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...
...TA risk categories for hereditary MTC s...
There should be two MEN2 syndromes: M...
...d method of initial genetic testing for MEN2A is...
Sequencing of the entire coding region...
...tients with the MEN2B phenotype should b...
...presumed sporadic MTC should have genetic...
...ing and genetic testing forRETgerml...
...academic reasons or physician preference, it is n...
...very rare families who meet the clinica...
...ing hereditary MTC, the duty to warn a compete...
...tients who have not reached the age of consent it...
...of genetic risk extends to both preconception...
...hould be aware that falsely high or lo...
...ing serum Ctn data clinicians should be a...
...serum Ctn and carcinoembryonic antigen (C...
...ment of a thyroid tumor with any feature sug...
...lete notation of the features of ever...
...h MTC morphological examination of the entire...
...yroid nodules that are ≥1 cm in size should...
...zing that opinions of experts vary regardin...
...ients presenting with a thyroid nodule on physical...
...DG-PET/CT nor F-DOPA-PET/CT is recommended t...
...Relationship of Common RET Mutations to Risk...
...A. American Joint Committee on Canc...
...Anatomic Stage/Prognostic Groups Sta...
Treatment
...Treat...
...with MTC and no evidence of neck lymph node meta...
...ts with MTC and no evidence of neck m...
...ients with MTC confined to the neck and cervical...
...the presence of extensive regional or...
...unilateral thyroidectomy for presumed sporadi...
...having an inadequate lymph node dissection a...
...ring a total thyroidectomy for MTC, normal par...
...stimulating hormone (TSH) should be meas...
Serum calcium levels should be monitored postoper...
Experienced physicians and surgeons in ter...
...the ATA-HST category with a RET codon M91...
...ATA-H category should have a thyroidectomy...
...en in the ATA-MOD category should...
...ening for PHEO should begin by age 11 years for...
...with MEN2A or MEN2B and a histological dia...
...y coexist, a PHEO should be removed prior to sur...
...appropriate preoperative preparatio...
...adrenal glands require glucocorticoid and mineral...
...the ATA-H and ATA-MOD categories should b...
...n patients with HPTH, only the visibly enlarged...
...develop HPTH subsequent to thyroidectom...
...uld consider the American Joint Committee on Cance...
...Ctn and CEA should be measured 3 mont...
...evated postoperative serum Ctn levels...
...e postoperative serum Ctn level exceeds 150 pg/mL,...
...th detectable serum levels of Ctn and CEA...
...ection of persistent or recurrent loco-regional M...
...dioactive iodine (RAI) is not indicated f...
...juvant EBRT to the neck and mediastinum sh...
...should not be administered to patien...
...h persistent or recurrent MTC following t...
Brain imaging should be performed in patie...
...with spinal cord compression require urgent t...
...C who have fractures or impending fractures requ...
...th denosumab or bisphosphonates is recom...
...tion should be considered in patients with large...
Surgical resection should be considered in patie...
...neous metastases should be excised surgical...
...herapy, including surgery, EBRT, or systemic...
...single agent or combinatorial cytotoxic ch...
...ment with radiolabeled molecules or...
In patients with significant tumor burde...
...ith advanced MTC and diarrhea should be treated...
...atients with metastatic MTC and Cushing’...
...ure 1. Management of Patients With a Thyroid No...
...2. Management of Patients with a RET Germline M...
...ment of Patients Following Thyroidectomy F...