National Cancer Institute


This evidence-based, expert-reviewed summary discusses the incidence, risk factors, molecular features, treatment, and outcome of pediatric intraocular (uveal) melanoma.

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of pediatric intraocular (uveal) melanoma. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Childhood Intraocular (Uveal) Melanoma Treatment

Incidence and Risk Factors

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

Pediatric uveal melanoma is extremely rare and accounts for 0.8% to 1.1% of all cases of uveal melanoma. A retrospective, multicenter, 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 at 24 centers. The median age at the time of 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.

Risk factors include the following:

  • Light eye color.
  • Fair skin color.
  • Inability to tan.
  • Oculodermal melanocytosis.
  • Presence of cutaneous nevi.

In a European Oncology Group study, 57% of children were females and four had a preexisting condition that included oculodermal melanocytosis (n = 2) and neurofibromatosis (n = 2). 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.

References

  1. Field MG, Harbour JW: Recent developments in prognostic and predictive testing in uveal melanoma. Curr Opin Ophthalmol 25 (3): 234-9, 2014.
  2. Singh AD, Bergman L, Seregard S: Uveal melanoma: epidemiologic aspects. Ophthalmol Clin North Am 18 (1): 75-84, viii, 2005.
  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.
  4. Shields CL, Kaliki S, Arepalli S, et al.: Uveal melanoma in children and teenagers. Saudi J Ophthalmol 27 (3): 197-201, 2013.
  5. Pogrzebielski A, Orłowska-Heitzman J, Romanowska-Dixon B: Uveal melanoma in young patients. Graefes Arch Clin Exp Ophthalmol 244 (12): 1646-9, 2006.
  6. 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.
  7. 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.
  8. 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.
  9. 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.

Prognostic Factors

Prognostic factors for uveal melanoma include the following:

  • Tumor size.
  • Age.
  • Ciliary body involvement.
  • Tumor outside the sclera.
  • Metastasis.
  • Genetic changes.

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.
  2. Shields CL, Kaliki S, Arepalli S, et al.: Uveal melanoma in children and teenagers. Saudi J Ophthalmol 27 (3): 197-201, 2013.

Molecular Features

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

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.
  2. Harbour JW, Onken MD, Roberson ED, et al.: Frequent mutation of BAP1 in metastasizing uveal melanomas. Science 330 (6009): 1410-3, 2010.
  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.
  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.
  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.
  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.

Treatment and Outcome of Childhood Intraocular (Uveal) Melanoma

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

  1. Surgery.
  2. Radiation therapy.
  3. Laser surgery.

(Refer to the PDQ summary on adult Intraocular [Uveal] Melanoma Treatment for information on the treatment of uveal melanoma in adults.)

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.

A retrospective single-institution review identified 18 patients younger than 21 years with uveal melanoma.[Level of evidence: 3iiA] Eight of these patients (44%) developed metastatic uveal melanoma, and all of these patients died of metastatic disease. The median overall survival of the 18 patients after treatment of the primary intraocular tumors was 11.9 years (95% CI, 7.3–16.5). In the eight patients who developed metastatic disease, the median survival time after detection of metastasis was 2.3 months (95% CI, 0.0–5.2).

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.
  2. Shields CL, Kaliki S, Arepalli S, et al.: Uveal melanoma in children and teenagers. Saudi J Ophthalmol 27 (3): 197-201, 2013.
  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.

Treatment Options Under Clinical Evaluation for Childhood Intraocular (Uveal) Melanoma

Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, refer to the ClinicalTrials.gov website.

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

  • APEC1621 (NCT03155620) (Pediatric MATCH: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients with Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders): NCI-COG Pediatric Molecular Analysis for Therapeutic Choice (MATCH), referred to as Pediatric MATCH, will match targeted agents with specific molecular changes identified using a next-generation sequencing targeted assay of more than 4,000 different mutations across more than 160 genes in refractory and recurrent solid tumors. Children and adolescents aged 1 to 21 years are eligible for the trial.

    Tumor tissue from progressive or recurrent disease must be available for molecular characterization. Patients with tumors that have molecular variants addressed by treatment arms included in the trial will be offered treatment on Pediatric MATCH. Additional information can be obtained on the NCI website and ClinicalTrials.gov website.

Special Considerations for the Treatment of Children With Cancer

Cancer in children and adolescents is rare, although the overall incidence of childhood cancer has been slowly increasing since 1975. Referral to medical centers with multidisciplinary teams of cancer specialists experienced in treating cancers that occur in childhood and adolescence should be considered for children and adolescents with cancer. This multidisciplinary team approach incorporates the skills of the following health care professionals and others to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life:

  • Primary care physicians.
  • Pediatric surgeons.
  • Radiation oncologists.
  • Pediatric medical oncologists/hematologists.
  • Rehabilitation specialists.
  • Pediatric nurse specialists.
  • Social workers.
  • Child-life professionals.
  • Psychologists.

