Non-Hodgkin lymphoma (NHL) is a type of blood cancer that starts in lymphocytes, the white blood cells that are part of your body’s immune system.
Non-Hodgkin lymphoma, or NHL, encompasses different types of lymphoma that all share some specific characteristics.
Non-Hodgkin lymphoma is separate from the other main type of lymphoma, Hodgkin lymphoma, which is treated differently. NHL most often affects adults, and usually starts in lymph nodes or other lymph tissue but can start in the skin.
Symptoms of non-Hodgkin lymphoma
If you experience any of these signs or symptoms, you should see your provider right away for an evaluation:
- Enlarged lymph nodes
- Weight loss
- Swollen abdomen
- Feeling full after only a small amount of food
- Chest pain or pressure
- Shortness of breath or cough
- Severe or frequent infections
- Easy bruising or bleeding
In addition, some people with NHL can experience these B symptoms:
- Fever without an infection, which can come and go over several days or weeks
- Drenching night sweats
- Weight loss without trying (at least 10% of body weight over 6 months)
We know that several factors can affect your chance of getting non-Hodgkin lymphoma:
- Age. Most cases occur in people age 60 or older.
- Gender. Overall, the risk of NHL is higher in men than in women.
- Race, ethnicity, and geography. In the United States, whites are more likely than African Americans and Asian Americans to develop non-Hodgkin lymphoma. Worldwide, NHL is more common in developed countries, with the United States and Europe having some of the highest rates.
- Family history. A first-degree relative (parent, child, sibling) with NHL means you are at increased risk.
- Exposure to certain chemicals and drugs. Benzene and certain herbicides and insecticides may be linked to an increased risk; some chemotherapy drugs used to treat other cancers may increase the risk of developing non-Hodgkin lymphoma many years later.
- Radiation exposure.
- A weakened immune system.
- Autoimmune diseases. Rheumatoid arthritis, systemic lupus erythematosus (SLE or lupus), Sjogren (Sjögren) disease, celiac disease (gluten-sensitive enteropathy) and others have been linked with an increased risk.
- Certain infections.
- Infection with human T-cell lymphotropic virus (HTLV-1) increases a person’s risk of certain types of T-cell lymphoma.
- The Epstein-Barr virus (EBV) is an important risk factor for Burkitt lymphoma in some parts of Africa. In developed countries such as the United States, EBV is more often linked with lymphomas in people also infected with HIV, the virus that causes AIDS.
- Human herpes virus 8 (HHV-8) can also infect lymphocytes, leading to a rare type of lymphoma called primary effusion lymphoma. HHV-8 infection is also linked to another cancer, Kaposi sarcoma, so another name for this virus is Kaposi sarcoma-associated herpes virus (KSHV).
- Infections that weaken the immune system. HIV infection is a risk factor for developing certain types of NHL, such as primary CNS lymphoma, Burkitt lymphoma, and diffuse large B-cell lymphoma.
- Infections that cause chronic immune stimulation. Some long-term infections may increase a person’s risk of lymphoma by forcing their immune system to be constantly active.
- Body weight and diet.
- Breast implants. Some women with breast implants develop a type of anaplastic large cell lymphoma (ALCL) in their breast.
Questions and answers (FAQs)
Yes. These side effects depend on the type of treatment and the patient’s age when treated, and may include:
- Second cancers
- Solid tumors
- Heart disease, such as heart attack
- Lung problems, such as trouble breathing
- Avascular necrosis of bone
- Severe infection
- Chronic fatigue
Yes, depending on the type of NHL, early diagnosis and treatment, and the condition of the patient, non-Hodgkin lymphoma can be cured.
Non-Hodgkin lymphoma diagnosis
Your doctor will perform a thorough diagnostic screening to determine what type of non-Hodgkin lymphoma you have and its stage. Diagnostic testing can include:
- Physical exam.
- Biopsies of enlarged lymph nodes or other abnormal areas.
- Blood tests.
- Imaging tests, such as a PET scan and CT scan.
- Bone marrow aspiration and biopsy.
- Lumbar puncture (spinal tap).
UCHealth follows the World Health Organization (WHO) classification system for the many types of non-Hodgkin lymphoma. Treatment for NHL depends on the type, so it’s critical that we determine the exact type of lymphoma you have.
The WHO system groups lymphomas based on:
- The type of lymphocyte the lymphoma starts in (see below).
- How the lymphoma looks under a microscope.
- The chromosome features of the lymphoma cells.
- The presence of certain proteins on the surface of the cancer cells.
