Other Rare Childhood Cancers
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 (MELTUMP). These lesions are biologically different from melanoma and benign nevi.[83,84] 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.[85,86] 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 the cases.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.
Overall 5-year survival of children and adolescents with melanoma is approximately 90%.[47,58,60] Approximately three-fourths of all children and adolescents present with localized disease and have an excellent outcome (>90% 5-year survival). The outcome for patients with nodal disease is intermediate, with about 60% expected to survive long term.[47,60] In one study, the outcome for patients with metastatic disease was favorable, but this figure was not duplicated in another study from the National Cancer Database. For patients with metastatic disease, prognosis is poor and single-agent chemotherapy with dacarbazine, temozolomide, sorafenib, or interleukin-2, or biochemotherapy may be used.[90,91] Newer therapies, such as ipilimumab, have been tested in very limited numbers of children and results are not yet available. (Refer to the PDQ summary on adult Skin Cancer Treatment for more information.)
Chordoma is a very rare tumor of bone that arises from remnants of the notochord within the clivus, spinal vertebrae, or sacrum. The incidence in the United States is approximately one case per one million people per year, and only 5% of all chordomas occur in patients younger than 20 years. In children and adolescents, chordomas are more likely to arise in the skull base rather than in the sacrum, making them relatively inaccessible to complete surgical excision. Most pediatric patients have the conventional or chondroid variant of chordoma.[93,94] Patients usually present with pain, with or without neurologic deficits such as cranial or other nerve impairment. Diagnosis is straightforward when the typical physaliferous (soap-bubble-bearing) cells are present. Differential diagnosis is sometimes difficult and includes dedifferentiated chordoma and chondrosarcoma. Standard treatment includes surgery, which is not commonly curative because of difficulty in obtaining clear margins, and external radiation therapy. The best results have been obtained using proton-beam therapy (charged-particle radiation therapy).[95,96]; [Level of evidence: 3iiiDiii] Recurrences are usually local but can include distant metastases to lungs or bone. Children younger than 5 years appear to have a worse outlook than older patients.[93,98,99] The survival rate in children and adolescents ranges from about 50% to 80%.[93,99] There is no known effective cytotoxic agent or combination chemotherapy for this disease. Imatinib mesylate has been shown to have antitumor activity in adults with chordoma, and its effect might be the result of inhibition of phosphorylation and activation of PDGFR alpha, beta, and KIT receptors. This therapy has not been tested in children with chordoma.