Melanoma is rare in children. However, it is the most common skin cancer in children, followed by basal cell carcinomas and squamous cell carcinomas.[1–8]

Approximately 300 cases of melanoma are diagnosed each year in patients younger than 20 years in the United States, accounting for 0.3% of all new cases of melanoma.[9] Melanoma accounts for about 3% of all cancers in children aged 15 to 19 years.[10]

Melanoma annual incidence in the United States increases with age, as shown in Figure 1 from the National Childhood Cancer Registry (NCCR).[10] For children younger than 10 years, the incidence rate is approximately 1 to 2 cases per 1 million. During adolescence, the rates increase steadily with age, although they are much lower than those observed in adults.[10,11]

Figure 1 also shows that among adolescents aged 15 to 19 years, melanoma rates are significantly higher for females (10.4 per 1 million; 95% confidence interval [CI], 9.4–11.5) than males (5.7 per 1 million; 95% CI, 5.0–6.6). Incidence rates for children younger than 15 years do not differ significantly between girls and boys.

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The incidence of pediatric melanoma (aged 0–19 years) increased by an average of 1.6% per year between 1975 and 1996. As shown in Figure 2, melanoma incidence continued to increase through 2003 for adolescents (aged 15–19 years), but it subsequently dropped significantly by approximately 6% per year.[10] During this same period, the incidence decreased slightly for children aged 0 to 14 years, but the change over time was not significant. The reason for the decline in melanoma incidence among adolescents aged 15 to 19 years is not known, but possible explanations include increased use of sunscreen and protective clothing, increased dermatological care, and reduced access to tanning beds.[11]

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A retrospective study of 22,524 skin pathology reports from patients younger than 20 years identified 38 melanomas, 33 of which occurred in patients aged 15 to 19 years. Investigators reported that the number of lesions that needed to be excised to identify one melanoma was 479.8, which is 20 times higher than in the adult population.[12]

References

1. Sasson M, Mallory SB: Malignant primary skin tumors in children. Curr Opin Pediatr 8 (4): 372-7, 1996. [PUBMED Abstract]
2. Fishman C, Mihm MC, Sober AJ: Diagnosis and management of nevi and cutaneous melanoma in infants and children. Clin Dermatol 20 (1): 44-50, 2002 Jan-Feb. [PUBMED Abstract]
3. Hamre MR, Chuba P, Bakhshi S, et al.: Cutaneous melanoma in childhood and adolescence. Pediatr Hematol Oncol 19 (5): 309-17, 2002 Jul-Aug. [PUBMED Abstract]
4. Ceballos PI, Ruiz-Maldonado R, Mihm MC: Melanoma in children. N Engl J Med 332 (10): 656-62, 1995. [PUBMED Abstract]
5. Schmid-Wendtner MH, Berking C, Baumert J, et al.: Cutaneous melanoma in childhood and adolescence: an analysis of 36 patients. J Am Acad Dermatol 46 (6): 874-9, 2002. [PUBMED Abstract]
6. Pappo AS: Melanoma in children and adolescents. Eur J Cancer 39 (18): 2651-61, 2003. [PUBMED Abstract]
7. Huynh PM, Grant-Kels JM, Grin CM: Childhood melanoma: update and treatment. Int J Dermatol 44 (9): 715-23, 2005. [PUBMED Abstract]
8. Christenson LJ, Borrowman TA, Vachon CM, et al.: Incidence of basal cell and squamous cell carcinomas in a population younger than 40 years. JAMA 294 (6): 681-90, 2005. [PUBMED Abstract]
9. National Cancer Institute: SEER Stat Fact Sheets: Melanoma of the Skin. Bethesda, Md: National Cancer Institute. Available online. Last accessed December 15, 2023.
10. National Cancer Institute: NCCR*Explorer: An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed February 25, 2025.
11. Paulson KG, Gupta D, Kim TS, et al.: Age-Specific Incidence of Melanoma in the United States. JAMA Dermatol 156 (1): 57-64, 2020. [PUBMED Abstract]
12. Moscarella E, Zalaudek I, Cerroni L, et al.: Excised melanocytic lesions in children and adolescents – a 10-year survey. Br J Dermatol 167 (2): 368-73, 2012. [PUBMED Abstract]

Conditions associated with an increased risk of developing melanoma in children and adolescents include the following:

Phenotypic traits associated with an increased risk of melanoma in adults have been documented in children and adolescents with melanoma and include the following:[10–16]

Germline pathogenic variants associated with an increased risk of melanoma in children include the following:

References

1. Ceballos PI, Ruiz-Maldonado R, Mihm MC: Melanoma in children. N Engl J Med 332 (10): 656-62, 1995. [PUBMED Abstract]
2. Pappo AS: Melanoma in children and adolescents. Eur J Cancer 39 (18): 2651-61, 2003. [PUBMED Abstract]
3. Kleinerman RA, Tucker MA, Tarone RE, et al.: Risk of new cancers after radiotherapy in long-term survivors of retinoblastoma: an extended follow-up. J Clin Oncol 23 (10): 2272-9, 2005. [PUBMED Abstract]
4. Shibuya H, Kato A, Kai N, et al.: A case of Werner syndrome with three primary lesions of malignant melanoma. J Dermatol 32 (9): 737-44, 2005. [PUBMED Abstract]
5. Kleinerman RA, Yu CL, Little MP, et al.: Variation of second cancer risk by family history of retinoblastoma among long-term survivors. J Clin Oncol 30 (9): 950-7, 2012. [PUBMED Abstract]
6. Hale EK, Stein J, Ben-Porat L, et al.: Association of melanoma and neurocutaneous melanocytosis with large congenital melanocytic naevi–results from the NYU-LCMN registry. Br J Dermatol 152 (3): 512-7, 2005. [PUBMED Abstract]
7. Makkar HS, Frieden IJ: Neurocutaneous melanosis. Semin Cutan Med Surg 23 (2): 138-44, 2004. [PUBMED Abstract]
8. Kinsler VA, O’Hare P, Jacques T, et al.: MEK inhibition appears to improve symptom control in primary NRAS-driven CNS melanoma in children. Br J Cancer 116 (8): 990-993, 2017. [PUBMED Abstract]
9. Abele M, Forchhammer S, Eigentler TK, et al.: Melanoma of the central nervous system based on neurocutaneous melanocytosis in childhood: A rare but fatal condition. Pediatr Blood Cancer 71 (4): e30859, 2024. [PUBMED Abstract]
10. Heffernan AE, O’Sullivan A: Pediatric sun exposure. Nurse Pract 23 (7): 67-8, 71-8, 83-6, 1998. [PUBMED Abstract]
11. Berg P, Lindelöf B: Differences in malignant melanoma between children and adolescents. A 35-year epidemiological study. Arch Dermatol 133 (3): 295-7, 1997. [PUBMED Abstract]
12. Elwood JM, Jopson J: Melanoma and sun exposure: an overview of published studies. Int J Cancer 73 (2): 198-203, 1997. [PUBMED Abstract]
13. Strouse JJ, Fears TR, Tucker MA, et al.: Pediatric melanoma: risk factor and survival analysis of the surveillance, epidemiology and end results database. J Clin Oncol 23 (21): 4735-41, 2005. [PUBMED Abstract]
14. Whiteman DC, Valery P, McWhirter W, et al.: Risk factors for childhood melanoma in Queensland, Australia. Int J Cancer 70 (1): 26-31, 1997. [PUBMED Abstract]
15. Tucker MA, Fraser MC, Goldstein AM, et al.: A natural history of melanomas and dysplastic nevi: an atlas of lesions in melanoma-prone families. Cancer 94 (12): 3192-209, 2002. [PUBMED Abstract]
16. Ducharme EE, Silverberg NB: Pediatric malignant melanoma: an update on epidemiology, detection, and prevention. Cutis 84 (4): 192-8, 2009. [PUBMED Abstract]
17. Pellegrini C, Botta F, Massi D, et al.: MC1R variants in childhood and adolescent melanoma: a retrospective pooled analysis of a multicentre cohort. Lancet Child Adolesc Health 3 (5): 332-342, 2019. [PUBMED Abstract]
18. Soufir N, Avril MF, Chompret A, et al.: Prevalence of p16 and CDK4 germline mutations in 48 melanoma-prone families in France. The French Familial Melanoma Study Group. Hum Mol Genet 7 (2): 209-16, 1998. [PUBMED Abstract]
19. Goldstein AM, Stidd KC, Yang XR, et al.: Pediatric melanoma in melanoma-prone families. Cancer 124 (18): 3715-3723, 2018. [PUBMED Abstract]
20. Pellegrini C, Raimondi S, Di Nardo L, et al.: Melanoma in children and adolescents: analysis of susceptibility genes in 123 Italian patients. J Eur Acad Dermatol Venereol 36 (2): 213-221, 2022. [PUBMED Abstract]
21. Guhan SM, Artomov M, McCormick S, et al.: Cancer risks associated with the germline MITF(E318K) variant. Sci Rep 10 (1): 17051, 2020. [PUBMED Abstract]

The diagnosis of pediatric melanomas may be difficult, and many of these lesions may be confused with so-called melanocytic lesions with unknown malignant potential.[1] These lesions are biologically different from melanoma and benign nevi.[1,2] The terms Spitz nevus and spitzoid melanoma are also commonly used, creating additional confusion. One retrospective study found that children aged 10 years or older were more likely to present with amelanotic lesions, bleeding, uniform color, variable diameter, and elevation (such as a de novo bump).[3][Level of evidence C1]

The diagnostic evaluation of pediatric melanomas includes the following:

A Children’s Oncology Group–led panel of experts from different specialties have developed recommendations for the diagnostic evaluation and surgical management of cutaneous melanomas, atypical Spitz tumors, and non-Spitz melanocytic tumors.[14]

References

1. Berk DR, LaBuz E, Dadras SS, et al.: Melanoma and melanocytic tumors of uncertain malignant potential in children, adolescents and young adults–the Stanford experience 1995-2008. Pediatr Dermatol 27 (3): 244-54, 2010 May-Jun. [PUBMED Abstract]
2. Cerroni L, Barnhill R, Elder D, et al.: Melanocytic tumors of uncertain malignant potential: results of a tutorial held at the XXIX Symposium of the International Society of Dermatopathology in Graz, October 2008. Am J Surg Pathol 34 (3): 314-26, 2010. [PUBMED Abstract]
3. Cordoro KM, Gupta D, Frieden IJ, et al.: Pediatric melanoma: results of a large cohort study and proposal for modified ABCD detection criteria for children. J Am Acad Dermatol 68 (6): 913-25, 2013. [PUBMED Abstract]
4. Ferrari A, Lopez Almaraz R, Reguerre Y, et al.: Cutaneous melanoma in children and adolescents: The EXPeRT/PARTNER diagnostic and therapeutic recommendations. Pediatr Blood Cancer 68 (Suppl 4): e28992, 2021. [PUBMED Abstract]
5. Arjunan A, Wardrop M, Malek MM, et al.: Treatment outcomes following partial shave biopsy of atypical and malignant melanocytic tumors in pediatric patients. Melanoma Res 34 (6): 544-548, 2024. [PUBMED Abstract]
6. Shah NC, Gerstle JT, Stuart M, et al.: Use of sentinel lymph node biopsy and high-dose interferon in pediatric patients with high-risk melanoma: the Hospital for Sick Children experience. J Pediatr Hematol Oncol 28 (8): 496-500, 2006. [PUBMED Abstract]
7. Kayton ML, La Quaglia MP: Sentinel node biopsy for melanocytic tumors in children. Semin Diagn Pathol 25 (2): 95-9, 2008. [PUBMED Abstract]
8. Swetter SM, Thompson JA, Albertini MR, et al.: NCCN Guidelines® Insights: Melanoma: Cutaneous, Version 2.2021. J Natl Compr Canc Netw 19 (4): 364-376, 2021. [PUBMED Abstract]
9. Ariyan CE, Coit DG: Clinical aspects of sentinel lymph node biopsy in melanoma. Semin Diagn Pathol 25 (2): 86-94, 2008. [PUBMED Abstract]
10. Pacella SJ, Lowe L, Bradford C, et al.: The utility of sentinel lymph node biopsy in head and neck melanoma in the pediatric population. Plast Reconstr Surg 112 (5): 1257-65, 2003. [PUBMED Abstract]
11. Lallas A, Kyrgidis A, Ferrara G, et al.: Atypical Spitz tumours and sentinel lymph node biopsy: a systematic review. Lancet Oncol 15 (4): e178-83, 2014. [PUBMED Abstract]
12. Lee S, Barnhill RL, Dummer R, et al.: TERT Promoter Mutations Are Predictive of Aggressive Clinical Behavior in Patients with Spitzoid Melanocytic Neoplasms. Sci Rep 5: 11200, 2015. [PUBMED Abstract]
13. Halalsheh H, Kaste SC, Navid F, et al.: The role of routine imaging in pediatric cutaneous melanoma. Pediatr Blood Cancer 65 (12): e27412, 2018. [PUBMED Abstract]
14. Sargen MR, Barnhill RL, Elder DE, et al.: Evaluation and Surgical Management of Pediatric Cutaneous Melanoma and Atypical Spitz and Non-Spitz Melanocytic Tumors (Melanocytomas): A Report From Children’s Oncology Group. J Clin Oncol 43 (9): 1157-1167, 2025. [PUBMED Abstract]

Accurate diagnosis of pediatric melanocytic lesions is essential for optimal risk stratification and treatment planning.

Melanoma-related conditions with malignant potential that arise in the pediatric population can be classified into the following three general groups:[1]

Lesions categorized as Spitz lesions are challenging to diagnose. Morphological assessment alone has significant limitations, and there is low interobserver expert agreement.[2]

Genomic alterations involving multiple genes have been reported in melanocytic lesions. The characteristics of each tumor are summarized in Table 1.

In another study, 128 lesions were classified as Spitz tumors based on morphology (80 Spitz tumors, 26 Spitz melanomas, 22 melanomas with Spitz features).[8]

Conventional melanoma. The genomic landscape of conventional melanoma in children is represented by many of the genomic alterations that are found in adults with melanoma.[1] A report from the Pediatric Cancer Genome Project observed that 15 cases of conventional melanoma had high burdens of somatic single-nucleotide variants (SNV), TERT promoter variants (12 of 13), and activating BRAF V600 variants (13 of 15). The melanoma cases also had variant spectrum signatures consistent with UV light damage. In addition, two-thirds of the cases had MC1R variants associated with an increased susceptibility to melanoma. An Australian study compared the whole-genome sequencing of melanomas in adolescents and young adults (age range, 15–30 years) with the sequencing of melanomas in older adults.[9] The frequencies of somatic variants in BRAF (96%) and PTEN (36%) in the adolescent and young adult cohort were double the rates observed in the adult cohort. Adolescent and young adult melanomas contained a higher proportion of variant signatures unrelated to UV radiation than did mature adult melanomas, as a proportion of total variant burden.

