Squamous cell carcinoma (SCC) is a type of malignant tumor that arises from squamous epithelial cells, commonly affecting horses' skin, eyes, and mucous membranes. It is one of the most frequently diagnosed cancers in equine species. This carcinoma is associated with prolonged exposure to ultraviolet light, particularly in areas with minimal pigmentation or hair coverage. SCC can present as ulcerated lesions or proliferative masses and may lead to local tissue destruction and metastasis if untreated. Diagnosis typically involves clinical examination, biopsy, and histopathological analysis. Treatment options vary depending on the tumor's location and stage and may include surgical excision, cryotherapy, or chemotherapy. This section aggregates peer-reviewed studies and scholarly articles that explore the pathogenesis, risk factors, diagnostic methods, and treatment approaches for squamous cell carcinoma in horses.
Greenwood S, Chow-Lockerbie B, Ramsauer S, Wachoski-Dark G, Knight C, Wobeser B. papillomavirus type 2 (EcPV-2) has been recognized as a potential cause of a subset of genital squamous cell carcinomas (SCCs) in horses. In the current study, we measured EcPV-2 seropositivity in 50 healthy horses from Western Canada, and these were compared to a herd of horses with known EcPV-2 exposure. Second, the presence of EcPV-2 DNA was measured using EcPV-2-specific PCR (polymerase chain reaction), performed on a variety of tissues collected at necropsy from 70 horses that lacked any history, gross, or histologic evidence of neoplasia or papillomavirus-associated disease. EcPV-2-spec...
Greenwood S, Chow-Lockerbie B, Epp T, Knight C, Wachoski-Dark G, MacDonald-Dickinson V, Wobeser B.Equus caballus papillomavirus type-2 (EcPV-2) has been proposed as a causal factor in equine genital squamous cell carcinoma (SCC). This study had 2 objectives: first, calculate the frequency of papillomavirus (PV) and EcPV-2 infection in papillomas, carcinomas in situ (CIS), and SCCs in Western Canadian horses; and second, determine if EcPV-2 status of equine SCCs is associated with overall survival (OS). EcPV-2 status of 115 archived tissue samples, spanning 6 years, was determined using broad spectrum (MY09/11) and EcPV-2-specific polymerase chain reaction (PCR) assays, EcPV-2-E6/E7 chromog...
Peters-Kennedy J, Lange CE, Ortved K.Aural plaques are associated with and thought to be caused by one or more Equus caballus papillomaviruses (EcPV). Aural plaques have not previously been reported to be associated with squamous cell carcinoma (SCC). Objective: To describe a horse with aural plaques and squamous cell carcinoma (SCC) on the right pinna. Methods: A 28-year-old thoroughbred gelding presented for multiple plaques and a mass on the right pinna. Methods: Pinnal resection, histopathological investigation, multiple conventional PCRs for papillomavirus DNA and Sanger sequencing were performed. Results: Multiple, raised, ...
Bellone RR.Horses perform in a variety of disciplines that are visually demanding, and any disease impacting the eye has the potential to threaten vision and thus the utility of the horse. Advances in equine genetics have enabled the understanding of some inherited ocular disorders and ocular manifestations and are enabling cross-species comparisons. Genetic testing for multiple congenital ocular anomalies, congenital stationary night blindness, equine recurrent uveitis, and squamous cell carcinoma can identify horses with or at risk for disease and thus can assist in clinical management and breeding dec...
Porcellato I, Modesto P, Cappelli K, Varello K, Peletto S, Brachelente C, Martini I, Mechelli L, Ferrari A, Ghelardi A, Razzuoli E.In horses, squamous cell carcinomas (SCCs) are the most common malignant tumors developing on non-pigmented skin, muco-cutaneous areas, like external genitalia, and, less frequently, in the stomach. Growing evidence suggests Equus caballus papillomavirus type 2 (EcPV2) as causative agent of genital SCCs. Our case report describes a 20-year-old, female, mixed-breed pony with co-occurring vulvar papilloma and in situ carcinoma and gastric SCC. Both lesions were positive for the same EcPV2, as confirmed by DNA sequencing. E6 mRNA expression was observed both in vulvar lesions and gastric SCC, whi...
Arthurs C, Suarez-Bonnet A, Willis C, Xie B, Machulla N, Mair TS, Cao K, Millar M, Thrasivoulou C, Priestnall SL, Ahmed A.Equine penile squamous cell carcinoma (EpSCC) is a relatively common cutaneous neoplasm with a poor prognosis. In this study, we aimed to determine the protein expression and colocalisation of FRA1, c-Myc, Cyclin D1, and MMP7 in normal (NT), tumour (T), hyperplastic epidermis and/or squamous papilloma (Hyp/Pap), poorly-differentiated (PDSCC), or well-differentiated (WDSCC) EpSCC using a tissue array approach. Further objectives were to correlate protein expression to (i) levels of inflammation, using a convolutional neural network (ii) equine papillomavirus 2 (EcPV2) infection, detected using ...
