Corneal squamous cell carcinoma in a dog: a case report

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.     

Corneal squamous cell carcinoma in two dogs

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.     

Piroxicam and carboplatin as a combination treatment of canine oral non-tonsillar squamous cell carcinoma: a pilot study and a literature review of a canine model of human head and neck squamous cell carcinoma

Results of the treatment with a combination of carboplatin and piroxicam in seven dogs with advanced non‐tonsillar oral squamous cell carcinoma (SCC) were retrospectively analysed. This multi‐agent protocol was well tolerated by all dogs and resulted in a complete regression of the tumour without additional surgery in four of seven patients. Additional surgery was necessary to remove a metastatic lymph node in one dog and residual tumour in a second dog, which achieved a partial response following medical therapy. Median follow‐up for all the dogs was 534 days, while the time‐to‐recurrence, time‐to‐progression and overall survival for this group of patients have not yet been reached. Our study, although limited in number of animals, suggests that this multiagent approach is a useful treatment option for oral non‐tonsillarSCC in dogs and warrants wider application.     

Co-existing squamous cell carcinoma and hemangioma on the ocular surface of a cat

A 14-year-old spayed female domestic short-haired cat was presented for evaluation of a mass in the right eye. Ophthalmic examination revealed a blind right eye and presence of two distinct masses: a pink and a red-to-brown mass, the latter occupying most of the cornea and part of the conjunctiva. Exenteration was performed under general anesthesia, and the ocular tissues were processed routinely for histopathology. Upon microscopic examination, a malignant epithelial neoplasm and a benign vascular neoplasm were present in the cornea. The conjunctiva and the third eyelid were also affected. Upon immunohistochemistry, the epithelial tumor was positive for cytokeratin and negative for vimentin and the endothelial tumor was negative for cytokeratin and positive for vimentin. A diagnosis of squamous cell carcinoma (SCC) and hemangioma was made. The SCC was affecting the cornea, bulbar conjunctiva (lateral and inferior) and the base of the third eyelid, whereas the hemangioma was affecting the cornea and medial limbus. To the authors' knowledge, this is the first report of concomitant SCC and hemangioma affecting the ocular surface in a cat.     

Superficial corneal squamous cell carcinoma occurring in dogs with chronic keratitis

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.     

The expression of calretinin and cytokeratins in canine acanthomatous ameloblastoma and oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) and canine acanthomatous ameloblastoma (CAA) represent two epithelium‐derived neoplasms that affect the oral cavity of dogs. The expression of cytokeratins (CKs) and calretinin has been previously established in the canine tooth bud and odontogenic tumours. The aim of this study was to characterize the CK and calretinin expression profile of OSCC in comparison to CAA and canine tooth bud tissues. Samples from 15 OSCC and 15 CAA cases, as well as 6 tooth buds and 2 normal gingival tissues were examined. OSCC CK expression was consistent with the CK expression profile of CAA and canine tooth bud tissue. Calretinin was positively expressed in 10 of 15 OSCC cases, with 5 cases demonstrating high staining intensity. Only 2 of 15 CAA cases demonstrated mild‐moderate staining intensity. The statistically significant difference in staining pattern and intensity of calretinin in OSCC and CAA can help distinguish between these two tumour types.     

Treatment of canine oral papillary squamous cell carcinoma using definitive‐intent radiation as a monotherapy—a case series

Canine oral papillary squamous cell carcinoma (COPSCC) is a rare neoplasm and although locally invasive it carries a favourable prognosis following wide surgical excision. Radiotherapy has been reported to be effective as an adjunct treatment to surgery. However, limited information is available on the role of radiotherapy as single treatment. This single‐institution retrospective study describes a series of 10 dogs diagnosed with macroscopic COPSCC that were treated with definitive‐intent radiotherapy (DRT) as a monotherapy. These dogs had a median age of 4 years (range: 0.4‐9.6 years). The tumour was located in the rostral oral cavity in all cases with a median tumour size of 2.5 cm (range: 0.8‐6.8 cm). No local or distant metastases were identified. All dogs were treated with electron beam DRT (>32Gy, 10‐16 daily fractions of 3.2Gy). The median follow‐up time was 961 days (range: 333‐3.498 days) with nine dogs achieving a complete response and one dog a partial response. The dog with the partial response developed disease progression at 228 days after initiation of radiotherapy. Two dogs died from non‐tumour‐related causes. The remaining seven dogs were still alive and in complete remission at the time of last follow‐up. Median progression‐free survival time and median survival time were not reached. DRT was generally well tolerated, but all dogs experienced self‐limiting acute radiation mucositis (grade 2‐3) and/or dermatitis (grade 1). No late radiation toxicity was observed. Macroscopic COPSCC appears to be a radiosensitive tumour that can be successfully treated with DRT eliminating the need for aggressive surgery in advanced cases.     

