Melanoma, although rare, is the most common skin cancer in children, followed by basal cell carcinomas and squamous cell carcinomas.[
Approximately 400 cases of melanoma are diagnosed each year in patients younger than 20 years in the United States, accounting for less than 1% of all new cases of melanoma.[
Melanoma accounts for about 4% of all cancers in children aged 15 to 19 years.[
The incidence of pediatric melanoma increased by an average of 1.7% per year between 1975 and 1994,[
Conditions associated with an increased risk of developing melanoma in children and adolescents include the following:
Patients with central nervous system melanoma arising in the context of congenital melanocytic nevi syndrome have a poor prognosis, with 100% mortality. Most of these patients will have NRAS mutations; therefore, there is potential rationale for treatment with mitogen-activated protein kinase pathway inhibitors. Transient symptomatic improvement was noted in four children receiving a MEK inhibitor, but all patients eventually died from disease progression.[
Phenotypic traits that are associated with an increased risk of melanoma in adults have been documented in children and adolescents with melanoma and include the following:[
A multinational consortium performed a retrospective review of germline variants in the MC1R gene.[
Familial melanoma comprises 8% to 12% of melanoma cases. p16 germline mutations have been described in up to 7% of families with two first-degree relatives with melanoma and in up to 80% of families having one member with multiple primary melanomas.[
In a prospective study of 60 families who had more than three members with melanoma,[
Pediatric melanoma shares many similarities with adult melanoma, and the prognosis is dependent on stage.[
The outcome for patients with nodal disease is intermediate, with about 60% expected to survive long term.[
Children younger than 10 years who have melanoma often present with poor prognostic features, are more often non-White, have head and neck primary tumors, thicker primary lesions, a higher incidence of spitzoid morphology vascular invasion and nodal metastases, and more often have syndromes that predispose them to melanoma.[
The use of sentinel lymph node biopsy for staging pediatric melanoma has become widespread, and the thickness of the primary tumor, as well as ulceration, have been correlated with a higher incidence of nodal involvement.[
The association of thickness with clinical outcome is controversial in pediatric melanoma.[
The European Cooperative Study Group for Pediatric Rare Tumors within the PARTNER project (Paediatric Rare Tumours Network - European Registry) has published recommendations for the diagnosis and treatment of children and adolescents with cutaneous melanoma. Some of these recommendations have been incorporated and summarized in the sections below.[
The diagnostic evaluation of melanoma includes the following:
The role of complete lymph node dissection after a positive sentinel node and the value of adjuvant therapies in these patients is discussed in the Treatment of Childhood Melanoma section of this summary.
Patients who present with conventional or adult-type melanoma should undergo laboratory and imaging evaluations on the basis of adult guidelines (refer to the Stage Information for Melanoma section in the PDQ summary on adult Melanoma Treatment for more information). In contrast, patients who are diagnosed with spitzoid melanomas have a low risk of recurrence and excellent clinical outcomes and do not require extensive radiographic evaluation either at diagnosis or follow-up.[
The diagnosis of pediatric melanoma may be difficult, and many of these lesions may be confused with the so-called melanocytic lesions with unknown malignant potential.[
Melanoma-related conditions with malignant potential that arise in the pediatric population can be classified into the following three general groups:[
The genomic characteristics of each tumor are summarized in Table 1.
The genomic landscape of conventional melanoma in children is represented by many of the genomic alterations that are found in adults with melanoma.[
The genomic landscape of spitzoid melanomas is characterized by kinase gene fusions involving various genes, including RET, MAP3K8, ROS1, NTRK1, ALK, MET, and BRAF.[
Large congenital melanocytic nevi are reported to have activating NRAS Q61 mutations with no other recurring mutations noted.[
Accurate diagnosis of pediatric melanocytic lesions, especially those categorized as Spitz lesions, is challenging. Morphological assessment alone has significant limitations, with low interobserver expert agreement.[
Integrating genomic analysis in the evaluation of pediatric melanocytic lesions can optimize diagnostic accuracy and provide important prognostic information for the treating physician. In a prospective registry of 70 patients with pediatric melanocytic lesions, the use of an integrated clinicopathological and genomic assessment optimized the pathological diagnosis and improved the ability to predict clinical outcomes in these patients. Patients with atypical Spitz tumors/Spitz melanomas were younger and had tumors predominantly located in the extremities. Genomic lesions in these patients were characterized by kinase fusions most often involving MAP3K8 and ALK. Even though 62% of patients who had nodes sampled had nodal disease, none developed distant metastases and two developed locoregional recurrences. Of the 33 patients tested, no patients had TERT promoter mutations. However, CDKN2A was deleted in 15 patients. These findings suggest that TERT promoter mutations might be a better predictor of aggressive clinical behavior (development of metastases) in these lesions. Patients with conventional melanoma (n = 17) were older and their tumors were more commonly located on the scalp or trunk. Seven of 12 patients had a positive sentinel node, and genomic abnormalities in 11 of 17 patients revealed BRAF V600E mutations. Seven of 16 patients had TERT promoter mutations, and three of these patients died of their disease. Of the four patients with melanoma arising in a giant nevi, all had NRAS Q61 mutations and all succumbed to their disease.[
In another study, 128 lesions were classified as Spitz tumors on the basis of morphology (80 Spitz tumors, 26 Spitz melanomas, 22 melanomas with Spitz features). Kinase fusions or truncations were present in 81% of Spitz tumor cases and in 77% of Spitz melanoma cases. By comparison, 84% of melanomas with Spitz features had BRAF, NRAS, or NF1 mutations, and 61% of these had TERT promoter mutations. Among patients in the Spitz tumor group whose melanoma recurred, one patient diagnosed with a BRAF V600E mutation and a TERT promoter mutation developed a distant recurrence and died. A second patient with a MAP3K8 fusion had a local recurrence. Two patients with Spitz melanoma had a recurrence and both had BRAF V600E mutations. Of the three patients in the melanoma with spitzoid features group who had a recurrence, all had a BRAF or NRAS mutation with concomitant TERT promoter mutations. After reclassifying these patients on the basis of their clinical and genomic characteristics, and by incorporating the BRAF or NRAS mutations into the melanoma with Spitz features category, a significant difference in recurrence-free survival rates could be detected among the groups with Spitz tumors. This finding suggests that incorporation of genomic features can greatly improve the classification of these lesions.[
|Spitz melanoma||Kinase fusions (RET,ROS,MET,ALK,BRAF,MAP3K8,NTRK1);BAP1loss in the presence ofBRAFmutation|
|Spitz nevus||HRAS;BRAFandNRAS(uncommon); kinase fusions (ROS,ALK,NTRK1,BRAF,RET,MAP3K8)|
Cancer in children and adolescents is rare, although the overall incidence has been slowly increasing since 1975.[
(Refer to the PDQ Supportive and Palliative Care summaries for specific information about supportive care for children and adolescents with cancer.)
