ARCHIVE FILE
See the original document
INSTITUTE OF INSPECTORS OF STOCK OF N.S.W. YEAR BOOK.
Cancer of the Bovine Eye
D. J. WALKER, B.V.Sc., Veterinary Inspector, Armidale.
INTRODUCTION
In the Armidale District increasing ante-mortem inspections of cattle result from application of the provisions of the Cattle Compensation Act and focus more attention on eye cancer. Prior to this Act actinomycosis, actinobacillosis and cancer were regarded casually by both stockowners and officialdom. Activity under this legislation now dominates all cattle disease control work in this District; these three diseases being scheduled as compensatable.
The cattle population of the area is largely of the Hereford breed. There are a few breeders who run Aberdeen Angus, and less who run Devons and Red Polls. Jerseys, grade Jerseys and other dairy breeds constitute one to two per cent of our cattle population.
Cancer-eye has great scientific interest, being of a surface tissue, as readily observed as the cattle handled, and of relatively high incidence.
IMPORTANCE AND INCIDENCE
Cancer is of such importance in human medicine that the disease in other mammals is significant for what might be referred to as its allied scientific interest. Neglected in bovines in the past, if Australian published work is a satisfactory criterion, in other parts of the world it has been the subject of intensive investigation.
Very limited investigations, such as have been attempted here, have shown clearly the considerable difficulties associated with making observations except with herds, the individuals of which can be handled closely and without damage to the stock. In general, herds, other than studs, are unstable in composition over the period of years needed for survey work.
Because stock become susceptible at about four years of age and appear to become more susceptible with increasing age, destruction of affected animals results in loss of breeding efficiency of herds. Russell et al. (1956) quote data which indicates that the age of peak incidence is eight years.
From our Cattle Compensation Act records the following information has been extracted. It is best set out in tabulated form:
TABLE ONE
| Year | 1953 | 1954 | 1955 | 1956 | 1957 | 1958 |
|---|---|---|---|---|---|---|
| Number Destroyed | 47 | 17 | 26 | 38 | 60 | 98 |
| Difference between market value and residual value | £707 | £220 | £336 | £627 | £864 | £1,770 |
| Average Difference | £15/1/- | £12/19/- | £12/18/- | £16/10/- | £14/8/- | £17/14/- |
| Totally Lost | 26 | 15 | 17 | 17 | 22 | 46 |
For the purposes of Table One. “Market Value” is agreed between inspecting officer and owner. It may be assessed on the basis of the beast as a breeder or a fat, but may not exceed thirty-six pounds (£36).
"Residual Value" is the price realised for the animal at disposal, whether by sale for slaughter or after slaughter. If destroyed on the holding, Residual Value is nil.
Animals were regarded as "totally lost" when they were too advanced to forward for slaughter on grounds of cruelty, objectionable nature of lesions or by virtue of economic reasons such as cost of transport in relation to the value of the animal as a carcass. The total cattle population on which our figures are based is: -
1956 - 97374;
1957 - 105,710;
1958 - 108,987.
Our figures only include cases which macroscopically were frank, well-established carcinomas. ("Precursors" were certainly not dealt with as Cancer.) They were, with very few exceptions, over four years old.
To these figures can be added the number of those destroyed by owners, either as a result of inspection and refusal of compensation or on their own initiative, and those which have been the subjects of surgery, which is probably a significant number, and those early cases which are present at slaughter but which do not come to notice. From these considerations and recorded data the overall incidence is estimated at 0.1 to 0.15 per cent.
A small scale direct study, based on cattle the subject of claims under the Cattle Compensation Act, indicated in 1953, an overall incidence of 0.3 per cent. (38 cases in 13,500). These were pure-bred and stud Hereford and the ratio of females four years and over to all other cattle on these holdings was approximately 1 to 5. To some extent this over-all incidence of 0.3 per cent. may have been influenced by accumulation of cases, so that it did not truly represent the incidence for one year.
