Diagnosis of childhood non-Hodgkin lymphoma

Diagnosis is the process of finding out the cause of a health problem. Diagnosing childhood non-Hodgkin lymphoma (NHL) usually begins with a visit to your child’s doctor. The doctor will ask about any symptoms your child has and do a physical exam. Based on this information, the doctor may refer your child to a specialist or order tests to check for lymphoma or other health problems.

It’s important for the healthcare team to rule out other reasons for a health problem before making a diagnosis of childhood NHL. If the doctor suspects childhood NHL, your child’s care will be managed by a healthcare team that specializes in caring for children with cancer.

The following tests are usually used to rule out or diagnose childhood NHL. Many of the same tests used to diagnose cancer are used to find out the stage (how much cancer there is, where it is and how far it has spread). Your child’s doctor may also order other tests to check your child’s general health and to help plan their treatment.

Your child’s health history is a record of their symptoms, risk factors and past medical events and problems. The doctor will ask questions about your child’s personal or family history of certain genetic or medical conditions, including:

• a weakened immune system
• ataxia-telangiectasia
• Wiskott-Aldrich syndrome
• X-linked lymphoproliferative syndrome
• Chediak-Higashi syndrome
• severe combined immunodeficiency disorder
• Epstein-Barr virus
• a personal history of certain genetic conditions

A physical exam allows the doctor to look for any signs of childhood NHL. During a physical exam, the doctor may:

• check if any lymph nodes are enlarged (larger than normal)
• feel the abdomen to see if the liver or spleen is larger than normal
• listen to the lungs for any breathing problems
• look for signs of a mediastinal mass (a mass in the chest), such as shortness of breath, especially when lying flat
• look for signs of superior vena cava syndrome (SVCS), such as swelling of the face and neck

SVCS is life-threatening and needs to be treated right away. It occurs when the superior vena cava (the large vein that carries blood from the head, neck, arms and chest to the heart) has a tumour pressing on it. This group of symptoms includes coughing, difficulty breathing, headache, dizziness, fainting and swelling or flushing of the neck, face and upper arms. Find out more about superior vena cava syndrome.

Find out more about physical exams.

A complete blood count (CBC) measures the number and types of white blood cells, red blood cells and platelets. A CBC is done to check for low red blood cell counts (called anemia), which may be more common in children with NHL. Doctors also use the results of a CBC as a baseline that they can check against during treatment.

Find out more about complete blood counts.

Blood chemistry tests measure certain chemicals in the blood. They show how well certain organs are functioning and can help find abnormalities. Blood chemistry tests that may be done include the following.

Uric acid and lactate dehydrogenase (LDH) levels are often elevated in children with NHL. The level of LDH at diagnosis is useful in prognosis in some lymphomas.

Electrolyte levels, such as potassium, calcium and phosphate levels, may be abnormal in childhood NHL.

Kidney function tests, such as blood urea nitrogen (BUN) and creatinine, may be done to show how well the kidneys are working. Higher levels of these substances may mean that the kidneys are not functioning well, which may be caused by the lymphoma.

Liver function tests, such as alanine transaminase (ALT) and alkaline phosphatase (ALP), show how well the liver is working.

Find out more about blood chemistry tests.

An x-ray uses small doses of radiation to make an image of the body’s structures on film. A chest x-ray may be used to check for:

• lymph nodes in the chest that are larger than normal
• a mass in the chest ( mediastinum)
• fluid around the lungs or heart

Find out more about x-rays.

A computed tomography (CT) scan uses special x-ray equipment to make 3D and cross-sectional images of organs, tissues, bones and blood vessels inside the body. A computer turns the images into detailed pictures.

A CT scan may be used to check for enlarged lymph nodes or a mass in the neck, chest, abdomen or pelvis. It also allows doctors to see if any organs or large blood vessels are being compressed and if there is any disease in the brain or near the spinal cord. A CT scan may also be used to see if the cancer has spread to any organs, such as the lungs, liver or spleen.

A CT scan is often combined with a PET scan (called a PET-CT) to get more information about the cancer.

Find out more about CT scans.

A PET scan uses a type of radioactive sugar to look for changes in metabolic activity of body tissues. A computer analyzes the radioactive patterns and makes 3D colour images of the area being scanned.

A PET scan may be used to look for NHL that has spread from where it started to other areas of the body or to measure how well treatment is working. It may be used instead of or in addition to bone scan. It is typically combined with a CT scan for a more complete picture and a 3D assessment of disease.

Your child will not be able to have any food or drink (other than water) on the night before the PET scan.

PET scans may not be available in all cancer treatment centres. Find out more about PET scans.

An ultrasound uses high-frequency sound waves to make images of structures in the body. It may be used to examine the abdomen and organs that may be affected by NHL, such as the kidneys, spleen or liver.

Find out more about ultrasounds.

Magnetic resonance imaging (MRI) uses powerful magnetic forces and radiofrequency waves to make cross-sectional images of organs, tissues, bones and blood vessels. A computer turns the images into 3D pictures.

