. In this capacity, they trap foreign substances such as viruses, bacteria , cancer cells, as well as any other encountered debris. For example, the examination of lymph nodes form people who live in cities typically detects gritty, dark material, which is not present in the lymph nodes of people who live in rural settings. This is because the lymph nodes of the city dweller have received fluid from the lungs, which contain debris from polluted city air.

Another component of the lymphatic system are lymphocytes. Lymphocytes are cells of the immune system. They are produced within bone marrow, lymph nodes, and spleen, and circulate throughout the body in both blood and lymph fluid. These cells work to identify and rid the body of any invaders that threaten health.

Still another component of the lymphatic system are clusters of scavenger-like immune cells. These exist in major organs, and provide immune surveillance on location. These include the tonsils and adenoids in the throat/pharynx, Kupffer cells in the liver, Peyer's patches in the intestine, and other specialized immune cells stationed in the lungs and the brain .

Cancer

Cancer is a general term that refers to a condition in which a particular type of cell within the body begins to multiply in an out-of-control fashion. This may mean that cancer cells multiply more quickly, or it may mean that cancer cells take on abnormal characteristics. For example, at a very early stage in embryonic development (development of a fetus within the uterus), generic body cells begin to differentiate. Cells acquire specific characteristics which ultimately allow liver cells to function as liver cells, blood cells as blood cells, brain cells as brain cells, and so on. Thus, cancer can be considered to be a process of "de-differentiation." In other words, a specialized type of cell loses whatever controls govern the expression of its individual characteristics and instead revert to a more embryonic cell. Such cells also lose their sense of organization and no longer position themselves appropriately within their resident tissue.

Cancer cells can also acquire the ability to invade other tissues. Normally, for example, breast cells are found only in breast tissue. However, cancerous breast cells can invade into other tissue spaces, so that breast cancer can spread to bone, liver, brain, etc.

Lymphoma is a cancer of the lymph system. Depending on the specific type, a lymphoma can have any or all of the characteristics of cancer. These characteristics include rapid multiplication of cells, abnormal cell types, loss of normal arrangement of cells with respect to each other, and invasive ability.

Causes and symptoms of Hodgkin's lymphoma

Hodgkin's lymphoma usually begins in a lymph node. This node enlarges, but may or may not cause the pain that typically results when lymph nodes enlarge as a consequence of an infection by a microorganism. Hodgkin's lymphoma progresses in a fairly predictable way, traveling from one group of lymph nodes on to the next. More advanced cases of Hodgkin's include involvement of the spleen, the liver, and bone marrow.

Constitutional symptoms (symptoms which affect the whole body) are common, and 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 on other nearby structures. This pressure produces other 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 that carry urine from the kidneys to the bladder. The face, neck, or legs 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 paralysis of the legs. 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 .

The exact cause of Hodgkin's disease is not known. Viruses, particularly the Epstein-Barr virus (a herpes virus that causes infectious mononucleosis), are found in tissues of 20-50% of people with Hodgkin's disease. However, a link between the virus and Hodgkins disease has not been established.

Another suggested cause is socio-economic conditions. Studies have demonstrated that Hodgkin's disease is more prevalent in wealthier people in the developed world. It has been speculated that the hygienic conditions that most of these people grow up in does not stress their immune systems in a way that is healthy for them. Other suggested causes include exposure to chemicals, and a genetic disposition (including the activity of cancerous genes known as oncogenes).

Diagnosis

As with many forms of cancer, diagnosis of Hodgkin's disease has two important components. First is the identification of Hodgkin's lymphoma as the cause of the patient's disease . Second is the staging of the disease; that is, an attempt to identify the degree of spread of the lymphoma.

Diagnosis of Hodgkin's lymphoma requires 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, which are called Reed-Sternberg cells, must be present in order to confirm the diagnosis. These cells usually contain two or more nuclei. The nucleus is the oval, centrally located structure within a cell that houses the genetic material of the cell. Reed-Sternberg cells also have other unique characteristics, which cause them to appear under the microscope as "owl's eyes" or yin-yang cells. 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 present.

Once Hodgkin's disease has been diagnosed, staging is the next important step. This involves computed tomography scans (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 lymphangiograms (a radiograph of the lymphatic vessels).

