Indian Journal of Paediatric Dermatology

REVIEW ARTICLE
Year
: 2020  |  Volume : 21  |  Issue : 2  |  Page : 81--86

Cutaneous melanoma in a 9-year-old girl: case report and review of literature


Athanasios Papas1, Prodromos Chitiroglou2, Efterpi Demiri1,  
1 Department of Plastic Surgery, Medical School, Papageorgiou Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
2 Department of Pathology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece

Correspondence Address:
Athanasios Papas
Department of Plastic Surgery, Medical School, Papageorgiou Hospital, Aristotle University of Thessaloniki 56403
Greece

Abstract

Melanoma in children is a rare entity with an estimated incidence of one/million/year. Only 1.3% of melanomas reported in the United States of America affect individuals under the age of 20 years, and this neoplasm accounts for only 0.9% of all malignancies in children under the age of 15 years. Melanoma is particularly rare in prepubertal children before the age of 10 years. We present a case of a 9-year-old girl with a melanoma of the right foot. Her sentinel node biopsy was positive for isolated melanoma cells, and none of 5 additional lymph nodes removed following inguinal dissection were found to contain malignant melanoma cells. To our knowledge, this is the youngest melanoma patient recorded in the Greek population. The histological diagnosis of melanoma in this age group can be extremely difficult, and physicians ought to be cautious. The rarity of the disease results in small series of cases from which reliable figures are difficult to obtain. Unfortunately, this also applies to currently available treatments whose effectiveness is unclear.



How to cite this article:
Papas A, Chitiroglou P, Demiri E. Cutaneous melanoma in a 9-year-old girl: case report and review of literature.Indian J Paediatr Dermatol 2020;21:81-86


How to cite this URL:
Papas A, Chitiroglou P, Demiri E. Cutaneous melanoma in a 9-year-old girl: case report and review of literature. Indian J Paediatr Dermatol [serial online] 2020 [cited 2020 May 26 ];21:81-86
Available from: http://www.ijpd.in/text.asp?2020/21/2/81/281725


Full Text



 Introduction



The incidence of cutaneous melanoma is rising worldwide, affecting predominantly white people, but also occurring in other races.[1] In childhood and adolescence, this malignancy is uncommon, accounting for 1%–4% of all melanomas and 3%–4% of all pediatric cancers.[2],[3],[4],[5],[6],[7] In the United States (US), according to the National Cancer Institute, approximately 500 children are diagnosed with melanoma every year; there is evidence, however, that the incidence in young ages is on the rise by 1%–4%/year, almost equal to the rise of incidence in the adult population (2%–5%).[2],[3],[4],[5],[8],[9],[10],[11],[12],[13],[14] The incidence of melanoma in Greece is estimated around 2%–4%. Despite being one of the lowest in the European Union, as well as in the Mediterranean population, it does exhibit an increasing trend.[15],[16]

The aim of our article is to present a rare case of melanoma in a 9-year-old girl and to review the literature on the incidence and therapeutic management of cutaneous melanoma in children.

 Case Report



A 9-year-old girl was referred for further assessment and treatment to our department in July 2010. She presented with three changing nevi in her right foot, one of which was on the nonweight bearing sole. All three nevi were excised under local anesthesia, and histological examination was performed.

One lesion on her right foot was composed of epithelioid cells with high nucleo-cytoplasmic ratio and prominent nucleoli [Figure 1]a and [Figure 1]b. These neoplastic cells were arranged at the dermoepidermal junction singly or in groups, extended into the epidermis in a pagetoid fashion [Figure 1]a, and infiltrated the papillary dermis, as well as a part of the reticular dermis [Figure 1]b. There was no cell maturation with descend. The lack of maturation was confirmed by the presence of occasional mitotic figures and several Ki-67 antigen-positive cells in the deep portion of the lesion. There were moderate chronic inflammatory cell infiltrates, predominantly composed of lymphocytes. Immunohistochemical staining with the antibodies for S100 and HMB45 was positive. The depth of invasion (according to Breslow) was 1.2 mm. The other two nevi showed evidence of mild dysplasia with no evidence of malignancy.{Figure 1}

