Non-Hodgkin's Lymphoma (NHL) - Blood Cancers in the Lymphatic System

The term “Non-Hodgkin lymphoma”, or NHL, describes a group of blood cancers that arise in the lymphatic system. NHL is divided into 61 subtypes, collectively responsible for more 66,000 annual diagnoses.

The lymphatic system performs a vital role in the body’s ability to fight off infection. Lymph vessels, lymphoid tissue, and lymph fluid (a clear liquid that carries waste and excess material away from tissues) compose the lymphatic system. Cells produced by the immune system work together to form the various components of the lymphatic system.

When cells displaying uncontrolled growth, invasion, and/or metastasis (spread) arise in the lymphatic system, a cancer is formed. Unlike Hodgkin lymphoma, NHL is not distinguished by the presence of the Reed-Sternberg cell.

Where is The Lymphatic System?

Lymphoid tissue, also known as lymphatic tissue, is located throughout the human body. As a result, non-Hodgkin lymphoma can develop in almost any organ, gland, or tissue. The highest concentrations of lymphoid tissue can be found in the following locations:

LYMPH NODES

Lymph nodes are bean-shaped masses of lymphoid tissue located throughout the body. Large concentrations of lymph nodes can be found in the neck, armpits (axilla), groin, and around the collarbone. The primary function of a lymph node is to trap waste products and bacteria traveling in lymph fluid. These small, round glands play a critical role in initiating immune reactions. These reactions provoke the body’s immune system to fight off infection.

When lymph nodes react to infection, they become enlarged. A sore throat, cold, or the flu often results in swollen lymph nodes in the neck. Swollen lymph nodes are the most common sign of lymphoma.

BONE MARROW

The bone marrow is a soft, spongy material found inside many bones. It is responsible for the production of blood cells:

Red Blood Cells: These cells enrich the body with oxygen. Red blood cells absorb oxygen in the lungs and carry it throughout
Platelets: Platelets coagulate around holes in blood vessels caused by scrapes, bumps, and cuts. This prevents bleeding.
White Blood Cells: These cells’ primary function is to fight infection. White blood cells are further divided into two main subtypes:
Granulocytes
Lymphocytes

Non-Hodgkin lymphoma may develop in the lymphocytes of the bone marrow.

SPLEEN

The spleen is a small gland situated beneath the lower part of the rib cage. Its primary function is to produce lymphocytes and other immune system cells. The spleen also filters out damaged blood cells and stores healthy ones.

THYMUS

The thymus is a gland located in front of the heart behind the upper part of the breastbone. The thymus plays a critical role in the development of T lymphocytes during fetal development. Over the first 20 years of life, the thymus’s functionality decreases; however, the gland continues to produce lymphocytes throughout life.

TONSILS AND ADENOIDS

These glands are located in the throat. Their primary function is produce antibodies against bacteria and toxins that are breathed in or swallowed. These glands are easily observed when they are swollen. Swollen glands in the neck are common indicators of non-Hodgkin lymphoma.

DIGESTIVE TRACT

The stomach, intestine, and other digestive organs contain lymphoid tissue.

Risk Factors

Non-Hodgkin lymphoma typically develops in the absence of any risk factors. Some factors, however, may contribute to a heightened state of lymphoma risk:

Chemical Exposure: Certain hazardous chemicals, primarily insecticides and herbicides, have been linked to NHL development. The link between chemical exposure and lymphoma has not been clearly established. Researchers believe that these chemicals cause cellular DNA mutations that may lead to cancer.
Age: NHL affects people of all ages. People in their 60s, however, are most at risk.
Weakened Immune System: Certain infections that weaken the immune system, such as HIV/AIDS, may contribute to lymphoma development.

The following infections may contribute to NHL development:

Epstein-Barr Virus
Helicobactor Pylori
Malaria
Organ Transplantation: Organ transplantation weakens a person’s immune system, which may lead to NHL development.

Signs and Symptoms

The signs and symptoms associated with non-Hodgkin lymphoma may also indicate other illnesses. This underscores the importance of immediate medical evaluation upon the observation of any health abnormalities. Non-Hodgkin lymphoma symptoms may include:

Fever
Night Sweats
Weight Loss
Fatigue / Tiredness
Abdominal Pain / Swelling
Chest Pain
Trouble Breathing
Incessant Coughing
Itchy Skin

Diagnosis

To properly diagnose NHL, a team of doctors may recommend the following diagnostic tests:

PHYSICAL EXAM

In a physical exam, your doctor will look for swollen lymph nodes. Using the naked eye and/or the sense of touch, the doctor will determine the lymph nodes’ size and consistency.

