Delayed metastasis of ocular squamous cell carcinoma following treatment in five horses

Identification of regional and/or distant metastasis following treatment and local resolution of primary ocular squamous cell carcinoma (SCC) was observed in 5 horses. In all cases, identification of metastasis occurred at least 18 months following treatment of the primary ocular lesions. In 3 cases, invasion of blood or lymphatic vessels by neoplastic cells was identified in the excisional biopsies of the primary tumour. Two horses developed SCC at 2 or more separate sites. At the time metastases were identified, there was no evidence of local recurrence of the ocular tumour in any of the horses. These cases confirm the importance of long‐term monitoring of horses for metastatic disease following treatment of ocular SCC even in the absence of local recurrence.     

Effects of treatment with and without adjuvant radiation therapy on recurrence of ocular and adnexal squamous cell carcinoma in horses: 157 cases (1985-2002)

OBJECTIVE: To determine the effects of treatment with and without adjuvant radiation therapy on recurrence of ocular and adnexal squamous cell carcinoma (SCC) at specific anatomic locations in horses. DESIGN: Retrospective study. ANIMALS: 91 horses. PROCEDURES: Medical records of horses with histologically confirmed ocular and adnexal SCC evaluated from 1985 to 2002 were reviewed. Sex, breed, age, type of treatment, location, and recurrence of SCC were recorded. Two treatment groups determined by recurrence of SCCs treated with and without adjuvant radiation therapy were established. RESULTS: The anatomic site with the highest recurrence rate was the limbus (junction of the cornea and sclera) or bulbar conjunctiva (477%), independent of treatment group. There was a significant difference in recurrence rates of ocular and adnexal SCCs between the 2 treatment groups, independent of anatomic location. Recurrence rates of SCCs treated with and without adjuvant radiation therapy were 11.9% and 44.1%, respectively. Recurrence rates for SCCs of the eyelid, limbus or bulbar conjunctiva, and cornea treated with adjuvant radiation therapy were significantly different from those for SCCs treated without adjuvant radiation therapy. The most frequently represented anatomic site for ocular and adnexal SCCs was the eyelid (28.7%). Coat color, breed, and the interaction of age and breed had a significant effect on tumor recurrence regardless of treatment type and anatomic location. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that ocular and adnexal SCCs treated with adjuvant radiation therapy had a significantly lower recurrence rate, compared with SCCs treated without adjuvant radiation therapy, independent of anatomic location.     

Penile and preputial squamous cell carcinoma in the horse: a retrospective study of treatment of 77 affected horses

Reasons for performing study: The most common penile and preputial neoplasm in the horse is the squamous cell carcinoma (SCC), but no large surveys of treatment and effects of the grade of the tumour, based on the degree of differentiation, on outcome of affected horses are available. Objectives: Analysis of treatment of male horses affected with SCC of the external genitalia and long‐term results of treatment. Methods: Seventy‐seven cases of SCC were evaluated. Data recorded included treatment, outcome, post operative histopathology and retrospective tumour grading. Results: Treatments included: cryosurgery, excision, partial phallectomy, partial phallectomy and sheath ablation, and en bloc penile and preputial resection with penile retroversion and removal of inguinal lymph nodes. The incidence of recurrence after partial phallectomy was 25.6% (10/39) and following incomplete removal was 17.9% (7/39). The incidence of recurrence after en bloc resection with retroversion was 12.5% (1/8). In horses with confirmed inguinal lymph node metastasis, the incidence of recurrence was 25.0% (1/4). Poorly differentiated SCCs were more likely to metastasise than well differentiated SCCs, and there was a greater chance that the treatment would be unsuccessful. The success of treatment, complete removal and in preventing recurrence of the tumour, of male horses with SCC of the external genitalia was 55.7%. Conclusions: Horses that receive only partial phallectomy for treatment for SCC of the external genitalia have a high incidence of recurrence in contrast to horses that receive an en bloc resection. Tumour grading of SCC can help predict prognosis and guide selection of treatment.     

