Lymphoma

Introduction

Lymphoma is a cancer that begins in the lymphatic system, the network of vessels, nodes, and organs that powers your immune defense. It starts when lymphocytes grow out of control. Because the lymphatic system reaches almost every organ, lymphoma can show up in surprising places: a lump in the neck, an enlarged spleen, or even a tumor in the gut.

This guide walks through the essentials. You'll learn how the lymphatic system normally works, how lymphoma differs from leukemia, what triggers it, how it's diagnosed and staged, and where treatment stands today. Modern lymphoma care looks very different from a decade ago. Targeted antibodies, CAR-T cells, and bispecific therapies have changed the conversation, especially for patients whose disease comes back.

How the lymphatic system normally works

Think of the lymphatic system as the body's drainage and surveillance network. Lymphatic vessels collect fluid that leaks out of blood vessels and return it to the bloodstream. Along the way, that fluid passes through lymph nodes which are small, bean-shaped filters packed with immune cells. The spleen filters blood and stores immune cells. The thymus, especially in childhood, is where T cells mature.

Three jobs matter most for understanding lymphoma:

• Producing lymphocytes (B cells and T cells) that recognize and destroy pathogens.
• Filtering pathogens and abnormal cells as lymph passes through nodes.
• Transporting immune cells to wherever they're needed.

When lymphocytes themselves become cancerous, the system meant to protect you starts working against you. That's lymphoma.

Lymphoma vs Leukemia

Signs and Symptoms

The most common first sign of lymphoma is a painless swollen lymph node in the neck, armpit, or groin. The node is often firm, smooth, and movable under the skin.

Other symptoms include:

• Fever that lingers for weeks without a clear cause
• Drenching night sweats that soak clothes and sheets
• Persistent fatigue that rest doesn't fix
• Unexplained weight loss of more than 10% of body weight over six months
• Itching, sometimes severe, especially in Hodgkin lymphoma

Together, fever, night sweats, and significant weight loss are called B symptoms, and they matter for staging and prognosis.

Red flags that need urgent evaluation

• A lymph node that grows quickly over days or weeks
• Drenching night sweats every night
• Fever lasting more than two weeks with no infection found
• Rapid, unexplained weight loss
• Difficulty breathing, chest pain, or new bone pain

These don't always mean lymphoma as most swollen nodes are reactive infections but they shouldn't be ignored.

Risk Factors

The exact cause of most lymphomas is unknown, but several factors raise the risk.

Age. Lymphoma has two peaks. Hodgkin lymphoma is most common in young adults aged 20–40, while non-Hodgkin lymphoma rises sharply after age 60 [1].

A weakened immune system. People living with HIV/AIDS, organ transplant recipients on immunosuppression, and patients with autoimmune diseases like rheumatoid arthritis or lupus have a higher risk.

Infections. This is one of the more interesting parts of lymphoma biology:

• Epstein-Barr virus (EBV) is linked to endemic Burkitt lymphoma, NK/T-cell lymphoma, and post-transplant lymphoproliferative disorder.
• Human T-cell lymphotropic virus (HTLV-1) causes adult T-cell leukemia/lymphoma in endemic regions.
• Helicobacter pylori drives most cases of gastric MALT lymphoma and treating the infection with antibiotics can cure the lymphoma [7].
• Hepatitis C virus is linked to splenic marginal zone lymphoma.
• Human herpesvirus 8 (HHV-8) causes primary effusion lymphoma, mainly in immunocompromised patients.

Family history. Having a close relative with lymphoma raises risk slightly. Most cases are not hereditary.

Other factors. Obesity and smoking show modest associations with certain non-Hodgkin lymphoma subtypes.

Types of Lymphoma

The 5th edition of the World Health Organization (WHO) classification, published in 2022, refined how lymphomas are grouped [2]. The two big categories remain Hodgkin lymphoma and non-Hodgkin lymphoma.

Hodgkin Lymphoma

Hodgkin lymphoma is defined by Reed-Sternberg cells which are large, abnormal B cells with two nuclei that look like owl eyes under a microscope.

• Classical Hodgkin lymphoma accounts for about 95% of cases and has four subtypes (nodular sclerosis, mixed cellularity, lymphocyte-rich, lymphocyte-depleted).
• Nodular lymphocyte-predominant B-cell lymphoma (NLPBL) — formerly called nodular lymphocyte-predominant Hodgkin lymphoma but was reclassified in 2022. It tends to be indolent with excellent prognosis [2].

Hodgkin lymphoma usually starts in the upper body (neck or chest) and spreads in an orderly way from one node group to the next. It generally responds well to treatment.

Non-Hodgkin Lymphoma (NHL)

Non-Hodgkin lymphoma is an umbrella term for more than 70 subtypes. It can arise from B cells (most common) or T cells, and behavior ranges from very slow to very aggressive.