A real source of loss is the time devoted by field officers and clerical staff to the administration of the Cattle Compensation Act as relating to cancer eye. Often we have felt that energies could be directed to activities which appeared to be potentially more profitable.
Much effort has been expended on surveys and collection of statistical data in other parts of the world. Multiplicity of variable factors, such as age, breed, herd structure and so on, often make it impossible properly to interpret this data.
Russell et al. (1956) quote direct studies by various workers. In New Mexico, Black (1934), in a study of 163,893 Herefords on 256 ranches, found an incidence of 0.35 per cent. In a twelve year study of a Californian herd, presumably Hereford, Guilbert et al. (1948) found a case rate of 4.4 per cent. in animals more than four years of age.
From observations over a period of twenty-four years, Woodward and Knapp (1950) reported an incidence of 4.7 per cent. in pure-bred Herefords. At the New Mexico Experiment Station, Knox (1949) observed over-all incidences as high as 4.5 per cent. in cows more than four years of age.
Brydon (1959) from survey at Homebush State Abattoir reported an incidence of 286 affected out of a total kill of 586,775 head during the period 4/7/55 to 30/76/58; an incidence of 0.05 per cent. The percentage of animals under three years old was high during this period and approximately 50 per cent of the kill were Hereford.
Harris (1959) reports that for the period 1/7/55 to 30/5/58, in his District, 1,189 head were destroyed "under supervision". His District embraces the Pastures Protection Districts of Armidale, Tamworth, Narrabri, Walgett, Walgett North, Moree, Warialda, Inverell, Tenterfield and Glen Innes, and carries a total of about 712,000 head of cattle, mostly beef breeds and predominantly Herefords.
Dodd (1924) reports Loeb and Jobson (1900) - also cited by Russell et al. — as reporting an incidence of one in 50,000 in a total kill of 2½ million head at Chicago, and that all were of the lacrymal caruncle and nictitating membranes. Though the feature of site of lesion was of primary interest to Dodd, we find interest in figures which suggest a greatly increased incidence in America during the last half century and the possibility of increase to similar levels in our own cattle, as well as a change in site of lesions.
BREED AND SEX INCIDENCE
There appears to be little reliable information to indicate whether either sex is more prone to be affected. No record of it appearing in Devons or Aberdeen Angus has been found.
In the Armidale Pastures Protection District cancer-eye has been seen solely as a disease of Herefords.
Brydon (1959) provides a valuable contribution to the information on breed susceptibility; as under:—
TABLE TWO
Showing Breed Distribution of Cancer Eye at Homebush State Abattoir: 4/7/55 - 30/6/58
| Herefords | 225 | 172 Cows |
| 9 Bullocks or steers | ||
| 11 Bulls | ||
| 31 Poll Hereford Cows | ||
| 2 Poll Hereford Bulls | ||
| Other Breeds | 61 | |
| A.I.S. | 7 Cows | |
| Friesians | 7 Cows | |
| Guernseys | 3 Cows | |
| Shorthorns | 17 Roan Cows | |
| 1 White Cow | ||
| 1 Bull | ||
| Ayrshires | 19 Cows | |
| 1 Bull | ||
| Jerseys | 4 Cows | |
| 1 Bullock |
Total kill was 586,775; approximately half Hereford.
PATHOLOGICAL ANATOMY
A scheme of developmental pathology of bovine ocular squamous carcinoma has been put forward by Russell et al. (1956). It is essentially the same as that put forward by Monlux et al. (1957). The concept envisages a continuous process of changes from initial stimulation to the final phase of autonomous infiltrating carcinoma. The earliest lesions are benign and it is postulated that these are in fact "precursors" to the assumption of malignancy. The concept appears to be based wholly on pictorial evidence.
Russell et al. (1957) classify benign lesions firstly on the basis of location, i.e. those in the conjunctival sac, including lesions on the nictitating membrane and caruncle, and then those on the periorbital skin including the eyelids. This classification has no apparent basis in the pathology of the disease.
