Causes
In most cases, there is no known cause of lymphoma. There are a couple of exceptions where causes have been found for certain subtypes.
Gastric MALT lymphoma
Gastric MALT lymphoma is often caused by a common bacterial infection called Helicobacter pylori. Treating the infection can put the lymphoma into remission and may even cure the lymphoma.
Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL)
Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is caused by having breast implants. It is more common in people with implants that have a rough, textured surface than people with smooth implants. For many people, removing the implants cures the lymphoma.
Risk Factors
A risk factor is something that might increase your likelihood of getting a disease. Having one or more risk factors does not mean you will get lymphoma, it means you are slightly more likely to get lymphoma than someone without any risk factors. Chances of developing lymphoma are still small.
Risk factors include:
Age
Most types of lymphoma are more common in older people. The exceptions are Hodgkin lymphoma, which is also common in teenagers and young adults, and Burkitt’s lymphoma, which is more common in children.
Biological sex
Many types of lymphoma are slightly more common in biological males than females.
Exposure to chemicals
Being exposed to high levels of certain chemicals, like solvents, weedkillers, and insecticides, may increase your risk of developing lymphoma. This is an area of continued research.
Family history of lymphoma or another blood cancer
Lymphoma is not hereditary, but there is evidence if you have a parent, sibling or child who has had lymphoma, you have a slightly higher chance of developing a blood cancer too.
Monoclonal gammopathy of unknown significance (known as ‘MGUS’)
Monoclonal gammopathy of unknown significance (known as ‘MGUS’) is a non-cancerous condition where the body makes an abnormal antibody, called a monoclonal protein or paraprotein. In a small number of cases, people with IgM MGUS develop a slow-growing lymphoma, such as Waldenström’s macroglobulinaemia or marginal zone lymphoma.
Physical fitness
Being obese, smoking, and drinking alcohol can increase your risk of developing many types of cancers. Regular exercise, not smoking, limiting alcohol and healthy eating reduces your risk of many health conditions, including lymphoma.
Previous cancer treatment
Previous cancer treatment, including chemotherapy, CAR T therapy or radiation can increase your risk of developing lymphoma, though most people never do.
Autoimmune conditions
Autoimmune conditions. Autoimmune conditions develop when your immune system mistakenly attacks your own body. Many people with autoimmune disorders never develop lymphoma, but it can increase the risk. This includes:
- Sjögren’s syndrome increases the risk of developing splenic marginal zone lymphoma, MALT lymphoma, diffuse large B-cell lymphoma (DLBCL), and Waldenström’s macroglobulinaemia.
- Hashimoto’s thyroiditis increases the risk of MALT lymphoma.
- Refractory coeliac disease is linked to a very rare type of lymphoma called enteropathy-associated T-cell lymphoma (EATL).
- Rheumatoid arthritis and systemic lupus erythematosus are both linked to splenic marginal zone lymphoma and diffuse large B-cell lymphoma (DLBCL).
Certain infections
Lymphoma is not an infection and is not contagious. There are some infections that slightly increase risk of developing lymphoma, though many people have these infections and are never diagnosed with lymphoma. These include:
- Epstein–Barr virus (EBV): EBV is a very common virus that can cause glandular fever.
- Hepatitis C virus (HCV): HCV is a virus that infects the liver.
- Human immunodeficiency virus (HIV): HIV weakens your immune system, making it harder for your body to fight infections.
- Bacterial infections: Bacterial infections like chlamydia psittaci which causes a rare lung infection called psittacosis, campylobacter jejuni, a common cause of food poisoning, and borrelia burgdorferi, the bacteria that causes Lyme disease, have all been linked to certain types of MALT lymphoma.
- Human herpesvirus 8 (HHV-8): HHV-8 infects lymphocytes. It is linked with a very rare form of lymphoma called primary effusion lymphoma (PEL).
- Human T-lymphotropic virus type 1 (HTLV-1): HTLV-1 infects T lymphocytes. It is strongly linked to a very rare lymphoma called adult T-cell leukaemia/lymphoma.
Lowered immune system
Lowered immune system, meaning your immune system is less likely to function properly and ward off disease. A dysfunctional can be caused by a disease or treatments for other conditions received in the past. For instance:
- Human immunodeficiency virus (HIV) increases risk of developing certain types of lymphoma including Burkitt lymphoma, diffuse large B-cell lymphoma (DLBCL), Hodgkin lymphoma, primary effusion lymphoma (PEL) and plasmablastic lymphoma.
- Post-transplant lymphoproliferative disorders (PTLDs) are lymphomas that may develop in people taking anti-rejection medicines after an organ transplant or after receiving an allogeneic stem cell transplant (where the cells come from a donor).
Prognoses
The International Prognostic Indices (IPIs) are the primary clinical tools used to predict outcomes in patients with certain types of lymphoma. These tools include the patient’s age, and can include certain blood test results, performance status (how much the lymphoma or other conditions have weakened the patient), the stage of the disease and if the lymphoma has spread outside of the lymphatic system. From this information, the lymphoma can be categorised low-, intermediate-, and high-risk. The higher the score, the higher the risk. While these tools give an overall idea of the aggressiveness of the lymphoma, they are not perfect and must be sensitively applied and analysed.
International Prognostic Index for Chronic Lymphocytic Leukemia (CLL-IPI)
| Factor | Score |
|---|---|
| Age >65 years | +1 point |
| Stage B-C (using Binet Staging System) or I-IV (using the Rai Staging System | +1 point |
| Elevated β2 microglobulin, mg/L (or µg/mL) levels | +2 point |
| IGHV mutational status is unmutated | +2 point |
| TP53 status shows deletion 17p and or TP53 mutation | +4 point |
| IPI Score | Sum of Points |
International Prognostic Index (IPI) for DLBCL
| Factor | Score |
|---|---|
| Age >60 years* | +1 point |
| Stage III or IV (using the Ann Arbor Staging system) | +1 point |
| ECOG performance status ≥2 | +1 point |
| Lactate dehydrogenase (LDH) level >upper limit of normal** | +1 point |
| ≥2 extranodal sites (lymphoma found outside of the lymph nodes in places like the bone marrow, GI tract, liver, lung, brain, skin, testes, nasal cavity, eyes) | +1 point |
| IPI Score | Sum of Points |
*The National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) breaks down age into 4 categories and scores between 0 (for age 40 and under) and 3 points (for those over age 75)
**The NCCN-IPI looks at the LDH ration and scores between 0 (for ≥1) and 3 (for +2)
Follicular Lymphoma International Prognostic Index (FLIPI)
| Factor | Score |
|---|---|
| Age >60 years | +1 point |
| Stage III or IV (using the Ann Arbor Staging system) | +1 point |
| Hemoglobin <120 g/L or 12 g/dL | +1 point |
| Lactate dehydrogenase (LDH) level elevated | +1 point |
| >4 lymph nodes involved | +1 point |
| IPI Score | Sum of Points |
Mantle Cell Lymphoma International Prognostic Index (MIPI)
The MIPI does not assign points for risk factors, Instead, it uses a mathematical formula taking into account the following variables:
- Age
- ECOG performance status
- Lactate dehydrogenase (LDH) level
- White blood cell count (WBC)
An additional variable (Ki67) can be included to calculate the biologic variant of the index (MIPIb). Ki67 is a marker of cell proliferation which can inform how fast cancer cells are multiplying.