Non-Hodgkin Lymphoma in Children

What is non-Hodgkin lymphoma (NHL)?

NHL is cancer in the lymphatic system. The lymphatic system is part of the immune system and functions to fight disease and infections.

The lymphatic system includes the following:

• Lymph fluid. Fluid containing lymphocyte cells.

• Lymph vessels. Thin tubes that carry lymph fluid throughout the body.

• Lymphocytes. Specific white blood cells that fight infections and disease.

• Lymph nodes. Bean-sized organs, found in the underarm, groin, neck, chest, abdomen, and other parts of the body, that act as filters for the lymph fluid as it circulates through the body.

NHL causes the cells in the lymphatic system to abnormally reproduce, eventually causing tumors to grow. The cells can also spread to other organs and tissues in the body.

Lymphomas (including both Hodgkin and non-Hodgkin lymphomas) are the third most common childhood cancer in the U.S. About 800 cases of NHL are diagnosed in children and teens in the U.S. each year. They can occur at any age from infancy to adulthood.

NHL affects males more often than females, and is more common among white children than among African-American children and children of other races.

Staging and classification of non-Hodgkin lymphoma is based on the extent of the disease and the specific cells involved.

What are the different types of non-Hodgkin lymphoma?

NHL in children is almost always one of three types:

• Lymphoblastic non-Hodgkin lymphoma. Lymphoblastic non-Hodgkin lymphoma accounts for about 30 percent of the cases, usually involves the T-cells (T-lymphocytes), and typically presents with a mass in the chest, swollen lymph node(s), with or without bone marrow and central nervous system involvement.

• Burkitt's and non-Burkitt's lymphoma. Burkitt's and non-Burkitt's lymphoma are fast-growing lymphomas in which the cells are undifferentiated and diffuse. This has also been referred to as small noncleaved cells. Burkitt's and non-Burkitt's lymphoma accounts for about 40 percent of the cases. They are usually characterized by a large abdominal tumor and may have bone marrow and central nervous system involvement.

• Large cell or diffuse histiocytic non-Hodgkin lymphoma. Large cell or diffuse histiocytic non-Hodgkin involves the B-cells or T-cells and accounts for about 25 percent of the cases. Children with this type of non-Hodgkin lymphoma usually have lymphatic system involvement, as well as a nonlymph structure (such as lung, jaw, skin, and bone) involvement. Anaplastic large cell lymphoma is a type of large cell lymphoma in children. Large cell lymphomas usually do not grow as quickly as other lymphomas in children.

How is non-Hodgkin lymphoma staged?

Staging is the process of determining whether cancer has spread and, if so, how far. There are various staging symptoms that are used for non-Hodgkin lymphoma. Always consult your child's doctor for information on staging. One method of staging non-Hodgkin lymphoma is the following:

• Stage I. The lymphoma is at one site, either nodal or elsewhere in the body, but not in the chest or abdomen. 

• Stage II. The lymphoma is at two or more sites on the same side of the body (above or below the diaphragm), but not in the chest. 

• Stage III. The lymphoma is in the chest or spine, or it has spread widely in the abdomen, or it is both above and below the diaphragm, but it does not involve bone marrow or the central nervous system.

• Stage IV. Any lymphoma that has bone marrow and/or central nervous system involvement when it is first found.

What causes non-Hodgkin lymphoma?

The specific cause of non-Hodgkin lymphoma is unclear. It is possible that genetics and exposure to viral infections may increase the risk for developing this malignancy. Non-Hodgkin lymphoma has also been linked to chemotherapy and radiation therapy. Non-Hodgkin may be a second malignancy as a result of the treatment for certain cancers.

There has been much investigation into the association of the Epstein-Barr virus that causes the mononucleosis infection, as well as HIV, which causes AIDS. Both of these infectious viruses have been linked to the development of Burkitt's lymphoma.

Children and adults with certain hereditary immune system abnormalities have an increased risk of developing non-Hodgkin lymphoma, including patients with ataxia telangiectasia, X-linked lymphoproliferative disease, or Wiskott-Aldrich syndrome. People who have had organ transplants and need to take medicines to suppress their immune systems are also at increased risk. 

What are the symptoms of non-Hodgkin lymphoma?

In many cases, non-Hodgkin lymphoma in children may not cause symptoms until it has grown or spread. Most children have stage III or IV disease at the time of diagnosis because of the sudden onset of symptoms and the fact that these lymphomas tend to grow very quickly. The disease can sometimes progress quickly from a few days to a few weeks. A child can go from otherwise healthy to having multisystem involvement in a short time period.

Some children with non-Hodgkin lymphoma have symptoms of an abdominal mass and have complaints of abdominal pain, fever, constipation, and decreased appetite due to the pressure and obstruction a large tumor in this area can cause.

Some children with non-Hodgkin lymphoma have symptoms of a mass in their chest and have complaints of respiratory problems, pain with deep breaths (dyspnea), cough, and/or wheezing. Lymphomas in the chest can also press on a main blood vessel (the superior vena cava), which can cause swelling and a bluish coloration in the head and arms. If left unchecked, it can also affect the brain and may even be life-threatening. 