Following the guidelines of the American Joint Committee on Cancer (AJCC),[17] we performed a wide local excision at 2 cm margin [Figure 2] and used a split-thickness skin graft to cover the surgical defect. She also underwent a sentinel lymph node biopsy (SLNB). Two sentinel lymph nodes (SLNs) were identified, one of which was positive for isolated melanoma cells [Figure 3]. The patient underwent a right inguinal dissection; five additional lymph nodes were found, which were negative for neoplastic cells.{Figure 2}{Figure 3}

Her wounds healed uneventfully within 2 weeks, and no postoperative complications were recorded. She was referred to the oncology department who offered interferon (IFN), but the family chose follow-up instead. Ten years postoperatively, the patient remains asymptomatic, with no evidence of metastasis or local recurrence. Her recent positron emission tomography–computed tomography (PET-CT) scan showed no evidence of metastasis.

 Discussion



For the purpose of discussion and review of the literature a PubMed search was completed in Clinical Queries using the terms pediatric, melanoma, adolescence, childhood, children, sentinel node biopsy and adjuvant therapy. The search included meta-analyses, randomized controlled trials, clinical trials, and reviews. Also searched were the Cochrane Database of Systematic Reviews (part of Ovid Evidence Based Medicine Reviews), MEDLINE, Google Scholar and UpToDate. Evidence was found through a systematic search for articles published from January 1973 to February 2020.

Cutaneous melanoma in children is rare. In the prepubertal population, before the age of 10, melanotic lesions are even more uncommon, accounting for only 0.3%–0.4% of newly diagnosed lesions, with an annual incidence of 0.7–0.8 per million in the first decade of life.[18],[19],[20],[21],[22],[23] Richardson et al. classified prepubertal melanomas into three categories: (1) congenital, when diagnosed in utero to birth, (2) infantile, when diagnosed from birth to 1 year, and (3) childhood, when diagnosed from 1 year to puberty.[24] The estimated annual incidence rate in those aged 15–19 years, according to the Surveillance, Epidemiology, and End Results (SEER) cancer statistics review 1975–2014 is nine per million.[25] A recent SEER study showed that the incidence of melanoma was found to increase with advancing age from 4% in patients aged 0–4 years to 72% in patients aged 15–19 years, identical to findings from the National Cancer Database for respective age groups.[26],[27]

When occurring in young ages, melanoma is reported to be more frequent in girls than boys.[4],[8],[27] Male gender and trunk lesions have been associated with worse prognosis,[22] although other studies report equal gender distribution and prognosis.[28] There is an age and gender variability regarding the anatomic distribution; primary melanomas most commonly appear on the head and neck of young children and less frequently on the trunk, compared with teenagers and young adults.[26],[28] Girls older than 4 years have a higher percentage of lower extremity lesions, whereas girls older than 9 years have a lower percentage of head-and-neck melanomas compared with boys of similar ages.[26]

Although risk factors for melanoma in older children are similar to those in adults (e.g., fair skin, sun exposure, and sunburns), the same does not apply to younger children. Various studies implicate predominantly the number of congenital nevi, which are considered to be precursor lesions of melanoma, regardless of their size.[5],[24],[29] Other studies have shown a higher percentage of melanoma in young patients with positive family history and presence of dysplastic nevi, suggesting a significant role of predisposing genetic components.[30]

Despite sharing similar risk factors with adult melanoma, pediatric melanoma is considered to be biologically distinct from adult melanoma due to several distinctive features: greater thickness at presentation, higher frequency of amelanotic lesions, greater rate of sentinel node positivity, and overall less aggressive clinical course.[31] Whether the greater thickness at presentation is due to delayed diagnosis or more rapid growth in children has not been determined.

