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Medically reviewed by Dr. C.H. Weaver M.D. 7/2021

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Cancers that begin in cells of the lymph system are referred to as malignant lymphomas. Lymphomas range from aggressive to slow growing or indolent and can be effectively treated. The lymph system includes the spleen, thymus, tonsils, bone marrow, lymph nodes and circulating white blood cells called lymphocytes. Lymphocytes and the lymph system are part of the immune system that protects the body from disease and infection. Cancers of the lymph system are referred to as Hodgkin lymphoma or non-Hodgkin lymphoma (NHL).

The majority of lymphomas are either curable or manageable with currently available therapies. The general type of treatment used is determined by the type (histologic diagnosis) and stage of the lymphoma and specific treatment is often further defined by unique genomic abnormalities identified by cytogenetics or biomarkers.

About the lymphatic system

The lymphatic system is made up lymph nodes connected by lymphatic vessels and organs throughout the body. The lymphatic system contains a type of white blood cell called a lymphocyte that is the key cell in the immune system to fight infection and lymphoma.

Other Key Organs of the Lymphatic System Include:

  • Spleen: located in the left upper abdomen, under the rib cage.
  • Thymus: located behind the breastbone and helps develop T-lymphocytes.
  • Tonsils: located in the throat which help trap bacteria entering through the mouth

Lymphoma may involve any part of the lymph system and even spread to other organs such as the lungs, liver, bone and bone marrow.

Symptoms & Signs of Lymphoma

People with lymphoma most often first suspect a problem when they notice an enlarged lymph node. This typically manifests as a lump or swelling in the neck, armpit or groin region. Many patients have no additional symptoms. The most common symptoms caused by lymphoma include:

  • Persistent painless swelling of lymph nodes in the neck, underarm, or groin.
  • Unexplained fever that does not go away
  • Unexplained weight loss
  • Night sweats
  • Fatigue
  • Pain in the lymph nodes triggered by drinking alcohol
  • Shortness of breath, cough, or chest discomfort may be caused if lymph nodes in the chest are affected.
  • A generalized itching that may be severe

Cause of Lymphoma

A lymphoma begins when healthy cells acquire a genetic change (mutation) that causes them to turn into abnormal cells.

Risk factors for Lymphoma

A risk factor is anything that increases a person’s chance of developing cancer. Risk factors can influence the development of cancer but most do not directly cause cancer. Many individuals with risk factors will never develop cancer and others with no known risk factors will. Lymphoma's typically develops sporadically, which means for no known reason. Some cancers however are more likely to develop in individuals with certain risk factors that increase an individual’s chance of developing cancer.

The following factors may raise a person’s risk for developing lymphoma1

  • People between the ages of 15 and 40 and older than 55 are more likely to develop Hodgkin lymphoma.
  • Men are slightly more likely than women to develop Hodgkin lymphoma.
  • Family history. Brothers and sisters of people with Hodgkin lymphoma have a higher chance of developing the disease although the increase in risk is small.
  • Virus exposure. The Epstein-Barr virus (EBV) causes infectious mononucleosis, often called “mono.” Nearly all adult Americans and many others around the world have an EBV infection. About 20% to 25% of people with cHL in the United States have lymphoma cells that test positive for EBV. Although a person’s immune system response to an infection with EBV may be important in the development of lymphoma, doctors still don’t understand why, when so many people have been infected with EBV, relatively very few people ever develop lymphoma.
  • Individuals with HIV have a higher risk of developing lymphoma.

Diagnosis & Tests for Lymphoma

In order to treat a lymphoma doctors must classify and stage the cancer. Many tests are used to diagnose, classify and stage lymphomas. A biopsy is the only certain way to confirm the diagnosis and is performed by taking a sample of tissue for testing in a laboratory. It is important that the biopsy sample is large enough to allow the pathologist to make an accurate diagnosis, classify the lymphoma, and perform bio-marker and genomic tests. Once a lymphoma is confirmed “staging” tests are performed to learn if cancer has spread to another part of the body.2,3

Genomic or Bio-marker Testing-Precision Cancer Medicine

The purpose of precision cancer medicine is to define the genomic alterations in the cancers DNA that are driving that specific cancer. Precision cancer medicine utilizes molecular diagnostic & genomic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. Once a genetic abnormality is identified, a specific targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed.

