Patient Care

Lymphoma (Children)

What Is Lymphoma in Children?

Lymphomas are malignant neoplasms (tumours that tend to grow, invade and spread) of the lymphoid lineage. A Lymphoma refers to a group of cancers of the lymph system which is part of the body's immune system. The immune system protects the body from foreign substances, infection and diseases. The lymph system is made up of lymph nodes, the spleen and the thymus (which produce and store infection-fighting cells) as well as other body areas that have collections of white blood cells within them such as the tonsils, stomach, small intestine and skin. Lymphoma affects a type of white blood cells known as lymphocytes. It occurs when lymphocytes grow and multiply uncontrollably.

Lymphoma can be broadly classified as either Hodgkin Lymphoma (Hodgkin's disease), or as non-Hodgkin Lymphoma. They can present in similar ways but are very different in the way they spread around the body, affect the body and respond to treatment. The presence of an abnormal cell called a Reed-Sternberg cell means it is Hodgkin Lymphoma while the absence means it is non-Hodgkin Lymphoma. Lymphoma, both Hodgkin lymphoma and non-Hodgkin Lymphoma combined, is the third most common cancer in children.

Hodgkin Lymphoma

Hodgkin Lymphoma is classically described as a B-lineage Lymphoma, characterised by the existence of Reed-Sternberg cells and lymphocytic infiltration (red patches and lumps on the face and body). Infections with the Epstein-Barr virus have also been implicated in the development of Hodgkin Lymphoma along with autoimmunity and immunodeficiency.

Hodgkin Lymphoma has a unique bimodal age distribution that differs geographically, meaning that there are two different peak periods during which a person may contract the disease. In developed countries such as Singapore, the early peak occurs in the mid to late 20s and the second peak occurs after the age of 50. The difference in developing countries is that the early peak occurs before adolescence (before 12 or 13 years old).

There are two major types of childhood Hodgkin Lymphoma:

1. Classical Hodgkin Lymphoma

There are four major sub-types in classical Hodgkin Lymphoma which are based on how the cancer cells look under a microscope:

  • Lymphocyte-rich classical Hodgkin Lymphoma
  • Nodular sclerosis Hodgkin Lymphoma
  • Mixed cellularity Hodgkin Lymphoma
  • Lymphocyte-depleted Hodgkin Lymphoma

2. Nodular lymphocyte-predominant Hodgkin Lymphoma

Non-Hodgkin Lymphoma

Non-Hodgkin Lymphoma can generally occur at any time throughout childhood and adolescence but is more commonly found in young children below 10 years of age as compared to Hodgkin Lymphoma.

There are three major types of non-Hodgkin Lymphoma found in children – mature B-cell Lymphoma, precursor lymphoid Lymphoma and mature T-cell Lymphoma.

Mature B-cell Lymphoma

This is the most common type of non-Hodgkin Lymphoma which involves the B-lymphocytes of the immune system. These Lymphomas make up about 40% of non-Hodgkin lymphoma cases1. Children with this type of non-Hodgkin Lymphoma usually have enlarged lymph nodes in the throat, neck or in the abdomen. It may be found in the bones or bone marrow. There are three major subtypes:

  • Burkitt's Lymphoma (BL)
  • Diffuse large B-cell Lymphoma (DLBCL)
  • Primary mediastinal B-cell Lymphoma (PMBL)

Mature B-cell Lymphoma develops from B-cells in the mediastinum (the area behind the breastbone). It may spread to nearby organs including the lungs and the sac around the heart. It may also spread to lymph nodes and distant organs including the kidneys. This Lymphoma occurs more frequently in older adolescents.

Precursor Lymphoid Lymphoma

Precursor Lymphoid Lymphoma, also known as Lymphoblastic Lymphoma, refers to either T-cell or B-cell and accounts for about 30% of non-Hodgkin Lymphoma in children1. It can cause swollen lymph nodes or glands in any part of the body. Some children with Lymphoblastic Lymphoma may have a large mass (tumour) in the mediastinum. Lymphoblastic Lymphoma can also invade the bone marrow or spinal fluid.

If there are more than 25% blasts in the bone marrow by convention, it is defined as Acute Lymphoblastic Leukaemia (ALL).

Mature T-cell Lymphoma

Anaplastic Large Cell Lymphoma (ALCL) and Peripheral T-cell Lymphoma (PTCL) make up the mature T-cell Lymphomas but PTCL is very rare. ALCL commonly involves lymph nodes and glands but may also occur in bones and primary organs. About 10% of childhood non-Hodgkin Lymphoma is caused by ALCL2. ALCL may also cause rashes or lumps in the skin. It is often rapidly growing and causes severe inflammation in the body. As a result, the child may have symptoms such as high fevers or loss of weight and appetite.

There is no known cause of Lymphoma in children. However, certain risk factors may cause a child to be more vulnerable and thus contract Lymphoma.

Children who are born with or acquire conditions that affect the immune system are more likely to develop Lymphoma. Having a sibling with Lymphoma also slightly raises a child's risk. Prior infection with the Epstein-Barr virus is also associated with a greater risk for Lymphoma. There are no known environmental toxins that increase the risk of Lymphoma in children.

Source: 1Principles and Practice of Paediatric Oncology (7th Edition), 2American Cancer Society

What are the signs & symptoms of Lymphoma in Children?

Lymphoma can present in various ways which can make diagnosis challenging at times. There may be no symptoms or signs until the Lymphoma is quite large or has spread around the body.

