Lymphoma: Types, Symptoms & Treatment Guide

What Is Lymphoma and How Does It Develop?

Lymphoma is a cancer that begins in the lymphatic system, specifically in white blood cells called lymphocytes. It develops when lymphocytes undergo genetic changes that cause them to grow uncontrollably and accumulate, forming tumors primarily in lymph nodes but potentially affecting any organ in the body.

The lymphatic system is a crucial part of your immune system, consisting of a network of vessels, tissues, and organs that work together to fight infection and maintain fluid balance in the body. Lymphocytes, the cells affected in lymphoma, are specialized white blood cells that normally help protect you from infections and diseases. There are two main types of lymphocytes: B-cells (which produce antibodies) and T-cells (which directly attack infected or abnormal cells).

When lymphoma develops, something goes wrong with the genetic programming of these lymphocytes. Instead of following their normal life cycle of growth, function, and death, the affected cells begin to multiply uncontrollably. These abnormal lymphocytes accumulate and form masses, typically first appearing in lymph nodes as painless swellings. However, because lymphocytes circulate throughout the body via the lymphatic system and bloodstream, lymphoma can develop in or spread to virtually any part of the body, including the spleen, bone marrow, liver, lungs, and other organs.

Unlike solid tumors that grow in one location, lymphoma is considered a systemic disease from the start. This means that even when it appears localized, doctors assume that abnormal cells may be present elsewhere in the lymphatic system. This understanding has important implications for staging and treatment approaches, which typically involve systemic therapies like chemotherapy and immunotherapy rather than surgery alone.

The Lymphatic System Explained

Understanding the lymphatic system helps explain why lymphoma behaves the way it does. The system includes lymph nodes (small, bean-shaped organs distributed throughout the body), the spleen (which filters blood and stores lymphocytes), the thymus (where T-cells mature), bone marrow (where lymphocytes are produced), and a network of thin tubes called lymphatic vessels that carry lymph fluid throughout the body.

Lymph nodes are concentrated in certain areas: the neck, armpits, chest, abdomen, and groin. When you're fighting an infection, nearby lymph nodes often swell as they work to filter out pathogens. This is why swollen lymph nodes are common with colds, sore throats, and other infections. However, lymph node swelling caused by infection typically resolves within 2-3 weeks and is often tender to touch, whereas lymphoma-related swelling persists and is usually painless.

What Are the Different Types of Lymphoma?

Lymphoma is divided into two main categories: Hodgkin lymphoma (HL), characterized by the presence of Reed-Sternberg cells, and non-Hodgkin lymphoma (NHL), which includes over 60 distinct subtypes. NHL accounts for approximately 90% of all lymphomas and is further classified as aggressive (fast-growing) or indolent (slow-growing).

Hodgkin Lymphoma

Hodgkin lymphoma is named after Dr. Thomas Hodgkin, who first described it in 1832. It is distinguished from other lymphomas by the presence of large, abnormal cells called Reed-Sternberg cells, which have a characteristic appearance under the microscope often described as "owl eyes." These malignant cells typically make up only about 1-2% of the tumor mass, with the rest consisting of normal immune cells that have been recruited to the area.

Hodgkin lymphoma accounts for approximately 10% of all lymphomas but has particular significance because it was one of the first cancers to be cured with modern treatment. It has a bimodal age distribution, meaning it most commonly affects two age groups: young adults aged 15-35 and older adults over 55. The disease typically spreads in a predictable, orderly fashion from one group of lymph nodes to adjacent groups, which helps with staging and treatment planning.

There are two main types of Hodgkin lymphoma: classical Hodgkin lymphoma (about 95% of cases) and nodular lymphocyte-predominant Hodgkin lymphoma (about 5% of cases). Classical Hodgkin lymphoma is further divided into four subtypes based on how the cells appear under the microscope: nodular sclerosis (most common, particularly in young adults), mixed cellularity, lymphocyte-rich, and lymphocyte-depleted.

