Chronic hyperproliferative process with major involvement of mast cells at ear tag sites of sows

(13.05.2012) Ear tags are commonly used worldwide for the appropriate identification of laboratory and farm animals.

The application of ear tags may induce local inflammatory or neoplastic reactions, which are observed mostly in combination with metallic tags (ROSCOE et al., 1975; WAALKES et al., 1987; JOHNSTON and EDWARDS, 1996; BARON et al., 2005).

This report for the first time describes the occurrence of massive inflammatory reactions with involvement of mast cells and eosinophils as well as fibroplasia at ear tag sites of sows after the application of commercially available and routinely used ear tags made of polyurethane.

On a pig farm in Lower Austria housing 300 Landrace sows, one gilt developed a severe local reaction shortly after ear tagging, therefore the farmer decided to remove the tag. Nevertheless, the reactive site increased in size over time, but was neither painful to the animal nor compromised its reproductive performance (Fig. 1).

Left auricle, sow; a three year old sow developed a chronic inflammatory and hyperplastic proliferation of the left auricle
Left auricle, sow; a three year old sow developed a chronic inflammatory and hyperplastic proliferation of the left auricle

Two years later the animal had to be culled due to pyometra. At the slaughterhouse, the affected auricle (dimensions of 37.0 x 26.0 cm, 3280 g) was removed (Fig. 2). The auricle had a cauliflowerlike appearance and its consistency was firm. The cut surface was dry and yellowish. The unaffected auricle had dimensions of 31.5 x 18.0 cm and a mass of 700 g.

Fig.2: Left auricle, sow; proliferation continued despite the ear tag had been removed soon after application when a pathologic reaction was observed by the farmer
Fig.2: Left auricle, sow; proliferation continued despite the ear tag had been removed soon after application when a pathologic reaction was observed by the farmer

Pieces of both auricles were fixed in a 3.8 % formaldehyde solution for 24 hrs, embedded in paraffin wax, and routinely processed for histological evaluation using haematoxylin/eosin, toluidine blue, and immunohistochemical stainings.

A massive increase of mature collagenous tissue as well as a perivascular inflammation dominated by lymphocytes, plasma cells, mast cells and eosinophils with no alteration of the epidermis were evident in the affected auricle (Fig. 3).

Fig. 3: Auricle, sow; proliferation of interweaving bundles of collagen fibers and prominent perivascular inflammatory infiltrates; a significant proportion of the inflammatory cells are eosinophils (inset); HE; bar = 150 µm, bar (inset) = 40 µ
Fig. 3: Auricle, sow; proliferation of interweaving bundles of collagen fibers and prominent perivascular inflammatory infiltrates; a significant proportion of the inflammatory cells are eosinophils (inset); HE; bar = 150 µm, bar (inset) = 40 µ

Due to the involvement of eosinophils and mast cells, an allergic component was suspected initially, although the highly proliferative nature of the process was not easily explained by this assumption.

Very similar reactions localized exclusively at ear tag sites could then be observed in another seven gilts or sows on this farm with variable time spans between application of the ear tag and onset of the pathological process.

To clarify whether these new cases had the same etiopathogenesis, biopsies were taken from two animals, one gilt and one sow. Histological evaluation showed again a perivascular inflammation with large amounts of eosinophils and mast cells.

The proliferative connective tissue contained more fibroblasts and less collagen fibres and thus the formation of fibromas could not be excluded (Fig. 4).

Fig. 4: Auricle, sow; fibroblast-rich newly formed connective tissue infiltrating between pre-existing thick collagen fibers of the corium; there are also prominent perivascular mast cell-rich infiltrates interspersed; HE. Inset: CD117 immunohistochemistr
Fig. 4: Auricle, sow; fibroblast-rich newly formed connective tissue infiltrating between pre-existing thick collagen fibers of the corium; there are also prominent perivascular mast cell-rich infiltrates interspersed; HE. Inset: CD117 immunohistochemistr

Next, we tested the therapeutic efficacy of a once daily local application of a dexamethasone ointment (Dexamethason Creme LAW 0,05 %) over one week in two affected sows. Dimensions of the reactive site of one animal were 6.5 x 4.5 x 4.0 cm before therapeutic intervention. The reactive site of the other animal had dimensions of 5.0 x 4.0 x 1.8 cm.

After treatment, an approximately 20 % dimension’s reduction could be observed in both animals. However, histological evaluation before and after therapy revealed no measurable changes in the severity of eosinophil and mast cell infiltration. After cessation of glucocorticoid treatment, reactive sites’ dimensions increased again.

Discussion

Slowly expanding masses at various connective tissue sites in ruminants are mostly attributed to semimalignant or malignant neoplasms (SIPOS et al., 2001, 2002; SIPOS u. SCHILCHER, 2006). In contrast to ruminants, pigs very rarely experience malignancies. One case of a cutaneous hyperproliferative alteration in a pig was classified as a fibroepithelial hamartoma (SIPOS et al., 2007).

The impressive multinodular mass of the proliferativesite of the first affected sow initially led to the suspicious diagnosis of a fibroma or fibropapilloma with a strong chronic inflammatory component due to the ear tag. Histologically, the number of eosinophils and mast cells in the inflammatory infiltrates was most impressive.

