Adult Hodgkin's Disease: The Basics

Eric Shinohara, MD, MSCI and Elizabeth N. Kuhn
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: September 16, 2013

What are lymph nodes?

Lymph nodes are small, bean-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 small 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 almost every other organ in the body. While there are certain areas in the body where lymph nodes are routinely found (eg. Underarms, groin, neck), the specific arrangement and number of these lymph nodes is different from person to person.

What is Hodgkin's disease?

Hodgkin's disease, or Hodgkin's lymphoma, is a cancer 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. Although non-Hodgkin's lymphomas are also a cancer of the lymph nodes, they are treated differently and are discussed in another overview article. Hodgkin's disease occurs when infection-fighting 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 lymphoma, which has four subtypes:
    • Nodular sclerosing (70%)
    • Mixed cellularity (20-25%)
    • Lymphocyte-depleted (5%)
    • Lymphocyte-rich (<1%)
  • Nodular lymphocyte-predominant Hodgkin's lymphoma

Overall, classical Hodgkin's lymphoma accounts for about 95% of all cases, while nodular lymphocyte-predominant (NLP) Hodgkin's lymphoma is quite rare. The type of Hodgkin's disease a person has is determined by a pathologist who examines a biopsy of the involved node(s). Pathologists look for a particular abnormal cell known as a Reed-Sternberg cell (also known as an "owl's eye" cell) in order to diagnose classic Hodgkin's disease, or a "popcorn" cell to diagnose NLP Hodgkin's disease. The distinction between classical Hodgkin's and NLP is important because they are treated differently.

Am I at risk for Hodgkin's disease?

Hodgkin's disease is a fairly uncommon cancer, with about 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 20-30s and those in their 50s. (Pediatric Hodgkin's Disease is discussed separately).

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. There seems to be a decreased risk of Hodgkin's lymphoma in people who were breastfed, or had childhood infection with measles, mumps, chicken pox, rubella or pertussis. Smoking may increase the risk of Hodgkin's lymphoma.

People with depressed immune function, such as patients with HIV/AIDS or those taking medications that suppress the immune system (eg. people with organ transplants or autoimmune diseases), 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.

How can I prevent Hodgkin's disease?

Because no one knows exactly what causes Hodgkin's disease, there are no specific steps you can take to prevent it.

What screening tests are available?

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 healthcare provider regularly for a thorough physical examination. Often, the patient is the first to notice a lump, and if this happens, one should see their healthcare provider for examination and further evaluation.

What are the signs of Hodgkin's disease?

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 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 healthcare provider 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.

How is Hodgkin's disease diagnosed and staged?

When a patient presents with symptoms suggestive of Hodgkin's disease, his/her healthcare provider 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 a 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. It is important that the doctor use an excisional biopsy—the alternative is a core-needle biopsy, where a small needle is inserted into the swollen lymph node and a sample of the lymph node is taken. However, core-needle biopsies may not provide enough tissue to make a diagnosis.

Once the diagnosis is made, a healthcare provider will order a number of tests to get a sense of the extent and severity of the disease. A few different blood tests will probably be ordered, including blood counts, liver function tests, kidney function tests, erythrocyte sedimentation rate (ESR, a marker of inflammation) and a pregnancy test in women of childbearing age. The physician will also get a PET-CT scan to stage the disease (see staging information below). A PET-CT scan combines a CT scan of the body, a 3D xray, with PET. The CT portion helps your doctor define the location of lymph nodes which are affected by cancer. The PET scan is a special type of scan where a sugar solution is injected through an IV; tissues that are very active (like cancer cells) use the sugar for energy. These areas "light up" when we scan them. The PET scan is important for two reasons: 1) It helps confirm where lymphoma is located in the body; and 2) It gives your doctor the "before-treatment" picture. PET scan is used after treatment to determine if the cancer has been killed and it is important to be able to compare the "after-treatment" PET with a "before-treatment" PET.

After obtaining a PET-CT, the stage of the disease can be determined which helps determine 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 I. Single lymph node region involved with disease.
  • Stage II. 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 III. Lymph node regions involved on both sides of the diaphragm.
  • Stage IV. 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 with an "X" and may require more aggressive treatment. Finally, if the spleen is involved, the stage includes an "S." All of these additional designations seem complicated, but they help doctors select the most appropriate treatment and enable everyone to use the same language, so to speak.