Large congenital melanocytic nevi. Large congenital melanocytic nevi are reported to have activating NRAS Q61 variants with no other recurring variants noted.[10] Somatic mosaicism for NRAS Q61 variants has also been reported in patients with multiple congenital melanocytic nevi and neurocutaneous melanosis.[11]

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.[12]

References

1. Lu C, Zhang J, Nagahawatte P, et al.: The genomic landscape of childhood and adolescent melanoma. J Invest Dermatol 135 (3): 816-23, 2015. [PUBMED Abstract]
2. Gerami P, Busam K, Cochran A, et al.: Histomorphologic assessment and interobserver diagnostic reproducibility of atypical spitzoid melanocytic neoplasms with long-term follow-up. Am J Surg Pathol 38 (7): 934-40, 2014. [PUBMED Abstract]
3. Wiesner T, He J, Yelensky R, et al.: Kinase fusions are frequent in Spitz tumours and spitzoid melanomas. Nat Commun 5: 3116, 2014. [PUBMED Abstract]
4. Lee S, Barnhill RL, Dummer R, et al.: TERT Promoter Mutations Are Predictive of Aggressive Clinical Behavior in Patients with Spitzoid Melanocytic Neoplasms. Sci Rep 5: 11200, 2015. [PUBMED Abstract]
5. Yeh I, Botton T, Talevich E, et al.: Activating MET kinase rearrangements in melanoma and Spitz tumours. Nat Commun 6: 7174, 2015. [PUBMED Abstract]
6. Newman S, Fan L, Pribnow A, et al.: Clinical genome sequencing uncovers potentially targetable truncations and fusions of MAP3K8 in spitzoid and other melanomas. Nat Med 25 (4): 597-602, 2019. [PUBMED Abstract]
7. Kervarrec T, Pissaloux D, Tirode F, et al.: Morphologic features in a series of 352 Spitz melanocytic proliferations help predict their oncogenic drivers. Virchows Arch 480 (2): 369-382, 2022. [PUBMED Abstract]
8. Quan VL, Zhang B, Zhang Y, et al.: Integrating Next-Generation Sequencing with Morphology Improves Prognostic and Biologic Classification of Spitz Neoplasms. J Invest Dermatol 140 (8): 1599-1608, 2020. [PUBMED Abstract]
9. Wilmott JS, Johansson PA, Newell F, et al.: Whole genome sequencing of melanomas in adolescent and young adults reveals distinct mutation landscapes and the potential role of germline variants in disease susceptibility. Int J Cancer 144 (5): 1049-1060, 2019. [PUBMED Abstract]
10. Charbel C, Fontaine RH, Malouf GG, et al.: NRAS mutation is the sole recurrent somatic mutation in large congenital melanocytic nevi. J Invest Dermatol 134 (4): 1067-74, 2014. [PUBMED Abstract]
11. Kinsler VA, Thomas AC, Ishida M, et al.: Multiple congenital melanocytic nevi and neurocutaneous melanosis are caused by postzygotic mutations in codon 61 of NRAS. J Invest Dermatol 133 (9): 2229-36, 2013. [PUBMED Abstract]
12. Pappo AS, McPherson V, Pan H, et al.: A prospective, comprehensive registry that integrates the molecular analysis of pediatric and adolescent melanocytic lesions. Cancer 127 (20): 3825-3831, 2021. [PUBMED Abstract]

Children and adolescents with melanoma generally have a favorable outcome. Table 2 shows the 5-year survival rates for children and adolescents with melanoma in the United States by age for the years between 2013 and 2019.[1]

Pediatric melanoma shares many similarities with adult melanoma, and the prognosis depends on disease stage.[2] As in adults, most pediatric patients (about 75%) have localized disease and excellent outcomes.[3–5]

The outcome for patients with nodal disease is intermediate, with about 60% expected to survive long term.[4–6] In one study, the outcome for patients with metastatic disease was favorable,[4] but this result was not duplicated in another study from the National Cancer Database.[6]

Children younger than 10 years who have melanoma often present with the following:[2,4,6,7]

The use of sentinel lymph node biopsy for staging pediatric melanoma has become widespread. Primary tumor thickness and ulceration have been correlated with a higher incidence of nodal involvement.[8] Studies addressing nodal involvement and the lack of effect on outcome have reported the following findings:

The association of lesion thickness with clinical outcome is controversial in pediatric melanoma.[4–6,14–18] In addition, it is unclear why some variables that correlate with survival in adults are not replicated in children. One possible explanation for this difference might be the inclusion of patients who have lesions that are not true melanomas in the adult series, considering the problematic histological distinction between true melanoma and melanocytic lesions with unknown malignant potential. These patients are not included in pediatric trials.[19,20]

References

1. National Cancer Institute: NCCR*Explorer: An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed February 25, 2025.
2. Paradela S, Fonseca E, Pita-Fernández S, et al.: Prognostic factors for melanoma in children and adolescents: a clinicopathologic, single-center study of 137 Patients. Cancer 116 (18): 4334-44, 2010. [PUBMED Abstract]
3. Wong JR, Harris JK, Rodriguez-Galindo C, et al.: Incidence of childhood and adolescent melanoma in the United States: 1973-2009. Pediatrics 131 (5): 846-54, 2013. [PUBMED Abstract]
4. Strouse JJ, Fears TR, Tucker MA, et al.: Pediatric melanoma: risk factor and survival analysis of the surveillance, epidemiology and end results database. J Clin Oncol 23 (21): 4735-41, 2005. [PUBMED Abstract]
5. Brecht IB, Garbe C, Gefeller O, et al.: 443 paediatric cases of malignant melanoma registered with the German Central Malignant Melanoma Registry between 1983 and 2011. Eur J Cancer 51 (7): 861-8, 2015. [PUBMED Abstract]
6. Lange JR, Palis BE, Chang DC, et al.: Melanoma in children and teenagers: an analysis of patients from the National Cancer Data Base. J Clin Oncol 25 (11): 1363-8, 2007. [PUBMED Abstract]
7. Moore-Olufemi S, Herzog C, Warneke C, et al.: Outcomes in pediatric melanoma: comparing prepubertal to adolescent pediatric patients. Ann Surg 253 (6): 1211-5, 2011. [PUBMED Abstract]
8. Mu E, Lange JR, Strouse JJ: Comparison of the use and results of sentinel lymph node biopsy in children and young adults with melanoma. Cancer 118 (10): 2700-7, 2012. [PUBMED Abstract]
9. Balch CM, Soong SJ, Gershenwald JE, et al.: Age as a prognostic factor in patients with localized melanoma and regional metastases. Ann Surg Oncol 20 (12): 3961-8, 2013. [PUBMED Abstract]
10. Gibbs P, Moore A, Robinson W, et al.: Pediatric melanoma: are recent advances in the management of adult melanoma relevant to the pediatric population. J Pediatr Hematol Oncol 22 (5): 428-32, 2000 Sep-Oct. [PUBMED Abstract]
11. Livestro DP, Kaine EM, Michaelson JS, et al.: Melanoma in the young: differences and similarities with adult melanoma: a case-matched controlled analysis. Cancer 110 (3): 614-24, 2007. [PUBMED Abstract]
12. Han D, Zager JS, Han G, et al.: The unique clinical characteristics of melanoma diagnosed in children. Ann Surg Oncol 19 (12): 3888-95, 2012. [PUBMED Abstract]
13. Lorimer PD, White RL, Walsh K, et al.: Pediatric and Adolescent Melanoma: A National Cancer Data Base Update. Ann Surg Oncol 23 (12): 4058-4066, 2016. [PUBMED Abstract]
14. Rao BN, Hayes FA, Pratt CB, et al.: Malignant melanoma in children: its management and prognosis. J Pediatr Surg 25 (2): 198-203, 1990. [PUBMED Abstract]
15. Aldrink JH, Selim MA, Diesen DL, et al.: Pediatric melanoma: a single-institution experience of 150 patients. J Pediatr Surg 44 (8): 1514-21, 2009. [PUBMED Abstract]
16. Tcheung WJ, Marcello JE, Puri PK, et al.: Evaluation of 39 cases of pediatric cutaneous head and neck melanoma. J Am Acad Dermatol 65 (2): e37-42, 2011. [PUBMED Abstract]
17. Ferrari A, Bisogno G, Cecchetto G, et al.: Cutaneous melanoma in children and adolescents: the Italian rare tumors in pediatric age project experience. J Pediatr 164 (2): 376-82.e1-2, 2014. [PUBMED Abstract]
18. Stanelle EJ, Busam KJ, Rich BS, et al.: Early-stage non-Spitzoid cutaneous melanoma in patients younger than 22 years of age at diagnosis: long-term follow-up and survival analysis. J Pediatr Surg 50 (6): 1019-23, 2015. [PUBMED Abstract]
19. Lohmann CM, Coit DG, Brady MS, et al.: Sentinel lymph node biopsy in patients with diagnostically controversial spitzoid melanocytic tumors. Am J Surg Pathol 26 (1): 47-55, 2002. [PUBMED Abstract]
20. Su LD, Fullen DR, Sondak VK, et al.: Sentinel lymph node biopsy for patients with problematic spitzoid melanocytic lesions: a report on 18 patients. Cancer 97 (2): 499-507, 2003. [PUBMED Abstract]

Cancer in children and adolescents is rare, although the overall incidence has slowly increased since 1975.[1] Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the following pediatric specialists and others to ensure that children receive treatment, supportive care, and rehabilitation to achieve optimal survival and quality of life:

For specific information about supportive care for children and adolescents with cancer, see the summaries on Supportive and Palliative Care.

The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of children and adolescents with cancer.[2] At these centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with current standard therapy. Other types of clinical trials test novel therapies when there is no standard therapy for a cancer diagnosis. Most of the progress in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.

Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2020, childhood cancer mortality decreased by more than 50%.[3–5] Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. For information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors, see Late Effects of Treatment for Childhood Cancer.

Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[6] The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 people in the United States. Therefore, all pediatric cancers are considered rare.

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.[7,8] In children and adolescents, the designation of a rare tumor is not uniform among international groups, as follows:

These rare cancers are extremely challenging to study because of the relatively few patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the small number 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 Melanoma Treatment.

References

1. Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010. [PUBMED Abstract]
2. American Academy of Pediatrics: Standards for pediatric cancer centers. Pediatrics 134 (2): 410-4, 2014. Also available online. Last accessed February 25, 2025.
3. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014. [PUBMED Abstract]
4. National Cancer Institute: NCCR*Explorer: An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed February 25, 2025.
5. Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed December 30, 2024.
6. Ward E, DeSantis C, Robbins A, et al.: Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 64 (2): 83-103, 2014 Mar-Apr. [PUBMED Abstract]
7. Gatta G, Capocaccia R, Botta L, et al.: Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet-a population-based study. Lancet Oncol 18 (8): 1022-1039, 2017. [PUBMED Abstract]
8. DeSantis CE, Kramer JL, Jemal A: The burden of rare cancers in the United States. CA Cancer J Clin 67 (4): 261-272, 2017. [PUBMED Abstract]
9. Ferrari A, Brecht IB, Gatta G, et al.: Defining and listing very rare cancers of paediatric age: consensus of the Joint Action on Rare Cancers in cooperation with the European Cooperative Study Group for Pediatric Rare Tumors. Eur J Cancer 110: 120-126, 2019. [PUBMED Abstract]
10. Pappo AS, Krailo M, Chen Z, et al.: Infrequent tumor initiative of the Children’s Oncology Group: initial lessons learned and their impact on future plans. J Clin Oncol 28 (33): 5011-6, 2010. [PUBMED Abstract]

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.[1] A Children’s Oncology Group–led panel of experts from different specialties have also developed recommendations for the diagnostic evaluation and surgical management of cutaneous melanomas, atypical Spitz tumors, and non-Spitz melanocytic tumors.[2]

Treatment options for childhood melanoma include the following:

References

1. Ferrari A, Lopez Almaraz R, Reguerre Y, et al.: Cutaneous melanoma in children and adolescents: The EXPeRT/PARTNER diagnostic and therapeutic recommendations. Pediatr Blood Cancer 68 (Suppl 4): e28992, 2021. [PUBMED Abstract]
2. Sargen MR, Barnhill RL, Elder DE, et al.: Evaluation and Surgical Management of Pediatric Cutaneous Melanoma and Atypical Spitz and Non-Spitz Melanocytic Tumors (Melanocytomas): A Report From Children’s Oncology Group. J Clin Oncol 43 (9): 1157-1167, 2025. [PUBMED Abstract]
3. Mu E, Lange JR, Strouse JJ: Comparison of the use and results of sentinel lymph node biopsy in children and young adults with melanoma. Cancer 118 (10): 2700-7, 2012. [PUBMED Abstract]
4. Han D, Zager JS, Han G, et al.: The unique clinical characteristics of melanoma diagnosed in children. Ann Surg Oncol 19 (12): 3888-95, 2012. [PUBMED Abstract]
5. Eggermont AM, Chiarion-Sileni V, Grob JJ, et al.: Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy. N Engl J Med 375 (19): 1845-1855, 2016. [PUBMED Abstract]
6. Merchant MS, Wright M, Baird K, et al.: Phase I Clinical Trial of Ipilimumab in Pediatric Patients with Advanced Solid Tumors. Clin Cancer Res 22 (6): 1364-70, 2016. [PUBMED Abstract]
7. Geoerger B, Bergeron C, Gore L, et al.: Phase II study of ipilimumab in adolescents with unresectable stage III or IV malignant melanoma. Eur J Cancer 86: 358-363, 2017. [PUBMED Abstract]
8. Davis KL, Fox E, Merchant MS, et al.: Nivolumab in children and young adults with relapsed or refractory solid tumours or lymphoma (ADVL1412): a multicentre, open-label, single-arm, phase 1-2 trial. Lancet Oncol 21 (4): 541-550, 2020. [PUBMED Abstract]
9. Geoerger B, Kang HJ, Yalon-Oren M, et al.: Pembrolizumab in paediatric patients with advanced melanoma or a PD-L1-positive, advanced, relapsed, or refractory solid tumour or lymphoma (KEYNOTE-051): interim analysis of an open-label, single-arm, phase 1-2 trial. Lancet Oncol 21 (1): 121-133, 2020. [PUBMED Abstract]
10. Davis KL, Fox E, Isikwei E, et al.: A Phase I/II Trial of Nivolumab plus Ipilimumab in Children and Young Adults with Relapsed/Refractory Solid Tumors: A Children’s Oncology Group Study ADVL1412. Clin Cancer Res 28 (23): 5088-5097, 2022. [PUBMED Abstract]
11. Mandalà M, Ferrari A, Brecht IB, et al.: Efficacy of anti PD-1 therapy in children and adolescent melanoma patients (MELCAYA study). Eur J Cancer 211: 114305, 2024. [PUBMED Abstract]
12. Hargrave DR, Bouffet E, Tabori U, et al.: Efficacy and Safety of Dabrafenib in Pediatric Patients with BRAF V600 Mutation-Positive Relapsed or Refractory Low-Grade Glioma: Results from a Phase I/IIa Study. Clin Cancer Res 25 (24): 7303-7311, 2019. [PUBMED Abstract]
13. Bouffet E, Hansford JR, Garrè ML, et al.: Dabrafenib plus Trametinib in Pediatric Glioma with BRAF V600 Mutations. N Engl J Med 389 (12): 1108-1120, 2023. [PUBMED Abstract]
14. Eggermont AMM, Blank CU, Mandala M, et al.: Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma. N Engl J Med 378 (19): 1789-1801, 2018. [PUBMED Abstract]
15. Luke JJ, Rutkowski P, Queirolo P, et al.: Pembrolizumab versus placebo as adjuvant therapy in completely resected stage IIB or IIC melanoma (KEYNOTE-716): a randomised, double-blind, phase 3 trial. Lancet 399 (10336): 1718-1729, 2022. [PUBMED Abstract]
16. Kirkwood JM, Del Vecchio M, Weber J, et al.: Adjuvant nivolumab in resected stage IIB/C melanoma: primary results from the randomized, phase 3 CheckMate 76K trial. Nat Med 29 (11): 2835-2843, 2023. [PUBMED Abstract]
17. Weber J, Mandala M, Del Vecchio M, et al.: Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma. N Engl J Med 377 (19): 1824-1835, 2017. [PUBMED Abstract]
18. Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al.: Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. N Engl J Med 377 (14): 1345-1356, 2017. [PUBMED Abstract]
19. Tawbi HA, Schadendorf D, Lipson EJ, et al.: Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma. N Engl J Med 386 (1): 24-34, 2022. [PUBMED Abstract]
20. Robert C, Karaszewska B, Schachter J, et al.: Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med 372 (1): 30-9, 2015. [PUBMED Abstract]
21. Long GV, Hauschild A, Santinami M, et al.: Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma. N Engl J Med 377 (19): 1813-1823, 2017. [PUBMED Abstract]

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, see the ClinicalTrials.gov website.

The following is an example of a national and/or institutional clinical trial that is currently being conducted:

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.

Diagnostic Evaluation

Added text to state that partial shave biopsy may compromise microstaging and is associated with more invasive, definitive surgical treatments (cited Arjunan et al. as reference 5).

Added text to state that a Children’s Oncology Group–led panel of experts from different specialties have developed recommendations for the diagnostic evaluation and surgical management of cutaneous melanomas, atypical Spitz tumors, and non-Spitz melanocytic tumors (cited Sargen et al. as reference 14).

Treatment of Childhood Melanoma

Added text to state that a Children’s Oncology Group–led panel of experts from different specialties have developed recommendations for the diagnostic evaluation and surgical management of cutaneous melanomas, atypical Spitz tumors, and non-Spitz melanocytic tumors (cited Sargen et al. as reference 2).

Added text about the results of a retrospective review that identified 99 patients with melanoma who were treated with systemic therapy, 81 of whom received anti–PD-1 therapy (cited Mandalà et al. as reference 11).

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® Cancer Information for Health Professionals pages.

Nonmelanoma skin cancers include basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). These skin cancers are very rare in children and adolescents. Based on National Childhood Cancer Registry data from 2016 to 2020, the incidence rate of skin carcinomas in children younger than 20 years was 0.1 cases per 1 million.[1]

In one series of 28 patients, approximately one-half of patients had predisposing conditions such as Gorlin syndrome (also known as nevoid basal cell carcinoma syndrome or basal cell nevus syndrome), and one-half of patients were exposed to iatrogenic conditions such as prolonged immunosuppression or radiation.[2]

Gorlin syndrome is a rare autosomal dominant disorder that is associated with germline PTCH1 or SUFU pathogenic variants.[3,4] This syndrome predisposes patients to develop early-onset neoplasms, including BCCs, ovarian fibromas, and desmoplastic medulloblastomas.[5–8] For more information, see the Basal cell nevus syndrome section in Genetics of Skin Cancer.

A retrospective analysis identified 25 BCCs in 11 patients with Gorlin syndrome.[9] Eighty percent of the BCCs occurred on the head and neck, and 64% of the specimens demonstrated infundibulocystic differentiation.

BCCs and SCCs in adults have been associated with exposure to solar UV radiation, iatrogenic immunosuppression, UVB radiation, and other risk factors.[10]

In one retrospective follow-up study of patients with xeroderma pigmentosum, development of melanoma of the skin increased by more than 2,000-fold and development of nonmelanoma skin cancers increased by 10,000-fold.[11] For more information about xeroderma pigmentosum, see Genetics of Skin Cancer.

