Childhood Leukemia and Lymphoma Diagnosis and Staging

April 26, 2024 
This page was reviewed under our medical and editorial policy by Lindsey Murphy, M.D., Pediatric Hematologist-Oncologist and Assistant Professor in the Department of Pediatrics, City of Hope Duarte

Childhood leukemia and lymphoma are diagnosed using various tests. While physical examination and blood test results may raise suspicion, a bone marrow test is often needed to diagnose childhood leukemia. For pediatric lymphoma, a lymph node biopsy is the definitive test to confirm a diagnosis. These tests are necessary, as many clinical signs and patient symptoms of childhood leukemia and lymphoma mirror those in other conditions.

Once a diagnosis is made, additional tests may be done to learn more about the characteristics of the cancer cells and the stage of disease. As soon as all this information is collected, the care team will explain the stage and what it means for the child’s treatment approach and outlook.

How Are Childhood Leukemia and Lymphoma Diagnosed?

For childhood leukemia and lymphoma, the diagnostic and staging process may include those listed below.

Physical exams: These office procedures are used in both childhood leukemia and childhood lymphoma testing. The doctors look for enlargement in the lymph nodes, spleen and liver, signs of infection, or areas with bleeding or bruising.

A medical history: Doctors collect patient information and health histories early on in both childhood leukemia and lymphoma testing. The doctor will try to learn about exposure to possible risk factors, such as genetic syndromes or immune system problems for suspected leukemia, or a weakened immune system or an Epstein-Barr virus infection for suspected lymphoma.

Blood tests: These are conducted for both childhood leukemia and lymphoma to look for abnormalities, but these tests alone do not diagnose these conditions. Only in some cases where leukemia cells have moved beyond the bone marrow and into the blood may leukemia cells be directly detected in blood tests.

A complete blood count (CBC) is a common test used to determine how many of each type of cell is in the blood. In children with leukemia, most will have too many white blood cells and too few red blood cells or platelets. Blood smears, which involve doctors looking at a blood sample under a microscope, are also examined for abnormal blood counts and changes in the blood cells’ appearance. The results of these tests may lead to a suspicion of leukemia.

Blood tests do not diagnose childhood lymphoma, but they may be performed to get a picture of what’s happening in the body and see if lymphoma is growing in the bone marrow. A blood measurement of lactate dehydrogenase (LDH) levels, which are usually high in aggressive lymphoma cases, may also be helpful. After diagnosis, blood may also be checked for liver and kidney problems associated with lymphoma and viruses such as HIV, hepatitis or Epstein-Barr. Doctors may also check for proper blood clotting.

These blood tests are followed up by bone marrow or lymph node biopsy examinations.

Lymph node biopsy: When diagnosing childhood lymphoma, doctors may use a surgical or needle biopsy to remove part of a lymph node for testing. A surgical biopsy involves an incision, and a needle biopsy uses a small needle to take out a piece of tissue without the need for general anesthesia. In some cases, the doctor may use a computed tomography (CT) scan to guide a needle biopsy to reach lymph nodes or tumors deep within the body. This is called a CT-guided biopsy.

Lymph node biopsies are not often used to diagnose childhood leukemia, as bone marrow tests are a more appropriate way to identify the disease.

Bone marrow tests: If childhood leukemia is suspected, a bone marrow aspiration and biopsy is performed to make a diagnosis. A bone marrow aspiration test uses a thin needle to remove a small amount of liquid marrow from the bone. Then, a larger needle is used to remove a small piece of bone and marrow for the biopsy. Both samples are usually taken from the back of the child’s pelvic (hip) bone. All the samples are sent to a laboratory for analysis.

Although these tests aren’t used to initially diagnose childhood lymphoma, they may be used after diagnosis to determine if the lymphoma has reached the bone marrow.

Lumbar puncture: Also known as a spinal tap, this test helps to identify lymphoma or leukemia cells that may have spread to the brain and spinal cord fluid (cerebrospinal fluid). A small needle is inserted into the space between the bones of the lower spine, and fluid is drawn out for laboratory testing.

Chromosome and protein tests: Chromosome testing may be used when diagnosing and classifying the type of childhood leukemia and lymphoma. These tests check for too few, too many or altered chromosomes. This testing may be done using:

• Fluorescent in situ hybridization (FISH) to examine chromosomes with fluorescent dye
• Polymerase chain reaction (PCR) to find tiny gene changes that are not visible with a microscope

Other tests on blood and bone marrow samples, including flow cytometry and immunohistochemistry, help to classify both conditions. For these tests, the samples are treated with antibodies to look for certain proteins on the cells that help to identify its subtype and other cell characteristics.

