Pediatric Melanoma in Review: Providing Considerations for Dermatologists

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Pediatric melanoma, though rare, is the most lethal skin cancer in children and adolescents, with unique diagnostic and clinical challenges compared with adult melanoma. In the US, pediatric melanoma is the most common skin cancer diagnosed in children, with 300 to 500 new diagnoses annually.¹ The annual incidence has been increasing by approximately 2% over the past few decades.^2,3 Most pediatric melanoma cases can be attributed to UV DNA damage.⁴ As children grow, there is a cumulative UV exposure effect, putting older children and adults at higher risk for melanoma. It is estimated that 25% to 50% of lifetime sun exposure occurs in the first 18 to 21 years of life, making these formative years crucial in avoiding UV light exposure and resultant damage.⁵

Twenty-two percent of pediatric patients with melanoma have nonmodifiable risk factors, such as fair skin, xeroderma pigmentosum (XP), family and genetic history, sun sensitivity, presence of congenital nevi, and nevus pattern.⁶ For example, 5% of individuals with XP will develop melanoma by a median age of 19 years.⁵ Mutations in CDKN2A, CDK4, and MITF have been implicated in familial melanoma and an increased susceptibility to melanoma.^7-9 Sun-sensitive children, such as those more prone to freckling and burns, have also been shown to have a higher incidence of melanoma.¹⁰ In a study of adolescents aged 15 to 19 years, patients with more than 100 nevi were found to have a 34-fold increased risk of melanoma, whereas those with more than 10 large nevi (greater than 5 mm in diameter) had a 15-fold increased risk.¹¹ Immunodeficient and immunosuppressed patients also may have increased nevus density and higher rates of melanoma when compared with the general population.⁵

Female youths show a slightly higher incidence of melanoma compared with their male counterparts.¹² Approximately 85% of pediatric melanoma cases occur in non-Hispanic White patients, followed by 5% in Hispanic patients and 5% in Asian/Pacific Islander patients.²

Diagnostic Challenges

Early recognition is crucial to preventing the progression of melanoma. It is important for clinicians to recognize that pediatric melanoma may present itself differently across different age and sex groups. In children aged 4 to 10 years, melanoma location is equally distributed across the body. Younger children aged 0 to 4 years have a lower incidence of truncal melanoma, and older children and adolescents aged 10 to 19 years have a higher incidence of truncal melanoma.12 In addition, female youths have a higher incidence of extremity melanoma, and male youths have a higher incidence of facial and truncal melanoma.^13,14

In addition, the traditional ABCDE criteria for the detection of melanoma (asymmetry, border irregularity, color variegation, diameter > 6 mm, evolution) were found to be unhelpful in detecting melanoma in up to 60% of pediatric patients with melanoma, with 82% of cases taking more than 6 months to complete a diagnosis after initial detection.15 Cordoro et al proposed an ABCDE criteria that is more specific to pediatric melanoma: A, amelanotic; B, bleeding, bump; C, color uniformity; D, de novo, any diameter; and E, evolution of mole.¹⁵

Because the appearance of new moles is typically benign in the first 2 decades of life,¹⁶ a high index of suspicions should be considered when evaluating pediatric patients for melanoma. Currently, there are no definitive screening guidelines, although a combination of home self-monitoring and subsequent clinical evaluation of suspicious lesions has been proposed.¹⁷ Dermatoscopic examination can help differentiate the morphologic features between melanoma and benign nevi.¹⁸ Full-thickness biopsies are indicated for suspicious and concerning lesions, with a negative margin of 1 to 3 mm. Shave biopsies are not recommended because they may interfere with pathologic diagnosis and evaluation of Breslow depth.¹⁹

Approaches to Treatment

Treatment guidelines for pediatric melanoma have been largely derived from adult protocols due to limited clinical trials and data from pediatric patients.20 The Table outlines the surgical management of melanoma as outlined by the National Comprehensive Cancer Network.^19,21

