Also called: Hodgkin’s Disease
Mark Oren, M.D., FACP
Hodgkin’s lymphoma, also known as Hodgkin’s disease, is a type of lymphoma, or cancer of the lymphoid tissue. Lymphoid tissue is part of the lymphatic system, a major component of the immune defense system. It consists of a network of organs, bone marrow, lymph nodes and vessels. This system manufactures and transports lymph (fluid made of plasma and white blood cells) from tissues to the bloodstream.
Lymphoma generally develops in the lymph nodes (small, bean-shaped organs located in various areas of the body). In some situations, it may develop in patches of lymphatic tissue in organs like the stomach or intestines.
There are two types of lymphoma, Hodgkin’s lymphoma and non-Hodgkin’s lymphoma. The cancer cells in Hodgkin’s lymphoma look different under a microscope than the cells of non-Hodgkin’s lymphoma. The cells associated with Hodgkin’s lymphoma (also called simply Hodgkin’s disease) are known as Reed-Sternberg cells. The disease is named after the physician who first identified it in 1832.
The cause of Hodgkin’s lymphoma has not been determined, but a number of factors may increase the risk of developing the disease. These risk factors include a compromised immune system and exposure to the Epstein Barr virus, which causes infectious mononucleosis.
Hodgkin’s lymphoma is a rare form of cancer that occurs in adults and children. It is most common in early adulthood (age 15 to 40) and late adulthood (after age 55). It is also more common in men. The American Cancer Society (ACS) estimates that about 7,350 new cases of Hodgkin’s lymphoma will be diagnosed in the United States in 2007.
Symptoms of Hodgkin’s lymphoma may include enlarged lymph nodes (swollen glands), night sweats and unexplained weight loss. Individuals who experience these symptoms are encouraged to contact their physician to determine the cause. If a physician suspects Hodgkin’s disease, a biopsy of the area may be ordered. The procedure involves removing a small sample of the lymph node tissue and examining it under a microscope.
After a diagnosis has been confirmed, the disease will be staged. Staging is the process of determining how far the cancer has spread and it is necessary for a physician to plan treatment. The lower the stage, the earlier the disease has been identified and the better the prognosis for recovery.
The main methods used to treat Hodgkin’s lymphoma are chemotherapy, radiation therapy and high-dose chemotherapy with blood restoring stem cell transplants.
Currently there are no established prevention methods for Hodgkin’s lymphoma. However, advances in diagnosis and treatment methods have helped to make the disease highly treatable with the potential for complete recovery in many patients. The death rates for this disease have decreased since the early 1970s.
About Hodgkin’s lymphoma
Hodgkin’s disease is a type of lymphoma, or cancer of the lymphoid tissue. Lymphoid tissue is part of the lymphatic system. A major component of the immune system, the lymph system consists of organs, lymph nodes and vessels. The lymphatic system is responsible for manufacturing and transporting lymph (fluid made of plasma and white blood cells) from tissues to the bloodstream.
Although Hodgkin’s lymphoma can start almost anywhere, it usually begins in the lymph nodes. In some instances, it can start in patches of lymphatic tissue in organs such as the stomach or intestines. Lymph nodes are small, bean-shaped organs located in groups in various areas of the body, including the neck, armpit, chest and groin. Their functions include producing immune cells (e.g., lymphocytes and plasma cells), and filtering bacteria, cancer cells and other foreign material from lymph. When the lymph nodes recognize antigens or foreign materials in the lymph fluid, they respond by enlarging and producing additional white blood cells. These white blood cells, which include lymphocytes and antibodies, help combat a variety of external threats.
The two types of lymphocytes are:
- B lymphocytes (B-cells). B-cells defend the body from invading bacteria and other harmful substances by changing into plasma cells, which produce antibodies. The antibodies then mark the antigens or foreign materials for destruction.
- T lymphocytes (T-cells). T-cells destroy antigens, infected and malignant cells directly.
As these abnormal cells continue to grow and expand, the lymph glands or other organs in which the lymphocytes grow begin to enlarge. The cells form lumps which begin to develop in the body. Organ function may become affected as the lymphocyte masses grow larger making it more difficult for normal cells to function.
Named after the physician who first identified it in 1832, Hodgkin’s lymphoma spreads through the lymph vessels to neighboring lymph nodes. The disease may spread to other areas of the body including the liver, bone marrow, spleen or lungs through the lymphatic system or the bloodstream.
