Controversies in thyroid pathology: the diagnosis of follicular neoplasms

Thyroid nodules are common; almost 20% of the population has a palpable thyroid nodule and approximately 70% has a nodule detected by ultrasound. Thyroid cancer is the most frequent endocrine malignancy, and incidence rates have steadily increased over the last decades. Papillary carcinoma (PTC) is the most common malignant neoplasm of the thyroid; the diagnosis of this most frequent type (85-90%) has been increasing, possibly due to changing recognition of morphologic criteria. PTC is defined histologically as a malignant tumor showing evidence of follicular epithelial differentiation and characterized by distinctive nuclear features. However, there are borderline lesions that do not completely fulfill these criteria, making the diagnosis difficult. The use of immunohistochemical and molecular markers adds objective criteria to this confusing and controversial area of pathology. We review the differential diagnosis of well-differentiated follicular thyroid neoplasms and the ancillary techniques and molecular characteristics that have been proposed for application in the diagnosis of PTC.