Table 7. Characteristics of Paraganglioma (PGL) and Pheochromocytoma (PCC) Associated with Susceptibility Genesa continued...
In pediatric melanoma, the association of thickness with clinical outcome is controversial.[78,85,86,87,88] In addition, pediatric melanoma appears to have a higher incidence of nodal involvement and this feature does not appear to have an impact on survival.[89,90] However, it is unclear how these findings truly affect clinical outcome since some series have included patients with atypical melanocytic lesions.[91,92] In a study of sentinel lymph node biopsies in children and adolescents, 25% were positive (compared with 17% in adults). However, only 0.7% of lymph nodes found on complete lymph node dissection were positive for melanoma. In this study, mortality was infrequent but was confined to sentinel lymph node–positive patients.[Level of evidence: 3iiA] In another study, 53% of patients younger than 10 years had positive sentinel lymph node biopsy compared with 26% of those who were aged 10 years and older.
Children younger than 10 years who have melanoma often present with poor prognostic features, are more often non-white, have head and neck primary tumors, and more often have syndromes that predispose them to melanoma.[78,84,85,94]
Biopsy or excision is necessary to determine the diagnosis of any skin cancer. Diagnosis is necessary for decisions regarding additional treatment. Although BCCs and SCCs are generally curable with surgery alone, the treatment of melanoma requires greater consideration because of its potential for metastasis. The width of surgical margins in melanoma is dictated by the site, size, and thickness of the lesion and ranges from 0.5 cm for in situ lesions to 2 cm or more for thicker lesions. To achieve negative margins in children, wide excision with skin grafting may become necessary in selected cases. Examination of regional lymph nodes using sentinel lymph node biopsy has become routine in many centers [95,96] and is recommended in patients with lesions measuring more than 1 mm in thickness or in those whose lesions are 1 mm or less in thickness and have unfavorable features such as ulceration, Clark level of invasion IV or V, or mitosis rate of 1 per mm2 or higher.[95,97,98]
Lymph node dissection is recommended if sentinel nodes are involved with tumor, and adjuvant therapy with high-dose interferon-alpha-2b for a period of 1 year should be considered in these patients.[64,95,99,100,101] Clinically benign melanocytic lesions can sometimes pose a significant diagnostic challenge, especially when they involve regional lymph nodes.[102,103,104]
The diagnosis of pediatric melanoma may be difficult and many of these lesions may be confused with the so-called melanocytic tumors of unknown metastatic potential. These lesions are biologically different from melanoma and benign nevi.[105,106] The term Spitz nevus and Spitzoid melanoma are also commonly used, creating additional confusion. Novel diagnostic techniques are actively being used by various centers in an attempt to differentiate melanoma from these challenging melanocytic lesions. For example, the absence of BRAF mutations or the presence of a normal chromosomal complement with or without 11p gains strongly argues against the diagnosis of melanoma.[107,108] In contrast, the use of FISH probes that target four specific regions in chromosomes 6 and 11 can help classify melanoma correctly in over 85% of cases; however, 24% of atypical Spitzoid lesions will have chromosomal alterations on FISH analysis and 75% will have BRAF V600E mutations.[109,110]HRAS mutations have been described in some cases of Spitz nevi but they have not been described in Spitzoid melanoma. The presence of a HRAS mutation may aid in the differential diagnosis of Spitz nevus and Spitzoid melanoma. Some of the characteristic genetic alterations seen in various melanocytic lesions are summarized in the table below:[112,113]