Lymphoma
What is lymphoma?

Lymphoma is a group of cancers of the lymphatic system. It develops when lymphocytes, a type of white blood cell, undergo changes that cause them to multiply and accumulate uncontrollably. Lymphoma most often affects the lymph nodes, but it can also involve the spleen, bone marrow, blood, or other organs, including the stomach, skin, lungs, bones, and central nervous system.

Lymphoma is not contagious. Enlarged lymph nodes do not necessarily mean lymphoma; infections are a much more common cause. Timely evaluation matters because some forms develop quickly but may respond well to treatment.

📌 For context: Non-Hodgkin lymphomas account for approximately 90% of lymphoma diagnoses. This is an international estimate, not a statistic specific to Albania.

How does lymphoma develop?

The lymphatic system is a network of lymph nodes, vessels, and organs that helps protect the body. Lymphocytes are white blood cells within this system that help fight infections.

In lymphoma, a lymphocyte develops changes in its genetic material that allow it to multiply uncontrollably. The resulting cells do not die when they should and may accumulate in lymph nodes, the spleen, bone marrow, or organs outside the lymphatic system. Lymphomas do not all develop at the same rate. Some are aggressive, grow quickly, and usually need prompt treatment. Others are indolent, develop slowly, and, in certain cases, can be monitored before treatment begins.

How lymphoma behaves depends mainly on its subtype, which is determined by examining tissue obtained through a biopsy and performing additional tests.

What are the main causes and risk factors?

Usually, no single cause can be identified for why a person develops lymphoma. The disease is associated with genetic changes acquired by lymphocytes that cause them to multiply and survive abnormally. These changes usually occur during a person’s lifetime and do not mean that lymphoma is directly inherited. Several factors may increase risk, but having them does not mean a person will develop lymphoma. Many patients have no known risk factors.

Factors related to the individual

Age: Many subtypes are more common in adults and older adults; Hodgkin lymphoma also occurs in adolescents and young adults.
Sex: Some subtypes are more common in males.
Family history: Having a close relative with lymphoma may be associated with a higher risk, but it generally does not mean family members need routine genetic testing.
A weakened immune system: Immunodeficiency, HIV infection, and treatments that suppress the immune system may increase the risk of certain subtypes.

Infections associated with certain subtypes

Helicobacter pylori is associated with gastric MALT lymphoma.
Epstein–Barr virus is associated with some forms of Hodgkin lymphoma and Burkitt lymphoma.
HIV, hepatitis C virus, and certain other microorganisms are associated with specific subtypes.
Chronic infections or inflammation may increase risk in certain circumstances.

Associated conditions and exposures

Some autoimmune diseases, such as Sjögren syndrome and rheumatoid arthritis, are associated with a higher risk of certain subtypes. Occupational and environmental exposures, including some pesticides and herbicides, have also been studied, but the association varies by exposure and rarely explains an individual case. Treatments that suppress the immune system, particularly after a transplant, may increase the risk of certain forms of lymphoma.

Types of lymphoma

Lymphoma includes many subtypes. The main division is between Hodgkin lymphoma and non-Hodgkin lymphomas. Further classification depends on the cell type, appearance under the microscope, biological markers, and clinical behavior.

Hodgkin lymphoma

Classical Hodgkin lymphoma is characterized by distinctive cells called Reed–Sternberg cells. It has several subtypes; nodular sclerosis is among the most common. In many cases, treatment can be given with the aim of curing the disease, but an individual’s outcome depends on the stage, their overall condition, and their response to treatment.

Non-Hodgkin lymphomas

This group includes many subtypes with different patterns of behavior. Most arise from B cells; others arise from T cells or NK cells.

Two well-known subtypes are diffuse large B-cell lymphoma (DLBCL), which is usually aggressive, and follicular lymphoma, which is often indolent. Other subtypes include mantle cell lymphoma, marginal zone lymphoma and MALT lymphoma, Burkitt lymphoma, and T-cell lymphomas. Each subtype can behave differently and require different treatment. Accurate identification through biopsy is essential to the treatment plan.

