Eric Shinohara, MD, MSCI
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: February 22, 2008
Lymph nodes are small, grape-sized glands that exist throughout the body and make up part of the lymphatic fluid circulation system. Lymphatic fluid is a clear fluid that leaks out of blood vessels, and in order for the body to keep the blood volume constant, lymphatic fluid is collected and returned to the blood via the lymphatic circulation. Lymph nodes are connected to each other by lymph vessels that transfer the lymphatic fluid. Before returning the lymph to the blood, lymph nodes clean up the fluid, looking for possible infection-causing germs (bacteria, viruses, etc.) the body using cells of the immune system. Most people can remember having swollen "glands" under their neck when they had an infection. Those "glands" were swollen lymph nodes that were reacting to the infection. In most cancers, this network of lymph nodes is one of the first areas to which cancer can spread. However, in Hodgkin’s Disease (also known as Hodgkin’s Lymphoma) the cancer arises from the lymph nodes themselves.
Clusters of lymph nodes exist in particular parts of the body, like the neck, the underarm, and the groin. There are also specific organs in the body that are considered part of the lymphatic system, like the spleen and the tonsils; however, small amounts of lymph tissue can also be found in many of the other organs in the body.
Hodgkin's disease, or Hodgkin’s lymphoma, is a disease of lymph nodes and lymphatic tissues, and is named after the pathologist who originally described the disease in 1832, Dr. Thomas Hodgkin. There are other types of lymphomas besides Hodgkin's disease, known as Non-Hodgkin’s lymphomas (NHL). Although NHLs are also a cancer of the lymph nodes, they are treated differently and are discussed in another overview. Hodgkin's disease occurs when cells in the lymph nodes begin to grow out of control and compress nearby tissues or spread throughout the body via the lymphatic circulation. Hodgkin's disease is distinguished from the other types of lymphomas by the way it looks under a microscope and by the way it grows and spreads.
Hodgkin’s disease itself can be broken down into several categories. The two main categories are classical Hodgkin’s disease and nodular lymphocyte-predominant Hodgkin's disease. Which type of Hodgkin’s disease a person has is determined by a pathologist who examines the biopsy of the involved node(s). Pathologists look for a particular abnormal cell known as a Reed-Sternberg cell in order to diagnose classic Hodgkin’s disease. The different types of Hodgkin’s disease behave slightly differently, but are generally approached in a similar fashion regarding treatment.
Hodgkin's disease is a fairly uncommon cancer, with 7,800 cases diagnosed annually in the United States.Hodgkin’s disease causes approximately 1400 deaths annually. Hodgkin's disease occurs slightly more commonly in men, and much more frequently in Caucasians. Hodgkin’s lymphoma most commonly affects people in two age groups, those in their 20-30’s and those in their 50’s.
No one knows what causes Hodgkin's disease, however several factors have been identified to be associated with Hodgkin’s disease It is important to note that these factors may increase the risk of developing Hodgkin’s disease, but that the majority of people with these conditions still do not develop Hodgkin’s disease. Infection with the Epstein-Barr virus may play a role in the development of certain types of Hodgkin’s disease. Epstein-Barr virus also causes mononucleosis, also known as “mono” or “kissing disease.” It appears that the relatives of people who develop Hodgkin’s disease at a very young age may be at increased risk of developing Hodgkin’s disease.
People with depressed immune function, such as patients with AIDS or with organ transplants ( and thus are taking medications which suppress the immune system), appear to be at increased risk for developing Hodgkin’s disease. It has been recognized that Hodgkin's disease in HIV-infected patients is generally more aggressive and advanced than in non-HIV-infected patients. However, researchers disagree as to the importance of this finding.
Because no one knows exactly what causes Hodgkin's disease, there are no specific steps anyone can take to prevent developing it.
Hodgkin's disease is rare enough that it is not screened for in the general population with any specific blood tests or radiology studies. The best way to pick up a diagnosis of Hodgkin's disease early is to see your doctor regularly for a thorough physical examination. Often, the person himself is the first to note a lump, and if this happens, one should go to the physician for examination and further evaluation.