Imaging tests: Imaging tests, such as X-rays, computed tomography (CT) scans, magnetic resonance imaging (MRI), ultrasounds and positron emission tomography (PET) scans, may be used for childhood leukemia and lymphoma, although for slightly different purposes. Because childhood leukemia does not form solid tumors, imaging tests might be used to look for secondary problems, such as a lung infection, that may be related to the cancer. They may also detect enlarged organs, such as the liver or spleen, where leukemia cells may be collecting. For childhood lymphoma, these scans may be used to determine the stage of the cancer, check for cancer-related symptoms, and verify that treatment is working.

Bone scans are not used often for childhood leukemia or childhood lymphoma. However, if the patient has bone pain and lab tests show that the cancer may have reached the bone, a bone scan may be recommended. Test results may show bone damage from childhood lymphoma, but they are not definitive. Additional testing is needed to verify the results of a bone scan in some cases.

Staging Childhood Leukemia and Lymphoma

Childhood leukemia does not have a traditional staging system. Instead, doctors use phases to describe its activity in response to treatment.

In cases of childhood lymphoma, the International Pediatric Non-Hodgkin Lymphoma Staging System (IPNHLSS) is used, as well as a four-stage system for childhood Hodgkin lymphoma.

Phases of Childhood Leukemia

The phases of childhood leukemia for the most common forms of leukemia in children — acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML) — are listed below.

Untreated: Newly diagnosed cancer

Remission: Cancer has responded to treatment with near-normal body function levels

Recurrent: Cancer has returned after remission

Refractory: Cancer is resistant to treatment and does not go into remission

There are also several subtypes of ALL and AML that help to classify leukemia further.

Chronic myeloid leukemia (CML), a less common and slower-growing leukemia in children, is described by the three phases below.

Chronic: Mild symptoms (if any) are present, and this early phase usually responds well to standard treatments.

Accelerated: Symptoms may include fever, night sweats, poor appetite and weight loss. This phase is more challenging to treat compared to the chronic phase.

Blast (also called acute phase or blast crisis): Symptoms may include fever, poor appetite and weight loss. Leukemia cells have spread beyond the bone marrow, and they behave like an acute leukemia.

Stages of Childhood Lymphoma

The stages of childhood non-Hodgkin lymphoma are listed below.

Stage 1: The lymphoma is in one place, as a single tumor or in one group of lymph nodes (not in the chest or abdomen).

Stage 2: The lymphoma is not in the chest and may present as one of the following:

• A single tumor that has spread to nearby lymph nodes in one part of the body
• Multiple sets of cancerous lymph nodes that are all located either above or below the diaphragm
• Operable cancer in the digestive tract that may or may not have spread to lymph nodes

Stage 3: Lymphoma appears in one of the following ways:

• Originates in the chest, often the lining of the lungs
• Begins in the abdomen and becomes too widespread to be removed by surgery
• Resides next to the spine
• Presents as multiple tumors outside of the lymph nodes above and below the diaphragm (possibly in the bones and skin)
• Inhabits more than one set of lymph nodes above and below the diaphragm
• Shows up as a single tumor in a bone as well as the nearby area

Stage 4: Lymphoma is found in the brain and spinal cord and/or bone marrow.

Childhood Hodgkin lymphoma is categorized into the four stages listed below.

Stage 1 (divided into Stage 1 and Stage 1E): The cancer is located in one or more lymph nodes in a single group of lymph nodes, in the thymus, spleen or Waldeyer’s ring, or outside of the lymph system (Stage 1E).

Stage 2 (divided into Stage 2 and Stage 2E): Lymphoma appears in two or more groups of lymph nodes above or below the diaphragm, or spreads to a nearby organ outside of the lymph system (Stage 2E).

Stage 3: Cancer presents in either:

• Lymph node groups both above and below the diaphragm
• Lymph node groups in the spleen and above the diaphragm

Stage 4: Lymphoma appears in four different variations:

• Spread to one or more organs outside the lymph system
• Resides in two or more groups of lymph nodes on one side of the diaphragm and in one organ outside of the lymph system
• Located in multiple groups of lymph nodes on both sides of the diaphragm and in an organ outside of the lymph system
• Found in lungs, liver or bone marrow far from the place of origin