Lymphoma

Lymphoma is a large group of cancers arising from B cells, T cells, or natural killer cells. The two broad families are Hodgkin lymphoma and non-Hodgkin lymphoma.

Non-Hodgkin lymphoma includes dozens of subtypes, such as diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma, Burkitt lymphoma, and multiple T-cell lymphomas. Their behavior ranges from indolent to highly aggressive, so one treatment summary cannot substitute for an exact pathologic diagnosis.

• Painless enlargement of lymph nodes in the neck, underarm, or groin
• Unexplained fever
• Drenching night sweats
• Unexplained weight loss
• Persistent fatigue
• Itching
• Cough, chest pressure, or shortness of breath from enlarged mediastinal nodes
• Abdominal pain, early satiety, or distention
• Anemia, infection, or bleeding when bone marrow is involved

The classic B symptoms are fever, drenching night sweats, and a defined degree of unintentional weight loss. Infections and autoimmune diseases can also enlarge lymph nodes, and diagnosis usually requires tissue biopsy.

• Age, with patterns that differ by subtype
• Immune suppression after organ transplantation, HIV, or inherited immune deficiency
• EBV, HTLV-1, hepatitis C, and other infections associated with selected subtypes
• H. pylori infection and gastric MALT lymphoma
• Certain autoimmune diseases
• A family history that may modestly increase risk
• Previous chemotherapy or radiation therapy
• Occupational or environmental exposures for which evidence is inconsistent across subtypes

Most lymphoma cases cannot be traced to a single cause.

• There is no routine screening program for asymptomatic people at average risk.
• Persistent, enlarging, painless lymph nodes or lymphadenopathy accompanied by B symptoms should be evaluated.
• Preventing HIV, HBV, and HCV infection and appropriately managing immune suppression support general health.
• Eradication of H. pylori can treat some localized gastric MALT lymphomas.
• Routine complete blood counts, tumor markers, or whole-body PET/CT should not be promoted as screening for healthy people.

Diagnosis is discussed within the Overview, Screening, Staging, and Biomarkers sections above for this cancer type. Specific tests depend on presentation, site, and pathology.

Many lymphomas use Lugano/Ann Arbor stages I through IV to describe lymph-node regions and extranodal organs.

PET/CT is important for staging and response assessment in many FDG-avid lymphomas.

Stage IV lymphoma is not automatically equivalent to incurable stage IV solid cancer; some advanced lymphomas remain highly curable.

Grade has a defined meaning in selected subtypes, such as follicular lymphoma, but cannot replace precise subtype diagnosis.

Prognostic indices may integrate age, LDH, performance status, stage, and extranodal involvement.

Normal B and T cells rearrange antigen-receptor genes and, in B cells, undergo somatic hypermutation and class-switch recombination. These normal processes create opportunities for translocations and mutation.

Different lymphomas arise from different stages of lymphocyte development.

In classical Hodgkin lymphoma, Reed-Sternberg cells may be relatively rare but shape a large immune microenvironment. Important non-Hodgkin lymphoma pathways include B-cell receptor signaling, NF-kappaB, apoptosis, epigenetic regulation, and immune evasion.

• Immunophenotype markers such as CD20, CD3, CD30, CD10, BCL6, MUM1, ALK, cyclin D1, and SOX11
• MYC, BCL2, and BCL6 rearrangements or protein expression
• t(14;18) in many follicular lymphomas
• CCND1 rearrangement in most mantle cell lymphomas
• ALK rearrangement in some anaplastic large cell lymphomas
• EBV testing by in situ hybridization
• PD-L1/9p24.1 biology in classical Hodgkin lymphoma
• TP53, EZH2, BTK, PLCG2, and other alterations in selected subtypes and resistance settings
• Metabolic response on PET and emerging circulating tumor DNA assays

An excisional or adequate core biopsy is often essential. Fine-needle aspiration alone may not provide enough architecture for definitive classification.