On a histopathological basis, benign precursors are classified as:—
(a) Plaques which macroscopically are greyish-white areas of thickened epithelium; whose surface may be smooth or roughened, occurring most frequently at the lateral and medial aspects of the corneo-scleral Junction. Monlux et al. (1957) refer to epidermal plaques which are histologically equivalent to plaques on the orbit. Russell et al. (1956) do not describe these.
(b) Papillomas occurring on conjunctiva or epidermis.
(c) Keratomas, or cutaneous horns, with varying degrees of hyperkeratosis. Macroscopically these are distinct, but on histopathological grounds Monlux et al. (1957) consider this term and classification superfluous and actually confusing. These they would have as epidermal plaques with varying degrees of hyperkeratinisation. To the extent that these forms of lesion are macroscopically so distinct, they warrant such terms as keratomas and epidermal plaques for more common use.
(d) Acanthosis with focal ulceration on the skin of the lids, or on the modified skin of the lacrymal lake, is the descriptive term given by Russell et al. (1956) to what appears macroscopically as a moist, diffuse, greyish-white roughened surface with irregular fissures. As observed here, fissures have not been a feature of the phase, though the description otherwise fits the macroscopic lesion admirably. Monlux et al. (1957) classify this type of lesion with epidermal plaques. Macroscopically, acanthosis is a lesion of considerable variation. Maceration by excessive lacrimation may perhaps cause changes like it. Doubtless because this form of lesion is so variable and ill-defined. it is not included in surveys of precursor lesions.
All the lesions described appear to result from proliferation of restricted areas of cutis and/or connective tissue; the form of the resultant lesion apparently depending on relative susceptibility of each tissue to the stimulant.
After the benign precursors are the phases of carcinoma in situ; followed by invasive, autonomous carcinoma.
INCIDENCE OF BENIGN PRECURSORS
Little appears to have been published concerning the incidence of benign precursors. Russell et al. (1956) found an incidence of 15.7 per cent. of papilloma plaque and keratoma in 830 eyes; most of which had been selected for examination because they carried lesions suspected of being precursors or carcinoma. The majority of specimens comprised the eyeball alone, without attached lids. Information concerning the incidence on whole heads has not come to notice.
Here eighteen stud Hereford cows, over four years old, were found, on macroscopic classification, to carry one keratoma, five papillomas and eight plaques. In all but two, the skin of the lacrymal lake or lids was abnormal; ranging from clearly defined acanthosis to an ill-defined, moist macerated condition.
As many as eighteen individual lesions have been seen on the head of one aged beast. General observation indicates that in this District any group of adult Hereford cattle will carry many lesions of varied types on unpigmented tissues of the orbit and peri-orbit.
During a week spent on the slaughtering floor of the Mid-Coast Meat Co-operative Society's Works at Macksville, lesions which appeared to warrant the terms plaque, papilloma and keratoma, without evidence of malignancy, were found frequently in all breeds examined. Seven-hundred head were killed. Sites of infection were the orbit, peri-orbit, external nares, muzzle, tongue, posterior palate and pharynx, teats, skin of the body and the rumen. Only in Herefords did lesions of the orbit and peri-orbit proceed beyond the plaque stage. The work of Olson and Palionis (1953) demonstrates that a papilloma of the mouth and oesophagus in bovines is due to a virus which appears to be distinct from that responsible for cutaneous papillomatosis of cattle. Ordinary skin appeared to be quite refractory to the disease, which they refer to as proliferative stomatitis.
Consequently the lesions of papilloma and plaquesetc., which were seen at Macksville on the orbit and peri-orbit are assumed due to the agent or agents responsible for cancer-eye; those in the external nares and muzzle (Olson and Palionis' macules), tongue and digestive tract generally to the virus of proliferative stomatitis; and papillomas of the skin, perhaps including teats, to the virus of bovine cutaneous papilloma.
This leaves two types of lesions, not previously referred to, which are not tentatively classified. There is the "brand cancer", which frequently develops at the site of fire-branding, and which is macroscopically a keratoma. The other is the small papilloma, arising from the modified skin, beneath the tail of young stock. This, when attached dried faeces are removed, has the appearance of belonging within the proliferative stomatitis group, principally because of size.
