Squamous cell carcinoma (SCC) of the cornea in French Bulldog: case report

doi:10.21203/rs.3.rs-5318296/v1

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Case Report

Squamous cell carcinoma (SCC) of the cornea in French Bulldog: case report

https://doi.org/10.21203/rs.3.rs-5318296/v1

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Background: Corneal squamous cell carcinoma (SCC) is considered as a rare condition in dogs and our aim is to report a case of the disease in French Bulldog and discus the factors leading to development of it. Misdiagnosing of SCC can potentially delay treatment and increase morbidity

Case presentation: A 2.6-year-old French Bulldog, with growing, nonpainful mass on the left eye was examined in University veterinary hospital of Trakia university in Stara Zagora. During the examination, a brown mass located on 6 o’clock with oval shape and diameter 4 mm, affection 20% of the cornea, was suspected as squamous cell carcinoma. A clinical examination showed no evidence of metastases and superficial keratectomy with further conjunctival flap were made and the mass was histologically examined and conformed the clinical diagnose. After 6 months from the surgery, there is no evidence of local or general metastasis.

Conclusion: surgical treatment must be considered the best therapeutic approach for ocular SCC in dogs even it is rare diagnosis.

squamous cell carcinoma (SCC)

French bulldog

cornea

Tumor masses of the cornea occur uncommonly in dogs [1]. Corneal squamous cell carcinoma (SCC) is considered as a rare condition in dogs. Ocular SCCs, in general, can affect any structure of the eye globe and adnexa [2]. Very few cases of canine primary SCC of the cornea have been described in the past 12 years [3]. Ocular SCCs frequently occur in large animals, originating from the cornea, conjunctiva, and eyelids [4, 5]. Misdiagnosing of SCC can potentially delay treatment and increase morbidity [6].

The beginning of pathogenesis of squamous cell tumors is connected with pretumoral dysplastic lesions, followed by papilloma, through carcinoma and reaching SCC [2]. In human medicine, these squamous epithelium tumors, are suggested to be unitied under the term, ocular surface squamous neoplasia. This includes dysplastic and carcinomatous lesions of the cornea and the conjunctiva [7]. The same term, perhaps, could also be adopted in veterinary ophthalmology [6].

The aim of the present study was to describe the clinical and histopathological appearance of a primary corneal SCC in an 2.6 year-old male pug dog, to report its histopathological findings, and to characterise the tumour.

An 2.5 yeas-old, 7kg, intact male French Bulldog was examined in the University veterinary hospital of Trakia university in Stara Zagora, Bulgaria. The history of the pation include progressive growing of mass on the left eye, over the cornea. During the first examination, on the lateral part of the cornea, there was a small (around 1 mm) brow spot, connected with the limbus. There were no other changes of the eye and its adnexa. Prescription of corticosteroid and antibiotic eye drops (Tobradex 3mg/ml eye drop, Alcon, Puurs, Belgium) was made and the animal was called again after two months for second examination.

On the second examination it was made full eye examination. Shirmer tear test I (Schirmer tear test strap with blue band, FioniaVet, Kochgade, Denmark) was made on the affected eye and the results show 17mm/min. Palpebral, corneal, dazzle and menace response reflexes were present. Evaluation of the direct and indirect pupillary light reflexes show no changes. The intraocular pressure was measured with rebound tonometry (iCare Tonovet, Vantaa, Finland) and was found to be 19 mmHg. The medial angle of the lower eyelid show slightly rotation to the cornea (entropium). Slit-lamp biomicroscopy (LED SLIT XL-1, Ohira CO., Japan ) showed hyperemia of the conjunctiva, neovascularization of the cornea and sclera, brown mass located on 6 o’clock with oval shape and diameter 4 mm, affection 20% of the cornea. The surface of the mass was swollen and smooth. (Fig. 1) The peripheral cornea, not involved by the lesion, was without any changes. The anterior chamber, the iris, the vitreous, and the fundus were not affected.

Diagnose of primary tumor of the cornea were made on the base of examination and the animal goes under further diagnostic. The CBC and serum biochemical profile were made and they don’t show any changes. X-ray of the chest, in two standard projections, reveal no evidence of the disease.

A superficial keratectomy with further conjunctival flap were made. The animal recovered very well from anesthesia and additional therapy with antibiotic (Tobrin 03% eye drops, Antibiotic, Razgrad, Bulgaria) and NSAID (Dicloabak 1mg/ml eye drops, Exel Vision, France) eye drops and generaly NSAID (Robexera 10mg, Krka, Novo Mesto, Slovenia) were prescribed for several days. The mass was immersed in 10 ml of 10% formalin and were refer to department of general and clinical pathology for histological examination.

