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Lymphoma is a blood cancer in which white blood cells called lymphocytes change and grow out of control. Lymphomas are cancers of the lymphatic system. The lymphatic system is part of the circulatory and immune systems, and it removes bacteria, excess fluid, and waste matter generated by old or damaged cells. The lymphatic system is composed of the bone marrow, spleen, lymph nodes, thymus, and lymph channels that transport the lymph fluids throughout the body. Lymphoma is related to leukemia, myeloma, and myeloproliferative neoplasms (MPNs).
The two main types of lymphoma are Hodgkin lymphoma (HL, also called Hodgkin disease or Hodgkin’s disease) and non-Hodgkin lymphoma (NHL, also called non-Hodgkin’s lymphoma). Hodgkin and non-Hodgkin lymphoma are both blood cancers that originate in the lymphatic system. They share many of the same symptoms and treatments, and they are often diagnosed using similar methods. However, they have many distinguishing features. Below are a few differences between the two illnesses.
Non-Hodgkin lymphoma occurs most frequently in older adults. NHL diagnoses are most common in adults 75 and older. NHL is relatively uncommon in children and young adults. Hodgkin lymphoma is most common among teens and young adults ages 15 through 39, and older adults ages 75 and above. Most HL cases are diagnosed between ages 15 and 34.
In the United States, non-Hodgkin lymphoma is more common than Hodgkin lymphoma. In 2021, the American Cancer Society estimates that 81,560 people will be diagnosed with NHL compared to 8,830 people diagnosed with HL.
Hodgkin and non-Hodgkin lymphoma are differentiated by the type of lymphocyte that has become cancerous. Most NHL originates in B lymphocytes (B cells), but it can also originate in T lymphocytes (T cells). Both B cells and T cells play important roles in the immune system. Hodgkin cells and Reed-Sternberg cells will likely be present with HL but not NHL. Reed-Sternberg cells are large, abnormal B lymphocytes with a double nucleus. The cells appear to have two round eyes in microscope images. Hodgkin cells are smaller than Reed-Sternberg cells, but larger than normal B lymphocytes.
Hodgkin lymphoma usually spreads in sequence from cancerous lymph nodes to nearby lymph nodes. Non-Hodgkin lymphoma spreads more unpredictably to lymph nodes across the body.
HL is considered one of the most curable types of cancer if caught in early stages. The five-year relative survival rate for HL is 87 percent, according to the National Cancer Institute. For NHL, the five-year relative survival rate is 73 percent. These survival rates are based on data from 2010 to 2016. A person’s prognosis depends greatly on the individual and their specific type of lymphoma.
Hodgkin lymphoma can be divided into two primary subtypes — classical HL and nodular lymphocyte predominant HL. Approximately 95 percent of people with Hodgkin lymphoma have classical HL. Hodgkin lymphoma can be treated with chemotherapy, radiation, targeted therapies, immunotherapy, and in some cases, stem cell transplant. Your treatment plan will be influenced by your type of HL, stage of disease, and other factors like your age and overall health.
Classical HL is defined by the presence of Reed-Sternberg cells and Hodgkin cells. These cells are often identified as part of a lymph node biopsy. There are four subtypes of classical Hodgkin lymphoma.
Nodular sclerosis classical Hodgkin lymphoma (NSCHL) is the most common type of classical HL, accounting for 70 percent of cases. This highly treatable form of HL is the most common type diagnosed in young adults. About 40 percent of people with nodular sclerosis classical Hodgkin lymphoma experience fever, night sweats, and weight loss — known collectively as B symptoms. This form of classical HL often affects lymph nodes in the chest.
Mixed cellularity classical Hodgkin lymphoma (MCCHL) is the second most common form of classical HL. It accounts for 20 percent to 25 percent of classical HL cases. MCCHL most frequently occurs in young children, older adults, people with HIV, and men. People with MCCHL often experience B symptoms. MCCHL often originates in the upper body.
Lymphocyte-rich Hodgkin lymphoma affects about 5 percent of people with classical Hodgkin lymphoma. It is usually diagnosed early and generally only affects a few lymph nodes in the upper part of the body. It behaves similarly to NHL and is often treated with similar methods.
Lymphocyte-depleted Hodgkin lymphoma is the rarest form of classical HL and is most often seen in people with HIV. In many cases, lymphocyte-depleted HL has already progressed by the time it’s diagnosed. It usually affects lymph nodes in the abdomen and is also frequently found in the bone marrow, liver, and spleen.
Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) makes up about 5 percent of HL cases. NLPHL is an indolent (slow-progressing) and generally highly curable form of lymphoma. In about 7 percent of cases, it transforms into an aggressive NHL.
NLPHL is usually found in the neck, armpits, and groin. NLPHL cancer cells are distinguished from classical HL cells by their appearance and by molecules called antigens that function as cell markers.