All ear tags were made of polyurethane, which are fabricated by a polyaddition of diols or polyols and polyisocyanates. The health and safety information sheet of the ISOPA (2011) says that polyurethans may sensitize skin.

On the other hand, contact allergies in farm animals have exclusively been described for metallic ear tags and the ear tags in our cases have additionally been removed soon after the first observation of a reactive process in most animals.

Therefore, the reason for the involvement of eosinophils and mast cells in this specific setting remains unclear. Presumably, these cells have a distinct, till now not clarified function in chronic inflammatory responses in the porcine species.

Mast cells may also be involved in chronic inflammatory processes other than those with a hypersensitivity background. In this context it is worth mentioning that mast cells have the ability to promote fibroblast collagen synthesis via tryptase (GALLI and TSAI, 2010).

Thus it cannot be ascertained in the observed cases whether the ear tags triggered some allergic reaction, which converted into a self-perpetuating, chronic inflammatory and probably also neoplastic process, or whether the auricles developed a chronic inflammation first, which then led to the increased recruitment of mast cell precursors.

Cutaneous mastocytomas were dropped as differential diagnosis as the pathologic processes of our animals could all be related to ear tagging and because local (as well as systemic) mast cell tumors in pigs have only been described as individually occuring neoplastic entities (MIGAKI and LANGHEINRICH, 1970; SIPOS et al., 2010).

Glucocorticoid treatment led to a reduction in the dimension of the proliferative sites on the one hand but failed to reduce the amount of eosinophils and mast cells. One explanation could be a possible failure of the used formulation to permeate into deeper layers of the affected tissue.

As animals were seemingly not handicapped by these reactive sites, glucocorticoid treatment cannot be recommended for future similar cases, also considering the severe adverse side affects of longer-lasting glucocorticoid treatment protocols.

Source of supply

Dexamethason Creme LAW, 0.05 % (Riemser Arzneimittel AG, Insel Riems, Germany)

References

BARON, B.W., LANGAN, G., HUO, D., BARON, J.M., MONTAG, A. (2005): Squamous cell carcinomas of the skin at ear tag sites in aged FVB/N mice. Comp Med 55, 231–235.

GALLI, S.J., TSAI, M. (2010): Mast cells in allergy and infection: versatile effector and regulatory cells in innate and adaptive immunity. Europ J Immunol 40, 1843–1851.

ISOPA – European Diisocyanate & Polyol Producers Association: Health & Safety Information, http://www.isopa.org, accessed 1st August 2011.

JOHNSTON, A.M., EDWARDS, D.S. (1996): Welfare implications of identification of cattle by ear tags. Vet Rec 138, 612–614.

MIGAKI, G., LANGHEINRICH, K.A. (1970): Mastocytoma in a pig. Pathologia Veterinaria 7, 353–355.

ROSCOE, D.E., VEIKLEY, L.R., MILLS jr, M., HINDS, L. (1975): Debiliating ossifying fibromas of a white-tailed deer associated with ear tagging. J Wildlife Dis 11, 62–65.

SIPOS, W., SCHILCHER, F., LEEB, B., BAUMGARTNER, W. (2001): Rezidivierendes Fibrosarkom bei einem Bergschaf. Tierärztl Umschau 56, 602–605.

SIPOS, W, HOCHSTEINER, W., SCHILCHER, F., FLÖCK, M., BAUMGARTNER, W. (2002): Genitales Leiomyosarkom bei einer Westafrikanischen Zwergziege. Wien Tierärztl Monat - Vet Med Austria 89, 319–324.

SIPOS, W., SCHILCHER, F. (2006): Fibropapillome in Haube und Pansen bei einem Jungrind als Ursache für eine chronische Indigestion. Wien Tierärztl Monat - Vet Med Austria 93, 53–56.

SIPOS, W., GRIESSLER, F., SCHILCHER, F., STUMPF, I., PIRKER, E., SCHMOLL, F. (2007): Fibroepithelial hamartoma in a domestic pig. Vet Pathol 44, 411–413.

SIPOS, W., HIRSCHBERGER, J., BREUER, W., ZENKER, I., ELICKER, S. (2010): Partial remission of mast cell leukemia in a minipig after chemotherapy. Vet Rec 166, 791–793.

WAALKES, M.P., REHM, S., KASPRZAK, K.S., ISSAQ, H.J. (1987): Inflammatory, proliferative, and neoplastic lesions at the site of metallic identification ear tags in Wistar [Crl:(WI)BR] rats. Cancer Res 47, 2445–2450.

Corresponding authors’ address:

Univ. Prof. Dr. Wolfgang Sipos, Veterinärplatz 1, 1210 Vienna, Austria.
e-mail: wolfgang.sipos@vetmeduni.ac.at

Literature

Chronic hyperproliferative process with major involvement of mast cells at ear tag sites of sows S. ELICKER, H. WEISSENBÖCK and W. SIPOS; Wien Tierärztl Monat – Vet Med Austria 99 (2012), S. 44 - 46

Vet Med Austria


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