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Este artículo se encuentra disponible en la página web de la revista en la siguiente URL: https://bmcvetres.biomedcentral.com/articles/10.1186/s12917-019-1790-3 Background: Primary corneal tumors are unusual in dogs although there has been a rise in the prevalence of canine corneal squamous cell carcinoma in the past decades due to different factors. Exposure to ultraviolet radiation, presence of chronic keratitis or history of superficial trauma are some of them. We report for the first time a highly infiltrative corneal neoplasia with both exophytic and deep stromal growth, which presented atypical histologic features of a squamous cell carcinoma. Case presentation: An adult male French bulldog was referred with an exophytic, pink to white gelatinous mass occupying approximately 70% of the central cornea on the right eye. Histological findings from the excisional biopsy were consistent with corneal carcinoma and transconjunctival enucleation was performed at the request of the owner. A final diagnosis of primary corneal squamous cell carcinoma was done based on the squamous differentiation observed in the neoplastic cells of the superficial layers. However, cells in deeper layers were less differentiated, showed pseudoacinar formations and did not expressed marker for stratified squamous epithelium (i.e., cytokeratin 5/6). The dramatic thickening of the cornea and the fact of observing neoplastic cells almost at the level of the Descemet’s membrane make this case very unusual as the squamous cell carcinoma in dogs tends to involve the superficial stroma or colonize the corneal surface as an exophytic lesion. Conclusions: Based on the histological findings, a high infiltrative and poorly differentiated corneal squamous cell carcinoma was diagnosed. In terms of clinical relevance, our results suggest that corneal lesions compatible with neoplasia need an early diagnosis in order to prevent the aggressive growth of the tumor and the enucleation of the eye.

The aim of this study was to report a case of isolated corneal squamous cell carcinoma in a patient with unilateral dry eye symptoms. The case was a 48 years old man with history of thermal corneal injury on his left eye two years ago with decreased visual acuity and dry eye symptoms a short time after, which was treated with the diagnosis of dry eye and had no improvement in symptoms. Examination revealed hypertrophy of near total corneal epithelium, without limbal and conjunctival involvement. The surface of the lesion was irregular with punctate epithelial erosions. The patient was underwent excisional biopsy which was revealed severe corneal dysplasia (carcinoma in situ). After excision, the patient was treated with Fluorouracil and there was no sign of recurrence till the time of last follow-up examination. Dry eye symptoms were disappeared completely. We conclude that, in the case of unilateral chronic dry eye which was resistant to the treatment with signs of corneal epithelial involvement, isolated corneal neoplasia should be considered even without limbal or conjunctival involvement.

Purpose To describe the use of a pulse-dose topical 5-fluorouracil (5-FU) treatment regimen in a Pug dog with corneal squamous cell carcinoma (SCC). Methods A 1-year-old, spayed female Pug was evaluated for a corneal perforation of the right eye, which was surgically stabilized with a conjunctival pedicle graft. At the time of medial canthoplasty 7 weeks later, two areas of gray–white discoloration had developed medial and lateral to the graft. Biopsy samples were obtained via superficial keratectomy while under general anesthesia. Results Definitive diagnosis of corneal SCC was made through histopathological examination of the surgical biopsies. Thoracic radiography and submandibular lymph node cytology revealed no evidence of metastatic neoplasia. Following healing of the corneal biopsy sites, topical 1% 5-FU ointment was applied four times daily for four consecutive days once a month, for six treatment cycles. Twenty-three months after diagnosis, the patient remains visual and comfortable with no evidence of SCC recurrence. Long-term therapy with once daily topical 1% cyclosporine solution was used to manage corneal pigmentation bilaterally. Conclusions The pulse-therapy 1% 5-FU protocol was a successful, convenient, and cost-effective adjunctive treatment with few adverse effects.

Purpose To report three cases of canine corneal squamous cell carcinoma (SCC) treated with strontium 90 beta radiation as an adjunct to surgical excision. Methods Corneal SCC was excised with lamellar keratectomy. This was followed by local application of strontium 90 beta radiation. Results Available case follow-up times range from 3 to 50 months. One case suffered a recurrence 5 months following initial excision and strontium 90 treatment. Conclusion and discussion Strontium 90 beta radiation has been used extensively as an adjunctive treatment for equine corneal SCC and in other canine ocular tumors; however, there is a paucity of information regarding use in canine corneal SCC. The cases presented here suggest its use following keratectomy may be helpful in preventing disease recurrence. At the dosage used, severe adverse effects were not observed.