Pediatric melanoma patients exhibit higher rates of lymph node metastases, compared with adult (thickness-matched) control patients, ranging from 25% to 40% and correlated with Breslow's thickness and age ≤10 years.[28],[30],[32],[33],[34],[35],[36],[37] Despite the higher incidence of nodal involvement, survival is equal or better than that reported for adults.[13],[30],[37],[38] A recent population-based study of 310 children with melanoma demonstrated that positive SLN status is associated with worse melanoma-specific survival and recommended performing a SLNB in children with clinically localized melanoma >0.75 mm in thickness to provide prognostic information and guide clinical decision-making.[39] It has also been noted that the majority of the recurrences and melanoma-related deaths are seen in pediatric melanoma patients more than 5 years after the initial diagnosis; therefore, a long-term follow-up is mandatory for the young population.[37]

Regarding the therapeutic recommendations for childhood melanomas, management should follow the guidelines of the AJCC melanoma staging committee for adults; a wide local excision is performed according to the Breslow's thickness, and a SLNB is offered in clinically localized melanomas of ≥1 mm thick and only selectively in thinner high-risk lesions.[17],[40] The SLNB technique is generally accepted as being a safe and accurate method for staging regional lymph nodes and establishing the need for elective nodal dissection.[41],[42],[43]

Due to the rarity of this disease in this specific age group, there remains a scarcity of literature concerning melanoma prognosis and the utility of lymph node dissection in pediatric patients. A recent SEER study with more than 900 pediatric extremity melanoma showed no disease-specific survival advantage between children undergoing sampling procedures versus no sampling for regional or distant disease.[27] This correlates with the findings from the MSLT-II trial.[44] However, the authors continue to support the utility of SLNB as a valuable prognostic tool in the treatment of melanoma.

A recent study by Palmer et al.[45] that included 125 pediatric melanoma patients showed similar rates and distribution of complications compared to those found in the adult studies with lymphedema occurring most often in patients undergoing complete lymph node dissection (CLND) and/or patients receiving dissection to the inguinal nodal region. The addition of a complete lymph node dissection significantly increases complication risk. Thus, it is critical to determine which patients truly benefit from this procedure.

The clinical and pathologic characteristics of melanomas in children can frequently make diagnosis difficult.[[46],[47],[48] Distinction between benign and malignant lesions, especially those with spitzoid features, may sometimes be impossible, leading to the diagnosis of “melanocytic tumor of uncertain malignant potential.” The misdiagnosis of pigmented lesions in pediatric ages is common, with a reported rate up to 40% of cases, and this may unfortunately result in therapeutic delay.[48] Lambie et al. describe the pediatric melanoma as a “triple threat” to the clinician: delayed diagnosis resulting in thick lesions with high risk for metastasis, histological uncertainty of diagnosis, and lack of data guiding regional node management and adjuvant therapy.[49]

The use of adjuvant high-dose IFN in adult and pediatric patients with high-risk melanoma is controversial. However, various studies suggest the use of high-dose IFN-alpha-2b therapy in children with advanced melanoma.[50],[51],[52],[53] The IFN treatment is reported as being well-tolerated with less associated toxicity than adults, both after resected high-risk melanoma[51],[52] and after positive sentinel node biopsy.[53],[54] A recent study showed that in children with high-risk melanoma, the convenient weekly subcutaneous pegylated IFN-α-2b is feasible as maintenance therapy with tolerable toxicity and appears to yield higher exposures than nonpegylated IFN-α-2b.[55]