What are the symptoms of lymphoma?

Symptoms vary according to the subtype, how quickly it develops, and the area affected. A common sign is painless swelling of one or more lymph nodes.

Symptoms by location

Neck or above the collarbone: A painless swelling or lump, a feeling of pressure, and, if the nodes become very large, difficulty swallowing or breathing.
Chest: The nodes cannot be felt from outside the body, but enlargement may cause a persistent cough, difficulty breathing, chest pressure, or difficulty swallowing.
Armpit: A painless swelling or lump; in some cases, the arm may become swollen.
Abdomen: The nodes usually cannot be seen or felt. Symptoms may include bloating, abdominal pain or pressure, feeling full quickly, reduced appetite, nausea, or changes in bowel movements.
Groin or pelvis: Swelling in the groin, heaviness, or leg swelling if circulation is obstructed.

Lymphoma can also affect organs outside the lymph nodes:

Spleen or liver: Heaviness in the upper abdomen, feeling full quickly, and reduced appetite.
Bone marrow: Fatigue or paleness due to anemia, frequent infections, or bruising or bleeding due to a low platelet count.
Digestive system: Abdominal pain or bloating, nausea, changes in bowel movements, loss of appetite, and, in some cases, blood in the stool.
Skin: Spots, plaques, or bumps, itching, and other skin changes.
Central nervous system: Headaches, changes in vision or behavior, confusion, limb weakness, difficulty speaking, or seizures.

General symptoms

Regardless of the area affected, a person may experience:

Fatigue and weakness that do not improve with rest
Loss of appetite
Itchy skin
Recurrent infections

B symptoms

Three symptoms are particularly important when evaluating and staging lymphoma:

A temperature above 38°C (100.4°F) without a clear infectious cause
Drenching night sweats that soak clothing or bedsheets
Unintentional loss of more than 10% of body weight within six months

An enlarged lymph node is more often caused by an infection than by lymphoma. However, it should be evaluated by a doctor if it remains enlarged, grows, is hard or fixed in place, is located above the collarbone, affects several areas, or occurs with general symptoms. In indolent lymphomas, nodes may grow and shrink over months or years. In aggressive lymphomas, they may grow over a short period.

What are the warning signs?

Warning signs depend on where the lymphoma is located and which structures it affects or compresses. Examples include:

Neck or chest: Severe difficulty breathing, a feeling of choking, inability to swallow, or rapid swelling of the face, neck, and arms.
Near the spine: Severe back pain with leg weakness, progressive numbness, or loss of bladder or bowel control.
Central nervous system: Loss of consciousness, seizures, severe confusion, or sudden weakness or difficulty speaking.
Abdomen: Very severe, sudden pain, particularly with persistent vomiting or a rapid decline in health.
During treatment: A temperature of 38°C (100.4°F) or higher during chemotherapy or when neutropenia is present, or severe bleeding that does not stop.

⚠️ These situations require immediate emergency medical evaluation.

How is lymphoma diagnosed?

Symptoms, blood tests, or imaging alone cannot establish the diagnosis. Diagnosing lymphoma and identifying its subtype require a pathologist to examine tissue obtained through a biopsy. Evaluation may include:

Medical history and physical examination. The doctor asks how long the nodes have been enlarged and about symptoms, infections, medications, and other conditions. The lymph node regions, liver, and spleen are examined.
Biopsy. When possible, an entire lymph node or a sufficiently large tissue sample is obtained. A core needle biopsy may be used in certain circumstances. Fine needle aspiration alone often does not provide enough tissue to classify lymphoma.
Tests on the biopsy sample. These may include examination under the microscope, immunohistochemistry, flow cytometry, and, when appropriate, cytogenetic or molecular tests.
Blood tests. These may include a complete blood count, tests of kidney function and liver function, electrolytes, LDH, uric acid, and other tests based on the clinical situation.
Staging. PET-CT or CT, depending on the subtype and clinical need, helps assess the extent of the disease.