By testing a cancer for specific unique biomarkers doctors can offer the most personalized treatment approach utilizing precision medicines. Lymphoma cells may have the biomarkers CD 20 or CD30, which can be targeted by the precision cancer medicines Rituxan (rituximab) and Adcetris (brentuximab vedotin) respectively.4,5

Lymphoma Classification

Lymphoma Staging Tests

It is important to determine how much the cancer has spread before initiating treatment in order to select the best treatment option. Of particular concern is the presence of cancer in lymph nodes, spread of cancer to distant sites or local extension of cancer into surrounding structures. The following diagnostic procedures may be used in addition to a through physical examination to complete the staging evaluation of lymphoma.1

  • Laboratory Tests: Blood tests may include a complete blood count and an analysis of the different types of white blood cells as well as test of kidney and liver function.
  • Positron Emission Tomography (PET): Positron emission tomography scanning is an advanced technique for imaging body tissues and organs. One characteristic of living tissue is the metabolism of sugar. Prior to a PET scan, a substance containing a type of sugar attached to a radioactive isotope (a molecule that emits radiation) is injected into the patient’s vein. The cancer cells “take up” the sugar and attached isotope, which emits positively charged, low energy radiation (positrons) that create the production of gamma rays that can be detected by the PET machine to produce a picture. If no gamma rays are detected in the scanned area, it is unlikely that the mass in question contains living cancer cells.
  • Computed Tomography (CT) Scan: A CT scan is a technique for imaging body tissues and organs, during which X-ray transmissions are converted to detailed images, using a computer to synthesize X-ray data. A CT scan is conducted with a large machine positioned outside the body that can rotate to capture detailed images of the organs and tissues inside the body.
  • Magnetic Resonance Imaging (MRI): MRI uses a magnetic field rather than X-rays, and can often distinguish more accurately between healthy and lymphoma tissue than a CT. An MRI gives a better picture of cancer located near bone than does CT, does not use radiation, and provides pictures from various angles that enable doctors to construct a three-dimensional image of the cancer.
  • Bone Marrow Aspiration and Biopsy: Bone marrow is the soft, spongy tissue found inside the center of bones. A bone marrow aspiration removes a sample of the fluid with a needle. A bone marrow biopsy is the removal of a small amount of solid tissue using a needle. Bone marrow procedures have been mostly replaced with PET-CT scans and are no longer required if the scan has been performed as part of the initial staging evaluation.(6)

Pretreatment Planning

In addition to determining the stage of the lymphoma tests may be performed to evaluate heart and lung function prior to beginning treatment in order to confirm an individual can receive certain lymphoma treatments. These tests may include:

  • Pulmonary Function Tests or PFTs: Assessment of lung function may be done if treatment includes certain chemotherapy drugs that could affect the lungs. PFT’s are designed to evaluate how much air the lungs can hold, how quickly air can move in and out of the lungs, and how well the lungs add oxygen and remove carbon dioxide from the blood.
  • Heart Evaluation: An echocardiogram or a multi-gated acquisition (MUGA) scan may be used to check the function of the heart if specific types of chemotherapy will be used.

Screening/Prevention of Lymphoma

Information about the prevention of cancer and the science of screening appropriate individuals at high-risk of developing cancer is gaining interest. Physicians and individuals alike recognize that the best “treatment” of cancer is preventing its occurrence in the first place or detecting it early when it may be most treatable.

At this time, the cause of lymphomas is unknown and researchers are trying to solve this problem. Scientists know that a lymphoma is not caused by injury and it is not infectious.

The chance of an individual developing cancer depends on both genetic and non-genetic factors. A genetic factor is an inherited, unchangeable trait, while a non-genetic factor is a variable in a person’s environment, which can often be changed. Non-genetic factors may include diet, exercise, or exposure to other substances present in our surroundings. These non-genetic factors are often referred to as environmental factors. Some non-genetic factors play a role in facilitating the process of healthy cells turning cancerous (i.e. the correlation between smoking and lung cancer) while other cancers have no known environmental correlation but are known to have a genetic predisposition, meaning a person may be at higher risk for a certain cancer if a family member has that type of cancer.

