Review ArticlesFollicular Neoplasm of Thyroid Revisited: Current Differential Diagnosis and the Impact of Molecular TestingOhori, N. Paul MD*; Nishino, Michiya MD, PhD† Author Information *Department of Pathology, University of Pittsburgh Medical Center-Presbyterian, Pittsburgh, PA †Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA The authors have no funding or conflicts of interest to disclose. Reprints: N. Paul Ohori, MD, Department of Pathology, A610, UPMC-Presbyterian, 200 Lothrop Street, Pittsburgh, PA 15213 (e-mail: [email protected]). All figures can be viewed online in color at www.anatomicpathology.com. Advances In Anatomic Pathology 30(1):p 11-23, January 2023. | DOI: 10.1097/PAP.0000000000000368 Buy Metrics Abstract The diagnosis of “follicular neoplasm” (FN) in thyroid cytopathology has a long history that originated not long after the practice of fine-needle aspiration (FNA) of thyroid nodules. From the outset, this interpretive category was intended to convey a set of differential diagnoses rather than a precise diagnosis, as key diagnostic features, such as capsular and vascular invasion, were not detectable on cytology preparations. Cytologic-histologic correlation studies over the past several decades have shown that FN interpretation can be applied to the spectrum of nonneoplastic tumors to carcinomas. Most tumors classified as FN include follicular adenoma, follicular carcinoma, noninvasive follicular thyroid tumor with papillary-like nuclear features, and follicular variant of papillary thyroid carcinoma. Less common entities that may be classified as FN on FNA include hyalinizing trabecular tumor (HTT), poorly differentiated thyroid carcinoma, medullary carcinoma, and nonthyroidal lesions such as parathyroid tissue, paraganglioma, and metastatic tumors. Advances in our ability to detect characteristic molecular alterations (eg, GLIS gene rearrangements for hyalinizing trabecular tumor) in FNA samples may assist in the identification of some of these entities. In this review, we summarize the pathophysiology, history, and evolution of the terminology and the current differential diagnosis according to the recently published 2022 World Health Organization classification, molecular testing, and management of nodules classified as FN. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.