Lymphoma is a cancer that starts in white blood cells called lymphocytes, which are a core part of your immune system. Unlike solid tumors that form in organs like the lung or breast, lymphoma develops within the lymphatic system, a network of nodes, vessels, and organs (including the spleen and bone marrow) that helps your body fight infection. It is one of the most common blood cancers, and overall five-year survival for non-Hodgkin lymphoma, the more common type, is about 74%.
How Lymphoma Develops
Your lymphocytes normally activate only when they encounter a specific threat, like a virus or bacteria. In lymphoma, genetic changes hijack that activation process. Mutations can cause the cell’s internal signaling to switch on permanently, so the lymphocyte keeps dividing even without an outside threat. In some B-cell lymphomas, for example, mutations disrupt the normal recycling of receptor proteins on the cell surface, locking signaling pathways into a constantly “on” state. The result is an ever-growing population of abnormal lymphocytes that crowd out healthy cells and accumulate in lymph nodes, the spleen, or other tissues.
Because lymphocytes travel freely through the bloodstream and lymphatic vessels, lymphoma can appear in many places at once, which is one reason it behaves differently from cancers that start as a single lump in one organ.
Hodgkin vs. Non-Hodgkin Lymphoma
Lymphomas are split into two broad categories: Hodgkin lymphoma and non-Hodgkin lymphoma (NHL). The key difference is the type of abnormal cell involved. Hodgkin lymphoma features distinctive giant cells visible under a microscope, historically called Reed-Sternberg cells. Non-Hodgkin lymphoma lacks these cells and instead encompasses a wide range of subtypes.
Non-Hodgkin lymphoma is far more common, accounting for roughly 90% of all lymphoma diagnoses. It can arise from either B-cells or T-cells, though the large majority are B-cell lymphomas. The two most frequent NHL subtypes are diffuse large B-cell lymphoma (DLBCL), which grows quickly, and follicular lymphoma, which tends to grow slowly. Because NHL includes dozens of subtypes with very different behaviors, treatment and outlook vary widely depending on the exact diagnosis.
Hodgkin lymphoma is rarer but tends to have high cure rates, especially when caught early. It most commonly appears in young adults (ages 20 to 30) and again in people over 55.
Symptoms to Recognize
The most common first sign of lymphoma is a painless, swollen lymph node, usually in the neck, armpit, or groin. Many people notice a lump that doesn’t go away after a few weeks. Beyond that, doctors look for a specific cluster known as “B symptoms,” which carry prognostic significance:
- Unexplained fever above 100.4°F (38°C)
- Drenching night sweats severe enough to require changing bedclothes
- Unexplained weight loss of more than 10% of body weight within six months
Having one or more of these symptoms generally signals more advanced or aggressive disease. Other symptoms like fatigue, itching, or pain in lymph nodes after drinking alcohol can also occur but are not formally classified as B symptoms.
What Raises Your Risk
Most people who develop lymphoma have no obvious risk factor, but several things are known to increase the odds. A weakened immune system is one of the strongest links. People living with HIV have a higher risk of several NHL subtypes, including DLBCL and Burkitt lymphoma. Organ transplant recipients taking immunosuppressive drugs also face elevated risk.
Certain viral infections play a direct role. The Epstein-Barr virus (the virus behind mono) is closely tied to Burkitt lymphoma, particularly in parts of Africa, and to lymphomas in people with HIV. Human T-cell lymphotropic virus (HTLV-1) raises the risk of specific T-cell lymphomas. Human herpes virus 8 can lead to a rare subtype called primary effusion lymphoma.
Environmental exposures matter as well. Long-term contact with chemicals like benzene and certain herbicides and insecticides has been linked to increased NHL risk. Previous cancer treatment, including both chemotherapy and radiation therapy, can raise the chance of developing lymphoma years later. People treated for Hodgkin lymphoma, for instance, have an increased risk of later developing NHL. Some drugs used for rheumatoid arthritis, including methotrexate and TNF inhibitors, have also been associated with a modest increase in risk.
How Lymphoma Is Diagnosed
A lymphoma diagnosis almost always requires a biopsy of an enlarged lymph node. The gold standard is an excisional biopsy, where a surgeon removes an entire lymph node so a pathologist can examine its full structure. This matters because lymphoma subtypes are distinguished by how abnormal cells are arranged within the node, not just what individual cells look like. A needle biopsy can sometimes point toward lymphoma, but it often cannot provide enough tissue for a definitive subtype and grade. National guidelines state that fine-needle aspiration alone is not sufficient for an initial lymphoma diagnosis.
Once lymphoma is confirmed, imaging helps determine how far it has spread. A PET/CT scan is the standard tool. It combines a CT scan’s detailed anatomy with a radioactive sugar tracer that highlights metabolically active (potentially cancerous) tissue. A bone marrow biopsy may also be performed to check whether lymphoma cells have reached the marrow.
Staging: How Far It Has Spread
Lymphoma staging uses a system that runs from Stage I through Stage IV, based on how many lymph node groups are involved and whether the disease has reached organs outside the lymphatic system.
- Stage I: Cancer is in a single lymph node region or a single organ site outside the lymph system.
- Stage II: Two or more lymph node regions are involved, but all are on the same side of the diaphragm (the muscle separating your chest from your abdomen).
- Stage III: Lymph node regions on both sides of the diaphragm are affected. The spleen may also be involved.
- Stage IV: Cancer has spread widely into at least one organ outside the lymph system, such as the liver, bone marrow, lungs, or cerebrospinal fluid.
About 33% of non-Hodgkin lymphoma cases are diagnosed at Stage IV. Five-year survival drops from roughly 88% for Stage I disease to about 64% for Stage IV, but even advanced-stage lymphoma is often treatable, and many subtypes respond well to therapy regardless of stage.
Treatment Options
Treatment depends heavily on whether the lymphoma is Hodgkin or non-Hodgkin, the specific subtype, and how aggressive it is. Slow-growing (indolent) lymphomas like follicular lymphoma may not need immediate treatment at all. Instead, doctors sometimes recommend a watch-and-wait approach, monitoring closely and starting therapy only when symptoms develop or the disease progresses.
For aggressive lymphomas, chemotherapy combined with an antibody drug is the most common frontline approach. The combination typically involves multiple medications given in cycles over several months. Hodgkin lymphoma and many B-cell non-Hodgkin lymphomas respond well to these regimens, and many patients achieve complete remission. Radiation therapy may be added for localized disease or bulky tumor masses.
If lymphoma returns after initial treatment or doesn’t respond, options include higher-dose chemotherapy followed by a stem cell transplant, which uses your own or a donor’s stem cells to rebuild the bone marrow after intensive treatment.
CAR T-Cell Therapy
For certain types of lymphoma that relapse or resist standard treatment, a newer approach called CAR T-cell therapy is available. In this treatment, your own immune cells are collected, genetically reprogrammed in a lab to recognize and attack lymphoma cells, then infused back into your body. Six CAR T-cell products are now FDA-approved for various blood cancers. In lymphoma specifically, approvals cover relapsed or refractory large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma. Some products are now approved for use as early as second-line therapy when lymphoma comes back within a year of initial treatment, rather than being reserved as a last resort.
CAR T-cell therapy can produce durable remissions in patients who have run out of other options, though it carries significant short-term side effects, including a severe inflammatory reaction that requires close hospital monitoring for one to two weeks after infusion.