Non-Hodgkin Lymphoma

Non-Hodgkin lymphoma encompasses all lymphomas that are not Hodgkin lymphoma, comprising a diverse group of over 60 distinct diseases. Unlike Hodgkin lymphoma, NHL does not contain Reed-Sternberg cells and tends to spread in a less predictable pattern. The risk of NHL generally increases with age, with most cases diagnosed in people over 60.

NHL is broadly categorized by the type of lymphocyte affected (B-cell lymphomas account for about 85% of cases, while T-cell and NK-cell lymphomas make up the remaining 15%) and by growth rate. Aggressive lymphomas grow quickly and require immediate treatment but are often curable. Indolent lymphomas grow slowly and may not require immediate treatment, but they are often more difficult to cure completely.

What Are the Symptoms of Lymphoma?

The most common symptom of lymphoma is painless swelling of lymph nodes, typically in the neck, armpits, or groin. Other symptoms include the "B symptoms" (unexplained fever, drenching night sweats, and significant weight loss), as well as fatigue, itching, shortness of breath, and abdominal discomfort if internal lymph nodes are affected.

Lymphoma symptoms can vary significantly depending on which lymph nodes or organs are affected, the type of lymphoma, and how quickly it is growing. Some people have minimal symptoms even with widespread disease, while others experience significant symptoms from localized involvement. Understanding these symptoms is important for early detection, though it's worth noting that many of these symptoms can also be caused by much more common, benign conditions.

Swollen Lymph Nodes

The hallmark symptom of lymphoma is painless, enlarged lymph nodes. Unlike the tender, swollen lymph nodes that occur with infections, lymphoma-affected nodes are typically rubbery in texture, movable, and not painful to touch. They most commonly appear in the neck (cervical lymph nodes), armpits (axillary lymph nodes), or groin (inguinal lymph nodes), but can occur anywhere lymph nodes exist.

What distinguishes lymphoma-related swelling from infection-related swelling is persistence. While lymph nodes swollen due to infection typically return to normal within 2-3 weeks as the infection resolves, lymphoma-related swelling persists and may gradually increase in size over time. Any lymph node that remains swollen for more than 3-4 weeks, or that continues to grow, should be evaluated by a healthcare provider.

B Symptoms

The term "B symptoms" refers to a specific set of systemic symptoms that have prognostic significance in lymphoma. These symptoms indicate that the disease is affecting the body more broadly and are used in staging to help determine treatment intensity. The classic B symptoms include:

• Unexplained fever: Temperatures above 38°C (100.4°F) that cannot be attributed to an infection or other identifiable cause, often occurring in cycles
• Drenching night sweats: Sweating so severe that it requires changing clothes or bedding, not simply feeling warm at night
• Unexplained weight loss: Losing more than 10% of body weight over 6 months without trying, such as losing 15 pounds if you weighed 150 pounds

The presence of B symptoms is indicated by adding "B" to the stage designation (for example, Stage IIB), while their absence is indicated by "A" (Stage IIA). Patients with B symptoms generally require more intensive treatment than those without.

Other Common Symptoms

Beyond swollen lymph nodes and B symptoms, lymphoma can cause a variety of other symptoms depending on where it develops and spreads:

• Persistent fatigue: Tiredness that doesn't improve with rest and interferes with daily activities
• Unexplained itching (pruritus): Particularly common in Hodgkin lymphoma, sometimes severe and affecting quality of life
• Chest symptoms: Cough, shortness of breath, or chest discomfort if lymph nodes in the chest (mediastinal) are enlarged
• Abdominal symptoms: Feeling of fullness, discomfort, or visible swelling if abdominal lymph nodes or the spleen are affected
• Skin changes: Rashes, lumps, or red or purple patches, particularly in certain T-cell lymphomas
• Pain after alcohol consumption: A rare but distinctive symptom sometimes seen in Hodgkin lymphoma

What Causes Lymphoma and Who Is at Risk?

The exact cause of most lymphomas is unknown, but several risk factors have been identified. These include weakened immune system (from HIV, organ transplant, or immunosuppressive medications), certain infections (Epstein-Barr virus, H. pylori, Hepatitis C), autoimmune diseases, family history, and exposure to certain chemicals. However, most people who develop lymphoma have no identifiable risk factors.