When normal Hereford skin of lids and hide was sectioned it seemed that on macroscopic examination, the unpigmented was thicker; with larger sebaceous and tarsal glands than adjoining skin. This may be a seasonal effect for, on occasion, marked excess of what appears to be sebaceous secretion is evident; particularly above and around the modified skin of the muzzle, in the ears and round the eyes. A chronic dermatitis has been observed, particularly in Guernsey and Ayrshire-type cattle within a zone of pigmented skin bearing white hair. This zone is half to one inch wide and occurs between zones of unpigmented skin bearing white hair and pigmented skin bearing pigmented hair. The dermatitis appears to result in skin thickening, with hairs carried more erect. Such animals are considered to be more subject to development of keratomas at the site of fire-branding ("brand cancers") and of malignancy at these sites.
Drabble (1929) has recognised an association of chronic dermatitis in unpigmented areas of cattle and localised hyperkeratosis and malignancy.
Though the term "precursor" or "precursor lesion" may be used, this is not to be considered too literally. The gross lesion is rather to be interpreted as an indication that the germinal epithelium is in a state particularly likely to assume malignancy.
Lesions stimulating plaques were seen on the darkly pigmented skin of the peri-orbit and external nares of Jerseys. Such lesions were infrequent and always small. On rare occasions well defined keratomas develop on the pigmented lids of Jersey cattle. On the two occasions when they have come to our notice, they fell off. In one case it was noted that a minute unpigmented spot remained at the site of the keratoma.
In Jerseys, lack of peri-orbital pigmentation is rare. In one series of one-hundred and seventy (170) head of mixed dairy breeds in herds at Armidale, seventeen (17) were observed to have one or both orbits and nictitating membranes substantially free of pigment.
EFFECT OF EYELID PIGMENTATION
It has become accepted that lack of eyelid pigmentation is an important factor in cancer of the lids. Anderson et al. (1957) studied the relationship between cancer-eye and eyelid pigmentation in eight-hundred and forty-two (842) Hereford cattle among which three-hundred and thirty-eight (338) had lesions; either benign, precursor or carcinoma, but excluding acanthosis. They found a real association between a decreasing amount of pigment on the eyelids and development of lesions on the skin of the lids. Association between eyelid pigmentation and lesions on the eyeball or nictitans and caruncle was not statistically significant.
Since Russell et al. (1956) found 85 per cent. of lesions (carcinoma, or benign precursors, plaque, papilloma and keratoma) arose in sites other than the skin of the lids and lacrymal lake, the importance of pigmentation of lids may be exaggerated. As Brydon (1959) has pointed out, pigmentation of the sclera, particularly at the corneo-scleral junction, appears to be very significant. Selection for increased pigmentation at this site may be the key to the problem of breeding for resistance.
RATE OF PROGRESSION
Russell et al. (ibid) state that there is almost no information on the rate of progression of ocular carcinomas in cattle. From an administrative point of view, the absence of information (except in very vague terms) on the rate of progression, after malignancy has been assumed. causes some problems. In general terms, malignant lesions on the orbit infiltrate and grow slowly, especially compared with those arising in skin and soft tissues.
AETIOLOGY
The concept of precursor lesions could indicate two phases in the aetiology of cancer-eye, i.e. a phase of development of the precursor and a phase of assumption of malignancy. Though a continuous process of change from initial cellular stimulation to malignancy may occur, that does not necessarily preclude two aetiological agencies being involved, one in producing the precursor and the other in inducing malignancy in the established precursor; one or both being necessary in each process.
Actinic irradiation and viral infection appear to warrant most attention.