IMAGING TESTS

These tests allow doctors to see internal body structures

X-Ray and Computerized Axial Tomography (CAT Scan): These tests use radiation beams to detect tumors in the neck, chest, abdomen, and pelvis.
Magnetic Resonance Imaging (MRI): This imaging test uses a powerful magnetic field and radio waves to determine whether or not NHL has affected the brain and/or spinal.
Positron Emission Tomography (PET Scan): Unlike other imaging tests, which generate detailed renderings of internal body structures, PET uses color variations to show chemical activity in the body. PET scans are the only imaging tests that can differentiate malignant (cancerous) cells from benign (non-cancerous) ones.

LYMPH NODE BIOPSY

In this test, a doctor will use a needle and syringe to extract swollen lymph node tissues. These tissues are then sent to a laboratory for microscopic evaluation. In some cases a lymph node biopsy necessitates surgery. In these cases, the patient is given local or general anesthesia, and incision is made, and the entire lymph node is removed.

BONE MARROW BIOPSY

In a bone marrow biopsy, a doctor inserts a needle into the pelvic bones to extract bone marrow cells. These cells are sent to a laboratory for microscopic evaluation.

BLOOD AND URINE TESTS

Swollen lymph nodes typically indicate infection, not lymphoma. Blood and urine tests are conducted to determine whether or not infection is causing lymph node swelling.

Staging

Non-Hodgkin lymphoma is staged in order to determine the extent of metastasis (spread). The staging system most commonly used to identify NHL is known as the Ann Arbor Staging System, which uses Roman numerals I through IV to describe the disease. Information obtained from staging will help the patient and his or her team of doctors determine the best treatment approach, and a proper prognosis (patient outlook).

The following stages describe NHL:

STAGE I

NHL is confined to lymph nodes in only one region (i.e. the neck, groin, or armpit).
NHL has developed in one area of a single organ outside the lymphatic system.

STAGE II

NHL is found in two or more lymph nodes on the same side of the diaphragm. NHL found in the neck and armpit is an example of a Stage II cancer.
NHL has invaded from a single group of lymph nodes into a nearby organ on the same side of the diaphragm.

STAGE III

NHL is found in lymph nodes on both sides of the diaphragm.
NHL has invaded into adjacent organs.

STAGE IV

NHL has metastasized (spread) beyond the lymphatic system into organs and structures throughout the body.
NHL has invaded the bone marrow, brain, spinal cord, liver, or the lining of the lungs.

ADDITIONAL STAGING DESCRIPTORS

The letters “A” and “B” are used to describe the following:

A: Patient does not have any signs or symptoms of lymphoma.
B: Patient exhibits:

Weight Loss (more than 10% of body weight)
Night Sweats
Fever

Treatment

A treatment strategy is determined after a patient’s overall health, age, type of NHL, and stage of NHL have been evaluated.
The following treatment modalities may be used alone or in conjunction with one another to treat non-Hodgkin lymphoma:

Chemotherapy: Chemotherapy is the use of chemical agents (drugs) to kill fast-growing cells. This is the treatment of choice for NHL.
Radiotherapy: Radiation therapy uses beams of ionizing radiation to kill cancer cells. Ionizing radiation may be administered with machines located outside the body, or with mechanisms placed inside the body.
Stem Cell Transplantation: In late-stage NHL, high-dose chemotherapy is often used to kill cancer cells. High-dose chemo also kills normal cells, especially the cells of the bone marrow. As a result, healthy stem cells (underdeveloped cells that are capable of producing new cells) are extracted from the patient prior to chemotherapy. After the patient undergoes high-dose chemo, they will be injected with their own healthy stem cells. These cells will regenerate bone marrow damaged be chemotherapeutic drugs.
Biotherapy: A drug known as rituximab (Rituxan) may be used to treat B-cell non-Hodgkin lymphoma. This drug is a monocional antibody that empowers the patient’s immune system to kill cancer cells. Biotherapy is commonly administered in conjunction with chemotherapy.
Interferon Therapy: The body produces interferon proteins naturally to help fight infection. Research suggests that genetically engineered interferon proteins may help slow or stop the progression of NHL. This is an experimental treatment. More research is needed to confirm its effects and proper usages.
Radioimmunotherapy: Radioimmunotherapy uses monocial antibody drugs, such as ibritumomab (Zevalin) and tositumomab (Bexxar), in conjunction with radioactive isotopes to kill cancer cells. This treatment option may result in serious, potentially life-threatening side effects. As a result, radioimmunotherapy is only been approved by the FDA when all other treatment strategies have failed.

Outlook (Prognosis)

Five-year NHL survival rates range from 20 to 95%, depending on a patient’s age, overall health, and the type and stage of their cancer.

A positive prognosis generally depends on a cross-evaluation of the following factors:

Being Male
Presence of B Symptoms (see “Additional Staging Descriptors”)
Stage III or IV NHL
Being Older

If one or more of the aforementioned factors are present, a patients five-year survival outlook drops below 65%. Additional factors may also be evaluated to establish a more accurate prognosis.