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
...nt ATA risk categories for hereditary...
...two MEN2 syndromes: MEN2A and MEN2B. W...
...method of initial genetic testing for M...
...uencing of the entire coding region sho...
...h the MEN2B phenotype should be tested fo...
...nts with presumed sporadic MTC should h...
...seling and genetic testing forRETgerml...
...an for academic reasons or physician pre...
In very rare families who meet the cli...
...ereditary MTC, the duty to warn a c...
...patients who have not reached the age of co...
...e duty to warn of genetic risk extends...
...should be aware that falsely high or l...
...g serum Ctn data clinicians should be aware that...
...of serum Ctn and carcinoembryonic antigen (CE...
...sment of a thyroid tumor with any fea...
...ete notation of the features of every MTC shoul...
...ith MTC morphological examination of the en...
...odules that are ≥1 cm in size should be evaluat...
Realizing that opinions of experts vary regarding...
...ents presenting with a thyroid nodule on phys...
...T/CT nor F-DOPA-PET/CT is recommen...
Table 2. Relationship of Common RET Mutation...
...American Joint Committee on Cancer TNM Cla...
...ble 3B. Anatomic Stage/Prognostic GroupsHavi...
Treatment
...Treatm...
Patients with MTC and no evidence of neck ly...
...ents with MTC and no evidence of neck metas...
...th MTC confined to the neck and cervical lym...
...e of extensive regional or metastatic disease,...
Following unilateral thyroidectomy for presumed...
In patients having an inadequate lymph node...
...total thyroidectomy for MTC, normal parathyroid...
...imulating hormone (TSH) should be measured...
...calcium levels should be monitored p...
...hysicians and surgeons in tertiary care...
...in the ATA-HST category with a RET codon M918T m...
...the ATA-H category should have a t...
...dren in the ATA-MOD category should have a physi...
...HEO should begin by age 11 years for children in...
...tients with MEN2A or MEN2B and a histologi...
...they coexist, a PHEO should be removed...
...r appropriate preoperative preparation a...
...with no adrenal glands require glucocorticoid an...
...the ATA-H and ATA-MOD categories sho...
...atients with HPTH, only the visibly enla...
...evelop HPTH subsequent to thyroidectomy...
...nicians should consider the American...
...rum levels of Ctn and CEA should be measure...
...ts with elevated postoperative serum Ctn l...
...ostoperative serum Ctn level exceeds...
...th detectable serum levels of Ctn an...
...ction of persistent or recurrent loco-r...
...adioactive iodine (RAI) is not indica...
...rative adjuvant EBRT to the neck and med...
...ystemic therapy should not be admin...
...ts with persistent or recurrent MTC followi...
...imaging should be performed in patie...
...atients with spinal cord compression r...
...MTC who have fractures or impending...
...denosumab or bisphosphonates is recomm...
...al resection should be considered in patien...
...resection should be considered in patients wit...
...sible cutaneous metastases should be excised su...
...py, including surgery, EBRT, or systemic th...
...single agent or combinatorial cytotoxic chemothera...
...ent with radiolabeled molecules or pre-...
...patients with significant tumor burden and...
...advanced MTC and diarrhea should be treated i...
...with metastatic MTC and Cushing’s s...
...gure 1. Management of Patients With a Thyroi...
...Management of Patients with a RET Germline Mu...
...ement of Patients Following Thyroidectomy...