Primary primitive neuroectodermal tumors of the retina and ciliary body in dogs Daniel P. Regan,* Richard R. Dubielzig,† Caroline J. Zeiss,‡ Brad Charles,* Sarah S. Hoy§ and E. J. Ehrhart* *Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA; †Department of Pathobiological Sciences, University of Wisconsin, Madison, WI, USA; ‡Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA; and §Vermont Veterinary Eye Clinic, Williston, VT, USA Address communications to: D. P. Regan Tel.: 970-297-5177 Fax: 970-297-1254 e-mail: Daniel.Regan@colostate. edu Abstract We describe the clinical, histological, and immunohistochemical features of primary intraocular primitive neuroectodermal tumors in eight dogs. Four of eight tumors exhibited histological features similar to human retinoblastomas characterized by Flex- ner–Wintersteiner rosettes, and fleurettes, and demonstrated variable immunoreactivity for retinal markers opsin, S-antigen (S-Ag) and interphotoreceptor retinoid-binding protein (IRBP). All dogs with tumors displaying histological and immunohistochemical features of retinal differentiation were  2 years of age. All tumors diagnosed as me- dulloepitheliomas (n = 4) did not display histological and immunohistochemical fea- tures of retinal differentiation and were present in dogs 7 years or older. Age of onset, in conjunction with immunohistochemistry for opsin, S-Ag, and IRBP, is an important aid in the differentiation of primary, primitive neuroectodermal tumors arising within the canine ciliary body, retina, and optic papilla. Key Words: canine, immunohistochemistry, medulloepithelioma, primitive neuroectodermal tumors, retinoblastoma INTRODUCTION Primitive neuroectodermal tumors (PNET) is a generic term for classification of all embryonal neoplasms that arise from the germinal neuroepithelium of the neural tube (neuroectoderm) and which cannot be distinguished from medulloblastomas. 1,2 In addition to tumors that can only be designated as PNET, this broad group of neo- plasms also includes such tumors as neuroblastomas, ependymoblastomas, retinoblastomas, and medulloepithe- liomas. 2,3 In both humans and animal species, primary PNET tumors can arise within the peripheral and central nervous systems, as well as the eye. 1,3–6 In humans, the majority of primary ocular PNET tumors are reported in the pediatric population, and most commonly include ret- inoblastomas and medulloepitheliomas. 7–9 Although both originate from the primitive neuroepithelial cells of the optic cup, retinoblastomas are malignant tumors arising from the primitive neuroepithelium of the immature ret- ina, while medulloepitheliomas, arise from the primitive medullary epithelium of the ciliary body. 7,10–12 Of these ocular primitive neuroectodermal tumors, retinoblastomas are the most frequently occurring, due in part because they are the most common primary intraocular neoplasm of children, with a reported incidence ranging from 1:17 000 to 1:24 000 live births. 9,13,14 In humans, retino- blastoma exists in two distinct clinical forms: While tumor cells from either form contain mutations in both alleles of the retinoblastoma (RB1) tumor suppressor gene, the spo- radic, nonheritable form arises from two independent spontaneous mutations in the gene, while the heritable form is secondary to an autosomal dominant germline mutation in one allele of the RB1 gene, with a subsequent spontaneous mutation arising in the second allele. 15 Familial retinoblastoma usually occurs in multiple loca- tions in both eyes and can also be associated with PNET tumors of the pineal gland. Tumors originate in prolifer- ating retinal neurons and, as such, these tumors are typi- cally diagnosed before the age of 5 years (90–95% of cases), and account for 11% of all cancers diagnosed before the age of 1 year. 7 Medulloepitheliomas, although far less common, are similar to retinoblastomas in that they are congenital tumors and typically have a juvenile onset, with only a handful of case reports dating as far back as the early 20th century of medulloepitheliomas occurring in adults. 3,4 In contrast to retinoblastomas, these tumors retain a pluripotent potential and have the ability to differentiate into retinal pigment epithelium, ciliary © 2013 American College of Veterinary Ophthalmologists Veterinary Ophthalmology (2013) 16, Supplement 1, 87–93 DOI:10.1111/vop.12056