Non-Hodgkin lymphoma is an umbrella term for many different types of NHL. The World Health Organization estimates that there are 85 subtypes of non-Hodgkin lymphoma. NHL is usually grouped by the type of white blood cell (lymphocyte) where the cancer originates, the way lymph node tissue looks under a microscope, and the aggressiveness of the cancer. The broad categories are B-cell lymphoma or T-cell lymphoma, and aggressive or indolent (slow-growing) lymphoma.
B-cell lymphoma accounts for 85 percent to 90 percent of non-Hodgkin lymphoma cases. B-cell lymphoma begins in B lymphocytes or B cells. B lymphocytes are white blood cells that produce proteins called antibodies or immunoglobulins. Antibodies attach to viruses, bacteria, or other pathogens (potential causes of disease), neutralizing them or signaling other cells in the immune system to attack them.
There are several types of aggressive and indolent B-cell non-Hodgkin lymphoma. Below are descriptions of some of the more common aggressive types, which can progress quickly and often require timely treatment.
Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma in the world. It most frequently affects older adults, though it accounts for about 15 percent of NHL cases in children. Rapidly swelling lymph nodes in the neck, armpits, and groin, combined with B symptoms, are early symptoms of DLBCL.
Diffuse large B-cell lymphoma gets its name from the appearance of its cells under a microscope. When evaluated under a microscope, the abnormal B cells that have become cancerous are diffuse, or spread out, rather than grouped closely together. Most DLBCL cases are a nonspecific type classified as “diffuse large B-cell lymphoma not otherwise specified,” or DLBCL-NOS.
While DLBCL is an aggressive form of NHL, it is highly treatable. Many people achieve complete remission, meaning there is no evidence of cancer after treatment. An individual’s prognosis will depend on the stage of their cancer and specific health factors.
Stage 1 or 2 diffuse large B-cell lymphoma is often treated with chemotherapy or chemoimmunotherapy. Chemotherapy may be followed by radiation therapy. Stage 3 or 4 DLBCL is usually treated with chemoimmunotherapy, but often with more cycles than would be used for earlier stages. Radiation may be used under specific circumstances.
Mantle cell lymphoma (MCL) accounts for about 3 percent of people with B-cell lymphoma in the U.S. Most cases of MCL occur in older adults. Symptoms of MCL can include B symptoms, nausea and vomiting, abdominal pain, and fatigue. MCL diagnosis usually begins with a lymph node biopsy, but additional tests will likely be necessary to identify MCL. A hematopathologist will be on the lookout for a specific genetic abnormality found in about 85 percent of MCL cases, as well as certain proteins.
MCL is caused by cancerous B cells in the outer part of the lymph node, called the mantle zone. Mantle cell lymphoma cells can spread throughout the body to other lymph nodes, bone marrow, the liver, and the intestines. Rarely, MCL can affect the brain and lungs.
Burkitt’s lymphoma (BL) accounts for approximately 40 percent of NHL cases in children in the U.S., but it is also more common among older people in the U.S. — and presents differently for them. Burkitt’s lymphoma was first identified in Africa, where it accounts for almost all cases of childhood non-Hodgkin lymphoma. Among children in Africa, BL usually develops in the jaw and facial bones. In other parts of the world, BL most commonly develops in the abdomen.
Burkitt’s lymphoma is extremely fast growing and requires multidrug, aggressive chemotherapy. Cancer recurrence is more likely in cases where lymphoma cells have spread to the brain and spinal cord.
Indolent B-cell lymphoma is a slow-growing cancer that originates in the B cells. Doctors may not recommend immediate treatment for people with indolent lymphoma. Instead, people with indolent lymphoma may undergo periodic monitoring to track their disease. This approach is referred to as “watchful waiting,” “watch and wait,” and “active surveillance.” In these cases, cancer is treated more like a chronic illness than an aggressive disease.
Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma diagnosed in the United States. FL primarily affects older adults. Swollen lymph nodes in the neck, underarms, and groin can be early signs of FL. Follicular lymphoma is a slow-growing form of NHL that is sometimes monitored with the watchful waiting approach. In some cases, FL can develop into a more aggressive form of lymphoma.
Marginal zone lymphoma (MZL) begins in B cells in the marginal zone of the lymph nodes. MZL accounts for approximately 7 percent of B-cell non-Hodgkin lymphoma cases. MZL subtypes are distinguished by where the lymphoma originates. The most common subtype is mucosa-associated lymphoid tissue lymphoma or MALT lymphoma. MALT lymphomas most frequently begin in the stomach.
Many people diagnosed with MALT lymphoma have a history of autoimmune disease or infection in the organ where the cancer started. MALT lymphoma can be treated with antibiotics, radiation therapy, targeted therapies, chemotherapy, and surgery.
Chronic lymphocytic leukemia and small-cell lymphocytic lymphoma are differentiated by where the majority of cancer cells are found, but are otherwise essentially the same condition. The condition is considered SLL when cancer cells are primarily in the lymph nodes, as opposed to the blood and bone marrow. People with CLL/SLL may have no symptoms, and their cancer may be found as a result of routine blood tests. In other cases, people may experience B symptoms, bruising, or infection.