A retrospective comparison of surgical removal and subsequent CO2 laser ablation versus topical administration of mitomycin C as therapy for equine corneolimbal squamous cell carcinoma

Objective To compare the complications and nonrecurrence rate following topical mitomycin C (MMC) therapy vs. CO₂ laser ablation for treating equine corneolimbal squamous cell carcinoma (SCC). Study design Retrospective study. Sample population Twenty‐five horses with corneolimbal SCC. Procedures Medical records of horses undergoing surgical tumor resection followed by either topical MMC therapy (0.04%) or CO₂ laser ablation between the years of 2004 and 2010 were reviewed. Recurrence and complications were compared between groups and within MMC subgroups defined by the time at which treatment was initiated relative to surgery. Results Therapy with topical MMC resulted in a nonrecurrence rate comparable to that achieved with CO₂ laser ablation (82.4% vs. 85.7%, respectively). Initiation of MMC following epithelialization of the surgical site a mean of 15 days postoperatively did not result in increased recurrence rates relative to treatment in the immediate postoperative period. Vision‐ or globe‐threatening complications tended to occur with greater frequency in horses receiving topical MMC in the immediate postoperative period (5 of 6 major complications) relative to following epithelialization of the surgical site (1 of 6 major complications). Conclusions Horses receiving adjunctive topical MMC therapy were no more likely to experience tumor recurrence than were horses undergoing CO₂ laser ablation in the horses in this study. Initiation of two to three rounds of MMC following epithelialization of the surgical site results in fewer major complications and achieves comparable disease resolution relative to treatment in the immediate postoperative period.     

Resection cystoplasty of a squamous cell carcinoma in a mare

A 22‐year‐old Arabian mare was examined for evaluation of haematuria of 2 months' duration. Complete blood cell count and chemistry revealed anaemia of chronic disease (i.e. normocytic, normochromic) and hypoproteinaemia. Cystoscopy revealed a haemorrhagic mass protruding into the lumen of the urinary bladder in the apical region. The mass was surgically removed by partial cystectomy performed through a caudal ventral midline laparotomy. Histological examination of the mass confirmed the diagnosis of squamous cell carcinoma. Tumours of the equine urinary bladder are rare, and when a partial cystectomy is indicated, a caudal ventral midline laparotomy may provide adequate surgical exposure even in adult horses.     

Multiple skeletal metastases from a penile squamous cell carcinoma in a horse

A 21‐year‐old gelding with ventral abdominal and preputial oedema was evaluated for right hindlimb lameness. Partial phallectomy had been performed 3 years prior for treatment of squamous cell carcinoma. Regional analgesia did not localise the source of lameness and nuclear scintigraphy was recommended. The results of the scan revealed severe increased radiopharmaceutical uptake in the proximal femur. Radiographic and ultrasound examinations were inconclusive. The horse was discharged with recommendations of stall confinement and a 2 week course of nonsteroidal anti‐inflammatory drugs. Four weeks later the horse presented for an inability to elevate his neck and persistent hindlimb lameness. The owner elected humane euthanasia. Post mortem examination revealed metastatic squamous cell carcinoma in the proximal femur and fifth cervical vertebrae consistent with metastasis from the penile squamous cell carcinoma. To the authors’ knowledge, multiple site bone metastasis of squamous cell carcinoma has not been reported previously in the horse.     

Primary corneal melanocytoma in a Collie

A 6‐year‐old female, spayed Collie was referred to the Western College of Veterinary Medicine for a 12‐month history of a progressive right corneal mass. A superficial keratectomy was performed and histopathology revealed a corneal melanocytoma with complete excision. There has been no recurrence of the neoplasm to date (12 months). This is the first known report of an isolated corneal melanocytoma in a canine.     

