72 | Oral Diseases. 2018;24:72–77. wileyonlinelibrary.com/journal/odi Received: 24 July 2017 | Revised: 8 August 2017 | Accepted: 9 August 2017 DOI: 10.1111/odi.12733 PROF SCULLY MEMORIAL ISSUE Primordial odontogenic tumor: Subepithelial expression of Syndecan-1 and Ki-67 suggests origin during early odontogenesis R Bologna-Molina 1 | T Mikami 2 | V Pereira-Prado 1 | G Tapia-Repetto 3 | FR Pires 4 | R Carlos 5 | A Mosqueda-Taylor 6 © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved 1 Molecular Pathology Area, Faculty of Dentistry, Universidad de la República, Montevideo, Uruguay 2 Division of Anatomical and Cellular Pathology, Department of Pathology, Iwate Medical University, Iwate, Japan 3 Histology Area, Faculty of Dentistry, Universidad de la República, Montevideo, Uruguay 4 School of Dentistry, State University of Rio de Janeiro, Rio de Janeiro, Brazil 5 Pathology Division, Centro Clínico de Cabeza y Cuello/Hospital Herrera-Llerandi, Guatemala City, Guatemala 6 Health Care Department, Universidad Autónoma Metropolitana Xochimilco, Mexico City, Mexico Correspondence Ronell Bologna-Molina, Molecular Pathology Area, Facultad de Odontología, Universidad de la Republica, Montevideo, Uruguay. Email: ronellbologna@odon.edu.uy Primordial odontogenic tumor (POT) is composed of variably cellular myxoid connective tissue, surrounded by cuboidal to columnar odontogenic epithelium resembling the inner epithelium of the enamel organ, which often invaginates into the underlying connective tissue. The tumor is delimited at least partially by a thin fibrous capsule. It derives from the early stages of tooth development. Syndecan-1 is a heparan sulfate proteoglycan that has a physiological role in several cellular functions, including maintenance of the epithelial architecture, cell-to-cell adhesion and interaction of cells with extracellular ma- trix, and with diverse growth factors, stimulating cell proliferation. Ki-67 is considered the gold standard as a cell proliferation marker. The aim of this study was to examine the expression of Syndecan-1 and Ki-67 proliferation index in POT and normal tooth germs to better understand the biological behavior of this tumor. Results showed that Syndecan-1 was more intensely expressed in subepithelial mesenchymal areas of POT, in a pattern that resembles the early stages of tooth development. The cell proliferation index (4.1%) suggests that POT is a slow growing tumor. Syndecan-1 expression in tooth germs in late cap and early bell stages was similar to POT, showing immunopositivity in subepithelial mesenchymal condensed areas. The immunohistochemical findings showed a pattern in which the population of subepithelial mesenchymal cells exhibited greater proliferative activity than the central portion of the dental papilla. KEYWORDS CD138, Ki-67, odontogenesis, primordial odontogenic tumor, Syndecan-1, tooth germ 1 | INTRODUCTION Odontogenic tumors comprise a heterogeneous group of lesions ranging from hamartomas or non-neoplastic growths to benign and malignant neoplasms. These originate from epithelial, ectomesenchy- mal, and/or mesenchymal tissues derived from odontogenesis (Barnes, Eveson, Reichart, & Sidransky, 2005). Primordial odontogenic tumor (POT) is a recently described entity (Mosqueda-Taylor et al., 2014), classified as a mixed epithelial mesen- chymal benign neoplasm in the current WHO histological classification of tumors (El-Naggar, Chan, Grandis, Takata, & Slootweg, 2017). It is composed of loosely arranged cellular fibrous connective tissue, re- sembling dental papilla, which is surrounded peripherally by cuboidal to columnar odontogenic epithelium closely resembling the inner epi- thelium of enamel organ, surrounded at least partially by a thin fibrous capsule. It occurs as a well-defined intra-osseous lesion, adjacent to the crown of an unerupted tooth, and may cause varying degrees of cortical bone expansion, root resorption, and tooth displacement (Slater, Eftimie, & Herford, 2016). To date, only eight cases of POT have been reported, with scant preliminary information regarding its