Understanding the causes and risk factors for lymphoma is complex because, unlike some cancers with clear causative factors (such as smoking and lung cancer), most lymphomas develop without an identifiable cause. The disease appears to result from a combination of genetic predisposition, immune system factors, and environmental exposures, though the specific interactions remain poorly understood.

Research has shown that lymphoma develops when lymphocytes acquire genetic mutations that allow them to escape normal growth controls. These mutations may be inherited (present from birth) or acquired (developing during a person's lifetime). Acquired mutations can result from errors during normal cell division, exposure to radiation or certain chemicals, or effects of viral infections. In most cases, it's impossible to determine what caused the specific mutations that led to an individual's lymphoma.

Immune System Factors

A weakened or dysfunctional immune system is one of the strongest risk factors for lymphoma, particularly non-Hodgkin lymphoma. This makes biological sense because the immune system normally identifies and eliminates abnormal cells before they can develop into cancer. When this surveillance system is impaired, abnormal lymphocytes are more likely to survive and multiply.

Conditions that increase lymphoma risk due to immune dysfunction include HIV/AIDS (which dramatically increases risk for certain lymphoma types), organ transplantation requiring long-term immunosuppressive drugs, inherited immune deficiency disorders, and autoimmune diseases such as rheumatoid arthritis, Sjogren's syndrome, and celiac disease. The risk from autoimmune diseases may be related to both chronic immune stimulation and the immunosuppressive medications used to treat these conditions.

Infectious Agents

Several viral and bacterial infections have been linked to increased lymphoma risk, though most people with these infections never develop lymphoma. The Epstein-Barr virus (EBV), which causes infectious mononucleosis, is associated with several lymphoma types including Burkitt lymphoma and some Hodgkin lymphomas. Human T-lymphotropic virus type 1 (HTLV-1) causes adult T-cell leukemia/lymphoma in a small percentage of infected individuals, primarily in endemic areas like Japan and the Caribbean.

Helicobacter pylori, the bacterium that causes stomach ulcers, is associated with MALT lymphoma of the stomach. Remarkably, eradicating this infection with antibiotics can cure early-stage gastric MALT lymphoma in many cases. Hepatitis C virus is associated with certain B-cell lymphomas, and treating the hepatitis can sometimes lead to lymphoma regression.

Other Risk Factors

Additional factors that may increase lymphoma risk include age (risk generally increases with age for NHL), family history of lymphoma, previous cancer treatment with radiation or chemotherapy, exposure to certain chemicals including some pesticides and herbicides, and benzene exposure. However, the absolute risk increase from most of these factors is relatively small, and most people with these exposures never develop lymphoma.

How Is Lymphoma Diagnosed?

Lymphoma diagnosis requires a tissue biopsy, typically of an enlarged lymph node. The tissue is examined under a microscope and tested with immunohistochemistry and genetic analysis to determine the exact lymphoma type. Additional tests including PET-CT scans, bone marrow biopsy, and blood tests are used to determine the extent of disease (staging).

Diagnosing lymphoma accurately is crucial because treatment approaches differ significantly between lymphoma types. The diagnostic process typically begins when someone notices persistent lymph node swelling or experiences concerning symptoms, leading to evaluation by their healthcare provider. The process involves several components: tissue diagnosis, subtype classification, and staging to determine the extent of disease.

Initial Evaluation

The diagnostic journey usually starts with a thorough medical history and physical examination. Your doctor will ask about your symptoms, when they started, and how they've changed over time. They will perform a physical exam, carefully checking for enlarged lymph nodes in your neck, armpits, groin, and other areas, as well as examining your abdomen for an enlarged spleen or liver.

Blood tests are typically ordered early in the evaluation. While blood tests alone cannot diagnose lymphoma, they provide important information. A complete blood count (CBC) can reveal abnormalities in blood cell counts that suggest bone marrow involvement. Lactate dehydrogenase (LDH) is often elevated in lymphoma and provides prognostic information. Other tests assess kidney and liver function, which is important for treatment planning.