In July 2017, the US Food and Drug Administration expanded the indication for ipilimumab (Yervoy) injection for intravenous use to include the treatment of unresectable or metastatic melanoma in pediatric patients 12 years of age and older.[56] Ipilimumab was evaluated in two trials of pediatric patients: a dose-finding study in 33 patients aged 2–21 years with relapsed or refractory solid tumors[57] and an open-label, single-arm trial in 12 adolescents (aged 12–16 years) with previously treated or untreated, unresectable Stage III or IV malignant melanoma.[58] The overall safety profile of ipilimumab in children and adolescents was consistent with the safety profile in adults; similarities in disease between adult and pediatric patients 12 years and older allow for extrapolation of data. There are no results that include a significant number of pediatric or adolescent patients with advanced melanoma from more recent immunotherapy trials (e.g., with single-agent programmed cell death 1 (PD-1) inhibitors or the combination of nivolumab plus ipilimumab) or with targeted therapies. These agents are likely to be more active than ipilimumab, based on the adult results.[58] Pediatric melanoma follow-up protocols are similar to the adult recommendations and include regular head-to-toe skin examination and lymph node surveillance to evaluate for recurrence or metastasis, respectively. Imaging surveillance with CT or PET scans is generally pursued less aggressively than in adults due to concerns about the cumulative impact of radiation exposure.[59] Typically, physical examination with special attention to regional recurrences is performed every 3 months for 1-year, then every 6 months for 5 years, followed by annual examinations thereafter.[60]

To our knowledge, the patient we are reporting represents the youngest case from the Greek population reported in the literature so far; unfortunately, due to the lack of a national registry, there are no documented data regarding childhood melanomas. The appropriate treatment was offered to our patient. Although adjuvant therapy did not follow, 7 years of clinical follow-up and annual PET-CT scans did not reveal any evidence of local recurrence or distant metastatic disease. It should also be noted that a lack of evidence-based management is admitted in the literature regarding the effectiveness of any adjuvant therapy.