References

1. National Cancer Institute: NCCR*Explorer: An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed February 25, 2025.
2. Khosravi H, Schmidt B, Huang JT: Characteristics and outcomes of nonmelanoma skin cancer (NMSC) in children and young adults. J Am Acad Dermatol 73 (5): 785-90, 2015. [PUBMED Abstract]
3. Hahn H, Wicking C, Zaphiropoulous PG, et al.: Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell 85 (6): 841-51, 1996. [PUBMED Abstract]
4. Johnson RL, Rothman AL, Xie J, et al.: Human homolog of patched, a candidate gene for the basal cell nevus syndrome. Science 272 (5268): 1668-71, 1996. [PUBMED Abstract]
5. Gorlin RJ: Nevoid basal cell carcinoma syndrome. Dermatol Clin 13 (1): 113-25, 1995. [PUBMED Abstract]
6. Kimonis VE, Goldstein AM, Pastakia B, et al.: Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome. Am J Med Genet 69 (3): 299-308, 1997. [PUBMED Abstract]
7. Amlashi SF, Riffaud L, Brassier G, et al.: Nevoid basal cell carcinoma syndrome: relation with desmoplastic medulloblastoma in infancy. A population-based study and review of the literature. Cancer 98 (3): 618-24, 2003. [PUBMED Abstract]
8. Veenstra-Knol HE, Scheewe JH, van der Vlist GJ, et al.: Early recognition of basal cell naevus syndrome. Eur J Pediatr 164 (3): 126-30, 2005. [PUBMED Abstract]
9. Nguyen CV, Rubin AI, Smith A, et al.: Retrospective analysis of the histopathologic features of basal cell carcinomas in pediatric patients with basal cell nevus syndrome. J Cutan Pathol 48 (3): 390-395, 2021. [PUBMED Abstract]
10. Madan V, Lear JT, Szeimies RM: Non-melanoma skin cancer. Lancet 375 (9715): 673-85, 2010. [PUBMED Abstract]
11. Bradford PT, Goldstein AM, Tamura D, et al.: Cancer and neurologic degeneration in xeroderma pigmentosum: long term follow-up characterises the role of DNA repair. J Med Genet 48 (3): 168-76, 2011. [PUBMED Abstract]

Basal cell carcinomas (BCCs) generally appear as raised lumps or ulcerated lesions, usually in areas with previous sun exposure.[1] Multiple BCCs may be present, and they are exacerbated by radiation therapy.[2] Squamous cell carcinomas (SCCs) are usually reddened lesions with varying degrees of scaling or crusting. SCCs have an appearance similar to eczema, infections, trauma, or psoriasis.

References

1. Efron PA, Chen MK, Glavin FL, et al.: Pediatric basal cell carcinoma: case reports and literature review. J Pediatr Surg 43 (12): 2277-80, 2008. [PUBMED Abstract]
2. Griffin JR, Cohen PR, Tschen JA, et al.: Basal cell carcinoma in childhood: case report and literature review. J Am Acad Dermatol 57 (5 Suppl): S97-102, 2007. [PUBMED Abstract]

Biopsy or excision is necessary to diagnose any skin cancer. A specific diagnosis is necessary for decisions regarding treatment. Basal cell carcinomas and squamous cell carcinomas are generally curable with surgery alone, and further diagnostic workup is not indicated.[1,2]

References

1. Rubin AI, Chen EH, Ratner D: Basal-cell carcinoma. N Engl J Med 353 (21): 2262-9, 2005. [PUBMED Abstract]
2. Alam M, Ratner D: Cutaneous squamous-cell carcinoma. N Engl J Med 344 (13): 975-83, 2001. [PUBMED Abstract]

Cancer in children and adolescents is rare, although the overall incidence has slowly increased since 1975.[1] Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the following pediatric specialists and others to ensure that children receive treatment, supportive care, and rehabilitation to achieve optimal survival and quality of life:

For specific information about supportive care for children and adolescents with cancer, see the summaries on Supportive and Palliative Care.

The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of children and adolescents with cancer.[2] At these centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with current standard therapy. Other types of clinical trials test novel therapies when there is no standard therapy for a cancer diagnosis. Most of the progress in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.

Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2020, childhood cancer mortality decreased by more than 50%.[3–5] Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. For information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors, see Late Effects of Treatment for Childhood Cancer.

Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[6] The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 people in the United States. Therefore, all pediatric cancers are considered rare.

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.[7,8] In children and adolescents, the designation of a rare tumor is not uniform among international groups, as follows:

These rare cancers are extremely challenging to study because of the relatively few patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the small number 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 Skin Cancer Treatment.

References

1. Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010. [PUBMED Abstract]
2. American Academy of Pediatrics: Standards for pediatric cancer centers. Pediatrics 134 (2): 410-4, 2014. Also available online. Last accessed February 25, 2025.
3. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014. [PUBMED Abstract]
4. National Cancer Institute: NCCR*Explorer: An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed February 25, 2025.
5. Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed December 30, 2024.
6. Ward E, DeSantis C, Robbins A, et al.: Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 64 (2): 83-103, 2014 Mar-Apr. [PUBMED Abstract]
7. Gatta G, Capocaccia R, Botta L, et al.: Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet-a population-based study. Lancet Oncol 18 (8): 1022-1039, 2017. [PUBMED Abstract]
8. DeSantis CE, Kramer JL, Jemal A: The burden of rare cancers in the United States. CA Cancer J Clin 67 (4): 261-272, 2017. [PUBMED Abstract]
9. Ferrari A, Brecht IB, Gatta G, et al.: Defining and listing very rare cancers of paediatric age: consensus of the Joint Action on Rare Cancers in cooperation with the European Cooperative Study Group for Pediatric Rare Tumors. Eur J Cancer 110: 120-126, 2019. [PUBMED Abstract]
10. Pappo AS, Krailo M, Chen Z, et al.: Infrequent tumor initiative of the Children’s Oncology Group: initial lessons learned and their impact on future plans. J Clin Oncol 28 (33): 5011-6, 2010. [PUBMED Abstract]

Treatment options for childhood BCC and SCC of the skin include the following:

For more information, see Skin Cancer Treatment.

References

1. Khosravi H, Schmidt B, Huang JT: Characteristics and outcomes of nonmelanoma skin cancer (NMSC) in children and young adults. J Am Acad Dermatol 73 (5): 785-90, 2015. [PUBMED Abstract]
2. Caro I, Low JA: The role of the hedgehog signaling pathway in the development of basal cell carcinoma and opportunities for treatment. Clin Cancer Res 16 (13): 3335-9, 2010. [PUBMED Abstract]
3. Von Hoff DD, LoRusso PM, Rudin CM, et al.: Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med 361 (12): 1164-72, 2009. [PUBMED Abstract]
4. Sekulic A, Migden MR, Oro AE, et al.: Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med 366 (23): 2171-9, 2012. [PUBMED Abstract]
5. Basset-Séguin N, Hauschild A, Kunstfeld R, et al.: Vismodegib in patients with advanced basal cell carcinoma: Primary analysis of STEVIE, an international, open-label trial. Eur J Cancer 86: 334-348, 2017. [PUBMED Abstract]
6. Tang JY, Mackay-Wiggan JM, Aszterbaum M, et al.: Inhibiting the hedgehog pathway in patients with the basal-cell nevus syndrome. N Engl J Med 366 (23): 2180-8, 2012. [PUBMED Abstract]
7. Fife D, Laitinen MA, Myers DJ, et al.: Vismodegib Therapy for Basal Cell Carcinoma in an 8-Year-Old Chinese Boy with Xeroderma Pigmentosum. Pediatr Dermatol 34 (2): 163-165, 2017. [PUBMED Abstract]
8. Stratigos AJ, Sekulic A, Peris K, et al.: Cemiplimab in locally advanced basal cell carcinoma after hedgehog inhibitor therapy: an open-label, multi-centre, single-arm, phase 2 trial. Lancet Oncol 22 (6): 848-857, 2021. [PUBMED Abstract]
9. Migden MR, Rischin D, Schmults CD, et al.: PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma. N Engl J Med 379 (4): 341-351, 2018. [PUBMED Abstract]

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, see the 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.

This summary was comprehensively reviewed.

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® Cancer Information for Health Professionals pages.

Chordoma is a very rare tumor of bone. It arises from remnants of the notochord within the clivus, spinal vertebrae, or sacrum. The most common site in children is the cranium.[1] The incidence in the United States is approximately 1 case per 1 million people per year. Only 5% of all chordomas occur in patients younger than 20 years.[2,3] Most pediatric patients have the classical or chondroid variant of chordoma, while the dedifferentiated variant is rare in children.[2,4]

References

1. Sebro R, DeLaney T, Hornicek F, et al.: Differences in sex distribution, anatomic location and MR imaging appearance of pediatric compared to adult chordomas. BMC Med Imaging 16 (1): 53, 2016. [PUBMED Abstract]
2. Hoch BL, Nielsen GP, Liebsch NJ, et al.: Base of skull chordomas in children and adolescents: a clinicopathologic study of 73 cases. Am J Surg Pathol 30 (7): 811-8, 2006. [PUBMED Abstract]
3. Lau CS, Mahendraraj K, Ward A, et al.: Pediatric Chordomas: A Population-Based Clinical Outcome Study Involving 86 Patients from the Surveillance, Epidemiology, and End Result (SEER) Database (1973-2011). Pediatr Neurosurg 51 (3): 127-36, 2016. [PUBMED Abstract]
4. McMaster ML, Goldstein AM, Bromley CM, et al.: Chordoma: incidence and survival patterns in the United States, 1973-1995. Cancer Causes Control 12 (1): 1-11, 2001. [PUBMED Abstract]

Patients with chordomas usually present with pain (headache or sacrum) or diplopia. Patients may also present with or without neurological deficits such as cranial or other nerve impairment.[1]

The diagnosis of a chordoma is straightforward when the typical physaliferous (soap bubble–bearing) cells are present. The differential diagnosis is sometimes difficult and includes dedifferentiated chordoma and chondrosarcoma. Childhood chordoma has been associated with tuberous sclerosis complex.[2]

References

1. John L, Smith H, Ilanchezhian M, et al.: The NIH pediatric/young adult chordoma clinic and natural history study: Making advances in a very rare tumor. Pediatr Blood Cancer : e30358, 2023. [PUBMED Abstract]
2. McMaster ML, Goldstein AM, Parry DM: Clinical features distinguish childhood chordoma associated with tuberous sclerosis complex (TSC) from chordoma in the general paediatric population. J Med Genet 48 (7): 444-9, 2011. [PUBMED Abstract]

Younger children with chordomas appear to have a worse outlook than older patients.[1–6] The survival rate ranges from about 50% to 80% for children and adolescents with cranial chordomas.[2,3,5] However, in a National Cancer Database review, the overall survival (OS) of pediatric and adult patients with cranial chordomas was similar (70% at 10 years).[7]

References

1. Coffin CM, Swanson PE, Wick MR, et al.: Chordoma in childhood and adolescence. A clinicopathologic analysis of 12 cases. Arch Pathol Lab Med 117 (9): 927-33, 1993. [PUBMED Abstract]
2. Borba LA, Al-Mefty O, Mrak RE, et al.: Cranial chordomas in children and adolescents. J Neurosurg 84 (4): 584-91, 1996. [PUBMED Abstract]
3. Hoch BL, Nielsen GP, Liebsch NJ, et al.: Base of skull chordomas in children and adolescents: a clinicopathologic study of 73 cases. Am J Surg Pathol 30 (7): 811-8, 2006. [PUBMED Abstract]
4. Jian BJ, Bloch OG, Yang I, et al.: A comprehensive analysis of intracranial chordoma and survival: a systematic review. Br J Neurosurg 25 (4): 446-53, 2011. [PUBMED Abstract]
5. Yasuda M, Bresson D, Chibbaro S, et al.: Chordomas of the skull base and cervical spine: clinical outcomes associated with a multimodal surgical resection combined with proton-beam radiation in 40 patients. Neurosurg Rev 35 (2): 171-82; discussion 182-3, 2012. [PUBMED Abstract]
6. Chambers KJ, Lin DT, Meier J, et al.: Incidence and survival patterns of cranial chordoma in the United States. Laryngoscope 124 (5): 1097-102, 2014. [PUBMED Abstract]
7. Xu JC, Lehrich BM, Yasaka TM, et al.: Characteristics and overall survival in pediatric versus adult skull base chordoma: a population-based study. Childs Nerv Syst 37 (6): 1901-1908, 2021. [PUBMED Abstract]
8. Zhou J, Sun J, Bai HX, et al.: Prognostic Factors in Patients With Spinal Chordoma: An Integrative Analysis of 682 Patients. Neurosurgery 81 (5): 812-823, 2017. [PUBMED Abstract]
9. Tsitouras V, Wang S, Dirks P, et al.: Management and outcome of chordomas in the pediatric population: The Hospital for Sick Children experience and review of the literature. J Clin Neurosci 34: 169-176, 2016. [PUBMED Abstract]
10. Beccaria K, Tauziède-Espariat A, Monnien F, et al.: Pediatric Chordomas: Results of a Multicentric Study of 40 Children and Proposal for a Histopathological Prognostic Grading System and New Therapeutic Strategies. J Neuropathol Exp Neurol 77 (3): 207-215, 2018. [PUBMED Abstract]
11. Hasselblatt M, Thomas C, Hovestadt V, et al.: Poorly differentiated chordoma with SMARCB1/INI1 loss: a distinct molecular entity with dismal prognosis. Acta Neuropathol 132 (1): 149-51, 2016. [PUBMED Abstract]
12. Raygada M, John L, Liu A, et al.: Germline findings in cancer predisposing genes from a small cohort of chordoma patients. J Cancer Res Clin Oncol 150 (5): 227, 2024. [PUBMED Abstract]
13. O’Halloran K, Hakimjavadi H, Bootwalla M, et al.: Pediatric Chordoma: A Tale of Two Genomes. Mol Cancer Res 22 (8): 721-729, 2024. [PUBMED Abstract]

Cancer in children and adolescents is rare, although the overall incidence has slowly increased since 1975.[1] Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the following pediatric specialists and others to ensure that children receive treatment, supportive care, and rehabilitation to achieve optimal survival and quality of life:

For specific information about supportive care for children and adolescents with cancer, see the summaries on Supportive and Palliative Care.

The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of children and adolescents with cancer.[2] At these centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with current standard therapy. Other types of clinical trials test novel therapies when there is no standard therapy for a cancer diagnosis. Most of the progress in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.

Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2020, childhood cancer mortality decreased by more than 50%.[3–5] Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. For information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors, see Late Effects of Treatment for Childhood Cancer.

Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[6] The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 people in the United States. Therefore, all pediatric cancers are considered rare.

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.[7,8] In children and adolescents, the designation of a rare tumor is not uniform among international groups, as follows:

These rare cancers are extremely challenging to study because of the relatively few patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the small number of clinical trials for adolescents with rare cancers.

References

1. Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010. [PUBMED Abstract]
2. American Academy of Pediatrics: Standards for pediatric cancer centers. Pediatrics 134 (2): 410-4, 2014. Also available online. Last accessed February 25, 2025.
3. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014. [PUBMED Abstract]
4. National Cancer Institute: NCCR*Explorer: An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed February 25, 2025.
5. Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed December 30, 2024.
6. Ward E, DeSantis C, Robbins A, et al.: Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 64 (2): 83-103, 2014 Mar-Apr. [PUBMED Abstract]
7. Gatta G, Capocaccia R, Botta L, et al.: Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet-a population-based study. Lancet Oncol 18 (8): 1022-1039, 2017. [PUBMED Abstract]
8. DeSantis CE, Kramer JL, Jemal A: The burden of rare cancers in the United States. CA Cancer J Clin 67 (4): 261-272, 2017. [PUBMED Abstract]
9. Ferrari A, Brecht IB, Gatta G, et al.: Defining and listing very rare cancers of paediatric age: consensus of the Joint Action on Rare Cancers in cooperation with the European Cooperative Study Group for Pediatric Rare Tumors. Eur J Cancer 110: 120-126, 2019. [PUBMED Abstract]
10. Pappo AS, Krailo M, Chen Z, et al.: Infrequent tumor initiative of the Children’s Oncology Group: initial lessons learned and their impact on future plans. J Clin Oncol 28 (33): 5011-6, 2010. [PUBMED Abstract]

One report described the value of using a multidisciplinary clinic for patients with these very rare tumors.[1] Treatment options for childhood chordoma include the following:

Recurrences are usually local but can include distant metastases to the lungs or bone.

