Laryngeal squamous cell carcinoma and papilloma associated with Equus caballus papillomavirus 2 in a horse

Hiroyuki HIBI, Shinichi HATAMA, Atsutoshi OBATA, Tomoyuki SHIBAHARA, Koichi KADOTA
2019 Journal of Veterinary Medical Science  
A case of laryngeal squamous cell carcinoma (SCC) and squamous papilloma in a 19-year-old Thoroughbred stallion is described. The animal exhibited severe wheezing caused by laryngopharyngeal stenosis. Histological examination identified laryngeal, laryngotracheal, and guttural pouch tumor masses consisting of areas of SCC. In the epiglottic lesion, the overlying epithelium was replaced by papilloma cells, and superficial cells frequently had nuclear inclusion bodies that expressed oncoprotein
more » ... essed oncoprotein E6, which is characteristic of high risk human papillomaviruses. The papillomatous epithelium was continuous with epithelium composed of SCC cells. Equus caballus papillomavirus 2 (EcPV2) DNA was detected in the guttural pouch tumor. These findings suggest that laryngeal SCC and papilloma are a continuum of EcPV2-induced neoplastic lesions in horses. KEY WORDS: Equus caballus papillomavirus 2, horse, larynx, papilloma, squamous cell carcinoma Squamous cell carcinoma (SCC) is the most common malignant skin neoplasm in horses and other equids, and accounts for 7-37% of equine skin lesions [21] . In the initial stage, the lesions present as whitish plaques or papillomas that can progress to carcinoma in situ and, ultimately, to invasive SCC [20] . SCC and related precursor lesions can arise at any site on the skin and mucosa, but preferentially develop on non-pigmented skin and at mucocutaneous junctions, such as the ocular and oral regions and the external genitalia [20, 23] . Papillomaviruses (PVs) are the causative agents of certain types of SCC in horses, but the biological mechanisms underlying tumor development and progression are still unclear [15] . Eight equine papillomaviruses, Equus caballus papillomavirus 1-8 (EcPV1-8), have been identified to date [13] . Each virus type is associated with a different form of skin disorder such as classic epithelial papillomatosis (EcPV1, 8), genital papillomas (EcPV2, 7), and aural plaques (EcPV3-6) [3, 6, 11, 13, 17] . One of the viruses, EcPV2, is believed to cause genital papillomas and carcinomas [10, 11, 19 ] as viral DNA has been detected in penile SCC but not in periocular or oral SCCs [15, 16] . Although absent from ocular SCCs, EcPV2 DNA is present in metastatic lesions formed in the retropharyngeal regions and the left jugular groove [9] . Human papillomavirus (HPV) is implicated in the development of oropharyngeal SCC [4]. In particular, HPV16 contributes significantly to carcinomas in the oropharynx [24] . High risk HPV types for cervical carcinomas such as HPV16 and 18, express E6 and E7 oncoproteins that can regulate the cell cycle and induce apoptosis in cells; both oncoproteins play pivotal roles in malignant transformation [14] . Oropharyngeal SCCs arise from squamous intraepithelial lesions (epithelial dysplasia) [24] . SCCs can also occur in recurrent respiratory papillomatosis in relation to infection with low risk HPV types, HPV6 or 11 [2, 7, 18] ; these virus types are known to be associated with condyloma acuminatum [22] . Immunohistochemical assessment of cell cyclerelated proteins such as cyclin D1 and Ki-67 can help to distinguish benign and malignant conditions of the cervix from squamous intraepithelial lesions [1]. In this paper, we report a case of laryngeal SCC and papilloma, in which EcPV2 DNA was demonstrated to be present. A 19-year-old Thoroughbred stallion was examined because of anorexia, a fever of 39°C, and the occurrence of abnormal sounds by cervical auscultation. The condition did not improve, and nosebleed and severe nasal discharge occurred 2 and 3 days later, respectively. Endoscopy revealed the presence of laryngopharyngeal stenosis with reddening of the mucosa. The epiglottis
doi:10.1292/jvms.18-0461 fatcat:64gca6hhd5fkfi37z6axw4camu