Lymphoma
The Children’s Mercy Leukemia and Lymphoma Program has compiled the following information for families who want to better understand the types, causes and treatments for lymphoma. You can also visit the Children’s Mercy Health Library or the Leukemia and Lymphoma Society for more information.
What is lymphoma?
Lymphoma is a cancer of the lymph nodes. Lymph nodes are part of the immune system and are located throughout the body.
Normal lymph nodes are usually less than 1 or 1.5 cm in size, depending on where they are located. In lymphoma, cells within the lymph nodes become malignant and cause the lymph node to grow in size. Often, when lymphoma is diagnosed in children and adolescents, it has spread to multiple lymph nodes.
Causes of lymphoma
Lymphoma is caused by genetic mutations that occur in a single cell that result in the loss of normal function and cause the cell to grow and divide very rapidly. In the majority of cases, these mutations occur randomly and are not inherited from family members. In most cases of childhood lymphoma, no cause can be found.
Risk factors
There are a few things that can place a child at increased risk for lymphoma. Defects in the immune system can place children at increased risk for several types of lymphoma. Immunosuppressive medications can also place children at risk for lymphoma, including those used after solid organ transplantation.
Symptoms of lymphoma
The most common symptom in lymphoma is one or more enlarged lymph nodes. These are typically not painful and are found most frequently in the neck, under the arm or in the groin, although they can be found anywhere.
Certain types of lymphoma can present with large masses in the chest or the abdomen. When this occurs, symptoms may be caused by pressure of the tumor on other organs and can include difficulty breathing, coughing, abdominal pain, vomiting and swelling. Children with lymphoma sometimes have other symptoms such as fever, fatigue, night sweats or weight loss.
Lymphoma diagnosis
Lymphoma is most often diagnosed from a lymph node biopsy. In most cases, the entire lymph node is removed and examined. Blood tests, bone marrow aspiration, and imaging tests may also be used to confirm the diagnosis.
Types of lymphoma
Hodgkin Lymphoma
Hodgkin lymphoma makes up almost half of all childhood lymphomas and 6% of all children diagnosed with cancer. Hodgkin lymphoma is typically diagnosed in older children and adolescents.
The first sign of Hodgkin lymphoma is usually an enlarged, non-tender lymph node. The most frequent location is the neck, but lymph nodes can also be found under the arm, above the clavicle or in the groin.
In most cases of Hodgkin lymphoma, multiple lymph node sites are involved, including lymph nodes in the chest that can be seen using an X-ray. In some cases, patients with Hodgkin lymphoma can also have ‘B’ symptoms. These include fever, drenching night sweats and significant weight loss.
There are multiple pathologic subtypes of Hodgkin, including nodular sclerosing (most common), mixed cellularity, lymphocyte-rich, lymphocyte-depleted and nodular lymphocyte-predominant. Except for nodular lymphocyte-predominant, the other subtypes are collectively referred to as Classical Hodgkin lymphoma and treated in the same manner.
Nodular lymphocyte-predominant Hodgkin lymphoma is associated with an excellent outcome and low stage at diagnosis. Patients with this subtype of lymphoma can be cured with surgery alone, if the lymphoma is isolated to a single lymph node that can be removed.
Classical Hodgkin lymphoma is curable for most children and adolescents using chemotherapy and radiation therapy. In select cases, radiation therapy can be avoided if the lymphoma responds well to chemotherapy and there are no other high-risk features.
Despite very high cure rates, the treatment for Hodgkin lymphoma is associated with infrequent but important long-term effects. These include chronic heart or lung damage, loss of fertility and an increased risk of developing a second cancer related to treatment, including thyroid and breast cancer.
Non-Hodgkin Lymphoma (NHL)
NHL includes a number of different lymphomas with some similar characteristics. In total, NHL makes up slightly more than half of all childhood lymphoma, and 7% of all childhood cancer. In the United States, approximately 800 children are diagnosed with NHL each year. There are five main types of NHL that are seen in children.
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Burkitts Lymphoma (BL): BL makes up about 40% of NHL in children. BL tends to be a very fast growing cancer and symptoms often develop very quickly. It can be present anywhere in the body at diagnosis including the central nervous system and the bone marrow. BL is very susceptible to most chemotherapy and cure rates exceed 90%.