References

1. John L, Smith H, Ilanchezhian M, et al.: The NIH pediatric/young adult chordoma clinic and natural history study: Making advances in a very rare tumor. Pediatr Blood Cancer : e30358, 2023. [PUBMED Abstract]
2. Yasuda M, Bresson D, Chibbaro S, et al.: Chordomas of the skull base and cervical spine: clinical outcomes associated with a multimodal surgical resection combined with proton-beam radiation in 40 patients. Neurosurg Rev 35 (2): 171-82; discussion 182-3, 2012. [PUBMED Abstract]
3. DeLaney TF, Liebsch NJ, Pedlow FX, et al.: Long-term results of Phase II study of high dose photon/proton radiotherapy in the management of spine chordomas, chondrosarcomas, and other sarcomas. J Surg Oncol 110 (2): 115-22, 2014. [PUBMED Abstract]
4. Rassi MS, Hulou MM, Almefty K, et al.: Pediatric Clival Chordoma: A Curable Disease that Conforms to Collins’ Law. Neurosurgery 82 (5): 652-660, 2018. [PUBMED Abstract]
5. Hug EB, Sweeney RA, Nurre PM, et al.: Proton radiotherapy in management of pediatric base of skull tumors. Int J Radiat Oncol Biol Phys 52 (4): 1017-24, 2002. [PUBMED Abstract]
6. Noël G, Habrand JL, Jauffret E, et al.: Radiation therapy for chordoma and chondrosarcoma of the skull base and the cervical spine. Prognostic factors and patterns of failure. Strahlenther Onkol 179 (4): 241-8, 2003. [PUBMED Abstract]
7. Lim PS, Tran S, Kroeze SGC, et al.: Outcomes of adolescents and young adults treated for brain and skull base tumors with pencil beam scanning proton therapy. Pediatr Blood Cancer 67 (12): e28664, 2020. [PUBMED Abstract]
8. Indelicato DJ, Rotondo RL, Mailhot Vega RB, et al.: Local Control After Proton Therapy for Pediatric Chordoma. Int J Radiat Oncol Biol Phys 109 (5): 1406-1413, 2021. [PUBMED Abstract]
9. Rombi B, Ares C, Hug EB, et al.: Spot-scanning proton radiation therapy for pediatric chordoma and chondrosarcoma: clinical outcome of 26 patients treated at paul scherrer institute. Int J Radiat Oncol Biol Phys 86 (3): 578-84, 2013. [PUBMED Abstract]
10. Rutz HP, Weber DC, Goitein G, et al.: Postoperative spot-scanning proton radiation therapy for chordoma and chondrosarcoma in children and adolescents: initial experience at paul scherrer institute. Int J Radiat Oncol Biol Phys 71 (1): 220-5, 2008. [PUBMED Abstract]
11. McDowell MM, Zwagerman NT, Wang EW, et al.: Long-term outcomes in the treatment of pediatric skull base chordomas in the endoscopic endonasal era. J Neurosurg Pediatr 27 (2): 170-179, 2020. [PUBMED Abstract]
12. Ioakeim-Ioannidou M, Niemierko A, Kim DW, et al.: Surgery and proton radiation therapy for pediatric base of skull chordomas: Long-term clinical outcomes for 204 patients. Neuro Oncol 25 (9): 1686-1697, 2023. [PUBMED Abstract]
13. Casali PG, Messina A, Stacchiotti S, et al.: Imatinib mesylate in chordoma. Cancer 101 (9): 2086-97, 2004. [PUBMED Abstract]
14. Stacchiotti S, Longhi A, Ferraresi V, et al.: Phase II study of imatinib in advanced chordoma. J Clin Oncol 30 (9): 914-20, 2012. [PUBMED Abstract]
15. Lindén O, Stenberg L, Kjellén E: Regression of cervical spinal cord compression in a patient with chordoma following treatment with cetuximab and gefitinib. Acta Oncol 48 (1): 158-9, 2009. [PUBMED Abstract]
16. Singhal N, Kotasek D, Parnis FX: Response to erlotinib in a patient with treatment refractory chordoma. Anticancer Drugs 20 (10): 953-5, 2009. [PUBMED Abstract]
17. Stacchiotti S, Marrari A, Tamborini E, et al.: Response to imatinib plus sirolimus in advanced chordoma. Ann Oncol 20 (11): 1886-94, 2009. [PUBMED Abstract]
18. Lebellec L, Chauffert B, Blay JY, et al.: Advanced chordoma treated by first-line molecular targeted therapies: Outcomes and prognostic factors. A retrospective study of the French Sarcoma Group (GSF/GETO) and the Association des Neuro-Oncologues d’Expression Française (ANOCEF). Eur J Cancer 79: 119-128, 2017. [PUBMED Abstract]
19. Dhall G, Traverso M, Finlay JL, et al.: The role of chemotherapy in pediatric clival chordomas. J Neurooncol 103 (3): 657-62, 2011. [PUBMED Abstract]
20. Al-Rahawan MM, Siebert JD, Mitchell CS, et al.: Durable complete response to chemotherapy in an infant with a clival chordoma. Pediatr Blood Cancer 59 (2): 323-5, 2012. [PUBMED Abstract]

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, see the ClinicalTrials.gov website.

The following is an example of a national and/or institutional clinical trial that is currently being conducted:

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.

Prognosis and Molecular Features

Added text about the results of a retrospective study that analyzed whole-exome and mitochondrial DNA genome sequencing of 29 chordomas from 23 pediatric patients and compared the findings with the results of whole-genome sequencing of chordomas from 80 adult patients (cited O’Halloran et al. as reference 13).

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® Cancer Information for Health Professionals pages.

Uveal melanoma (iris, ciliary body, choroid) is the most common primary intraocular malignancy. About 2,000 cases of uveal melanoma are diagnosed each year in the United States. It accounts for 5% of all cases of melanoma.[1] This tumor is most commonly diagnosed in older patients, and the incidence peaks at age 70 years.[2]

Pediatric uveal melanoma is extremely rare and accounts for 0.8% to 1.1% of all cases of uveal melanoma.[3] A retrospective, 24-center, observational study conducted by the European Ophthalmic Oncology Group from 1968 to 2014 identified 114 children (aged 1–17 years) and 185 young adults (aged 18–25 years) with ocular melanoma.[3] The median age at diagnosis for children was 15.1 years. The incidence of disease increased by 0.8% per year between the ages of 5 and 10 years and 8.8% per year between the ages of 17 and 24 years. Other series have also documented the higher incidence of the disease in adolescents.[4,5]

References

1. Field MG, Harbour JW: Recent developments in prognostic and predictive testing in uveal melanoma. Curr Opin Ophthalmol 25 (3): 234-9, 2014. [PUBMED Abstract]
2. Singh AD, Bergman L, Seregard S: Uveal melanoma: epidemiologic aspects. Ophthalmol Clin North Am 18 (1): 75-84, viii, 2005. [PUBMED Abstract]
3. Al-Jamal RT, Cassoux N, Desjardins L, et al.: The Pediatric Choroidal and Ciliary Body Melanoma Study: A Survey by the European Ophthalmic Oncology Group. Ophthalmology 123 (4): 898-907, 2016. [PUBMED Abstract]
4. Shields CL, Kaliki S, Arepalli S, et al.: Uveal melanoma in children and teenagers. Saudi J Ophthalmol 27 (3): 197-201, 2013. [PUBMED Abstract]
5. Pogrzebielski A, Orłowska-Heitzman J, Romanowska-Dixon B: Uveal melanoma in young patients. Graefes Arch Clin Exp Ophthalmol 244 (12): 1646-9, 2006. [PUBMED Abstract]

Risk factors for developing uveal melanoma include the following:[1–3]

In a European Oncology Group study, 57% of the pediatric patients were female. Four patients had a preexisting condition that included oculodermal melanocytosis (n = 2) and neurofibromatosis (n = 2).[4] In a review of 13 cases of uveal melanoma in the first 2 years of life, four patients had familial atypical melanoma mole syndrome, one patient had dysplastic nevus syndrome, and one patient had café au lait spots.[5]

References

1. Weis E, Shah CP, Lajous M, et al.: The association between host susceptibility factors and uveal melanoma: a meta-analysis. Arch Ophthalmol 124 (1): 54-60, 2006. [PUBMED Abstract]
2. Weis E, Shah CP, Lajous M, et al.: The association of cutaneous and iris nevi with uveal melanoma: a meta-analysis. Ophthalmology 116 (3): 536-543.e2, 2009. [PUBMED Abstract]
3. Singh AD, De Potter P, Fijal BA, et al.: Lifetime prevalence of uveal melanoma in white patients with oculo(dermal) melanocytosis. Ophthalmology 105 (1): 195-8, 1998. [PUBMED Abstract]
4. Al-Jamal RT, Cassoux N, Desjardins L, et al.: The Pediatric Choroidal and Ciliary Body Melanoma Study: A Survey by the European Ophthalmic Oncology Group. Ophthalmology 123 (4): 898-907, 2016. [PUBMED Abstract]
5. Yousef YA, Alkilany M: Characterization, treatment, and outcome of uveal melanoma in the first two years of life. Hematol Oncol Stem Cell Ther 8 (1): 1-5, 2015. [PUBMED Abstract]

Uveal melanoma is characterized by activating variants of GNAQ and GNA11, which lead to activation of the mitogen-activated protein kinases (MAPK) pathway. In addition, variants in BAP1 are seen in 84% of metastasizing tumors. Variants in SF3B1 and EIF1AX are associated with a good prognosis.[1–6]

References

1. Van Raamsdonk CD, Griewank KG, Crosby MB, et al.: Mutations in GNA11 in uveal melanoma. N Engl J Med 363 (23): 2191-9, 2010. [PUBMED Abstract]
2. Harbour JW, Onken MD, Roberson ED, et al.: Frequent mutation of BAP1 in metastasizing uveal melanomas. Science 330 (6009): 1410-3, 2010. [PUBMED Abstract]
3. Gupta MP, Lane AM, DeAngelis MM, et al.: Clinical Characteristics of Uveal Melanoma in Patients With Germline BAP1 Mutations. JAMA Ophthalmol 133 (8): 881-7, 2015. [PUBMED Abstract]
4. Harbour JW, Roberson ED, Anbunathan H, et al.: Recurrent mutations at codon 625 of the splicing factor SF3B1 in uveal melanoma. Nat Genet 45 (2): 133-5, 2013. [PUBMED Abstract]
5. Martin M, Maßhöfer L, Temming P, et al.: Exome sequencing identifies recurrent somatic mutations in EIF1AX and SF3B1 in uveal melanoma with disomy 3. Nat Genet 45 (8): 933-6, 2013. [PUBMED Abstract]
6. Van Raamsdonk CD, Bezrookove V, Green G, et al.: Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature 457 (7229): 599-602, 2009. [PUBMED Abstract]

Prognostic factors for uveal melanoma include the following:[1,2]

The survival of children appears to be more favorable than that of young adults and adults, suggesting that the biology of ocular melanoma might be different in children.[1,2]

A retrospective, multicenter, cohort study identified 133 young children aged 1 to 12 years with choroidal or ciliary body (n = 66; 50%), iris (n = 33; 25%), conjunctival (n = 26; 19%), and eyelid (n = 8; 6%) melanomas.[3]

References

1. Al-Jamal RT, Cassoux N, Desjardins L, et al.: The Pediatric Choroidal and Ciliary Body Melanoma Study: A Survey by the European Ophthalmic Oncology Group. Ophthalmology 123 (4): 898-907, 2016. [PUBMED Abstract]
2. Shields CL, Kaliki S, Arepalli S, et al.: Uveal melanoma in children and teenagers. Saudi J Ophthalmol 27 (3): 197-201, 2013. [PUBMED Abstract]
3. Masoomian B, Dalvin LA, Riazi-Esfahani H, et al.: Pediatric ocular melanoma: a collaborative multicenter study and meta-analysis. J AAPOS 27 (6): 316-324, 2023. [PUBMED Abstract]

Cancer in children and adolescents is rare, although the overall incidence has slowly increased since 1975.[1] Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the following pediatric specialists and others to ensure that children receive treatment, supportive care, and rehabilitation to achieve optimal survival and quality of life:

For specific information about supportive care for children and adolescents with cancer, see the summaries on Supportive and Palliative Care.

The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of children and adolescents with cancer.[2] At these centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with current standard therapy. Other types of clinical trials test novel therapies when there is no standard therapy for a cancer diagnosis. Most of the progress in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.

Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2020, childhood cancer mortality decreased by more than 50%.[3–5] Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. For information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors, see Late Effects of Treatment for Childhood Cancer.

Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[6] The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 people in the United States. Therefore, all pediatric cancers are considered rare.

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.[7,8] In children and adolescents, the designation of a rare tumor is not uniform among international groups, as follows:

These rare cancers are extremely challenging to study because of the relatively few patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the small number 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 Intraocular (Uveal) Melanoma Treatment.

References

1. Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010. [PUBMED Abstract]
2. American Academy of Pediatrics: Standards for pediatric cancer centers. Pediatrics 134 (2): 410-4, 2014. Also available online. Last accessed February 25, 2025.
3. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014. [PUBMED Abstract]
4. National Cancer Institute: NCCR*Explorer: An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed February 25, 2025.
5. Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed December 30, 2024.
6. Ward E, DeSantis C, Robbins A, et al.: Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 64 (2): 83-103, 2014 Mar-Apr. [PUBMED Abstract]
7. Gatta G, Capocaccia R, Botta L, et al.: Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet-a population-based study. Lancet Oncol 18 (8): 1022-1039, 2017. [PUBMED Abstract]
8. DeSantis CE, Kramer JL, Jemal A: The burden of rare cancers in the United States. CA Cancer J Clin 67 (4): 261-272, 2017. [PUBMED Abstract]
9. Ferrari A, Brecht IB, Gatta G, et al.: Defining and listing very rare cancers of paediatric age: consensus of the Joint Action on Rare Cancers in cooperation with the European Cooperative Study Group for Pediatric Rare Tumors. Eur J Cancer 110: 120-126, 2019. [PUBMED Abstract]
10. Pappo AS, Krailo M, Chen Z, et al.: Infrequent tumor initiative of the Children’s Oncology Group: initial lessons learned and their impact on future plans. J Clin Oncol 28 (33): 5011-6, 2010. [PUBMED Abstract]

Treatment options for childhood intraocular (uveal) melanoma include the following:

A retrospective single-institution review identified 18 patients younger than 21 years with uveal melanoma.[3][Level of evidence C1] Patients were treated with enucleation (n = 9), transscleral en bloc resection (n = 3), plaque radiation therapy (n = 5), or proton-beam radiation therapy (n = 1).

Laser surgery has been used to treat childhood intraocular melanoma.[1,2]

An open-label, randomized, phase III trial of adult patients with previously untreated HLA-A*02:01–positive metastatic uveal melanoma investigated treatment with tebentafusp. Tebentafusp is a bispecific restricted T-cell receptor for the glycoprotein 100 peptide; it is fused to a CD3 single-chain variable fragment. Patients were randomly assigned to receive either tebentafusp or treatment according to the investigator’s choice.[4]

For information about the treatment of uveal melanoma in adults, see Intraocular (Uveal) Melanoma Treatment.

References

1. Al-Jamal RT, Cassoux N, Desjardins L, et al.: The Pediatric Choroidal and Ciliary Body Melanoma Study: A Survey by the European Ophthalmic Oncology Group. Ophthalmology 123 (4): 898-907, 2016. [PUBMED Abstract]
2. Shields CL, Kaliki S, Arepalli S, et al.: Uveal melanoma in children and teenagers. Saudi J Ophthalmol 27 (3): 197-201, 2013. [PUBMED Abstract]
3. Fry MV, Augsburger JJ, Corrêa ZM: Clinical Features, Metastasis, and Survival in Patients Younger Than 21 Years With Posterior Uveal Melanoma. JAMA Ophthalmol 137 (1): 75-81, 2019. [PUBMED Abstract]
4. Nathan P, Hassel JC, Rutkowski P, et al.: Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. N Engl J Med 385 (13): 1196-1206, 2021. [PUBMED Abstract]

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, see the 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.

This summary was comprehensively reviewed.

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® Cancer Information for Health Professionals pages.

This executive summary reviews the topics covered in this PDQ summary on the genetics of skin cancer, with hyperlinks to detailed sections below that describe the evidence on each topic.

Structure of the Skin

The genetics of skin cancer is an extremely broad topic. More than 100 types of tumors are clinically apparent on the skin; many of them have familial components, either in isolation or as part of a syndrome with other features. This is, in part, because the skin itself is a complex organ made up of multiple cell types. Furthermore, many of these cell types can undergo malignant transformation at various points in their differentiation, leading to tumors with distinct histology and dramatically different biological behaviors, such as squamous cell carcinoma (SCC) and basal cell cancer (BCC). These have been called nonmelanoma skin cancers or keratinocyte cancers.

Figure 1 is a simple diagram of normal skin structure. It also indicates the major cell types that are normally found in each compartment. Broadly speaking, there are two large compartments—the avascular epidermis and the vascular dermis—with many cell types distributed in a connective tissue matrix, largely created by fibroblasts.[1]

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The outer layer or epidermis is made primarily of keratinocytes but has several other minor cell populations. The bottom layer is formed of basal keratinocytes abutting the basement membrane, along with interspersed melanocytes. The basement membrane is formed from products of keratinocytes and dermal fibroblasts, such as collagen and laminin, and is an important anatomical and functional structure. Basal keratinocytes lose contact with the basement membrane as they divide. As basal keratinocytes migrate toward the skin’s surface, they progressively differentiate, lose their nuclei, and form the spinous cell layer; the granular cell layer; and the keratinized outer layer, or stratum corneum, which serves as a protective covering of the body.

