Non-Hodgkin lymphoma is a diverse group of blood cancers that starts in the lymphatic system, the network of vessels and glands that helps protect the body from infections and diseases. When certain white blood cells called lymphocytes begin to grow abnormally, they can form tumors in lymph nodes, organs, and other parts of the body, leading to a variety of symptoms and health challenges that require specialized medical attention.

Epidemiology

Non-Hodgkin lymphoma represents one of the more common cancer diagnoses across the globe. In the United Kingdom, more than thirteen thousand people receive this diagnosis each year, making it a significant health concern for the population.^[3] In the United States, approximately eighty thousand new cases are expected in 2024, making it the eighth most common cancer diagnosis in the country and the eleventh most common cancer worldwide.^[2] These numbers highlight how frequently this condition occurs compared to many other types of cancer.

When looking at who is most affected by this disease, several clear patterns emerge. Non-Hodgkin lymphoma can develop at any age, but the risk increases significantly as people get older. Just over one-third of all cases are diagnosed in people who are seventy-five years old or older.^[3] This means that older adults face a much higher likelihood of developing this condition than younger individuals.

Gender also plays a role in how frequently this cancer occurs. Statistics show that slightly more men than women are affected by non-Hodgkin lymphoma.^[3] This gender difference exists across various age groups and populations, though researchers are still working to fully understand why men face a somewhat higher risk than women.

Compared to the other main type of lymphoma, known as Hodgkin lymphoma, non-Hodgkin lymphoma is much more common. This distinction is important because the two types of lymphoma differ not only in how frequently they occur but also in how they behave and how they are treated.^[2]

Causes

The exact cause of non-Hodgkin lymphoma remains unknown to medical science. However, what researchers do understand is that at some point during a person’s lifetime, genes inside B lymphocytes (B cells) or T lymphocytes (T cells) undergo mutations or changes. These lymphocytes are specialized white blood cells that normally help the body fight infections by identifying and destroying harmful organisms.^[2] When these genetic changes occur, the affected lymphocytes begin to multiply abnormally and lose their ability to function properly in fighting disease.

The abnormal lymphoma cells typically start to accumulate in lymph nodes, which are small bean-shaped structures found throughout the body, including in the neck, armpits, and groin. These cancerous cells can also collect in other parts of the lymphatic system, such as the thymus (an organ in the chest), the spleen (an organ on the left side of the abdomen), or in lymph tissue located in other areas of the body.^[7] Without treatment, the abnormal cells can spread beyond the lymphatic system to other organs and tissues.

While scientists cannot point to one specific cause, they have identified that viruses may be responsible for triggering some types of non-Hodgkin lymphoma. Various infections, exposure to certain toxins, chromosomal translocations (when parts of chromosomes break off and reattach in the wrong place), and chronic inflammation may all contribute to the development of this cancer.^[4] However, in most cases, there is no clear, identifiable trigger that explains why the disease develops in a particular individual.

Risk Factors

Several factors can increase a person’s likelihood of developing non-Hodgkin lymphoma. Understanding these risk factors helps people recognize when they might be more vulnerable to this condition, though having one or more risk factors does not mean that a person will definitely develop the disease.

One of the most significant risk factors is having a medical condition that weakens the immune system. When the body’s natural defense system is compromised, it becomes less able to control the growth of abnormal cells, including those that lead to lymphoma.^[3] People who take immunosuppressant medications, which are drugs that deliberately reduce immune system activity (often prescribed after organ transplants or for autoimmune diseases), also face an increased risk of developing non-Hodgkin lymphoma.

Previous exposure to certain viruses can raise the risk as well. The Epstein-Barr virus, which is the common virus that causes glandular fever (also known as infectious mononucleosis), has been linked to an increased chance of developing this cancer.^[3] This does not mean that everyone who has had glandular fever will develop lymphoma, but the connection exists and is recognized by medical researchers.

Family history plays a role in risk as well. If a close relative such as a parent or sibling has had non-Hodgkin lymphoma, a person’s own risk increases slightly compared to someone with no family history of the condition.^[3] This suggests that some genetic factors may make certain families more susceptible to developing this type of cancer.

Age is another important risk factor, as mentioned earlier in the epidemiology section. The chances of developing non-Hodgkin lymphoma increase steadily as people grow older, with the highest rates seen in people over seventy-five years old.^[7] Being male also slightly increases the risk compared to being female, though both genders can certainly develop this condition.

Symptoms

The symptoms of non-Hodgkin lymphoma can vary considerably depending on where in the body the abnormal lymphocytes have accumulated and how the disease is progressing. The most common and often earliest symptom is painless swelling in lymph nodes located in the neck, armpits, or groin. Unlike swollen lymph nodes caused by infections, which are often tender to the touch, lymph nodes affected by lymphoma typically do not hurt.^[1] This swelling occurs because cancer cells are building up inside these nodes, causing them to enlarge.

Many people with non-Hodgkin lymphoma experience a group of symptoms that doctors specifically refer to as “B symptoms.” These include fever that occurs without an obvious infection, night sweats that are so intense they soak through sheets and clothing, and unexplained weight loss where a person loses ten percent of their total body weight over six months without trying.^[2] These symptoms are particularly important because they help doctors classify the type and severity of the lymphoma.