Early stage Hodgkin's lymphoma (Stage I-II) is divided further into two groups, "favorable" and "unfavorable", to help predict which patients may benefit from more aggressive treatment. The criteria for unfavorable disease are as follows:

  • Bulky disease (tumor >10 cm in size)
  • Extension outside of lymph nodes ("extranodal" disease)
  • Involvement of three or more lymph node areas, or
  • ESR > 50 mm (or ESR > 30 mm plus B symptoms)

What are the treatments for Hodgkin's disease?

Chemotherapy & Biotherapy

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 is frequently used for patients with Hodgkin's disease, and combinations of different chemotherapy drugs are used to kill the tumor cells. The most common chemotherapy regimens are called ABVD, BEACOPP, and Stanford Five (V). ABVD is an acronym for the combination of four different drugs: adriamycin, bleomycin, vinblastine, and dacarbazine. BEACOPP stands for: bleomycin, etoposide, adriamycin, cyclophosphamide, oncovin (vincristine), procarbazine, and prednisone. Stanford V is the combination of doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone. As you may imagine, ABVD is a less rigorous chemotherapy regimen than either BEACOPP or Stanford V. It is not always clear that one chemotherapy regimen is better than the others, and thus, the regimen selected may vary between oncologists. Your oncologist can explain why he or she recommends one particular regimen over another.

Another class of drugs often used to treat lymphomas are the monoclonal antibodies, which are a type of targeted therapy. Antibodies are produced normally in the body and are used to "mark" abnormal things (eg. bacteria, viruses, cancer cells), so that the immune system will attack and kill those cells. Monoclonal antibodies are man-made antibodies that are designed to attack specific kinds of cells (in this case, lymphoma cells), taking advantage of the bodies own defense systems to kill cancer. The most common monoclonal antibody used in Hodgkin's lymphoma is Rituximab, though there are others that are currently being investigated.

There are a number of side effects associated with chemotherapy. These vary based on which kind of chemotherapy is used, and more detailed explanations of chemotherapy can be found here.

Radiation Therapy

Radiation therapy uses high-energy rays (similar to x-rays) delivered from an external source to kill cancer cells. Unlike chemotherapy, which goes everywhere in the body, radiation therapy is a local treatment. It can be targeted only to areas where there is known disease, or areas with a large volume of lymphoma cells, or even areas where your physician is worried about cancer spreading or recurring. There are two main types of radiation used to treat Hodgkin's lymphoma: photon and proton therapy. Proton therapy is only available at a few centers nation-wide and is not as well-studied in Hodgkin's lymphoma as photon therapy. You should discuss with your doctor if proton therapy may be right for you.

Radiation therapy typically requires patients to come to a radiation therapy treatment center 5 days a week for about 4-5 weeks. Radiation dose is measured in Gray (Gy) and doses for lymphoma are typically 20-40 Gy total, given in 150-200 cGy "fractions" for about 10-25 treatments. The treatment takes just a few minutes, and it is painless. You shouldn't feel anything, though you may see some lights on the machines and hear them as they move around. Most radiation oncologists see patients weekly while they are receiving treatment to monitor for side effects and answer questions. 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 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. More information about side effects of radiation can be found here. Your radiation oncologist can answer questions about the indications, process, and specific side effects of radiation therapy for you.

Stem Cell Transplantation

Sometimes patients receive chemotherapy and/or radiation therapy, but the Hodgkin's disease is still present. When this happens, the oncologist may recommend 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 a 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 an 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. Another option is an allogeneic stem cell transplant, where the stem cells are taken from a donor whose cells "match" those of the recipient. These cells are used in the same way, given to the patient after high dose chemotherapy. In both cases, bone marrow cells can re-grow from the stem cells. This enables a patient to tolerate the 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 treatment regimens of chemotherapy and/or radiation therapy. Stem cell transplants can also be used in people who have a relapse (recurrence) of their Hodgkin's disease.

Which treatment is right for me?

Hodgkin's disease was once believed to be incurable, but tremendous advancements in treatment have led to 5-year survival of about 85%. Even patients with advanced (Stage III-IV) disease have a 5-year survival around 70-75%. The type and duration of treatment depends on the stage of Hodgkin's lymphoma, whether it is favorable or unfavorable, and if it is NLP Hodgkin's. Most often, however, a combination of both chemotherapy and radiation is used. The following discussion of specific treatments will explain more based on stage and other prognostic information.