The true cytologic origin of BCC is unclear. BCC and basal cell keratinocytes share many histological similarities, as is reflected in the name. Alternatively, the outer root sheath cells of the hair follicle have also been proposed as the cell of origin for BCC.[2] This is suggested by the fact that BCCs occur predominantly on hair-bearing skin. BCCs rarely metastasize but can invade tissue locally or regionally, sometimes traveling along nerves.[3]

Some debate remains about the origin of SCC; however, these cancers are likely derived from epidermal stem cells associated with the hair follicle.[4] A variety of tissues, such as the lung and the uterine cervix, can give rise to SCCs. This cancer has somewhat differing behavior depending on its tissue source. Even in cancer derived from the skin, SCC from different anatomic locations can have differing levels of aggressiveness; for example, SCC from glabrous (smooth, hairless) sun-exposed skin has a lower metastatic rate than SCC arising from the vermillion border of the lip or from scars.[3]

Additionally, in the epidermal compartment, melanocytes distribute singly along the basement membrane and can undergo malignant transformation into melanoma. Melanocytes are derived from neural crest cells and migrate to the epidermal compartment near the eighth week of gestational age. Melanocytes contain melanin, which is packaged into melanosomes and transported to nearby keratinocytes to induce pigmentation of the skin. Melanin provides a barrier for the nuclei of keratinocytes against ultraviolet radiation and also plays a role in the immune system.[5]

Langerhans cells, or dendritic cells, are another cell type in the epidermis and have a primary function of antigen presentation. These cells reside in the skin for an extended period of time and respond to different stimuli, such as ultraviolet radiation or topical steroids, which cause them to migrate out of the skin.[6]

The dermis is largely composed of an extracellular matrix. Prominent cell types and organelles in this compartment are fibroblasts, endothelial cells, smooth muscle cells, transient immune system cells, blood vessels, and nerves. When malignant transformation occurs, fibroblasts form fibrosarcomas and endothelial cells form angiosarcomas, Kaposi sarcoma, or other vascular tumors. There are a number of immune cell types that move in and out of the skin to blood vessels and lymphatics; these include mast cells, lymphocytes, mononuclear cells, histiocytes, and granulocytes. These cells can increase in number in inflammatory diseases and can form tumors within the skin. For example, urticaria pigmentosa is a condition that arises from mast cells and is occasionally associated with mast cell leukemia; cutaneous T-cell lymphoma is often confined to the skin throughout its course. Overall, 10% of leukemias and lymphomas have prominent expression in the skin.[7]

Epidermal appendages are also found in the dermal compartment. These are derivatives of the epidermal keratinocytes, such as hair follicles, sweat glands, and the sebaceous glands associated with the hair follicles. These structures are generally formed in the first and second trimesters of fetal development. These can form a large variety of benign or malignant tumors with diverse biological behaviors. Several of these tumors are associated with familial syndromes. Overall, there are dozens of different histological subtypes of these tumors associated with individual components of the adnexal structures.[8]

Finally, the subcutis is a layer that extends below the dermis with varying depth, depending on the anatomic location. This deeper boundary can include muscle, fascia, bone, or cartilage. The subcutis can be affected by inflammatory conditions such as panniculitis and malignancies such as liposarcoma.[9]

These compartments give rise to their own malignancies but are also the region of immediate adjacent spread of localized skin cancers from other compartments. The boundaries of each skin compartment are used to define the staging of skin cancers. For example, an in situ melanoma is confined to the epidermis. Once the cancer crosses the basement membrane into the dermis, it is invasive. Internal malignancies also commonly metastasize to the skin. The dermis and subcutis are the most common locations, but the epidermis can also be involved in conditions such as Pagetoid breast cancer.

Clinical Presentation of Skin Cancers

While the appearance of any one skin cancer can vary, there are general physical presentations that can be used in screening. BCCs most commonly have a pearly rim or can appear somewhat eczematous (for more information, see Figure 2 and Figure 3). They often ulcerate (for more information, see Figure 2). SCCs frequently have a thick keratin top layer (for more information, see Figure 4). Both BCCs and SCCs are associated with a history of sun-damaged skin. Melanomas are characterized by dark pigment with asymmetry, border irregularity, color variation, a diameter of more than 6 mm, and evolution (ABCDE criteria). For more information about ABCDE criteria, see What Does Melanoma Look Like? on NCI’s website. Photographs representing typical clinical presentations of these cancers are shown below.

Basal cell carcinomas

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Squamous cell carcinomas

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Melanomas

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References

1. Vandergriff TW, Bergstresser PR: Anatomy and physiology. In: Bolognia JL, Jorizzo JL, Schaffer JV: Dermatology. 3rd ed. Elsevier Saunders, 2012, pp 43-54.
2. Schirren CG, Rütten A, Kaudewitz P, et al.: Trichoblastoma and basal cell carcinoma are neoplasms with follicular differentiation sharing the same profile of cytokeratin intermediate filaments. Am J Dermatopathol 19 (4): 341-50, 1997. [PUBMED Abstract]
3. Soyer HP, Rigel DS, Wurm EM: Actinic keratosis, basal cell carcinoma and squamous cell carcinoma. In: Bolognia JL, Jorizzo JL, Schaffer JV: Dermatology. 3rd ed. Elsevier Saunders, 2012, pp 1773-93.
4. Lapouge G, Youssef KK, Vokaer B, et al.: Identifying the cellular origin of squamous skin tumors. Proc Natl Acad Sci U S A 108 (18): 7431-6, 2011. [PUBMED Abstract]
5. Lin JY, Fisher DE: Melanocyte biology and skin pigmentation. Nature 445 (7130): 843-50, 2007. [PUBMED Abstract]
6. Koster MI, Loomis CA, Koss TK, et al.: Skin development and maintenance. In: Bolognia JL, Jorizzo JL, Schaffer JV: Dermatology. 3rd ed. Elsevier Saunders, 2012, pp 55-64.
7. Kamino H, Reddy VB, Pui J: Fibrous and fibrohistiocytic proliferations of the skin and tendons. In: Bolognia JL, Jorizzo JL, Schaffer JV: Dermatology. 3rd ed. Elsevier Saunders, 2012, pp 1961-77.
8. McCalmont TH: Adnexal neoplasms. In: Bolognia JL, Jorizzo JL, Schaffer JV: Dermatology. 3rd ed. Elsevier Saunders, 2012, pp 1829-50.
9. Kaddu S, Kohler S: Muscle, adipose and cartilage neoplasms. In: Bolognia JL, Jorizzo JL, Schaffer JV: Dermatology. 3rd ed. Elsevier Saunders, 2012, pp 1979-92.
10. Harrington LE, Mangan PR, Weaver CT: Expanding the effector CD4 T-cell repertoire: the Th17 lineage. Curr Opin Immunol 18 (3): 349-56, 2006. [PUBMED Abstract]

References

1. Miller DL, Weinstock MA: Nonmelanoma skin cancer in the United States: incidence. J Am Acad Dermatol 30 (5 Pt 1): 774-8, 1994. [PUBMED Abstract]
2. Gon A, Minelli L: Risk factors for basal cell carcinoma in a southern Brazilian population: a case-control study. Int J Dermatol 50 (10): 1286-90, 2011. [PUBMED Abstract]
3. Wu S, Han J, Li WQ, et al.: Basal-cell carcinoma incidence and associated risk factors in U.S. women and men. Am J Epidemiol 178 (6): 890-7, 2013. [PUBMED Abstract]
4. Wei EX, Li X, Nan H: Having a first-degree relative with melanoma increases lifetime risk of melanoma, squamous cell carcinoma, and basal cell carcinoma. J Am Acad Dermatol 81 (2): 489-499, 2019. [PUBMED Abstract]
5. Berlin NL, Cartmel B, Leffell DJ, et al.: Family history of skin cancer is associated with early-onset basal cell carcinoma independent of MC1R genotype. Cancer Epidemiol 39 (6): 1078-83, 2015. [PUBMED Abstract]
6. Mucci LA, Hjelmborg JB, Harris JR, et al.: Familial Risk and Heritability of Cancer Among Twins in Nordic Countries. JAMA 315 (1): 68-76, 2016. [PUBMED Abstract]
7. Epstein E: Value of follow-up after treatment of basal cell carcinoma. Arch Dermatol 108 (6): 798-800, 1973. [PUBMED Abstract]
8. Møller R, Nielsen A, Reymann F: Multiple basal cell carcinoma and internal malignant tumors. Arch Dermatol 111 (5): 584-5, 1975. [PUBMED Abstract]
9. Bergstresser PR, Halprin KM: Multiple sequential skin cancers. The risk of skin cancer in patients with previous skin cancer. Arch Dermatol 111 (8): 995-6, 1975. [PUBMED Abstract]
10. Robinson JK: Risk of developing another basal cell carcinoma. A 5-year prospective study. Cancer 60 (1): 118-20, 1987. [PUBMED Abstract]
11. Greenberg ER, Baron JA, Stukel TA, et al.: A clinical trial of beta carotene to prevent basal-cell and squamous-cell cancers of the skin. The Skin Cancer Prevention Study Group. N Engl J Med 323 (12): 789-95, 1990. [PUBMED Abstract]
12. Karagas MR, Stukel TA, Greenberg ER, et al.: Risk of subsequent basal cell carcinoma and squamous cell carcinoma of the skin among patients with prior skin cancer. Skin Cancer Prevention Study Group. JAMA 267 (24): 3305-10, 1992. [PUBMED Abstract]
13. Cantwell MM, Murray LJ, Catney D, et al.: Second primary cancers in patients with skin cancer: a population-based study in Northern Ireland. Br J Cancer 100 (1): 174-7, 2009. [PUBMED Abstract]
14. Efird JT, Friedman GD, Habel L, et al.: Risk of subsequent cancer following invasive or in situ squamous cell skin cancer. Ann Epidemiol 12 (7): 469-75, 2002. [PUBMED Abstract]
15. Wheless L, Black J, Alberg AJ: Nonmelanoma skin cancer and the risk of second primary cancers: a systematic review. Cancer Epidemiol Biomarkers Prev 19 (7): 1686-95, 2010. [PUBMED Abstract]
16. Frisch M, Hjalgrim H, Olsen JH, et al.: Risk for subsequent cancer after diagnosis of basal-cell carcinoma. A population-based, epidemiologic study. Ann Intern Med 125 (10): 815-21, 1996. [PUBMED Abstract]
17. Cho HG, Kuo KY, Li S, et al.: Frequent basal cell cancer development is a clinical marker for inherited cancer susceptibility. JCI Insight 3 (15): , 2018. [PUBMED Abstract]
18. Small J, Wallace K, Hill EG, et al.: A cohort study of personal and family history of skin cancer in relation to future risk of non-cutaneous malignancies. Cancer Causes Control 30 (11): 1213-1221, 2019. [PUBMED Abstract]
19. Tuohimaa P, Pukkala E, Scélo G, et al.: Does solar exposure, as indicated by the non-melanoma skin cancers, protect from solid cancers: vitamin D as a possible explanation. Eur J Cancer 43 (11): 1701-12, 2007. [PUBMED Abstract]
20. de Vries E, Soerjomataram I, Houterman S, et al.: Decreased risk of prostate cancer after skin cancer diagnosis: a protective role of ultraviolet radiation? Am J Epidemiol 165 (8): 966-72, 2007. [PUBMED Abstract]
21. Grant WB: A meta-analysis of second cancers after a diagnosis of nonmelanoma skin cancer: additional evidence that solar ultraviolet-B irradiance reduces the risk of internal cancers. J Steroid Biochem Mol Biol 103 (3-5): 668-74, 2007. [PUBMED Abstract]
22. Soerjomataram I, Louwman WJ, Lemmens VE, et al.: Are patients with skin cancer at lower risk of developing colorectal or breast cancer? Am J Epidemiol 167 (12): 1421-9, 2008. [PUBMED Abstract]
23. Tabata T, Kornberg TB: Hedgehog is a signaling protein with a key role in patterning Drosophila imaginal discs. Cell 76 (1): 89-102, 1994. [PUBMED Abstract]
24. Lum L, Beachy PA: The Hedgehog response network: sensors, switches, and routers. Science 304 (5678): 1755-9, 2004. [PUBMED Abstract]
25. Tojo M, Kiyosawa H, Iwatsuki K, et al.: Expression of the GLI2 oncogene and its isoforms in human basal cell carcinoma. Br J Dermatol 148 (5): 892-7, 2003. [PUBMED Abstract]
26. Gailani MR, Bale SJ, Leffell DJ, et al.: Developmental defects in Gorlin syndrome related to a putative tumor suppressor gene on chromosome 9. Cell 69 (1): 111-7, 1992. [PUBMED Abstract]
27. Shanley SM, Dawkins H, Wainwright BJ, et al.: Fine deletion mapping on the long arm of chromosome 9 in sporadic and familial basal cell carcinomas. Hum Mol Genet 4 (1): 129-33, 1995. [PUBMED Abstract]
28. Hahn H, Christiansen J, Wicking C, et al.: A mammalian patched homolog is expressed in target tissues of sonic hedgehog and maps to a region associated with developmental abnormalities. J Biol Chem 271 (21): 12125-8, 1996. [PUBMED Abstract]
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264. Paganelli A, Giordano E, Fiorentini C, et al.: Surgical management and oncological follow-up of cutaneous squamous cell carcinomas arising in epidermolysis bullosa patients. Int J Dermatol 61 (10): 1171-1174, 2022. [PUBMED Abstract]
265. Mellerio JE, Weiner M, Denyer JE, et al.: Medical management of epidermolysis bullosa: Proceedings of the IInd International Symposium on Epidermolysis Bullosa, Santiago, Chile, 2005. Int J Dermatol 46 (8): 795-800, 2007. [PUBMED Abstract]
266. Hammersen J, Neuner A, Wild F, et al.: Attenuation of Severe Generalized Junctional Epidermolysis Bullosa by Systemic Treatment with Gentamicin. Dermatology 235 (4): 315-322, 2019. [PUBMED Abstract]
267. Wagner JE, Ishida-Yamamoto A, McGrath JA, et al.: Bone marrow transplantation for recessive dystrophic epidermolysis bullosa. N Engl J Med 363 (7): 629-39, 2010. [PUBMED Abstract]
268. El-Darouti M, Fawzy M, Amin I, et al.: Treatment of dystrophic epidermolysis bullosa with bone marrow non-hematopoeitic stem cells: a randomized controlled trial. Dermatol Ther 29 (2): 96-100, 2016 Mar-Apr. [PUBMED Abstract]
269. Hainzl S, Peking P, Kocher T, et al.: COL7A1 Editing via CRISPR/Cas9 in Recessive Dystrophic Epidermolysis Bullosa. Mol Ther 25 (11): 2573-2584, 2017. [PUBMED Abstract]
270. Shinkuma S, Guo Z, Christiano AM: Site-specific genome editing for correction of induced pluripotent stem cells derived from dominant dystrophic epidermolysis bullosa. Proc Natl Acad Sci U S A 113 (20): 5676-81, 2016. [PUBMED Abstract]
271. Siprashvili Z, Nguyen NT, Gorell ES, et al.: Safety and Wound Outcomes Following Genetically Corrected Autologous Epidermal Grafts in Patients With Recessive Dystrophic Epidermolysis Bullosa. JAMA 316 (17): 1808-1817, 2016. [PUBMED Abstract]
272. Webber BR, Osborn MJ, McElroy AN, et al.: CRISPR/Cas9-based genetic correction for recessive dystrophic epidermolysis bullosa. NPJ Regen Med 1: , 2016. [PUBMED Abstract]
273. Mosallaei D, Hao M, Antaya RJ, et al.: Molecular and Clinical Outcomes After Intravenous Gentamicin Treatment for Patients With Junctional Epidermolysis Bullosa Caused by Nonsense Variants. JAMA Dermatol 158 (4): 366-374, 2022. [PUBMED Abstract]
274. Guide SV, Gonzalez ME, Bağcı IS, et al.: Trial of Beremagene Geperpavec (B-VEC) for Dystrophic Epidermolysis Bullosa. N Engl J Med 387 (24): 2211-2219, 2022. [PUBMED Abstract]

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68. van der Rhee JI, Krijnen P, Grui
    

Pheochromocytoma and paraganglioma are rare catecholamine-producing tumors with a combined annual incidence of three cases per 1 million individuals. These tumors are also rare in the pediatric and adolescent population, accounting for approximately 20% of all cases.[1,2]

References

1. Barontini M, Levin G, Sanso G: Characteristics of pheochromocytoma in a 4- to 20-year-old population. Ann N Y Acad Sci 1073: 30-7, 2006. [PUBMED Abstract]
2. King KS, Prodanov T, Kantorovich V, et al.: Metastatic pheochromocytoma/paraganglioma related to primary tumor development in childhood or adolescence: significant link to SDHB mutations. J Clin Oncol 29 (31): 4137-42, 2011. [PUBMED Abstract]

Tumors arising within the adrenal gland are known as pheochromocytomas, whereas morphologically identical tumors arising elsewhere are termed paragangliomas. Paragangliomas are further divided into the following subtypes:[1,2]

References

1. Lenders JW, Eisenhofer G, Mannelli M, et al.: Phaeochromocytoma. Lancet 366 (9486): 665-75, 2005 Aug 20-26. [PUBMED Abstract]
2. Waguespack SG, Rich T, Grubbs E, et al.: A current review of the etiology, diagnosis, and treatment of pediatric pheochromocytoma and paraganglioma. J Clin Endocrinol Metab 95 (5): 2023-37, 2010. [PUBMED Abstract]

Comprehensive molecular profiling of 173 cases of pheochromocytomas and paragangliomas (mean age at diagnosis, 47 years) identified three well-defined molecular subgroups: pseudohypoxia-related clusters 1A and 1B, kinase signaling–related cluster 2, and WNT signaling–related cluster 3.[1] About 70% of patients with pheochromocytoma and paraganglioma can be assigned to one of these clusters. Each cluster has unique clinical, biochemical, and imaging characteristics that may help guide the treatment and follow-up of patients.[2,3]