 Conclusion



The incidence of melanoma in prepubertal children is very low; thus, individual institutions have access to clinical information on only a small group from which to draw conclusions. Pigmented skin lesions in the pediatric population represent a diagnostic challenge to pathologists and clinicians.[33],[61] The histological diagnosis of melanoma in this age group can be extremely difficult, and physicians ought to be cautious. The rarity of the disease results in small number of cases from which reliable figures are difficult to obtain. Subsequently, this also applies to currently available treatments whose effectiveness is unclear. If diagnosis is doubtful, it is prudent to perform excision with appropriate margins and if necessary also perform SLNB. The benefit of CLND after positive is SLNB is still under discussion. Despite the differences between pediatric and adult melanoma, survival rates are similar and are improving in both populations.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1National Cancer Institute. Cancer Stat Facts: Melanoma of the Skin. National Cancer Institute; Available from: https://seer.cancer.gov/statfacts/html/melan.html. [Last accessed on 2020 Feb 01].
2Siegel R, Naishadham D, Jemal A. Cancer statistics 2012. CA Cancer J Clin 2012;62:10-29.
3Howlader N, Noone AM, Krapcho M, Neyman N, Aminou R, Waldron W, et al. SEER Cancer Statistics Review, 1975–2008. Bethesda: National Cancer Institute; 2011. Available from: https://seer.cancer.gov/archive/csr/1975_2008/results_merged/sect_16_melanoma_skin.pdf. [Last accessed on 2020 Feb 28].
4Brecht IB, De Paoli A, Bisogno G, Orbach D, Schneider DT, Leiter U. Pediatric patients with cutaneous melanoma: A European study. Pediatr Blood Cancer 2018;65:e26974.
5Indini A, Brecht I, Del Vecchio M, Sultan I, Signoroni S, Ferrari A. et al. Cutaneous melanoma in adolescents and young adults. Pediatr Blood Cancer 2018;65:e27292.
6National Cancer Registration and Analysis Service. Cancer in Children, Teenagers and Young Adults, Childhood Cancer Statistics, England. Available from: http://www.ncin.org.uk/cancer_type_and_topic_specific_work/cancer_type_specific_work/cancer_in_children_teenagers_and_young_adults/. [Last accessed on 2020 Feb 01].
7Austin MT, Xing Y, Hayes-Jordan AA, Lally KP, Cormier JN. Melanoma incidence rises for children and adolescents: An epidemiologic review of pediatric melanoma in the United States. J Pediatr Surg 2013;48:2207-13.
8Campbell LB, Kreicher KL, Gittleman HR, Strodtbeck K, Barnholtz-Sloan J, Bordeaux JS. Melanoma Incidence in Children and Adolescents: Decreasing Trends in the United States. J Pediatr 2015;166:1505-13.
9Saiyed FK, Hamilton EC, Austin MT. Pediatric melanoma: incidence, treatment, and prognosis. Pediatric Health Med Ther 2017;8:39-45.
10Jen M, Murphy M, Grant-Kels JM. Childhood melanoma. Clin Dermatol 2009;27:529-36.
11Hamre MR, Chuba P, Bakhshi S, Thomas R, Severson RK. Cutaneous melanoma in childhood and adolescence. Pediatr Hematol Oncol 2002;19:309-17.
12Downard CD, Rapkin LB, Gow KW. Melanoma in children and adolescents. Surg Oncol 2007;16:215-20.
13Mills O, Messina JL. Pediatric melanoma: A review. Cancer Control 2009;16:225-33.
14Paradela S, Fonseca E, Prieto VG. Melanoma in children. Arch Pathol Lab Med 2011;135:307-16.
15Lasithiotakis K, Krüger-Krasagakis S, Manousaki A, Ioannidou D, Panagiotides I, Tosca A. The incidence of cutaneous melanoma on Crete, Greece. Int J Dermatol 2006;45:397-401.
16Roussaki-Schulze AV, Rammos C, Rallis E, Terzis A, Archontonis N, Sarmanta A, et al. Increasing incidence of melanoma in central Greece: A retrospective epidemiological study. Int J Tissue React 2005;27:173-9.
17Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 2009;27:6199-206.
18Brecht IB, Dunkel IJ, Garbe C. Melanoma in Children and Teenagers. In: Balch CM, Atkins MB, Garbe C, Gershenwald JE, Halpern AC, Kirkwood JM, et al. Cutaneous Melanoma. 6th ed. Springer Nature Switzerland AG; 2020: p. 970-71