Tissue Biopsy

The definitive diagnosis of lymphoma requires examining tissue under a microscope. This typically involves removing an enlarged lymph node (excisional biopsy) or a large portion of it (incisional biopsy). In some cases, a core needle biopsy may be used, though this provides less tissue and may not always allow complete classification. Fine needle aspiration (FNA) alone is generally not sufficient for initial lymphoma diagnosis because it doesn't preserve the tissue architecture needed for accurate classification.

The pathologist examines the tissue using multiple techniques. Standard microscopy reveals the pattern of cell growth and the appearance of individual cells. Immunohistochemistry uses antibodies to identify specific proteins on the cell surface, helping distinguish between B-cell and T-cell lymphomas and identify specific subtypes. Flow cytometry can analyze cells in suspension, providing additional information about cell surface markers. Genetic and molecular testing looks for specific chromosomal abnormalities and genetic mutations characteristic of certain lymphoma types.

Staging Workup

Once lymphoma is diagnosed, staging determines how far the disease has spread. This information is critical for treatment planning and prognosis. The staging workup typically includes:

• PET-CT scan: The most important imaging test for staging most lymphomas. PET (positron emission tomography) detects metabolically active tumor cells, while CT (computed tomography) provides detailed anatomical images. Together, they show both where disease is located and how active it is.
• Bone marrow biopsy: A sample of bone marrow is taken, usually from the hip bone, to check if lymphoma has spread to the bone marrow. This test is important because bone marrow involvement affects staging and treatment.
• Additional imaging: MRI of the brain or spine may be needed if central nervous system involvement is suspected. CT scans of specific areas may provide additional detail.
• Lumbar puncture: For certain high-risk lymphomas, spinal fluid is tested for cancer cells.

How Is Lymphoma Treated?

Lymphoma treatment depends on the specific type, stage, and patient factors. Main treatment options include chemotherapy (often combined with immunotherapy such as rituximab), radiation therapy, targeted therapy, stem cell transplantation, and CAR-T cell therapy. Many lymphomas are highly curable, especially Hodgkin lymphoma and certain aggressive NHL subtypes.

Treatment for lymphoma has advanced dramatically over the past several decades, transforming many types from fatal diseases to highly curable or manageable conditions. The choice of treatment depends on multiple factors: the specific lymphoma type and subtype, stage of disease, presence of B symptoms, patient age and overall health, and patient preferences. Treatment decisions are typically made by a multidisciplinary team including hematologists/oncologists, radiation oncologists, and other specialists.

Chemotherapy

Chemotherapy remains a cornerstone of lymphoma treatment. These drugs work by killing rapidly dividing cells, including cancer cells. For most lymphomas, chemotherapy is given in combinations (regimens) that have been optimized through decades of clinical trials to maximize effectiveness while managing side effects.

For Hodgkin lymphoma, the ABVD regimen (Adriamycin, Bleomycin, Vinblastine, Dacarbazine) has been a standard treatment for decades, though newer approaches including immunotherapy are changing treatment paradigms. For diffuse large B-cell lymphoma, R-CHOP (Rituximab plus Cyclophosphamide, Doxorubicin, Vincristine, Prednisone) is the standard first-line treatment. Chemotherapy is typically given in cycles, with treatment periods followed by rest periods to allow the body to recover.

Immunotherapy

Immunotherapy has revolutionized lymphoma treatment. Rituximab, a monoclonal antibody targeting the CD20 protein on B-cells, was one of the first successful cancer immunotherapies and has dramatically improved outcomes for B-cell lymphomas. Adding rituximab to chemotherapy has increased cure rates for aggressive B-cell lymphomas and improved control of indolent lymphomas.

Newer immunotherapy approaches include checkpoint inhibitors (such as pembrolizumab and nivolumab), which help the immune system recognize and attack cancer cells. These have shown particular benefit in Hodgkin lymphoma and certain other lymphoma types. Antibody-drug conjugates combine a targeting antibody with a chemotherapy payload, delivering treatment directly to cancer cells while sparing normal cells.

