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.
Ramsauer AS, Wachoski-Dark GL, Fraefel C, Ackermann M, Brandt S, Grest P, Knight CG, Favrot C, Tobler K.There is growing evidence that equine papillomavirus type 2 (EcPV2) infection is etiologically associated with the development of genital squamous cell carcinoma (SCC) and precursor lesions in equids. However, the precise mechanisms underlying neoplastic progression remain unknown. To allow the study of EcPV2-induced carcinogenesis, we aimed to establish a primary equine cell culture model of EcPV2 infection. Three-dimensional (3D) raft cultures were generated from equine penile perilesional skin, plaques and SCCs. Using histological, molecular biological and immunohistochemical methods, rafts...
Porcellato I, Mecocci S, Brachelente C, Cappelli K, Armando F, Tognoloni A, Chiaradia E, Stefanetti V, Mechelli L, Pepe M, Gialletti R, Passeri B....In horses, penile squamous cell carcinomas (epSCCs) are among the most common cutaneous neoplastic lesions. These tumors usually arise in benign lesions such as viral plaques and papillomas frequently induced by papillomavirus type 2 (EcPV2) infection. In the last decade, the introduction of immune checkpoint inhibitors (ICI) for the treatment of human cancers has demonstrated promising results. Among the most commonly targeted pathways, there is PD-1/PD-L1 and CTLA-4. The aim of this study is to investigate the expression of the PD-1/PD-L1 pathway and CTLA-4 in the tumor microenvironment of ...
Abu-Seida AM, Wafy MN, Hassan EA, Ahmed KA.Ocular neoplasms represent 10% of all equine neoplasms and ocular squamous cell carcinoma (OSCC) is the most common one. This report describes the clinical presentation, laboratory, ultrasonography, postmortem, histopathology and immunohistochemistry findings of a mixed ocular neoplasm in a 10-year-old draft mare. The mare had a one-year history of left ocular mass. Complete destruction of the left eye with loss of vision was observed. A large ulcerated mass oozing blood replaced the left eye. Left parotid lymph node was swollen and had a sinus tract discharging pus. Ultrasonography revealed a...
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...
Keenan AV, Townsend WM.To describe the clinical use of ultrasound biomicroscopy (UBM) to evaluate equine corneal disease. Methods: Images were obtained using a 50-MHz probe ultrasound biomicroscopy system (Quantel Aviso) and Clear Scan® probe cover. Six horses with corneal disease were evaluated via UBM for lesion size, lesion depth, and continuity of Descemet's membrane. Horses were sedated and received auriculopalpebral nerve blocks and application of topical anesthetic prior to UBM. Results: Ultrasound biomicroscopy was easily performed in all cases. UBM evaluation of three cases of corneo-limbal squamous cell c...
Veado HC, Silva AS, Fagundes JLA, Bittencourt AA, de Castro MB, Câmara ACL.Skin lesions are among the leading diseases in equids, and the urogenital region is considered the third most frequently affected body location with tumors and tumor-like skin lesions in horses. Tumor-like skin lesions or multiple tumors of different types in the equine prepuce and penis are a challenging clinical presentation leading to misdiagnosis and subsequent ineffective treatment. An 18-year-old 395-kg male mixed-breed gelding was referred for evaluation of preputial enlargement. Clinical examination revealed a 2.5 × 2.0 × 0.8 cm proliferative ulcerated lesion on the penile mucosa...
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...
Crausaz M, Launois T, Smith-Fleming K, McCoy AM, Knickelbein KE, Bellone RR.Squamous cell carcinoma (SCC) is the most common cancer affecting the equine eye. A missense variant within the gene damage-specific DNA binding protein 2 (DDB2 c.1013C>T, p.Thr338Met) was previously identified as a causal recessive genetic risk factor for the development of ocular SCC within Haflingers, Belgian Draft horses, and Rocky Mountain Horses, but not in the Appaloosa or Arabian breeds. This study aimed to evaluate three cases of ocular SCC in additional breeds and determine if DNA testing for the DDB2 variant in warmblood horses and Connemara ponies is warranted. Histopathology confi...
Raś A, Otrocka-Domagała I, Raś-Noryńska M.Genital malignant neoplasms in mares are relatively rare. The treatment involve surgical removal of the tumour masses, chemotherapy or both. Methods: Two elderly warmblood mares, aged 16 and 20 were presented in University Clinic with the lumpy lesions at the region of perineum and left labia. Surgical removals of tumour masses were performed on standing animals. Removed tissues were subjected to histopathological examination which confirmed SCC. Conclusions: Clinical and ultrasound examination of reproductive organs in both mares showed no inflammatory or neoplastic changes. Both mares healed...
