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
...A risk categories for hereditary MTC...
...e should be two MEN2 syndromes: MEN2A...
...ecommended method of initial genetic testing for M...
...of the entire coding region should...
...s with the MEN2B phenotype should be tested for th...
...ts with presumed sporadic MTC should have...
...ling and genetic testing forRETgermline mut...
Other than for academic reasons or ph...
...milies who meet the clinical criteria...
...arding hereditary MTC, the duty to warn...
...pediatric patients who have not reached the a...
...of genetic risk extends to both pre...
...hould be aware that falsely high or low serum c...
...n interpreting serum Ctn data clinicians should b...
...serum Ctn and carcinoembryonic antigen (CEA) shou...
...of a thyroid tumor with any feature sugges...
...otation of the features of every MTC should...
...s with MTC morphological examination of th...
...d nodules that are ≥1 cm in size sh...
Realizing that opinions of experts vary regard...
...ting with a thyroid nodule on physical ex...
...her FDG-PET/CT nor F-DOPA-PET/CT is re...
...ionship of Common RET Mutations to Risk of...
...ble 3A. American Joint Committee on Cancer T...
...ble 3B. Anatomic Stage/Prognostic GroupsHaving t...
Treatment
...eatment
...s with MTC and no evidence of neck lymph node met...
...atients with MTC and no evidence o...
...ents with MTC confined to the neck and cervical...
...the presence of extensive regional...
...ateral thyroidectomy for presumed sporadic M...
...n patients having an inadequate lymp...
...hyroidectomy for MTC, normal parathyr...
...thyroid stimulating hormone (TSH) should be measu...
...um levels should be monitored postope...
...ced physicians and surgeons in tertiary care c...
...ATA-HST category with a RET codon...
...ren in the ATA-H category should have a...
...ildren in the ATA-MOD category should have a...
...g for PHEO should begin by age 11 yea...
...ents with MEN2A or MEN2B and a histological d...
...f they coexist, a PHEO should be removed prior...
...opriate preoperative preparation a PHEO should...
...with no adrenal glands require glucocortico...
...he ATA-H and ATA-MOD categories should be s...
...ts with HPTH, only the visibly enl...
...who develop HPTH subsequent to thyroidectomy for M...
...ans should consider the American Joint Commit...
...f Ctn and CEA should be measured 3 months postope...
...ts with elevated postoperative serum...
...rative serum Ctn level exceeds 150 pg/mL, pat...
...h detectable serum levels of Ctn and CEA followin...
...ection of persistent or recurrent loc...
...ative radioactive iodine (RAI) is not indicated...
Postoperative adjuvant EBRT to the neck and me...
...therapy should not be administered to patients who...
...with persistent or recurrent MTC following thyroid...
...should be performed in patients with metastati...
...with spinal cord compression requir...
...ients with MTC who have fractures or...
...ent with denosumab or bisphosphonates is recom...
...section should be considered in pati...
Surgical resection should be considered in pa...
...ible cutaneous metastases should be excis...
...ve therapy, including surgery, EBRT, or s...
...e use of single agent or combinatorial cyt...
...t with radiolabeled molecules or pre-targeted radi...
...atients with significant tumor burden and sympto...
...th advanced MTC and diarrhea shoul...
...atients with metastatic MTC and Cu...
...Management of Patients With a Thyroid Nodule A...
...igure 2. Management of Patients with a R...
...Management of Patients Following Thy...