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What Is Lymphoma?
Lymphoma is a cancer that starts in a type of white blood cells called lymphocytes, which are part of the body’s immune system. There are nearly 85 different types of lymphomas. Broadly, they are divided into Hodgkin and non-Hodgkin lymphoma. Non-Hodgkin lymphomas are further divided into B-cell, T-cell, and NK-cell lymphomas. These lymphomas can either be aggressive or non-aggressive (indolent) lymphomas.
Lymphoma Prognosis and Survival Rates
Lymphoma prognosis primarily depends upon the subtype at diagnosis. Non-Hodgkin lymphoma is one of the most common cancers in the U.S., making up around 4% of all cancers. Aggressive lymphomas typically need intensive therapy and have a good chance of cure. Indolent lymphomas (lymphomas that grow and spread slowly), on the other hand, are chronic treatable diseases.
Why Come to CU Cancer Center for Lymphoma
As the only National Cancer Institute-Designated Comprehensive Cancer Center in Colorado and one of only four in the Rocky Mountain region, the University of Colorado Cancer Center has doctors who provide cutting-edge, patient-centered lymphoma care, and researchers focused on diagnostic and treatment innovations.
There are numerous lymphoma clinical trials being conducted by CU Cancer Center members at any time. These trials offer patients alternatives to traditional lymphoma treatment and can result in remission or increased life spans.
→ Learn more about the lymphoma program at CU Cancer Center
Our clinical partnership with UCHealth has produced survival rates higher than the state average for all stages of Hodgkin lymphoma and non-Hodgkin lymphoma.
Number of Patients Diagnosed – UCHealth 155 – State of Colorado 140
Number of Patients Surviving – UCHealth 604 – State of Colorado 532
*n<30, 5 Year Survival – (Date of diagnosis 1/1/2010–12/31/2014)
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)
Hodgkin lymphoma
There are two primary types of Hodgkin lymphoma.
Classic Hodgkin lymphoma (cHL) accounts for around 90% of Hodgkin lymphoma cases. The cancer cells in cHL are known as Reed-Sternberg cells, an abnormal type of B lymphocyte.
Classic Hodgkin lymphoma has four subtypes:
- Nodular sclerosis Hodgkin lymphoma (NSCHL) is the most common type of Hodgkin disease. It typically begins in lymph nodes in the neck or chest.
- Mixed cellularity Hodgkin lymphoma (MCCHL) is the second most common type of Hodgkin lymphoma and is found most often in people with HIV infection. It can begin in any lymph node, but it occurs most often in the upper half of the body.
- Lymphocyte-rich Hodgkin lymphoma is a rare subtype that typically occurs in the upper half of the body.
- Lymphocyte-depleted Hodgkin lymphoma is a rare form of cancer found primarily in older people and those with HIV infection. It is seen most often in lymph nodes in the abdomen, liver, spleen, and bone marrow.
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) makes up around 5% of cases. The cancer cells in NLPHL, called popcorn cells (because they look like popcorn), are variants of Reed-Sternberg cells. NLPHL typically begins in lymph nodes in the neck and under the arm. It is more common in men than in women.
Non-Hodgkin lymphoma
Non-Hodgkin lymphoma (NHL) is largely categorized into two types, named for the type of white blood cell in which the cancer forms: B-cell lymphoma and T-cell lymphoma.
B-cell lymphoma
Around 85% of the NHL diagnosed in the United States are B-cell lymphomas — lymphomas that affect B lymphocytes. The most common types of B-cell lymphomas include:
Diffuse large B-cell lymphoma is the most common type of NHL. It accounts for around one out of every three lymphomas. It earned this name because the lymphoma cells appear relatively large under a microscope.
→ New hope for patients with relapsed large B-cell lymphoma
Follicular lymphoma typically is a slow-growing (indolent) lymphoma, though some follicular lymphomas can grow quickly. Follicular lymphoma tends to occur in multiple lymph node sites in the body, as well as the bone marrow.
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are closely related diseases that involve the same type of small lymphocyte. The biggest difference between the two has to do with where the cancer cells are found — in CLL, most are in the blood and bone marrow; and in SLL, cancer cells are found primarily in the spleen and lymph nodes.
Mantle cell lymphoma tends to be widespread in the bone marrow, lymph nodes, and often the spleen. Mantle cell lymphoma is more common in men than in women, and it most often occurs in people 60 and older.
