Immunocytochemistry in thyroid cytology and its multiple roles: a systematic review

The limits of morphological analysis, mostly encountered in the diagnosis of “follicular thyroid neoplasms (FN)”, were clearly reported in many papers. For this reason, the application of ancillary techniques, including immunocytochemistry (ICC) and molecular testing, contributes to a better definition of the risk of malignancy (ROM) and management of thyroid nodules (TN). This review discusses the diagnostic and prognostic role of the most relevant immunomarkers in TN, including HBME-1, Galectin-3, CD56, and VE1-BRAF among the others. Furthermore, we also analyzed the growing interest for the so-called next-generation immunomarkers, which represent one of the new frontiers for cancer scientific research. According to the literature, the diagnostic and prognostic relevance of their performance is able to help the morphological evaluation, especially for the indeterminate categories and controversial diagnoses. In fact, even though ancillary techniques cannot substitute the relevance of morphological evaluation of thyroid samples, they might represent a valid adjunct for those cases in which controversial features are not able to lead to a univocal diagnosis. Herein the review of literature about each of the immunomarkers in thyroid nodules.