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
Diagnosis
...rrent ATA risk categories for hereditary...
...hould be two MEN2 syndromes: MEN2A and MEN2B....
...ommended method of initial genetic test...
...uencing of the entire coding region should...
...h the MEN2B phenotype should be tested for...
...s with presumed sporadic MTC should have genetic...
...ounseling and genetic testing forRETgerml...
...han for academic reasons or physician prefe...
...milies who meet the clinical criteria for M...
...egarding hereditary MTC, the duty to w...
...c patients who have not reached the age o...
...duty to warn of genetic risk extends to both p...
...ould be aware that falsely high or...
...reting serum Ctn data clinicians should be awa...
...s of serum Ctn and carcinoembryonic...
...f a thyroid tumor with any feature suggestiv...
...notation of the features of every MTC should fo...
...ts with MTC morphological examination of the enti...
...les that are ≥1 cm in size should...
...ealizing that opinions of experts vary regardin...
...ients presenting with a thyroid nodu...
...ither FDG-PET/CT nor F-DOPA-PET/CT is recommended...
...2. Relationship of Common RET Mutations to Ri...
...able 3A. American Joint Committee on...
...le 3B. Anatomic Stage/Prognostic GroupsHaving trou...
Treatment
Treatme...
...h MTC and no evidence of neck lymph node metas...
...ith MTC and no evidence of neck metastases...
...ts with MTC confined to the neck and cervic...
In the presence of extensive regional or metastat...
...unilateral thyroidectomy for presumed s...
...patients having an inadequate lymph node...
...l thyroidectomy for MTC, normal parathyr...
...hyroid stimulating hormone (TSH) should be m...
...erum calcium levels should be monitored...
...erienced physicians and surgeons in tertiar...
...en in the ATA-HST category with a RET codon M918...
...ATA-H category should have a thyroidectomy perf...
...in the ATA-MOD category should have a physical e...
...g for PHEO should begin by age 11 years f...
...MEN2A or MEN2B and a histological diagnosis of MT...
If they coexist, a PHEO should be rem...
...e preoperative preparation a PHEO should be...
...o adrenal glands require glucocorticoid a...
...the ATA-H and ATA-MOD categories should be s...
...ents with HPTH, only the visibly enl...
...ts who develop HPTH subsequent to thyroidectomy...
...linicians should consider the American Joi...
Serum levels of Ctn and CEA should be meas...
Patients with elevated postoperati...
...perative serum Ctn level exceeds 150 pg/m...
...ith detectable serum levels of Ctn and CEA follow...
...section of persistent or recurrent...
...perative radioactive iodine (RAI) is no...
...stoperative adjuvant EBRT to the nec...
...y should not be administered to patients who d...
...ients with persistent or recurrent...
...ould be performed in patients with metas...
...tients with spinal cord compression require ur...
...MTC who have fractures or impending fra...
...denosumab or bisphosphonates is recommende...
...cal resection should be considered i...
...cal resection should be considered in pat...
...cutaneous metastases should be excised...
...lliative therapy, including surgery, EBRT, o...
...he use of single agent or combinatorial cytotoxi...
...nt with radiolabeled molecules or pr...
...th significant tumor burden and symptomatic or pro...
...advanced MTC and diarrhea should be treated ini...
...ents with metastatic MTC and Cushing’s...
...agement of Patients With a Thyroid...
.... Management of Patients with a RET...
...Management of Patients Following Thyroidec...