Though Russell et al. (ibid) survey an extensive literature, their only reference to anything in the nature of transmission was the failure of homologous transplantation by Loeb et al. (1900). It would not seem unlikely that among numerous workers there have been some unsuccessful attempts at transmission of malignant lesions. Though Drabble (1929) speculated on the possibility of keratomas eventually becoming malignant and stated that he considered any fairly extensive papillomatous condition of the bovine skin as pre-cancerous, this concept was apparently not applied specifically to cancer-eye until the work of Russell et al. and their contemporaries. So probably little attempt at transmission of benign precursors has been made.
A viral factor in aetiology is suggested by a number of considerations:
Russell et al. (ibid) have reported the regular observation of large intranuclear bodies (inclusion bodies?) in lesions at all stages from plaque to papilloma. They do not attribute any particular significance to this observation.
In milking goats, Moulton (1954) recorded an outbreak of cutaneous papilloma of the udder. Carcinomas were associated with this outbreak. Lesions were confined to fifty (50) white animals; none of the same number of black ones being affected.
Plowright (1955) reported the incidence of malignancy associated with papillomas of the oesophagus, pharynx and rumen of Zebu-type cattle in Kenya. Olson and Palionis (1953) have described, under the term proliferative stomatitis, & viral infection resulting in papillomas and ulceration in the bovine mouth and oesophagus.
Russell et al. (ibid) point out that the sequence in development of benign precursor lesions toward malignancy is similar to that of the Shope papilloma; while Chandrasekharan, Nair and Sastry (1954) have expressed the opinion that viral causation is likely because some of the tumours are papillary and are derived from papillomas.
No amount of such opinion or circumstantial evidence can prove viral causation which, by virtue of its nature, can, if existing, be proved by transmission.
Actinic irradiation is held most widely to be the primary factor. This is supported by general acceptance of irradiation as responsible for carcinoma of lightly pigmented human skins. Paralleled by the situation in human skin cancer, the incidence in bovine eyes is believed to rise as one moves toward the Tropics.
If lesions which we accept as precursors are due solely to irradiation we have the interesting situation of papillomas due to viral infection, irradiation, and perhaps due to coccidial infection also for as Seddon (1952) has pointed out papillomatous masses may be observed in the more chronic forms of ovine coccidiosis.
The work of Olson and Palionis (1953), demonstrating that under their conditions a hyperkeratosis-producing agent was necessary for production of demonstrable lesions of proliferative stomatitis in animals other than very young calves, suggests not only an approach to exploring transmissibility of precursor lesions but also how two main theories of cancer-eye aetiology may be reconciled.
Burnett (1957) points out it is by no means inevitable that initiation of cellular infection must be followed by production of a new brood of virus (i.e. infective particles) and that this phase, in certain circumstances, may be prolonged. Gledhill (1955) instances mouse hepatitis virus as a persistent, inapparent viral infection which may be activated by infection with Eperythrozoon coccoides, and Lwoff (1950) reports activation of latent lysogenic bacteria by ultraviolet light. Consequently, if lesions do not become evident, that fact cannot invariably be interpreted as evidence that infection has not become established.
CONCLUSION.
Two features of cancer-eye appear to have received little attention, especially as regards any significance they may have in understanding the aetiology of the disease. The first is its age incidence and the other the predilection for tissues of the orbit and peri-orbit, to the almost total exclusion of carcinomas on other unpigmented surface epithelium such as muzzle, teats and perineum.
It is of more than passing interest to note that vital aetiology in cancer is stated by Burnett (1957) to be "simply one rather potent means by which what is functionally equivalent to a somatic mutation can be produced".
Casual studies, as in the past, are not likely to yield much essential understanding of the problem, though interest in the findings of any of the newer fields, such as biochemistry, virology, tissue culture and the like, may give clearer understanding of the processes involved.
It seems warranted to make direct observations on the incidence of cancer-eye with a view to establishing & reliable reference point against which future incidence may be measured. Otherwise it cannot be known whether increase is occurring. Incidence to levels reported in America could not be accepted with complacency.
The immediate prospect facing field veterinarians is of control of loss by surgery in operable cases, salvage of part of value by slaughter of breeding stock, and administrative control of the diseased animal with little, if any, control of the disease itself.