The use of mitomycin C as an adjunctive treatment for equine ocular squamous cell carcinoma

OBJECTIVE: To assess the effectiveness of topical mitomycin C application as an alternative adjunctive therapy to CO2 laser ablation in the treatment of equine ocular squamous cell carcinoma. DESIGN: A retrospective clinical study of eight client owned horses in which 10 affected eyes were treated for ocular squamous cell carcinoma over a 17 month period. (March 2003 to August 2004). PROCEDURE: Each horse was given a general anaesthetic to allow CO2 laser ablation of the lesion(s). Mitomycin C at a concentration of 0.4 mg/mL was then applied intraoperatively to the affected areas for 1 or 5 minutes. Postoperatively a triple antibiotic eye ointment was applied to the eye twice daily and each horse was treated with systemic non-steroidal anti-inflammatory drugs for 7 days. RESULTS: Recurrence following treatment was noted in three eyes. Two of these were retreated and no further signs developed. The remaining eye was enucleated at the request of the owner. Overall 90% of treated eyes appeared free of tumour a minimum of 11 months post treatment. CONCLUSION: In this case series mitomycin C appeared to offer a valid alternative to other adjunctive therapies currently employed in the treatment of equine ocular squamous cell carcinoma.     

Combined keratectomy, strontium-90 irradiation and permanent bulbar conjunctival grafts for corneolimbal squamous cell carcinomas in horses (1990-2002): 38 horses

OBJECTIVE: The purpose of this study was to evaluate the effectiveness of postoperative beta-irradiation with strontium-90 as an adjunctive treatment to superficial keratectomy and permanent bulbar conjunctival graft for removal of equine corneolimbal squamous cell carcinoma (SCC), in decreasing recurrence rate. STUDY: The retrospective case study included 38 horses diagnosed and treated for SCC of the eye that involved the limbus and/or cornea. The patients were treated between 1990 and 2002, with strontium-90 irradiation immediately after corneal and conjunctival graft surgery. Recurrence was defined as the postoperative and postirradiation regrowth of SCC in the same site and globe that was previously treated. RESULTS: The Appaloosa was the most commonly represented breed and horses that had more than one base coat color represented the majority of the cases (53%). The coat colors of white, chestnut/sorrel and gray were the most commonly represented colors of the horses treated. Eight horses (21%) could not be assessed for tumor recurrence due to lack of two or more post-treatment examinations, and another horse was enucleated 6 days postoperatively due to progressive corneal ulceration. Twenty-four horses (63% of the entire study population; 83% of the followed cases) had a mean +/- SD of 1754 +/- 1319 days without tumor recurrence, ranging from 14 days to 5110 days. Five horses (13% of the entire study population; 17% of the assessed horses) had tumor recurrence at a mean +/- SD of 449 +/- 339 days with a range of 29 days to 900 days. For the five recurrences, treatment included local excision (n = 1), enucleation (n = 2), and additional strontium-90 therapy (n = 3). CONCLUSIONS: The combination of superficial keratectomy, beta-irradiation and permanent bulbar conjunctival grafts for limbal, corneal or corneolimbal SCC in horses is effective in at least 83% of the horses. Recurrence occurred in about 17% of the horses. Multiple biannual re-examinations are recommended to observe for tumor recurrence.     

Challenges in the treatment of equine periocular squamous cell carcinoma

Management of periocular squamous cell carcinoma is challenging because of the need for adjunctive therapy, the adverse effects of therapies and the frequent recurrence of SCC. Appropriate treatment of equine ocular SCC usually involves surgical excision combined with adjunctive therapy selected as appropriate for the anatomic site of the lesion. Metastasis of periocular SCC has been reported to occur in approximately 6–15% of cases. The horse owner should be carefully educated to understand that for best long‐term results from the treatment of periocular SCC, they must be diligent in observing signs of recurrence or metastasis and be willing to have the horse examined as soon as adverse signs are observed. Furthermore, external beam radiation may be effective in the treatment of metastatic SCC and further clinical studies of this treatment modality are needed.     

Amniotic membrane transplantation for corneal surface reconstruction after excision of corneolimbal squamous cell carcinomas in nine horses