References

1. Fishbein L, Leshchiner I, Walter V, et al.: Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma. Cancer Cell 31 (2): 181-193, 2017. [PUBMED Abstract]
2. Nölting S, Bechmann N, Taieb D, et al.: Personalized Management of Pheochromocytoma and Paraganglioma. Endocr Rev 43 (2): 199-239, 2022. [PUBMED Abstract]
3. Crona J, Taïeb D, Pacak K: New Perspectives on Pheochromocytoma and Paraganglioma: Toward a Molecular Classification. Endocr Rev 38 (6): 489-515, 2017. [PUBMED Abstract]
4. Nölting S, Ullrich M, Pietzsch J, et al.: Current Management of Pheochromocytoma/Paraganglioma: A Guide for the Practicing Clinician in the Era of Precision Medicine. Cancers (Basel) 11 (10): , 2019. [PUBMED Abstract]
5. Alrezk R, Suarez A, Tena I, et al.: Update of Pheochromocytoma Syndromes: Genetics, Biochemical Evaluation, and Imaging. Front Endocrinol (Lausanne) 9: 515, 2018. [PUBMED Abstract]

Up to 30% of all pheochromocytomas and paragangliomas are estimated to be familial, and several susceptibility genes have been described (see Table 2). The median age at presentation in most familial syndromes is 30 to 35 years, and up to 50% of patients have the disease by age 26 years.[1–4]

Genetic factors and syndromes associated with an increased risk of pheochromocytoma and paraganglioma include the following:

References

1. Welander J, Söderkvist P, Gimm O: Genetics and clinical characteristics of hereditary pheochromocytomas and paragangliomas. Endocr Relat Cancer 18 (6): R253-76, 2011. [PUBMED Abstract]
2. Timmers HJ, Gimenez-Roqueplo AP, Mannelli M, et al.: Clinical aspects of SDHx-related pheochromocytoma and paraganglioma. Endocr Relat Cancer 16 (2): 391-400, 2009. [PUBMED Abstract]
3. Ricketts CJ, Forman JR, Rattenberry E, et al.: Tumor risks and genotype-phenotype-proteotype analysis in 358 patients with germline mutations in SDHB and SDHD. Hum Mutat 31 (1): 41-51, 2010. [PUBMED Abstract]
4. Burnichon N, Cascón A, Schiavi F, et al.: MAX mutations cause hereditary and sporadic pheochromocytoma and paraganglioma. Clin Cancer Res 18 (10): 2828-37, 2012. [PUBMED Abstract]
5. Boikos SA, Xekouki P, Fumagalli E, et al.: Carney triad can be (rarely) associated with germline succinate dehydrogenase defects. Eur J Hum Genet 24 (4): 569-73, 2016. [PUBMED Abstract]
6. Stratakis CA, Carney JA: The triad of paragangliomas, gastric stromal tumours and pulmonary chondromas (Carney triad), and the dyad of paragangliomas and gastric stromal sarcomas (Carney-Stratakis syndrome): molecular genetics and clinical implications. J Intern Med 266 (1): 43-52, 2009. [PUBMED Abstract]
7. Abdallah A, Pappo A, Reiss U, et al.: Clinical manifestations of Pacak-Zhuang syndrome in a male pediatric patient. Pediatr Blood Cancer 67 (4): e28096, 2020. [PUBMED Abstract]
8. Kamihara J, Hamilton KV, Pollard JA, et al.: Belzutifan, a Potent HIF2α Inhibitor, in the Pacak-Zhuang Syndrome. N Engl J Med 385 (22): 2059-2065, 2021. [PUBMED Abstract]

Studies of germline variants in young patients with pheochromocytoma or paraganglioma have shown that these patients have a high prevalence (70%–80%) of germline pathogenic variants and have further characterized this group of neoplasms, as follows:

Immunohistochemical SDHB staining may help triage genetic testing. Tumors of patients with SDHB, SDHC, and SDHD variants have absent or weak staining, while sporadic tumors and those associated with other constitutional syndromes have positive staining.[8,9] Therefore, immunohistochemical SDHB staining can help identify potential carriers of SDH variants early, obviating the need for extensive and costly testing of other genes. Early identification of young patients with SDHB variants using radiographic, serological, and immunohistochemical markers could potentially decrease mortality and identify other family members who carry a germline SDHB pathogenic variant.

Given the higher prevalence of germline alterations in children and adolescents with pheochromocytoma and paraganglioma, genetic counseling and testing should be considered in this younger population.

References

1. King KS, Prodanov T, Kantorovich V, et al.: Metastatic pheochromocytoma/paraganglioma related to primary tumor development in childhood or adolescence: significant link to SDHB mutations. J Clin Oncol 29 (31): 4137-42, 2011. [PUBMED Abstract]
2. Neumann HP, Bausch B, McWhinney SR, et al.: Germ-line mutations in nonsyndromic pheochromocytoma. N Engl J Med 346 (19): 1459-66, 2002. [PUBMED Abstract]
3. Babic B, Patel D, Aufforth R, et al.: Pediatric patients with pheochromocytoma and paraganglioma should have routine preoperative genetic testing for common susceptibility genes in addition to imaging to detect extra-adrenal and metastatic tumors. Surgery 161 (1): 220-227, 2017. [PUBMED Abstract]
4. Redlich A, Pamporaki C, Lessel L, et al.: Pseudohypoxic pheochromocytomas and paragangliomas dominate in children. Pediatr Blood Cancer 68 (7): e28981, 2021. [PUBMED Abstract]
5. Bausch B, Wellner U, Bausch D, et al.: Long-term prognosis of patients with pediatric pheochromocytoma. Endocr Relat Cancer 21 (1): 17-25, 2014. [PUBMED Abstract]
6. Pamporaki C, Hamplova B, Peitzsch M, et al.: Characteristics of Pediatric vs Adult Pheochromocytomas and Paragangliomas. J Clin Endocrinol Metab 102 (4): 1122-1132, 2017. [PUBMED Abstract]
7. Jochmanova I, Abcede AMT, Guerrero RJS, et al.: Clinical characteristics and outcomes of SDHB-related pheochromocytoma and paraganglioma in children and adolescents. J Cancer Res Clin Oncol 146 (4): 1051-1063, 2020. [PUBMED Abstract]
8. Gill AJ, Benn DE, Chou A, et al.: Immunohistochemistry for SDHB triages genetic testing of SDHB, SDHC, and SDHD in paraganglioma-pheochromocytoma syndromes. Hum Pathol 41 (6): 805-14, 2010. [PUBMED Abstract]
9. van Nederveen FH, Gaal J, Favier J, et al.: An immunohistochemical procedure to detect patients with paraganglioma and phaeochromocytoma with germline SDHB, SDHC, or SDHD gene mutations: a retrospective and prospective analysis. Lancet Oncol 10 (8): 764-71, 2009. [PUBMED Abstract]
10. Geroula A, Deutschbein T, Langton K, et al.: Pheochromocytoma and paraganglioma: clinical feature-based disease probability in relation to catecholamine biochemistry and reason for disease suspicion. Eur J Endocrinol 181 (4): 409-420, 2019. [PUBMED Abstract]
11. Lenders JW, Eisenhofer G, Mannelli M, et al.: Phaeochromocytoma. Lancet 366 (9486): 665-75, 2005 Aug 20-26. [PUBMED Abstract]
12. Pham TH, Moir C, Thompson GB, et al.: Pheochromocytoma and paraganglioma in children: a review of medical and surgical management at a tertiary care center. Pediatrics 118 (3): 1109-17, 2006. [PUBMED Abstract]
13. Waguespack SG, Rich T, Grubbs E, et al.: A current review of the etiology, diagnosis, and treatment of pediatric pheochromocytoma and paraganglioma. J Clin Endocrinol Metab 95 (5): 2023-37, 2010. [PUBMED Abstract]
14. Lenders JW, Pacak K, Walther MM, et al.: Biochemical diagnosis of pheochromocytoma: which test is best? JAMA 287 (11): 1427-34, 2002. [PUBMED Abstract]
15. Sarathi V, Pandit R, Patil VK, et al.: Performance of plasma fractionated free metanephrines by enzyme immunoassay in the diagnosis of pheochromocytoma and paraganglioma in children. Endocr Pract 18 (5): 694-9, 2012 Sep-Oct. [PUBMED Abstract]
16. Eisenhofer G, Pacak K, Huynh TT, et al.: Catecholamine metabolomic and secretory phenotypes in phaeochromocytoma. Endocr Relat Cancer 18 (1): 97-111, 2011. [PUBMED Abstract]
17. Eisenhofer G, Timmers HJ, Lenders JW, et al.: Age at diagnosis of pheochromocytoma differs according to catecholamine phenotype and tumor location. J Clin Endocrinol Metab 96 (2): 375-84, 2011. [PUBMED Abstract]
18. Taïeb D, Neumann H, Rubello D, et al.: Modern nuclear imaging for paragangliomas: beyond SPECT. J Nucl Med 53 (2): 264-74, 2012. [PUBMED Abstract]
19. Janssen I, Blanchet EM, Adams K, et al.: Superiority of [68Ga]-DOTATATE PET/CT to Other Functional Imaging Modalities in the Localization of SDHB-Associated Metastatic Pheochromocytoma and Paraganglioma. Clin Cancer Res 21 (17): 3888-95, 2015. [PUBMED Abstract]
20. Timmers HJ, Chen CC, Carrasquillo JA, et al.: Comparison of 18F-fluoro-L-DOPA, 18F-fluoro-deoxyglucose, and 18F-fluorodopamine PET and 123I-MIBG scintigraphy in the localization of pheochromocytoma and paraganglioma. J Clin Endocrinol Metab 94 (12): 4757-67, 2009. [PUBMED Abstract]
21. Sait S, Pandit-Taskar N, Modak S: Failure of MIBG scan to detect metastases in SDHB-mutated pediatric metastatic pheochromocytoma. Pediatr Blood Cancer 64 (11): , 2017. [PUBMED Abstract]
22. Nölting S, Bechmann N, Taieb D, et al.: Personalized Management of Pheochromocytoma and Paraganglioma. Endocr Rev 43 (2): 199-239, 2022. [PUBMED Abstract]
23. Jaiswal SK, Sarathi V, Malhotra G, et al.: The utility of 68Ga-DOTATATE PET/CT in localizing primary/metastatic pheochromocytoma and paraganglioma in children and adolescents - a single-center experience. J Pediatr Endocrinol Metab 34 (1): 109-119, 2021. [PUBMED Abstract]
24. Amar L, Pacak K, Steichen O, et al.: International consensus on initial screening and follow-up of asymptomatic SDHx mutation carriers. Nat Rev Endocrinol 17 (7): 435-444, 2021. [PUBMED Abstract]

Cancer in children and adolescents is rare, although the overall incidence has slowly increased since 1975.[1] Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the following pediatric specialists and others to ensure that children receive treatment, supportive care, and rehabilitation to achieve optimal survival and quality of life:

For specific information about supportive care for children and adolescents with cancer, see the summaries on Supportive and Palliative Care.

The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of children and adolescents with cancer.[2] At these centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with current standard therapy. Other types of clinical trials test novel therapies when there is no standard therapy for a cancer diagnosis. Most of the progress in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.

Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2020, childhood cancer mortality decreased by more than 50%.[3–5] Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. For information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors, see Late Effects of Treatment for Childhood Cancer.

Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[6] The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 people in the United States. Therefore, all pediatric cancers are considered rare.

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.[7,8] In children and adolescents, the designation of a rare tumor is not uniform among international groups, as follows:

These rare cancers are extremely challenging to study because of the relatively few patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the small number 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 Pheochromocytoma and Paraganglioma Treatment.

References

1. Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010. [PUBMED Abstract]
2. American Academy of Pediatrics: Standards for pediatric cancer centers. Pediatrics 134 (2): 410-4, 2014. Also available online. Last accessed February 25, 2025.
3. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014. [PUBMED Abstract]
4. National Cancer Institute: NCCR*Explorer: An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed February 25, 2025.
5. Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed December 30, 2024.
6. Ward E, DeSantis C, Robbins A, et al.: Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 64 (2): 83-103, 2014 Mar-Apr. [PUBMED Abstract]
7. Gatta G, Capocaccia R, Botta L, et al.: Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet-a population-based study. Lancet Oncol 18 (8): 1022-1039, 2017. [PUBMED Abstract]
8. DeSantis CE, Kramer JL, Jemal A: The burden of rare cancers in the United States. CA Cancer J Clin 67 (4): 261-272, 2017. [PUBMED Abstract]
9. Ferrari A, Brecht IB, Gatta G, et al.: Defining and listing very rare cancers of paediatric age: consensus of the Joint Action on Rare Cancers in cooperation with the European Cooperative Study Group for Pediatric Rare Tumors. Eur J Cancer 110: 120-126, 2019. [PUBMED Abstract]
10. Pappo AS, Krailo M, Chen Z, et al.: Infrequent tumor initiative of the Children’s Oncology Group: initial lessons learned and their impact on future plans. J Clin Oncol 28 (33): 5011-6, 2010. [PUBMED Abstract]

Treatment options for childhood paraganglioma and pheochromocytoma include the following:

Treatment of paraganglioma and pheochromocytoma is surgical. For secreting tumors, alpha- and beta-adrenergic blockade must be optimized before surgery. A single-institution study reviewed the experience of laparoscopic partial adrenalectomy for bilateral pheochromocytoma in patients with von Hippel-Lindau disease.[2] In eight patients, all 16 adrenalectomies were performed laparoscopically. Fourteen of the procedures were partial adrenalectomies, and two patients required a contralateral total adrenalectomy because of tumor size and diffuse multinodularity. Two patients had new ipsilateral tumors identified after a median follow-up of 5 years (range, 4–6 years), with one patient who underwent repeat partial adrenalectomy. There were no deaths during the study period.

For patients with metastatic disease, responses have been documented to some chemotherapeutic regimens such as gemcitabine and docetaxel or different combinations of vincristine, cyclophosphamide, doxorubicin, and dacarbazine.[3–5] Chemotherapy may help alleviate symptoms and facilitate surgery, although its impact on overall survival is less clear.

Responses have also been obtained with high-dose 131I-MIBG and sunitinib.[6,7]

Specific consensus guidelines for the diagnosis and management of pheochromocytoma and paraganglioma in patients with germline SDHB and SDHD pathogenic variants have been published.[8,9]

References

1. Granberg D, Juhlin CC, Falhammar H: Metastatic Pheochromocytomas and Abdominal Paragangliomas. J Clin Endocrinol Metab 106 (5): e1937-e1952, 2021. [PUBMED Abstract]
2. Rubalcava NS, Overman RE, Kartal TT, et al.: Laparoscopic adrenal-sparing approach for children with bilateral pheochromocytoma in Von Hippel-Lindau disease. J Pediatr Surg 57 (3): 414-417, 2022. [PUBMED Abstract]
3. Mora J, Cruz O, Parareda A, et al.: Treatment of disseminated paraganglioma with gemcitabine and docetaxel. Pediatr Blood Cancer 53 (4): 663-5, 2009. [PUBMED Abstract]
4. Huang H, Abraham J, Hung E, et al.: Treatment of malignant pheochromocytoma/paraganglioma with cyclophosphamide, vincristine, and dacarbazine: recommendation from a 22-year follow-up of 18 patients. Cancer 113 (8): 2020-8, 2008. [PUBMED Abstract]
5. Patel SR, Winchester DJ, Benjamin RS: A 15-year experience with chemotherapy of patients with paraganglioma. Cancer 76 (8): 1476-80, 1995. [PUBMED Abstract]
6. Gonias S, Goldsby R, Matthay KK, et al.: Phase II study of high-dose [131I]metaiodobenzylguanidine therapy for patients with metastatic pheochromocytoma and paraganglioma. J Clin Oncol 27 (25): 4162-8, 2009. [PUBMED Abstract]
7. Joshua AM, Ezzat S, Asa SL, et al.: Rationale and evidence for sunitinib in the treatment of malignant paraganglioma/pheochromocytoma. J Clin Endocrinol Metab 94 (1): 5-9, 2009. [PUBMED Abstract]
8. Taïeb D, Wanna GB, Ahmad M, et al.: Clinical consensus guideline on the management of phaeochromocytoma and paraganglioma in patients harbouring germline SDHD pathogenic variants. Lancet Diabetes Endocrinol 11 (5): 345-361, 2023. [PUBMED Abstract]
9. Taïeb D, Nölting S, Perrier ND, et al.: Management of phaeochromocytoma and paraganglioma in patients with germline SDHB pathogenic variants: an international expert Consensus statement. Nat Rev Endocrinol 20 (3): 168-184, 2024. [PUBMED Abstract]

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, see the ClinicalTrials.gov website.

The following are examples of national and/or institutional clinical trials that are currently being conducted:

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.

This summary was comprehensively reviewed.

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® Cancer Information for Health Professionals pages.

MEN syndromes are familial disorders characterized by neoplastic changes that affect multiple endocrine organs.[1] Changes may include hyperplasia, benign adenomas, and carcinomas.

There are three types of MEN syndromes:

For more information about MEN syndromes, see Genetics of Endocrine and Neuroendocrine Neoplasias and Multiple Endocrine Neoplasia Type 2 (MEN2).

References

1. de Krijger RR: Endocrine tumor syndromes in infancy and childhood. Endocr Pathol 15 (3): 223-6, 2004. [PUBMED Abstract]

The main clinical features and genetic alterations of the multiple endocrine neoplasia (MEN) syndromes are shown in Table 1.