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Heredity and Genetic Factors

Environmental factors appear much more important than genetic factors in the development of lymphoma. It is a scientific mystery as to why only one of a pair of identical twins will develop a lymphoma, since the genetics are identical and environmental exposures are similar, if not the same. Any form of genetic or familial immunodeficiency may be associated with an increased incidence of lymphoma.

Environmental or Non-Genetic Factors

The fact that only one of a pair of identical twins usually develops a lymphoma suggests that finding the specific cause for lymphoma is difficult. However, by studying large numbers of people all over the world, researchers have found certain factors that increase a person’s risk of getting a lymphoma.

Many, but not all, studies show a consistent link between woodworking and lymphoma. Trichloroethylene is an organic chemical used in dry cleaning, metal degreasing and as a solvent for oils and resins and has been identified to cause liver and kidney cancer in animals. Exposure to trichloroethylene has been associated with an increased chance of developing lymphoma and other cancers. Machinists in the metal working industry have also been reported to have a higher than average incidence of lymphoma. Exposure to pesticides has been associated with an increased incidence of lymphoma in some, but not all, clinical studies.

Exposure to low levels of radiation may cause an increased incidence of lymphoma. Workers at some nuclear facilities have been found to have an increased incidence of pancreatic cancer and lymphoma compared to the normal population. An increased incidence of lymphoma has been reported in farmers compared to people living in cities.

Immunosuppressive or Cytotoxic Treatment of Other Lymphomas: Autoimmune lymphomas and cancers treated with immunosuppressive and/or cytotoxic chemotherapy drugs appear to increase the incidence of lymphoma. For instance, lymphoma has been reported after methotrexate treatment of rheumatoid arthritis.

Other Lymphomas and Hodgkin lymphoma: There is an increased incidence of Hodgkin lymphoma among people who are immunodeficient, regardless of whether this immunodeficiency is naturally occurring or medically induced. Therefore, researchers have difficulty determining whether associations are natural or due to treatment.

Some, but not all, clinical studies have reported an increased incidence of lymphomas in individuals with the human immuno-deficiency virus (HIV).

Viruses and Hodgkin lymphoma: The Epstein-Barr virus, which causes infectious mononucleosis, infects B lymphocytes and is found in cancer cells from some lymphoid malignancies including Burkitt’s lymphoma, nasopharyngeal carcinoma and Hodgkin lymphoma. Thus, people with a history of infectious mononucleosis appear to have an increased chance of developing Hodgkin lymphoma later in life. Researchers currently believe that early childhood exposure to the Epstein-Barr virus is not associated with an increased incidence of Hodgkin lymphoma, but late exposure, as with infectious mononucleosis, is associated with an increased chance of developing Hodgkin lymphoma.

The Epstein-Barr virus can be found in the biopsy samples of individuals with Hodgkin lymphoma. In one clinical study from Africa, 87% of patients with Hodgkin lymphoma tested positive for the Epstein-Barr virus. The relationship between the Epstein-Barr virus and Hodgkin lymphoma is complex and does not appear to be a direct cause and effect relationship. In other words, the Epstein-Barr virus can be found in individuals with Hodgkin lymphoma, but the reverse is not often true. While 90-95% of adults have evidence of an infection from the Epstein-Barr virus, only a small percentage of these individuals will ever develop Hodgkin lymphoma. It is thought that the development of Hodgkin lymphoma may be accompanied or triggered by viral reactivation. Scientists are still trying to understand why the peak incidence of Hodgkin lymphoma occurs in young individuals and have further speculated that the additional involvement of an as yet undetected second virus may be involved.


Cancer is largely a preventable illness. Two-thirds of cancer deaths in the U.S. can be linked to tobacco use, poor diet, obesity, and lack of exercise. All of these factors can be modified. Nevertheless, an awareness of the opportunity to prevent cancer through changes in lifestyle is still under-appreciated. The overwhelming majority of cases of lymphoma cannot be prevented since we do not know the cause.

Scientists around the world have been working on vaccine strategies against Epstein-Barr virus associated lymphomas. This work has been hampered by an inability to identify the characteristics of the virus when it remains dormant in the body. However, there is currently some optimism that vaccine trials aimed at controlling infectious mononucleosis, post-transplant lymphoproliferative lymphoma, nasopharyngeal carcinoma and Hodgkin lymphoma may soon be justified.