Early stage (Stage I-II), favorable

Treatment of early stage Hodgkin's disease consists of chemotherapy plus radiation. The large HD10 clinical trial found that two cycles of ABVD chemotherapy plus 20 Gy radiation has equivalent outcomes and less toxicity compared to other therapy combinations (which involved more chemotherapy and higher doses of radiation). Some clinicians may opt for four cycles of ABVD in patients who are on the border between favorable and unfavorable disease. Another acceptable option for chemotherapy is eight weeks of Stanford V followed by radiation. After completing chemotherapy, your doctor will likely obtain a repeat PET scan to see how well the lymphoma responded to treatment. If it responded well, radiation is recommended. There are currently ongoing clinical trials investigating whether radiation is necessary in cases where the lymphoma is completely eradicated after two cycles of chemotherapy—at the present time, however, post-chemotherapy radiation is the standard of care. If there was a suboptimal response, no response, or worsening of the disease despite chemotherapy, most clinicians will repeat a biopsy and then proceed with additional chemotherapy.

Early stage (Stage I-II), unfavorable

Treatment of early stage, unfavorable Hodgkin's disease also consists of both chemotherapy and radiation, but as you may suspect, more intense therapy is used. The two most commonly used treatment regimens are four cycles of ABVD chemotherapy plus 30 Gy radiation (based on results from the large HD11 clinical trial), or 12 weeks of Stanford V chemotherapy plus radiation. Again, after completing chemotherapy, your doctor will obtain a repeat PET scan to see how well the lymphoma responded to treatment and if additional treatment is necessary. If there was a suboptimal response, no response, or worsening of the disease despite chemotherapy, most clinicians will repeat a biopsy and then proceed with additional chemotherapy.

Stage III-IV

Treatment of Stage III-IV Hodgkin's disease is even more intense than unfavorable early-stage disease. It begins with intense chemotherapy: 6 cycles of ABVD, 12 weeks of Stanford V, or 4-8 cycles of BEACOPP. After chemotherapy, a PET scan is obtained, and radiation is added to areas of disease that were bulky (>10 cm) before chemotherapy, or that remain active on PET after chemotherapy (ie. Not completely killed by chemo alone). If there was a suboptimal response, no response, or worsening of the disease despite chemotherapy, most clinicians will repeat a biopsy and then proceed with additional chemotherapy or a bone marrow transplant.

Nodular lymphocyte predominant (NLP)

NLP Hodgkin's lymphoma tends to be less aggressive than classical Hodgkin's, and more than 75% of patients present with early-stage (Stage I-II) disease. Because experience has shown that NLP responds in a distinctly different way from classical Hodgkin's lymphoma, the National Comprehensive Cancer Network has a distinct set of treatment recommendations for NLP Hodgkin's lymphoma based on available studies and consensus opinion. Stage I-II NLP can be treated with radiation alone; studies have shown that adding chemotherapy in these patients does not improve survival or decrease the risk of relapse (though it increases side effects). Advanced disease (Stage III-IV) is treated similarly to advanced-stage classical Hodgkin's lymphoma, with chemotherapy as the primary treatment. Typically, MOPP (mechlorethamine, vincristine, procarbazine, prednisone) or ABVD is used. More recently, there has been interest in using Rituximab along with traditional chemotherapy to increase the likelihood of achieving a complete remission. Radiation therapy can also be added if areas of lymphoma are causing pain, discomfort, or impairing the normal function of organs. In these cases, radiation therapy is done for comfort, not necessarily to increase the likelihood of cure.

Follow-up Testing

Once a patient has been treated for Hodgkin's disease, he or she needs to be closely followed for recurrence, or return of the cancer. Your oncologist will tell you when he or she wants follow-up CT scans or PET scans. Most relapses are detected clinically (ie. your doctor taking a thorough history and performing a good physical exam). Screening PET scans are not recommended because they have a high false-positive rate, meaning that most things that look like relapse on PET scan turn out not to be cancer. At first, follow-up visits will be fairly frequent. The longer a patient is free of disease, the less often the checkups. Usually, follow-up with an oncologist lasts for 5 years as long as no lymphoma returns; however, relapses can occur even after 5 years of being disease-free, especially in the lymphocyte-predominant subtype of Hodgkin's lymphoma.

Fortunately, Hodgkin's lymphoma has high cure rates and patients who are cured of their Hodgkin's disease can be expected to live many decades after their treatment. Unfortunately, this also means that some of the very late effects of treatment can be seen. There is little to no evidence showing that specific surveillance measures improve long-term outcomes; however, groups such as the National Comprehensive Cancer Network (NCCN) and American College of Radiology, among others, have created consensus guidelines for long-term surveillance in Hodgkin's disease survivors. You can also create a personalized LIVESTRONG Care Plan to summarize potential late effects of treatment, recommended testing, psychosocial effects, effective preventive options, and available support resources. More detailed recommendations for survivors of childhood cancer are available from the Children's Oncology Group. Be sure to discuss your survivorship care plan with your oncology team, as they can answer questions and provide additional information.