SUMMARY.
1. The importance of cancer eye in this part of the State lies in its scientific interest, loss of breeding efficiency through culling, and in administration of disease control legislation. Incidence over-all is estimated at 0.1 to 0.3 per cent.
2. In this area it has been found exclusively a Hereford and Hereford-cross disease, whereas at Homebush State Abattoir a relatively high proportion of dairy breed animals was found affected.
3. Developmental pathology as described by American workers is outlined.
4. Observations made here on benign precursors are outlined and discussed.
5. Possible relationship of actinic irradiation and viral infection as casual agents is discussed.
ACKNOWLEDGMENTS.
Grateful acknowledgment is made of approval freely given by Mr. P. Brydon, B.V.Sc., Veterinary Officer at Homebush State Abattoir, to quote figures extracted from records by him; and to Mr. A. N. A. Harris, B.V.Sc., District Veterinary Officer at Armidale, to quote figures which he extracted from records. It is a pleasure also to acknowledge the assistance given by Mid-Coast Meat Society's staff and particularly Mr. H. Ellis, Meat Inspector-in-Charge, during a very informative week spent on the slaughtering floor.
REFERENCES.
Anderson, D. E. Lush, J. L. and Chambers, D. (1957) - J. Animal Sci., 16 : 739.
Black. W. L. (1934) - Extension Animal Husbandman, 33 : 9; cited by Russel et al. (1956) Cancer, 9 : 1.
Brydon, P. (1959) - NS.W. Dept. of Ag. records - unpublished.
Burnett, McFarlane (1957) - Brit. Med. J., April, 1957.
Chandrasekharan Nair, K. P. and Sastry, G. A. (1954) - Indian Vet. J., 30 : 325; cited by Russell et al. (1956) - Cancer, 9: 1.
Dodd, Sydney (1924) - Proc. Australasian Assn. for the Adv. of Sci, 7: 689.
Drabble, J. (1929) - Aust. vet. J., 4 : 71.
Gledhill, A. W. and Niven, Janet S. F. (1955) - Vet. Rev. & Annot, 1 : 82
Guibbert, H. R., Wahid, A., Wagnon. K. A. and Gregory, P. W. (1948) J. Animal Sci., 7 : 426.
Harris, A. N. A. (1959) - N.S.W. Dept. of Ag. records - unpublished.
Knox, J. H. (1949) - New Mexico Experiment Station. Ranch Day, Oct. 10. 1949 (12-13): cited by Russell et al.
i> (1956) Cancer 9 : 1.Liess, J. (1934) - cited by Cotchin. E., Review Series No. 4 of the Commonwealth Bureau of Animal Health.
Loeb. Land Jobson, G. (1900) - J. Comp. Med. & Vet. Arch., 21: 1900. Cited by Dodd, Sydney (1924) Proc. Australasian Assn. for the Adv. of Sci., 7 : 689.
Lwoff et al. (1950) - Ann. Inst. Pasteur. 79 : 815; cited by Gledhill, A. W. and Niven, Janet, S. F. (1955) - Vet. Rev. & Annot.. 1 : 82.
Monlux, A. W. Anderson, W. A. and Davis, C. L. (1957) - A. M. J. Vet. Res., 18 : 5.
Moulton, J. E. (1954) - N. Amer. Vet., 35 : 29.
Olson, C., Jr. and Palionis, T. (1953) - J.A.V.M.A., 123: 419.
Plowright, W. (1955) - J. Comp. Path., 65 : 108.
Russell, W. O. Staten, Wynne E. and Loquvam, G. S. (1956) - Cancer, 9 : 1.
Seddon, H. R. (1952) - "Diseases of Domestic Animals in Australia", Part 4, Service Publication (Division of Veterinary Hygiene) No. 8. Dept. of Health, Canberra, A.C.T.
Woodward, R. R. and Knapp. B. Jr. (1950) - J. Animal Sci., 9 : 578; cited by Russell et al. (1956) - Cancer, 9 : 1.