Original ArticlesRecurrent DICER1 Hotspot Mutations in Malignant Thyroid Gland Teratomas Molecular Characterization and Proposal for a Separate ClassificationRooper, Lisa M. MD*; Bynum, Jennifer P. MD*; Miller, Karin P. MD*; Lin, Ming T. MD, PhD*; Gagan, Jeffrey MD, PhD†; Thompson, Lester D.R. MD‡; Bishop, Justin A. MD†Author Information *Department of Pathology, The Johns University School of Medicine, Baltimore, MD †Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX ‡Southern California Permanente Medical Group, Woodland Hills Medical Center, Woodland Hills, CA Conflicts of Interest and Source of Funding: Supported in part by the Jane B. and Edwin P. Jenevein M.D. Endowment for Pathology at UT Southwestern Medical Center. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Lisa M. Rooper, MD, The Johns Hopkins Medical Institutions, 401 North Broadway, Weinberg 2242, Baltimore, MD 21231-2410 (e-mail: [email protected]). The American Journal of Surgical Pathology: June 2020 - Volume 44 - Issue 6 - p 826-833 doi: 10.1097/PAS.0000000000001430 Buy Metrics Abstract Thyroid gland teratomas are rare tumors that span a wide clinicopathologic spectrum. Although benign and immature teratomas arise in infants and young children and generally have good outcomes, malignant teratomas affect adults and follow an aggressive course. This divergent behavior raises the possibility that benign/immature and malignant teratomas are separate entities rather than different grades of a single tumor. However, the histogenesis and molecular underpinnings of thyroid gland teratomas are poorly understood regardless of grade. In this study, we performed next-generation sequencing on 8 thyroid gland teratomas, including 4 malignant, 3 benign, and 1 immature. We identified DICER1 hotspot mutations in all 4 malignant cases (100%) but not in any benign/immature cases (0%). No clinically significant mutations in other genes were found in either group. We also performed immunohistochemistry to characterize the primitive components of malignant teratomas. Not only did all cases consistently contain immature neural elements (synaptophysin and INSM1 positive), but also spindled cells with rhabdomyoblastic differentiation (desmin and myogenin positive) and bland epithelial proliferations of thyroid follicular origin (TTF-1 and PAX8 positive). Although DICER1 mutations have previously been implicated in multinodular hyperplasia and well-differentiated thyroid carcinomas, these findings demonstrate the first recurrent role for DICER1 in primitive thyroid tumors. The combined neural, rhabdomyoblastic, and homologous epithelial elements highlighted in this series of malignant thyroid gland teratomas parallel the components of DICER1-mutated tumors in other organs. Overall, these molecular findings further expand the differences between benign/immature teratomas and malignant teratomas, supporting the classification of these tumors as separate entities. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.