Non-Hodgkin lymphoma is a cancer that starts in white blood cells called lymphocytes, which are part of your immune system. It accounts for about 4% of all cancers in the United States, with roughly 80,000 new cases diagnosed each year. The overall five-year survival rate is 74.2%, though outcomes vary widely depending on the type and how far the disease has spread.
How It Differs From Hodgkin Lymphoma
Both Hodgkin and non-Hodgkin lymphoma are cancers of the lymphatic system, but the distinction comes down to what doctors see under a microscope. Hodgkin lymphoma contains a specific abnormal cell called a Reed-Sternberg cell. If that cell is absent, the lymphoma is classified as non-Hodgkin. This isn’t just a naming convention. The two cancers behave differently, respond to different treatments, and carry different prognoses.
Non-Hodgkin lymphoma is far more common than Hodgkin lymphoma and includes over 60 distinct subtypes. Most cases develop from B cells, a type of lymphocyte that normally produces antibodies. A smaller portion, roughly 8% of cases, develops from T cells, which play a different role in immune defense.
Common Subtypes
The two most common subtypes are diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma, making up about 17% and 14% of all lymphoma cases respectively. DLBCL is aggressive, meaning it grows quickly and typically requires prompt treatment. Follicular lymphoma, by contrast, is usually indolent (slow-growing) and may not need immediate treatment in its early stages.
This distinction between aggressive and indolent subtypes is one of the most important factors shaping treatment decisions. Some slow-growing lymphomas are monitored for months or years before treatment begins, a strategy called watchful waiting. Aggressive subtypes demand faster action but often respond well to treatment, with a realistic chance of complete remission.
Symptoms to Recognize
The most common first sign is painless swelling in one or more lymph nodes, typically in the neck, armpit, groin, or abdomen. Because swollen lymph nodes also occur with ordinary infections, the key difference is persistence. Lymph node swelling from an infection usually resolves within a few weeks. Swelling caused by lymphoma doesn’t go away on its own and may gradually enlarge.
Beyond swollen nodes, doctors look for a specific cluster of symptoms known as B symptoms:
- Unexplained fever that comes and goes without an obvious infection
- Drenching night sweats severe enough to soak through clothing or bedsheets
- Unexplained weight loss of more than 10% of body weight over six months
Persistent fatigue that doesn’t improve with rest is another common complaint. Some people also experience pain or a feeling of fullness in the abdomen if lymphoma develops in the spleen or abdominal lymph nodes.
Risk Factors
There is no single cause of non-Hodgkin lymphoma, but research has identified several factors that meaningfully increase the risk. The strongest associations fall into three categories: immune system problems, certain infections, and environmental exposures.
Conditions that suppress or dysregulate the immune system carry the highest risk. People who have received organ transplants (particularly kidney transplants) and take immunosuppressive medications face a significantly elevated risk. HIV/AIDS also increases vulnerability because of the immune damage it causes. Autoimmune diseases, including rheumatoid arthritis, lupus, Sjögren’s syndrome, and celiac disease, are all linked to higher rates of non-Hodgkin lymphoma. Celiac disease in particular is associated with T-cell lymphoma.
Several viral and bacterial infections play a role as well. Hepatitis B and hepatitis C viruses both show strong associations, with hepatitis C linked specifically to DLBCL. Epstein-Barr virus, the same virus that causes mono, is connected to certain subtypes. Tuberculosis has also emerged as a risk factor in large analyses. Among environmental exposures, insecticides and certain chemical solvents have been studied most extensively, though the strength of those associations is more modest than the immune-related risks.
How It’s Diagnosed
Accurate diagnosis of non-Hodgkin lymphoma requires a tissue biopsy, and the type of biopsy matters. A surgical excision biopsy, where an entire lymph node or a large portion of tissue is removed, is considered the gold standard. This approach gives pathologists enough material to examine the cell architecture, run specialized staining tests, and perform genetic analyses that pinpoint the exact subtype.
Needle biopsies (where a thin core of tissue is extracted with a needle) can sometimes be adequate, but they carry a real risk of providing too little tissue for a confident diagnosis. Single thin cores of 5 millimeters or less severely limit what tests can be performed. Since treatment depends entirely on getting the subtype right, most guidelines recommend excision biopsy when it’s surgically feasible. After the biopsy confirms a diagnosis, imaging scans and sometimes a bone marrow biopsy help determine how far the disease has spread.
Staging
Non-Hodgkin lymphoma is staged using the Ann Arbor system, which has four stages based on how many areas of the body are involved:
- Stage I: Cancer is in a single lymph node region or a single organ outside the lymphatic system.
- Stage II: Cancer is in two or more lymph node regions, but all on the same side of the diaphragm (the muscle separating the chest from the abdomen).
- Stage III: Cancer is in lymph node regions on both sides of the diaphragm, possibly including the spleen.
- Stage IV: Cancer has spread widely into organs outside the lymphatic system, such as the liver, bone marrow, lungs, or cerebrospinal fluid.
About 21% of cases are diagnosed at Stage I, where the five-year survival rate is 87.7%. Roughly 33% are diagnosed at Stage IV, where the five-year survival rate drops to 63.8%. The letter “B” is added to the stage number if a patient has B symptoms (fever, night sweats, weight loss), while “A” indicates those symptoms are absent.
Treatment Approaches
Treatment varies enormously depending on the subtype, stage, and how quickly the cancer is growing. For aggressive subtypes like DLBCL, the standard first-line approach is a combination chemotherapy regimen paired with a targeted antibody therapy. This combination typically involves multiple chemotherapy drugs given in cycles over several months, often alongside radiation therapy for localized disease. Most people receive treatment as outpatients, returning to the clinic every few weeks for infusion sessions.
For indolent (slow-growing) subtypes like follicular lymphoma, treatment may not be necessary right away. If the disease is causing no symptoms and progressing slowly, your doctor may recommend regular monitoring with physical exams and imaging scans every few months. Treatment begins when symptoms develop or the disease shows signs of accelerating.
When non-Hodgkin lymphoma returns after initial treatment or doesn’t respond to it, options include different chemotherapy combinations, stem cell transplants, and increasingly, CAR T-cell therapy. CAR T-cell therapy works by collecting your own immune cells, genetically engineering them in a lab to recognize a specific marker on the surface of lymphoma cells (called CD19), and infusing them back into your body. These modified cells then seek out and destroy the cancer. CAR T-cell therapy has traditionally been reserved for patients who have already gone through multiple rounds of treatment, but recent clinical trials (ZUMA-7 and TRANSFORM) have shown that using it earlier, after just one round of chemotherapy, can lead to longer periods without disease progression compared to the traditional path of additional chemotherapy followed by a stem cell transplant.
What Survival Looks Like by Stage
The overall five-year relative survival rate of 74.2% is an average across all subtypes and stages, so it can be misleading if applied to any one person’s situation. Indolent lymphomas often allow people to live for decades, sometimes with little or no treatment. Aggressive lymphomas, while more immediately dangerous, frequently achieve complete remission with treatment, meaning no detectable cancer remains.
Stage at diagnosis is one of the strongest predictors of outcome. Localized disease (Stage I) carries a five-year survival rate near 88%, while widely spread disease (Stage IV) still has a five-year survival rate above 63%. These numbers have been improving steadily over the past two decades as targeted therapies and immunotherapies have become standard parts of care. The specific subtype, your age, overall health, and how the cancer responds to initial treatment all influence your individual outlook far more than stage alone.