Christopher Dolinsky, MD and Christine Hill-Kayser, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: February 27, 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 (or lymph) is a clear fluid that leaks out of blood vessels, and in order for the body to keep the blood volume constant, 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, filtering out infection-causing germs (bacteria, viruses, etc.) and helping to fight any infections that may be present. 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.
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. These organs and the lymph nodes are the major regions of the body where lymphatic tissue is found, but small amounts of can also be found in many of the other organs in the body.
Hodgkin's disease is a disease of lymph nodes and lymphatic tissues, called a lymphoma. There are other types of lymphomas besides Hodgkin's disease, but they will be discussed in a separate review. 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 is an uncommon cancer in children, making up 6% of all childhood cancers. It occurs much more commonly in males, and is more more common during adolescence than in early childhood. In fact, Hodgkin's disease is extremely rare in children under the age of 5 years.
No one knows what causes Hodgkin's disease. It has been theorized that the development of Hodgkin's disease is related to infection with a virus, although this is not known for certain. No clear-cut associations have been found with exposures to toxins, chemicals, or environmental agents. First degree relatives of patients with Hodgkin's disease have a higher chance of developing the disease, but exactly how genetics control this disease is poorly understood.
Contracting the HIV virus may be a risk factor 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 to prevent developing it.
Hodgkin's disease is rare enough that it is not screened for with any specific tests. The best way to pick up a diagnosis of Hodgkin's disease early is to see a doctor regularly for a thorough physical examination.
Unfortunately, the early stages of Hodgkin's disease may not have any symptoms. As the tumor grows in size, it can produce a variety of symptoms including:
Many of these symptoms are non-specific, and could represent a variety of different conditions; however, any child with any of these problems should be seen by a physician. The most common presenting symptom of Hodgkin's disease in childhood is swelling of nodes in the neck.
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 lymph node that is enlarged, it will likely be surgically removed with 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 patient. Often, a PET scan will be ordered as well. Staging is performed in order to guide the choice of treatment and offer information about prognosis. 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, this can affect the stage classification. High fevers, night sweats, or weight loss (greater than 10% of original body weight) 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, any disease that is found in regions other than lymph nodes (like other organs), is called extranodal disease. Any patient with extranodal disease will have the letter E included in their stage. Finally, patients with large (bulky) lymph nodes may have the letter X included in their stage.
Over the years, the cure rates for pediatric Hodgkin's disease have increased dramatically. Given the excellent results achieved with older regimens, newer research efforts have focused on decreasing the toxicity of the available curative therapies in order to decrease long-term treatment-related side effects in the surviving patients. There are a number of side effects that both chemotherapy and radiation can cause when given to child, so newer treatment strategies have lowered chemotherapy doses, used less toxic agents, and decreased the amount of radiation used.
Chemotherapy is the use of anti-cancer drugs that go throughout the entire body. These drugs may be given through a vein as a liquid or by mouth as pills. Chemotherapy has become the mainstay of treatment for patients with Hodgkin's disease, and combinations of different chemotherapy drugs are used to kill the tumor cells. One of the more common chemotherapy regimens is called "ABVD". ABVD stands for four different drugs: Adriamycin, Bleomycin, Vinblastine, and Dacarbazine. Another common regimen in pediatric Hodgkin's disease is called "COPP". COPP stands for Cyclophosphamide, Vincristine, Prednisone, and Procarbazine. Oftentimes, more than one chemotherapy regimen is recommended. There are many other chemotherapy drugs besides ABVD and COPP that are used for Hodgkin's disease, and your oncologist can explain why he or she recommends one particular regimen over another.
Pediatric Hodgkin's disease patients are generally treated with radiation therapy after they receive chemotherapy. Radiation therapy uses high-energy rays (similar to x-rays) from an external source to kill cancer cells. It requires patients to come in 5 days a week for 3-4 weeks to a radiation therapy treatment center. The treatment takes just a few minutes, and it is painless. Children receive lower doses of radiation than adults with this disease. Patients are usually given some chemotherapy first, and then they receive radiation to the sites of their body that are involved by disease. Radiation is also used for big, bulky areas of disease. Your radiation oncologist can answer questions about the utility, process, and side effects of radiation therapy in your child's particular case.
Sometimes patients receive chemotherapy and radiation therapy and their Hodgkin's disease isn't cured. When this happens, further chemotherapy and radiation, or stem cell transplantation may be recommended. Stem cells are cells in everyone’s body that can develop into other types of cells when placed in certain environments. Stem cell transplantation is used along with high doses of chemotherapy. The high doses of chemotherapy are so intense that they destroy a patient'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 used. In the case of autologous stem cell transplants, a patient's own stem cells are harvested before the high dose chemotherapy is given, then stored, and 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. In allogeneic stem cell transplants, the stem cells of another person may be used to re-grow the bone marrow of a patient needing high-dose chemotherapy to treat Hodgkin’s disease. 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 and radiation therapy.
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 occur fairly often. The longer a patient is free of disease, the less often he or she will have to go for checkups. Your doctor will tell you when he or she wants follow-up CT scans or PET scans.. Unfortunately, anyone who receives radiation may be at higher risk for a second cancer later in life. This risk may be higher for children who receive radiation, and children who have had cancer treatment should be followed by a specialist who is able to screen for second cancers. The American Cancer Society has recently identified an increased risk of breast cancer in women who receive radiation to the chest as part of Hodgkin’s disease. For this reason, the American Cancer Society recommends that women who have had chest radiation in the past be screened for breast cancer with MRI scans starting 8 years after their radiation treatment, or at age 30 (whichever is first).
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 pediatric Hodgkin's disease. You may find this information useful when meeting with your physician, making treatment decisions, and continuing your search for information. You can learn more about pediatric Hodgkin's disease on OncoLink through the related links to the left.