References

1. Thakker RV: Multiple endocrine neoplasia–syndromes of the twentieth century. J Clin Endocrinol Metab 83 (8): 2617-20, 1998. [PUBMED Abstract]
2. Thakker RV: Multiple endocrine neoplasia type 1 (MEN1). Best Pract Res Clin Endocrinol Metab 24 (3): 355-70, 2010. [PUBMED Abstract]
3. Vannucci L, Marini F, Giusti F, et al.: MEN1 in children and adolescents: Data from patients of a regional referral center for hereditary endocrine tumors. Endocrine 59 (2): 438-448, 2018. [PUBMED Abstract]
4. Thakker RV, Newey PJ, Walls GV, et al.: Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab 97 (9): 2990-3011, 2012. [PUBMED Abstract]
5. Goudet P, Dalac A, Le Bras M, et al.: MEN1 disease occurring before 21 years old: a 160-patient cohort study from the Groupe d’étude des Tumeurs Endocrines. J Clin Endocrinol Metab 100 (4): 1568-77, 2015. [PUBMED Abstract]
6. Romero Arenas MA, Morris LF, Rich TA, et al.: Preoperative multiple endocrine neoplasia type 1 diagnosis improves the surgical outcomes of pediatric patients with primary hyperparathyroidism. J Pediatr Surg 49 (4): 546-50, 2014. [PUBMED Abstract]
7. Farnebo F, Teh BT, Kytölä S, et al.: Alterations of the MEN1 gene in sporadic parathyroid tumors. J Clin Endocrinol Metab 83 (8): 2627-30, 1998. [PUBMED Abstract]
8. Field M, Shanley S, Kirk J: Inherited cancer susceptibility syndromes in paediatric practice. J Paediatr Child Health 43 (4): 219-29, 2007. [PUBMED Abstract]
9. Sanso GE, Domene HM, Garcia R, et al.: Very early detection of RET proto-oncogene mutation is crucial for preventive thyroidectomy in multiple endocrine neoplasia type 2 children: presence of C-cell malignant disease in asymptomatic carriers. Cancer 94 (2): 323-30, 2002. [PUBMED Abstract]
10. Alsanea O, Clark OH: Familial thyroid cancer. Curr Opin Oncol 13 (1): 44-51, 2001. [PUBMED Abstract]
11. Fitze G: Management of patients with hereditary medullary thyroid carcinoma. Eur J Pediatr Surg 14 (6): 375-83, 2004. [PUBMED Abstract]
12. Puñales MK, da Rocha AP, Meotti C, et al.: Clinical and oncological features of children and young adults with multiple endocrine neoplasia type 2A. Thyroid 18 (12): 1261-8, 2008. [PUBMED Abstract]
13. Wells SA, Asa SL, Dralle H, et al.: Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid 25 (6): 567-610, 2015. [PUBMED Abstract]
14. Waguespack SG, Rich TA, Perrier ND, et al.: Management of medullary thyroid carcinoma and MEN2 syndromes in childhood. Nat Rev Endocrinol 7 (10): 596-607, 2011. [PUBMED Abstract]
15. Decker RA, Peacock ML, Watson P: Hirschsprung disease in MEN 2A: increased spectrum of RET exon 10 genotypes and strong genotype-phenotype correlation. Hum Mol Genet 7 (1): 129-34, 1998. [PUBMED Abstract]
16. Eng C, Clayton D, Schuffenecker I, et al.: The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis. JAMA 276 (19): 1575-9, 1996. [PUBMED Abstract]
17. Fialkowski EA, DeBenedetti MK, Moley JF, et al.: RET proto-oncogene testing in infants presenting with Hirschsprung disease identifies 2 new multiple endocrine neoplasia 2A kindreds. J Pediatr Surg 43 (1): 188-90, 2008. [PUBMED Abstract]
18. Skába R, Dvoráková S, Václavíková E, et al.: The risk of medullary thyroid carcinoma in patients with Hirschsprung’s disease. Pediatr Surg Int 22 (12): 991-5, 2006. [PUBMED Abstract]
19. Moore SW, Zaahl MG: Multiple endocrine neoplasia syndromes, children, Hirschsprung’s disease and RET. Pediatr Surg Int 24 (5): 521-30, 2008. [PUBMED Abstract]
20. Skinner MA, DeBenedetti MK, Moley JF, et al.: Medullary thyroid carcinoma in children with multiple endocrine neoplasia types 2A and 2B. J Pediatr Surg 31 (1): 177-81; discussion 181-2, 1996. [PUBMED Abstract]
21. Brauckhoff M, Gimm O, Weiss CL, et al.: Multiple endocrine neoplasia 2B syndrome due to codon 918 mutation: clinical manifestation and course in early and late onset disease. World J Surg 28 (12): 1305-11, 2004. [PUBMED Abstract]
22. Sakorafas GH, Friess H, Peros G: The genetic basis of hereditary medullary thyroid cancer: clinical implications for the surgeon, with a particular emphasis on the role of prophylactic thyroidectomy. Endocr Relat Cancer 15 (4): 871-84, 2008. [PUBMED Abstract]
23. Makri A, Akshintala S, Derse-Anthony C, et al.: Pheochromocytoma in Children and Adolescents With Multiple Endocrine Neoplasia Type 2B. J Clin Endocrinol Metab 104 (1): 7-12, 2019. [PUBMED Abstract]
24. Machens A, Elwerr M, Lorenz K, et al.: Long-term outcome of prophylactic thyroidectomy in children carrying RET germline mutations. Br J Surg 105 (2): e150-e157, 2018. [PUBMED Abstract]
25. Kloos RT, Eng C, Evans DB, et al.: Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid 19 (6): 565-612, 2009. [PUBMED Abstract]
26. de Krijger RR: Endocrine tumor syndromes in infancy and childhood. Endocr Pathol 15 (3): 223-6, 2004. [PUBMED Abstract]
27. Pellegata NS, Quintanilla-Martinez L, Siggelkow H, et al.: Germ-line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans. Proc Natl Acad Sci U S A 103 (42): 15558-63, 2006. [PUBMED Abstract]
28. Chevalier B, Coppin L, Romanet P, et al.: Beyond MEN1, When to Think About MEN4? Retrospective Study on 5600 Patients in the French Population and Literature Review. J Clin Endocrinol Metab 109 (7): e1482-e1493, 2024. [PUBMED Abstract]
29. Chasseloup F, Pankratz N, Lane J, et al.: Germline CDKN1B Loss-of-Function Variants Cause Pediatric Cushing’s Disease With or Without an MEN4 Phenotype. J Clin Endocrinol Metab 105 (6): 1983-2005, 2020. [PUBMED Abstract]

Cancer in children and adolescents is rare, although the overall incidence has slowly increased since 1975.[1] Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the following pediatric specialists and others to ensure that children receive treatment, supportive care, and rehabilitation to achieve optimal survival and quality of life:

For specific information about supportive care for children and adolescents with cancer, see the summaries on Supportive and Palliative Care.

The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of children and adolescents with cancer.[2] At these centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with current standard therapy. Other types of clinical trials test novel therapies when there is no standard therapy for a cancer diagnosis. Most of the progress in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.

Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2020, childhood cancer mortality decreased by more than 50%.[3–5] Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. For information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors, see Late Effects of Treatment for Childhood Cancer.

Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[6] The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 people in the United States. Therefore, all pediatric cancers are considered rare.

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.[7,8] In children and adolescents, the designation of a rare tumor is not uniform among international groups, as follows:

These rare cancers are extremely challenging to study because of the relatively few patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the small number of clinical trials for adolescents with rare cancers.

References

1. Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010. [PUBMED Abstract]
2. American Academy of Pediatrics: Standards for pediatric cancer centers. Pediatrics 134 (2): 410-4, 2014. Also available online. Last accessed February 25, 2025.
3. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014. [PUBMED Abstract]
4. National Cancer Institute: NCCR*Explorer: An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed February 25, 2025.
5. Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed December 30, 2024.
6. Ward E, DeSantis C, Robbins A, et al.: Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 64 (2): 83-103, 2014 Mar-Apr. [PUBMED Abstract]
7. Gatta G, Capocaccia R, Botta L, et al.: Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet-a population-based study. Lancet Oncol 18 (8): 1022-1039, 2017. [PUBMED Abstract]
8. DeSantis CE, Kramer JL, Jemal A: The burden of rare cancers in the United States. CA Cancer J Clin 67 (4): 261-272, 2017. [PUBMED Abstract]
9. Ferrari A, Brecht IB, Gatta G, et al.: Defining and listing very rare cancers of paediatric age: consensus of the Joint Action on Rare Cancers in cooperation with the European Cooperative Study Group for Pediatric Rare Tumors. Eur J Cancer 110: 120-126, 2019. [PUBMED Abstract]
10. Pappo AS, Krailo M, Chen Z, et al.: Infrequent tumor initiative of the Children’s Oncology Group: initial lessons learned and their impact on future plans. J Clin Oncol 28 (33): 5011-6, 2010. [PUBMED Abstract]

Treatment options for childhood MEN syndromes, according to type, are as follows:

References

1. Romero Arenas MA, Morris LF, Rich TA, et al.: Preoperative multiple endocrine neoplasia type 1 diagnosis improves the surgical outcomes of pediatric patients with primary hyperparathyroidism. J Pediatr Surg 49 (4): 546-50, 2014. [PUBMED Abstract]
2. Skinner MA, Moley JA, Dilley WG, et al.: Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A. N Engl J Med 353 (11): 1105-13, 2005. [PUBMED Abstract]
3. Skinner MA: Management of hereditary thyroid cancer in children. Surg Oncol 12 (2): 101-4, 2003. [PUBMED Abstract]
4. Fitze G: Management of patients with hereditary medullary thyroid carcinoma. Eur J Pediatr Surg 14 (6): 375-83, 2004. [PUBMED Abstract]
5. Learoyd DL, Gosnell J, Elston MS, et al.: Experience of prophylactic thyroidectomy in multiple endocrine neoplasia type 2A kindreds with RET codon 804 mutations. Clin Endocrinol (Oxf) 63 (6): 636-41, 2005. [PUBMED Abstract]
6. Guillem JG, Wood WC, Moley JF, et al.: ASCO/SSO review of current role of risk-reducing surgery in common hereditary cancer syndromes. J Clin Oncol 24 (28): 4642-60, 2006. [PUBMED Abstract]
7. National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Thyroid Carcinoma. Version 2.2019. Plymouth Meeting, Pa: National Comprehensive Cancer Network, 2019. Available online with free subscription. Last accessed June 08, 2020.
8. Lallier M, St-Vil D, Giroux M, et al.: Prophylactic thyroidectomy for medullary thyroid carcinoma in gene carriers of MEN2 syndrome. J Pediatr Surg 33 (6): 846-8, 1998. [PUBMED Abstract]
9. Dralle H, Gimm O, Simon D, et al.: Prophylactic thyroidectomy in 75 children and adolescents with hereditary medullary thyroid carcinoma: German and Austrian experience. World J Surg 22 (7): 744-50; discussion 750-1, 1998. [PUBMED Abstract]
10. Skinner MA, Wells SA: Medullary carcinoma of the thyroid gland and the MEN 2 syndromes. Semin Pediatr Surg 6 (3): 134-40, 1997. [PUBMED Abstract]
11. Voss RK, Feng L, Lee JE, et al.: Medullary Thyroid Carcinoma in MEN2A: ATA Moderate- or High-Risk RET Mutations Do Not Predict Disease Aggressiveness. J Clin Endocrinol Metab 102 (8): 2807-2813, 2017. [PUBMED Abstract]
12. Heizmann O, Haecker FM, Zumsteg U, et al.: Presymptomatic thyroidectomy in multiple endocrine neoplasia 2a. Eur J Surg Oncol 32 (1): 98-102, 2006. [PUBMED Abstract]
13. Frank-Raue K, Buhr H, Dralle H, et al.: Long-term outcome in 46 gene carriers of hereditary medullary thyroid carcinoma after prophylactic thyroidectomy: impact of individual RET genotype. Eur J Endocrinol 155 (2): 229-36, 2006. [PUBMED Abstract]
14. Piolat C, Dyon JF, Sturm N, et al.: Very early prophylactic thyroid surgery for infants with a mutation of the RET proto-oncogene at codon 634: evaluation of the implementation of international guidelines for MEN type 2 in a single centre. Clin Endocrinol (Oxf) 65 (1): 118-24, 2006. [PUBMED Abstract]
15. National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Thyroid Carcinoma. Version 1.2018. Fort Washington, Pa: National Comprehensive Cancer Network, 2018. Available online with free subscription. Last accessed July 5, 2018.
16. Leboulleux S, Travagli JP, Caillou B, et al.: Medullary thyroid carcinoma as part of a multiple endocrine neoplasia type 2B syndrome: influence of the stage on the clinical course. Cancer 94 (1): 44-50, 2002. [PUBMED Abstract]
17. Sakorafas GH, Friess H, Peros G: The genetic basis of hereditary medullary thyroid cancer: clinical implications for the surgeon, with a particular emphasis on the role of prophylactic thyroidectomy. Endocr Relat Cancer 15 (4): 871-84, 2008. [PUBMED Abstract]
18. Zenaty D, Aigrain Y, Peuchmaur M, et al.: Medullary thyroid carcinoma identified within the first year of life in children with hereditary multiple endocrine neoplasia type 2A (codon 634) and 2B. Eur J Endocrinol 160 (5): 807-13, 2009. [PUBMED Abstract]
19. Brauckhoff M, Machens A, Lorenz K, et al.: Surgical curability of medullary thyroid cancer in multiple endocrine neoplasia 2B: a changing perspective. Ann Surg 259 (4): 800-6, 2014. [PUBMED Abstract]
20. Wells SA, Robinson BG, Gagel RF, et al.: Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol 30 (2): 134-41, 2012. [PUBMED Abstract]
21. Fox E, Widemann BC, Chuk MK, et al.: Vandetanib in children and adolescents with multiple endocrine neoplasia type 2B associated medullary thyroid carcinoma. Clin Cancer Res 19 (15): 4239-48, 2013. [PUBMED Abstract]
22. Kraft IL, Akshintala S, Zhu Y, et al.: Outcomes of Children and Adolescents with Advanced Hereditary Medullary Thyroid Carcinoma Treated with Vandetanib. Clin Cancer Res 24 (4): 753-765, 2018. [PUBMED Abstract]
23. Kurzrock R, Sherman SI, Ball DW, et al.: Activity of XL184 (Cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer. J Clin Oncol 29 (19): 2660-6, 2011. [PUBMED Abstract]
24. Elisei R, Schlumberger MJ, Müller SP, et al.: Cabozantinib in progressive medullary thyroid cancer. J Clin Oncol 31 (29): 3639-46, 2013. [PUBMED Abstract]
25. Wirth LJ, Sherman E, Robinson B, et al.: Efficacy of Selpercatinib in RET-Altered Thyroid Cancers. N Engl J Med 383 (9): 825-835, 2020. [PUBMED Abstract]
26. Eli Lilly and Company: RETEVMO (selpercatinib): Prescribing Information. Indianapolis, Ind: Lilly USA, LLC, 2024. Available online. Last accessed November 29, 2024.

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, see the 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® Cancer Information for Health Professionals pages.

Mesothelioma is extremely rare in children and adolescents, with only 2% to 5% of patients presenting during the first two decades of life.[1] Fewer than 300 cases in children have been reported.[2] An analysis from the National Cancer Database identified 46 pediatric patients (aged 0–21 years) and 524 young adult patients (aged 22–39 years) with mesothelioma (363 peritoneal and 207 pleural).[3] Patients with peritoneal mesothelioma were more frequently female (63.1%). The mean overall survival was higher in patients with peritoneal mesothelioma (125 months) than in those with pleural mesothelioma (69 months), which remained significant after stratification of pediatric and young adult patients.

In adults, increased mesothelioma risk is associated with inherited BAP1 variants, exposures to asbestos, and exposures to radiation therapy during previous cancer treatments. These risk factors are rare in pediatric patients, and there are limited data that address cancer risk in children with asbestos exposures. The amount of radiation exposure required to develop cancer is also unknown.[4–8]

Mesothelioma may present in the thoracic/pleural region or in the peritoneum. These presentations have different clinical courses and prognoses. This cancer can involve the membranous coverings of the lung, the heart, or the abdominal organs.[9–11]; [12][Level of evidence C1] Mesothelioma can spread onto organ surfaces without invading far into the underlying tissue. This cancer may also spread to regional or distant lymph nodes.

Benign and malignant mesotheliomas cannot be differentiated using histological criteria. Benign mesotheliomas are exceedingly rare and often occur in the peritoneal cavity. A poor prognosis is associated with mesotheliomas that are diffuse and invasive or with mesotheliomas that recur.