The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer.[
Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2010, childhood cancer mortality decreased by more than 50%.[
Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[
The designation of a rare tumor is not uniform among pediatric and adult groups. In adults, rare cancers are defined as those with an annual incidence of fewer than six cases per 100,000 people. They account for up to 24% of all cancers diagnosed in the European Union and about 20% of all cancers diagnosed in the United States.[
Most cancers in subgroup XI are either melanomas or thyroid cancer, with other types accounting for only 1.3% of cancers in children aged 0 to 14 years and 5.3% of cancers in adolescents aged 15 to 19 years.
These rare cancers are extremely challenging to study because of the low number of patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the lack of clinical trials for adolescents with rare cancers.
Information about these tumors may also be found in sources relevant to adults with cancer, such as the PDQ summary on adult Melanoma Treatment.
Treatment options for childhood melanoma include the following:
Surgery is the treatment of choice for patients with localized melanoma. Current guidelines recommend margins of resection as follows:
Sentinel lymph node biopsy should be considered in patients with thin lesions (≤1 mm) and ulceration, mitotic rate greater than 1 mm2, young age, and lesions larger than 1 mm with or without adverse features. Young patients have a higher incidence of sentinel lymph node positivity, and this feature adversely affects clinical outcomes.[
If the sentinel lymph node is positive, the option to undergo a complete lymph node dissection should be discussed. An adult trial randomly assigned 1,934 patients with a positive sentinel node, identified by either immunohistochemistry or polymerase chain reaction, to either complete lymph node dissection or observation. The 3-year melanoma-specific survival rate was similar in both groups (86%), whereas the disease-free survival (DFS) rate was slightly higher in the dissection group (68% vs. 63%; P = .05). This advantage in DFS was related to a decrease in the rate of nodal recurrences because there was no difference in the distant metastases–free survival rates. It remains unknown how these results will affect the future surgical management of children and adolescents with melanoma.[
Immune Checkpoint Inhibitors or BRAF/MEK Inhibitors
Patients with high-risk primary cutaneous melanoma, such as those with regional lymph node involvement, may be offered adjuvant treatment with immune checkpoint or BRAF inhibitors, as recently described in adults.[
Targeted therapies and immunotherapy that have been shown to be effective in adults with melanoma should be pursued in pediatric patients with conventional melanoma and metastatic, recurrent, or progressive disease.
Evidence (targeted therapy and immunotherapy):
Ipilimumab and nivolumab or nivolumab alone, as well as combinations of BRAF and MEK inhibitors for BRAF-mutant melanoma, have become the standard of care for adult patients with advanced-stage, metastatic melanoma.[
The use of BRAF and MEK inhibitors, as well as PD-L1 inhibitors, in the adjuvant setting have also become the standard of care for adult patients with high-risk, resected melanoma. This treatment may be considered for children with conventional melanoma and high-risk features such as stage IIIA or higher disease.[
The studies listed below are investigating the activity of targeted BRAF inhibitors, MEK inhibitors, and PD-L1 inhibitors in pediatric patients with melanoma.[
(Refer to the PDQ summary on adult Melanoma Treatment for more information.)
Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, refer to the ClinicalTrials.gov website.
The following are examples of national and/or institutional clinical trials that are currently being conducted:
Patients with tumors that have molecular variants addressed by treatment arms included in the trial will be offered treatment on Pediatric MATCH. Additional information can be obtained on the NCI website and ClinicalTrials.gov website.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Editorial changes were made to this summary.
This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of pediatric melanoma. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Childhood Melanoma Treatment are:
Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Pediatric Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
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The preferred citation for this PDQ summary is:
PDQ® Pediatric Treatment Editorial Board. PDQ Childhood Melanoma Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/skin/hp/child-melanoma-treatment-pdq. Accessed <MM/DD/YYYY>.
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Last Revised: 2022-04-19
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