Review The Diagnostic Challenges of Ovine Pulmonary Adenocarcinoma Hélder Quintas 1, * , Isabel Pires 2,3 , Andreia Garcês 4,5 , Justina Prada 2,3 , Filipe Silva 2,3 and Nuno Alegria 2   Citation: Quintas, H.; Pires, I.; Garcês, A.; Prada, J.; Silva, F.; Alegria, N. The Diagnostic Challenges of Ovine Pulmonary Adenocarcinoma. Ruminants 2021, 1, 58–71. https:// doi.org/10.3390/ruminants1010005 Academic Editor: Ceferino Manuel López Received: 7 August 2021 Accepted: 15 September 2021 Published: 18 September 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Mountain Research Center (CIMO), School of Agriculture, Polytechnic Institute of Bragança (IPB), Campus de Santa Apolónia, 5300-253 Bragança, Portugal 2 Department of Veterinary Science, University of Trás-os-Montes and Alto Douro Quinta dos Prados, 5001-801 Vila Real, Portugal; ipires@utad.pt (I.P.); jprada@utad.pt (J.P.); fsilva@utad.pt (F.S.); nalegria@utad.pt (N.A.) 3 CITAB—Centre for the Research and Technology of Agro-Environmental and Biological Sciences, University of Trás-os-Montes and Alto Douro, Quinta dos Prados, 5001-801 Vila Real, Portugal 4 INNO Veterinary Laboratory, R. Cândido de Sousa 15, 4710-503 Braga, Portugal; andreiagarces@inno.pt 5 Instituto Universitário de Ciências da Saúde, CESPU, Instituto de Investigacão e Formação Avançada em Ciências e Tecnologias da Saúde (IINFACTS), Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal * Correspondence: helder5tas@ipb.pt Abstract: Ovine pulmonary adenocarcinoma (OPA), also known as sheep pulmonary adenomatosis and jaagsiekte, is a contagious pulmonary tumor of sheep, characterized by neoplastic proliferation of type II pneumocyte and club cells. OPA is induced by the oncogenic activity of the envelope glycoprotein (Env) of exogenous jaagsiekte sheep retrovirus (JSRV). This disease is associated with significant economic losses in numerous sheep raising countries. The onset of suggestive clinical signs is often late, making difficult the early diagnosis of the disease and timely implementation of control measures on the affected farms. Further, the lack of diagnostic tests that can be performed routinely by veterinary clinicians to accurately assess infected animals (e.g., serological or others) means that the true prevalence at flock level is not known. Imaging diagnostic methods (e.g., ultrasound, X-ray and computed tomography) can be used to support the clinical diagnosis, even in pre-clinical stages in affected flocks. The diagnosis must be confirmed by PCR of nasal excretions or immunohistochemistry and PCR of tumor lesions. No vaccine for OPA has yet been developed. Thus, in this work, we review the main methods of diagnosis of OPA in order to support the clinician in the identification of the disease, avoid underdiagnosis and allow the implementation of suitable measures to prevent and control its spread. Keywords: ovine pulmonary adenocarcinoma; jaagsiekte sheep retrovirus; PCR; histopathology; ultrasound; X-ray; computed tomography 1. Introduction Ovine pulmonary adenocarcinoma (OPA), also known as pulmonary adenomatosis and jaagsiekte, is a contagious neoplasia derived from type II pneumocytes and club cells, that occurs in sheep and, exceptionally, in goats and mouflons. The disease is associated with high economic losses not only due to the related mortality but also due to the lack of a vaccine or methods of early detection of the disease [1,2]. One of the first known records of this disease is a letter dated 1825, addressed to the magistrate of the Cape of Good Hope in South Africa, a farmer complained about the loss of many sheep due to a disease called “jaagziekte”, German word translated into africander as jaagsiekte (in Africander, “jaag” means to drive, drive and “siekte” means illness). The origin of the name of the disease reflects the breathing difficulties experienced by the affected animals, particularly evident during herd movements [3]. Ruminants 2021, 1, 58–71. https://doi.org/10.3390/ruminants1010005 https://www.mdpi.com/journal/ruminants