The symptoms of Hodgkin Lymphoma tends to be more straightforward. Patients, usually adolescent males, typically come with fevers, cervical lymph node enlargement and possibly some night sweats and loss of weight and appetite.

Non-Hodgkin Lymphoma is slightly trickier compared to Hodgkin Lymphoma as its presentation can be slightly more varied. It ranges from non-specific symptoms like loss of appetite and weight to abdominal pain and swellings, non-specific skin lumps and rashes as well as cough with shortness of breath.

A child who displays these symptoms may have Lymphoma:

  • Fevers
  • Loss of appetite and loss of weight that cannot be explained
  • Night sweats
  • Enlarged lymph nodes (seen or felt as lumps under the skin)
  • Shortness of breath or cough
  • Fatigue (extreme tiredness)

Due to this varied presentation, Lymphoma is often first diagnosed as something else. Multiple tests are performed before the diagnosis is reached. For example, there are instances where a child with Lymphoma is being treated for tuberculosis because of the fever and cough. A child with pain from a fall is sometimes treated for a fracture when there is an underlying Lymphoma. There were also children who only had abdominal pain and were treated for constipation for a long time before their diagnosis surfaced.

How is Lymphoma in Children diagnosed?

Tests and procedures that may be carried out include the following:

Blood Tests

These include tests to examine the blood and marrow profile. Other additional tests may include biochemistry and liver function tests.

For children with Lymphoma, they often have an inflammatory picture on their full blood count (FBC). This is associated particularly with certain types of Lymphoma such as Hodgkin Lymphoma, ALCL, BL and DLBCL.

An inflammatory picture on the FBC may present as elevated leukocyte count, elevated neutrophils, elevated eosinophils, lymphopenia, elevated platelet count or anaemia.

Imaging Studies
  • X-ray of the chest
  • Computed Tomography (CT) scan
  • Positron Emission Tomography (PET) scan - A small amount of radioactive glucose (sugar) is injected into a vein to test for malignant tumour cells in the body. These cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.
Other Additional Tests
  • Lumbar puncture: The removal of some spinal fluid to test for involvement of the central nervous system.
  • Bone marrow aspiration and trephine biopsy: The removal of bone marrow and a small piece of bone by inserting a hollow needle into the hipbone or breastbone.
  • Directed biopsy: A sample of the tissue (biopsy) will be taken depending on where the rash, lump, or lymph node is.
What are the treatment options for Lymphoma?

The following are the treatment options for Lymphoma.


Chemotherapy is the mainstay of cancer treatment, including Lymphoma. The medications are very effective in killing cancer cells or stopping them from growing or dividing but there are side effects involved. These medications are usually injected into the bloodstream but some may be given by mouth. A combination therapy of various chemotherapy drugs are usually employed at the same time. The duration of treatment depends on the type and stage of cancer.

Please approach your paediatrician specialising in oncology if you have questions regarding chemotherapy and its side effects such as hair loss and future fertility problems.

Radiation Therapy

Radiation therapy uses high-energy X-rays or other types of radiation to kill cancer cells or stop them from growing. The side effect of radiation therapy is that it may disrupt the growth of bones and soft tissues in young children. It may also increase the risk of heart disease and second cancers as patients grow older. Radiation therapy is not commonly used for treating children with Hodgkin Lymphoma.


There is often no specific tumour site for Lymphoma since it spreads throughout the lymph system. However, large numbers of Lymphoma cells may collect in one area for some children. In this case, doctors may suggest surgery to remove the tumour.

Targeted Therapy

Targeted therapy is increasingly popular as it is effective in the treatment of advanced Lymphomas and also those that are resistant to treatment. Targeted therapy fights cancer by finding a specific substance (target), such as a protein on cancer cells or a substance that helps cancer grow, without harming normal cells. Different targeted therapies work in different ways.

An example of this include using Brentuximab, which is an anti-CD30 antibody-drug conjugate. This medication seeks out CD30, a target found on Lymphoma cells, and delivers chemotherapy drug only to these cells.

Crizotinib, an anti-Anaplastic Lymphoma Kinase (ALK) inhibitor, is used as upfront therapy to target ALK-positive ALCL for high-risk cases.

Stem Cell Transplant

High-dose chemotherapy treats tumours more effectively than lower-dose chemotherapy but the drugs will damage the bone marrow's ability to make new blood cells. If the Lymphoma is difficult to treat or returns after receiving chemotherapy, high doses of chemotherapy may be suggested followed by a transplant of the child's own blood-forming (haematopoietic) stem cells. This is called an autologous transplant. Before high-dose chemotherapy starts, doctors will remove stem cells from the child, after which they are frozen and stored, and subsequently returned to the child's body through a vein.

In some cases, a donor's stem cells may be required. This is called an allogeneic transplant and it may be recommended if the child's Lymphoma relapses or has failed autologous stem cell transplant.

Caring for children with Lymphoma?

During treatment, follow-up care is essential. The follow-up routine will depend on the child's cancer and the treatments. Children under treatment may be followed up weekly to monthly.

Follow-up care is also required for all children with cancer after their treatment ends. The follow-up visits generally happen about every three months for the first year, then twice a year for the next year. After that, the child may have one follow-up visit each year.

During these visits, blood tests and possibly imaging tests such as PET-CT scans will be scheduled to ensure that there is no recurrence of the lymphoma. We will also look for late effects of cancer treatment such as growth and hormone disturbances as well as problems with various body organ functions in the liver, kidney, lung and heart.

Source: 3National Cancer Institute

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