CAR-T Cell Therapy

Chimeric antigen receptor T-cell (CAR-T) therapy represents a major advance for patients with lymphomas that have not responded to or have returned after other treatments. In this approach, a patient's own T-cells are collected, genetically modified in a laboratory to express a receptor that recognizes lymphoma cells, expanded in number, and then infused back into the patient.

CAR-T therapy has produced remarkable responses in some patients with aggressive lymphomas who had exhausted other options, with a significant proportion achieving long-term remissions. However, it can cause serious side effects including cytokine release syndrome (a systemic inflammatory response) and neurological toxicity, requiring treatment at specialized centers with experienced teams.

Radiation Therapy

Radiation therapy uses high-energy rays to kill cancer cells. It is most effective for localized disease and is often used in combination with chemotherapy. For early-stage Hodgkin lymphoma, radiation to involved sites after abbreviated chemotherapy can achieve excellent cure rates. For some indolent lymphomas, radiation alone can be curative when disease is very localized.

Modern radiation techniques allow precise targeting of tumors while minimizing exposure to surrounding healthy tissues. This is particularly important for young patients, who are at risk for late effects from radiation including secondary cancers and cardiovascular disease decades after treatment.

Stem Cell Transplantation

Stem cell transplantation (also called bone marrow transplantation) allows delivery of very high doses of chemotherapy that would otherwise be too toxic because they destroy the bone marrow. After the high-dose treatment, stem cells are infused to "rescue" the bone marrow and allow blood cell production to recover.

Autologous transplantation uses the patient's own stem cells, collected before high-dose treatment. This approach is commonly used for lymphomas that have relapsed after initial treatment. Allogeneic transplantation uses stem cells from a donor and provides both high-dose treatment and an immune effect against the lymphoma (graft-versus-lymphoma effect). It carries higher risks but may be the best option for some patients.

What Is the Prognosis for Lymphoma?

Prognosis varies significantly by lymphoma type and stage. Hodgkin lymphoma has a 5-year survival rate of approximately 89% overall, with early-stage disease often exceeding 95%. Non-Hodgkin lymphoma has a 5-year survival rate of approximately 73% overall, but ranges from over 90% for favorable subtypes to lower rates for aggressive types. Advances in treatment continue to improve outcomes.

When discussing lymphoma prognosis, it's important to understand that statistics represent averages across many patients and cannot predict what will happen to any individual. Outcomes vary enormously based on the specific lymphoma type, stage at diagnosis, patient age and overall health, response to initial treatment, and availability of effective subsequent treatments if needed. Many patients do far better than statistics might suggest, particularly as newer treatments become available.

Hodgkin Lymphoma Prognosis

Hodgkin lymphoma is one of the most curable cancers. For early-stage disease (stages I and II), cure rates exceed 90% with modern treatment. Even for advanced-stage disease (stages III and IV), approximately 75-80% of patients are cured with initial treatment. Overall, the 5-year relative survival rate for Hodgkin lymphoma is approximately 89%, meaning that people with Hodgkin lymphoma are, on average, 89% as likely to live at least 5 years as people without cancer.

For patients who relapse after initial treatment, outcomes depend on factors including duration of first remission and response to salvage therapy. High-dose chemotherapy with stem cell rescue achieves long-term remissions in approximately 50% of transplant-eligible patients with relapsed disease. Newer options including checkpoint inhibitors and brentuximab vedotin have improved outcomes for patients who relapse after transplant or are not transplant candidates.

Non-Hodgkin Lymphoma Prognosis

Because NHL encompasses over 60 different diseases, prognosis varies enormously. For aggressive lymphomas like diffuse large B-cell lymphoma, approximately 60-70% of patients are cured with R-CHOP immunochemotherapy. Younger patients and those with limited-stage disease have higher cure rates. For patients who relapse, options including salvage chemotherapy, stem cell transplantation, and CAR-T cell therapy offer potential for cure or long-term remission.