Hemangiosarcoma and squamous cell carcinoma in the third eyelid of a horse

A 12-year-old Belgian draft horse presented for a right eye third eyelid mass and red-tinged ocular discharge of 3 months' duration. The third eyelid was excised and submitted for histopathology. On histopathologic examination, the mass was composed of both hemangiosarcoma and squamous cell carcinoma. The horse developed thickened eyelids and hemorrhagic ocular discharge from the right eye approximately 16 months following surgery, and was euthanized. Necropsy and histopathology confirmed local recurrence and regional metastasis of the hemangiosarcoma. This was an unusual case because there were two distinct neoplastic processes composing the same mass that could not be differentiated grossly.     

Pigmented squamous cell carcinoma of the conjunctiva of a horse

Abstract A heavily pigmented tumor was removed from the lateral, perilimbal, bulbar conjunctiva of a bay Thoroughbred horse. Excision was incomplete and the base of the tumor was lasered on the assumption that the tumor was a melanoma. No other ophthalmic lesions were seen. Histology showed the mass to be a pigmented squamous cell carcinoma (SCC). The prognosis and recommended treatment protocols are different for SCC and melanoma. This is, to the best of our knowledge, the first report of an ocular, pigmented SCC in the veterinary literature.     

Hypoglycemia associated with disseminated metastatic tonsillar squamous cell carcinoma producing insulin‐like growth factor‐I in a Pomeranian dog

A 13‐year‐old spayed female Pomeranian dog was presented for persistent, severe hypoglycemia (37 mg/dL; reference interval [RI] 75‐128 mg/dL). Progressive nonregenerative anemia (hematocrit 23.3%‐15.9%; RI 37.0%‐55.0%) and severe thrombocytopenia (36 000/µL; RI 200‐500 000/µL) were also noted. The serum insulin concentration was low (0.24 ng/mL; RI 0.302‐1.277 ng/mL). Computed tomography revealed multiple splenic nodules (1‐6 mm in diameter) and several hepatic nodules (7.6, 12 mm in diameter). Ultrasound‐guided fine‐needle aspiration of the splenic and hepatic nodules revealed low numbers of epithelial cells with mild cellular atypia, suggestive of a metastatic epithelial tumor, but the primary site was unknown at that time. On careful oral examination under general anesthesia, an enlarged right tonsil was noted grossly, and histopathologic examination of the tonsil diagnosed squamous cell carcinoma. Bone marrow aspirates and biopsies of the splenic and hepatic nodules were performed; all samples were diagnosed as metastatic carcinoma on histopathologic examination. No nodules were present in the pancreas, despite careful palpation during exploratory laparotomy. On immunohistochemistry, the neoplastic cells were positive for cytokeratin AE1/3 and insulin‐like growth factor (IGF)‐I but were negative for chromogranin A, PGP9.5, insulin, and inconclusive for IGF‐II. This is the first report of a primary IGF‐I‐producing squamous cell carcinoma in the tonsil of a dog with metastases to bone marrow, liver, and spleen, resulting in hypoglycemia.     

Topical 5-fluorouracil as an adjunct treatment in equine corneolimbal squamous cell carcinoma

An 11-year-old crossbreed mare was presented with a nodular, pink mass at the temporal corneolimbal junction of the right eye. Histopathology confirmed the diagnosis of invasive squamous cell carcinoma. The mare underwent lamellar keratectomy and conjunctivectomy under general anaesthesia, followed by adjunctive topical chemotherapy with 1% 5-fluorouracil solution for 10 days post-operatively. Adverse effects included moderate conjunctival inflammation and exuberant granulation tissue formation at the surgical site, responding to surgical debulking and topical corticosteroid application. No mass regrowth was present at 12 months following discharge. This report describes the successful use of topical 1% 5-FU as an adjunctive treatment for equine ocular squamous cell carcinoma.     

Neoadjuvant chemoradiotherapy and surgery as treatment for oral maxillary squamous cell carcinoma in a dog

A gingival maxillary squamous cell carcinoma was diagnosed in a 12-year-old male Yorkshire Terrier. After a complete diagnostic work-up, including a computed tomography scan, the tumour was staged as T3bN1aM0 and considered non-resectable at presentation. The combination of neoadjuvant megavoltage radiotherapy and neoadjuvant and adjuvant chemotherapy with carboplatin and doxorubicin decreased the size of the tumour, allowing for surgery. The dog was free from local disease for 421 days after which it was euthanased at the owners' request.