|Year : 2020 | Volume
| 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
|Date of Submission||26-Nov-2019|
|Date of Decision||24-Dec-2019|
|Date of Acceptance||10-Feb-2020|
|Date of Web Publication||01-Apr-2020|
Department of Plastic Surgery, Medical School, Papageorgiou Hospital, Aristotle University of Thessaloniki 56403
Source of Support: None, Conflict of Interest: None
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.
Keywords: Adjuvant therapy, childhood, melanoma, metastasis, pediatric, sentinel lymph node biopsy
|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;21:81-6
|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 Jun 1];21:81-6. Available from: http://www.ijpd.in/text.asp?2020/21/2/81/281725
| Introduction|| |
The incidence of cutaneous melanoma is rising worldwide, affecting predominantly white people, but also occurring in other races. In childhood and adolescence, this malignancy is uncommon, accounting for 1%–4% of all melanomas and 3%–4% of all pediatric cancers.,,,,, 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%).,,,,,,,,,, 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.,
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: Representative histological features of the right foot melanoma: (a) presence of epithelioid neoplastic cells in the dermis, with pagetoid extension into the epidermis (H and E, ×100). Representative histological features of the right foot melanoma: (b) neoplastic cells with high nucleo-cytoplasmic ratio and large nucleoli (H and E, ×200)|
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Following the guidelines of the American Joint Committee on Cancer (AJCC), 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: Wide local excision at 2 cm margin, around the scar of the excised melanoma over the instep of the right foot|
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|Figure 3: Small group of melanoma cells in the sentinel lymph node, as seen on immunohistochemical stain for melan-A antigen (×400)|
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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.,,,,, 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. 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. 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.,
When occurring in young ages, melanoma is reported to be more frequent in girls than boys.,, Male gender and trunk lesions have been associated with worse prognosis, although other studies report equal gender distribution and prognosis. 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., 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.
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.,, 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.
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. 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.,,,,,,, Despite the higher incidence of nodal involvement, survival is equal or better than that reported for adults.,,, 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. 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.
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., 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.,,
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. This correlates with the findings from the MSLT-II trial. 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. 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.[,, 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. 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.
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.,,, The IFN treatment is reported as being well-tolerated with less associated toxicity than adults, both after resected high-risk melanoma, and after positive sentinel node biopsy., 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.
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. 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 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. 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. 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. 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.
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., 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
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]