Definitive excision of the tumor is the primary treatment for cutaneous malignant melanoma, which is typically done with wide local excision with appropriate negative margins.¹⁹ Microscopic Mohs surgery may be recommended for patients with facial or acral melanomas that would otherwise be difficult to excise without disfiguring scarring.¹⁹

Systemic therapies, such as immune checkpoint inhibitors and targeted molecular therapies, are recommended for patients with stage III and IV melanoma.^19,21 In the light of current limited evidence, it is recommended that therapy for children follow guidelines for adults, with precautions taken to monitor for adverse effects.²⁰

If possible, children should be treated within clinical trials, and adolescents should be included in adult trials if indicated. Previously, clinical trials for pediatric patients with melanoma have been terminated due to low enrollment numbers. Current ongoing clinical trials recruiting pediatric patients with melanoma include autologous B7-H3–specific chimeric antigen receptor T-cell therapy (3CAR; phase 1; NCT04897321); tegavivint therapy (phase 1/2; NCT04851119); donor natural killer cell, cyclophosphamide, and etoposide therapy (phase 1; NCT03420963); and pembrolizumab (Keytruda) therapy (KEYNOTE-051; phase 1/2; NCT02332668).^22-25

Prognostic Considerations

Overall, survival for pediatric patients with melanoma has improved over the past 30 years.³ The main predictor of outcomes in pediatric melanoma is the stage at the time of diagnosis; patients with stage IV metastatic melanoma have a median survival time of less than 1 year and a 5-year survival rate of less than 12%.¹³ The stage-for-stage prognosis for pediatric melanoma is better than that seen in adults; however, children typically present with higher rates of lymph node metastasis, thicker lesions, and more advanced disease stage.^26-28 This may in part be due to the delayed diagnosis of melanoma in children.^13,15

Tumor ulceration and increasing thickness have been demonstrated to have worse outcomes in pediatric patients.¹² In addition, a positive sentinel lymph node biopsy is associated with a poorer prognosis.²⁹ However, other traditional risk factors, such as vascular invasion and high mitotic activity, have not been correlated with increased mortality in pediatric patients.³⁰

Prevention

The World Health Organization classifies UV exposure as a class I carcinogen, and it is directly associated with a higher incidence of melanoma.⁶ UV exposure is a highly preventable cause of pediatric melanoma and can be easily avoided if proper sun-safety protocols are followed. Educational initiatives and legislation limiting the use of tanning beds for minors have been shown to be effective in encouraging sun-protective behaviors.^31,32 A survey of adolescents suggested that targeting normative and control beliefs relating to sun safety may increase sun-protective behaviors in this population.³³ For example, educating patients and parents on the importance of sun safety encourages sun-protective behaviors and attitudes, as demonstrated by the SPOTS³⁴ and Live Sun Smart³⁵ programs. In the age of social media, influencers extolling the importance of wearing sunscreen can also change normative beliefs regarding sun protection. Helping pediatric patients set small goals (eg, “I will put on sunscreen once a day”) can help improve their perceived self-efficacy. Implementing sun-protective policies at school, such as sunscreen application prior to outdoor activities, is also crucial in limiting UV exposure in children.³⁶

Conclusion

Despite its rarity, pediatric melanoma remains a pressing issue for dermatologists, with unique diagnostic and clinical challenges compared with adult melanoma. Current guidelines for treatment are largely derived from adult protocols due to limited clinical trials in pediatric patients. UV protection is key for prevention of melanoma, especially in high-risk patients. Educational and legislative interventions have been shown to positively influence sun-protective behaviors in children. Tailored interventions and focused research will be crucial to reducing disease incidence and mortality.

Sana Suhail is a fourth-year medical student at The University of Texas Health Science Center in San Antonio.

Bernard Cohen, MD, is a professor of pediatrics and dermatology at Johns Hopkins University School of Medicine in Baltimore, Maryland.

References

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