Studies on neoplasms of sheep : with emphasis on adenocarcinoma of the small intestine

Abstract

Scarcity of data has lead to confusion concerning the prevalence, common sites and types of neoplastic diseases in sheep. Sheep neoplasm diagnoses were retrieved from veterinary pathology laboratories in New Zealand (316 cases), New South Wales (109 cases), Britain (679 cases) and Glasgow University (42 cases). Data of this type contains certain biases and cannot be used to calculate prevalence rates but it can provide a guide to common sites and types of neoplasms.

Tumours of epithelial, lymphoid and other mesenchymal tissues were all diagnosed regularly and affected a wide range of organs and tissues in sheep. They were most frequently situated in the lung (Britain and Glasgow series only), lymphoid tissues, intestines, skin and liver, followed at lower frequencies by cartilage and heart.

The most common neoplastic diseases were: lymphosarcoma, small intestinal adenocarcinoma (SIA), pulmonary adenomatosis (Britain and Glasgow only) and cutaneous squamous cell carcinoma (NSW only). Some tumours were associated with certain age groups. Nephroblastoma and melanoma occurred predominantly in young lambs. SIA, cutaneous squamous cell carcinoma, bile duct carcinoma, renal carcinoma and tumours of cartilage were found in old (> 5 yr) sheep. Lymphosarcoma and hepatocellular tumours were found in all age groups.

Whilst SIA was known to occur regularly in New Zealand (NZ) the frequency of its occurrence in Australia was unknown. The prevalence rate of SIA in Australian sheep was of epidemiological interest. Its presence or absence would focus attention on potential carcinogens that were either present in both countries or unique to New Zealand.

A survey of 6,248 adult sheep in 3 export abattoirs in southern New South Wales detected 17 cases of SIA (0.27%). Gross and histological appearance of the tumours was similar to that described in NZ. Factors causing SIA were widespread as 8 of the 30 groups inspected contained affected animals (27%). It was concluded that SIA was seen regularly in adult sheep at abattoirs in New South Wales. A larger NZ study of age-matched groups of adult female sheep from 88 plains, hill and high country farms was conducted in the South Island to investigate the relative influence of genotype and farm environment on the prevalence rate of SIA. A total of 20,678 female sheep aged 5.5-7.5 years were examined at slaughter, 125 cases of SIA were found in animals from 61 of 88 farms (69%). Mean prevalence rate was 0.6% (range 0-3.8%). Non-Merino breeds (0.88%) had a significantly higher rate (P < 0.001) than Merino (0.37%) and Merino-Cross (0.40%) breeds. Differences between rates in the 3 farm environments were not significant (P = 0.215).

A correlational study of questionnaire data from the 88 groups of adult female sheep surveyed revealed a strong (P <0.001) relationship between prevalence rate of SIA and exposure to phenoxy (Ph), picolinic (Pi) and PhPi acid herbicides. Other variables were also related to tumour rate but the herbicide effect explained the strength of the relationship between all these variables and tumour rate. Further examination of the herbicide data revealed that tumour rate rose significantly in sheep exposed to MCPA, MCPB, 2,4,5-T plus picloram and picloram plus chlornitrofen. The trend was consistent across several exposure categories and was remarkably strong given the small size of the data set. The evidence suggested that there may be a biological relationship between Ph, Pi and PhPi herbicides and SIA in sheep. More specific toxicological and epidemiological studies are warranted.

Ultrastructural studies of SIA have described the primary site and the appearance of tumour cells in tissue culture but none has examined metastatic sites and the observations of the previous studies have not been confirmed. Ultrastructure at the primary and metastatic sites of 10 cases of SIA was studied. Examination of the lymphatic metastases was particularly valuable in confirming the histogenesis of the tumour. SIA is best classified as a scirrhous tubular adenocarcinoma. Polygonal undifferentiated tumour cells exhibited desmosomes, folded nuclei, moderate numbers of mitochondria but few other organelles. More differentiated cells were columnar with apical microvilli and basal nuclei. They contained GERL, Golgi and secretory granules. Microvillus-lined cysts (5-10 m dia) were seen in all 10 cases and confirmed as true intracytoplasmic lumina with the assistance of serial section studies. Fibrous filaments (10 nm dia. up to 1.4 um length) and tubular paracrystalline arrays (hexagonal symmetry, 37 nm periodicity) in lumina and secretory granules were seen in some tumour cells at primary and metastatic sites.

Certain areas of SIA research have been hampered by the lack of an experimental system either in vivo or in vitro. An attempt was made to transplant or transmit SIA to 40 ovine foetuses. Whole cell extract, subcell extract or a control solution was injected into the foetal abdomen at 90-120 days gestation. Thirty four live lambs were monitored and necropsied at 6 yr. One case of SIA was found in a female from the sub-cell extract group which died at 52 mth. It was likely that this case was due to non-treatment causes. Experiments using immunosuppressed or tolerant hosts may have had a greater chance of success.