Histopathological specimens were fixed in 10% neutral formalin and processed by staining with haematoxylin and eosin (HE) [8, 9]. The observed microscopic changes from the histopathological examination of the excised formation were as follows: the epithelium covering the cornea was focally affected by an encapsulated proliferation of squamous corneal epithelial cells reaching the underlying connective tissue. Intraepithelial keratinization was observed in some of the cells (Fig. 2.). Signs of malignancy such as pleomorphism, polychromasia, anisokaryosis, and mitotic figures were present in the neoplastic cells (Fig. 3.). An inflammatory cellular infiltrate composed primarily of lymphocytes was also present. Neoangiogenesis processes were found in the tumor stroma. Hemorrhages were observed in the core of the formation. Based on the changes in the epithelial cells, a diagnosis of squamous cell carcinoma was confirm.

Primary corneal squamous cell carcinoma (SCC) is considered rare in dogs [10]. In the past 12 years, some case reports have been published, and occurrence of this type of tumor seems to be increasing [3]. The etiopathogenesis of SCCs of the ocular and periocular region is not fully known. Some causes including trauma, the ultraviolet solar radiation, viral agents, species predipostion, hormonal, genetic and immunologic factors [4], may lead to increasing of the tumor expression [7]. Most of the dogs presenting with corneal SCC had had a history of chronic keratitis [11], such as keratoconjunctivitis sicca, pigmentary keratitis [12] or keratitis secondary to eyelid abnormalities or trauma [13]. In our case and in only a few other dogs, there was not evidence of any concurrent ocular surface disease at the time of the diagnosis [11].

Brachycephalic dogs, especially French Bulldogs, have breed predisposition for developing corneal squamous cell carcinoma. Almost 50% of presentet dogs, affected with a primary corneal SCC were bulldogs [14], as is the dog of the present case report. Exophthalmos, macroblepharon, and lagophthalmos, or the combination of this three anatomic disadvantages, causes improper blinking and exposure to development of keratopathy syndrome [3]. It is known that SCCs can grow in areas of trauma on the cornea [13]. In one case the development of the primary corneal SCC was a result of the sustained microtrauma and chronic keratitis caused by continuous irritation exerted by the chronic eyelid abnormality (entropion) In addition, many brachycephalic dogs, show a nasal fold trichiasis and a mild medial entropion of the lower eyelid. The severe corneal irritation, connected with eyelid defects, might explain the high prevalence of primary SCC cases in this dogs [6]. In our case there was evidence of entropion of the lower eyelid in affecter eye, but without corneal surface changes.

The animal, presented in this case, lives in Gabrobvo, Bulgaria (42°52.209N and 025°19.081E). The area has very high levels of ultraviolet UV index (greater than 11) during the summer period [15]. Primary corneal SCC might be a related consequence of ultraviolet radiation exposure as reported by Montiani Ferreira et al. [6]. It is well known, that UV radiation is a complete carcinogen by itself and is capable of inducing and promoting neoplastic changes. The effect of UV radiation is by inducing mutations in the p53 tumor suppressor gene [16]. Thus, it is also conceivable, that ultraviolet radiation has contributed as a carcinogen to the development of this corneal SCC. In other hand, Takiyama et al. [19] and Barsotti et. al [3], didn’t found mutation of this protein in their case reports. They explain this with a lower UV index in Italy and Japan, compared with Brazil [6], where one of the cases were presented. In our case, we didn’t examine the sample for p53 tumor suppressed gen to approve or not this, but because of the higher UVE, we assume is more likely unlocking factor.

In conclusion, the surgical treatment must be considered as a best therapeutic approach for ocular SCC in dogs even it is rare diagnosis. Further studies would be useful to better understand the development mechanism, expression and treatment in corneal SCC of the dog. We believe that the present case report, give some clinical and histological diagnostic information and will contribute understanding of the possible causes of corneal SCCs.

CBC

complete blood count

haematoxylin and eosin

NSAID

non-steroidal anti-inflammatory drusg

SCC

squamous cell carcinoma

ultraviolet

Ethics approval and consent to participate:

The manuscript doesn’t involve human participants, human data or human tissue.

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The manuscript doesn’t contain any individual person’s data in any form.

Competing interests:

The authors declare that they have no competing interests.

Funding:

The manuscript doesn’t use any form of funding.

Author Contribution

VN collect and interpreted the patient data regarding to the clinical appearance and it was major contributor in writing the manuscript. IK performed the histological examination of the neoplastic mass. All authors read and approved the final manuscript.

Acknowledgements:

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Availability of data and materials:

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Squamous cell carcinoma (SCC) of the cornea in French Bulldog: case report

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