Lymphoma

Overview

Lymphoma is a cancer that begins in infection-fighting cells of the immune system, called lymphocytes. These cells are found in the lymph nodes, spleen, thymus, bone marrow, and other parts of the body. When you have lymphoma, lymphocytes change and grow out of control, forming tumors throughout the lymphatic system.

The lymphatic system is part of the body's immune system, helping to fight infections and diseases. It consists of a network of vessels that carry lymph fluid, lymph nodes that filter this fluid, and organs like the spleen and thymus. Lymphoma can affect any of these components, disrupting the body's ability to fight infections and maintain fluid balance.

There are two main categories of lymphoma: Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Non-Hodgkin lymphoma is more common, comprising about 90% of all lymphomas, with over 70 different subtypes. Each type has different behaviors, treatment approaches, and prognoses. Modern treatments have significantly improved outcomes, with many lymphomas now considered curable or manageable as chronic conditions.

Symptoms

Lymphoma symptoms can vary widely depending on the type, location, and stage of the disease. Some people may have no symptoms initially, with lymphoma discovered during routine examinations or tests for other conditions.

Most Common Symptoms

B Symptoms (Constitutional Symptoms)

These symptoms affect prognosis and treatment decisions:

• Unexplained weight loss (>10% in 6 months)
• Fever above 100.4°F (38°C) without infection
• Drenching night sweats

Additional Common Symptoms

• Groin swelling or lumps
• Hoarse voice (from chest lymph nodes)
• Itchy skin all over the body
• Shortness of breath or cough
• Abdominal pain or swelling
• Feeling full after small amounts of food
• Easy bruising or bleeding
• Frequent infections

Location-Specific Symptoms

Chest lymphoma:

• Cough, chest pain
• Difficulty breathing
• Superior vena cava syndrome (facial swelling)

Abdominal lymphoma:

• Abdominal pain or swelling
• Nausea or vomiting
• Bowel obstruction symptoms

CNS lymphoma:

• Headaches
• Confusion or personality changes
• Seizures
• Vision problems

Hodgkin vs Non-Hodgkin Symptoms

Hodgkin lymphoma often presents with:

• Orderly spread from one lymph node group to adjacent ones
• More likely to have B symptoms
• Alcohol-induced pain in lymph nodes (rare but specific)

Non-Hodgkin lymphoma may include:

• More widespread involvement at diagnosis
• Extranodal involvement more common
• GI symptoms if gut involvement

Causes

The exact cause of most lymphomas is unknown. Lymphoma develops when lymphocytes acquire genetic mutations that cause them to multiply uncontrollably and avoid normal cell death. Multiple factors likely contribute to these changes.

Genetic Changes

• Chromosomal translocations: Common in many lymphomas
• Gene mutations: Affect cell growth and death pathways
• Epigenetic changes: Alter gene expression
• Oncogene activation: Promotes cell growth
• Tumor suppressor loss: Removes growth controls

Infections Associated with Lymphoma

Viral Infections

• Epstein-Barr virus (EBV): Burkitt lymphoma, some Hodgkin lymphoma
• Human T-cell lymphotropic virus (HTLV-1): Adult T-cell lymphoma
• Hepatitis C virus: Some B-cell lymphomas
• HIV: Increased risk of aggressive lymphomas
• Human herpesvirus 8 (HHV-8): Primary effusion lymphoma

Bacterial Infections

• Helicobacter pylori: Gastric MALT lymphoma
• Chlamydia psittaci: Ocular adnexal lymphoma
• Campylobacter jejuni: Small intestinal lymphoma
• Borrelia burgdorferi: Cutaneous lymphoma (Europe)

Immune System Factors

• Immunodeficiency: Congenital or acquired
• Autoimmune diseases: Chronic immune stimulation
• Organ transplantation: Immunosuppressive drugs
• Chronic inflammation: Persistent immune activation

Environmental and Chemical Exposures

• Pesticides and herbicides
• Industrial chemicals (benzene, solvents)
• Previous chemotherapy or radiation
• Hair dyes (older formulations)

Genetic Predisposition

• Family history increases risk slightly
• Inherited immune disorders
• Genetic syndromes (ataxia-telangiectasia)
• Common genetic variants affecting immunity

Risk Factors

Various factors can increase the risk of developing lymphoma, though having risk factors doesn't mean you will develop the disease. Most people with risk factors never develop lymphoma.