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Lymphoblastic Lymphoma (LL): LL makes up about 30% of NHL seen in children. When children are diagnosed with LL, they often have multiple large lymph nodes, an enlarged spleen and can have a large mass in the chest than can cause difficulty breathing. Treatment for LL is nearly identical to the treatment of acute lymphoblastic leukemia and cure rates are high at around 90%.
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Diffuse Large B Cell Lymphoma (DLBCL): DLBCL makes up about 20% of NHL in children. It can present with enlarged lymph nodes anywhere throughout the body. DLBCL is similar to Burkitts lymphoma but tends to progress more slowly. Treatment is the same as for Burkitts with survival rates that exceed 90%.
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Anaplastic Large Cell Lymphoma (ALCL): ALCL makes up about 10% of childhood NHL. Symptoms at diagnosis range from simply having an enlarged lymph node to a more widespread illness that can involve multiple lymph nodes, the soft tissue and the skin. ALCL rarely spreads to the central nervous system. Treatment includes chemotherapy only and cure rates are about 70%.
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Primary Mediastinal B-Cell Lymphoma (PMBCL): PMBCL is a rare type of NHL diagnosed in children that typically presents with a large chest mass. Patients with PMBCL are treated with a unique chemotherapy regimen adopted from adult patients.
Lymphoma staging
Hodgkin Lymphoma
Hodgkin lymphoma is slowly progressive and has frequently spread to multiple lymph nodes at the time of diagnosis. Involvement of other organs, including the bone marrow, is rare.
Hodgkin lymphoma is staged using the Ann Arbor staging criteria:
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Stage I: Involvement of a single lymphatic site, or localized involvement of a single extralymphatic organ or site in the absence of any lymph node involvement
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Stage II: Involvement of two or more lymph node regions on the same side of the diaphragm; or localized involvement of a single extralymphatic organ or site in association with regional lymph node involvement with or without involvement of other lymph node regions on the same side of the diaphragm
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Stage III: Involvement of lymph node regions on both sides of the diaphragm, which also may be accompanied by extralymphatic extension in association with adjacent lymph node involvement or by involvement of the spleen or both.
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Stage IV: Diffuse or disseminated involvement of one or more extralymphatic organs, with or without associated lymph node involvement; or isolated extralymphatic organ involvement in the absence of adjacent regional lymph node involvement, but in conjunction with disease in distant site(s). Stage IV includes any involvement of the liver or bone marrow, lungs (other than by direct extension from another site), or cerebrospinal fluid.
In addition to the staging, the following designations can be applicable to any stage:
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A: No symptoms
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B: Fever (temperature >38⁰C/100.4⁰F), drenching night sweats, unexplained loss of >10% of body weight within the preceding 6 months
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E: Involvement of a single extranodal site that is contiguous or proximal to the known nodal site
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S: Involvement of the spleen
Non-Hodgkin Lymphoma (NHL)
NHL is typically fast growing and often presents with multiple tumors. Involvement of organs in addition to lymph nodes is not uncommon. The presence of cancer in the central nervous system or bone marrow is more likely to occur than with Hodgkin lymphoma. NHL is staged using the St. Jude or Murphy staging criteria:
Stage I:
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A single tumor (not a lymph node) or involvement of a single anatomic area (lymph node), with the exclusion of chest and abdomen
Stage II:
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Single tumor (extranodal) with regional node involvement
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Two or more nodal areas on the same side of the diaphragm
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Two single (extranodal) tumors, with or without regional node involvement on the same side of the diaphragm
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Primary gastrointestinal tumor, with or without involvement of associated mesenteric nodes that is completely resectable
Stage III:
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Two single tumors (extranodal) on opposite sides of the diaphragm
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Two or more nodal areas above and below the diaphragm
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Any primary intrathoracic tumor
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Extensive primary intra-abdominal disease
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Any tumor near the spine, whether or not other sites are involved
Stage IV:
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Any of the above findings with initial involvement of the central nervous system, bone marrow, or both
Lymphoma treatment
Lymphoma treatment is based on the type of lymphoma that is diagnosed. For classical Hodgkin lymphoma, the intensity and length of treatment is based upon several factors, including the lymphoma stage, presence of B symptoms, and the size and location of the tumor(s).