Alloway E, Linder K, May S, Rose T, DeLay J, Bender S, Tucker A, Luff J.Squamous cell carcinoma (SCC) is the most common neoplasm of the equine stomach. However, the mechanisms underlying malignant transformation are unknown. As papillomavirus-2 (EcPV-2) is a likely cause of some genital SCCs, we hypothesized that EcPV-2 is associated with a subset of equine gastric SCCs. To this aim, we performed polymerase chain reaction (PCR) and in situ hybridization (ISH) for EcPV-2 E6/ E7 oncogenes on 11 gastric SCCs and on gastric samples from 15 control horses with no SCC. PCR for EcPV-2 was positive in 7/11 (64%) gastric SCCs; non-SCC gastric samples were all negative. I...
Ramsauer AS, Wachoski-Dark GL, Fraefel C, Tobler K, Brandt S, Knight CG, Favrot C, Grest P.There is growing evidence that equine papillomavirus type 2 (EcPV2) infection is causally associated with the development of equine genital squamous cell carcinomas (SCCs). Early stages of disease present clinically as plaques or wart-like lesions which can gradually progress to tumoural lesions. Histologically these lesions are inconsistently described as benign hyperplasia, papilloma, penile intraepithelial neoplasia (PIN), carcinoma in situ (CIS) or SCC. Guidelines for histological classification of early SCC precursor lesions are not precisely defined, leading to potential misdiagnosis. Th...
Singer-Berk MH, Knickelbein KE, Lounsberry ZT, Crausaz M, Vig S, Joshi N, Britton M, Settles ML, Reilly CM, Bentley E, Nunnery C, Dwyer A....Squamous cell carcinoma (SCC) is the most common periocular cancer in horses and the second most common tumor of the horse overall. A missense mutation in damage-specific DNA-binding protein 2 (DDB2, c.1012 C>T, p.Thr338Met) was previously found to be strongly associated with ocular SCC in Haflinger and Belgian horses, explaining 76% of cases across both breeds. To determine if this same variant in DDB2 contributes to risk for ocular SCC in the Arabian, Appaloosa, and Percheron breeds and to determine if the variant contributes to risk for oral or urogenital SCC, histologically confirmed SCC c...
Byron CR, DeWitt MR, Latouche EL, Davalos RV, Robertson JL.Irreversible electroporation is a proven ablation modality for local ablation of soft tissue tumors in animals and humans. However, the strong muscle contractions associated with the electrical impulses (duration, 50-100 μs) requires the use of general anesthesia and, in most situations, application of neuromuscular blockade. As such, this technology is not used in an outpatient setting for ablating common cutaneous tumors (e.g., squamous cell carcinoma or melanoma) in humans or animals. Recently, high-frequency irreversible electroporation (H-FIRE) technology has been developed to enable ele...
Hibi H, Hatama S, Obata A, Shibahara T, Kadota K.A case of laryngeal squamous cell carcinoma (SCC) and squamous papilloma in a 19-year-old Thoroughbred stallion is described. The animal exhibited severe wheezing caused by laryngopharyngeal stenosis. Histological examination identified laryngeal, laryngotracheal, and guttural pouch tumor masses consisting of areas of SCC. In the epiglottic lesion, the overlying epithelium was replaced by papilloma cells, and superficial cells frequently had nuclear inclusion bodies that expressed oncoprotein E6, which is characteristic of high risk human papillomaviruses. The papillomatous epithelium was cont...
Morrison ML, Groover E, Schumacher J, Newton J, Pereira MM.Squamous cell carcinoma (SCC) is one of the most common malignant neoplasms in horses, but lingual SCC has seldom been reported. On separate occasions, a 12-year-old American Quarter Horse mare and an 18-year-old American Saddlebred stallion were presented to the Auburn University Large Animal Teaching Hospital for evaluation of weight loss, dysphagia, and ptyalism. Evaluation of each horse included physical examination, skull radiographs, oral examination, complete blood count and serum biochemistry profile, endoscopic evaluation of the mouth, and biopsy of tissue from a lesion found on the t...
Ramsauer AS, Kubacki J, Favrot C, Ackermann M, Fraefel C, Tobler K.Equine papillomavirus type 2 (EcPV2) was discovered only recently, but it is found consistently in the context of genital squamous cell carcinomas (SCCs). Since neither cell cultures nor animal models exist, the characterization of this potential disease agent relies on the analysis of patient materials. To analyse the host and viral transcriptome in EcPV2-affected horses, genital tissue samples were collected from horses with EcPV2-positive lesions as well as from healthy EcPV2-negative horses. It was determined by RNA-seq analysis that there were 1957 differentially expressed (DE) host genes...