Strohmayer C, Klang A, Kneissl S.Squamous cell carcinoma (SCC) is the most common equine sinonasal and feline oral tumour. This study aimed to describe the computed tomographic and histopathological characteristics of equine and feline SCC. Thirteen horses and 10 cats that had been histopathologically diagnosed with oral or sinonasal SCC and had undergone computed tomography (CT) of the head were retrospectively included in the study. CT characteristics of the mass and involved structures were noted. Histological examinations were evaluated according to a human malignancy grading system for oral SCC, which considered four gra...
DNA repairNovember 12, 2020
Volume 97 103022 doi: 10.1016/j.dnarep.2020.103022
Chen L, Bellone RR, Wang Y, Singer-Berk M, Sugasawa K, Ford JM, Artandi SE.Squamous cell carcinoma (SCC) occurs frequently in the human Xeroderma Pigmentosum (XP) syndrome and is characterized by deficient UV-damage repair. SCC is the most common equine ocular cancer and the only associated genetic risk factor is a UV-damage repair protein. Specifically, a missense mutation in horse DDB2 (T338M) was strongly associated with both limbal SCC and third eyelid SCC in three breeds of horses (Halflinger, Belgian, and Rocky Mountain Horses) and was hypothesized to impair binding to UV-damaged DNA. Here, we investigate DDB2-T338M mutant's capacity to recognize UV lesions in ...
Porcellato I, Mecocci S, Mechelli L, Cappelli K, Brachelente C, Pepe M, Orlandi M, Gialletti R, Passeri B, Ferrari A, Modesto P, Ghelardi A....Penile squamous cell carcinomas (SCCs) are common tumors in older horses, with poor prognosis mostly due to local invasion and recurrence. These tumors are thought to be mainly caused by papillomavirus type 2 (EcPV-2). The aim of this study is to characterize the tumor immune environment (TIME) in equine penile tumors. Equine penile epithelial tumors (17 epSCCs; 2 carcinomas , CIS; 1 papilloma, P) were retrospectively selected; immune infiltrate was assessed by histology and immunohistochemistry; RT-qPCR tested the expression of selected chemokines and EcPV-2 DNA and RNA. The results confirme...
Morandi L, Sabattini S, Renzi A, Rigillo A, Bettini G, Dervas E, Schauer A, Morandi M, Gissi DB, Tarsitano A, Evangelisti S, Tonon C.Ultra-conserved non-coding elements (UCNEs) are genomic sequences that exhibit > 95% sequence identity between humans, mammals, birds, reptiles, and fish. Recent findings reported their functional role in cancer. The aim of this study was to evaluate the DNA methylation modifications of UNCEs in squamous cell carcinoma (SCC) from different mammal species. Fifty SCCs from 26 humans, 17 cats, 3 dogs, 1 horse, 1 bovine, 1 badger, and 1 porcupine were investigated. Fourteen feline stomatitis and normal samples from 36 healthy human donors, 7 cats, 5 dogs, 5 horses, 2 bovines and 1 badger were c...
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...
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...
Mosunic CB, Moore PA, Carmicheal KP, Chandler MJ, Vidyashankar A, Zhao Y, Roberts RE, Dietrich UM.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. Methods: Retrospective study. Methods: 91 horses. Methods: 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 ...
Teifke JP, Löhr CV.One hundred and six squamous cell carcinomas (SCCs) of cattle, horses, cats and dogs were analysed immunohistochemically for overexpression of p53 protein. The monoclonal antibody pAb 240, which recognizes only mutant p53, was used. Of 41 bovine ocular SCCs, 26 (63.4%) showed p53 nuclear reactivity. All of six (100%) equine ocular SCCs and seven of nine (77.7%) SCCs of the equine penis or vulva gave positive reactions. In nine of 11 (81.8%) feline SCCs of the ear and in seven of 14 (50%) feline SCCs of other locations, p53 immunoreactivity was detected. Only seven of 25 (29.5%) canine cutaneou...