The other main form of lymphoma is non-Hodgkin’s lymphoma (NHL). Hodgkin’s lymphoma can usually be distinguished from NHL when tissue is examined under a microscope. The characteristic cells found in Hodgkin’s lymphoma, known as Reed-Sternberg cells, are named after the physicians who first described them in detail. Many researchers believe that Reed-Sternberg cells are a form of malignant B-cells. Hodgkin’s lymphoma is less common than NHL.
According to the National Institutes of Health (NIH) the incidence of Hodgkin’s lymphoma is two in every 10,000 people. The disease occurs in both adults and children. However, it is most common in early adulthood (age 15 to 40, particularly ages 25 to 30) and late adulthood (after age 55). Only 10 to 15 percent of cases are diagnosed in children age 16 and younger. It is slightly more common in men than women.
The American Cancer Society (ACS) estimates that nearly 1,400 people will die of Hodgkin’s lymphoma in 2007. The five-year survival rate for all Hodgkin’s lymphoma patients after treatment is 85 percent. At 10 years, the survival rate is 77 percent and at 15 years it is 68 percent.
A number of factors, including the stage of the disease and the patient’s general health, affect a patient’s chance of survival. Death rates have fallen more than 60 percent since the 1970s due to advances in treatments. By 2001, the ACS estimates that more than 123,000 people had survived this disease.
Types and differences of Hodgkin’s lymphoma
The two main types of Hodgkin’s lymphoma are classical Hodgkin’s lymphoma and nodular lymphocyte predominant Hodgkin’s lymphoma.
- Classical Hodgkin’s lymphoma has four subtypes, all of which have classically appearing Reed-Sternberg cells.
- Nodular sclerosis Hodgkin’s lymphoma. This type mainly occurs in younger people, usually in females. The most common type of Hodgkin’s lymphoma in developed countries, this form tends to start in the lymph nodes of the chest and neck.
- Mixed cellularity Hodgkin’s lymphoma. Seen mainly in adults, this is the second most common type of Hodgkin’s lymphoma. Although it can occur in any lymph node, it most often occurs in the upper half of the body.
- Lymphocyte-rich Hodgkin’s lymphoma. This type is very similar to mixed cellularity Hodgkin’s lymphoma, except when examined under a microscope, most of its cells are small lymphocytes. It also occurs most often in the upper half of the body and is rarely found in more than a few lymph nodes.
- Lymphocyte-depleted Hodgkin’s lymphoma. The least common type of Hodgkin’s lymphoma, this form is more likely to involve the abdominal lymph nodes, as well as the spleen, liver and bone marrow. It is usually seen in older adults.
- Nodular sclerosis Hodgkin’s lymphoma. This type mainly occurs in younger people, usually in females. The most common type of Hodgkin’s lymphoma in developed countries, this form tends to start in the lymph nodes of the chest and neck.
- Nodular lymphocyte predominant Hodgkin’s lymphoma. This type does not usually contain Reed-Sternberg cells. Instead, it contains large cells that resemble popcorn. These “popcorn cells” are somewhat of a cross between the Reed-Sternberg cell and normal lymphocytes. Capable of occurring at any age, this type usually involves lymph nodes in the neck and under the arm.
Risk factors and causes of Hodgkin’s lymphoma
There is no single cause of Hodgkin’s lymphoma. However, researchers have identified a number of factors that appear to make a person more likely to develop Hodgkin’s lymphoma. These risk factors include:
- Infectious mononucleosis (a viral infection typically caused by the Epstein-Barr virus). People who have had this infection are at a greater risk for Hodgkin’s lymphoma.
A member of the herpes virus family, the Epstein-Barr virus is one of the most common human viruses. Researchers have found a link between the virus and Hodgkin’s lymphoma. The virus may cause suppression in the factor that prevents B-cells from growing too fast. Studies are investigating whether this suppression leads to the development of Reed-Sternberg cells and Hodgkin’s lymphoma.
- Lowered immunity. Patients with reduced immunity are at much greater risk for developing Hodgkin’s lymphoma and non-Hodgkin’s lymphomas. Lowered immunity may be found in people infected with the human immunodeficiency virus (HIV), those born with immune deficiencies, and those who have been treated with immunosuppressive drugs, such as those used with organ transplants.
