Symptoms and risk factors

The symptoms that may suggest lymphoma are non-specific. This means they can raise suspicion, but none of them alone is enough to make a diagnosis. For this reason, it is essential to consult a doctor, who can recommend the appropriate tests needed for an accurate diagnosis.

There are two main types of lymphoma symptoms:

1. Local symptoms, caused by the enlargement (swelling) of lymphatic tissue where the tumor is growing;
2. Systemic symptoms, caused by substances released by the tumor that affect the whole body.

These symptoms, however, are not specific to lymphomas; a biopsy of the lymph node or of non-lymph node lesions is thus essential to exclude other diseases and make the diagnosis.

Symptoms related to enlarged lymphatic tissue

The most common sign of lymphoma is the enlargement of one or more lymph nodes. These are often noticed in the neck, armpits, or groin. Enlarged lymph nodes are usually painless and may involve more than one area. Their size, consistency, and the presence or absence of inflammation can help doctors evaluate the suspicion of lymphoma.

Sometimes, enlarged lymph nodes are not visible because they are located deep in the body, such as in the chest or abdomen, or the disease may involve the spleen. More rarely, lymphoma can affect the bone marrow or other organs (such as the liver, stomach, or intestines). In these cases, symptoms depend on the affected organ.

Common symptoms may include:

• Cough, shortness of breath, chest pain, or swelling of the neck, if lymph nodes in the chest are involved
• Loss of appetite, early feeling of fullness, or upper abdominal pain, if the stomach is involved
• Abdominal discomfort or pain, sometimes with a detectable mass, if deep abdominal lymph nodes are involved
• Intestinal problems such as diarrhea or blood in the faeces, if the intestines are involved
• Neurological symptoms such as confusion, personality changes, speech difficulties, or weakness in limbs, if the central nervous system is involved

Systemic symptoms (b symptoms)

These are general symptoms that are more common in aggressive lymphomas or in certain types such as Hodgkin lymphoma. The most important are:

• Fever
• Generalized itching
• Night sweats
• Unintentional weight loss

Because lymphoma symptoms are non-specific, medical history and physical examination alone are not enough for diagnosis. Further tests are always needed.

Blood tests may sometimes indicate an infection or another condition, but in most cases, doctors will need to perform a biopsy of a lymph node or affected tissue to confirm the diagnosis.

Causes and risk factors

The exact causes of lymphoma are still not fully understood. As with many cancers, lymphoma develops as a result of changes (mutations) in the DNA of certain cells. These mutations can be triggered by exposure to chemicals and environmental pollutants, viruses, autoimmune diseases, or radiation.

It is important to remember that having a risk factor does not mean that a person will definitely develop lymphoma—it only indicates a higher probability compared to those without that factor.

Some infectious agents have been linked to the development of specific types of lymphoma. Among the most relevant are:

• Helicobacter pylori (HP): infection of the stomach with HP may be associated with the development of gastric MALT lymphoma.
• Hepatitis C virus (HCV): chronic infection is a known risk factor for certain non-Hodgkin lymphomas, particularly marginal zone lymphoma.
• Chlamydia psittaci: infection affecting the tissues around the eye has been associated with lymphoma of the ocular adnexa.
• Epstein-Barr virus (EBV): linked to Burkitt lymphoma and to some lymphomas that develop in patients who have undergone organ transplantation.
• Human Immunodeficiency Virus (HIV): may increase the risk of developing aggressive lymphomas in some HIV-positive individuals.

Additional risk factors

Long-term immunosuppressive therapies—such as those used after solid organ transplants (heart, lung, etc.)—can also increase the risk of lymphoma. These are often aggressive forms and may be associated with Epstein-Barr virus (EBV).

Family history is often discussed in relation to lymphoma, as with many cancers. However, there is currently no clear evidence that lymphoma is directly inherited. The genetic changes responsible for cancer are typically somatic, meaning they occur in individual cells during a person’s lifetime and are not passed down from parents to children.

That said, some individuals may have a greater inherited susceptibility to developing these mutations over time, especially with aging or exposure to risk factors such as smoking or other carcinogens. At present, however, no specific genetic profile has been identified that clearly predicts an increased risk of lymphoma, unlike what has been established for other cancers such as breast cancer.