OBJECTIVE: The purpose of this study was to evaluate the usefulness and effectiveness of permanent amniotic membrane transplantation as an adjunctive treatment to superficial keratectomy alone or combined with strontium-90 irradiation for treatment of equine corneolimbal squamous cell carcinoma (SCC) to decrease corneal scarring and recurrence rate. STUDY: The retrospective case study included 11 horses (n = 12 eyes) diagnosed and treated for ocular SCC that involved the limbus and cornea. Nine of those horses (n = 9 eyes) were treated between 2002 and 2006, with superficial lamellar keratectomy alone or combined with strontium-90 irradiation and followed by placement of a permanent amniotic membrane graft in the surgical defect. The level of scarring (i.e. the clarity of the cornea) resulting with the use of amniotic membrane was subjectively compared to cases where a permanent bulbar conjunctival graft was performed following keratectomy combined with strontium-90 irradiation or cryotherapy (n = 3 eyes). Recurrence was defined as the postoperative and postirradiation regrowth of SCC in the same site and globe. RESULTS: The nine horses that received an amniotic membrane graft after keratectomy alone or combined with irradiation showed a minimal level of scarring in a cornea that regained a greater transparency in comparison to the horses that were treated with a bulbar conjunctival graft. All of the horses that received an amniotic membrane graft had 226 +/- 218 days of follow-up without tumor recurrence (mean +/- SD), ranging from 21 days to 778 days. CONCLUSIONS: The combination of superficial keratectomy alone or associated with beta-irradiation and permanent amniotic membrane transplantation is an effective treatment of corneal or corneolimbal SCC in horses. The placement of an amniotic membrane material represents an alternative surgical procedure to bulbar conjunctival grafts, especially if there is a lack of bulbar conjunctiva tissue available after tumor resection or if a particularly large corneal resection is necessary. The amniotic membrane is incorporated into the corneal defect and seems to create noticeably much less scarring than a corneal defect covered by bulbar conjunctiva.     

Factors influencing morbidity and outcome of equine ocular squamous cell carcinoma

A retrospective review of 41 cases of equine ocular squamous cell carcinoma with follow up information for 33 horses is presented. An apparent prevalence in heavy horse breeds was identified. Age and sex distribution were similar to those previously reported. High recurrence (42.4 per cent) and low metastasis (6 per cent) rates were seen. Initial tumour location, primary treatment used, or patient case history had no apparent influence on final outcome. The willingness of owners to pursue with continuous treatment correlated with a high degree of success.     

Prognostic factors and survival of horses with ocular/adnexal squamous cell carcinoma: 147 cases (1978-1988)

Between January 1978 and December 1988, 147 horses with ocular/adnexal squamous cell carcinoma (SCC) were admitted to the Colorado State University Veterinary Teaching Hospital (CSU-VTH). Diagnosis was confirmed by histologic examination of appropriate tissue specimens. Medical records and communication with owners, referring veterinarians, or both provided information regarding initial examination, treatment at the CSU-VTH, and final outcome. At initial examination, 123 (83.7%) horses had unilateral involvement and 24 (16.3%) horses had bilateral involvement. The nictitating membrane, nasal canthus, or both (28.1%); limbus (27.5%); and eyelid (22.8%) were most commonly affected. In addition to the ocular/adnexal location, SCC was found elsewhere in 14 (9.5%) horses at initial examination. Adequate follow-up (greater than or equal to 4 months) for examination of tumor recurrence and survival analysis was obtained for 125 (85.0%) cases. After treatment at the CSU-VTH, tumor recurred in 30.4% of the cases. Tumor location, multiple vs single tumors at initial diagnosis, and CSU-VTH treatment modality influenced the recurrence of tumors. Survival analysis revealed a good prognosis for horses with ocular/adnexal SCC. Although undefined, a conservative estimate of the median survival time was 47 months. Six factors (treatment prior to referral, tumor location, tumor size, single or multiple tumors, treatment modality at the CSU-VTH, and recurrence or nonrecurrence) were analyzed to determine their relation with survival. Treatment prior to referral, multiple vs single tumors at initial examination, and treatment modality used at the CSU-VTH did not influence survival. Tumor location influenced survival; SCC involving the eyelid or orbit was associated with the poorest prognosis. Tumor stage (maximal dimension) was inversely related with survival.(ABSTRACT TRUNCATED AT 250 WORDS)     

A Review of Current Treatment Options in the Treatment of Ocular and/or Periocular Squamous Cell Carcinoma in Horses: Is There a Definitive “Best” Practice?