Lymphocyte types: B-cell v. T-cell
Your lymph system is made up mainly of lymphocytes, a type of white blood cell that helps the body fight infections. The first criteria for WHO classification is the type of lymphocyte involved. There are two main types of lymphocytes:
- B lymphocytes (B cells). B cells normally help protect the body against bacteria and viruses by making proteins called antibodies. The antibodies attach to the germs, marking them for destruction by other parts of the immune system.
- T lymphocytes (T cells). There are several types. Some T cells destroy germs or abnormal cells in the body, while other T cells help boost or slow the activity of other immune system cells.
NHL types grouped by speed of growth and spread
- Indolent lymphomas grow and spread slowly Some indolent lymphomas might not need to be treated right away, but can be watched closely instead. The most common type of indolent lymphoma in the United States is follicular lymphoma.
- Aggressive lymphomas grow and spread quickly, and usually need to be treated right away. The most common type of aggressive lymphoma in the United States is diffuse large B cell lymphoma (DLBCL).
Some types of lymphoma, like mantle cell lymphoma, don’t fit neatly into either of these categories.
Regardless of how quickly they grow, all non-Hodgkin lymphomas can spread to other parts of the lymph system if not treated. Eventually, they can also spread to other parts of the body, such as the liver, brain, or bone marrow.
Staging of Non-Hodgkin lymphoma
UCHealth follows the Lugano classification for staging NHL in adults, which uses Roman numerals I through IV (1-4). Limited stage (I or II) lymphomas that affect an organ outside the lymph system have an E added.
The lymphoma is in only one lymph node area or lymphoid organ such as the tonsils (I).
The cancer is found only in one area of a single organ outside of the lymph system (IE).
The lymphoma is in two or more groups of lymph nodes on the same side of (above or below) the diaphragm (the thin band of muscle that separates the chest and abdomen). For example, this might include nodes in the underarm and neck area (II) but not the combination of underarm and groin nodes (III).
The lymphoma is in a group of lymph nodes) and in one area of a nearby organ (IIE). It may also affect other groups of lymph nodes on the same side of the diaphragm.
The lymphoma is in lymph node areas on both sides of (above and below) the diaphragm.
The lymphoma is in lymph nodes above the diaphragm, as well as in the spleen.
The lymphoma has spread widely into at least one organ outside the lymph system, such as the bone marrow, liver, or lung.
Treatment and recovery
Treatment for blood cancer varies greatly from person to person, and depends on the type of blood cancer. Your medical team may use any combination of chemotherapy, drug therapy, bone and marrow transplants, radiation, or new targeted therapies to treat or control your cancer:
Chemotherapy. Drugs that slow down, damage, or kill cancer cells. It may involve single drugs or combinations of drugs taken intravenously or by mouth. Chemotherapy is often taken in cycles lasting three or four weeks each. Your team may also prescribe drugs to reduce or eliminate chemotherapy’s side effects.
Radiation therapy. X-rays and other types of medical radiation aimed at specific parts of the body. The radiation kills cancer cells, prevents cancer cells from developing or recurring, and improves many of cancer’s symptoms. For certain cancers, radiation therapy is combined with chemotherapy and called chemo-radiotherapy.
Targeted therapies. Single drugs or combinations of drugs taken through intravenous injections or as prescribed tablets/capsules help fight the cancer itself or the side effects from chemotherapy. Drugs may be taken in repeating patterns (cycles) that usually last three to four weeks. Anti-cancer drugs or other substances that directly interfere with cancer growth and progression at the molecular level may be taken-with few side effects on their own or combined with standard chemotherapy. Many new targeted therapies, including vaccines and gene therapies, are currently in development.
Blood and marrow transplantation. Because intensive chemotherapy and/or radiation treatment can severely damage the bone marrow’s ability to produce cells, stem cell transplantation helps restore normal blood production.
Platelet transfusion. Platelets are small cells that stick to the site of a blood vessel injury and seal it to stop bleeding. Apheresis is the process that removes platelets from a donor’s blood by a machine that then returns plasma and other cells to the donor. People experiencing lymphoma often need an infusion of donor platelets.
Bisphosphonates. This class of drugs-including pamidronate and zoledronic acid-helps limit bone loss, bone thinning, and fractures, especially in people experiencing myeloma.
We know that NHL is linked with a number of risk factors, but we are still researching the cause of most lymphomas.
We do have a better understanding now how certain changes in DNA can cause normal lymphocytes to become lymphoma cells. Oncogenes are genes that help cells grow, divide, and stay alive—tumor suppressor genes help keep cell division under control, or make cells die at the right time. We know that some lymphoma cancers are caused by DNA mutations that turn on oncogenes or turn off tumor suppressor genes. A family history of lymphoma does seem to increase the risk of lymphoma.