The following are the most common symptoms of non-Hodgkin lymphoma. However, each child may experience the symptoms differently. Symptoms may include:

• Painless swelling of the lymph nodes in neck, chest, abdomen, underarm, or groin

• Fever

• Sore throat

• Fullness in groin area from node involvement

• Bone and joint pain

• Night sweats

• Tiring easily (fatigue)

• Weight loss/decreased appetite

• Itching of the skin

• Recurring infections

The symptoms of non-Hodgkin lymphoma may resemble other blood disorders or medical problems. Always consult your child's doctor for a diagnosis.

How is non-Hodgkin lymphoma diagnosed?

In addition to a complete medical history and physical examination, diagnostic procedures for non-Hodgkin lymphoma may include:

• Blood and urine tests

• Lymph node biopsy. A sample of tissue is removed from the lymph node and examined under a microscope. This test is needed to confirm a diagnosis of non-Hodgkin lymphoma. 

• X-rays of the chest. The use of invisible electromagnetic energy beams to produce images of internal tissues, bones, and organs onto film. This test is sometimes done to see if the lymphoma has spread to lymph nodes in the chest. 

• Computed tomography scan of the abdomen, chest, and pelvis (also called a CT or CAT scan). A diagnostic imaging procedure that uses a combination of X-rays and computer technology to produce images (often called slices) of the body. A CT scan shows detailed images of any part of the body, including the bones, muscles, fat, and organs. CT scans are more detailed than general X-rays.

• Positron emission tomography (PET) scan. Radioactive-tagged glucose (sugar) is injected into the bloodstream. Tissues that use the glucose more than normal tissues (such as tumors) can be detected by a scanning machine. The images from a PET scan are not finely detailed like a CT or a MRI scan, but they can show areas of increased cellular activity anywhere in the body, even if they don't show up on other tests. PET scans can be used to find small tumors or to check if treatment for a known tumor is working. Many medical centers now have machines that combine PET and CT scans (PET/CT scanners), which let doctors compare the information from the PET scan with the detailed image of the CT scan.

• Magnetic resonance imaging (also called an MRI scan). MRIs use radio waves and magnets. The energy from the radio waves creates patterns formed by different types of tissue and diseases. This produces detailed cross-sectional pictures that look like slices of the body. This test is helpful in examining the brain and spinal cord. Or it may be used if the results of an X-ray or CT scan aren't entirely clear.

• Ultrasound (also called sonography). A diagnostic imaging technique that uses high-frequency sound waves and a computer to create images of blood vessels, tissues, and organs. Ultrasounds are used to view internal organs as they function, and to assess blood flow through various vessels. 

• Bone marrow aspiration and/or biopsy. A procedure that involves taking a small amount of bone marrow fluid (aspiration) and/or solid bone marrow tissue (called a core biopsy), usually from the hip bones, to be examined for the number, size, and maturity of blood cells and/or abnormal cells. This test is done to see if the lymphoma has reached the bone marrow. 

• Lumbar puncture. A special needle is placed into the lower back, into the spinal canal (the area around the spinal cord). This is done to evaluate central nervous system disease for cancer cells. A small amount of cerebral spinal fluid (CSF) can be removed and sent for testing. CSF is the fluid that bathes the brain and spinal cord.

• Removal of fluids from the chest or abdomen

Treatment of non-Hodgkin lymphoma

Specific treatment for non-Hodgkin lymphoma will be determined by your child's doctor based on:

• Your child's age, overall health, and medical history

• The type, location, and extent of the disease

• Your child's tolerance for specific medications, procedures, or therapies

• The expectations for the course of the disease

• Your opinion or preference

Treatment may include (alone or in combination):

• Chemotherapy

• Radiation therapy

• Surgery

• Monoclonal antibodies

• High-dose chemotherapy with a stem cell transplant

• Antibiotics to prevent or treat infections

• Supportive care for side effects of treatment

• Long-term follow-up care to determine response to treatment, detect recurrent disease, and manage late effects of treatment

Long-term outlook for a child with non-Hodgkin lymphoma

With modern treatments, most children with non-Hodgkin lymphoma can be cured. But the prognosis greatly depends on:

• The type of lymphoma

• The extent of the disease

• The presence or absence of metastasis

• The response to therapy

• Age and overall health of the child

• Your child's tolerance of specific medications, procedures, or therapies

• New developments in treatment

As with any cancer, prognosis and long-term survival can vary greatly from child to child. Every child is unique and treatment and prognosis is structured around the child. Prompt medical attention and aggressive therapy are important for the best prognosis. Continuous follow-up care is essential for the child diagnosed with non-Hodgkin lymphoma. Side effects of radiation and chemotherapy, as well as second malignancies, can occur in survivors of non-Hodgkin lymphoma. New methods are continually being discovered to improve treatment and to decrease side effects.