Other risk factors include:
- Age. Patients in young adulthood (age 15 to 40) or late adulthood (older than 55) are at an increased risk.
- Gender. Men are at a slightly increased risk, except for nodular sclerosis Hodgkin’s lymphoma (which occurs more often in women).
- Having a first degree relative with Hodgkin’s lymphoma. Patients with a parent, brother or sister with the disease are at an increased risk of developing it. However, family history is still uncommon and accounts for less than 10 percent of all the cases.
Hodgkin’s lymphoma does not appear to be related to specific gene mutations or environmental factors, as found with many other cancers. Even though it may occur in several family members, researchers do not have reason to believe the disease is related to defective genes.
Signs and symptoms of Hodgkin’s lymphoma
Many patients with Hodgkin’s lymphoma may not experience any symptoms, while others may mistakenly associate their symptoms with another disorder, such as influenza.
Common symptoms include:
- Enlarged lymph node (swollen glands) in the neck, armpits or groin
- Fever and chills
- Excessive sweating, particularly at night
- Unexplained weight loss
- Decreased appetite
- Coughing or breathing difficulty
The most common symptom of Hodgkin’s lymphoma, an enlarged lymph node, is usually caused by a less serious and noncancerous condition, such as an infection. However, if the nodes are enlarged more than an inch, especially with no history of a recent infection or illness, it is important to have a physician examine the area.
Patients experiencing any of these symptoms are encouraged to contact their physician. The earlier Hodgkin’s lymphoma is diagnosed, the earlier treatment may begin and the better a person’s chance for recovery. There are no recommended screening tests for early detection of Hodgkin’s lymphoma.
Diagnosis methods for Hodgkin’s lymphoma
To diagnose Hodgkin’s lymphoma, a physician first will take the patient’s medical history and perform a complete physical examination. Because infections are the most common cause of enlarged lymph nodes, the physician will examine the area surrounding the swollen lymph nodes for an infection. If the physician suspects Hodgkin’s lymphoma, a biopsy of the area may be ordered.
Biopsies are the only way to definitively diagnose and classify Hodgkin’s lymphoma. The procedure involves removing a sample of lymph node tissue for examination under a microscope by a pathologist. Excisional and incisional biopsies are the two procedures used to diagnose Hodgkin’s lymphoma. In these procedures, the physician cuts through the skin to remove an entire lymph node (excisional biopsy), or a small section of a large tumor (incisional biopsy). When the lymph node is located near the skin surface, the procedure is relatively simple, and can be done with local anesthesia. When the lymph node is inside the chest or abdomen, general anesthesia is required.
A fine needle aspiration (FNA) biopsy is another type of biopsy that may be ordered. In this procedure, a thin needle and a syringe are used to remove a small amount of fluid and tissue. Although this procedure cannot be used to diagnose Hodgkin’s lymphoma, it may be ordered when a physicians suspects lymph node swelling to be the result of infection or the spread of cancer from another body part. After Hodgkin’s lymphoma has been treated, an FNA may be ordered to check the body for signs that the disease is metastasizing (spreading) or recurring (coming back).
After the tissue has been removed, it is examined for abnormalities. The size and shape of the cells are examined to determine if any of them are Reed-Sternberg cells. In some cases, biopsy results are inconclusive and additional biopsies may be needed. Special stains are sometimes ordered to examine the sample for the presence of CD 15 and CD 30 molecules, molecules usually found in Hodgkin’s lymphoma.
After a diagnosis has been confirmed, the disease will be staged. Staging is the process of determining how far the cancer has spread and the patient’s outlook for recovery (prognosis). Results from the physical exam, biopsies, imaging tests and other tests are used to determine the stage of the disease. It is necessary to plan the most effective course of treatment.
Imaging tests used during the staging of Hodgkin’s lymphoma include:
- Chest x-ray. This test uses low doses of radiation to produce images of the chest. With Hodgkin’s lymphoma, enlarged lymph nodes may be detected in the chest.
- CAT scan (computed axial tomography). Also known as a CT scan, this test allows for multiple x-rays to be taken from different angles around the patient. The cross-sectional images of the patient’s body are analyzed by a computer. Frequently after the first set of images is taken, the patient receives an intravenous (I.V.) injection of a contrast material (dye) to better outline body parts and a second set of images is taken. CAT scans give a physician an enhanced look at the lymph nodes and organs (such as the liver and spleen).