Knickelbein KE, Lassaline ME, Singer-Berk M, Reilly CM, Clode AB, Famula TR, Michau TM, Bellone RR.Belgian horses are commonly affected with ocular squamous cell carcinoma (SCC), the most common cancer of the equine eye. A missense mutation in damage-specific DNA binding protein 2 (DDB2 c.1013C>T, p.Thr338Met) has been established as a recessive genetic risk factor for ocular SCC in the Haflinger breed. A sample of Belgian horses with unknown SCC phenotype was shown to possess this variant at a similar frequency to the Haflinger breed. Retrospective studies indicate that chestnut coat colour may predispose to the development of SCC. Objective: To determine if DDB2 c.1013C>T is a risk ...
Bogedale K, Jagannathan V, Gerber V, Unger L.The aim of this study was to investigate microRNA (miRNA) differential expression in the two most common equine skin tumours, equine sarcoid (ES) and squamous cell carcinoma (SCC), and its potential influence on the tumour microenvironment at post-transcriptional level. We investigated miRNA fingerprints in four subgroups: mild (ESM) and aggressive (ESA) ES and ocular SCC (oSCC) and genital SCC (gSCC). Three tumours and three control samples were included in each of the four subgroups. Following next generation sequencing, miRNA differential expression analysis using DESeq2 was carried out. Pa...
Stein L, Sledge D, Smedley R, Kiupel M, Thaiwong T.A 15-y-old Miniature horse mare had a 6-mo history of an ulcerated mass on the right lower eyelid. An incisional biopsy and a subsequent excisional biopsy were submitted to the Michigan State University Veterinary Diagnostic Laboratory for microscopic evaluation. Histologically, the incisional biopsy was composed of sheets of large neoplastic vacuolated polygonal cells. A few regions contained poorly differentiated neoplastic round-to-basaloid cells that rimmed the sheets of highly vacuolated polygonal cells. Both vacuolated and basaloid cells exhibited strong perimembranous and cytoplasmic im...
Peters-Kennedy J, Lange CE, Rine SL, Hackett RP.Equus caballus papillomavirus 8, a recently discovered virus, has been reported to cause generalised papillomavirus in horses. Objective: To describe a case in which multiple viral plaques, viral papillomas, squamous cell carcinoma (SCC) in situ and invasive squamous cell carcinoma (ISCC) were associated with EcPV8 in a horse. Methods: Case report. Methods: A 16-year-old mixed breed horse presented with dozens of raised crusted papular to nodular lesions over a course of 4 years. Masses had been surgically excised four times and cisplatin beads and emulsion were implanted on three different ...
Jeanes EC, Koll-Hampp S, Dawson C, Dunkel B, Tetas Pont R.A rhomboid blepharoplasty can be used to achieve functional and cosmetic eyelid reconstruction at the medial canthus in the horse. Combination of a rhomboid blepharoplasty with cryotherapy is a treatment option for eyelid ocular squamous cell carcinomas.
Lee SK, Lee JK, Lee I.Equus caballus papillomavirus type 2 (EcPV-2) is implicated in genital neoplasms in horses, including equine penile papillomas, penile intraepithelial neoplasia, and squamous cell carcinoma (SCC). This virus seldom regresses spontaneously and can result in the development of SCC, which may result in significant clinical damage and economic cost. However, the prevalence of this virus is unknown in clinically unaffected horses. The aim of this study was to determine the prevalence of EcPV-2 DNA in genital swabs from healthy horses in the Republic of Korea and to investigate genetic variability w...
Knickelbein KE, Lassaline ME, Bellone RR.To document a case of limbal squamous cell carcinoma (SCC) in a Rocky Mountain Horse stallion determined to be homozygous for the genetic risk factor (DDB2 c.1013C>T) strongly associated with the disease in Haflinger and Belgian horses, and to determine the frequency of this allele in a larger population of Rocky Mountain Horses. Methods: One privately owned Rocky Mountain Horse and 84 Rocky Mountain Horses screened for allelic frequency. Methods: A complete ophthalmic examination was performed on a Rocky Mountain Horse stallion for assessment of a mass affecting the right eye. A clinical diag...
