Nodular thyroid disease in the elderly: novel molecular approaches for the diagnosis of malignancy

Epithelial thyroid cancers (TC) comprise two differentiated histotypes (DTC), the papillary (PTC) and the follicular (FTC) thyroid carcinomas which, following dedifferentiation, are assumed to give rise to the poorly differentiated thyroid carcinomas and the rare, but highly aggressive and invariably fatal, anaplastic thyroid carcinomas. Although thyroid cancer mortality has not been changed, its annual incidence has increased over the last two decades, mainly because of the improved ability to diagnose malignant transformation in small non-palpable thyroid nodules. Despite DTC patients have a favorable prognosis, aggressive disease is more frequently observed in the elderly showing a higher disease-specific mortality. Of relevance is the high prevalence of nodular thyroid disease in aged patients being higher than 90%, in women older than 60 year, and 60% in men older than 80 year. This implies a careful evaluation of thyroid nodules in this group of patients in order to exclude malignancy. In fact, despite the tremendous progress in the comprehension of the underlying molecular mechanisms deregulated in DTC progression, several aspects of their clinical management remain to be solved and novel diagnostic strategies are sorely needed. Here, we will attempt to review new molecular approaches, which are currently being exploited in order to ameliorate the diagnosis of thyroid nodules.