An MRI can be used to check for enlarged lymph nodes in the chest, abdomen or pelvis. It can also be used to see if the cancer has spread to the brain or spinal cord.

Find out more about MRIs.

During a biopsy, the doctor removes tissues or cells from the body so that they can be tested in a lab. The report from the lab will confirm whether cancer cells are present in the sample.

A biopsy may be done on an enlarged lymph node in the neck, under the arm or in the groin. A biopsy may also be taken from a tumour in the chest or abdomen. Children are usually under a general anesthetic so that the surgeon can get an adequate tissue sample. This requires close assistance of a pediatric anesthesiologist who ensures that sedation is safe in a child suspected to have lymphoma.

The type of biopsy done depends on where the doctors need to collect samples from.

A surgical excisional lymph node biopsy is usually done to collect samples from lymph nodes. The surgeon may do an excisional biopsy, which removes all of a lymph node. In some cases, doctors may use an incisional biopsy to remove part of a lymph node.

A core needle biopsy may be used for some types of tumours, such as a large tumour in the chest or a tumour in the bone. The surgeon may use a CT scan to guide the needle to the tumour during the biopsy.

Find out more about surgical biopsies and core needle biopsies.

During a bone marrow aspiration and biopsy, the doctor removes tissues or cells from the bone marrow so they can be tested in a lab. This test may be used to diagnose and stage childhood NHL that has spread to the bone marrow. Doctors can also use it to tell some types of NHL from acute lymphoblastic leukemia (ALL) or other forms of leukemia.

Find out more about a bone marrow aspiration and biopsy.

A lumbar puncture (spinal tap) removes a small amount of cerebrospinal fluid (CSF) from the spine so it can be looked at under a microscope. It is done to see if childhood NHL has spread to the brain and spinal cord (called the central nervous system, or CNS).

Find out more about lumbar punctures.

Doctors sometimes examine fluid from inside the chest (called pleural fluid) or fluid from inside the abdomen (called peritoneal fluid). They collect the fluid by passing a needle through the skin into the chest or abdomen. The fluid is then looked at under a microscope to check for cancer cells.

Sometimes a tumour in the mediastinum (chest) can block (obstruct) the airway. When this happens, it may be more difficult to perform a biopsy under general anesthesia because of the risk of breathing difficulty. In this case, doctors may try to use a less invasive procedure to diagnose NHL, such as biopsy of a lymph node, bone marrow biopsy, thoracentesis or paracentesis. A pediatric anesthesiologist is almost always involved.

A thoracentesis is done to remove fluid from the chest. A paracentesis is used to remove fluid from the abdomen. Find out more about a thoracentesis and a paracentesis.

Doctors can use the following types of cell and tissue studies to diagnose childhood NHL.

Cytogenetics is the analysis of a cell’s chromosomes, including their number, size, shape and arrangement. Cytogenetic techniques show chromosomal abnormalities, which help doctors confirm the diagnosis and identify the type or subtype of lymphoma. The results of cytogenetic studies also help doctors plan treatment and predict how well the treatment will work.

Some major chromosomal abnormalities can be found by looking at cells under a microscope. But most changes in DNA are subtler and can only be found with a closer analysis using molecular techniques. These molecular techniques include:

Fluorescence in situ hybridization (FISH) is a molecular genetic test. It is used to identify specific chromosomal abnormalities and other genetic changes in cancer cells.

Polymerase chain reaction (PCR) is a method used to make many copies of a particular gene segment so that it can be tested in the lab.

Immunophenotyping is the study of proteins expressed by cells. It uses a very specific antigen-antibody reaction to identify specific proteins in tissues or cells. It uses antibodies marked with a fluorescent label that bind only to specific proteins. The fluorescent label and the pattern of proteins that are expressed allow doctors to identify the lymphoma cells so that they can diagnose the specific type or subtype of NHL.

The following methods are the most commonly used in immunophenotyping.

Immunohistochemistry uses a microscope to view the fluorescent labels. It also allows doctors to look at cells and their surroundings.

Flow cytometry is a technique used to sort and classify cells by their cell surface proteins. The cells are labelled with fluorescent tracers and then can be sorted to look at many different cell surface proteins at the same time. The cells are exposed to a laser, which makes them give off a light. A computer measures and analyzes the light. This allows the computer to quickly collect data from thousands of cells in a single sample.

A bone scan uses bone-seeking radioactive materials (called radiopharmaceuticals) and a computer to create a picture of the bones. It is used to see if childhood NHL has spread to the bones (called bone metastasis). This test is not needed for all types of lymphoma and may not be needed if PET scan is being used.

Bone metastasis is not common in children with NHL, so this test is usually only done if the child has bone pain or if blood tests suggest a problem with the bones. PET scans have now replaced bone scans in many centres.

Find out more about bone scans.

To make the decisions that are right for your child, ask the healthcare team questions about a diagnosis.