Major subtypes include:

• Diffuse large B-cell lymphoma (DLBCL) — the most common aggressive lymphoma. Curable in many patients with combination therapy.
• Follicular lymphoma — slow-growing, often managed for years rather than cured.
• Burkitt lymphoma — extremely fast-growing; requires immediate intensive treatment. Strongly linked to EBV in its endemic (African) form.
• Mantle cell lymphoma — a B-cell lymphoma with characteristics of both indolent and aggressive disease.
• Marginal zone lymphomas — including gastric MALT lymphoma, often driven by chronic infection or inflammation.
• T-cell lymphomas — about 10% of NHL, with diverse subtypes and prognoses.

Comparison of Hodgkin and Non-Hodgkin Lymphoma

Diagnosis and Investigations

A proper lymphoma workup combines clinical assessment, blood work, imaging, and tissue diagnosis. The goal is to confirm the type, define the stage, and plan treatment.

Tissue biopsy: the cornerstone

Excisional biopsy of an affected lymph node is preferred. Removing the whole node lets pathologists see how cells are organized which is critical for accurate subtype classification. Fine-needle aspiration alone is usually not enough [1].

Blood tests

A complete blood count (CBC) may show:

• Anemia if the bone marrow is involved
• Leukocytosis with abnormal lymphocytes on the blood smear
• Thrombocytopenia (low platelets) in some cases

Lactate dehydrogenase (LDH) is often elevated in aggressive disease and is part of the International Prognostic Index for NHL. Beta-2 microglobulin is another prognostic marker.

Imaging: PET-CT is now standard

FDG-PET/CT has become the standard imaging tool for staging and response assessment in most lymphomas. It picks up disease that CT alone might miss [4]. After treatment, the Deauville 5-point scale scores residual PET uptake from 1 (no uptake) to 5 (markedly increased), guiding decisions about further therapy.

Staging: the Lugano classification

The Lugano classification (2014) replaced the older Ann Arbor system for lymphoma. It still uses stages I through IV but incorporates PET-CT findings and removes some older labels [4].

• Stage I: one node group
• Stage II: two or more node groups on the same side of the diaphragm
• Stage III: node groups on both sides of the diaphragm
• Stage IV: widespread disease involving non-lymphatic organs (liver, lung, bone marrow)

Other tests

• Flow cytometry identifies the lymphoma's surface marker pattern (immunophenotype), distinguishing B-cell from T-cell disease and pinpointing subtypes.
• Bone marrow biopsy checks for marrow involvement, although PET-CT has reduced its routine use in some cases.
• Cytogenetic and molecular tests look for specific translocations and mutations (such as MYC, BCL2, BCL6 rearrangements in high-grade B-cell lymphoma).
• Circulating tumor DNA (ctDNA) testing is now standard practice for monitoring minimal residual disease (MRD) in certain aggressive lymphomas. According to the 2025 NCCN Guidelines, for patients with diffuse large B-cell lymphoma (DLBCL) who have an equivocal or positive PET-CT scan at the end of first-line therapy, ultra-sensitive ctDNA testing is now officially recommended as an alternative to an invasive tissue biopsy to confirm disease status [9].

Current Treatment Options

Lymphoma treatment is one of the fastest-changing areas in oncology. The right plan depends on the subtype, stage, patient age, and overall health.

Frontline therapy

Hodgkin lymphoma. For advanced-stage classical Hodgkin lymphoma, the SWOG S1826 trial showed that nivolumab plus AVD (N-AVD) outperformed brentuximab vedotin plus AVD, with 1-year progression-free survival of 94% versus 86% [3]. Based on these results, NCCN now lists N-AVD as the preferred (category 1) frontline regimen for stage III–IV disease. Early-stage Hodgkin lymphoma is often treated with shorter chemotherapy followed by involved-site radiation.

DLBCL. Standard frontline therapy is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) for six cycles. Pola-R-CHP (substituting polatuzumab vedotin for vincristine) is now an option for higher-risk patients.

Follicular lymphoma. Slow-growing disease may be observed (watchful waiting). When treatment is needed, options include rituximab alone, R-CHOP, R-bendamustine, or rituximab plus lenalidomide. For patients whose disease returns or resists initial treatments (relapsed/refractory), the treatment paradigm shifted significantly in November 2025 when the FDA approved the bispecific antibody epcoritamab in combination with lenalidomide and rituximab. This provides a highly effective, chemotherapy-free targeted regimen with superior progression-free survival compared to standard therapies [10].

Burkitt lymphoma. Requires immediate, intensive multi-agent chemotherapy with central nervous system prophylaxis. Treatment must start fast because of the risk of tumor lysis syndrome.