Singer-Berk M, Knickelbein KE, Vig S, Liu J, Bentley E, Nunnery C, Reilly C, Dwyer A, Drögemüller C, Unger L, Gerber V, Lassaline M, Bellone RR.Squamous cell carcinoma (SCC) is the most common cancer affecting the equine eye, with a higher incidence documented in Haflinger horses. Recently, a missense variant in the gene damage specific DNA binding protein 2 (DDB2, p.Thr338Met) on ECA12 was identified as a risk factor for the development of limbal SCC in Haflinger horses. SCC also occurs on the nictitating membrane; therefore, investigating the role of this missense variant in nictitating membrane SCC is warranted. In this study, a common ancestor was identified among Haflinger horses affected with limbal SCC or with nictitating membr...
Spugnini EP, Bolaffio C, Scacco L, Baldi A.A twenty-year-old female saddle horse was referred for evaluation of a seven month, non-healing erosive lesion of the right hind hoof with proliferation and bleeding of the underlying soft tissues. This lesion had been twice surgically treated as a canker but rapidly recurred. Histological examination of the second excision revealed a well-differentiated squamous cell carcinoma. At presentation, the horse was mildly depressed, lame and partially non-weight-bearing on the right hind leg, which exhibited a 10 x 10 cm erosive and proliferative lesion remodeling the hoof. After completing staging ...
Sykora S, Brandt S.Squamous cell carcinoma (SCC) is a common disease that seriously impairs the health and welfare of affected horses and other equids. In humans, almost all cervical carcinomas, a high percentage of anogenital SCCs and a subset of SCCs of the head and neck are caused by high-risk human papillomavirus (hrHPV) infection. Since hrHPV-induced human cancers and equine SCC have similar cytological and histopathological features, it has been hypothesised that equine SCCs could also be induced by papillomaviruses. This review provides an overview of the current evidence for an aetiological association b...
Bellone RR, Liu J, Petersen JL, Mack M, Singer-Berk M, Drögemüller C, Malvick J, Wallner B, Brem G, Penedo MC, Lassaline M.Squamous cell carcinoma (SCC) is the most common cancer of the equine eye, frequently originating at the limbus, with the potential to invade the cornea, cause visual impairment, and result in loss of the eye. Several breeds of horses have a high occurrence of limbal SCC implicating a genetic basis for limbal SCC predisposition. Pedigree analysis in the Haflinger breed supports a simple recessive mode of inheritance and a genome-wide association study (N = 23) identified a 1.5 Mb locus on ECA12 significantly associated with limbal SCC (Pcorrected = 0.04). Sequencing the most physiologicall...
Sykora S, Jindra C, Hofer M, Steinborn R, Brandt S.In horses, squamous cell carcinomas (SCC) commonly affect the external genitals. There is growing evidence that equine papillomavirus type 2 (EcPV2) infection promotes disease development. To assess the possible association of EcPV2 with equine SCCs of the head (HSCC), 15 HSCC DNA samples were screened by E6/E7, E2, and LCR PCR and amplicons were analysed for sequence variations. The physical form of EcPV2 in HSCC, genital lesions, and smegma from horses with SCC was then addressed using EcPV2 immunocapture PCR (IC/PCR) for detection of virion, and E6 vs. E2 qPCR to investigate possible integr...
Davis CR, Valentine BA, Gordon E, McDonough SP, Schaffer PA, Allen AL, Pesavento P.A diagnosis of neoplasia was noted in 125 of 357 donkeys (35%) in our review of medical records from 5 veterinary schools in the United States and Canada. Equine sarcoid was the most common tumor in our study, accounting for 72% of all tumors and 82% of cutaneous tumors. Soft-tissue sarcomas were the second most common skin tumors. All other types of neoplasia were rare. Important differences in the occurrence of neoplasia in donkeys compared to horses included the rarity or absence of squamous cell carcinoma in any organ system and gray horse melanoma. Lymphosarcoma, the most common malignant...
Schellenbacher C, Shafti-Keramat S, Huber B, Fink D, Brandt S, Kirnbauer R.The consistent and specific presence of Equus caballus papillomavirus type 2 (EcPV2) DNA and mRNA in equine genital squamous cell carcinoma (gSCC) is suggestive of an etiological role in tumor development. To further validate this concept, EcPV2-neutralizing serum antibody titers were determined by an EcPV2 pseudovirion (PsV) neutralization assay. Furthermore, an EcPV2 L1 virus-like particle (VLP)-based vaccine was generated and its prophylactic efficacy evaluated in vivo. All 6/6 gSCC-affected, but only 3/20 tumor-free age-matched animals revealed EcPV2-neutralizing serum antibody titers by P...