Staging is important because it helps to determine what kind of treatment a patient should receive. 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. All available treatments, however, have potentially serious side effects. The goal of staging, then, is to allow the patient to have the type of treatment necessary to achieve a remission, but to minimize the severity of short and long-term side effects from which the patient may suffer.

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 x rays which kill cancer cells).

Both chemotherapy and radiotherapy often have side effects. Chemotherapy can result in nausea, vomiting, hair loss, and increased susceptibility to infection. Radiotherapy can cause sore throat, difficulty swallowing, diarrhea, and growth abnormalities in children. Both forms of treatment, especially in combination, can result in sterility (the permanent inability to produce offspring), as well as heart and lung damage.

The most serious negative result of the currently available treatments for Hodgkin's disease is the possible development in the future of another form of cancer. This phenomenon is referred to as second malignancy. Examples of second cancers include leukemia (cancer of a blood component), breast cancer, bone cancer, or thyroid cancer. A great deal of cancer research is devoted to preventing these second malignancies.

Prognosis

Hodgkin's is one of the most curable forms of cancer. Current treatments are quite effective. Children have a particularly high rate of cure from the disease, with about 75% still living cancer-free 20 years after the original diagnosis. Adults with the most severe form of the disease have about a 50% cure rate.

See also Genetic disorders.

Resources

books

Jaffe, E.S., N.L. Harris, H. Stein, et al. Pathology and Genetics of Tumours of the Haematopoietic and Lymphoid Tissues. Lyon: IARC Press, 2001.

organizations

The Leukemia and Lymphoma Society. 1311 Mamaroneck Ave. White Plains, NY 10605 (914) 949–5213 [cited November 19, 2002]. <http://www.leukemia-lymphoma.org>.

Brian Hoyle

HODGKIN'S DISEASE

DEFINITION

Hodgkin's disease is a cancer of the lymphatic (pronounced lim-FAT-ic) system. The lymphatic system consists of blood vessels, tissues, and other structures that carry lymph (pronounced limf) through the body. Lymph is a bloodlike fluid that carries substances from cells to blood vessels.

A variety of cancers can affect lymph tissue. These cancers are called lymphomas. Hodgkin's disease is one kind of lymphoma. It is also called Hodgkin's lymphoma. The cause of Hodgkin's disease is unknown. Many experts believe that genetic and environmental factors work together to cause the disease.

DESCRIPTION

Hodgkin's lymphoma can occur at any age. It is most common, however, in people between the ages of fifteen and thirty-four and after the age of sixty. An understanding of the lymphatic system is necessary in order to understand the nature of Hodgkin's lymphoma.

The Lymphatic System

Lymph is usually a clear, colorless liquid that forms in the space between cells throughout the body. It consists of waste products from those cells.

Lymph is drained into tiny vessels, like blood vessels. These vessels form a network of tubes that eventually leads to large veins at the base of the neck and inside the abdomen. At various points in this network, lymph passes through small lumps of tissue known as lymph nodes.

Lymph nodes contain special kinds of cells that act as filters. These cells remove foreign substances, such as viruses, bacteria, and cancer cells, from lymph. For this reason, they are part of the body's immune system, protecting it from infection.

Hodgkin's Disease: Words to Know

Biopsy:

The removal of a small sample of tissue and its examination under a microscope for the purpose of diagnosing

Chemotherapy:

Treatment of a disease with certain chemicals or drugs that destroy cancer cells.

Radiotherapy:

Treatment of a disease using some form of radiation, such as X rays.

One kind of cell found in lymph is a white blood cell called a lymphocyte. The role of lymphocytes is to identify foreign bodies in lymph and to help eliminate those materials from the lymph.

Cancer of the Lymph System

Cancer is a condition in which cells grow out of control (see cancer entry). Cancer can appear in any part of the lymph system. Cells within a lymph node, for example, may begin to grow rapidly. They may take on unusual shapes and begin to spread throughout the body. Cancers that affect any part of the lymph system are known as lymphomas.

CAUSES

Hodgkin's lymphoma usually begins in a lymph node. The node enlarges and may or may not become painful. The cancer typically moves from one lymph node to another nearby lymph node. Eventually, cancer cells can be carried to other organs in the body, including the spleen, liver, and bone marrow.

