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
...agnosis...
...rent ATA risk categories for heredita...
...be two MEN2 syndromes: MEN2A and M...
...ended method of initial genetic testing for MEN...
...the entire coding region should be reserved f...
...the MEN2B phenotype should be teste...
...ts with presumed sporadic MTC should have genetic...
...eling and genetic testing forRETgermline mutati...
...er than for academic reasons or physician prefe...
...ery rare families who meet the clinica...
...tary MTC, the duty to warn a competent and...
...pediatric patients who have not reached...
...to warn of genetic risk extends to b...
...ld be aware that falsely high or low serum cal...
...interpreting serum Ctn data clinicians should be...
...serum Ctn and carcinoembryonic antig...
...of a thyroid tumor with any feature s...
...plete notation of the features of eve...
...tients with MTC morphological examination of t...
Thyroid nodules that are ≥1 cm in size shou...
...ng that opinions of experts vary regarding th...
...nting with a thyroid nodule on physical examin...
...r FDG-PET/CT nor F-DOPA-PET/CT is recom...
...able 2. Relationship of Common RET Mutations t...
...American Joint Committee on Cancer TNM Classi...
...atomic Stage/Prognostic GroupsHaving trouble...
Treatment
Treatme...
...ents with MTC and no evidence of neck lymph no...
...with MTC and no evidence of neck me...
Patients with MTC confined to the neck and cervi...
...sence of extensive regional or metastati...
...eral thyroidectomy for presumed spora...
...aving an inadequate lymph node dissectio...
...otal thyroidectomy for MTC, normal parathyr...
...stimulating hormone (TSH) should be measured...
Serum calcium levels should be monitored p...
...d physicians and surgeons in tertiary care ce...
...dren in the ATA-HST category with...
...e ATA-H category should have a thyroidectomy perfo...
...e ATA-MOD category should have a physical exam...
...or PHEO should begin by age 11 years for...
...ients with MEN2A or MEN2B and a histo...
...they coexist, a PHEO should be removed...
...r appropriate preoperative preparation...
...no adrenal glands require glucocortic...
...nts in the ATA-H and ATA-MOD categories should be...
...n patients with HPTH, only the visibly enlarged p...
...develop HPTH subsequent to thyroidectomy for MTC...
...uld consider the American Joint Committee on C...
...rum levels of Ctn and CEA should be me...
...s with elevated postoperative serum C...
...postoperative serum Ctn level exceeds 150 pg/...
...n patients with detectable serum level...
...rgical resection of persistent or...
...erative radioactive iodine (RAI) i...
Postoperative adjuvant EBRT to the...
...therapy should not be administered to pati...
In patients with persistent or recur...
...imaging should be performed in patients with me...
...spinal cord compression require urgent treatment...
...MTC who have fractures or impending fractures req...
...denosumab or bisphosphonates is recommended...
...tion should be considered in patients wit...
...on should be considered in patients with large is...
...possible cutaneous metastases should be excise...
...e therapy, including surgery, EBRT, or systemi...
...gle agent or combinatorial cytotoxic ch...
...ith radiolabeled molecules or pre-targeted radio...
In patients with significant tumor burden and s...
...s with advanced MTC and diarrhea should...
...with metastatic MTC and Cushing’s s...
...anagement of Patients With a Thyroid...
...gure 2. Management of Patients with a RET Germlin...
...agement of Patients Following Thyroidec...