(Refer to the PDQ Supportive and Palliative Care summaries for specific information about supportive care for children and adolescents with cancer.)

Guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer have been outlined by the American Academy of Pediatrics. At these pediatric cancer centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate in these trials 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 therapy that is currently accepted as standard. Most of the progress made in identifying curative therapy 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 2010, childhood cancer mortality decreased by more than 50%. Childhood and adolescent cancer survivors require close monitoring because cancer therapy side effects may persist or develop months or years after treatment. (Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.)

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

The designation of a rare tumor is not uniform among pediatric and adult groups. Adult rare cancers are defined as those with an annual incidence of fewer than six cases per 100,000 people, and they are estimated to account for up to 24% of all cancers diagnosed in the European Union and about 20% of all cancers diagnosed in the United States. Also, the designation of a pediatric rare tumor is not uniform among international groups, as follows:

  • The Italian cooperative project on rare pediatric tumors (Tumori Rari in Eta Pediatrica [TREP]) defines a pediatric rare tumor as one with an incidence of less than two cases per 1 million population per year and is not included in other clinical trials.
  • The Children's Oncology Group has opted to define rare pediatric cancers as those listed in the International Classification of Childhood Cancer subgroup XI, which includes thyroid cancer, melanoma and nonmelanoma skin cancers, and multiple types of carcinomas (e.g., adrenocortical carcinoma, nasopharyngeal carcinoma, and most adult-type carcinomas such as breast cancer, colorectal cancer, etc.). These diagnoses account for about 4% of cancers diagnosed in children aged 0 to 14 years, compared with about 20% of cancers diagnosed in adolescents aged 15 to 19 years.

    Most cancers within subgroup XI are either melanomas or thyroid cancer, with the remaining subgroup XI cancer types accounting for only 1.3% of cancers in children aged 0 to 14 years and 5.3% of cancers in adolescents aged 15 to 19 years.

These rare cancers are extremely challenging to study because of the low incidence of patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the lack of clinical trials for adolescents with rare cancers.

Information about these tumors may also be found in sources relevant to adults with cancer such as the PDQ summary on adult 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.
  2. Corrigan JJ, Feig SA; American Academy of Pediatrics: Guidelines for pediatric cancer centers. Pediatrics 113 (6): 1833-5, 2004.
  3. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014.
  4. 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.
  5. 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.
  6. DeSantis CE, Kramer JL, Jemal A: The burden of rare cancers in the United States. CA Cancer J Clin 67 (4): 261-272, 2017.
  7. Ferrari A, Bisogno G, De Salvo GL, et al.: The challenge of very rare tumours in childhood: the Italian TREP project. Eur J Cancer 43 (4): 654-9, 2007.
  8. 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.
  9. Howlader N, Noone AM, Krapcho M, et al., eds.: SEER Cancer Statistics Review, 1975-2012. Bethesda, Md: National Cancer Institute, 2015. Also available online. Last accessed February 20, 2020.

Changes to This Summary (06/08/2020)

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.

Treatment and Outcome of Childhood Intraocular (Uveal) Melanoma

Added text about the outcome results of a retrospective single-institution review that identified 18 patients younger than 21 years with uveal melanoma (cited Fry et al. as reference 3 and level of evidence 3iiA).

This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of pediatric intraocular (uveal) melanoma. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

  • be discussed at a meeting,
  • be cited with text, or
  • replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewers for Childhood Intraocular (Uveal) Melanoma Treatment are:

  • Denise Adams, MD (Children's Hospital Boston)
  • Karen J. Marcus, MD, FACR (Dana-Farber Cancer Institute/Boston Children's Hospital)
  • Paul A. Meyers, MD (Memorial Sloan-Kettering Cancer Center)
  • Thomas A. Olson, MD (Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta - Egleston Campus)
  • Alberto S. Pappo, MD (St. Jude Children's Research Hospital)
  • Arthur Kim Ritchey, MD (Children's Hospital of Pittsburgh of UPMC)
  • Carlos Rodriguez-Galindo, MD (St. Jude Children's Research Hospital)
  • Stephen J. Shochat, MD (St. Jude Children's Research Hospital)

Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Pediatric Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

Permission to Use This Summary

PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”

The preferred citation for this PDQ summary is:

PDQ® Pediatric Treatment Editorial Board. PDQ Childhood Intraocular (Uveal) Melanoma Treatment. Bethesda, MD: National Cancer Institute. Updated . Available at: https://www.cancer.gov/types/eye/hp/child-intraocular-melanoma-treatment-pdq. Accessed .

Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.

Disclaimer

Based on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.

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More information about contacting us or receiving help with the Cancer.gov website can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the website’s Email Us.

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