Indolent lymphomas like follicular lymphoma have a different pattern. While they are often not cured with available treatments, they typically grow slowly and can be controlled for many years. The median survival for follicular lymphoma now exceeds 20 years. Some patients require no treatment for years, while others need multiple treatments over time. Research continues into approaches that might make these lymphomas curable.

Prognostic Factors

Several factors help doctors estimate prognosis and guide treatment intensity. For Hodgkin lymphoma, the International Prognostic Score (IPS) considers factors including age, stage, blood counts, and albumin level. For aggressive NHL, the International Prognostic Index (IPI) considers age, stage, LDH level, performance status, and number of extranodal sites. Higher scores on these indices indicate higher risk, though many high-risk patients are still cured with appropriate treatment.

What Is It Like Living With Lymphoma?

Living with lymphoma involves managing treatment side effects, coping with uncertainty, and adapting to a new normal. During treatment, fatigue and infection risk are common concerns. After treatment, regular follow-up monitors for recurrence. Many survivors experience lasting effects including fatigue and anxiety, but support resources and survivorship programs can help with adjustment and quality of life.

A lymphoma diagnosis affects every aspect of life, from physical health to emotional wellbeing, relationships, and work. The experience varies considerably depending on the type of lymphoma, treatment required, and individual circumstances. Understanding what to expect can help patients and families prepare and cope with the challenges ahead.

During Treatment

Treatment for lymphoma can be intensive and demanding. Chemotherapy often causes fatigue, nausea, hair loss, and increased infection risk. The degree of these side effects varies between regimens and individuals. Supportive medications can help manage nausea and other symptoms, and most side effects improve after treatment ends.

Maintaining nutrition, staying as active as possible, getting adequate rest, and accepting help from others are all important during treatment. Many patients continue working with accommodations, while others need to take leave. Clear communication with employers about needs and limitations is important. Treatment schedules are often predictable, allowing some planning around better and worse days.

After Treatment

Completing treatment brings relief but also challenges. Regular follow-up appointments monitor for recurrence, with the schedule varying based on lymphoma type and individual risk. Follow-up typically includes physical exams, blood tests, and periodic imaging, with the intensity of surveillance decreasing over time as the risk of recurrence falls.

Many survivors experience lasting effects from treatment. Fatigue is the most common, sometimes persisting for months or even years. Other possible late effects include peripheral neuropathy (numbness or tingling in hands and feet), cardiac effects from certain chemotherapy drugs, fertility problems, and risk of secondary cancers. Long-term survivorship care addresses these issues and promotes overall health.

Emotional and Psychological Aspects

The psychological impact of a cancer diagnosis is significant. Anxiety, depression, fear of recurrence, and difficulty returning to "normal" life are all common experiences. Many cancer centers offer counseling and support groups. For some survivors, connecting with others who have had similar experiences provides valuable perspective and support.

When Should You Seek Medical Care?

See a doctor if you have lymph node swelling lasting more than 2-3 weeks, especially if painless and not associated with infection. Seek prompt evaluation for B symptoms (unexplained fever, drenching night sweats, significant weight loss). During lymphoma treatment, contact your care team for fever, infection signs, severe side effects, or any concerning new symptoms.

Early detection of lymphoma can improve treatment outcomes, so it's important to know when symptoms warrant medical evaluation. At the same time, the symptoms of lymphoma are nonspecific and overlap with many common, benign conditions, so there's no need to panic about every swollen lymph node.

When to See Your Doctor

Schedule an appointment with your doctor if you notice:

• Lymph node swelling that persists for more than 2-3 weeks, especially if it's painless and not associated with an obvious infection
• Lymph nodes that continue to grow over time
• Unexplained fever, particularly if recurring
• Night sweats severe enough to require changing clothes or bedding
• Unexplained weight loss of more than 10% of body weight
• Persistent fatigue that doesn't improve with rest
• Unexplained itching, especially if severe or widespread

During Treatment

If you're undergoing lymphoma treatment, maintain close communication with your care team. Contact them promptly for fever (especially if above 38°C/100.4°F, which could indicate infection), signs of infection, severe or unexpected side effects, or any symptoms that concern you.