Towards an evidence-based standardised approach for the management of penile and preputial tumours in the horse

Abstract

Modern management practices will affect equine health and welfare positively and with these life expectancy, with the consequence an increasing number of older horses. Neoplasms are one of the most diagnosed diseases in geriatric horses, with penile and preputial squamous cell carcinoma (SCC) the most common neoplasm of the external genitalia. The overall aim of this thesis was to perform a comprehensive study on penile and preputial SCC in horses, including the course of the disease, etiological factors, pathogenesis and outcome of treatment, to serve as a basis for guideline development. Chapter 2 represents a review of the literature on equine penile and preputial tumours that outlines the most important characteristics of this disorder that are relevant for the development of guidelines for a standardised diagnostic and therapeutic approach. Chapters 3 and 4 contain retrospective analyses. A large group of horses with penile and preputial neoplasia were evaluated to find relationships between factors such as age, castration status, type and site of the lesion and involvement of lymph nodes and stage, and course of the disease. Common presenting clinical signs were irregularities on the integument of the penis and prepuce, and purulent or sanguineous discharge from preputial orifice. SCC is the most common urogenital tumour and occurs primarily in older horses. Horses with poorly differentiated SCCs tend to have a higher incidence of regional metastases and a greater chance that the treatment would be unsuccessful. Therefore, pathology of lymph nodes is a valuable diagnostic exercise and grading of SCC can help predict prognosis and guide selection of treatment. The expression of COX-1, COX-2 and mPGES-1 in equine penile and preputial normal tissue, papillomas and SCC is investigated in relation to the degree of inflammation and the differentiation grade of the tumour (chapter 5). Retrospective study using archived material shows that expression of COX-1 and COX-2 in penile and preputial SCC in the horse is poor and COX inhibitors may thus be of little value for prevention or treatment. mPGES-1 is more prominently expressed in well-differentiated tissue compared with poorly differentiated tissue, but further research on the role of mPGES-1 in carcinogenesis is needed. Chapter 6 describes the relationship various tumour characteristics and their possible role as a prognosticator. Equus caballus papillomavirus type 2 (EcPV2) DNA was detected in 89.4% of horses. No differences in quantitative expression of E2, E6 and L1 oncogenes between well and poorly differentiated tumours were found. Expression of p53 and occurrence of metastasis were significantly positively correlated to a less differentiated subtype. Comparable to chapter 4, this study shows also that horses with less differentiated tumours were more likely to die of the disease and that that tumour grading appears to be an important prognosticator for survival and a predictor for presence of metastases. Based on tumour grading and staging, a standardised approach for the management of penile and preputial tumours in the horse is finally proposed.