SYMPTOMS

Some of the early symptoms of Hodgkin's lymphoma include fever, weight loss, heavy sweating at night, and itching. Some patients report that drinking alcoholic beverages may cause pain in the infected area.

As lymph nodes swell, they may push on other nearby structures. This pressure may also cause pain and other kinds of discomfort. For example, nerves may be pinched, causing pain and loss of muscular control. Pressure on the ureters, the tubes that carry urine from the kidneys to the bladder, can cause kidney failure. Pressure on veins in the face, neck, and legs can reduce blood flow and cause swelling in those areas. Pressure on the spinal cord can cause paralysis of the legs. Pressure on the upper respiratory (breathing) system can cause wheezing and shortness of breath. Abnormal tissue growth in the liver can cause an accumulation of toxins (poisons), resulting in jaundice. Jaundice is a yellowish discoloration of the skin and whites of the eyes. It is a common sign of liver disease.

As Hodgkin's disease worsens, the lymphatic system becomes less effective in fighting off infections. Patients with the disease are more likely to develop infections caused by bacteria, viruses, and other types of germs.

DIAGNOSIS

Diagnosis involves two steps. First, the doctor must identify Hodgkin's disease as the cause of the patient's symptoms. Second, the doctor must determine how far the disease has progressed.

Hodgkin's disease is usually diagnosed by means of a biopsy. A biopsy is a process in which a small sample of tissue is removed from the infected part

of the patient's body. In the case of Hodgkin's disease, the biopsy is usually done on a lymph node. The sample is then examined under a microscope. The presence of certain characteristic types of cells is evidence of a lymphoma.

Additional procedures are necessary to see how far the disease has spread. For example, a bone marrow biopsy may be conducted to see if the disease has spread to this part of the body. A computed tomography (CT) scan may be ordered to see if the disease has spread to the abdomen, chest, pelvis, and other parts of the body. A CT scan is a procedure by which X rays are directed at a patient's body from various angles and the set of photographs thus obtained assembled by a computer program. This procedure is sometimes called a computerized axial tomography (CAT) scan. A lymphangiogram can also be performed. A lymphangiogram is similar to an X ray of the lymphatic system. It indicates the parts of the system that have become cancerous.

Finding out how far the disease has spread is important because it determines the kind of treatment the patient should have. Most treatments have serious side effects. A doctor wants to use only enough of a treatment to kill the lymphoma, not enough to do other serious damage to the body.

TREATMENT

Two forms of treatment are used with Hodgkin's disease: chemotherapy and radiotherapy. Chemotherapy involves the use of drugs to kill cancer cells. Radiotherapy uses X rays or other forms of radiation to achieve the same result. Both methods of treatment work quite well with Hodgkin's lymphoma.

Unfortunately, both treatments also have unpleasant side effects. Chemotherapy can result in nausea, vomiting, hair loss, and an increased risk for infections. Radiotherapy can cause sore throat, difficulty in swallowing, diarrhea, and changes in growth patterns for children. Both forms of treatment, especially when they are used together, can cause sterility. Sterility is the loss of the ability to have children. Heart and lung damage are also possible side effects when the two treatments are used together.

One of the most serious problems in the treatment of Hodgkin's disease is the possibility of a secondary cancer. A secondary cancer is a new cancer that occurs elsewhere in the body after the Hodgkin's lymphoma has been cured. Secondary cancers can occur in blood, bone, the thyroid, or other parts of the body.

PROGNOSIS

The cure rate for Hodgkin's disease is among the highest for any form of cancer. Treatments seem to work best with children. About 75 percent of children treated for Hodgkin's disease are still alive twenty years after the original diagnosis. For adults with the most serious forms of the disease, the cure rate is still as high as 50 percent.

PREVENTION

There is no know method of preventing Hodgkin's disease.

FOR MORE INFORMATION

Books

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

Murphy, Gerald P., et al. Informed Decisions. New York: Viking Press, 1997.

Periodicals

Stoval, Ellen. "A Cancer Survivor Discusses Her Experiences." Washington Post (February 14, 1995): pp. WH15+.

Organizations

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

Web sites

"Ask NOAH About: Cancer." NOAH: New York Online Access to Health. [Online] http://www.noah.cuny.edu/cancer/cantypes.html#H (accessed on October 25, 1999).