Original Contribution Carcinoma ex pleomorphic adenoma of minor salivary glands with major epithelial-myoepithelial component: clinicopathologic and immunohistochemical study of 3 cases ☆ Bruno Tavares Sedassari, DDS a, ⁎, Harim Tavares dos Santos, DDS, MSc b , Fernanda Viviane Mariano, DDS, PhD c , Nelise Alexandre da Silva Lascane, DDS, PhD a , Albina Altemani, MD, PhD c , Suzana Sousa, DDS, PhD a a University of São Paulo, School of Dentistry, Department of Oral and Maxillofacial Pathology. Av. Professor Lineu Prestes, 2227, São Paulo, São Paulo, Brazil-CEP: 05508-000 b State University of Campinas, Piracicaba School of Dentistry, Department of Oral Diagnosis. Av. Limeira, 901, Piracicaba, São Paulo, Brazil-CEP: 13414-903 c State University of Campinas, School of Medicine, Department of Anatomic Pathology. R. Tessália Vieira de Camargo, 126, Campinas, São Paulo, Brazil-CEP: 13084-971 abstract article info Available online xxxx Keywords: Carcinoma ex pleomorphic adenoma Epithelial-myoepithelial carcinoma Salivary gland Salivary gland tumors In the present study, 3 cases of very rare intraoral carcinomas ex pleomorphic adenomas showing a striking differentiation of the malignant component towards epithelial-myoepithelial carcinoma were described. The tumors occurred in 2 men and 1 woman with median age of 56 years. Involved sites included palate and buccal mucosa. Two patients experienced local recurrences, of which one died of disease complications. In all cases, residual pleomorphic adenoma was present. The malignant component in all cases shared morphological aspects with epithelial-myoepithelial carcinoma. Those areas were characterized by eosinophilic duct-forming cells surrounded by layers of clear cells. The studied immunohistochemical markers highlighted a biphasic cell population. Duct-forming cells expressed pan-cytokeratin, cytokeratin 7, and focally cytokeratin 14, whereas the clear cell component strongly stained to cytokeratin 14, vimentin, and p63 but weakly stained to pan- cytokeratin and focally to α-smooth muscle actin, an immunophenotype compatible with both epithelial and myoepithelial differentiation. The Ki-67 proliferation index was up to 40% in malignant areas. Carcinoma ex pleomorphic adenomas of minor salivary glands with major epithelial-myoepithelial component are rare, locally aggressive, and potentially lethal tumors. The peculiar morphological and immunohistochemical aspects described may raise problems in diagnosis and classification of such cases, particularly in incisional biopsies. © 2015 Elsevier Inc. All rights reserved. 1. Introduction The term epithelial-myoepithelial carcinoma (EMC) lays emphasis on the characteristic biphasic cellular composition of a low-grade malig- nancy that can affect the salivary glands, initially described by Donath et al in 1972 [1–3]. Epithelial-myoepithelial carcinoma is a rare tumor, accounting for about 1% to 2% of all salivary gland tumors and 2% to 5% of all malignancies of the salivary glands, mainly in patients aged between the sixth and seventh decades of life with a slight female predilection [1,2]. Approximately 60% to 80% of the EMC cases occur in the parotid glands, with the remaining cases distributed almost equally among the submandibular and minor salivary glands, most commonly those of the palate. Rare cases were reported in sublingual glands [1,2,4,5]. Under histopathological examination, EMC is characterized by a dual cell population: intercalated duct-like luminal cells determine ductal structures and are surrounded by layers of large, polygonal, and clear neoplastic myoepithelial/abluminal differentiated cells [1,2]. Most cases are circumscribed masses and, rarely, encapsulated, often having a multilobular fashion [1,2]. Cytologic atypia is usually mild or absent [1,2,4]. Although they arise de novo, less than 2% of EMCs develop in a preexisting pleomorphic adenoma (PA), giving rise to an epithelial- myoepithelial carcinoma ex pleomorphic adenoma (CXPA) [4]. This event is exceptional and may represent a diagnostic dilemma, especially in small biopsy samples from the oral cavity, once EMC shares similar cellular composition and some morphological features with benign and malignant salivary gland tumors, including PA without carcinoma- tous transformation [1,2]. Therefore, we describe and discuss the clinical and histopathological aspects, as well as the immunohistochemical find- ings, in 3 cases of intraoral CXPA with major epithelial-myoepithelial component (CXPA-EMC). Annals of Diagnostic Pathology xxx (2015) xxx–xxx ☆ Statement: The study was conducted in full accordance with ethical principles. The authors have no conflicts of interest to declare.The study did not have any financial support.All authors support the submission of the present manuscript. ⁎ Corresponding author at: University of São Paulo, School of Dentistry, Oral and Maxillofacial Pathology. Av Prof Lineu Prestes 2227, São Paulo, CEP: 05508-000, São Paulo, Brazil. Tel.: +55 1130917912. E-mail addresses: brunosedassari@usp.br (B.T. Sedassari), harimtavares@gmail.com (H.T. dos Santos), fevimariano@gmail.com (F.V. Mariano), nelise@usp.br (N.A. da Silva Lascane), aaltemani@uol.com.br (A. Altemani), scmsouza@usp.br (S. Sousa). http://dx.doi.org/10.1016/j.anndiagpath.2015.03.011 1092-9134/© 2015 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Annals of Diagnostic Pathology Please cite this article as: Sedassari BT, et al, Carcinoma ex pleomorphic adenoma of minor salivary glands with major epithelial-myoepithelial component: clinicopathologic and imm..., Ann Diagn Pathol (2015), http://dx.doi.org/10.1016/j.anndiagpath.2015.03.011