This review examines the most commonly reported treatment options for ocular squamous cell carcinoma (OSCC) and periocular squamous cell carcinoma (POSCC) in horses and proposes to conclude on the most viable method based on available published studies in terms of treatment outcome, known side effects, advantages, disadvantages, and reliability of available evidence. After a literature search for peer-reviewed published articles, seven most commonly reported on treatments for OSCC and/or POSCC were identified: surgery, photodynamic therapy, carbon dioxide (CO₂) laser ablation, radiofrequency hyperthermia, cryotherapy, chemotherapy, and radiation therapy. Combination therapies were supported as a most successful recommendation; however, when considering site-specific outcomes, the following conclusions may be drawn: limbal squamous cell carcinoma (SCC) was most effectively treated with surgery and adjunctive therapy including CO₂ laser ablation, mitomycin C, and brachytherapy; third eyelid SCC reported good outcomes when treated with surgery alone (clear margins) and in combination with brachytherapy for unclear margins; eyelid SCC, surgical resection was usually limited and most reports supported the use of adjunctive brachytherapy, although photodynamic therapy appeared to be a promising new treatment. It was deemed unreasonable to conclude on the best treatment for cornea, conjunctivae (palpebral and bulbar), and medial canthi in isolation because of lack of evidence. A consistently favored treatment for OSCC and/or POSCC in horses does not currently exist. The presentation of data in the literature and its lack of consistency make it impossible to statistically analyze and make comparative conclusions on treatment outcomes. This review provides a basis for further research to establish a best-practice protocol.     

Preliminary results of maxillectomy in the dog and cat

Maxillectomy was used in the treatment of 23 dogs and four cats with oral tumours and one dog with osteomyelitis. The major post-operative complication was wound dehiscence. All dehiscences occurred in dogs with tumour epicentres caudal to PM¹. Maxillectomy in eight dogs with oral fibrosarcoma gave disappointing results (median survival time of 7 months and a median tumour-free interval of 3½ months). Three of four dogs with squamous cell carcinoma were tumour free after a minimum follow-up period of 6 months; two of these dogs received orthovoltage radiation therapy following surgery. Maxillectomy provided excellent local control of benign tumours: three epulides and one atypical odontogenic tumour did not recur (minimum follow-up period was 10 months); an osteoma recurred after 17 months. Four cats, three with squamous cell carcinoma and one with fibrosarcoma, developed local tumour recurrence within 4 months.     

Tattooing of the Equine Eyelid: A Retrospective Study

In this retrospective study, medical records of 26 horses whose eyelids were tattooed were analyzed, and data regarding age, breed, eyelid pigment, eye color, sex, and reproductive status of the horses were compiled. Owners of the horses were contacted by telephone and questioned about their horses. Twenty-six horses were tattooed at Colorado State University (CSU), and one of them was tattooed twice. Records were available for 26 horses, and follow-up results by telephone were completed for 22 of those. Telephone follow-up times ranged from 3 months to 17 years after tattooing. American Paint Horses constituted 62% (16/26) of the cases, followed by Appaloosas (19% = 5/26), and Quarter Horses (8% = 2/26). In 100% (22/22) of cases, the reason for presenting the horse for a tattoo was lack of periocular pigmentation. Only two horses developed ocular or periocular squamous cell carcinoma (SCC) after their tattoos. Although the results of this study suggest that tattooing may be protective against SCC and solar blepharitis, it is by no means conclusive. However it appears to have no deleterious effects, and often owners like the appearance of the tattooed eyelid.     

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.     

Multimodal therapeutic approach and interdisciplinary challenge for the treatment of unresectable head and neck squamous cell carcinoma in six cats: a pilot study

Feline head and neck squamous cell carcinoma (SCC) is a loco‐regional disease harbouring a poor prognosis. The complex anatomic location precludes aggressive surgical resection and tumours recur within weeks to few months. Response to chemotherapy and local control after radiation therapy has been disappointing. In this study, a multimodal approach including medical treatment (thalidomide, piroxicam and bleomycin), radiation therapy (accelerated, hypofractionated protocol) and surgery was attempted in six cats. Treatment was well tolerated. Three cats with sublingual SCC were alive and in complete remission at data analysis closure after 759, 458 and 362 days. One cat with laryngeal SCC died of renal lymphoma after 51 days and the other with maxillary SCC died of a primary lung tumour 82 days after diagnosis. In both cats, the SCC was in complete remission. Only one cat developed metastases after 144 days. These encouraging preliminary results merit further evaluation in future trials.     

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.     

Xenotransplantation of cryopreserved equine squamous cell carcinoma to athymic nude and SCID mice

Cryopreserved equine ocular squamous cell carcinoma (SCC) was inoculated subcutaneously into 15 athymic nude and 15 SCID mice. Xenotransplantation resulted in tumor growth in two athymic nude mice and 1 SCID mouse. Histological appearance and immunohistochemical characterization using cytokeratin 5/6 markers and p53 markers of the tumor grown in mice was in full accord with the original equine tumors. No evidence of metastasis was noted in any mouse. This model may serve as a relevant in vivo model for studying the biology of equine ocular SCC and for the testing of new therapeutic modalities.     

