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The incidence of thyroid cancer has steadily increased over the past 2 decades; this rise is attributable more to the earlier detection of papillary thyroid cancers rather than a true increase in disease incidence. Early diagnosis may be due to the increase in use of transcutaneous ultrasonography and the more widespread use of fine-needle aspiration biopsy (FNAB). Although the incidence and prevalence of thyroid cancer is increasing, the mortality rate from this disease has remained very low.

Exposure to ionizing radiation remains the only established environmental risk factor for thyroid cancer. A significant minority of thyroid cancers are caused by inherited genetic mutations. Several rare familial syndromes are associated with a high prevalence of medullary (MTC) and non-medullary thyroid cancers, including multiple endocrine neoplasia (MEN) types 2A and 2B, familial (non-MEN) MTC, Werner’s syndrome, familial adenomatoid polyposis, and Cowden’s syndrome. Inherited/germline RET mutations are transmitted in an autosomal dominant fashion and are responsible for 25% of MTC. Even among patients with apparently sporadic non-medullary thyroid cancer, epidemiologic data reveal that the patients’ first-degree relatives have a 4- to 10-fold higher risk of thyroid cancer than the general population. Subtle inherited modifiers of individual susceptibility to sporadic cancers may exist. It has been hypothesized that potential predisposing genetic factors affect an individual’s sensitivity to gamma radiation and similar causes of genetic damage, thereby influencing his or her susceptibility to thyroid cancer. Identifying at-risk patients in the general population would have a profound impact on primary prevention, early detection, and secondary prevention strategies.

The molecular mechanisms of tumor development in papillary thyroid carcinoma are most often characterized by rearrangements of RET or activation of BRAF protooncogenes, whereas follicular thyroid carcinoma is usually associated with RAS gene mutations. Signaling through growth factors and their receptors has been implicated in thyroid neoplasia progression. Increased expression of the receptors for fibroblastic growth factor, epidermal growth factor, and vascular endothelial growth factor have all been reported in thyroid carcinomas, often correlating with poor prognosis. Aberrant cell-cycle regulation is also present in thyroid cancer with CDK inhibitors often downregulated.

The subjects of diagnosis and treatment of thyroid cancer continue to spark controversy among endocrinologists and endocrine/head and neck surgeons. Over the last decade, the use of pretreatment ultrasonography has become routine for both diagnosis and staging. Ultrasound-guided FNAB of thyroid nodules has become routine if there is clinical concern for malignancy or if any suspicious sonographic characteristics are present within a thyroid nodule. From a pathologic standpoint, the implementation of a uniform set of terms for the reporting of FNAB results is needed, as is an understanding by the treating physician of specimen adequacy and the roles and limitations of FNAB in the diagnosis of thyroid nodules.

The main contribution of ultrasound in the pre-surgical staging of thyroid cancer is the detection of early, clinically occult ipsi- or contralateral cervical lymph node metastasis that would not otherwise have been included in the surgical dissection. In these patients the operative management is to compartmentally remove the involved nodes. More controversial is the extent of dissection that should be performed in the radiographically and clinically N0 neck. In patients with MTC, because lymph node metastasis impacts overall survival, an aggressive approach to include central and selective lateral neck dissection is widely accepted. In well-differentiated thyroid cancer the survival benefits of such extended dissections are less clear and risk of recurrence becomes the focus of therapy. The extent of surgical dissection must be weighted against the risk for complications such as recurrent laryngeal nerve injury and hypoparathyroidism.

Equally as controversial in the surgical approach to thyroid cancer is the routine use of laryngeal nerve monitoring to avoid recurrent laryngeal nerve injury. Proponents suggest that although monitoring is most helpful when nerve identification is less than straightforward, routine use in non-high risk situations is necessary to gain the experience needed for those difficult cases. Using parathyroid preservation and autografting to avoid the complication of permanent hypoparathyroidism is a tool that should be in the armamentarium of every endocrine/head and neck surgeon.

Postoperative treatment of well-differentiated thyroid cancer includes the routine use of pharmacologic thyroid-stimulating hormone (TSH) suppression to prevent recurrence or tumor progression that can be stimulated by this hormone. The correct dosing will depend on the extent of the suppression desired, which is commonly based upon the risk stratification of the patient. Radioiodone ablation is also a useful postoperative tool in these patients. Unfortunately, non-surgical therapies for MTC are less abundant, although RET has become an important potential therapeutic target in this disease. Treatments targeting RET autophosphorylation and activation of intracellular signaling pathways show the most clinical promise. Future treatments for advanced and recurrent thyroid cancer will capitalize on the evolving understanding of the molecular basis of this disease while primary surgical treatment of localized disease will continue to emphasize the importance of accurate high-quality preoperative staging.