However, we now know that gene changes related to NHL are usually acquired during life rather than being inherited. This can happen from exposure to risk factors, but these changes can also occur for no apparent reason and seem to happen more often as we age.
Types and subtypes of non-Hodgkins lymphoma
There are three major groups of non-Hodgkin lymphoma as determined by the type of cell the lymphoma started in:
- B-cell lymphoma. Occurs in about 90% of cases in western countries.
- T-cell lymphoma. Occurs in about 10% of cases in western countries.
- NK-cell lymphoma. Occurs in less than 1% of cases.
In addition to the three main types, we can also classify NHL by how quickly the cancer is growing, either indolent or aggressive.
Indolent and aggressive non-Hodgkin lymphomas are equally common in adults; in children, aggressive NHL is more common.
- Indolent NHL. These types grow slowly, so you may not need to start treatment when first diagnosed.
- Aggressive NHL. These types may develop rapidly, so we usually start treatment right away.
Some subtypes of lymphoma cannot easily be classified as indolent or aggressive.
Subtypes of B-cell lymphoma
- Diffuse large B-cell lymphoma (DLBCL). The most common form.
- Follicular lymphoma. The second-most common form.
- Mantle cell lymphoma. Only 5% to 7% of people with NHL have mantle cell lymphoma.
- Small lymphocytic lymphoma.
- Double hit lymphoma. A highly aggressive subtype of DLBCL, accounting for about 5% of cases.
- Primary mediastinal large B-cell lymphoma. An aggressive form of DLBCL, appearing as a large mass in the chest area.
- Splenic marginal zone B-cell lymphoma. Begins in the spleen and usually involves the bone marrow and the blood.
- Extranodal marginal zone B-cell lymphoma of MALT. Most commonly occurs in the stomach. Patients may have a history of autoimmune disease such as lupus, rheumatoid arthritis, or Sjögren syndrome. When MALT occurs in the stomach, it is may be caused by the bacteria Helicobacter pylori—antibiotics can effectively treat this.
- Nodal marginal zone B-cell lymphoma. A rare type of indolent lymphoma involves the lymph nodes.
- Lymphoplasmacytic lymphoma. A rare type of indolent form of lymphoma, often involving the bone marrow, and sometimes the lymph nodes and spleen. This type can result in a condition called Waldenstrom’s macroglobulinemia (WM).
- Primary effusion lymphoma. A rare and very aggressive form.
- Burkitt lymphoma or Burkitt cell leukemia. A very rare and aggressive type, with three forms: endemic, sporadic and Iimmunodeficiency-related lymphoma. Burkitt lymphoma is often curable.
Subtypes of T-cell and NK-cell lymphoma
- Anaplastic large cell lymphoma, primary cutaneous type. Involves only the skin.
- Anaplastic large cell lymphoma, systemic type. Makes up about 2% of all lymphomas and about 10% of all childhood lymphomas.
- Peripheral T-cell lymphoma, not otherwise specified (NOS). An aggressive form that is often advanced when diagnosed.
- Angioimmunoblastic T-cell lymphoma. An aggressive form.
- Adult T-cell lymphoma/leukemia (human T-cell lymphotropic virus type I positive). An aggressive type that often involves the bone and skin.
- Extranodal NK/T-cell lymphoma, nasal type. An aggressive type, very rare in the United States.
- Enteropathy-associated T-cell lymphoma. Rare in the United States but more common in Europe.
- Gamma/delta hepatosplenic T-cell lymphoma. An aggressive form of peripheral T-cell lymphoma that involves the liver and spleen.
- Subcutaneous panniculitis-like T-cell lymphoma. A form of peripheral T-cell lymphoma, similar to gamma/delta hepatosplenic T-cell lymphoma.
- Mycosis fungoides. A rare T-cell lymphoma that primarily involves the skin.
Five-year Non-Hodgkin lymphoma survival rates
Number of Patients Diagnosed – UCHealth 690 – State of Colorado – 3,350
Number of Patients Surviving – UCHealth 496 – State of Colorado – 2,231
*n<30, 5 Year Survival – (Date of diagnosis 1/1/2010–12/31/2014)
National Cancer Institute (NCI). Lymphoma (https://www.cancer.gov/types/lymphoma)
National Center for Biotechnology Information (NCBI): National Library of Medicine. Non-Hodgkin Lymphoma (https://www.ncbi.nlm.nih.gov/books/NBK559328/)
Lymphoma Research Foundation. Non-Hodgkin Lymphoma (https://lymphoma.org/understanding-lymphoma/aboutlymphoma/nhl/)
MedlinePlus: National Library of Medicine. Lymphoma (https://medlineplus.gov/lymphoma.html)