Age and Gender

• Age: Risk increases with age for most types
• Hodgkin lymphoma: Peaks in 20s and late 50s
• Non-Hodgkin lymphoma: More common after age 60
• Gender: Slightly more common in men overall
• Specific types: Some show gender preferences

Immune System Conditions

• HIV/AIDS: Significantly increased risk
• Organ transplant recipients: Immunosuppressive drugs
• Primary immunodeficiency disorders: Various genetic conditions
• Autoimmune diseases:
  • Sjögren's syndrome
  • Rheumatoid arthritis
  • Systemic lupus erythematosus
  • Celiac disease

Infections

• Epstein-Barr virus: Previous infection increases risk
• H. pylori: Stomach lymphoma risk
• Hepatitis C: Certain B-cell lymphomas
• HTLV-1: Endemic areas (Japan, Caribbean)

Previous Cancer Treatment

• Radiation therapy, especially at young age
• Certain chemotherapy drugs
• Combined modality treatment
• Risk persists for decades

Chemical Exposures

• Agricultural chemicals: Pesticides, herbicides
• Industrial solvents: Benzene, toluene
• Hair dyes: Especially dark, permanent dyes (historical)
• Agent Orange: Military exposure

Lifestyle Factors

• Obesity: Linked to some NHL subtypes
• Diet: High meat/fat intake may increase risk
• UV exposure: Cutaneous lymphomas
• Breast implants: Rare anaplastic large cell lymphoma

Family History

• First-degree relative with lymphoma
• Familial clustering suggests genetic component
• Shared environmental factors possible
• Inherited immune disorders

Diagnosis

Accurate diagnosis of lymphoma requires tissue examination to determine the specific type, which is crucial for treatment planning. A comprehensive workup includes various tests and procedures.

Initial Evaluation

• Medical history: Symptoms, duration, B symptoms
• Physical examination: Lymph nodes, spleen, liver
• Performance status: Overall health assessment
• Review of systems: Check for organ involvement

Biopsy - The Gold Standard

Excisional Biopsy (Preferred)

• Entire lymph node removal
• Preserves architecture for diagnosis
• Allows comprehensive testing
• Most accurate method

Core Needle Biopsy

• When excisional not feasible
• Multiple samples needed
• Image guidance often used
• May need repeat if insufficient

Pathology Studies

• Histopathology: Microscopic examination
• Immunohistochemistry: Identifies cell markers
• Flow cytometry: Analyzes cell surface proteins
• Cytogenetics: Chromosomal abnormalities
• Molecular testing: Gene rearrangements, mutations

Blood Tests

• Complete blood count: Check for cytopenias
• Comprehensive metabolic panel: Organ function
• LDH: Tumor burden marker
• Beta-2 microglobulin: Prognostic marker
• ESR: Inflammation marker
• Viral serologies: HIV, hepatitis, EBV

Imaging Studies

PET/CT Scan (Standard)

• Most sensitive for staging
• Detects metabolically active disease
• Helps determine stage
• Used for response assessment

Other Imaging

• CT scan: If PET not available
• MRI: CNS involvement
• Ultrasound: Superficial nodes
• Chest X-ray: Initial assessment

Staging Procedures

• Bone marrow biopsy: Check for involvement
• Lumbar puncture: If CNS symptoms
• GI endoscopy: If GI symptoms
• Additional biopsies: Of involved sites

Staging Systems

Ann Arbor Staging

• Stage I: Single lymph node region
• Stage II: Two or more regions, same side of diaphragm
• Stage III: Both sides of diaphragm
• Stage IV: Widespread, including organs
• Modifiers: A (no B symptoms), B (B symptoms present)

Treatment Options

Lymphoma treatment varies significantly based on the specific type, stage, and individual factors. Many lymphomas are curable, while others are managed as chronic diseases with excellent long-term outcomes.