- Magnetic resonance imaging (MRI). A powerful magnetic field creates images of structures and organs within the body allowing a computer to produce very clear cross-sectional or three-dimensional images. Although this test is rarely used with Hodgkin’s lymphoma, it may be ordered to determine if the disease has spread to the spinal cord or brain. As with CAT scans, a contrast material may be injected in the patient to improve the quality of the images.
- Gallium scan. In this procedure, a patient receives an injection of gallium-67, a slightly radioactive substance that is often absorbed by areas of the body where Hodgkin’s lymphoma is present. A couple of hours after the injection, the patient is placed under a scanner that detects where the gallium has accumulated in the body and the image is recorded on film. These tests are useful for locating the disease in bones and organs.
- Positron emission tomography (PET) scan. In this procedure, the patient receives an injection of glucose (sugar) containing a small amount of radioactive material. The radioactive glucose is absorbed by the cancer cells in the body. A camera then scans the patient and detects where the radioactive glucose was absorbed. Areas of cancer appear as “hot spots” on the image. This test may be used to detect if and where cancer has spread in the body.
- Lymphangiogram. An x-ray examines the lymph nodes in the pelvis and abdomen. Blue dye is injected into the skin between the patient’s toes. The dye is picked up by lymph vessels causing them to become blue and allowing the physician to easily recognize them. This test is not used as often now for diagnosing and staging the disease.
Additional tests that may be ordered include:
- Blood tests. Although Hodgkin’s lymphoma cells do not appear in blood, a complete blood count (CBC) may be ordered to reveal signs of the disease including anemia and increased white blood cells. When Hodgkin’s lymphoma is in the liver, blood tests of liver function can have abnormal results. Sedimentation rate and blood chemistry studies may also be ordered.
- Bone marrow biopsy and aspiration. Usually completed together during the same procedure, a bone marrow biopsy and a bone marrow aspiration may be ordered to detect if the Hodgkin’s lymphoma is in the bone marrow. Although generally used for staging the disease, a bone marrow biopsy may be ordered on a rare occasion to diagnose Hodgkin’s lymphoma.
- Immunophenotyping. A sample of white blood cells is taken to determine the specific cell type and characteristics. The test may be used to determine if the malignant cells developed from B lymphocytes (B-cells) or T lymphocytes (T-cells).
Treatment and prevention of Hodgkin’s
Treatment for Hodgkin’s lymphoma is based on the stage of the disease, as well as the patient’s age, general health, and the type and site of the cancer. A cancer care team, usually headed by a medical oncologist, may coordinate the patient’s treatment. In the early stages, cases may be classified as favorable or unfavorable depending on certain factors. These factors can include the presence of a large tumor in the chest, the patient’s age, or whether the cancer has spread outside the lymph nodes or to other regions of within lymph nodes.
When Hodgkin’s lymphoma is classified as unfavorable, more intensive treatment is usually recommended. Other factors that may require more intensive treatment include:
- Being male
- Having a high white blood cell count (above 15,000)
- Having a low red blood cell count (hemoglobin level below 10.5).
- Having a low blood lymphocyte count (below 600).
The two main methods used to treat Hodgkin’s lymphoma are chemotherapy and radiation therapy. The best treatment approach may require one or both of these methods.
- Chemotherapy. This treatment method uses powerful drugs to kill cancer cells. The standard drug combination used to treat Hodgkin’s disease in the United States is known as ABVD. This combination includes:
Other commonly used combinations include:
- Stanford V
For some patients, high-dose chemotherapy with blood-forming stem cell transplants may be recommended. This treatment involves giving the patient very high doses of chemotherapy, followed by an infusion of their own previously collected blood-forming stem cells or stem cells from a matched donor. This treatment method may be recommended for:
- Patients who did not completely respond to standard treatments of chemotherapy and radiation therapy
- Patients who responded to standard treatment, but whose cancer returned soon after
In the procedure, the stored stem cells are thawed and placed back into the patient through a vein. Within a week or two, the cells begin restoring the body’s blood cells.
Follow-up care is very important after the treatment of Hodgkin’s lymphoma. The patient needs to be monitored for many years or decades. The patient’s cancer care team will provide information as to the type and schedule of tests needed following treatment.
