Medullary Thyroid Carcinoma

Publication Date: June 3, 2015

Key Points

Key Points

Medullary Thyroid Carcinoma (MTC) represents a unique thyroid cancer that occurs either sporadically or in a hereditary form as a component of the type 2 multiple endocrine neoplasia (MEN) syndromes, MEN2A, MEN2B, and the related syndrome, familial MTC (FMTC).

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.
RET is a remarkable oncogene that is central not only to the development of sporadic and hereditary MTC but also to other malignant and non-malignant diseases.

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

...he current ATA risk categories for hereditary MTC...


...d be two MEN2 syndromes: MEN2A and...


The recommended method of initial genetic tes...


...quencing of the entire coding region...


...the MEN2B phenotype should be tested for the RE...


...nts with presumed sporadic MTC should have gen...


...c counseling and genetic testing forRETgermli...


...cademic reasons or physician preference, it...


...are families who meet the clinical c...


...hereditary MTC, the duty to warn a c...


In pediatric patients who have not r...


...to warn of genetic risk extends to bot...


...should be aware that falsely high o...


In interpreting serum Ctn data clinici...


...ls of serum Ctn and carcinoembryonic anti...


...ssessment of a thyroid tumor with a...


...n of the features of every MTC should follow the...


...th MTC morphological examination of t...


...oid nodules that are ≥1 cm in size should b...


...t opinions of experts vary regarding the usef...


...ents presenting with a thyroid nodule on physic...


...G-PET/CT nor F-DOPA-PET/CT is reco...


...Relationship of Common RET Mutations t...

...American Joint Committee on Cancer TNM Cl...

.... Anatomic Stage/Prognostic GroupsHavi...


Treatment

Treatmen...

...MTC and no evidence of neck lymph...


...with MTC and no evidence of neck m...


...with MTC confined to the neck and cervical ly...


...ce of extensive regional or metastatic disease...


...owing unilateral thyroidectomy for presumed sporad...


...ing an inadequate lymph node dissection at th...


...otal thyroidectomy for MTC, normal...


...d stimulating hormone (TSH) should be measured...


...levels should be monitored postoperatively....


...sicians and surgeons in tertiary care ce...


...n in the ATA-HST category with a RET...


...dren in the ATA-H category should have a thyroi...


Children in the ATA-MOD category should...


...creening for PHEO should begin by...


...th MEN2A or MEN2B and a histological diagno...


...ey coexist, a PHEO should be remove...


...iate preoperative preparation a PHEO shou...


...with no adrenal glands require glucocortico...


...e ATA-H and ATA-MOD categories should...


...ients with HPTH, only the visibly enlarged pa...


...atients who develop HPTH subsequent to thyroide...


...s should consider the American Joint Committee...


...m levels of Ctn and CEA should be measured 3 mont...


...evated postoperative serum Ctn levels...


...operative serum Ctn level exceeds 150 pg...


...h detectable serum levels of Ctn and CEA fo...


...al resection of persistent or recurrent loco-regio...


...radioactive iodine (RAI) is not indicated f...


Postoperative adjuvant EBRT to the neck...


...stemic therapy should not be administered...


...persistent or recurrent MTC followin...


...hould be performed in patients with m...


...s with spinal cord compression requir...


...tients with MTC who have fractures or impending fr...


...atment with denosumab or bisphosphona...


...urgical resection should be considered in...


...ion should be considered in patients w...


...le cutaneous metastases should be excised su...


...therapy, including surgery, EBRT, o...


...ngle agent or combinatorial cytotoxi...


Treatment with radiolabeled molecules or pre...


...with significant tumor burden and symptomatic o...


...dvanced MTC and diarrhea should be treated...


...with metastatic MTC and Cushingâ€...


...ment of Patients With a Thyroid No...


...2. Management of Patients with a RET Germl...


...3. Management of Patients Following Thyroi...