Diet: A poor diet is a fertile area for immediate individual and societal intervention to decrease the risk of developing certain cancers. Numerous studies have provided a wealth of information about the detrimental and protective factors of different foods.

There is convincing evidence that excess body fat substantially increases the risk for many types of cancer. While much of the cancer-related nutrition information cautions against a high-fat diet, the real culprit is an excess of calories. Studies indicate that there is little, if any, relationship between body fat and fat composition of the diet. These studies show that excessive caloric intake from both fats and carbohydrates have the same result of excess body fat. The ideal way to avoid excess body fat is to limit caloric intake and/or balance caloric intake with ample exercise.

It is still important, however, to limit fat intake, as evidence still supports a relationship between cancer and polyunsaturated, saturated and animal fats. Specifically, studies show that high consumption of red meat and dairy products can increase the risk of certain cancers. One strategy for positive dietary change is to replace red meat with chicken, fish, nuts and legumes.

High fruit and vegetable consumption has been associated with a reduced risk for developing at least 10 different cancers. This may be a result of potentially protective factors such as carotenoids, folic acid, vitamin C, flavonoids, phytoestrogens and isothiocyanates.

There is strong evidence that moderate to high alcohol consumption also increases the risk of certain cancers. One reason for this relationship may be that alcohol interferes with the availability of folic acid. Alcohol in combination with tobacco creates an even greater risk.

Exercise: Higher levels of physical activity may reduce the incidence of some cancers. According to researchers at Harvard, if the entire population increased their level of physical activity by 30 minutes of brisk walking per day (or the equivalent energy expenditure in other activities), we would observe a 15% reduction in the incidence of colon cancer.

Screening and Early Diagnosis

For many types of cancer, progress in the areas of cancer screening and treatment has offered promise for earlier detection and higher cure rates. The term screening refers to the regular use of certain examinations or tests in persons who do not have any symptoms of a cancer but are at high risk for that cancer. When individuals are at high risk for a type of cancer, this means that they have certain characteristics or exposures, called risk factors that make them more likely to develop that type of cancer than those who do not have these risk factors. The risk factors are different for different types of cancer. An awareness of these risk factors is important because 1) some risk factors can be changed (such as smoking or dietary intake), thus decreasing the risk for developing the associated cancer; and 2) persons who are at high risk for developing a cancer can often undergo regular screening measures that are recommended for that cancer type. Researchers continue to study which characteristics or exposures are associated with an increased risk for various cancers, allowing for the use of more effective prevention, early detection, and treatment strategies.

Lymphoma is usually diagnosed because patients have signs and symptoms including a painless swelling in the lymph nodes in the neck, under the arm or in the groin; unexplained fevers; night sweats; unexplained weight loss and/or itchy skin.

In order for screening to be effective, patients at risk for lymphoma need to be identifiable. This is not currently possible, with the exception of identifying patients who have one of a few genetic lymphomas and screening them accordingly.


  1. American Cancer Society: Cancer Facts and Figures 2017. Atlanta, Ga: American Cancer Society, 2017. Last accessed October 13, 2017.
  2. Brenner H, Gondos A, Pulte D: Ongoing improvement in long-term survival of patients with Hodgkin lymphoma at all ages and recent catch-up of older patients. Blood 111 (6): 2977-83, 2008.
  3. Lister TA, Crowther D, Sutcliffe SB, et al.: Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin’s disease: Cotswolds meeting. J Clin Oncol 7 (11): 1630-6, 1989.
  4. Gopal AK, Ramchandren R, O’Connor OA, et al.: Safety and efficacy of brentuximab vedotin for Hodgkin lymphoma recurring after allogeneic stem cell transplantation. Blood 120 (3): 560-8, 2012.
  5. Younes A, Bartlett NL, Leonard JP, et al.: Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med 363 (19): 1812-21, 2010.
  6. Adams HJ, Kwee TC, de Keizer B, et al.: Systematic review and meta-analysis on the diagnostic performance of FDG-PET/CT in detecting bone marrow involvement in newly diagnosed Hodgkin lymphoma: is bone marrow biopsy still necessary? Ann Oncol 25 (5): 921-7, 2014.