Non-Hodgkin Lymphoma: Classifications, Causes, Symptoms, Diagnosis, Stages and Treatment

It is a cancer that starts in the lymphocytes.

In non-Hodgkin’s lymphoma the abnormal growth of cells can not be controlled by the body’s natural defenses.

Cancer cells can grow and eventually form tumors that affect the lymphatic system.

Non-Hodgkin lymphoma is not a single disease but rather a group of several closely related cancers, called lymphoid neoplasms .

The most recent 2016 review of the classification of lymphoid neoplasms of the World Health Organization estimates that there are at least 86 types of non-Hodgkin’s lymphoma.

Although the various types of non-Hodgkin’s lymphoma share many common characteristics, they differ in certain characteristics, including their appearance under the microscope.

Its molecular characteristics and growth patterns, its impact on the body and how they respond to different types of treatment.

The lymphatic system

To understand what lymphoma is, it is useful to know the lymphatic system of the body.

The lymphatic system is part of the immune system , which has the function of helping to fight infections and other diseases, it also helps the fluids to move through the body.

This system is formed by a network of lymphatic vessels, lymph nodes and lymphatic organs.

The lymphatic vessels carry lymphatic fluid, which contains lymphocytes and other white blood cells, antibodies and nutrients. The lymph nodes are bean-shaped structures that are located along the lymphatic vessels.

The organs of the lymphatic system include the spleen, the thymus, the adenoids, the tonsils and the bone marrow.

Lymphocytes develop in the bone marrow from basic cells called stem cells.

Stem cells develop into different types of cells that have different functions. The main types of lymphocytes are:

  • B cells, these produce antibodies to fight bacteria, viruses and fungi, producing proteins called antibodies. Antibodies bind to germs, marking them for destruction by other parts of the immune system.
  • The T cells, these fight the infection, and destroy the abnormal cells and control the immune response. Other T cells help increase or decrease the activity of other cells of the immune system.
  • Natural killer cells attack abnormal or foreign cells.

The lymphocytes sometimes change, so they no longer grow or behave normally. These abnormal cells can form tumors called lymphomas.

Because lymphocytes are found throughout the lymphatic system, non-Hodgkin’s lymphoma can begin almost anywhere in the body.

It usually starts in a group of lymph nodes in one part of the body, such as in the neck, above the clavicle, under the arms, in the abdomen, or in the groin.

Non-Hodgkin’s lymphoma can spread to almost any tissue or organ in the body through the lymphatic system or the bloodstream.

The abnormal lymphocytes, or lymphoma cells, can remain in the lymph nodes or form solid tumors in the body.

Classifications of non-Hodgkin lymphoma

The World Health Organization (WHO) includes both lymphomas and lymphocytic leukemias, or non-Hodgkin’s lymphoma.

Both start in the lymphocytes, but the lymphoma cells are found in different places in the body.

If the tumors develop in the lymph nodes or other organs, it is considered a lymphoma.

If the lymphoma cells are in the blood or in the bone marrow and a tumor develops, it is considered a leukemia lymphoma.

Other cancers of the lymphatic system are called Hodgkin’s lymphoma.

The abnormal cells of Hodgkin’s lymphoma look and behave differently than non-Hodgkin’s lymphoma cells and their treatment is different.

There are different types of lymphomas, approximately 30 different types.

They are grouped according to the type of lymphocyte from which they are started.

Different types of non-Hodgkin’s lymphomas look different under a microscope.

They also develop and grow differently.

The degree of non-Hodgkin lymphomas is based on how different or abnormal the lymphoma cells are compared to normal lymphocytes.

Non-Hodgkin lymphoma is broadly classified into two groups:

B cell lymphomas:

B-cell lymphomas develop from abnormal B cells and account for about 85 percent of all non-Hodgkin’s lymphomas.

Most types of non-Hodgkin lymphomas start in these cells.

Natural killer lymphoma of T lymphocytes:

T-cell lymphomas develop from abnormal T cells or killer cells and account for about 15 percent of all non-Hodgkin’s lymphomas.

Non-Hodgkin lymphoma that begins in killer cells is clustered with T-cell lymphomas.

Non-Hodgkin lymphomas are also classified as indolent (slow-growing) or aggressive lymphomas that grow rapidly and usually need immediate treatment. They are also called intermediate or high grade lymphomas.

  1. Indolent (low grade) non-Hodgkin lymphoma: Represents cancer cells that are well differentiated. They look and act like normal cells and tend to have slow growth. These tend to grow slowly.
  2. Aggressive (high-grade) non-Hodgkin lymphoma:  Represents cancer cells that are poorly differentiated or not differentiated. They look and act less normal. These non-Hodgkin’s lymphomas tend to grow rapidly.

Each type of non-Hodgkin’s lymphoma may behave differently and may need different treatments.


Non-Hodgkin’s lymphoma is linked to a series of risk factors, however, the specific cause of most lymphomas is not known.

It is assumed that some changes in DNA cause normal lymphocytes to become lymphoma cells.

Genes responsible for controlling cell division or causing cells to die at a certain time are called tumor suppressor genes.

Lymphomas can be caused by mutations or changes in DNA, which can deactivate tumor suppressor genes.

Genetic changes related to non-Hodgkin’s lymphoma are usually acquired during life, rather than inherited.

They can be caused by exposure to radioactive substances, but sometimes occur for no apparent reason, appear to be associated with age since most lymphomas occur in elderly patients.