Treatment modalities at a glance

Chemotherapy uses drugs that kill rapidly dividing cells. Common regimens include CHOP, R-CHOP, AVD, and N-AVD. Side effects include nausea, hair loss, low blood counts, and infection risk.

Radiation therapy uses high-energy beams aimed at affected sites. It's often combined with chemotherapy for early-stage disease.

Targeted therapy and immunotherapy focus on specific features of the lymphoma cell:

• Rituximab — an anti-CD20 antibody, the backbone of B-cell lymphoma treatment.
• Brentuximab vedotin — an antibody-drug conjugate targeting CD30, used in Hodgkin lymphoma and some T-cell lymphomas.
• Polatuzumab vedotin — an anti-CD79b antibody-drug conjugate used in DLBCL.
• Checkpoint inhibitors like nivolumab and pembrolizumab block the PD-1 pathway, releasing the brakes on T cells.

Stem cell transplantation replaces damaged bone marrow with healthy stem cells after high-dose chemotherapy. It's used in select relapsed cases.

CAR-T cell therapy

In CAR-T therapy, doctors collect a patient's own T cells, engineer them in a lab to recognize a specific lymphoma marker (usually CD19), and infuse them back. Three CD19-targeted CAR-T products are now approved for large B-cell lymphoma: axicabtagene ciloleucel, lisocabtagene maraleucel, and tisagenlecleucel. As of 2022, axicabtagene and lisocabtagene are approved as second-line therapy for primary refractory or early-relapsed DLBCL [6].

CAR-T can cause two serious early complications:

• Cytokine release syndrome (CRS) — fever, low blood pressure, and inflammation from massive T-cell activation. Mostly manageable with the IL-6 blocker tocilizumab.
• Immune effector cell-associated neurotoxicity syndrome (ICANS) — confusion, tremor, or seizures, usually reversible with supportive care and steroids.

Bispecific antibodies

Bispecific antibodies are designed to grab two targets at once. CD20×CD3 bispecifics latch onto a CD20-positive lymphoma cell with one arm and a T cell with the other, forcing the T cell to kill the cancer. Three are now approved:

• Mosunetuzumab — for relapsed/refractory follicular lymphoma after two or more prior therapies.
• Epcoritamab and glofitamab — for relapsed/refractory DLBCL after two or more prior lines [5,8].

These drugs are off-the-shelf, unlike CAR-T, which needs custom manufacturing for each patient. They can also cause CRS, though usually milder than with CAR-T. Recent pharmacological advancements have also drastically improved the patient experience by shifting away from lengthy IV treatments. In December 2025, the FDA approved a new formulation of mosunetuzumab administered as a one-minute subcutaneous injection. This allows patients to receive advanced T-cell engaging immunotherapy during a standard, brief outpatient clinic visit [11].

Special cases

For gastric MALT lymphoma, antibiotic eradication of H. pylori induces remission in most early-stage patients. This is a striking example of treating the cause instead of the cancer [7].

Supportive care

Symptom management, nutritional support, and infection prevention are central. Patients on intensive treatment often need transfusions, growth factors, and prophylaxis against pneumocystis and viral reactivation.

Prognosis and Survival Rates

Outcomes vary widely by subtype and stage, and early diagnosis remains the single biggest lever.

• Hodgkin lymphoma: 5-year survival above 80% for early stages, around 50–70% for advanced stages with modern therapy.
• DLBCL: approximately 70% 5-year survival for early-stage, lower for advanced or high-risk disease, but novel therapies are improving relapsed outcomes.
• Follicular lymphoma: 10-year survival above 90% for early-stage disease, though relapses are common.
• Burkitt lymphoma: 5-year survival of 80–90% with intensive treatment in early stages.
• T-cell lymphomas: highly variable; some indolent forms do well, others remain difficult.

Living with Lymphoma: Practical Guidance

Nutrition during treatment

There's no single "lymphoma diet," but treatment increases calorie needs and can blunt appetite. Practical principles:

• Eat plenty of fruits, vegetables, and whole grains.
• Choose lean protein to maintain muscle mass.
• Stay well-hydrated.
• For nausea, try small frequent meals, ginger, and bland foods.
• For mouth sores, soft cool foods and alcohol-free mouthwash help.
• A registered dietitian can tailor a plan around treatment side effects.

Exercise

Regular physical activity reduces fatigue, improves mood, and helps preserve muscle and bone during treatment. Start gently. Walking, swimming, and light resistance work are usually well-tolerated. Patients with neutropenia should avoid crowded gyms; those with bone involvement should skip high-impact activities. Always coordinate with the treating team.