Marginal zone lymphomas account for around 5% to 10% of all lymphomas. They tend to be slow-growing (indolent). The three primary types of marginal zone lymphomas are:
- Extranodal marginal zone B-cell lymphoma, also known as mucosa-associated lymphoid tissue (MALT) lymphoma: The most common type of marginal zone lymphoma, this cancer starts in locations other than the lymph nodes, including the stomach, lung, skin, salivary glands, thyroid, or tissues around the eye.
- Nodal marginal zone B-cell lymphoma: This rare disease tends to start and stay in the lymph nodes, although cancer cells are sometimes found in the bone marrow.
- Splenic marginal zone B-cell lymphoma: This rare lymphoma is most often found in the spleen, blood, and bone marrow.
Burkitt lymphoma is a fast-growing lymphoma named for the doctor who first described the disease in children and young adults in Africa. Different varieties of Burkitt lymphoma are seen in different parts of the world:
- The endemic, or African variety of Burkitt lymphoma typically begins as a tumor of the jaw or other facial bones. Most cases of endemic Burkitt lymphoma are linked to infection with the Epstein-Barr virus. This disease is rare in the United States.
- Nonendemic, or sporadic Burkitt lymphoma is the variety seen more often in the U.S. The lymphoma most often begins in the abdomen, where it forms a large tumor. Nonendemic Burkitt lymphoma also can begin in the testicles, ovaries, or other organs and can spread to the brain and spinal fluid.
- Immunodeficiency-associated Burkitt lymphoma is associated with immune system problems such as HIV or AIDS or people who have had an organ transplant.
Lymphoplasmacytic lymphoma is a slow-growing lymphoma that accounts for just 1% to 2% of lymphomas. It is characterized by small lymphoma cells that are found primarily in the lymph nodes, spleen, and bone marrow.
Hairy cell leukemia is a rare leukemia that is sometimes considered to be a type of lymphoma. The cancerous cells are small B lymphocytes with protruding projections that give them a “hairy” appearance. They are typically found in the bone marrow, spleen, and blood.
Primary central nervous system lymphoma primarily involves the brain or spinal cord, though it is sometimes seen in tissues around the spinal cord.
Primary intraocular lymphoma, or lymphoma of the eye, is a rare lymphoma that begins in the eyeball. It is often seen along with primary central nervous system lymphoma. It is the second most common eye cancer in adults, after ocular melanoma.
T-cell lymphomas
T-cell lymphomas make up less than 15% of non-Hodgkin lymphomas in the U.S. The most common T-cell lymphomas are:
Peripheral T-cell lymphomas are rare lymphomas that develop from more mature T cells.
Angioimmunoblastic T-cell lymphoma involves the lymph nodes and bone marrow, as well as the spleen or liver.
Extranodal natural killer/T-cell lymphoma, nasal type is a rare lymphoma that typically affects the upper airway passages, such as the nose and upper throat. It also can affect the skin, digestive tract, and other organs.
Enteropathy-associated intestinal T-cell lymphoma (EATL) is a lymphoma that occurs in the lining of the intestine — most often the small intestine, but sometimes the colon.
Anaplastic large cell lymphoma (ALCL) is more common in young people, including children, but it can also affect older adults. ALCL can affect the skin, lymph nodes, and other organs.
Adult T-cell leukemia/lymphoma is caused by infection with the HTLV-1 virus. It is more common in Japan, Africa, and the Caribbean. It affects the bone marrow, lymph nodes, liver, spleen, skin, and other organs.
Lymphoma of the skin
Skin lymphomas (also known as cutaneous lymphomas) are lymphomas that develop in the skin and do not affect any other areas of the body at the time they are diagnosed. In most cases, they are slow-growing and do not affect life expectancy. Skin lymphoma is not considered a type of skin cancer (where the cancer develops from skin cells).
Lymphoma has multiple risk factors: behaviors or conditions that increase a person’s chances of getting a disease such as cancer. Risk factors for lymphoma include:
- Epstein-Barr virus infection or mononucleosis.
- Weakened immune system from HIV, autoimmune diseases, or drugs that weaken the immune system.
- Age: Overall, lymphoma occurs most often in people 60 and older, though Hodgkin lymphoma is often found in early adulthood (20s) as well.