Miller MA, Moore GE, Bertin FR, Kritchevsky JE.Postmortem findings in 241 equids admitted to a teaching hospital that were at least 15 years old at autopsy were reviewed (1) to determine disease prevalence, (2) to compare the cause of death (or euthanasia) in equids 15 to 19 years of age (n = 116) with that in equids ≥20 years of age (n = 125), and (3) to catalog coexisting lesions in equids with pituitary pars intermedia dysfunction (PPID). Breed and sex were evenly distributed between the age groups. Death or euthanasia was attributed to disease of the digestive system (41.5%), pituitary gland (12.9%), locomotor system (10.0%), nervous...
Zhu KW, Affolter VK, Gaynor AM, Dela Cruz FN, Pesavento PA.Equus caballus papillomavirus 2 (EcPV2) has been proposed as an etiologic agent for genital squamous cell carcinoma (SCC), the most common malignant tumor of the horse penis. EcPV2 is commonly detected by polymerase chain reaction (PCR) on normal horse genitalia; therefore, unraveling the virus' role in oncogenic transformation requires other methods of detection. In this study, a highly sensitive multiple-probe chromogenic in situ hybridization (ISH) technique was designed to recognize the E6/E7 oncogenes of EcPV2. ISH demonstrated abundant virus within 6 of 13 penile and preputial SCCs, wher...
Knowles EJ, Tremaine WH, Pearson GR, Mair TS.Survey data on equine tumours are sparse compared with other species and may have changed over time. Objective: To describe the most frequently diagnosed equine tumours recorded by a diagnostic pathology laboratory over 29 years, to identify background factors associated with tumour type, and to identify any changes in the tumours diagnosed or the background of cases submitted during the study period. Methods: Observational; cross-sectional analysis of records of a diagnostic pathology laboratory. Methods: The records of all neoplastic equine histology submissions to the University of Bristol ...
Alloway E, Linder K, May S, Rose T, DeLay J, Bender S, Tucker A, Luff J.Squamous cell carcinoma (SCC) is the most common neoplasm of the equine stomach. However, the mechanisms underlying malignant transformation are unknown. As papillomavirus-2 (EcPV-2) is a likely cause of some genital SCCs, we hypothesized that EcPV-2 is associated with a subset of equine gastric SCCs. To this aim, we performed polymerase chain reaction (PCR) and in situ hybridization (ISH) for EcPV-2 E6/ E7 oncogenes on 11 gastric SCCs and on gastric samples from 15 control horses with no SCC. PCR for EcPV-2 was positive in 7/11 (64%) gastric SCCs; non-SCC gastric samples were all negative. I...
Pascoe RR, Summers PM.The results of a retrospective survey of tumours and tumour-like lesions encountered in horses in a veterinary practice in south east Queensland between 1956 and 1978 are presented. Forty-two per cent of the lesions were examined histologically. The most commonly occurring neoplasms were the equine sarcoid, papilloma and squamous cell carcinoma of the eye and external genitalia. Neurofibroma was an important problem in the eyelid region. Intra-abdominal tumours were rarely encountered in this series.
Lassaline M, Cranford TL, Latimer CA, Bellone RR.To describe the prevalence of LSCC in Haflinger horses and to analyze affected horses' pedigrees investigating the genetic mode of inheritance. Methods: Fifteen horses met inclusion criterion of (i) being of the Haflinger breed, as confirmed by North American Haflinger Registry pedigree and (ii) being diagnosed with LSCC, as confirmed by clinical examination by a veterinary ophthalmologist or by histopathology. Pedigrees could not be obtained for four additional horses diagnosed with LSCC that had been identified as Haflingers. Methods: Retrospective medical record review of all 19 horses was ...
Mair TS, Walmsley JP, Phillips TJ.The medical records of 45 horses treated for suspected squamous cell carcinoma of the penis and/or prepuce were reviewed. The age of 40 horses was known, and these had a mean age of 17.4 years. The duration of neoplasia was known for only 3 of the 45 horses. The results of histological evaluation of lesions, available for 35 horses, confirmed that the diseased tissue was squamous cell carcinoma. The location of gross neoplastic lesions was recorded for 43 horses; the glans penis was involved in 24 horses, the body of the penis or the inner lamina of the preputial fold in 27 horses, and the ext...
Greenwood S, Chow-Lockerbie B, Epp T, Knight C, Wachoski-Dark G, MacDonald-Dickinson V, Wobeser B.Equus caballus papillomavirus type-2 (EcPV-2) has been proposed as a causal factor in equine genital squamous cell carcinoma (SCC). This study had 2 objectives: first, calculate the frequency of papillomavirus (PV) and EcPV-2 infection in papillomas, carcinomas in situ (CIS), and SCCs in Western Canadian horses; and second, determine if EcPV-2 status of equine SCCs is associated with overall survival (OS). EcPV-2 status of 115 archived tissue samples, spanning 6 years, was determined using broad spectrum (MY09/11) and EcPV-2-specific polymerase chain reaction (PCR) assays, EcPV-2-E6/E7 chromog...