Lymphocytes (the cells from which lymphomas originate) are cells of the immune system, so it is not surprising that changes in the immune system seem to play an important role in many cases of lymphoma:

  • People with immune deficiencies, due to hereditary conditions, treatment with certain medications, organ transplants or AIDS infection, are much more likely to develop lymphoma than people without a weakened immune system.
  • People suffering from certain autoimmune diseases, in this type of disease the immune system constantly attacks certain cells, individuals have an increased risk of suffering from lymphoma.
  • People with certain chronic infections are at increased risk, probably because the immune system is constantly producing large numbers of lymphocytes to fight the infection, which increases the chances of DNA errors.


It is important to keep in mind that most patients with these symptoms do not have lymphoma, since diseases or conditions unrelated to lymphoma can cause many of these symptoms.

Some general signs and symptoms include:

Enlarged lymph nodes:

Non-Hodgkin’s lymphoma can cause enlarged lymph nodes.

When affected are lymph nodes near the surface of the body (such as in the groin, on the sides of the neck, above the clavicle or in the armpits), they can be perceived as lumps under the skin.

Vomiting, nausea, abdominal pain:

Lymphomas in the stomach or intestines can cause nausea, abdominal pain, or vomiting.

Problems associated with the nervous system:

Lymphomas located in the brain and spinal cord can cause headache, weakness, personality changes, double vision, facial numbness, difficulty speaking and sometimes convulsions.

Fatigue, trouble breathing, bruising or bleeding:

The superior vena cava is responsible for transporting blood from the head and arms to the heart.

Passing very close to the thymus and the lymph nodes inside the chest.

Lymphomas that originate in this area can press on these organs, causing swelling and even a purple color in the head, arms and upper chest.

It can also cause breathing problems and a change in consciousness if it affects the brain.

It can endanger life and should be treated immediately.

Swollen abdomen:

This can be caused by lymph nodes or organs such as the inflamed spleen or liver, or by retention of large amounts of fluid.

Fullness sensation:

The inflamed spleen can put pressure on the stomach, leading to a loss of appetite and the feeling of fullness after eating small amounts of food.

Pain or pressure in the chest, shortness of breath or cough:

If the lymphoma starts in the thymus or in the lymph nodes located in the chest, they can press on the trachea, causing coughing, difficulty breathing or a feeling of pressure or pain in the chest.

And other symptoms such as frequent infections, fever, since infections are the common features of swollen lymph nodes.

Symptoms such as itchy lumps or bumps, red or purple, typical of skin lymphoma.


Medical history and physical examination:

Symptoms, risk factors and other conditions. Exams to the lymph nodes and other areas of the body, such as the spleen and liver.

Lab tests:

Blood test:

To detect infections or other problems. As a complete blood count, hepatitis C virus, lactate dehydrogenase, blood chemistry tests, hepatitis B virus, or human immunodeficiency virus.

Flow cytometry and immunohistochemistry:

These tests help determine if the cause of lymph node inflammation is due to a lymphoma, any other type of cancer or due to a non-cancerous disease.

Chromosomal tests:

In some types of lymphoma, cells have changes in their chromosomes and these changes can often help identify the type of lymphoma.

These laboratory tests are: Cytogenetics, fluorescent in situ hybridization, polymerase chain reaction.


This is the only way to confirm the diagnosis of a non-Hodgkin lymphoma.

  • Excisional biopsy: When the entire lymph node is removed.
  • Incisional biopsy: When a small part of a tumor or ganglion is removed.

The size and shape of the cells and the way they are organized can show not only whether the patient has a lymphoma, but also what type of lymphoma it is.

Image tests:

Chest x-ray, computerized tomography, magnetic resonance imaging, ultrasound, positron emission tomography. These tests can be performed for several reasons, including:

  1. To look for possible causes of certain symptoms.
  2. To help determine the stage or extent of the lymphoma.
  3. To show that the treatment is working.
  4. To look for possible signs of lymphoma that come back after treatment.

Other tests:

Tests of cardiac and pulmonary function, echocardiogram (an ultrasound of the heart), pulmonary function tests.

Stages of non-Hodgkin lymphoma

The current staging system for adult non-Hodgkin’s lymphoma is known as the Lugano classification.

The stages are described by Roman numerals I to IV.

Etapa I:

When the lymphoma is located in an area of ​​the lymph node or a lymphoid organ, or only in an area of ​​a single organ outside the lymphatic system.

Stage II:

When the lymphoma is in two or more groups of lymph nodes on the same side, either from the area above or below the diaphragm, or affects groups of lymph nodes located on the same side of the diaphragm.

Step III:

When the lymphoma is located in the areas of the lymph nodes on both sides, both above and below the diaphragm or is located in the lymph nodes above the diaphragm.

Etapa IV:

At this stage, lymphoma has spread widely in more than one organ outside the lymphatic system, such as in the bone marrow, liver, or lung.

The lymphoma stage is important in determining the patient’s treatment options.

For many of the most common types of non-Hodgkin lymphoma, treatment is based in part on whether the lymphoma is “limited” (stage I or non-bulky stage II) or “advanced” (stage III or IV).

For some other types of non-Hodgkin’s lymphoma, such as rapidly growing lymphomas such as Burkitt’s lymphoma, the stage is less important when deciding on treatment.


Treatment options for patients with non-Hodgkin’s lymphoma may include:

  • Chemotherapy treatment.
  • Immunotherapy or biological therapy.
  • The molecularly directed therapies.
  • Radiotherapy.
  • The transplant of stem cells.
  • Surgery.

Another very important part of the treatment is palliative or supportive care, which consists in relieving symptoms caused by non-Hodgkin’s lymphoma, to help the patient feel more comfortable.