Objective Canine corneal squamous cell carcinoma (SCC) is a rare tumor, with only eight cases previously published in the veterinary literature. The Comparative Ocular Pathology Lab of Wisconsin (COPLOW) has diagnosed 26 spontaneously occurring cases, 23 in the past 4 years. This retrospective study describes age and breed prevalence, concurrent therapy, biologic behavior, tumor size and character, and 6-month survival rates after diagnosis. Results A search of the COPLOW database identified 26 corneal SCC cases diagnosed from 1978 to 2008. There is a strong breed predilection (77%) in brachycephalic breeds, particularly those prone to keratoconjunctivitis sicca. The mean age was 9.6 years (range 6–14.5 years). Follow-up information >6 months was available for 15 of 26 cases. Recurrence occurred in the same eye in nine cases, seven of which were incompletely excised at the time of first keratectomy. No cases were known to have tumor growth in the contralateral eye and no cases of distant metastases are known. Where drug history is known, 16 of 21 dogs had a history of treatment with topical immunosuppressive therapy (cyclosporine or tacrolimus) at the time of diagnosis. Conclusion Chronic inflammatory conditions of the cornea and topical immunosuppressive therapy may be risk factors for developing primary corneal SCC in dogs. SCC should be considered in any differential diagnosis of corneal proliferative lesions. Superficial keratectomy with complete excision is recommended, and the metastatic potential appears to be low.

Background: : : Squamous cell carcinoma (SCC) is a neoplastic disease of the squamous epithelial cells that has been rarely described in the literature. This neoplasm affects the eyelid, conjunctiva and third eyelid, as well as the cornea. Corneal SCC is a neoplastic lesion characterized by a pink, typically irregular mass protruding from the epithelial surface of the cornea. Canine corneal SCC has been associated with chronic keratoconjunctivitis sicca, or keratitis secondary to exophthalmia and is common in humans, horses and cows. The treatment is surgical with excision of the lesion of the ocular surface. This paper reported a study of a dog with corneal SCC, which was successfully treated with a superficial lamellar keratectomy excision combined with cryosurgery. Case: An 8-year-old male English bulldog was presented for the evaluation of a red mass on its left eye that had progressively grown over a 1-year period. The mass was approximately 6mm in diameter and it was elevated from 3 to 4 mm above the corneal surface with no expansion onto bulbar conjunctiva. At physical examination it was normal except for the ocular disease. A complete blood cell count and serum chemical profiles were unremarkable. The radiographic evaluation did not demonstrate any evidence of metastasis. The mass was excised by a superficial lamellar keratectomy and the surgical bed was frozen with nitrous oxide. The surgical procedures consisted in excising a rim of grossly normal conjunctiva with 2mm along the mass that was sent for histopathological examination. The postoperative measures included the administration of topical tobramycin at 0.3%, four times a day, and systemic carprofen 4 mg/kg, daily, for 5 days. A reexamination was performed after 14, 21, 30, 42, 70 and 180 days postoperatively. When the cornea was healed, topical dexamethasone at 1% was prescribed, twice a day for 2 weeks to control an excessive vascularization at the limbus. In 70 days, the postoperative result was very satisfactory and there was no evidence of ocular inflammation. Two years after the surgical procedure the dog had not developed metastasis or recorrence of the ocular neoplasm. Discussion: Ocular or adnexal SCC in animals and humans is suspected to be a result of the chronic effect of ultraviolet light on the epithelium. Also, in dogs the SCC has been associated with a chronic source of irritation. The dog observed in our study was brachycephalic, with natural exophthalmic eyes and oversized palpebral fissures that may have caused excessive and chronic corneal exposure to solar radiation. The treatment of choice was excision of the lesion with a wide surgical margin, because it is the standard treatment for SCC of the cornea and cryotherapy has been a common modality of treatment. A histological examination revealed islands and nests of pleomorphic epithelial cells and keratin pearls and the diagnosis of the corneal SCC was made. No evidence of metastasis or recurrence has been found since the surgical procedure. Although, recurrence rates following the excision of this neoplasm of the ocular surface ranged an average of 30%. The treatment of the neoplasm was successful in both procedures, once no visible evidence of regrowth presented two years after the keratectomy. Despite being a rare entity, squamous cell carcinoma of cornea should be considered as differential diagnosis in dogs with any corneal mass.

