Bilateral Medullary Thyroid Carcinoma in a 3-Year-Old Female Patient with Multiple Endocrine Neoplasia 2A Syndrome Undergoing Prophylactic Thyroidectomy: Should Current Guidelines Be Revised?

Abstract

Background: Multiple endocrine neoplasia (MEN) 2A is an autosomal dominant disorder that results from a mutation in the RET proto-oncogene on chromosome 10. Almost all of the affected patients develop medullary thyroid carcinoma (MTC). The American Thyroid Association recommends prophylactic thyroidectomy in MEN 2A pediatric patients, with the age of the recommended thyroidectomy varying according to the codon mutation present. Objectives: This report questions the reliability of the currently placed guidelines and whether the age threshold for prophylactic thyroidectomy in patients with known codon 634 mutations should be lowered, in parallel with an earlier evaluation of calcitonin levels in the serum. Methods: We report the preoperative diagnosis as well as operative and postoperative course of a 3-year-old female patient with MEN 2A (codon 634 mutation) who underwent prophylactic thyroidectomy. The postoperative histopathologic findings are presented and discussed. Results: Despite the prophylactic nature of the operation, in parallel with a borderline calcitonin increase in the serum, bilateral MTC was discovered on pathology. Conclusion: It is likely that the current guidelines should be revised to recommend calcitonin screening and prophylactic thyroidectomy at an earlier age for MEN 2A patients with known codon 634 mutations.

RET Proto-Oncogene Variants in Patients with Medullary Thyroid Carcinoma from the Mediterranean Basin: A Brief Report

“…Not unexpectedly, all p.Gly533Cys carriers shared an identical core haplotype, indicating a common ancestor, and as a result of the frequent migratory currents in the Mediterranean region, this was also likely taken to the Iberian Peninsula [53,55,56]. Recent reports from Cyprus and Israel identified the ATA-MOD risk p.Cys618Arg variant as the most prevalent, found in 69% and 55% of the probands, respectively [57][58][59][60][61]. The p.Cys618Arg variant was reported in nine apparently unrelated families from Cyprus who all shared a common haplotype (Table 1).…”

Clinical characteristics of a large familial cohort with Medullary thyroid cancer and germline Cys618Arg RET mutation in an Israeli multicenter study

“…Correlation between patient age at surgery and tumor size for cohorts with Cys618Arg and Cys634Arg/Thr/Tyr mutations. (21). Seven patients in the Cys618Arg cohort were diagnosed in childhood or adolescence (aged 8-16 years).…”