References

1. Nagata S, Nakanishi R: Malignant pleural mesothelioma with cavity formation in a 16-year-old boy. Chest 127 (2): 655-7, 2005. [PUBMED Abstract]
2. Rosas-Salazar C, Gunawardena SW, Spahr JE: Malignant pleural mesothelioma in a child with ataxia-telangiectasia. Pediatr Pulmonol 48 (1): 94-7, 2013. [PUBMED Abstract]
3. Nofi CP, Roberts BK, Rich BS, et al.: Pediatric, Adolescent and Young Adult (AYA) Peritoneal and Pleural Mesothelioma: A National Cancer Database Review. J Pediatr Surg 59 (6): 1113-1120, 2024. [PUBMED Abstract]
4. Orbach D, André N, Brecht IB, et al.: Mesothelioma in children and adolescents: the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) contribution. Eur J Cancer 140: 63-70, 2020. [PUBMED Abstract]
5. Tsao AS, Wistuba I, Roth JA, et al.: Malignant pleural mesothelioma. J Clin Oncol 27 (12): 2081-90, 2009. [PUBMED Abstract]
6. Carbone M, Ferris LK, Baumann F, et al.: BAP1 cancer syndrome: malignant mesothelioma, uveal and cutaneous melanoma, and MBAITs. J Transl Med 10: 179, 2012. [PUBMED Abstract]
7. Janes SM, Alrifai D, Fennell DA: Perspectives on the Treatment of Malignant Pleural Mesothelioma. N Engl J Med 385 (13): 1207-1218, 2021. [PUBMED Abstract]
8. Pappo AS, Santana VM, Furman WL, et al.: Post-irradiation malignant mesothelioma. Cancer 79 (1): 192-3, 1997. [PUBMED Abstract]
9. Kelsey A: Mesothelioma in childhood. Pediatr Hematol Oncol 11 (5): 461-2, 1994 Sep-Oct. [PUBMED Abstract]
10. Moran CA, Albores-Saavedra J, Suster S: Primary peritoneal mesotheliomas in children: a clinicopathological and immunohistochemical study of eight cases. Histopathology 52 (7): 824-30, 2008. [PUBMED Abstract]
11. Cioffredi LA, Jänne PA, Jackman DM: Treatment of peritoneal mesothelioma in pediatric patients. Pediatr Blood Cancer 52 (1): 127-9, 2009. [PUBMED Abstract]
12. Vermersch S, Arnaud A, Orbach D, et al.: Multicystic and diffuse malignant peritoneal mesothelioma in children. Pediatr Blood Cancer 67 (6): e28286, 2020. [PUBMED Abstract]

Malignant mesotheliomas found in children, adolescents, and young adults are not often associated with asbestos exposures. This differs from most malignant mesotheliomas seen in adults. Recurring ALK gene fusions have been described in children and adolescents with mesothelioma. These fusions occur most often in female patients with peritoneal primary mesotheliomas. ALK gene fusions involve various partner genes, including STRN, TPM1, and EML4.[1]

References

1. Argani P, Lian DWQ, Agaimy A, et al.: Pediatric Mesothelioma With ALK Fusions: A Molecular and Pathologic Study of 5 Cases. Am J Surg Pathol 45 (5): 653-661, 2021. [PUBMED Abstract]

In suspicious cases of malignant mesotheliomas, diagnostic thoracoscopy should be considered to confirm the diagnosis.[1] Cross-sectional imaging may suggest the diagnosis of peritoneal mesothelioma, but diagnostic biopsy by laparoscopy or open laparotomy is required.

References

1. Nagata S, Nakanishi R: Malignant pleural mesothelioma with cavity formation in a 16-year-old boy. Chest 127 (2): 655-7, 2005. [PUBMED Abstract]

Cancer in children and adolescents is rare, although the overall incidence has slowly increased since 1975.[1] Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the following pediatric specialists and others to ensure that children receive treatment, supportive care, and rehabilitation to achieve optimal survival and quality of life:

For specific information about supportive care for children and adolescents with cancer, see the summaries on Supportive and Palliative Care.

The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of children and adolescents with cancer.[2] At these centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with current standard therapy. Other types of clinical trials test novel therapies when there is no standard therapy for a cancer diagnosis. Most of the progress in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.

Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2020, childhood cancer mortality decreased by more than 50%.[3–5] Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. For information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors, see Late Effects of Treatment for Childhood Cancer.

Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[6] The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 people in the United States. Therefore, all pediatric cancers are considered rare.

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.[7,8] In children and adolescents, the designation of a rare tumor is not uniform among international groups, as follows:

These rare cancers are extremely challenging to study because of the relatively few patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the small number 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 Malignant Mesothelioma Treatment.

References

1. Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010. [PUBMED Abstract]
2. American Academy of Pediatrics: Standards for pediatric cancer centers. Pediatrics 134 (2): 410-4, 2014. Also available online. Last accessed February 25, 2025.
3. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014. [PUBMED Abstract]
4. National Cancer Institute: NCCR*Explorer: An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed February 25, 2025.
5. Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed December 30, 2024.
6. Ward E, DeSantis C, Robbins A, et al.: Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 64 (2): 83-103, 2014 Mar-Apr. [PUBMED Abstract]
7. Gatta G, Capocaccia R, Botta L, et al.: Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet-a population-based study. Lancet Oncol 18 (8): 1022-1039, 2017. [PUBMED Abstract]
8. DeSantis CE, Kramer JL, Jemal A: The burden of rare cancers in the United States. CA Cancer J Clin 67 (4): 261-272, 2017. [PUBMED Abstract]
9. Ferrari A, Brecht IB, Gatta G, et al.: Defining and listing very rare cancers of paediatric age: consensus of the Joint Action on Rare Cancers in cooperation with the European Cooperative Study Group for Pediatric Rare Tumors. Eur J Cancer 110: 120-126, 2019. [PUBMED Abstract]
10. Pappo AS, Krailo M, Chen Z, et al.: Infrequent tumor initiative of the Children’s Oncology Group: initial lessons learned and their impact on future plans. J Clin Oncol 28 (33): 5011-6, 2010. [PUBMED Abstract]

Treatment options for pediatric patients with malignant pleural mesotheliomas are controversial. Outcomes are often poor in these individuals despite treatment with radical surgical resection, chemotherapy, and radiation therapy. Treatments that use newer chemotherapy agents and immunotherapies are under investigation.[1]

Treatment options for childhood malignant mesothelioma include the following:

For more information, see Malignant Mesothelioma Treatment.

References

1. Carbone M, Adusumilli PS, Alexander HR, et al.: Mesothelioma: Scientific clues for prevention, diagnosis, and therapy. CA Cancer J Clin 69 (5): 402-429, 2019. [PUBMED Abstract]
2. Maziak DE, Gagliardi A, Haynes AE, et al.: Surgical management of malignant pleural mesothelioma: a systematic review and evidence summary. Lung Cancer 48 (2): 157-69, 2005. [PUBMED Abstract]
3. Krug LM, Pass HI, Rusch VW, et al.: Multicenter phase II trial of neoadjuvant pemetrexed plus cisplatin followed by extrapleural pneumonectomy and radiation for malignant pleural mesothelioma. J Clin Oncol 27 (18): 3007-13, 2009. [PUBMED Abstract]
4. Treasure T: What is the best approach for surgery of malignant pleural mesothelioma? It is to put our efforts into obtaining trustworthy evidence for practice. J Thorac Cardiovasc Surg 151 (2): 307-9, 2016. [PUBMED Abstract]
5. Orbach D, André N, Brecht IB, et al.: Mesothelioma in children and adolescents: the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) contribution. Eur J Cancer 140: 63-70, 2020. [PUBMED Abstract]
6. Nguyen D, Sugarbaker DJ, Burt BM: Therapeutic R2 resection for pleural mesothelioma. J Thorac Cardiovasc Surg 155 (6): 2734-2735, 2018. [PUBMED Abstract]
7. Wald O, Sugarbaker DJ: New Concepts in the Treatment of Malignant Pleural Mesothelioma. Annu Rev Med 69: 365-377, 2018. [PUBMED Abstract]
8. Malekzadeh P, Good M, Hughes MS: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin in pediatric patients with peritoneal mesothelioma: a single institution experience and long term follow up. Int J Hyperthermia 38 (1): 326-331, 2021. [PUBMED Abstract]
9. Rüschoff JH, Gradhand E, Kahraman A, et al.: STRN -ALK Rearranged Malignant Peritoneal Mesothelioma With Dramatic Response Following Ceritinib Treatment. JCO Precis Oncol 3: , 2019. [PUBMED Abstract]

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, see the 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.

This summary was comprehensively reviewed.

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® Cancer Information for Health Professionals pages.

Adenocarcinoma of the cervix and vagina is rare in childhood and adolescence.[1,2] Two-thirds of cases in previous reports have been associated with exposure to diethylstilbestrol (DES) in utero.[3] However, the few case reports of vaginal cancer in children in the last decade have not been associated with exposure to DES in utero.[4]

The median age at presentation is 15 years, with a range of 7 months to 18 years. Most patients present with vaginal bleeding. Adults with adenocarcinoma of the cervix or vagina present with stage I or stage II disease 90% of the time.[1] In children and adolescents, there is a high incidence of stage III and stage IV disease (24%). This difference may be explained by the practice of routine pelvic examinations in adults and the hesitancy to perform them in children.

References

1. McNall RY, Nowicki PD, Miller B, et al.: Adenocarcinoma of the cervix and vagina in pediatric patients. Pediatr Blood Cancer 43 (3): 289-94, 2004. [PUBMED Abstract]
2. You W, Dainty LA, Rose GS, et al.: Gynecologic malignancies in women aged less than 25 years. Obstet Gynecol 105 (6): 1405-9, 2005. [PUBMED Abstract]
3. Huo D, Anderson D, Palmer JR, et al.: Incidence rates and risks of diethylstilbestrol-related clear-cell adenocarcinoma of the vagina and cervix: Update after 40-year follow-up. Gynecol Oncol 146 (3): 566-571, 2017. [PUBMED Abstract]
4. Fernandez-Pineda I, Spunt SL, Parida L, et al.: Vaginal tumors in childhood: the experience of St. Jude Children’s Research Hospital. J Pediatr Surg 46 (11): 2071-5, 2011. [PUBMED Abstract]

The Fédération Internationale de Gynécologie et d’Obstétrique (FIGO) system is used to stage cervical and vaginal cancer. For more information, see the Staging Information for Cervical Cancer section in Cervical Cancer Treatment and the Staging Information for Vaginal Cancer section in Vaginal Cancer Treatment.

Treatment options for childhood carcinoma of the cervix and vagina include the following:

The treatment of choice is surgical resection,[1] followed by radiation therapy for residual microscopic disease or lymphatic metastases. The role of chemotherapy in management is unknown. However, drugs commonly given for the treatment of gynecological malignancies, such as carboplatin and paclitaxel, have been used.[2,3]

In a retrospective report, 37 patients with cervical clear cell adenocarcinoma or cervical mesonephric adenocarcinoma were treated with various modalities (surgery, radiation therapy, and/or chemotherapy). The 3-year event-free survival rate was 71% (± 11%) for patients with all stages of tumors, 82% (± 11%) for patients with stage I and stage II tumors, and 57% (± 22%) for patients with stage III and stage IV tumors.[4]

References

1. Abu-Rustum NR, Su W, Levine DA, et al.: Pediatric radical abdominal trachelectomy for cervical clear cell carcinoma: a novel surgical approach. Gynecol Oncol 97 (1): 296-300, 2005. [PUBMED Abstract]
2. Baykara M, Benekli M, Erdem O, et al.: Clear cell adenocarcinoma of the uterine cervix: a case report and review of the literature. J Pediatr Hematol Oncol 36 (2): e131-3, 2014. [PUBMED Abstract]
3. Singh P, Nicklin J, Hassall T: Neoadjuvant chemotherapy followed by radical vaginal trachelectomy and adjuvant chemotherapy for clear cell cancer of the cervix: a feasible approach and review. Int J Gynecol Cancer 21 (1): 137-40, 2011. [PUBMED Abstract]
4. McNall RY, Nowicki PD, Miller B, et al.: Adenocarcinoma of the cervix and vagina in pediatric patients. Pediatr Blood Cancer 43 (3): 289-94, 2004. [PUBMED Abstract]

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, see the ClinicalTrials.gov website.

Cancer in children and adolescents is rare, although the overall incidence has slowly increased since 1975.[1] Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the following pediatric specialists and others to ensure that children receive treatment, supportive care, and rehabilitation to achieve optimal survival and quality of life:

For specific information about supportive care for children and adolescents with cancer, see the summaries on Supportive and Palliative Care.

The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of children and adolescents with cancer.[2] At these centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with current standard therapy. Other types of clinical trials test novel therapies when there is no standard therapy for a cancer diagnosis. Most of the progress in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.

Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2020, childhood cancer mortality decreased by more than 50%.[3–5] Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. For information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors, see Late Effects of Treatment for Childhood Cancer.

Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[6] The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 people in the United States. Therefore, all pediatric cancers are considered rare.

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.[7,8] In children and adolescents, the designation of a rare tumor is not uniform among international groups, as follows:

These rare cancers are extremely challenging to study because of the relatively few patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the small number 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 Cervical Cancer Treatment and Vaginal Cancer Treatment.

References

1. Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010. [PUBMED Abstract]
2. American Academy of Pediatrics: Standards for pediatric cancer centers. Pediatrics 134 (2): 410-4, 2014. Also available online. Last accessed February 25, 2025.
3. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014. [PUBMED Abstract]
4. National Cancer Institute: NCCR*Explorer: An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed February 25, 2025.
5. Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed December 30, 2024.
6. Ward E, DeSantis C, Robbins A, et al.: Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 64 (2): 83-103, 2014 Mar-Apr. [PUBMED Abstract]
7. Gatta G, Capocaccia R, Botta L, et al.: Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet-a population-based study. Lancet Oncol 18 (8): 1022-1039, 2017. [PUBMED Abstract]
8. DeSantis CE, Kramer JL, Jemal A: The burden of rare cancers in the United States. CA Cancer J Clin 67 (4): 261-272, 2017. [PUBMED Abstract]
9. Ferrari A, Brecht IB, Gatta G, et al.: Defining and listing very rare cancers of paediatric age: consensus of the Joint Action on Rare Cancers in cooperation with the European Cooperative Study Group for Pediatric Rare Tumors. Eur J Cancer 110: 120-126, 2019. [PUBMED Abstract]
10. Pappo AS, Krailo M, Chen Z, et al.: Infrequent tumor initiative of the Children’s Oncology Group: initial lessons learned and their impact on future plans. J Clin Oncol 28 (33): 5011-6, 2010. [PUBMED Abstract]

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.

This summary was comprehensively reviewed.

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® Cancer Information for Health Professionals pages.

Most ovarian masses in children are not malignant.[1] The most common malignant neoplasms are germ cell tumors, followed by epithelial tumors, stromal tumors, and then other tumors such as Burkitt lymphoma.[2–5]

Most malignant ovarian tumors occur in girls aged 15 to 19 years.[6]

References

1. Lawrence AE, Gonzalez DO, Fallat ME, et al.: Factors Associated With Management of Pediatric Ovarian Neoplasms. Pediatrics 144 (1): , 2019. [PUBMED Abstract]
2. Morowitz M, Huff D, von Allmen D: Epithelial ovarian tumors in children: a retrospective analysis. J Pediatr Surg 38 (3): 331-5; discussion 331-5, 2003. [PUBMED Abstract]
3. Schultz KA, Sencer SF, Messinger Y, et al.: Pediatric ovarian tumors: a review of 67 cases. Pediatr Blood Cancer 44 (2): 167-73, 2005. [PUBMED Abstract]
4. Aggarwal A, Lucco KL, Lacy J, et al.: Ovarian epithelial tumors of low malignant potential: a case series of 5 adolescent patients. J Pediatr Surg 44 (10): 2023-7, 2009. [PUBMED Abstract]
5. You W, Dainty LA, Rose GS, et al.: Gynecologic malignancies in women aged less than 25 years. Obstet Gynecol 105 (6): 1405-9, 2005. [PUBMED Abstract]
6. Brookfield KF, Cheung MC, Koniaris LG, et al.: A population-based analysis of 1037 malignant ovarian tumors in the pediatric population. J Surg Res 156 (1): 45-9, 2009. [PUBMED Abstract]

The Fédération Internationale de Gynécologie et d’Obstétrique (FIGO) staging system has been used for ovarian cancers (see Table 1).

References

1. Berek JS, Renz M, Kehoe S, et al.: Cancer of the ovary, fallopian tube, and peritoneum: 2021 update. Int J Gynaecol Obstet 155 (Suppl 1): 61-85, 2021. [PUBMED Abstract]

References

1. Childress KJ, Patil NM, Muscal JA, et al.: Borderline Ovarian Tumor in the Pediatric and Adolescent Population: A Case Series and Literature Review. J Pediatr Adolesc Gynecol 31 (1): 48-54, 2018. [PUBMED Abstract]
2. Hazard FK, Longacre TA: Ovarian surface epithelial neoplasms in the pediatric population: incidence, histologic subtype, and natural history. Am J Surg Pathol 37 (4): 548-53, 2013. [PUBMED Abstract]
3. Virgone C, Alaggio R, Dall’Igna P, et al.: Epithelial Tumors of the Ovary in Children and Teenagers: A Prospective Study from the Italian TREP Project. J Pediatr Adolesc Gynecol 28 (6): 441-6, 2015. [PUBMED Abstract]
4. Tsai JY, Saigo PE, Brown C, et al.: Diagnosis, pathology, staging, treatment, and outcome of epithelial ovarian neoplasia in patients age < 21 years. Cancer 91 (11): 2065-70, 2001. [PUBMED Abstract]
5. Nasioudis D, Alevizakos M, Holcomb K, et al.: Malignant and borderline epithelial ovarian tumors in the pediatric and adolescent population. Maturitas 96: 45-50, 2017. [PUBMED Abstract]