Purpose To report two cases of corneal squamous cell carcinoma (SCC) in dogs. Methods Corneal tumors were resected by superficial keratectomy in two cases. Immunohistochemistry of the corneal tissues was performed using anti-p53 antibody. Results The prominent features of the cases were a clinical history of pigmentary keratitis and chronic keratitis. In each case, a corneal mass was surgically removed with a superficial keratectomy and histologically diagnosed as corneal SCC. Both masses were negative for p53. To reduce chronic corneal irritation, 0.1% hyaluronate sodium ophthalmic solution was applied. After more than 15 months of postsurgical follow-up there has been no recurrence of either neoplasm. Conclusion and discussion Chronic corneal irritation was suspected as the primary etiology for the corneal SCC. Appropriate surgical removal of the mass and subsequent conservative treatment for keratitis provided effective therapy in these two cases.

乾性角結膜炎をシクロスポリンで治療中のシーズー 雄 10歳の右眼角膜に結節状の分葉した腫瘤を認めた。吸入麻酔下で角膜表層切除術を実施し腫瘤を切除した。病理組織学的検査で腫瘤は扁平上皮癌で、その組織像は扁平上皮細胞に異型細胞の増殖と少数のリンパ球や形質細胞浸潤が見られたものの、深部組織への浸潤はなかった。術後は角膜潰瘍の治療を自己血清、抗生剤、ソフトコンタクトレンズの使用を行い、潰瘍治癒後はシクロスポリンでKCSの治療を継続した。本症例は術後良好な経過を得ていたが、1年5ヶ月後に左側顔面に転移がみられ死亡した。

Purpose: To report a case of primary corneal squamous cell carcinoma (SCC) in an English Bulldog. In addition, immunohistochemistry of the corneal tissue mass was performed using a panel of antibodies. A prominent feature of the present case was the clinical history of chronic keratitis due to eyelid abnormalities. Results: No papillomavirus antigen was detected in section of normal or neoplastic corneal tissue. The corneal epithelial cells were positive for pancytokeratins AE1/AE3 and MNF116, and E-cadherin. The neoplastic cells in close proximity to the normal epithelial lining were positive for both pancytokeratins and E-cadherin with gradual loss of staining toward the center of the neoplastic mass. Rare neoplastic cells demonstrated positive staining for caspase 3 and a large number was strongly positive for GADD45 and p53. Conclusion and discussion: The observed loss of the various cytokeratins, the strong p53 expression, and low numbers of caspase 3 positive cells were suggestive that a p53 mutation may have caused this primary corneal SCC. Over-expression of the tumor-suppressor gene p53 is likely to be a consequence of ultraviolet radiation exposure. Two factors, however, may have played a role in the formation of this primary corneal SCC: chronic irritation of the corneal surface (microtrauma) and exposure to UV radiation.

A 6-year-old, female, spayed Border Collie was presented to the Unit of Comparative Ophthalmology at the Animal Health Trust with a 6-month history of a progressive nonpainful opacity of the left cornea. A keratectomy was performed and the tissue submitted for histopathology. The diagnosis was squamous cell carcinoma. There has been no recurrence of the neoplasm to date (5 months). Canine corneal squamous cell carcinoma (SCC) has not been reported previously in the UK.

Objective—To evaluate expression of cyclooxygenase (COX)-1 and COX-2 in the cornea, eyelid, and third eyelid of healthy horses and those affected with squamous cell carcinoma (SCC) by use of immunohistochemical techniques. Animals—15 horses with SCC involving ocular tissues and 5 unaffected control horses. Procedures—SCC-affected tissues were obtained from the cornea (n = 5 horses), eyelid (5), and third eyelid (5). Site-matched control tissues were obtained from 5 horses unaffected with SCC. Tissue sections of affected and control cornea, eyelid, and third eyelid were stained immunohistochemically for COX-1 and COX-2 via standard techniques. Stain uptake was quantified by use of computer-assisted image analysis of digital photomicrographs. Results—Immunoreactivity for both COX-1 and COX-2 was significantly greater in equine corneas with SCC than in control corneas. No significant differences in COX-1 or COX-2 immunoreactivity were detected in eyelid and third-eyelid SCC, compared with site-matched control tissues. Conclusions and Clinical Relevance—Immunoreactivity for COX-1 and COX-2 is high in equine corneal SCC, possibly indicating that COX plays a role in oncogenesis or progression of this tumor type at this site. Pharmacologic inhibition of COX may represent a useful adjunctive treatment for corneal SCC in horses.

