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Cancer Health Center

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Unusual Cancers of Childhood Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Other Rare Childhood Cancers

Table 7. Characteristics of Paraganglioma (PGL) and Pheochromocytoma (PCC) Associated with Susceptibility Genesa continued...

Lymph node dissection is recommended if sentinel nodes are involved with tumor, and adjuvant therapy with high-dose interferon alfa-2b for a period of 1 year should be considered in these patients.[62,95,99,100,101] 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.[105] 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. One retrospective study found that children aged 10 years or older were more likely to present with amelanotic lesions, bleeding, uniform color, variable diameter, and elevation (such as a de novo bump).[107][Level of evidence: 3iiA]

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.[108,109] In contrast, the use of fluorescence in situ hybridization (FISH) probes that target four specific regions in chromosomes 6 and 11 can help classify melanoma correctly in more than 85% of cases; however, 24% of atypical Spitzoid lesions will have chromosomal alterations on FISH analysis and 75% will have BRAF V600E mutations.[110,111]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.[112] Some of the characteristic genetic alterations seen in various melanocytic lesions are summarized in the table below:[113,114]

Table 8. Characteristics of Melanocytic Lesions

TumorAffected Gene
Spitz nevusHRAS;BRAFandNRAS(uncommon)
Acquired nevusBRAF
Dysplastic nevusBRAF,NRAS
Blue nevusGNAQ
Ocular melanomaGNAQ
Congenital neviBRAF,NRAS
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