Detection of papillomaviral DNA sequences in a feline oral squamous cell carcinoma

Oral squamous cell carcinomas (OSCCs) are common and often fatal feline neoplasms. Factors that predispose to neoplasm development in cats are poorly defined. Around 25% of human OSCCs are caused by papillomaviruses (PVs). To determine if PVs are associated with OSCCs in cats, three sets of consensus primers were used to evaluate 20 feline OSCCs and 20 non-neoplastic feline oral lesions for the presence of PV DNA. Papillomaviral sequences were detected within one OSCC, but no non-neoplastic lesion. Sequencing of the amplified DNA revealed a previously unreported PV that was most similar to human PV type 76. This is the first time PV DNA has been amplified from the oral cavity of a cat. However, while these results suggest that feline gingival epithelial cells can be infected by PVs, they do not support a causal association between viral infection and the development of feline OSCCs.     

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.     

Demodex cati infestation in association with feline cutaneous squamous cell carcinoma in situ: a report of five cases

Demodex cati infestation was identified at lesional sites of multicentric squamous cell carcinoma in situ (Bowen's disease) in five elderly domestic shorthaired cats. Lesions were observed on the face, neck, shoulders, stifles and limbs. Deep skin scrapings taken from lesional skin contained D. cati eggs, larvae and adults in four cases. D. cati were discovered histologically in four cases. Histopathology of skin biopsy specimens confirmed the diagnosis of squamous cell carcinoma in situ in all cases. Serology for feline immunodeficiency virus (FIV) was positive in three cats. Remission of Bowen's disease lesions was obtained in 4–6 months using oral retinoids etretinate (one case) or acitretin (one case). It is suspected that local immunodeficiency due to epithelial dysplasia might have predisposed the skin to a focal multiplication of D. cati. Alternatively, FIV infection may have led to immune suppression predisposing the cats to both papillomavirus-induced epithelial dysplasia and D. cati infestation.     

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.     

Vulvar squamous cell carcinoma in situ within viral papillomas in an aged Quarter Horse mare

This report describes the diagnosis and treatment of vulvar papillomatosis with carcinoma in situ in a 25‐year‐old mare. Papillomavirus was demonstrated via immunohistochemical staining of biopsies of the lesion. The papillomas were removed via laser excision and the surrounding vulvar tissue injected with 5‐fluorouracil. Additional more extensive laser excisions were required due to recurrence.     

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.     

Corneal squamous cell carcinoma in a Border Collie

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.     

Evaluation of feline oral squamous cell carcinomas for p16 protein immunoreactivity and the presence of papillomaviral DNA

Oral squamous cell carcinomas (OSCCs) develop commonly in cats. While the cause of the feline neoplasms is unknown, a quarter of human OSCCs are caused by papillomavirus (PV) infection. As PV DNA has been previously detected in a feline OSCC, it was hypothesised that PV infection could be a significant cause of feline OSCCs. Human OSCCs that are caused by PVs contain increased p16^CDKN2A protein (p16), which can be detected using immunohistochemistry. In cats, increased p16 immunoreactivity has been reported within PV-associated skin lesions. This study evaluated p16 immunoreactivity within 30 feline OSCCs. Additionally, PCR was used to amplify PV DNA from the OSCCs. Increased p16 immunoreactivity was present within 2 OSCCs. However, as PV DNA was not amplified from any OSCC in this study, it cannot be confirmed that the increased p16 was caused by PV infection. Therefore, these results do not support the hypothesis that PVs are a significant cause of OSCCs in cats. Loss of p16 expression is considered an important process in the development of human non-PV-induced OSCCs. In contrast, loss of p16 immunoreactivity was only present in 2 feline OSCCs. This suggests that human and feline OSCCs develop due to different molecular mechanisms.     

A multi-institutional epidemiologic study evaluating environmental risk factors for feline oral squamous cell carcinoma

Feline oral squamous cell carcinoma (FOSCC) is an aggressive cancer in domestic cats that has no effective treatment option when advanced. Preventative or early diagnostic measures are thus crucial. FOSCC is also a model for human head and neck SCC (HNSCC); strong risk factors in HNSCC include exposure to alcohol, tobacco, areca nut, and high-risk human papillomavirus. Previous studies have identified flea collar and tobacco smoke exposure, feeding canned tuna, canned cat food and cat foods with chemical additives, living in a rural environment, and having outdoor access as risk factors for FOSCC but there was no overlap in the risk factors between studies. In our study, risks for FOSCC were evaluated in an online epidemiologic survey study in 67 cats with FOSCC and 129 control cats. Clumping clay cat litter and flea collar use were significant risk factors for FOSCC on multiple logistic regression with odds ratios of 1.66 (95% CI 1.20–2.30) and 4.48 (95% CI 1.46–13.75) respectively. Crystalline silica is a carcinogen that may be present in all clay cat litters and tetrachlorvinphos is a carcinogen that is present in the most commonly used flea collars in our study. We recommend further investigation into the association between FOSCC and clay-based litter and/or flea collars containing tetrachlorvinphos.     