PURPOSE: To evaluate the efficacy of topical mitomycin C for extensive recurrent conjunctival and corneal squamous cell carcinoma (SCC). DESIGN: Interventional case series METHODS: A prospective study was conducted in a single institution. Ten patients (ten eyes) with extensive recurrent conjunctival and corneal SCC were studied. The patients received topical mitomycin C 0.04% one drop four times daily in the eye with SCC. Treatment cycles were defined as 1 week using medication followed by 1 week without medication. Such treatment cycles were repeated until resolution of the conjunctival malignancy was clinically evident. The main outcome measures were tumor response and medication-related complications. RESULTS: Of the ten patients, the median age was 66 years (range 33–77 years). Before referral, the patients had undergone a median of two previous conjunctival tumor resections revealing the diagnosis of in situ SCC in three cases and locally invasive SCC in six cases. At presentation, the tumor involved the limbus and cornea in all ten eyes, forniceal conjunctiva in three eyes, and tarsal conjunctiva in one eye. The extensive tumor affected a median of 10 clock hours of limbal conjunctiva and 10 clock hours of cornea, with corneal epithelial invasion for a median of 50% (range 20%–100%) of its surface. Mitomycin C 0.04% four times daily was applied for a median of three cycles (range 1–4 cycles). Complete tumor regression was documented in all ten cases (100%). There was no recurrence over a mean follow up of 22 months (range 6–50 months). Mitomycin C caused moderate temporary local irritation and conjunctival erythema and chemosis, but no long-term intraocular or extraocular complications. CONCLUSIONS: Based on this small series, topical mitomycin C 0.04% appears to be a safe and effective therapy for conjunctival or corneal SCC, even when there is extensive recurrent tumor.

A 10-year-old female West Highland white terrier was presented with refractory hyperplastic keratitis of the left cornea of one month’s duration. At this time, a vascularised and rough lesion 5 mm in diameter was observed on the left cornea. No other abnormality was recognised on the affected eye. The corneal neoplasm was surgically removed and histologically diagnosed as a squamous cell carcinoma. For two months after the surgery, 0·04 per cent mitomycin C (MMC) eye drops were applied as adjuvant chemotherapy. Primary corneal squamous cell carcinoma with no history of keratoconjunctivitis sicca is rare in dogs. In the present report, surgical removal of the neoplasm was combined with the topical administration of the anticancer drug mitomycin C and a good prognosis was obtained. The result indicates that the combination treatment used in this case may be an appropriate therapeutic choice for corneal squamous cell carcinoma in dogs.

An 8-year-old male pug with a 12-month history of a progressive nonpainful mass on the left cornea was evaluated. Ocular examination showed a severe bilateral keratoconjunctivitis sicca, pigmentary keratitis, and an exophytic irregular pink mass occupying approximately 75% of the total corneal surface of the left eye. A squamous cell carcinoma (SCC) was suspected on cytology, and clinical investigations showed no evidence of metastases. A transpalpebral enucleation was therefore performed, and the diagnosis of SCC was confirmed on histopathology. Immunohistochemical investigations showed that the neoplastic cells were pan-cytokeratin positive and vimentin negative. Additionally, nuclei immunoreactive to Ki-67 antigen were detected. Tumor cells were also negative to p53. Immunoreactivity to COX-2 was found in less than 10% of the neoplastic cells. No adjuvant therapies were instituted, and no evidence of local recurrence or distance metastasis was identified during the 24-month follow-up period.

The cornea is one of the few human tissues where the in situ locations of stem cells (SCs), transient-amplifying (TA) cells and terminally-differentiated (TD) cells have been relatively well localised and characterised. Mid-infrared (IR) (4000-400 cm(-1)) is absorbed by biological molecules and facilitates the acquisition in the biochemical-cell fingerprint region (1800-900 cm(-1)) of spectra representative of structure and function. Human cornea derived from normal or squamous cell carcinoma (SCC) samples were acquired, cryosectioned (10 µm), floated onto BaF(2) windows and interrogated using synchrotron-based radiation (SRS) Fourier-transform IR (FTIR) microspectroscopy. Spectra were analysed using principal component analysis (PCA) with or without linear discriminant analysis (LDA) to allow cluster analysis of the cell categories. A clear cell lineage emanating from SCs to TA cells to TD cells was noted in normal samples. Within the SCC samples, a small sub-population of the cell-derived spectra pointed to a SC-like phenotype with the vast majority pointing to a TA cell-like character; these cells would tend to be the most proliferative within a tissue. Our findings suggest that SRS FTIR microspectroscopy has the potential to identify and characterise cancer SCs.