Unfortunately, the early stages of Hodgkin's disease often do not cause any symptoms.. As the tumor grows in size, however, it can produce a variety of symptoms. The most common lymph node site affected by Hodgkin’s disease is in the neck, and neck swelling is what often brings people to the doctor. However, Hodgkin’s disease can also cause swelling of the groin or nodes of the underarm; these swellings are often not painful but can feel rubbery. Hodgkin’s disease can also cause fevers, drenching night sweats, weight loss, and even generalized itching. Hodgkin’s disease can also cause lymph nodes in the chest to swell, which is are not typically seen or felt, but can cause symptoms such as cough, shortness of breath, or chest pain. A chest X-ray can often detect these swollen nodes in the chest. Interestingly, some people with Hodgkin’s disease will note pain in the lymph nodes after minimal alcohol consumption.
Many of these symptoms are non-specific, and could represent a variety of different conditions; however, your doctor needs to see you if you have any of these problems. The most common presenting symptom of Hodgkin's disease is swelling of nodes in the neck or underarm.
When a patient presents with symptoms suggestive of Hodgkin's disease, his/her physician will perform a thorough history and physical examination. If there is a node that is enlarged, it will likely be surgically removed in what is called an "excisional biopsy". The entire node is removed so that another doctor known as a pathologist can look at it under a microscope. A biopsy specimen is required to make the diagnosis of Hodgkin's disease.
Once the diagnosis is made, a physician will order a number of tests to get a sense of the extent of the disease. A few different blood tests will probably be ordered. The physician will also get a CT scan (3D X-ray) to stage the person. Often, a PET scan will be ordered as well. By determining the extent of the disease, the stage of the disease can be determined which is important in determining the optimal treatment and the prognosis for each individual. A simplified version of the staging system for Hodgkin's disease (called the Modified Ann Arbor Staging System) is offered below:
Stage 1. Single lymph node region involved with disease
Stage 2. Two or more lymph node regions involved on the same side of the diaphragm (the muscle that controls breathing and that separates the chest from the abdomen)
Stage 3. Lymph node regions involved on both sides of the diaphragm
Stage 4. Diffuse involvement of an organ that is not considered part of the lymphatic system (like the lung or liver)
If a patient has certain symptoms, such as the ones we described above, this can affect the stage classification. High fevers, night sweats, or weight loss (greater than 10% of original body weight over 6 months) are all called "B" symptoms. If a patient has B symptoms, then his/her stage will include the letter "B" after the stage number. If a patient doesn't have any of these B symptoms, then his/her stage will include the letter "A" after the stage number. Additionally, if the disease has spread to areas outside of the lymph nodes the stage will include an “E.” If the disease is considered “bulky” (greater than 10 cm in size) this is also noted in staging and may require more aggressive treatment. Bulky disease is designated with an “X.”
Chemotherapy is the use of anti-cancer drugs that go throughout the entire body. These drugs may be given through a vein as liquid or by mouth as pills. Chemotherapy has become the first-line treatment for patients with Hodgkin's disease, and combinations of different chemotherapy drugs are used to kill the tumor cells. One of the most common chemotherapy regimens is called "ABVD". ABVD stands for four different drugs: Adriamycin, Bleomycin, Vinblastine, and Dacarbazine. There are many other chemotherapy drugs besides ABVD, such as the Stanford V and BEACOPP, that are used for Hodgkin's disease. Currently there are several trials comparing these chemotherapy regimens, as well as the duration and intensity of chemotherapy necessary to adequately treat Hodgkin’s disease. There are several toxicities associated with ABVD. There can be damage to the heart tissue and lungs, as well as effects on fertility. There is also the risk of developing a secondary malignancy, such as leukemia, after treatment with chemotherapy, although this risk is lower with ABVD compared with older chemotherapy treatments. Your oncologist can explain why he or she recommends one particular regimen over another.