• Hodgkin lymphoma: multi-agent chemotherapy, sometimes combined with radiation; PET response may guide treatment intensity. Relapsed disease may involve anti-CD30 therapy, PD-1 inhibitors, transplantation, or other approaches.
• Diffuse large B-cell lymphoma: anti-CD20 antibody plus combination chemotherapy is a common first-line framework. Relapsed or refractory disease may involve salvage chemotherapy, autologous transplantation, CAR T-cell therapy, bispecific antibodies, or antibody-drug conjugates.
• Follicular lymphoma: selected asymptomatic, low-burden patients can be observed. When treatment is needed, anti-CD20 antibodies, chemotherapy, targeted therapy, or immunotherapy may be used.
• Mantle cell lymphoma: treatment can include chemoimmunotherapy, BTK inhibitors, transplantation, CAR T-cell therapy, and newer BCL-2-directed strategies, depending on age and risk.
• Gastric MALT lymphoma: H. pylori eradication alone can be effective in selected cases.
• T-cell lymphomas: therapy is highly subtype-specific and often benefits from expert-center review.

• Anti-CD20 antibodies: rituximab and obinutuzumab
• Chemotherapy: cyclophosphamide, doxorubicin, vincristine, prednisone, bendamustine, etoposide, gemcitabine, and platinum agents
• Hodgkin treatment frameworks: ABVD; AVD with brentuximab vedotin or nivolumab in selected settings
• BTK inhibitors: ibrutinib, acalabrutinib, zanubrutinib, and pirtobrutinib
• BCL-2-directed therapy: venetoclax and newer agents in selected subtypes or trials
• Anti-CD30 therapy: brentuximab vedotin
• PD-1 inhibitors: nivolumab and pembrolizumab
• Bispecific antibodies: glofitamab, epcoritamab, mosunetuzumab, and others in approved subtypes
• CD19-directed CAR T-cell products for eligible relapsed or refractory B-cell lymphomas
• Other targeted or antibody-drug approaches: lenalidomide, tafasitamab, polatuzumab vedotin, and subtype-specific agents

• Chemotherapy: infection, anemia, bleeding, hair loss, nausea, neuropathy, and cardiac toxicity
• Anti-CD20 antibodies: infusion reactions, hepatitis B reactivation, and infection
• Brentuximab vedotin: peripheral neuropathy
• PD-1 inhibitors: immune-related toxicities
• BTK inhibitors: bleeding, atrial fibrillation, hypertension, and infection, depending on the agent
• Bispecific antibodies and CAR T-cell therapy: cytokine release syndrome, neurotoxicity, prolonged cytopenias, and low immunoglobulin levels
• Radiation: site-dependent thyroid, heart, lung, fertility, and second-cancer risks
• Supportive care may include vaccination planning, infection prevention, HBV screening, tumor lysis prevention, fertility preservation, cardiac monitoring, and long-term survivorship follow-up.

Rapidly worsening shortness of breath, facial or neck swelling, high fever during treatment, confusion, or severe weakness needs urgent assessment.

• Bispecific antibodies are expanding in relapsed or refractory B-cell lymphomas and are moving into earlier treatment lines.
• CAR T-cell therapy is being studied earlier, with efforts to reduce toxicity and develop off-the-shelf products.
• Circulating tumor DNA is being evaluated for early response and relapse detection.
• PET-adapted approaches aim to reduce chemotherapy or radiation exposure in patients who respond well.
• New strategies are addressing TP53-high-risk mantle cell lymphoma and other aggressive subtypes.
• Tumor microenvironment and immune biomarkers are being used to refine Hodgkin lymphoma therapy.
• A recent U.S. regulatory example is FDA approval on March 20, 2026, of nivolumab with doxorubicin, vinblastine, and dacarbazine for adults and patients age 12 or older with previously untreated stage III or IV classical Hodgkin lymphoma.

• What is the complete WHO/International Consensus lymphoma subtype?
• Has the biopsy been reviewed by a hematopathologist?
• What are the stage, LDH, PET findings, and prognostic score?
• Is this an indolent or aggressive lymphoma, and is the goal cure or long-term control?
• Is observation without immediate treatment safe?
• Do I need MYC, BCL2, BCL6, TP53, or other molecular tests?
• Might radiation, transplantation, CAR T-cell therapy, or a bispecific antibody be appropriate?
• How will infection and tumor lysis be prevented?
• What are the potential effects on the heart, lungs, fertility, and second-cancer risk?
• Are there clinical trials for my subtype and treatment history?