Medullary Thyroid Carcinoma
Key Points
Key Points
Medullary thyroid carcinoma accounts for 1-2% of thyroid cancers in the United States, a much lower range than frequently cited (3-5%) primarily due to the marked increase in the relative incidence of papillary thyroid carcinoma (PTC) over the last three decades.
Virtually all patients with MEN2A, MEN2B, and FMTC have RET germline mutations, and approximately 50% of sporadic MTCs have somatic RET mutations.
- The RET protooncogene (REarranged during Transfection), located on chromosome 10q11.2, encodes a single-pass transmembrane receptor of the tyrosine kinase family. Of sporadic MTCs lacking somatic RET mutations, 18-80% have somatic mutations of HRAS, KRAS, or rarely NRAS.
Over 100 mutations, duplications, insertions, or deletions involving RET have been identified in patients with MTC. The aggressiveness of MTC varies with the RET mutation. Therefore, treatment should be guided by genetic testing. (Table 2 summarizes the relative risk of developing an aggressive MTC and the other endocrine tumors and diseases associated with MEN2A and MEN2B.)
Diagnosis
...gnosis...
...rent ATA risk categories for hereditary MTC sho...
...two MEN2 syndromes: MEN2A and MEN2B. Within MEN2...
...ended method of initial genetic testing for...
...he entire coding region should be reserved...
...nts with the MEN2B phenotype should be t...
...tients with presumed sporadic MTC should have...
...ling and genetic testing forRETgermline mutati...
...n for academic reasons or physician pre...
...rare families who meet the clinical cr...
...arding hereditary MTC, the duty to warn a...
...c patients who have not reached the age of conse...
...n of genetic risk extends to both preconceptio...
...icians should be aware that falsely high or low se...
...nterpreting serum Ctn data clinicians sh...
...f serum Ctn and carcinoembryonic antigen...
...ent of a thyroid tumor with any feature sugg...
...on of the features of every MTC should...
...s with MTC morphological examination of th...
...nodules that are ≥1 cm in size sho...
...that opinions of experts vary regarding...
...presenting with a thyroid nodule on physical exa...
...ither FDG-PET/CT nor F-DOPA-PET/CT is...
...able 2. Relationship of Common RET Mutatio...
...ican Joint Committee on Cancer TNM Classification...
...omic Stage/Prognostic GroupsHaving trouble viewing...
Treatment
...atment
...tients with MTC and no evidence of neck...
...ients with MTC and no evidence of neck metasta...
...ents with MTC confined to the neck and...
...of extensive regional or metastatic dis...
...llowing unilateral thyroidectomy for...
...nts having an inadequate lymph node...
...al thyroidectomy for MTC, normal pa...
...stimulating hormone (TSH) should be measured w...
...um calcium levels should be monito...
...physicians and surgeons in tertiary care...
...the ATA-HST category with a RET codon M918T mutat...
...ren in the ATA-H category should have...
...the ATA-MOD category should have a physical exami...
...HEO should begin by age 11 years for children...
...with MEN2A or MEN2B and a histological dia...
...t, a PHEO should be removed prior to s...
...ropriate preoperative preparation a PHEO...
...no adrenal glands require glucocorticoid and...
...in the ATA-H and ATA-MOD categories sho...
...h HPTH, only the visibly enlarged para...
...nts who develop HPTH subsequent to thy...
...ians should consider the American Joint C...
...vels of Ctn and CEA should be measured 3 months...
...ients with elevated postoperative serum Ctn level...
...tive serum Ctn level exceeds 150 pg/mL, patients...
...atients with detectable serum levels of Ct...
...al resection of persistent or recurrent...
...perative radioactive iodine (RAI) is...
...erative adjuvant EBRT to the neck a...
...py should not be administered to patients...
...tients with persistent or recurrent...
...aging should be performed in patients with metas...
...nts with spinal cord compression require urg...
...tients with MTC who have fractures or im...
...denosumab or bisphosphonates is recommended fo...
...urgical resection should be considered in pati...
...resection should be considered in...
...le cutaneous metastases should be excised s...
...ative therapy, including surgery, EB...
...use of single agent or combinatorial cytotoxic...
...adiolabeled molecules or pre-targeted radio-immu...
...n patients with significant tumor burden a...
...advanced MTC and diarrhea should b...
...ith metastatic MTC and Cushing’s syndrome due...
...nagement of Patients With a Thyroid Nod...
...gement of Patients with a RET Germline Mutati...
Figure 3. Management of Patients Following Thyr...