Medullary thyroid cancer: molecular factors, management and treatment

Abstract

Medullary thyroid cancer (MTC) is an infrequent neuroendocrine tumor, which amounts to 3–5% of all thyroid malignancies. Approximately 75–80% of MTCs are sporadic neoplasms. The rest of 20–25% are familial cases that belong to multiple endocrine neoplasia (MEN) syndromes, specifically MEN2 and MEN3. These cases of familial MTC are attributed to an activating germline mutation of a tyrosine kinase receptor gene, the rearranged during transfection ( RET ) proto-oncogene, located on chromosome 10q11.21. These mutations are also found in some cases of sporadic MTC. This review sets forth in summary the accepted guidelines and approaches regarding diagnosis, management, and treatment of MTC. Surgical resection is the standard care, and an early, prophylactic intervention is performed in genetic cases. Further investigation and understanding of the molecular pathways involved in the growth and advancement of MTC is required in order to provide efficient therapy in cases of progressive disease.

Update on the Diagnosis and Management of Medullary Thyroid Cancer: What Has Changed in Recent Years?

“…The primary technique cited by most of the papers and guidelines we found as the valid technique for initial treatment of MTC was total thyroidectomy (TT) combined with central compartment lymph node dissection (CCLND) [ 25 , 33 , 64 , 65 , 66 , 67 , 68 ]. The reason for choosing TT over hemithyroidectomy is the fact that multifocal and bilateral disease is present in most hereditary and 6% of sporadic MTC cases [ 5 , 62 ], and according to some sources, even in all hereditary and as many as 30% of sporadic MTC cases [ 7 ]. A slightly different approach was presented by a former Japanese researcher Miyauchi et al [ 69 ], who suggested that, among patients with sporadic MTC who lack mutations in the RET gene, the chance of bilateral primary lesions is close to 0%.…”

“…Currently, lateral compartment lymph node dissection (LCLND) is the most controversial [ 5 , 7 , 25 , 33 , 64 , 65 , 72 , 73 ]. One view on deciding whether to perform prophylactic LCLND when there is no evidence of neck metastases on the US is based on the Ctn level [ 5 , 8 , 25 , 70 ].…”

“…In addition, diarrhea, flushing and chest pain are sometimes observed. Recurrent respiratory infections may be associated with advanced disease [ 6 , 7 ].…”

“…The RET gene is a protooncogene encoding a protein that is part of the receptor for tyrosine kinase. The RET gene is essential for the regulation of cell differentiation, proliferation and apoptosis [ 7 , 11 ]. Mutations involving codons C630 and A883, as well as H568 and S1024, are mainly reported in sporadic cases.…”

“…The 5-year survival rate is estimated at 80–97%, and the 10-year survival rate is estimated at 75–88%. Recurrences occur in up to 50% of patients [ 5 , 7 ].…”