Persistent fatigue is another common symptom. This is not just normal tiredness that goes away with rest, but rather an overwhelming sense of exhaustion that interferes with daily activities and does not improve even after sleeping.^[2] This fatigue can result from the cancer itself or from anemia, which is a condition where the body has too few red blood cells to carry oxygen effectively.

When lymphoma affects specific parts of the body, it can cause symptoms related to those areas. Chest pain, coughing, or trouble breathing may occur when enlarged lymph nodes in the chest press against airways or other structures.^[1] Belly pain or swelling, along with a feeling of fullness even after eating very little, can happen when the lymphoma affects lymph nodes or organs in the abdomen.^[2]

In children, the first symptoms may present differently. Instead of swollen lymph nodes being the primary sign, children might first show signs of anemia, develop a rash, or experience weakness and unusual sensations in their bodies.^[5] This difference in presentation makes it especially important for parents and caregivers to pay attention to any persistent changes in a child’s health.

Prevention

Because the exact causes of non-Hodgkin lymphoma are not fully understood, there are no guaranteed ways to prevent this disease. However, understanding the risk factors and taking steps to maintain overall health may help reduce the likelihood of developing this cancer.

One preventive measure involves protecting the immune system. Since weakened immunity is a known risk factor, maintaining a healthy immune system through good nutrition, regular exercise, adequate sleep, and stress management may be beneficial. People who need to take immunosuppressant medications for legitimate medical reasons should continue to do so under their doctor’s supervision, but they should be aware of the increased risk and discuss monitoring options with their healthcare team.^[3]

Avoiding infections that can increase lymphoma risk is another consideration. While it is not always possible to prevent viral infections like Epstein-Barr virus, practicing good hygiene, avoiding sharing drinking glasses or eating utensils, and taking precautions during illness can help reduce exposure to some viruses.^[3]

There is no specific screening test recommended for the general population to detect non-Hodgkin lymphoma early. Unlike some cancers where regular screening tests are standard (such as mammograms for breast cancer or colonoscopies for colon cancer), non-Hodgkin lymphoma does not have a similar screening approach for people without symptoms or specific risk factors. This makes it even more important to pay attention to body changes and report persistent symptoms to a doctor promptly.

For people with a family history of non-Hodgkin lymphoma or other significant risk factors, discussing concerns with a healthcare provider may be worthwhile. While specific preventive measures are limited, awareness of increased risk can help ensure that any concerning symptoms are evaluated promptly and thoroughly.

Pathophysiology

Understanding what happens in the body when non-Hodgkin lymphoma develops helps explain why the symptoms occur and how treatments work. The lymphatic system normally functions as a crucial part of the body’s immune defense, with lymph fluid traveling through vessels and carrying lymphocytes throughout the body to fight infections and diseases.

In a healthy immune system, B lymphocytes produce antibodies that help fight infections by recognizing and marking harmful organisms for destruction. T lymphocytes help B cells make these antibodies and also directly attack infected cells. These lymphocytes travel through the blood vessels and then through the lymphatic system, passing through lymph nodes where they can encounter and respond to threats.^[7]

When non-Hodgkin lymphoma develops, the genetic mutations that occur in B cells or T cells cause these lymphocytes to lose their normal growth controls. Instead of dividing in an orderly, controlled way and dying when they should, the abnormal lymphocytes continue to multiply uncontrollably. They also lose their infection-fighting properties, which means they no longer perform their intended protective function.^[3]

As these abnormal lymphocytes accumulate, they begin to collect in lymph nodes, causing them to swell. The cancerous cells can also build up in other parts of the lymphatic system, including the spleen, thymus, tonsils, and bone marrow (the soft tissue inside bones where blood cells are made).^[7] When bone marrow becomes involved, it can interfere with the production of normal blood cells, leading to low counts of red blood cells (causing anemia and fatigue), white blood cells (increasing infection risk), or platelets (causing easy bruising and bleeding).

There are more than seventy different subtypes of non-Hodgkin lymphoma, and they are classified based on which type of lymphocyte is affected and how quickly the cancer grows. About eighty-five percent of non-Hodgkin lymphoma cases involve B cells, while the remaining cases involve T cells.^[2] Healthcare providers further classify these lymphomas as either aggressive or indolent. Aggressive lymphomas grow and spread quickly, requiring immediate intensive treatment but often responding well to therapy. Indolent lymphomas grow slowly and may not cause symptoms for many years, sometimes not requiring immediate treatment but being harder to cure completely.^[2]

The cancerous lymphocytes can spread beyond the lymphatic system to other organs and tissues throughout the body, a process called metastasis. Between ten and thirty-five percent of patients have lymphoma in organs outside the lymphatic system (called primary extranodal lymphoma) at the time of diagnosis, and approximately half of patients develop secondary spread to other organs during their disease.^[4] This can lead to symptoms affecting those specific organs, such as digestive problems if the lymphoma affects the stomach or intestines, or neurological symptoms if it spreads to the brain or spinal cord.