Watch and Wait (Active Surveillance)

For some slow-growing lymphomas without symptoms:

• Regular monitoring without immediate treatment
• Avoids treatment side effects
• Treatment started when needed
• Common for follicular lymphoma, CLL/SLL

Chemotherapy

Standard Regimens

• CHOP: Classic combination for many lymphomas
• R-CHOP: CHOP plus rituximab (B-cell lymphomas)
• ABVD: Standard for Hodgkin lymphoma
• Bendamustine combinations: For indolent lymphomas
• Intensive regimens: For aggressive subtypes

Immunotherapy

Monoclonal Antibodies

• Rituximab: Anti-CD20 for B-cell lymphomas
• Obinutuzumab: Next-generation anti-CD20
• Brentuximab vedotin: For CD30+ lymphomas
• Mogamulizumab: For cutaneous T-cell lymphoma

Checkpoint Inhibitors

• Pembrolizumab for Hodgkin lymphoma
• Nivolumab for various lymphomas
• Ongoing trials in other types

CAR T-cell Therapy

• Genetically modified patient T-cells
• For relapsed/refractory B-cell lymphomas
• Potentially curative for some patients
• Axicabtagene ciloleucel, tisagenlecleucel

Radiation Therapy

• Involved site radiation: Limited to affected areas
• Total body irradiation: Before transplant
• Palliative radiation: Symptom control
• Often combined with chemotherapy
• Curative for early-stage lymphomas

Targeted Therapy

• BTK inhibitors: Ibrutinib, acalabrutinib
• PI3K inhibitors: Idelalisib, copanlisib
• BCL-2 inhibitors: Venetoclax
• Proteasome inhibitors: Bortezomib
• Immunomodulators: Lenalidomide

Stem Cell Transplantation

Autologous Transplant

• Using patient's own stem cells
• For relapsed/refractory disease
• High-dose chemotherapy followed by rescue
• Standard for relapsed Hodgkin lymphoma

Allogeneic Transplant

• Donor stem cells
• Graft-versus-lymphoma effect
• Higher risk but potentially curative
• For aggressive or multiply relapsed disease

Treatment by Type

Hodgkin Lymphoma

• Early stage: Combined modality or chemotherapy alone
• Advanced stage: Chemotherapy (ABVD, escalated BEACOPP)
• Relapsed: Salvage chemotherapy + transplant
• Excellent cure rates overall

Aggressive NHL

• R-CHOP or similar intensive regimens
• CNS prophylaxis if high risk
• Consolidation with transplant in some cases
• Goal is cure

Indolent NHL

• Watch and wait often appropriate
• Single-agent antibody therapy
• Combination chemoimmunotherapy
• Maintenance therapy common

Prevention

Most lymphomas cannot be prevented because their causes are not well understood or are not modifiable. However, some risk factors can be addressed to potentially reduce risk.

