Other rare childhood cancers include multiple endocrine neoplasia syndromes and Carney complex, skin cancer, chordoma, and cancer of unknown primary site. The prognosis, diagnosis, classification, and treatment of these other rare childhood cancers are discussed below. It must be emphasized that these cancers are seen very infrequently in patients younger than 15 years, and most of the evidence is derived from case series.
Multiple Endocrine Neoplasia (MEN) Syndromes and Carney Complex
MEN syndromes are familial disorders that are characterized by neoplastic changes that affect multiple endocrine organs. Changes may include hyperplasia, benign adenomas, and carcinomas. There are two main types of MEN syndrome: type 1 and type 2. Type 2 can be further subdivided into three subtypes: type 2A, type 2B, and familial medullary thyroid carcinoma (FMTC). The most salient clinical and genetic alterations of the MEN syndromes are shown in Table 1.
Table 1. MEN Syndromes with Associated Clinical and Genetic Alterations
|Syndrome||Clinical Features/Tumors||Genetic Alterations|
|MEN type 1: Werner syndrome||Parathyroid||11q13 (MEN1 gene)|
|Pancreatic islets: ||Gastrinoma||11q13 (MEN1 gene)|
|Pituitary:||Prolactinoma||11q13 (MEN1 gene)|
|Other associated tumors: ||Carcinoid||11q13 (MEN1 gene)|
|MEN type 2A: Sipple syndrome||Medullary thyroid carcinoma||10q11.2 (RET gene)|
|MEN type 2B||Medullary thyroid carcinoma||10q11.2 (RET gene)|
|Familial medullary thyroid carcinoma||Medullary thyroid carcinoma||10q11.2 (RET gene)|
The MEN 1 syndrome, also referred to as Werner syndrome, is an autosomal dominant disorder characterized by the presence of tumors in the parathyroid, pancreatic islet cells, and anterior pituitary. Diagnosis of this syndrome should be considered when two of the three endocrine tumors listed in the table above are present. Less common tumors associated with this syndrome include adrenocortical tumors, carcinoid tumors, lipomas, angiofibromas, and collagenomas. The first manifestation of the disease in 90% of patients is hypercalcemia; the most common cause of morbidity and mortality in these patients is the development of gastrinomas, leading to Zollinger-Ellison syndrome.[2,3] Germline mutations of the MEN1 gene located on chromosome 11q13 are found in 70% to 90% of patients; however, this gene has also been shown to be frequently inactivated in sporadic tumors. Mutation testing should be combined with clinical screening for patients and family members with proven at-risk MEN 1 syndrome. There are guidelines that may be followed for screening patients with MEN 1 syndrome. Treatment of patients with MEN 1 syndrome is based on the type of tumor.
MEN 2A is characterized by the presence of two or more endocrine tumors (see Table 2) in an individual or in close relatives.RET mutations in these patients are usually confined to exons 10 and 11. MEN 2B is characterized by medullary thyroid carcinomas, parathyroid hyperplasias, adenomas, pheochromocytomas, mucosal neuromas, and ganglioneuromas.[6,7,8] The medullary thyroid carcinomas that develop in these patients are extremely aggressive. More than 95% of mutations in these patients are confined to codon 918 in exon 16, causing receptor autophosphorylation and activation. Patients also have medullated corneal nerve fibers, distinctive faces with enlarged lips, and an asthenic Marfanoid body habitus. A pentagastrin stimulation test can be used to detect the presence of medullary thyroid carcinoma in such patients, although management of patients is driven primarily by the results of genetic analysis for RET mutations. There are guidelines that may be followed for screening patients with MEN 2 syndromes.