Review ArticlesHigh-grade Transformation/Dedifferentiation in Salivary Gland Carcinomas: Occurrence Across Subtypes and Clinical SignificanceSkalova, Alena MD, PhD*; Leivo, Ilmo MD, PhD†,‡; Hellquist, Henrik MD, PhD§; Agaimy, Abbas MD∥; Simpson, Roderick H.W. MD¶; Stenman, Göran DMD, PhD#; Vander Poorten, Vincent MD, PhD, MSc**,††; Bishop, Justin A. MD‡‡; Franchi, Alessandro MD§§; Hernandez-Prera, Juan C. MD∥∥; Slouka, David MD, PhD¶¶; Willems, Stefan M. MD, PhD, MBA##; Olsen, Kerry D. MD***; Ferlito, Alfio MD, DLO, DPath, FRCSEd, FRCS, FDSRCS, FACS, FHKCORL, FRCPath, FASCP, IFCAP†††Author Information Departments of *Pathology ¶¶Otorhinolaryngology, Charles University Faculty of Medicine in Plzen, Plzen, Czech Republic †Institute of Biomedicine, Pathology, University of Turku ‡Department of Pathology, Turku University Hospital, Turku, Finland §Department of Biomedical Sciences and Medicine, Epigenetics and Human Disease, University of Algarve, Faro, Portugal ∥Institute of Pathology, Friedrich Alexander University Erlangen-Nürnberg, University Hospital, Erlangen, Germany ¶Department of Anatomical Pathology, University of Calgary, Calgary, AB, Canada #Department of Pathology, Sahlgrenska Center for Cancer Research, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden **Otorhinolaryngology-Head and Neck Surgery, University Hospitals Leuven ††Department of Oncology, Section Head and Neck Oncology, KU Leuven, Leuven, Belgium ‡‡Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX §§Department of Translational Research and of New Technologies in Medicine and Surgery, University of Pisa, Pisa †††International Head and Neck Scientific Group, Padua, Italy ∥∥Department of Pathology, Moffitt Cancer Center, Tampa, FL ##Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, The Netherlands ***Department of Otorhinolaryngology, Mayo Clinic, Rochester, MN This article was written by members and invitees of the International Head and Neck Scientific Group (www.IHNSG.com). The authors have no funding or conflicts of interest to disclose. Reprints: Alena Skálová, MD, PhD, Department of Pathology, Medical Faculty of Charles University, Faculty Hospital, E. Benese 13, Plzen 305 99, Czech Republic (e-mail: [email protected]). Advances In Anatomic Pathology: May 2021 - Volume 28 - Issue 3 - p 107-118 doi: 10.1097/PAP.0000000000000298 Buy Metrics Abstract High-grade transformation (HGT) or dedifferentiation has been described in a variety of salivary gland carcinomas, including acinic cell carcinoma, secretory carcinoma, adenoid cystic carcinoma, epithelial-myoepithelial carcinoma, polymorphous adenocarcinoma, low-grade mucoepidermoid carcinoma, and hyalinizing clear cell carcinoma. High-grade (HG) transformed tumors are composed of a conventional low-grade component characterized by specific microscopic and immunohistochemical features for the given entity, intermingled with or juxtaposed to areas of HG morphology. This is usually either poorly differentiated adenocarcinoma, carcinoma not otherwise specified, or undifferentiated carcinoma, in which the original line of differentiation is lost. The HG component is composed of solid nests of anaplastic cells with large vesicular pleomorphic nuclei, prominent nucleoli, and abundant cytoplasm. Frequent mitoses and extensive necrosis may be present. The Ki-67 labeling index is consistently higher in the HG component. The molecular genetic mechanisms responsible for HGT of salivary gland carcinomas are largely unknown, though p53 inactivation and human epidermal growth factor receptor 2 overexpression and/or gene amplification have been demonstrated in the HG component in a few examples, the frequency varies for each histologic type. Salivary gland carcinomas with HGT are more aggressive than conventional carcinomas, with a higher local recurrence rate and a poorer prognosis. They have a high propensity for cervical lymph node metastasis suggesting a need for a wider resection and neck dissection. HGT of salivary gland carcinoma can occur either at initial presentation or less commonly at the time of recurrence, sometimes following postoperative radiotherapy. The potential for HGT in almost any type of salivary gland carcinoma warrants a thorough sampling of all salivary gland malignancies to prevent oversight of a HG component. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.