Symptoms of lymphoma may include:
- Enlarged lymph nodes (non-painful lumps under the skin).
- Drenching night sweats.
- Unintentional weight loss.
- Severe fatigue.
- Swollen abdomen.
- Feeling full after eating only a small amount of food.
- Chest pressure or pain.
- Shortness of breath or cough.
- Severe or frequent infections.
- Easy bruising or bleeding.
- Fever.
- Itchy rash (may appear as reddish or purple scaly area).
Screening for Lymphoma
Screening is used to look for cancer before a person shows any symptoms of the disease. There are no standard screenings for lymphoma, but symptoms such as enlarged lymph nodes — which cause lumps or bumps under the skin — or any of the symptoms listed above should be evaluated by a doctor as soon as possible.
Diagnosing Lymphoma
Based on a patient’s symptoms and after an initial physical examination, a doctor may order certain tests to determine whether the patient has lymphoma. Though testing procedures can vary based on the type of lymphoma the doctor is looking for, common screenings for lymphoma include:
Biopsy: During a biopsy, a doctor extracts a sample (or multiple samples) of tissue from the lymph nodes and/or bone marrow. These are sent to a laboratory for analysis by a pathologist to determine whether the cells in the sample are cancerous.
Computed tomography (CT or CAT) scan: A CT scan uses x-rays to take detailed images of the body and can help determine if any lymph nodes or organs are enlarged.
Positron emission tomography (PET) scan: A slightly radioactive form of sugar is injected into the blood, where it is taken in by cells in the body. Since cancer cells grow faster than normal cells, they take in larger amounts of the sugar. Doctors use PET scans to look for possible areas of cancer spread, and to determine if suspicious areas seen in other imaging tests are cancer or not. PET is considered the diagnostic imaging of choice for patients with aggressive lymphomas and some indolent lymphomas
Ultrasound: This imaging test uses sound waves to create pictures of internal organs or masses. Ultrasound can be used to view lymph nodes near the surface of the body or to look inside the abdomen for enlarged lymph nodes or organs.
Stages of Lymphoma
After diagnosing the presence of lymphoma, the doctor will identify the stage of the disease. The stage is determined by several factors, including where exactly the disease formed, how extensive it is, and whether and how much it has spread.
Many of the same tests used to diagnose lymphoma are also used to identify the stage, including biopsies, x-rays, CT/CAT scans, and PET scans.
The staging system for lymphoma is called the Ann Arbor classification. It has four stages, described by Roman numerals I through IV. It is important to highlight that the stage at diagnosis does not have the same ramifications as stage at diagnosis for solid cancers. Most indolent lymphomas are diagnosed in stage III or IV and have excellent outcomes. In patients with aggressive lymphoma, staging assists the oncologist to determine the number of cycles of treatment to be given to patients.
Lymphoma Stages
Stage I: Lymphoma is found in only one lymph node area or lymphoid organ such as the thymus, or the cancer is found only in one part of one organ outside the lymph system.
Stage II: Lymphoma is found in two or more lymph node areas on the same side of (above or below) the diaphragm, or the cancer extends locally from one lymph node area into a nearby organ.
Stage III: Lymphoma is found in lymph node areas on both sides of (above and below) the diaphragm, or the cancer is in lymph nodes above the diaphragm and in the spleen.
Stage IV: Lymphoma has spread widely into at least one organ outside of the lymph system, such as the liver, bone marrow, or lungs.Treatments for Lymphoma
The treatment for lymphoma is customized to each patient and depends on the stage at which the patient is diagnosed, and the patient’s general health. Lymphoma care teams may include multiple health care specialists, including primary care providers, medical oncologists, hematologists, and radiation oncologists, as well as nurse practitioners, physician assistants, nurses, psychologists, social workers, and rehabilitation specialists. CU Cancer Center doctors offer specialized care for patients with lymphoma.
Treatments for lymphoma include radiation therapy, chemotherapy, immunotherapy, and targeted drug therapy. Patients may receive one or more of these treatments in combination. Some patients may also be eligible to participate in clinical trials — doctor-led research studies of new or experimental procedures or treatments.
Radiation Therapy for Lymphoma
Radiation therapy uses high-powered energy to kill cancer cells. A doctor who specializes in radiation therapy to treat cancer is a radiation oncologist.