Early stage Hodgkin's disease patients (stage IA or IIA) can be treated with radiation therapy alone, however the trend has been towards combined treatment with chemotherapy followed by radiation. There are several trials underway to determine the optimal dose of radiation, and there are trials underway to see if chemotherapy alone is adequate, although early results suggest that there is a slightly higher recurrence without the radiation. Radiation therapy uses high-energy rays (similar to x-rays) from an external source to kill cancer cells. Radiation therapy requires patients to come in 5 days a week for about 4-5 weeks to a radiation therapy treatment center. The treatment takes just a few minutes, and it is painless. As stated above, stage IA or IIA patients are usually given some chemotherapy first, and then they receive radiation to the sites of their body that are (or were, before the chemotherapy) involved by disease. Radiation is also used for big, bulky areas of disease. In advanced Hodgkin’s disease (stage III or IV), radiation can be used to “boost” areas which have not fully responded to chemotherapy. Radiation side effects are generally limited to the area of treatment. Hence, if the chest is being treated, there is the potential for heart damage and having earlier onset of coronary artery disease. The lungs also can be injured. If the abdomen and/or pelvis require radiation, fertility can be affected as well as the abdominal and pelvic organs. Your radiation oncologist can answer questions about the indications, process, and side effects of radiation therapy in your particular case.
Sometimes patients receive chemotherapy +/- radiation therapy, but their Hodgkin's disease still isn't cured. When this happens, they may be recommended to undergo a stem cell transplantation. Stem cells are precursor cells that can develop into other cells of the body when placed in the right environment. Stem cell transplantation is used along with high doses of chemotherapy. The high doses of chemotherapy are so intense that they wipe out the person’s bone marrow. Without bone marrow, a person can't make the components of blood and the immune system that are necessary to survive. In order to replace the patient's bone marrow, stem cells are given. In the case of autologous stem cell transplants, a patient's own stem cells are harvested before the high dose chemotherapy is given, stored, and then finally returned to the patient after the chemotherapy is done. This way, the bone marrow can re-grow from the stem cells. This enables a patient to tolerate the super high doses of chemotherapy that work against Hodgkin's disease but have the unwanted side effect of wiping out healthy bone marrow. Stem cell transplantation can sometimes cure patients when other treatment strategies have failed. However, stem cell transplantation is a complex and intense treatment, so it is typically reserved for patients who aren't cured with the initial regimens of chemotherapy +/- radiation therapy. Stem cell transplants can also be used in people who have a relapse (recurrence) of their Hodgkin’s disease.
Once a patient has been treated for Hodgkin's disease, he or she needs to be closely followed for a recurrence. At first, follow-up visits will be fairly frequent. The longer a patient is free of disease, the less often the checkups. The oncologist will tell you when he or she wants follow-up CT scans or PET scans. It will also be very important to screen all Hodgkin's patients for the development of any new cancers that may arise. Due to the side effects associated with treatment for Hodgkin’s disease there needs to be close follow up for other health problems related to treatment. This included closer breast cancer surveillance for young women who received chest radiation as well as good control of blood pressure and cholesterol as prior chest radiation may increase the risk of atherosclerosis. Chemotherapy can also damage the lungs and heart and people who have received chemotherapy should have these organ systems, among others followed.
Clinical trials are extremely important in furthering our knowledge of this disease. It is through clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your doctor about participating in clinical trials in your area.
This article is meant to give you a better understanding of Hodgkin's disease. Use this knowledge when meeting with your physician, making treatment decisions, and continuing your search for information. You can learn more about Hodgkin's disease on OncoLink through the related links to the left.
Connors, Joseph M. "Hodgkin's Lymphoma" from Clinical Oncology 3rd Edition., Abeloff et al. Elsevier Churchill Livingstone. Philadelphia, PA, 2004. pg. 2985-3014
Yung, Lynny and Lynch, David. Hodgkin's Lymphoma. The Lancet. Vol 361, March 15,, 2003. pg943-951