Hodgkin lymphoma treatment
Historically, treatment for Hodgkin lymphoma has included chemotherapy and radiation therapy. Due to the excellent survival (>90%) of children and adolescents with Hodgkin lymphoma, recent efforts have focused on decreasing the long-term side effects related to therapy. This has been done by reducing the amount of radiation used, eliminating radiation therapy for select patients that have a rapid response to chemotherapy and avoiding or minimize certain chemotherapy drugs that are known to cause harmful side effects.
Patients with nodular lymphocyte-predominant Hodgkin lymphoma have excellent outcomes. In some cases where the lymphoma has been completely removed by surgery, no further treatment is needed and most patients will not have a recurrence of lymphoma. For patients that still have disease following surgery, or have their lymphoma return after their surgery, a short course of chemotherapy will result in cure for nearly all patients. Radiation therapy is not typically used for this subtype of Hodgkin lymphoma.
For patients with Hodgkin lymphoma that relapses, cure remains a realistic goal. Treatment includes chemotherapy with a goal of a second remission, radiation therapy if it was not administered as part of initial therapy, followed by an autologous bone marrow transplant. Newer agents such as brentuximab vedotin and nivolumab are being evaluated as less toxic alternatives to aggressive chemotherapy in relapsed Hodgkin lymphoma.
Non Hodgkin lymphoma treatment
For children and adolescents with NHL, treatment is dependent on the specific lymphoma subtype. Mature B-cell lymphomas (Burkitt lymphoma and DLBCL) are treated using intensive chemotherapy for a short duration of time. In rare cases, patients with an abdominal tumor that is completely removed by surgery can be treated with very little chemotherapy and still have excellent outcomes.
Lymphoblastic lymphoma is treated with the same regimens that are used to treat ALL in children and include several months of intensive chemotherapy followed by an extended maintenance phase of chemotherapy that lasts nearly two years. Burkitt lymphoma, DLBCL and lymphoblastic lymphoma all require additional chemotherapy treatment of the central nervous system (CNS) due to the risk of experiencing a relapse in this location. ALCL is treated with intensive chemotherapy and requires minimal CNS treatment. Radiation therapy is not routinely used for NHL in children and adolescents as part of initial treatment.
Treatment for relapse of NHL is variable and depends on the NHL subtype and several other factors. Often, chemotherapy will be used first and then patients will receive a BMT once they are in remission.
Hodgkin lymphoma: Magnus' story
Meet Magnus, a 10-year-old battling Hodgkin lymphoma. This cancer journey is told from a perspective we don't get too often — his.
#MagnusStrong
Hodgkin lymphoma: Pepito's story
Three-year-old Pepito has Hodgkin lymphoma, a cancer rarely found in children his age. Alan Gamis, MD, a pediatric oncologist at Children’s Mercy, prescribes chemotherapy and radiation to shrink the softball-sized tumor in his neck, and stop the cancer in its tracks.
Late effects of lymphoma treatment
Since children and adolescents diagnosed with lymphoma have very good survival rates, we are learning a great deal about the impact that treatment can have later on in life.
Secondary cancers
Radiation therapy is known to cause secondary cancers, and patients treated decades ago for Hodgkin lymphoma have very high rates of cancer as adults, including breast and thyroid cancer. Current treatment regimens use significantly less radiation and in some cases, no radiation treatment is recommended for patients who have a good response to chemotherapy.
Medication side effects
Doxorubicin, which is used in most treatment plans, increases the risk of heart failure and coronary artery disease decades after treatment, especially when given in combination with chest radiation therapy. Dexrazoxane is a medication that may be used to reduce the risk of heart toxicity if large doses of doxorubicin are needed for treatment. Bleomycin is commonly used for the treatment of Hodgkin lymphoma and may affect the function of the lungs.
Fertility
Fertility can be impacted by chemotherapy and regimens have been developed for younger patients with Hodgkin lymphoma to reduce or eliminate certain chemotherapy medications that can impact fertility. In some cases, fertility preservation is an option prior to starting treatment.
Survive & Thrive Program
Read more about how Children’s Mercy helps to monitor and care for children for many years after their cancer treatment through the Survive & Thrive Program.