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

Diagnosi...

...risk categories for hereditary MTC should be...


...re should be two MEN2 syndromes: MEN2A...


...ed method of initial genetic testing for...


...the entire coding region should be r...


...the MEN2B phenotype should be tested f...


...esumed sporadic MTC should have genetic...


...c counseling and genetic testing forRETge...


...an for academic reasons or physici...


...families who meet the clinical criteria for MEN2...


...rding hereditary MTC, the duty to...


...iatric patients who have not reached the age o...


...duty to warn of genetic risk exte...


...linicians should be aware that falsely high or low...


...preting serum Ctn data clinicians should b...


...l levels of serum Ctn and carcinoembryo...


...of a thyroid tumor with any featur...


...ete notation of the features of eve...


In patients with MTC morphological exa...


...yroid nodules that are ≥1 cm in size should be e...


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


...presenting with a thyroid nodule on physical...


...her FDG-PET/CT nor F-DOPA-PET/CT is recomme...


...able 2. Relationship of Common RET Mutations to R...

...American Joint Committee on Cancer TNM Classif...

...able 3B. Anatomic Stage/Prognostic GroupsH...


Treatment

...eatment...

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


...n patients with MTC and no evidence of n...


...ients with MTC confined to the neck and cervica...


...resence of extensive regional or met...


...ilateral thyroidectomy for presumed...


...having an inadequate lymph node dissection at the...


...g a total thyroidectomy for MTC, normal parathyr...


...oid stimulating hormone (TSH) should be measu...


...evels should be monitored postoperative...


...perienced physicians and surgeons in tertiary ca...


...ATA-HST category with a RET codon M918T...


...hildren in the ATA-H category shou...


...ren in the ATA-MOD category should have a ph...


...ening for PHEO should begin by age 11 ye...


...tients with MEN2A or MEN2B and a histologi...


If they coexist, a PHEO should be...


...iate preoperative preparation a PHEO...


...adrenal glands require glucocorticoid an...


...nts in the ATA-H and ATA-MOD categories should...


...ents with HPTH, only the visibly enlar...


...s who develop HPTH subsequent to thyroidectomy fo...


...should consider the American Joint...


...of Ctn and CEA should be measured 3...


...ents with elevated postoperative serum Ct...


...tive serum Ctn level exceeds 150 pg/mL, pa...


...ith detectable serum levels of Ctn a...


...resection of persistent or recurrent loco-r...


...perative radioactive iodine (RAI) is not indicate...


...ative adjuvant EBRT to the neck and mediastinum...


Systemic therapy should not be admin...


...s with persistent or recurrent MTC fo...


...should be performed in patients with metasta...


...ents with spinal cord compression requ...


...TC who have fractures or impending fr...


...t with denosumab or bisphosphonates...


...ection should be considered in patients with...


...ction should be considered in patients with large...


...cutaneous metastases should be exc...


...tive therapy, including surgery, EBRT,...


...se of single agent or combinatorial cytoto...


...eatment with radiolabeled molecules or pre-targete...


...with significant tumor burden and symptomat...


...with advanced MTC and diarrhea should...


...with metastatic MTC and Cushing’s syndrome due...


...igure 1. Management of Patients With a...


...ure 2. Management of Patients with a RET Ger...


...agement of Patients Following Thyr...