Metastatic synovial cell sarcoma in two cats

Synovial cell sarcoma (SCS) with metastasis to the regional lymph node was diagnosed in two cats. Synovial cell sarcomas are rare in cats and metastatic SCS has not previously been reported. In both cases, treatment consisted of limb amputation and adjuvant doxorubicin. Local tumour recurrence and pulmonary metastases were diagnosed in one cat 316 days postoperatively. This cat died of chronic renal failure 444 days after limb amputation. The second cat died of an acute pulmonary thromboembolism 41 days postoperatively without evidence of local tumour recurrence or metastatic disease.     

Xenotransplantation of cryopreserved equine squamous cell carcinoma to athymic nude and SCID mice

Cryopreserved equine ocular squamous cell carcinoma (SCC) was inoculated subcutaneously into 15 athymic nude and 15 SCID mice. Xenotransplantation resulted in tumor growth in two athymic nude mice and 1 SCID mouse. Histological appearance and immunohistochemical characterization using cytokeratin 5/6 markers and p53 markers of the tumor grown in mice was in full accord with the original equine tumors. No evidence of metastasis was noted in any mouse. This model may serve as a relevant in vivo model for studying the biology of equine ocular SCC and for the testing of new therapeutic modalities.     

Prevalence of ophthalmic disease in blue‐eyed horses

A perception exists amongst referring veterinarians and the lay public that blue‐eyed horses have increased frequency of ocular disease. The aim of this retrospective study was to assess the prevalence of ocular disease in horses with blue or heterochromic eyes relative to those with brown eyes. The medical records of horses presenting to either the Comparative Ophthalmology services or Equine Medicine/Surgery services at 2 institutions were reviewed. Signalment, ocular and nonocular diagnoses were recorded. Ocular disease was divided into 4 categories: adnexa, cornea, intraocular/orbit and squamous cell carcinoma (SCC). Owners were contacted by telephone to confirm iris colour. Chi‐square analysis was used to compare group proportions. A total of 164 eyes of horses with ocular disease and 212 eyes of horses without ocular disease were included. Blue eyes were equally common in the ocular disease and nonocular disease groups (P = 0.265). There was no significant difference in the proportion of blue‐ and brown‐eyed horses when comparing the adnexal and corneal (P = 0.548), corneal and intraocular/orbit (P = 0.379) and adnexal and intraocular/orbit (P = 0.843) categories. A significant difference was detected in the proportion of blue‐eyed horses between the adnexal (P = 0.000), corneal (P = 0.033), intraocular/orbital (P = 0.000) and SCC categories, with a higher proportion of blue‐eyed horses in the SCC than in the other 3 groups. Horses with blue or heterochromic irides are more likely to develop ocular SCC than horses with brown irides, but are not more likely to have adnexal, corneal or intraocular/orbital disease or to be presented for evaluation of ophthalmic disease. Veterinarians should consider the results of this study when answering questions from the lay public regarding the predisposition of blue‐eyed horses to ocular disease.     

Marjolin’s Ulcer in Two Horses with Hereditary Equine Regional Dermal Asthenia

Two Quarter Horse mares with hereditary equine regional dermal asthenia (HERDA) were diagnosed with metastatic squamous cell carcinoma (SCC) associated with chronic nonhealing wounds. The lesions were similar to the development of SCC from chronic nonhealing ulcers, known as Marjolin’s ulcers in humans. The horses showed recurrent skin wounds in the saddle and paralumbar regions and were confirmed by molecular techniques as having HERDA. Both horses were maintained as research animals for prolonged periods and received regular veterinary care and wound treatment. Both horses were ultimately euthanized because of their chronic progressive wounds, coupled with declining health. At necropsy, the nonhealing wounds were found to be complicated by infiltrative SCC; both horses had metastasis to lungs. Chronically inflamed, recurrent skin wounds that heal slowly and incompletely as a consequence of HERDA are proposed as a major pathogenetic factor in tumorigenesis. Consistent findings with respect to proliferation index (Ki-67) and mutations of p53 tumor suppressor gene were confirmed by immunohistochemistry in one horse. SCC consistent with Marjolin’s ulcer has been previously suggested in association with chronic ulcers or burn scars in horses, but this is the first report of an association with chronic poor healing wounds in HERDA horses.