Persistent local-regional MTC was present following the initial cervical operation in 12 of 22 patients (55%); including 4 of 13 with MEN2B diagnosed prior to initial surgery and 8 of 9 with MEN2B diagnosed after initial surgery.
Medullary thyroid cancer (MTC) is a rare tumor arising from the calcitonin-producing parafollicular C cells of the thyroid gland, occurring either sporadically or alternatively in a hereditary form based on germline RET mutations in approximately one-third of cases.
Since the association of RET proto-oncogene mutations and medullary thyroid carcinoma in children there has been much discussion regarding timing of surgery.
Multiple endocrine neoplasia type 2A (MEN2A) is a condition with inherited autosomal dominant mutations in RET (rearranged during transfection) gene that predisposes the carrier to extremely high risk of medullary thyroid cancer (MTC) and other MEN2A-associated tumors such as parathyroid cancer and/or pheochromocytoma.
Children belonging to families with FMTC are usually identified by RET genetic screening shortly after birth or during childhood but they likely develop MTC later in adult life.
MTC is mostly associated with variations in the 5 cysteine RET radicals and codon-risk management protocols are of considerable value but not infallible.
Germline mutations of RET are responsible for the development of heritable forms of medullary thyroid carcinoma (MTC) while somatic mutations of this oncogene are found in a significant proportion of sporadic MTCs.
We now report a case of MTC in which a RET somatic mutation at codon 918 was detected in fine-needle aspiration specimens obtained from both the thyroid nodule and two enlarged neck lymph nodes but not in peripheral blood.
We found no correlation between the presence of other somatic genetic events, such as loss of heterozygosity on chromosome arms 1p and 22q, and RET mutation status in the various subpopulations of MTC.
Because many patients with MEN 2A and B show gastrointestinal symptoms before the development of MTC, the possibility of MEN 2 should be recognized, and genetic testing for the presence of RET mutations should be included in the explorative diagnosis for megacolon.
BRAF mutation testing plays an increasingly important role in perioperative management and has potential for targeted molecular therapies.Prophylactic thyroidectomy is indicated early in life for RET mutation carriers at risk for medullary thyroid cancer.
In this review, the structure and signalling properties of the RET proto-oncogene in its wild-type and mutant forms, and its role in hereditary and sporadic MTC, are discussed.
Association between the position and type of germline mutation in the RET proto-oncogene and the presence or absence of MTC, pheo, HPT, and/or other features in a family.
Although reported gene variants in the RET oncogene have been directly associated with multiple endocrine neoplasia type 2 and hereditary medullary thyroid carcinoma, other mutations are classified as variants of uncertain significance (VUS) until the associated clinical phenotype is made clear.
The different RET-activating capability of mutations of cysteine 620 or cysteine 634 correlates with the multiple endocrine neoplasia type 2 disease phenotype.
The data show a higher rate of inherited MTC than previously described, although MEN2A was found to be the most common inherited form of MTC, the same as in earlier studies.
All patients diagnosed with medullary thyroid carcinoma (MTC) should undergo RET mutation analysis to exclude familial disease - multiple endocrine neoplasia (MEN)-2A and -2B and familial medullary thyroid carcinoma (FMTC).
Four children were at risk of being carriers of a mutated gene, as their fathers had histologically proven MTC and had tested positive for the mutation at codon 618 on exon 10 of the RET proto-oncogene.