Prognostic factors for melanoma in children and adolescents: A ...

Original Article

Prognostic Factors for Melanoma in Children and Adolescents A Clinicopathologic, Single-Center Study of 137 Patients ´ ndez, MD, PhD2; Sara M. Kantrow, MD3; Sabela Paradela, MD1; Eduardo Fonseca, MD, PhD1; Salvador Pita-Ferna Abdul H. Diwan, MD, PhD4; Cynthia Herzog, MD5; and Victor G. Prieto, MD, PhD4

BACKGROUND: Cutaneous melanoma in childhood is rare; therefore, its prognostic factors and biologic behavior and the effectiveness of adjuvant diagnostic techniques in this group remain mostly unknown. METHODS: The authors conducted a retrospective, observational study on the prognostic significance of clinical and pathologic findings from 137 cutaneous and mucosal melanomas in patients aged 10 years, previous nonmelanocytic malignancy, high Breslow thickness, high Clark level, and the presence of metastases at diagnosis. All patients who died were aged
11 years, and 8 of those patients had metastases at diagnosis. In multivariate analysis, higher Breslow thickness predicted an increased risk of metastases, whereas age >10 years and the presence of metastases at diagnosis were associated with decreased survival. CONCLUSIONS: Similar to adults, the detection of metastases at diagnosis in children with melanoma was 1 of the main factors that influenced overall survival. Melanomas that were detected in children aged 30)

Melanoma in Children/Paradela et al

of melanoma in young patients, all deaths occurred after age 12 years. In a multicenter study of 354 patients aged 100 nevi and a 15-fold increased risk in patients who had
10 large nevi.31 There were numerous nevi in 21% of our patients. Patients with inherited immunodeficiency have a 3fold to 6-fold increased risk for developing melanoma,32 and that increased risk is 4-fold in organ transplantation recipients. In the current series, 1 patient had an immuno-

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deficiency, and another patient had received immunosuppressive therapy. Survivors of childhood cancer have a relative risk of 14.8 of developing a second neoplasm,33 and there seems to be a link between previous malignancies and melanoma.34 In our current series, 2 patients had previous malignancies. Some authors have observed that melanomas tend to be deeper and indicate a poor prognosis in patients who have other malignancies,34 and those investigators have proposed that tumor-related immunodeficiency mechanisms mediated by the neoplasm itself are the cause.34 All of these findings encourage prompt diagnostic and therapeutic interventions in children who have neoplasm or immunosuppression and pigmented lesions.30 Histologic Features Although nodular melanoma was the predominant type in some reports,16,35 in our series, as in several others,10,11,24,25,36,37 superficial spreading melanoma was the most common type. Nodular histology has been related to worse survival in children.21 We detected a greater frequency of metastasis in this group, probably related to a greater Breslow thickness. However, this association was not significant in multivariate analysis or in the analysis of overall survival. A high percentage of reported childhood and adolescent melanomas are relatively thick, possibly because of delayed suspicion of malignancy.14,38,39 In comparisons between adult melanomas and pediatric melanomas,36 the latter tumors were significantly thicker. Like what we observed in the current series, analyses of 2 national cancer databases21,39 revealed that young adults and older teenagers had thinner lesions than children ages 1 to 14 years. When this factor was analyzed, thicker melanoma in children portended a significantly poor prognosis.24,39 Lymph node metastases were detected in up to 66% of children with Clark level IV and V disease or melanomas >1.5 mm thick.40 Conversely, metastases or recurrences were unusual in patients who had melanomas 1 mm reported in adults.6,52,53 In our series, the rate of positivity approached 40% (Table 1). Given the small number of patients, it is unclear whether these findings reflect the higher mean tumor depth38 or are related to an inverse correlation between positive SLNB and age.46 In contrast to findings in adults, we observed that a positive SLNB was not associated significantly with additional positive lymph nodes identified at therapeutic lymph node dissection (10%)41,48,50,51 or with a greater risk of death.37 Similar to other reports,18 we observed a higher SLNB-positive rate in patients aged 10 years (probably related to greater Breslow thickness), although the prognosis for survival was worse in the older group. Some authors have suggested that the better prognosis for children with a positive SLNB may be because of age-related changes in lymphatic flow density and the immune system, which is able to clear micrometastases.54 Long-term follow-up studies will be necessary to determine whether the prognostic value of SLNB in children is different from that in adults. In summary, we studied our single-institution experience in a large series of primary melanomas in children. Age >10 years, high Breslow thickness, and presence of metastasis at diagnosis were associated with an impaired prognosis, whereas patients who had disease associated with a nevus appeared to have a better prognosis. We emphasize that children aged 10 years had better survival despite having thicker tumors and a higher SLNBpositive rate; this may have been caused by the influence of sexual maturity on the biologic tumor behavior.

CONFLICT OF INTEREST DISCLOSURES The authors made no disclosures.

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Melanoma in Children/Paradela et al

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