Purpose: Corneal conjunctival squamous carcinoma is a rare form of slowly progressive carcinoma of low malignant potential. Mitomycin C (MMC) is a chemiotherapic antibiotic isolated from Streptomyces Caespitosus and medical literature reports efficacy of MMC in the treatment of squamous cell carcinoma. We present a case of conjunctival and corneal squamous cell carcinoma which was treated with both surgical excision and topical use of MMC 0.02%. Methods: A 78-year old man with a red-grey vascularized elevated epithelial lesion that started at the conjunctiva and extended past the corneoscleral limbus on to the cornea for about 1.5 mm. The patient was given surgical exeresis of the conjunctival neoformation and the histological exam highlighted a corneal conjunctival squamous cell carcinoma. after three monthes a recurrence of the neoformation was displayed and we therefore decided to start topical MMC 0.02% eye drops treatment four times daily for 7 days. Four cycles of treatment were done with a one-week interval during which only sodium hyaluronate 0.4% lubricant eye drops were administered. Results: During the period of treatment with the MMC 0.02% eye drops, the patient did not display any adverse systemic or ocular reactions. At the end of the treatment we found a complete regression of the disease. Twelve months after treatment he was without conjunctival and corneal epithelial dysplasia. Conclusions: This case highlights the efficacy of MMC 0.02% eye drops in the treatment of conjunctival and corneal squamous cell carcinoma that can avoid the topical use with sponge of MMC at higher concentration that it would present a not predictable long term effects on the conjunctival fornix and on lachrymal secretion.

Ocular tumors play an increasing concern in veterinary ophthalmology. Corneal squamous cell carcinoma is unfrequent in dogs, and by this way it has little studies. Studies that investigated the carcinogenesis mechanisms wich could help to the development of ocular squamous cell carcinoma (SCC) in dog are rare. The aim of this work was to identify by immunohistochemical techniques, the p53 protein expression in the spontaneous dog corneal SCC. For this work, were used five cases of corneal SCC and one case of actinic keratitis. The sections were obtained from paraffin-wax blocks and submitted to histopathological and immunohistochemical analysis. All the six samples showed immunolabeling to cytokeratin and p53 protein. These results support the conclusions that the immunoreactivity of p53 protein by immunohistochemistry is present in canine corneal SCC suppporting its role in carcinogenesis of this tumor, but not provides prognostic indicators in cases of SCC corneal in dog; and can be a association of exposure to solar radiation with the possible mutation of the TP53 gene.

WOS: 000241098900022 PubMed: 17011863 PURPOSE: To determine the efficiency of topical cyclosporine,A (CSA) combined with mitomycin C (MMC) as an adjunctive treatment in diffuse conjunctival and corneal squamous cell carcinoma (CCSC). DESIGN: Interventional case reports. METHODS: Two patients who had positive margins following surgical excision of CCSC were treated by topical CSA (0.05%) four times a day for 12 weeks, and topical MMC (0.01%) four times a day was combined with CSA at the second, fourth, and sixth weeks of the treatment. We controlled the tumor recurrence, vision, and ocular surface healing during the follow-up. RESULTS: There was no tumor recurrence during the follow up of 18 months. Limbal vascularization regressed considerably and the vision improved without any ocular surface problems in both patients. CONCLUSIONS: As an adjunctive treatment, topical CSA (0.05%) combined with MMC (0.01%), may prevent tumor recurrence and provide excellent ocular surface healing in diffuse CCSC.

In this paper, a case of corneal squamous cell carcinoma is reported. Invasive squamous cell carcinoma of the cornea is a rare disorder and has not been previously described in the Korean literature. In this case, the invasive squamous cell carcinoma of the cornea was treated by complete excision and cryotherapy. No evidence of metastasis or recurrence has been found since the procedure. Complete excision and adjunctive cryotherapy has become the treatment of choice because of the higher recurrence rate following a simple excision.

Twenty-one eyes with conjunctival and corneal squamous cell carcinoma underwent microscopically controlled, frozen section guided excisions. Fresh/M.K./glycerine- preserved donor corneas were used to cover the defect with a lamellar graft. No recurrence was seen over a mean follow up of 5.5 ± 2 years (range 1–15 years). Useful visual acuity of ≥ 6/24 was achieved in 67% of the eyes and no eye had astigmatism >4D at the end of 1 year. Poor visual acuity (