Chemotherapy for Lymphoma
Chemotherapy uses drugs to kill rapidly growing cancer cells. Drugs are either injected into a vein or taken orally. Depending on the type of lymphoma, chemotherapy may be combined with immunotherapy or followed by radiation therapy.
In some cases, high-dose chemotherapy is delivered in conjunction with a stem cell transplant (also called a bone marrow transplant) that helps to negate the damage done by the high-dose chemo. Transplants can be autologous, using the patient’s own stem cells, or allogenic, using stem cells from someone else.
Immunotherapy for Lymphoma
Sometimes the body’s immune system does not attack cancer because cancer cells produce proteins that help them hide from immune system cells. Immunotherapy, also called biologic therapy, boosts the patient’s immune system to help it attack and destroy cancer cells.
Monoclonal antibodies are man-made antibodies that target proteins and other substances on lymphoma cells, enabling them to get to and attack the cancer directly. Monoclonal antibodies used to treat lymphoma include:
- Rituximab (Rituxan).
- Obinutuzumab (Gazyva).
- Ofatumumab (Arzerra).
- Ibritumomab tiuxetan (Zevalin).
- Brentuximab vedotin (Adcetris).
- Tafasitamab (Monjuvil).
- Polatuzumab vedotin (Polivy).
- Loncastuximab tesirine-lpyl (Zynlonta).
- Rituximab (Rituxan).
Another immunotherapy approach to lymphoma cancer is the use of immune checkpoint inhibitors or checkpoint blockade therapies — drugs that target the body’s checkpoint proteins, helping restore the immune system’s natural defenses against cancer cells.
Chimeric antigen receptor (CAR) T-cell therapy is a relatively new treatment in which immune cells called T cells are removed from the patient’s blood and altered in the lab to place receptors called chimeric antigen receptors, or CARs, on their surface. These receptors attach to proteins on the surface of lymphoma cells. The T cells are multiplied in the lab and put back into the patient’s blood, where they seek out and destroy lymphoma cells.
→ Patient cancer-free after CAR T-cell therapy at University of Colorado
Targeted Drug Therapy for Lymphoma
Targeted therapy focuses on the specific genes, proteins, or tissue environments that contribute to lymphoma, limiting damage to non-cancerous cells and tissues.
The most common targeted drug therapies for lymphoma include:
Proteasome inhibitors work by preventing enzyme complexes called proteasomes from breaking down proteins that help keep cell division under control. They are typically used to treat multiple myeloma but can be useful in treating some forms of non-Hodgkin lymphoma as well.
Histone deacetylase (HDAC) inhibitors affect which genes are active in a cancer cell by interacting with proteins in chromosomes called histones.
BTK inhibitors: Bruton’s tyrosine kinase is a protein that helps some lymphoma cells grow and survive. Targeting this protein and inhibiting its activity is useful in treating some types of B-cell non-Hodgkin lymphomas.
PI3K inhibitors work by slowing the processes of phosphatidylinositol 3-kinases (PI3Ks), a family of proteins that help regulate cell growth.
EZH2 inhibitors target EZH2, a protein called a methyltransferase that helps some cancer cells grow.
Nuclear export inhibitors block a protein that helps cells survive by carrying other proteins from the nucleus of a cell to other parts of the cell. When this process is blocked, it causes the cell to die.
The University of Colorado (CU) Cancer Center partners with UCHealth, Children’s Hospital Colorado, and Rocky Mountain Regional VA to provide clinical care. Please make an appointment with one of our clinical partners to be seen by a CU Cancer Center doctor.
UCHealth Cancer Care - Anschutz Medical Campus
1665 Aurora Court Anschutz Cancer Pavilion
Aurora, CO 80045
720-848-0300
UCHealth Cherry Creek Medical Center
100 Cook Street
Denver, CO 80206
720-848-0000
UCHealth Cancer Center - Highlands Ranch
1500 Park Central Drive
Highlands Ranch, CO 80129
720-516-1100
UCHealth Lone Tree Medical Center
9548 Park Meadows Drive
Lone Tree, CO 80124
720-848-2200
Children's Hospital Colorado:
13123 East 16th Avenue
Aurora, CO 80045
720-777-6740
Rocky Mountain Regional VA Medical Center:
1700 North Wheeling Street
Aurora, CO 80045-7211
303-399-8020
Latest in Lymphoma from the CU Cancer Center
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Information reviewed by Manali Kamdar, MD, in May 2022.