Gionfriddo JR, Gionfriddo JP, Krohne SG.To identify ocular and adnexal diseases to which llamas in North America are susceptible, to determine prevalence of these diseases in llamas, and to compare prevalences of the major ocular diseases of llamas, cattle, and horses. Methods: Retrospective study. Methods: 194 llamas, 4,937 cows, and 11,950 horses with ocular disease. Methods: Medical records of all llamas entered into the Veterinary Medical Database between 1980 and 1993 were reviewed. Data on ocular structures affected and types of ocular disease were compiled. Prevalences of uveitis, corneal ulcers, and ocular squamous cell carc...
Sironi G, Riccaboni P, Mertel L, Cammarata G, Brooks DE.The expression of p53 protein was investigated in eight formalin-fixed, paraffin-embedded conjunctival squamous cell carcinomas of five horses and one cow, dog and cat each by an immunohistochemical procedure in order to evaluate protein overexpression. Anti-human p53 protein mouse monoclonal antibodies known to be cross-reactive with p53 protein of the animal species examined were used. Positive p53 nuclear immunostaining was detected in five equine, one bovine and one feline cases. Conversely, no p53 immunostaining was found in the only canine case examined. These results demonstrate a frequ...
Strafuss AC.In a review of neoplasm registry records at Kansas State University (1961 through 1971), 58 squamous cell carcinomas were reported in 10 breeds of horses. Mean age of the affected horses was 12.4 years. The head, eye and ocular adnexa accounted for 43.1%, the external male genitalia, 44.8%, and female perineal region, 12.0% of the squamous cell carcinomas, altogether representing 20.2% of 287 neoplasms recorded.
Schwink K.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.
van den Top JG, Harkema L, Lange C, Ensink JM, van de Lest CH, Barneveld A, van Weeren PR, Gröne A, Martens A.Equine penile and preputial squamous cell carcinoma (SCC) is a potentially lethal disease of which little is known regarding the relationship between tumour characteristics and prognosis. Objective: To assess the relationship between tumour differentiation grade (tumour subtype), presence of papillomaviruses, expression of viral genes (E2, E6, L1), nuclear proteins p53 and Ki67 and metastasis in equine penile and preputial SCC and to assess the relationship of tumour subtype, presence of papillomavirus type 2, p53 and Ki67 with survival. Methods: Retrospective case-control study using archived...
Singer-Berk M, Knickelbein KE, Vig S, Liu J, Bentley E, Nunnery C, Reilly C, Dwyer A, Drögemüller C, Unger L, Gerber V, Lassaline M, Bellone RR.Squamous cell carcinoma (SCC) is the most common cancer affecting the equine eye, with a higher incidence documented in Haflinger horses. Recently, a missense variant in the gene damage specific DNA binding protein 2 (DDB2, p.Thr338Met) on ECA12 was identified as a risk factor for the development of limbal SCC in Haflinger horses. SCC also occurs on the nictitating membrane; therefore, investigating the role of this missense variant in nictitating membrane SCC is warranted. In this study, a common ancestor was identified among Haflinger horses affected with limbal SCC or with nictitating membr...
De Ridder T, Ruppin M, Wheeless M, Williams S, Reddell P.Tigilanol tiglate is a novel small molecule approved as a veterinary pharmaceutical in Europe for intratumoural treatment of non-metastatic, non-resectable canine mast cell tumors. The drug has a "tumor agnostic" mode of action associated with induction of an acute inflammatory response at the treatment site, immune cell recruitment, and disruption of tumor vasculature. Consequently, tigilanol tiglate has potential in treating a range of tumor types in humans and companion animals. However, it is likely that species-specific dosing and concomitant medication protocols will be required, especia...
Knickelbein KE, Lassaline ME, Singer-Berk M, Reilly CM, Clode AB, Famula TR, Michau TM, Bellone RR.Belgian horses are commonly affected with ocular squamous cell carcinoma (SCC), the most common cancer of the equine eye. A missense mutation in damage-specific DNA binding protein 2 (DDB2 c.1013C>T, p.Thr338Met) has been established as a recessive genetic risk factor for ocular SCC in the Haflinger breed. A sample of Belgian horses with unknown SCC phenotype was shown to possess this variant at a similar frequency to the Haflinger breed. Retrospective studies indicate that chestnut coat colour may predispose to the development of SCC. Objective: To determine if DDB2 c.1013C>T is a risk ...