Armando F, Mecocci S, Orlandi V, Porcellato I, Cappelli K, Mechelli L, Brachelente C, Pepe M, Gialletti R, Ghelardi A, Passeri B, Razzuoli E.Equine penile squamous cell carcinoma (epSCC) is the most frequent tumor of the external male genitalia, representing 67.5% of equine genital cancers. epSCC is associated with papilloma virus (PV) infection and has been recently proposed as a model for human PV-induced squamous cell carcinomas. It has already been suggested that epSCC might undergo epithelial-to-mesenchymal transition (EMT). This work aims to investigate in detail this process and the possible role of PV oncoproteins in epSCC. For this purpose, 18 penile SCCs were retrospectively selected and tested for both EcPV2 presence and...
Torres SM, Koch SN.This article reviews various aspects of 3 clinical disorders associated with papillomavirus in horses commonly known as classical viral papillomatosis, genital papillomas/papillomatosis, and aural plaques. Classical papillomatosis is usually asymptomatic and spontaneously resolves within 1 to 9 months; therefore, treatment is often not required. Genital papillomas/papillomatosis have not been reported to spontaneously resolve, and there is increasing evidence that genital papillomas may evolve to in situ or invasive squamous cell carcinomas. Horses with aural plaques may be asymptomatic or may...
Théon AP, Pascoe JR, Carlson GP, Krag DN.Twenty horses with 30 lesions were studied to evaluate the effects of intratumoral chemotherapy with cisplatin in sesame oil on equine sarcoids (n = 19), squamous cell carcinomas (n = 7), and squamous cell papillomas (n = 4). Treatment consisted of 4 sessions of intratumoral cisplatin chemotherapy at 2-week intervals. A controlled-release formulation of cisplatin in sesame oil was used to limit drug egress from the injection site. Mean dosage per session was 0.97 (+/- 0.17, SEM) mg of cisplatin/cm3 of tumor tissue treated for tumor volumes ranging from 10 to 20 cm3. Dosage tended to be slightl...
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...
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...
Taylor SD, Haldorson GJ, Vaughan B, Pusterla N.Gastric neoplasia of horses is incompletely described. Objective: Provide history, clinical signs, and clinicopathological and pathological findings associated with gastric neoplasia in horses. Methods: Twenty-four horses with gastric neoplasia. Methods: Retrospective study. History, clinical signs, and clinicopathological and pathologic findings in horses diagnosed histologically with gastric neoplasia were reviewed. Results: Horses ranged in age from 9 to 25 years (median 18 years at presentation). There was no apparent breed or sex predisposition. The most common presenting complaints were ...
King TC, Priehs DR, Gum GG, Miller TR.The records of 50 horses with ocular squamous cell carcinoma (OSCC) presented to the University of Florida Veterinary Medical Teaching Hospital over an 11 year period were reviewed to determine the influence of therapy on the outcome of the case. Follow-up information was obtained for 43 of the 50 cases. The disease was more prevalent in the light horse breeds; however, the draft breeds also were at risk. There was no sex predisposition and the average age was 11.8 years. Tumour recurrence was significant when surgery alone was performed. The eyelid and nictitating membrane were the primary si...
Murray DR, Ladds PW, Campbell RS.Lesions encountered in a clinicopathological study of cutaneous lesions resembling 'swamp cancer' from horses in North Queensland included 37 cases of subcutaneous phycomycosis, 5 of which were also infected with Habronema sp larvae. In addition 9 cases of primary cutaneous habronemiasis, 58 sarcoids, 12 fibromas, 8 fibrosarcomas, 10 squamous cell carcinomas, 4 haemangiomas, 3 melanomas, 1 papilloma, 1 palpebral adenocarcinoma and 7 cases of simple granulation were diagnosed. Subcutaneous phycomycosis resulted in the most extensive lesions. These were rapidly growing and provided the poorest p...
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 ...
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...
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...
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...
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...
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...
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. ...
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...
Fischer NM, Favrot C, Birkmann K, Jackson M, Schwarzwald CC, Müller M, Tobler K, Geisseler M, Lange CE.The DNA of equine papillomavirus type 2 (EcPV2) is consistently found in equine papillomas and squamous cell carcinomas, indicating a causal association of EcPV2 in the pathogenesis of these tumours; however, little is known about the prevalence of this virus. Objective: The aim of this study was to determine the geno- and seroprevalence of EcPV2 in clinically healthy horses in Switzerland. Methods: Fifty horses presented to the equine department of the university clinic, displaying no skin or mucous membrane lesions or severe signs of other diseases, were sampled. Methods: Cytobrush samples ...
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...