One of the most serious side effects of the treatment for Hodgkin’s lymphoma is developing a second cancer, particularly acute myelogenous leukemia (AML). The American Cancer Society (ACS) estimates that 5 percent of patients receiving certain types of treatment for Hodgkin’s lymphoma can develop this cancer. It appears more often in older individuals and usually occurs within the first few years after treatment. For this reason, patients should adhere to their designated follow-up medical plan.
Currently there are no established prevention methods for Hodgkin’s lymphoma. However, advances in diagnosis, staging and treatment methods have helped to make the disease highly treatable with the potential for complete recovery. According to the ACS, the 15-year relative survival rate for all patients after treatment is 68 percent.
Ongoing research on Hodgkin’s lymphoma
There is a considerable amount of research being conducted by various groups in Hodgkin’s lymphoma. The Lymphoma Research Foundation is one such organization that is active in research and clinical trials. Some of the most promising areas for Hodgkin’s lymphoma detection and treatment include:
- Better classification of types of the disease
- Improvement of monoclonal antibody therapy
- Use of advanced biologic therapies
- Trials of new drug agents and drug combinations
- Improved treatments with fewer side effects
- Development of tumor-specific vaccines
- Use of immune-cell therapy
- Advancing stem cell transplantation
Staging Hodgkin’s lymphoma
The staging system for Hodgkin’s lymphoma consists of four categories. Depending on how far the cancer has spread, the disease will be placed in either stage I, II, III or IV. The letter “E” is added to the stage when an organ outside of the lymph system is affected.
Stage I. Hodgkin’s lymphoma is considered to be at stage I when one of the following factors is present
- The cancer is found in only one lymph node area such as the neck, armpit or groin.
- The cancer is found in only one area of a single organ outside of the lymph system (IE).
Stage II. Hodgkin’s lymphoma is considered to be at stage II when one of the following factors is present:
- The cancer is found in two or more lymph node areas on the same side (above or below) of the diaphragm (the muscle that separates the chest and abdominal cavities, and aids breathing).
- The cancer has spread locally from the lymph nodes into nearby tissue (IIE).
Stage III. Hodgkin’s lymphoma is considered to be at stage III when one of the following factors is present:
- The cancer is found in lymph node areas on both sides (above and below) of the diaphragm.
- The cancer may have spread into an organ or area next to the lymph node (IIIE), into the spleen (IIIS), or both (IIISE).
Stage IV. Hodgkin’s lymphoma is considered to be at stage IV when one of the following factors is present:
- The cancer has extended to more than one area in an organ or to two or more organs outside of the lymph system.
- The cancer has extended to only one organ outside of the lymph system, but lymph nodes far from the organ are involved.
These stages may be further separated into “A” (symptoms are not present) and “B” (certain symptoms are present) categories. A patient is placed in the “B” category when the following symptoms are present:
- A loss of more than 10 percent of total body weight over the previous six months.
- A fever at or above 100 degrees Fahrenheit (38 degrees Celsius) without a known cause (except the cancer).
- Drenching night sweats.
According to the American Cancer Society (ACS), five-year relative survival rates based on stage are:
|Stage||5-Year Relative Survival Rate|
|Stage I||90 to 95 percent|
|Stage II||90 to 95 percent|
|Stage III||85 to 90 percent|
|Stage IV||About 80 percent|
Questions for your doctor
Preparing questions in advance can help patients have more meaningful discussions with their physicians regarding their condition. Patients may wish to ask their doctor the following questions about Hodgkin’s lymphoma (HL):
- What is the difference between Hodgkin’s lymphoma and non-Hodgkin’s lymphoma?
- How will I know the cause of a swollen lymph node?
- What tests will be performed to determine if I have HL?
- What type of biopsy will I need? Where can it be performed?
- When and from whom will I learn the biopsy results?
- What is the type and stage of my HL?
- What is my prognosis with this type of cancer?
- What are my treatment options?
- What are the risks associated with these treatments?
- Am I a candidate for a stem cell transplant?
- Can I donate my own stem cells? If not, how will a donor be found?
- What are the chances that my HL will return?
- Can I do anything to prevent a recurrence?
- What will be done to monitor my HL?
- Will my children be at higher risk if I have HL?