19Leiter U, Eigentler T, Garbe C Epidemiology of skin cancer. Adv Exp Med Biol 2014;810:120-40.
20Offenmueller S, Leiter U, Bernbeck B, Garbe C, Eigentler T, Borkhardt A, et al. Clinical characteristics and outcome of 60 pediatric patients with malignant melanoma registered with the German Pediatric Rare Tumor Registry (Step). Klin Padiatr 2017;229:322-28.
21Wong JR, Harris JK, Rodriguez-Galindo C, Johnson KJ Incidence of childhood and adolescent melanoma in the United States: 1973–2009. Pediatrics 2013;131:846-54.
22Baade PD, Youlden DR, Valery PC, Hassall T, Ward L, Green AC, et al. Trends in incidence of childhood cancer in Australia, 1983-2006. Br J Cancer 2010;102:620-6.
23Larsen AK, Jensen MB, Krag CMS. Long-term Survival after Metastatic Childhood Melanoma. Plast Reconstr Surg Glob Open 2014;2:e163.
24Richardson SK, Tannous ZS, Mihm MC Jr. Congenital and infantile melanoma: Review of the literature and report of an uncommon variant, pigment-synthesizing melanoma. J Am Acad Dermatol 2002;47:77-90.
25National Cancer Institute. SEER Cancer Statistics Review (CSR) 1975-2015. Available from: https://seer.cancer.gov/archive/csr/1975_2015/. [Last updated on 2018 Sep 10; Last accessed on 2020 Feb 01].
26Lange JR, Palis BE, Chang DC, Soong SJ, Balch CM. Melanoma in children and teenagers: An analysis of patients from the national cancer data base. J Clin Oncol 2007;25:1363-8.
27Parikh PP, Tashiro J, Rubio GA, Sola JE, Neville HL, Hogan AR, et al. Incidence and outcomes of pediatric extremity melanoma: A propensity score matched seer study. J Pediatr Surg 2018;53:1753-60.
28Paradela S, Fonseca E, Pita-Fernández S, Kantrow SM, Diwan AH, Herzog C, et al. Prognostic factors for melanoma in children and adolescents: A clinicopathologic, single-center study of 137 patients. Cancer 2010;116:4334-44.
29Schaffer JV. Update on melanocytic nevi in children. Clinics in Dermatology, 2015;33:368-86.
30Livestro DP, Kaine EM, Michaelson JS, Mihm MC, Haluska FG, Muzikansky A, et al. Melanoma in the young: Differences and similarities with adult melanoma: A case-matched controlled analysis. Cancer 2007;110:614-24.
31Averbook BJ, Lee SJ, Delman KA, Gow KW, Zager JS, Sondak VK, et al. Pediatric melanoma: Analysis of an international registry. Cancer 2013;119:4012-9.
32Moore-Olufemi S, Herzog C, Warneke C, Gershenwald JE, Mansfield P, Ross M, et al. Outcomes in pediatric melanoma: Comparing prepubertal to adolescent pediatric patients. Ann Surg 2011;253:1211-5.
33Aldrink JH, Selim MA, Diesen DL, Johnson J, Pruitt SK, Tyler DS, et al. Pediatric melanoma: A single-institution experience of 150 patients. J Pediatr Surg 2009;44:1514-21.
34Mills OL, Marzban S, Zager JS, Sondak VK, Messina JLSurg. Sentinel node biopsy in atypical melanocytic neoplasms in childhood: a single institution experience in 24 patients.J Cutan Pathol 2012;39 :331-6.
35Howman-Giles R, Shaw HM, Scolyer RA, Murali R, Wilmott J, Mccarthy SW, et al. Sentinel lymph node biopsy in pediatric and adolescent cutaneous melanoma patients. Ann Surg Oncol 2010;17:138-43.
36Kirkwood JM, Jukic DM, Averbook BJ, Sender LS. Melanoma in pediatric, adolescent, and young adult patients. Semin Oncol 2009;36:419-31.
37Han D, Zager JS, Han G, Marzban SS, Puleo CA, Sarnaik AA, et al. The unique clinical characteristics of melanoma diagnosed in children. Ann Surg Oncol 2012;19:3888-95.
38Sassen S, Shaw HM, Colman MH, Scolyer RA, Thompson JF. The complex relationships between sentinel node positivity, patient age, and primary tumor desmoplasia: Analysis of 2303 melanoma patients treated at a single center. Ann Surg Oncol 2008;15:630-7.
39Kim J, Sun Z, Gulack BC, Adam MA, Mosca PJ, Rice HE, et al. Sentinel lymph node biopsy is a prognostic measure in pediatric melanoma. J Pediatr Surg 2016;51:986-90.
40Phan GQ, Messina JL, Sondak VK, Zager JS. Sentinel lymph node biopsy for melanoma: Indications and rationale. Cancer Control 2009;16:234-9.