McCauley CT, Hawkins JF, Adams SB, Fessler JF.To determine outcome of horses in which cutaneous masses were removed with a carbon dioxide laser. Methods: Retrospective study. Methods: 32 horses. Methods: Medical records of horses with 1 or more cutaneous masses treated with a carbon dioxide laser were examined. Follow-up information was obtained through telephone interviews with owners and referring veterinarians. Results: Cutaneous masses were classified as sarcoids (15 horses), neoplastic masses other than sarcoids (squamous cell carcinoma [91; fibroma [1]; and melanoma [1]), and nonneoplastic masses (6). Minimum follow-up time was 6 mo...
Newkirk KM, Hendrix DV, Anis EA, Rohrbach BW, Ehrhart EJ, Lyons JA, Kania SA.Squamous cell carcinoma (SCC) is the most common tumor arising in the periocular and penile areas of horses. Both ultraviolet radiation and papillomaviruses have been implicated in the pathogenesis of SCC in various species, including the horse. This retrospective study used polymerase chain reaction (PCR) to detect papillomavirus DNA in archival biopsy samples from equine periocular and penile SCC from 3 different geographic areas (northeast, southeast, and central United States). Forty-two periocular SCCs were tested; none contained papillomavirus DNA. Twenty-two penile SCCs were tested, and...
Bogedale K, Jagannathan V, Gerber V, Unger L.The aim of this study was to investigate microRNA (miRNA) differential expression in the two most common equine skin tumours, equine sarcoid (ES) and squamous cell carcinoma (SCC), and its potential influence on the tumour microenvironment at post-transcriptional level. We investigated miRNA fingerprints in four subgroups: mild (ESM) and aggressive (ESA) ES and ocular SCC (oSCC) and genital SCC (gSCC). Three tumours and three control samples were included in each of the four subgroups. Following next generation sequencing, miRNA differential expression analysis using DESeq2 was carried out. Pa...
Kainzbauer C, Rushton J, Tober R, Scase T, Nell B, Sykora S, Brandt S.In January 2010, 18 months after excision of an ocular squamous cell carcinoma (SCC), a Connemara mare presented with anorexia and periorbital/parotideal lesions. Post mortem examination revealed these lesions as forming one entity, with 2 additional growths in the retropharyngeal region and the left jugular groove, respectively. The lesions were confirmed histopathologically as SCCs. Using PCR, peripheral blood mononuclear cells (PBMCs) from 2008 and 2010, tumour tissue, intact skin and vulval mucosa were screened for Equus caballus papillomavirus type 2 (EcPV-2) and bovine papillomavirus typ...
Bogaert L, Willemsen A, Vanderstraeten E, Bracho MA, De Baere C, Bravo IG, Martens A.Squamous cell carcinoma (SCC) represents the most common genital malignant tumor in horses. Similar to humans, papillomaviruses (PVs) have been proposed as etiological agents and recently Equine papillomavirus type 2 (EcPV2) has been identified in a subset of genital SCCs. The goals of this study were (1) to determine the prevalence of EcPV2 DNA in tissue samples from equine genital SCCs, penile intraepithelial neoplasia (PIN) and penile papillomas, using EcPV2-specific PCR, (2) to examine the prevalence of latent EcPV2 infection in healthy genital mucosa and (3) to determine genetic variabili...
Cotchin E.Published figures from veterinary schools indicate that tumours may account for about 1 to 3 per cent of surgical cases. In this paper an account is given of clinical and pathological aspects of the tumours that are most likely to be encountered in practice, either as visibly or palpably detectable masses of tissue, or as internal tumours responsible for clinical signs. Amongst the common and important tumours dealt with, the most prominent are "equine sarcoid", squamous-cell carcinoma (of eye region and of glans penis), granulosa-cell tumours and melanomas. Well over a hundred references prov...
Steinbach F, Bischoff S, Freund H, Metzner-Flemisch S, Ibrahim S, Walter J, Wilke I, Mauel S.Dendritic cells (DCs) are antigen-presenting cells, which are well known for their capacity to stimulate immunity. The ex vivo generation of myeloid DC from monocytes has facilitated the development of DC-vaccination protocols which have been extensively evaluated in tumour immunology and are regarded by some as a gold mine for clinical research. However, there is a considerable amount of work required to overcome the potential risks associated with such therapy. It is therefore mandatory to characterize the system to be applied and to study the reactions, particularly at the level of T cell r...
Baker JR, Leyland A.In a histological survey of 244 tumerous growths from 155 horses, the tumours commonly found were fibromas, squamous cell carcinomas, sarcoids and papillomas, most frequently affecting the skin, external genitalia, eye and orbit. The histological features that differentiate fibroblastic citaneous growths are detailed so that the clinical behaviour of these distinct neoplasms can be studied.