General Health

After completing treatment for Hodgkin's lymphoma, you should see a physician every 2-4 months for the first two years, then every 3-6 months for the next 3-5 years, and annually thereafter.

  • Basic blood counts and chemistry profiles should be obtained at these visits to monitor for organ damage that may not be causing any symptoms.
  • You should get an influenza vaccine every year.
  • If you were treated with radiation to your spleen or splenectomy (surgical removal of the spleen), you are at increased risk of certain types of infections and will need to follow certain precautions.
  • Five years after treatment, the NCCN recommends vaccination against meningococcus (which can cause meningitis), pneumococcus (which causes some types of pneumonia) and H. influenza (which can cause a number of infections, including both meningitis and pneumonia).
  • Ask your oncology team if you have any questions about reproduction or fertility, general health habits, or psychosocial issues.

Cancer Screening

In people who survive Hodgkin's lymphoma, the leading cause of death is a second cancer (especially breast, colon and lung cancer). In fact, it is estimated that about 30% of women who receive chest radiation for Hodgkin's lymphoma will develop breast cancer during their lifetime. For this reason, it is recommended that Hodgkin's survivors have earlier and more frequent cancer screening.

  • If you received radiation to your chest or chemotherapy with an "alkylating" agent (eg. Cyclophosphamide, mechlorethamine, cisplatin, carboplatin, procarbazine), you are at increased risk for lung cancer. Beginning five years after treatment, the recommended lung cancer screening is a yearly chest x-ray or CT scan.
  • Females who received radiation to the chest or axilla (arm pit area) should receive frequent breast cancer screening, beginning 8-10 years after completing cancer treatment or at age 40, whichever comes first. The NCCN and American College of Surgery recommend yearly mammogram and breast MRI.
  • The risk of colon cancer is increased in patients who received radiation to their spine or pelvis during the course of cancer treatment. In those people, screening colonoscopy is recommended beginning 10 years after completing treatment.
  • To reduce the risk of skin cancer, always take care to wear sunscreen and protective clothing when you may be exposed to the sun. Also, it is important that your primary doctor or dermatologist look at your skin for abnormal moles or skin cancers every year.

Cardiovascular Disease

It is well demonstrated that survivors of Hodgkin's lymphoma have higher rates of cardiovascular disease and are at increased risk of death from heart attack and stroke. The factors that lead to higher risk of heart attack and heart disease in cancer survivors are many, but include chemotherapy, radiation, high levels of stress on the body and changes in the body's metabolic systems. The risk of heart disease is even higher if you have a family history of heart disease or have other risk factors for heart disease, like smoking, obesity, or diabetes. Symptoms from heart disease can begin quite early after cancer treatment and can be life-threatening. One of the most important things patients can do to reduce the risk of cardiovascular disease is to live a healthy lifestyle – engage in regular exercise, maintain a healthy body weight, and quit smoking.

Beginning five years after finishing treatment, your physician should check your blood pressure and cholesterol levels at least once per year. If they are abnormal, your doctor should start you on medication to lower them to the recommended range. Additionally, the NCCN recommends a baseline stress test or echocardiogram at 10 years. This will look for problems with the valves, how well the heart is pumping, and whether the arteries to the heart are clogged. Finally, if you received radiation to the neck, you may have a higher risk of stroke due to problems with the large blood vessels in the neck. It is controversial whether specific imaging of these blood vessels is indicated, but professionals agree that risk factors for stroke, like high blood pressure, high cholesterol, and diabetes, should be controlled.

Hormone Dysfunction

The thyroid gland is located in the neck and can be affected by radiation therapy. If you received radiation to the neck, you should receive yearly thyroid tests to monitor for poor thyroid function. Symptoms of low thyroid levels (hypothyroidism) include fatigue, weight gain, decreased appetite, dry skin, constipation, depression, and brittle hair or nails. If you have these symptoms, ask your doctor if he or she recommends a thyroid test.

Clinical Trials

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. You can also explore currently open clinical trials using the OncoLink Clinical Trials Matching Service.

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 both embedded in this article and from the Hodgkin's disease homepage on OncoLink.


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