Non-Hodgkin Lymphoma

What is non-Hodgkin lymphoma

The lymphatic system includes lymph nodes, spleen, thymus, bone marrow and lymphoid tissue in the gut, skin and other organs. Lymphocytes in these tissues fight infection. In lymphoma, a lymphocyte acquires genetic changes, multiplies uncontrollably, and forms tumors. Hodgkin lymphoma is a distinct type with characteristic Reed-Sternberg cells; all other lymphomas are non-Hodgkin. See Hodgkin lymphoma and the overview of lymphoma.

Types of non-Hodgkin lymphoma

Indolent lymphomas can sometimes transform into aggressive lymphoma.

Symptoms

• Painless swollen lymph nodes in the neck, armpit or groin, often rubbery and slowly growing
• B symptoms: fevers without infection, drenching night sweats, and unexplained loss of more than 10% of body weight over 6 months
• Fatigue
• Itching
• Abdominal swelling, pain or early fullness from an enlarged spleen or abdominal nodes
• Chest symptoms: cough, chest pain or breathlessness from nodes in the chest
• Symptoms from other organs: stomach pain (gastric lymphoma), skin patches (skin lymphoma), headaches or confusion (brain lymphoma)
• Frequent infections, bruising or anemia if the bone marrow is involved

Swollen lymph nodes are far more often caused by infections than lymphoma. Nodes from infection are usually tender and shrink within 2 to 3 weeks.

Risk factors

• Age over 60
• Weakened immune system: HIV, organ transplant medicines, inherited immune deficiencies
• Autoimmune diseases: rheumatoid arthritis, Sjögren syndrome, celiac disease, lupus
• Infections: Epstein-Barr virus (Burkitt and other lymphomas), Helicobacter pylori (gastric MALT lymphoma), hepatitis C, HTLV-1
• Previous chemotherapy or radiation
• Some chemical exposures, such as certain pesticides and solvents
• Breast implants (rare anaplastic large cell lymphoma)
• Family history

Diagnosis

1. Examination of lymph nodes, spleen and liver.
2. Biopsy: removal of a whole lymph node (excisional biopsy) or a core needle biopsy is essential. A fine-needle aspiration alone is usually not enough. Pathologists use immunohistochemistry, flow cytometry and genetic tests to determine the exact subtype.
3. Blood tests: full blood count, LDH, kidney and liver function, HIV and hepatitis B and C tests.
4. PET-CT scan to stage the disease.
5. Bone marrow biopsy in some cases.
6. Lumbar puncture if there is a risk of spread to the brain.

Staging

The Lugano system stages NHL from I (one node region) to IV (widespread, including organs like bone marrow or liver). The suffix "B" indicates B symptoms. For aggressive lymphomas, prognostic scores such as the International Prognostic Index (IPI) combine age, stage, LDH, performance status and organ involvement.

Treatment

Treatment depends on subtype, stage, symptoms and overall health.

Indolent lymphomas

• Watch and wait (active monitoring): for people without symptoms or bulky disease. Starting treatment early does not improve survival in this situation
• Radiation for localized early-stage disease, which can be curative
• Rituximab alone or with chemotherapy
• Targeted therapies, such as BTK inhibitors for some types
• Antibiotics to eradicate H. pylori, which can cure early gastric MALT lymphoma

Aggressive lymphomas

• Chemoimmunotherapy: for DLBCL, standard regimens such as R-CHOP or pola-R-CHP, typically over about 4 to 6 months, cure a majority of patients
• Radiation to bulky or localized disease
• CNS-directed therapy for those at high risk of brain involvement

Relapsed or refractory disease

• CAR T-cell therapy: the patient's own T cells are engineered to attack the lymphoma
• Bispecific antibodies
• High-dose chemotherapy with autologous stem cell transplant
• Allogeneic (donor) transplant in selected cases
• Clinical trials

Supportive care

Infection prevention, blood transfusions, management of side effects, and psychological support. See chemotherapy side effects.

Outlook

The overall 5-year relative survival for NHL in the US is about 74%. For DLBCL, about 60 to 70% of people are cured with first-line treatment. Follicular lymphoma typically has a long course, with median survival often exceeding 15 to 20 years. Outcomes depend strongly on subtype, stage and response to treatment.

Frequently asked questions

What are the first signs of non-Hodgkin lymphoma?

The most common first sign is a painless swollen lymph node in the neck, armpit or groin that does not go away. Others include fevers, drenching night sweats, unexplained weight loss, tiredness and itching. Many people feel well at diagnosis.

What is the difference between Hodgkin and non-Hodgkin lymphoma?

Both are cancers of lymphocytes. Hodgkin lymphoma contains characteristic Reed-Sternberg cells, tends to spread in an orderly way between node groups and is common in young adults. Non-Hodgkin lymphoma includes many subtypes, is more common in older adults, and spreads less predictably.

Is non-Hodgkin lymphoma curable?

Many aggressive types, such as diffuse large B-cell lymphoma, are curable with chemoimmunotherapy. Indolent types such as follicular lymphoma are usually not cured but can be controlled for many years. New therapies like CAR T-cells help when lymphoma returns.

What causes non-Hodgkin lymphoma?

The exact cause is usually unknown. Risk is higher with older age, weakened immunity (such as HIV or transplant medicines), autoimmune diseases, certain infections like Epstein-Barr virus and H. pylori, previous cancer treatment and some chemical exposures.

Can swollen lymph nodes from lung cancer or other cancers be mistaken for lymphoma?

Yes. Swollen nodes can result from infection, lymphoma or cancer spread from elsewhere, such as the lung, breast or head and neck. A biopsy is needed to tell them apart and guides the correct treatment.