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
...A risk categories for hereditary MTC should be...
...re should be two MEN2 syndromes: ME...
...mmended method of initial genetic t...
...he entire coding region should be rese...
...tients with the MEN2B phenotype should...
...with presumed sporadic MTC should have...
...eling and genetic testing forRETgermline mut...
...or academic reasons or physician pref...
...very rare families who meet the cli...
...reditary MTC, the duty to warn a compete...
...patients who have not reached the age...
...y to warn of genetic risk extends to bot...
...hould be aware that falsely high or lo...
...ing serum Ctn data clinicians should...
...els of serum Ctn and carcinoembryoni...
...of a thyroid tumor with any feature suggestive...
...notation of the features of every MTC sh...
...tients with MTC morphological examination of...
...dules that are ≥1 cm in size should be e...
...ng that opinions of experts vary regard...
...presenting with a thyroid nodule on p...
...er FDG-PET/CT nor F-DOPA-PET/CT is rec...
Table 2. Relationship of Common RET Mu...
...American Joint Committee on Cancer TNM Cla...
...atomic Stage/Prognostic GroupsHavin...
Treatment
Treatme...
...ients with MTC and no evidence of neck lymph n...
...h MTC and no evidence of neck metast...
...th MTC confined to the neck and cervic...
...of extensive regional or metastatic dis...
...lowing unilateral thyroidectomy for presu...
...ents having an inadequate lymph node dissec...
...al thyroidectomy for MTC, normal par...
...d stimulating hormone (TSH) should be measured...
...evels should be monitored postoperativ...
...ed physicians and surgeons in tertiary care...
...in the ATA-HST category with a RET c...
...in the ATA-H category should have a thyroidectom...
...ren in the ATA-MOD category should have a phys...
...creening for PHEO should begin by ag...
...nts with MEN2A or MEN2B and a histological diagno...
...they coexist, a PHEO should be remov...
...opriate preoperative preparation a PHEO...
...adrenal glands require glucocorticoid a...
...s in the ATA-H and ATA-MOD categories...
...ith HPTH, only the visibly enlarged par...
...ients who develop HPTH subsequent to thyroidec...
...uld consider the American Joint Committ...
...erum levels of Ctn and CEA should be measured 3 mo...
...atients with elevated postoperative se...
...e postoperative serum Ctn level exceeds 150 pg/...
...nts with detectable serum levels of Ctn and CEA...
...gical resection of persistent or recurrent...
...e radioactive iodine (RAI) is not indicated...
...e adjuvant EBRT to the neck and mediastinu...
...c therapy should not be administered...
...th persistent or recurrent MTC followi...
...ain imaging should be performed in patients wi...
...spinal cord compression require urgent...
...with MTC who have fractures or impendi...
...enosumab or bisphosphonates is recommende...
...resection should be considered in patients...
...urgical resection should be considered in patien...
...ble cutaneous metastases should be ex...
...rapy, including surgery, EBRT, or system...
...of single agent or combinatorial cytotoxic c...
Treatment with radiolabeled molecules...
In patients with significant tumor b...
...with advanced MTC and diarrhea should be treated...
...etastatic MTC and Cushing’s syndrome du...
...ure 1. Management of Patients With a Thyroid...
...nagement of Patients with a RET Ge...
...re 3. Management of Patients Following Thy...