A bone marrow biopsy, lumbar puncture, and other examinations are performed when indicated.

How is lymphoma treated?

Treatment is tailored to the subtype, stage, symptoms, age, other health conditions, patient preferences, and previous treatments. Options include:

Active surveillance: For some indolent lymphomas without symptoms, treatment may be deferred while the patient is monitored regularly.
Chemotherapy: Combinations of medications that act against lymphoma cells.
Immunotherapy and monoclonal antibodies: Such as rituximab for appropriate subtypes.
Radiation therapy: For localized disease, as consolidation, or to control symptoms, depending on the situation.
Other specialized therapies: Including CAR T-cell therapy, bispecific antibodies, and antibody–drug conjugates for selected subtypes and situations.
Stem cell transplantation: In certain cases, usually at specialized centers.
Treatment of an associated infection: For example, treating H. pylori may be the first step for some gastric MALT lymphomas.
Supportive care: Prevention and treatment of infections, transfusions when needed, symptom control, nutritional and psychological support, and rehabilitation.

Surgery is usually used to obtain a biopsy or treat complications; it is rarely the main treatment for systemic lymphoma. Patients of reproductive age should have an opportunity to discuss fertility preservation before treatment when time and their clinical condition allow.

Can lymphoma be cured?

The answer depends on the subtype, stage, and response to treatment. Complete remission means that current examinations show no detectable signs of lymphoma. It is not always the same as a permanent cure, because some subtypes can return and require long-term follow-up.

Classical Hodgkin lymphoma and some aggressive non-Hodgkin lymphomas can be treated with the aim of curing them. Although they grow quickly, some aggressive forms respond well to treatment.

Widespread indolent lymphomas are often managed as long-term conditions. They may remain controlled and in remission for many years; if they return, further treatment may be needed.

The doctor assesses each patient’s outlook based on the subtype, test results, and time spent without signs of disease.

Can lymphoma be prevented?

There is no certain way to prevent lymphoma, and there is no routine screening program for people without symptoms. Practical measures focus on recognizing warning signs, caring for general health, and protecting health during treatment. General health advice includes:

Do not smoke, limit alcohol, and maintain a healthy weight through a varied diet and physical activity suited to your condition.
Follow medical advice on preventing and treating chronic infections, such as H. pylori or hepatitis C.
Follow workplace safety measures for chemical exposures.
During treatment, follow your medical team’s advice on hygiene, vaccinations, and reducing infection risk.
Discuss supplements, herbal products, or restrictive diets with your doctor before using them, as they may interact with treatment or affect nutrition.

When should you see a doctor?

If you have not been diagnosed with lymphoma, contact a doctor if:

A lymph node remains enlarged for several weeks, grows, or feels hard and fixed in place.
You have enlarged nodes above the collarbone or in several areas of the body.
You have an unexplained fever, drenching night sweats, or unexplained weight loss.
You have persistent fatigue, itching, cough, difficulty breathing, abdominal bloating, frequent infections, or unusual bleeding.

These signs do not necessarily mean lymphoma, but they warrant medical evaluation.

If you have been diagnosed with lymphoma, contact your medical team if a new node appears or an existing one grows; fever, night sweats, or weight loss return; or you develop pain, difficulty breathing, infections, bleeding, or severe treatment side effects. Also tell your team if symptoms persist or worsen during follow-up.

Why do accurate diagnosis and follow-up matter?

Lymphoma includes many diseases with different patterns of behavior and treatments. Enlarged lymph nodes, B symptoms, and other unexplained signs need evaluation. Diagnosis relies on a biopsy and accurate identification of the subtype and stage. Modern treatments have improved outcomes for many patients. An individual plan, care, and long-term follow-up help control the disease and protect physical health, fertility, emotional well-being, and quality of life.

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📌 Reviewed by Dr. Irma Lapaj, Hematologist, Klinika Kajo.

Lymphoma