41Balch CM, Thompson JF, Gershenwald JE, Soong SJ, Ding S, McMasters KM, et al. Age as a predictor of sentinel node metastasis among patients with localized melanoma: An inverse correlation of melanoma mortality and incidence of sentinel node metastasis among young and old patients. Ann Surg Oncol 2014; 21:1075-81.
42Venna SS, Thummala S, Nosrati M, Leong SP, Miller JR 3rd, Sagebiel RW, et al. Analysis of sentinel lymph node positivity in patients with thin primary melanoma. J Am Acad Dermatol 2013;68:560-7.
43Rhodes AR. Prognostic usefulness of sentinel lymph node biopsy for patients who have clinically node negative, localized, primary invasive cutaneous melanoma: A Bayesian analysis using informative published reports. Arch Dermatol 2011;147:408-15.
44Faries MB, Thompson JF, Cochran AJ, Andtbacka RH, Mozzillo N, Zager JS, et al. Completion dissection or observation for sentinel-node metastasis in melanoma. N Engl J Med 2017;376:2211-22.
45Palmer PE 3rd, Warneke CL, Hayes-Jordan AA, Herzog CE, Hughes DP, Lally KP, et al. Complications in the surgical treatment of pediatric melanoma. J Pediatr Surg 2013;48:1249-53.
46Cerroni L, Barnhill R, Elder D, Gottlieb G, Heenan P, Kutzner 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 2010;34:314-26.
47Gerami P, Li G, Pouryazdanparast P, Blondin B, Beilfuss B, Slenk C, et al. A highly specific and discriminatory Fish assay for distinguishing between benign and malignant melanocytic neoplasms. Am J Surg Pathol 2012;36:808-17.
48Cordoro KM, Gupta D, Frieden IJ, McCalmont T, Kashani-Sabet M. Pediatric melanoma: Results of a large cohort study and proposal for modified ABCD detection criteria for children. J Am Acad Dermatol. 2013;68:913-25.
49Lambie M, Nadler C, Glat P, van Duzer S, Halligan G, Geller E. Infantile melanoma – A triple threat: Diagnosis and management. Ann Plast Surg 2011;67:85-9.
50Kolandijan NA, Wei C, Burke A, Bedikian AY. Malignant melanoma in teenagers and young adults. J Pediatr Hematol Oncol 2014;36:552-8.
51Navid F, Furman WL, Fleming M, Rao BN, Kovach S, Billups CA, et al. The feasibility of adjuvant interferon alpha-2b in children with high-risk melanoma. Cancer 2005;103:780-7.
52Chao MM, Schwartz JL, Wechsler DS, Thornburg CD, Griffith KA, Williams JA. High-risk surgically resected pediatric melanoma and adjuvant interferon therapy. Pediatr Blood Cancer 2005;44:441-8.
53Shah NC, Gerstle JT, Stuart M, Winter C, Pappo A. 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 2006;28:496-500.
54McCormack C, Conyers R, Scolyer, R, Friyana B, Saxon S. How should melanoma in children be managed? Cancer Council Australia Melanoma Guidelines Working Party. Available from: https://wiki.cancer.org.au/australiawiki/index.php?oldid=207957. [Last accessed on 2020 Mar 15].
55Navid F, Herzog CE, Sandoval J, Daryani VM, Stewart CF, Gattuso J, et al. Feasibility of pegylated interferon in children and young adults with resected high-risk melanoma. Pediatr Blood Cancer 2016;63:1207-13.
56FDA Ipilimumab Clinical Review 125377/Supplement 87. Available from: https://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DevelopmentResources/UCM572924.pdf. [Last accessed on 2020 Feb 01].
57Merchant MS, Wright M, Baird K, Wexler LH, Rodriguez-Galindo C, Bernstein D, et al. Phase I clinical trial of ipilimumab in pediatric patients with advanced solid tumors. Clin Cancer Res 2016;22:1364-70.
58Geoerger B, Bergeron C, Gore L, Sender L, Dunkel IJ, Herzog C, et al. Phase II study of ipilimumab in adolescents with unresectable Stage III or IV malignant melanoma. Eur J Cancer 2017;86:358-63.
59McHugh K, Roebuck DJ. Pediatric oncology surveillance imaging: Two recommendations. Abandon CT scanning, and randomize to imaging or solely clinical follow-up. Pediatr Blood Cancer 2014;61:3-6.
60Sosman JA. UPTODATE® Overview of the Management of the Advanced Cutaneous Melanoma. Available from: https://www.uptodate.com/contents/overview-of-the-management-of-advanced-cutaneous-melanoma. [Last accessed on 2020 Feb 01].
61Cockerell CJ. The pathology of melanoma. Dermatol Clin 2012;30:445-68.