Immunohistochemical Biomarkers in Thyroid Pathology

The application of immunohistochemistry to the diagnosis of thyroid lesions has increased as new biomarkers have emerged. In this review, we discuss the biomarkers that are critical for accurate diagnosis, prognosis, and management. Immunohistochemical markers are used to confirm that an unusual tumor in the thyroid is indeed of thyroid origin, either of follicular epithelial or C-cell differentiation; the various mimics include nonthyroidal lesions such as parathyroid tumors, paragangliomas, thymic neoplasms, and metastatic malignancies. Tumors of thyroid follicular epithelial cells can be further subclassified using a number of immunohistochemical biomarkers that can distinguish follicular-derived from C-cell lesions and others that support malignancy in borderline cases. The use of mutation-specific antibodies can distinguish papillary carcinomas harboring a BRAF mutation from RAS-like neoplasms. Immunostains have been developed to further identify molecular alterations underlying tumor development, including some rearrangements. Altered expression of several biomarkers that are known to be epigenetically modified in thyroid cancer can be used to assist in predicting more aggressive behavior such as a propensity to develop locoregional lymphatic spread. Immunohistochemistry can assist in identifying lymphatic and vascular invasion. Biomarkers can be applied to determine dedifferentiation and to further classify poorly differentiated and anaplastic carcinomas. The rare tumors associated with genetic predisposition to endocrine neoplasia can also be identified using some immunohistochemical stains. The application of these ancillary tools allows more accurate diagnosis and better understanding of pathogenesis while improving prediction and prognosis for patients with thyroid neoplasms.