Infection Prevention and Treatment

• HIV prevention: Safe sex practices, avoid needle sharing
• H. pylori treatment: Antibiotics for stomach infection
• Hepatitis C treatment: Antiviral therapy
• EBV exposure: No prevention available
• Vaccination: Stay up-to-date with recommended vaccines

Immune System Health

• Maintain overall good health
• Manage autoimmune conditions properly
• Avoid unnecessary immunosuppression
• Regular medical care for chronic conditions
• Healthy lifestyle to support immunity

Chemical Exposure Reduction

• Occupational safety: Follow workplace guidelines
• Pesticide exposure: Use protective equipment
• Choose organic: When possible for high-exposure foods
• Home chemicals: Use safer alternatives
• Professional application: For necessary pesticides

Lifestyle Factors

• Maintain healthy weight: May reduce NHL risk
• Balanced diet: Rich in fruits and vegetables
• Regular exercise: Supports immune function
• Limit alcohol: Moderate consumption
• Don't smoke: Reduces overall cancer risk

For High-Risk Individuals

• Regular monitoring: If immunosuppressed
• Genetic counseling: For familial cases
• Preventive treatment: For certain infections
• Early detection: Know warning signs
• Specialist care: For underlying conditions

Post-Treatment Considerations

For cancer survivors at risk:

• Long-term follow-up care
• Monitor for second cancers
• Healthy lifestyle choices
• Regular screening as recommended

When to See a Doctor

Many lymphoma symptoms are common and usually caused by less serious conditions. However, persistent symptoms warrant medical evaluation for proper diagnosis.

See a Doctor Promptly For:

• Swollen lymph nodes lasting more than 2 weeks
• Lymph nodes that are growing or spreading
• Hard, fixed, or rapidly growing nodes
• Unexplained weight loss (>10% in 6 months)
• Persistent fever without obvious cause
• Drenching night sweats for several nights
• Severe, unexplained fatigue
• Persistent itching all over the body

Seek Immediate Care For:

• Difficulty breathing or chest pain
• Superior vena cava syndrome (facial/neck swelling)
• Severe abdominal pain or swelling
• Signs of spinal cord compression
• Confusion or neurological symptoms
• Severe infections with lymph node swelling

Important Considerations

• Most swollen lymph nodes are from infections
• Painful nodes are usually not lymphoma
• Multiple symptoms together are more concerning
• Duration matters - persistent symptoms need evaluation
• Don't panic, but don't ignore persistent symptoms

What to Tell Your Doctor

• Complete symptom history and timeline
• Any B symptoms (fever, night sweats, weight loss)
• Recent infections or illnesses
• Travel history
• Family history of cancer
• Occupational or chemical exposures
• Current medications
• Previous cancer or treatments

For Lymphoma Survivors

Contact your oncologist for:

• New lumps or swelling
• Return of B symptoms
• Unusual infections
• Side effects from treatment
• Concerns about relapse
• Follow-up scheduling

Related Conditions

Lymphoma is connected to various other conditions through shared risk factors, similar presentations, or as part of disease progression:

Conditions That Mimic Lymphoma

• Infectious mononucleosis: EBV infection
• Toxoplasmosis: Parasitic infection
• Sarcoidosis: Inflammatory condition
• Tuberculosis: Can cause lymph node swelling
• Cat scratch disease: Bacterial infection
• Reactive lymph nodes: From various infections

Associated Conditions

• Celiac disease - Increased T-cell lymphoma risk
• Sjögren's syndrome - MALT lymphoma risk
• Rheumatoid arthritis - Slightly increased risk
• Hepatitis C - Splenic marginal zone lymphoma
• H. pylori infection - Gastric MALT lymphoma

Complications of Lymphoma

• Superior vena cava syndrome
• Tumor lysis syndrome
• Hypercalcemia
• Kidney dysfunction
• Immune deficiency
• Secondary cancers

Frequently Asked Questions

References

1. Swerdlow SH, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 2017.
2. National Comprehensive Cancer Network. NCCN Guidelines: B-Cell Lymphomas. Version 2.2024.
3. Armitage JO, et al. Non-Hodgkin lymphoma. Lancet. 2017;390(10091):298-310.
4. Connors JM, et al. Hodgkin lymphoma. Nat Rev Dis Primers. 2020;6(1):61.
5. American Cancer Society. Lymphoma. ACS. 2024.
6. Lymphoma Research Foundation. Understanding Lymphoma. LRF. 2024.