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
...he current ATA risk categories for hereditary...
...be two MEN2 syndromes: MEN2A and MEN2B. Within...
...e recommended method of initial gene...
...ing of the entire coding region should be reserv...
...he MEN2B phenotype should be tested for t...
...ts with presumed sporadic MTC should h...
...nseling and genetic testing forRETgermline m...
...han for academic reasons or physician prefer...
...y rare families who meet the clinical criteria...
...ng hereditary MTC, the duty to warn a c...
...atients who have not reached the age of consent...
...o warn of genetic risk extends to both pr...
...should be aware that falsely high...
In interpreting serum Ctn data clinician...
Basal levels of serum Ctn and carcinoem...
...t of a thyroid tumor with any feature sugge...
Complete notation of the features of e...
In patients with MTC morphological...
...that are ≥1 cm in size should be...
...ng that opinions of experts vary regarding t...
...tients presenting with a thyroid nodule...
...ither FDG-PET/CT nor F-DOPA-PET/CT is...
...le 2. Relationship of Common RET Mutations t...
...ican Joint Committee on Cancer TNM...
...omic Stage/Prognostic GroupsHaving tr...
Treatment
Treatmen...
...C and no evidence of neck lymph node me...
...with MTC and no evidence of neck met...
...ients with MTC confined to the neck and cervica...
...esence of extensive regional or me...
...g unilateral thyroidectomy for presumed sp...
In patients having an inadequate lymph no...
...a total thyroidectomy for MTC, normal p...
...timulating hormone (TSH) should be measured wit...
...vels should be monitored postoperatively....
...erienced physicians and surgeons in...
...ildren in the ATA-HST category with a RET...
...ildren in the ATA-H category should ha...
Children in the ATA-MOD category should...
...or PHEO should begin by age 11 year...
...EN2A or MEN2B and a histological dia...
...xist, a PHEO should be removed prior to surgery...
...te preoperative preparation a PHEO should be res...
Patients with no adrenal glands require glucocor...
...in the ATA-H and ATA-MOD categories sho...
...ients with HPTH, only the visibly e...
...evelop HPTH subsequent to thyroidectomy for MTC sh...
...ns should consider the American Joint Commit...
...vels of Ctn and CEA should be measured 3 months...
...elevated postoperative serum Ctn l...
...tive serum Ctn level exceeds 150 pg/m...
...th detectable serum levels of Ctn...
...ical resection of persistent or recurrent...
...adioactive iodine (RAI) is not indicated fol...
...ve adjuvant EBRT to the neck and mediastinum sh...
Systemic therapy should not be administered to...
...nts with persistent or recurrent MTC follo...
...ing should be performed in patients with m...
...nts with spinal cord compression r...
...ents with MTC who have fractures or imp...
...h denosumab or bisphosphonates is recommended fo...
...ction should be considered in pati...
...urgical resection should be considered i...
...ible cutaneous metastases should be excised...
...alliative therapy, including surgery, EBRT, or...
...single agent or combinatorial cytotoxic c...
...with radiolabeled molecules or pre-tar...
...patients with significant tumor burd...
...atients with advanced MTC and diarrhea should be...
...s with metastatic MTC and Cushing’s syndrome...
...Management of Patients With a Thyroid Nodule...
.... Management of Patients with a RET Germline...
...agement of Patients Following Thyroidectomy...