When to seek immediate medical help

Caregivers should watch for:

• Fever above 38°C (100.4°F) during chemotherapy
• Sudden severe shortness of breath or chest pain
• Confusion or new neurological symptoms (especially after CAR-T or bispecifics)
• Uncontrolled bleeding or bruising
• Severe vomiting or inability to keep fluids down

These can signal infection, CRS, ICANS, or treatment-related complications and need urgent evaluation.

Frequently Asked Questions (FAQs)

Is lymphoma a serious cancer?

Lymphoma is a serious diagnosis but covers a wide range of behaviors. Hodgkin lymphoma and indolent non-Hodgkin lymphomas often have excellent long-term outcomes, while aggressive subtypes need urgent treatment. Stage at diagnosis and access to current therapy are major factors in outcome.

Where does lymphoma usually start?

It most often starts in lymph nodes — neck, armpit, groin, chest, or abdomen. It can also begin in the spleen, bone marrow, thymus, or extranodal sites like the stomach, skin, or central nervous system.

Is lymphoma painful?

Lymphoma itself is usually painless. Pain can occur if a swollen node presses on a nerve, if disease spreads to bone, or from B symptoms like fever. Drinking alcohol sometimes triggers pain in Hodgkin lymphoma nodes. This is a classic but uncommon clue.

Are lymphoma lumps movable?

Yes, typically. A lymphoma node tends to be firm, smooth, painless, and movable under the skin. Hard, fixed, irregular nodes are more suspicious for other cancers, but any persistent lump deserves evaluation.

What new treatments are available for lymphoma?

Recent additions include nivolumab plus AVD as preferred frontline therapy for advanced classical Hodgkin lymphoma [3], CAR-T cell therapy used as second-line treatment for refractory DLBCL [6], and bispecific antibodies (mosunetuzumab, epcoritamab, glofitamab) for relapsed B-cell lymphomas [5,8].

Why does lymphoma cause itching?

The leading explanation is that lymphoma cells, especially in Hodgkin lymphoma, release cytokines that irritate skin nerve endings. Itching can also reflect skin involvement directly. It often improves once treatment starts.

Glossary of Related Medical Terms

• Lymphoma — A cancer that starts in lymphocytes, the white blood cells that fight infection.
• Lymphocyte — A type of white blood cell. The two main kinds are B cells (make antibodies) and T cells (kill infected cells and coordinate the immune response).
• Lymph node — A small bean-shaped filter scattered along lymph vessels, packed with immune cells.
• Reed-Sternberg cell — A large abnormal B-cell with two nuclei (often called "owl-eye"). Its presence defines classical Hodgkin lymphoma.
• Hodgkin lymphoma (HL) — A lymphoma defined by Reed-Sternberg cells; tends to spread orderly from one node group to the next.
• Non-Hodgkin lymphoma (NHL) — An umbrella term for over 70 lymphomas that do not contain Reed-Sternberg cells. Behavior ranges from indolent (slow) to aggressive (fast-growing).
• DLBCL (diffuse large B-cell lymphoma) — The most common aggressive NHL. Curable in many patients with combination therapy.
• Follicular lymphoma — A common indolent NHL. Often managed long-term rather than cured outright.
• Burkitt lymphoma — A very fast-growing B-cell NHL strongly linked with Epstein-Barr virus in its endemic form.
• Lymphadenopathy — Swollen lymph nodes.
• B symptoms — A specific trio: unexplained fevers, drenching night sweats, and weight loss greater than 10% body weight in 6 months. Used in staging.
• Lugano classification — Modern staging system for lymphoma (replaces Ann Arbor); incorporates PET-CT findings.
• Deauville 5-point scale — A scoring system on FDG-PET/CT used to judge how well lymphoma is responding to treatment.
• Immunophenotyping — Identifying a cell by the proteins on its surface, usually with flow cytometry. Used to classify lymphoma.
• Chemotherapy — Drugs that kill rapidly dividing cells, including cancer cells.
• R-CHOP — A standard chemotherapy combination for DLBCL: rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone.
• CAR-T cell therapy — Treatment in which a patient's own T cells are engineered in a lab to recognize and kill the lymphoma, then infused back.
• Bispecific antibody — An antibody designed to grab two targets at once, typically pulling a T cell next to a lymphoma cell to trigger a kill.
• Cytokine release syndrome (CRS) — A flu-like systemic inflammatory reaction that can occur with CAR-T or bispecific antibody therapy. Ranges from mild to life-threatening.
• Stem cell transplant — Replacing diseased bone marrow with healthy stem cells, often after high-dose chemotherapy.

Disclaimer: This article is intended for educational and informational purposes only. It is not intended to be a substitute for informed professional medical advice, diagnosis, or treatment. While the information presented here is derived from credible medical sources and is believed to be accurate and up-to-date, it is not guaranteed to be complete or error-free. See additional information.

References

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