Assessment of predictive molecular variables in feline oral squamous cell carcinoma treated with stereotactic radiation therapy

This study evaluated molecular characteristics that are potentially prognostic in cats with oral squamous cell carcinoma (SCC) that underwent stereotactic radiation therapy (SRT). Survival time (ST) and progression‐free interval (PFI) were correlated with mitotic index, histopathological grades, Ki67 and epidermal growth factor receptor expressions, tumour microvascular density (MVD), and tumour oxygen tension (pO₂). Median ST and PFI were 106 and 87 days, respectively (n = 20). Overall response rate was 38.5% with rapid improvement of clinical symptoms in many cases. Patients with higher MVD or more keratinized SCC had significantly shorter ST or PFI than patients with lower MVD or less keratinized SCC (P = 0.041 and 0.049, respectively). Females had significantly longer PFI and ST than males (P ≤ 0.016). Acute toxicities were minimal. However, treatment‐related complications such as fractured mandible impacted quality of life. In conclusion, SRT alone should be considered as a palliative treatment. MVD and degree of keratinization may be useful prognostic markers.     

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.     

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.     

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.     

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.     

Photodynamic therapy for the treatment of periocular squamous cell carcinoma in horses: a pilot study

Objective  Local photodynamic therapy (PDT) is a novel cancer therapy in veterinary ophthalmology. A prospective pilot study seeking to demonstrate proof of principle and safety for the treatment of equine periocular squamous cell carcinoma (PSCC) was therefore conducted. We hypothesized that surgical excision with adjunctive local PDT is an effective and safe treatment for equine PSCC.
Procedures  Nine horses (10 eyes) with PSCC were treated with surgical resection, local infiltration of resulting wound beds with 2-[1-hexyloxyethyl]-2-devinylpyropheophorbide-a (HPPH) and irradiation with 665-nm wavelength diode laser. Regular follow-up ophthalmic examinations were performed.
Results  Surgical resection and PDT yielded disease-free intervals of 25–68 months in our study horses as of January, 2008. These results were obtained following a single treatment in seven horses and two treatments in one horse. In one horse, carcinoma in situ developed 2.5 months after partial surgical excision and PDT, requiring local excision under standing sedation.
Conclusions  Preliminary results suggest that surgical resection and adjunctive local PDT is a safe and effective novel treatment for PSCC in horses. More research is needed before PDT for the treatment of equine PSCC can be adequately compared with other current modalities. Important to future investigations regarding PDT, tumor recurrence rate, length of hospitalization, number of treatment episodes required to effect tumor remission, and total treatment costs should be examined in a controlled manner. Our present results and experiences suggest that this treatment may be useful in the treatment of equine PSCC.     

Evaluation of 18F‐FDG PET/CT as a diagnostic imaging and staging tool for feline oral squamous cell carcinoma

18F‐fluorodeoxyglucose positron emission tomography combined with computed tomography (18FDG‐PET/CT) has been shown to be effective for staging human oral squamous cell carcinoma (SCC) but its application for cats with oral SCC is unknown. Twelve cats with biopsy‐proven oral SCC were imaged with whole body 18FDG‐PET/CT to determine its value as a diagnostic imaging and staging tool and fine needle aspirates were obtained of accessible regional lymph nodes. All tumors were FDG avid and conspicuous on 18FDG‐PET/CT images, with an average of the maximum standardized uptake value 9.88 ± 5.33 SD (range 2.9–24.9). Soft tissue infiltrative tumors that were subtle and ill defined on CT were highly visible and more extensive on FDG‐PET/CT. Tumors invading the osseous structures were more similar in extent on 18FDG‐PET/CT and CT although they were more conspicuous on PET images. Three cytologically confirmed metastases were hypermetabolic on PET, while two of those metastases were equivocal on CT.     

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.