People with low-risk CLL/SLL may not begin treatment right away and instead undergo periodic monitoring as part of a watchful waiting approach. In cases where treatment is necessary, targeted therapies that attack cancer cells or chemotherapy may be used.
Also referred to as lymphoplasmacytic lymphoma, Waldenström’s macroglobulinemia (WM) is a rare type of NHL. WM cancer cells are primarily found in the bone marrow. High levels of immune proteins known as immunoglobulins or antibodies in the blood are a sign of WM. Elevated levels of immunoglobulins can cause hyperviscosity or thickened blood. The resulting symptoms can include nosebleeds, fatigue, headaches, dizziness, and pain. WM is usually diagnosed through blood tests and a bone marrow biopsy.
In some cases, people with WM undergo plasmapheresis, a procedure that helps to reduce the symptoms of hyperviscosity by filtering out excess immunoglobulins. Plasmapheresis does not treat the cancer itself. In cases where watchful waiting is no longer appropriate, WM can be treated with targeted therapy and chemotherapy.
In some cases, lymphoma develops from lymphocytes in the skin. B-cell cutaneous lymphoma is a rare type of skin lymphoma that is most often indolent in nature. Most skin lymphomas are T-cell lymphomas.
T-cell lymphoma is the least common type of non-Hodgkin lymphoma. T-cell lymphoma is caused by changes to T lymphocytes, or T cells. Various types of T cells play key roles in the body’s immune response. Some T cells directly attack infected cells, while others help to regulate the immune system. There are multiple types of aggressive and indolent T-cell lymphoma.
Below are explanations of some of the more common types of aggressive T-cell lymphoma. These types of lymphoma are fast-growing and often require treatment soon after diagnosis.
Peripheral T-cell lymphoma (PTCL) accounts for just over half of T-cell non-Hodgkin lymphoma cases in the U.S. Peripheral T-cell lymphoma gets its name from the location of the cancer cells, which originate outside of (or peripheral to) the bone marrow. In PTCL, cancer cells develop in the lymph nodes, spleen, skin, or gastrointestinal tract.
There are several subtypes that fall under the PTCL umbrella, including:
Certain subtypes of PTCL are more common in certain parts of the world. For example, PTCL-NOS occurs more frequently in North America, while AITL occurs more frequently in Europe.
Peripheral T-cell lymphomas may be treated with high-dose chemotherapy and sometimes with chemotherapy followed by stem cell transplant. Clinical trials may also be an option for people with PTCL.
Lymphoblastic lymphoma (LBL) is also referred to as lymphoblastic leukemia/lymphoma. While some cases of LBL are B-cell lymphomas, the vast majority are T-cell lymphomas. Lymphoblastic lymphoma often occurs in children and young adults. LBL accounts for about a quarter of NHL cases in children in the United States.
Lymphoblastic lymphoma often begins in the thymus, an organ located between the lungs that is only active until puberty. Breathing problems caused by tumor growth can be a symptom of LBL. Other symptoms include B symptoms, bruising, and fever. While LBL is an aggressive cancer, it is treatable with chemotherapy.
Indolent T-cell lymphoma is usually slow-growing, but can be aggressive in certain cases.
Cutaneous T-cell lymphoma (CTCL) occurs when cancerous T cells accumulate in the skin. Cutaneous T-cell lymphoma is rare — it accounts for approximately 4 percent of all NHL cases. Early symptoms of CTCL, like redness, itchiness, and scaly patches, can mimic other skin conditions. Skin tumors may develop in advanced stages of CTCL. Some instances of CTCL can be aggressive.
CTCL is twice as prevalent in men than women and is also more common in African Americans. People are usually diagnosed in their 50s and 60s. The two most common types of CTCL, mycosis fungoides and Sézary syndrome, are incurable but treatable. Subcutaneous panniculitis-like T-cell lymphoma is a rare type of CTCL, occurring more often in women but accounting for less than 1 percent of NHL diagnoses. Treatment options may include topical treatments, phototherapy, targeted therapies, and chemotherapy.
Staging is important for determining a treatment plan. Each type of Hodgkin and non-Hodgkin lymphoma can be assigned a stage from 1 to 4 depending on how advanced it is. Stage 1 is the least advanced, involving just one lymph node region or lymphoid organ, such as a tonsil. Stage 4 is the most advanced. In stage 4, lymphoma cells are in the lymph nodes and have spread to organs outside the lymphatic system. The letters A and B, describing the presence or absence of lymphoma-related symptoms, can also be added after the stage number to further describe HL and NHL.
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Mark Levin, M.D.
is a hematology and oncology specialist with over 37 years of experience in internal medicine. Review provided by VeriMed Healthcare Network.
Learn more about him here.
Alison Channon
has nearly a decade of experience writing about chronic health conditions, mental health, and women's health.
Learn more about her here.
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