Greenwood S, Chow-Lockerbie B, Ramsauer S, Wachoski-Dark G, Knight C, Wobeser B. papillomavirus type 2 (EcPV-2) has been recognized as a potential cause of a subset of genital squamous cell carcinomas (SCCs) in horses. In the current study, we measured EcPV-2 seropositivity in 50 healthy horses from Western Canada, and these were compared to a herd of horses with known EcPV-2 exposure. Second, the presence of EcPV-2 DNA was measured using EcPV-2-specific PCR (polymerase chain reaction), performed on a variety of tissues collected at necropsy from 70 horses that lacked any history, gross, or histologic evidence of neoplasia or papillomavirus-associated disease. EcPV-2-spec...
Théon AP, Pascoe JR.One hundred and fifteen horses with periocular tumours were treated with iridium-192 interstitial brachytherapy. Tumours included squamous cell carcinomas (n = 52) and sarcoids (n = 63). All horses were scheduled to receive 60 Gy (minimal tumour dose) given at a low dose rate (0.034 +/- 0.010 Gy/h). The mean and median follow-up times to last contact or death were 24 and 16 months, respectively. Chronic radiation reactions included palpebral fibrosis (10.4%), cataract (7.8%), keratitis and corneal ulceration (6.9%). Cosmetic changes included permanent epilation (21.7%) and hair dyspigmentation...
Ollivier FJ, Kallberg ME, Plummer CE, Barrie KP, O'Reilly S, Taylor DP, Gelatt KN, Brooks DE.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. Methods: 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 ...
Michau TM, Davidson MG, Gilger BC. To determine the complications and nonrecurrence rates following superficial lamellar keratectomy, bulbar conjunctivectomy, and adjunctive carbon dioxide (CO(2)) photoablation for corneolimbal squamous cell carcinoma (SCC) in the horse. Methods: Retrospective study. Sample population Twenty-four horses with corneolimbal SCC. Methods: Medical records of horses diagnosed with corneolimbal SCC that was surgically excised and where CO(2) photoablation was used as an adjunctive therapy from 2000 to 2007 were reviewed. Signalment, prior therapy, tumor location and size, complications,...
Murray MJ.Ulceration of the gastric squamous epithelial mucosa was induced in 10 horses using a feeding protocol previously shown to expose the gastric mucosa to repeated periods of high acidity. The feeding protocol consisted of alternating feed deprivation with free access to hay. Over a period of seven days, each horse was provided hay for 84 hr and deprived of hay for 84 hr. Hay was never withheld for longer than 24 hr at a time. Gastroscopy was performed on each horse at the beginning of the protocol after 12 hr of feed deprivation, and after a total of 36 hr, 60 hr, and 84 hr of feed deprivation. ...
Armando F, Godizzi F, Razzuoli E, Leonardi F, Angelone M, Corradi A, Meloni D, Ferrari L, Passeri B.Squamous cell carcinoma (SCC) is one of the most frequent tumors of skin and muco-cutaneous junctions in the horse. Equine papillomavirus type 2 (EcPV2) has been detected in equine SCC of the oral tract and genitals, and recently also in the larynx. As human squamous cell carcinoma of the larynx (SCCL), it is strongly etiologically associated with high-risk papillomavirus (h-HPV) infection. This study focuses on tumor cells behavior in a naturally occurring tumor that can undergo the so-called epithelial to mesenchymal transition (EMT). A SCCL in a horse was investigated by immunohistochemistr...
Mecocci S, Porcellato I, Armando F, Mechelli L, Brachelente C, Pepe M, Gialletti R, Passeri B, Modesto P, Ghelardi A, Cappelli K, Razzuoli E.Equine genital squamous cell carcinomas (egSCCs) are among the most common equine tumors after sarcoids, severely impairing animal health and welfare. papillomavirus type 2 (EcPV2) infection is often related to these tumors. The aim of this study was to clarify the molecular mechanisms behind egSCCs associated with EcPV2 infection, investigating receptor activator of nuclear factor-kappa B ligand (RANKL) signaling in NF-kB pathway, together with the Wnt and IL17 signaling pathways. We analyzed the innate immune response through gene expression evaluation of key cytokines and transcription fac...
Dugan SJ.Except for two neoplasms, notably SCC and sarcoid, ocular and periocular tumors are uncommon in horses. The practitioner must accurately determine the type of tumor by histopathology so appropriate treatment and a legitimate prognosis can be offered. The first attempt at treatment has the greatest chance to result in a cure; an aggressive treatment regimen therefore should be selected from the start.
McCue PM.Granulosa cell tumors of the ovary and SCC and melanoma of the external genitalia are the most common neoplasms in the mare. Tumors of the tubular reproductive tract and the mammary gland are rare.
