Ovine pulmonary adenocarcinoma associated with Jaagsiekte sheep retrovirus: Morphological, immunohistochemical and molecular findings

Abstract

Ovine pulmonary adenocarcinoma is a contagious pulmonary neoplasm of sheep associated with exogenous Jaagsiekte sheep retrovirus. This retrospective descriptive case series characterized seven suspected ovine pulmonary adenocarcinoma cases using histopathology, immunohistochemistry, and semi-nested polymerase chain reaction on archived formalin-fixed, paraffin-embedded lung tissues. Fresh pulmonary tissue from two cases was also examined by transmission electron microscopy. Histopathological findings were compatible with ovine pulmonary adenocarcinoma in all cases and consisted of well-differentiated bronchioloalveolar epithelial proliferations arranged in papillary and acinar/tubular patterns. Cytoplasmic immunoreactivity for the jaagsiekte sheep retrovirus envelope protein was detected in neoplastic epithelial cells and in non-neoplastic type II pneumocytes. Immunolabel ling was also observed in alveolar macrophages and lymphocytes in some cases; this finding was interpreted cautiously because it may reflect uptake of viral antigen rather than productive infection. Nuclear thyroid transcription factor-1 immunolabelling in neoplastic cells supported pulmonary epithelial differentiation. Semi-nested polymerase chain reaction provided molecular support by amplifying the expected 133 bp jaagsiekte sheep retrovirus-specific product in clearly positive samples, although band intensity varied among lanes. Transmission electron microscopy demonstrated lamellar body-like structures, cytoplasmic vacuolation, vesiculation, and membranous-lamellar degeneration in alveolar epithelial cells, but clearly identifiable viral particles were not demonstrated. Therefore, the findings should be interpreted as descriptive evidence supporting jaagsiekte sheep retrovirus-associated ovine pulmonary adenocarcinoma, rather than as proof of productive jaagsiekte sheep retrovirus infection or as a diagnostic-performance study. Larger prospective studies incorporating viral ribonucleic acid detection, sequencing, or direct virion demonstration are required.