Tumors in horses are abnormal growths of tissue that result from uncontrolled cell division. They can be benign or malignant and may affect various tissues and organs within the equine body. Common types of tumors in horses include sarcoids, melanomas, and squamous cell carcinomas. The presence and progression of tumors can impact a horse's health, performance, and quality of life. Diagnosis often involves clinical examination, imaging techniques, and histopathological analysis. This page compiles peer-reviewed research studies and scholarly articles that explore the types, diagnosis, treatment options, and prognostic factors associated with tumors in equine medicine.
Brodesser DM, Kummer S, Eichberger JA, Schlangen K, Corteggio A, Borzacchiello G, Bertram CA, Brandt S, Pratscher B.The ability of human melanoma cells to switch from an epithelial to a mesenchymal phenotype contributes to the metastatic potential of disease. Metalloproteinases (MPs) are crucially involved in this process by promoting the detachment of tumor cells from the primary lesion and their migration to the vasculature. In gray horse melanoma, epithelial-mesenchymal transition (EMT) is poorly understood, prompting us to address MP expression in lesions versus intact skin by transcriptome analyses and the immunofluorescence staining (IF) of gray horse tumor tissue and primary melanoma cells. RNAseq re...
Lardone E, Landi A, Franci P.During electrochemotherapy (ECT), a chemotherapeutic drug is injected into the tumor and then an electroporation is provided. In horses, ear manipulation may be very painful, and combining a loco-regional technique with sedation might be a good option to avoid anesthesia-related risks. A two-injection-point block of the internal and external pinna and acoustic meatus was described in horse cadavers, and it permitted complete stain of all three branches of the great auricular nerve (GAN), internal auricular nerve branch (IAB), lateral auricular branch (LAB), and caudal auricular nerve (CAN), su...
Singh A, Johnson T, Wotman K, Leary D.Veterinary personnel exposure due to scattered x rays, when present during superficial radiation treatment (SRT), was evaluated. Veterinary personnel presence is needed during SRT to minimize the degree of required aesthesia to horses. Animal treatment was simulated, and exposure rates determined for 50, 70, and 100 kV x rays using eight different SRT applicators. Exposure rates at the surface of a solid water phantom (SWP) phantom ranged from 3.9 mR h-1 to 396 mR h-1 for 50 kV, from 41 mR h-1 to 2,880 mR h-1 for 70 kV, and from 235 mR h-1 to 7,500 mR h-1, for 100 kV, respectively. A horse pha...
Pereira R, Gillespie S, Rapezzano G, Withers J, Duz M, Foote A.A 15-month-old, grey, Thoroughbred filly presented for investigation of a 6-week history of corneal oedema and blepharospasm on the right eye (OD). The filly was otherwise healthy. Following ophthalmic examination, glaucoma on the OD was diagnosed. A space occupying mass within the anterior chamber was documented on transpalpebral ultrasonographic examination. This mass obliterated most of the anterior intraocular structures on the peripheral nasal side (corneal endothelium and drainage angle), leading to secondary glaucoma. After systemic and topical treatment addressing secondary glaucoma, t...
Blohm KO, Nell B.A 17-year-old Appaloosa mare was referred for evaluation of presumed refractory keratitis of the left eye. Gross examination revealed ocular discomfort and corneal neovascularization with a nasal focal opacification affecting approximately 40% of the corneal surface. On ophthalmic examination, extensive subepithelial to mid-stromal vascular branching accompanied by a homogeneous white, dense opacification, which affected up to 80% of the total corneal thickness, were apparent. Signs of concurrent uveitis were absent. Deep-stromal lamellar keratectomy with a conjunctival pedicle graft was perfo...
Pimenta J, Prada J, Pires I, Cotovio M.Equine melanomas are a common neoplasm in gray horses. However, scientific knowledge about their progression over time is quite scarce. Some owners and veterinarians still believe that early intervention is not necessary, stating that tumors evolve very slowly and intervention could worsen the animal's condition. This work aims to identify clinical and histological differences that may exist between equine melanomas with different excision intervals (time between tumor detection and surgical excision). A total of 42 tumors (13 benign and 29 malignant) from 34 horses were included in this study...
Barrantes Murillo DF, Cattley RC, Cullen JM, Withers C, Towns J, Pfeifle R, Wooldridge A, Neto RLALT.A 17-y-old Arabian mare was presented to the Auburn Large Animal Veterinary Teaching Hospital with a long-term history of intermittent mild recurrent colic that responded to medical treatment. CBC revealed mild lymphopenia; serum biochemistry findings were of increased gamma-glutamyl transferase and creatine kinase activities, hyperferremia, hyperglycemia, hypomagnesemia, and hypokalemia. Abdominocentesis was compatible with low-protein transudate. Due to the progression and duration of clinical signs, the owner elected euthanasia. Postmortem examination and histopathology confirmed a cholangi...
Chow L, Flaherty E, Pezzanite L, Williams M, Dow S, Wotman K.Ocular surface squamous neoplasia (OSSN) represents the most common conjunctival tumor in horses and frequently results in vision loss and surgical removal of the affected globe. Multiple etiologic factors have been identified as contributing to OSSN progression, including solar radiation exposure, genetic mutations, and a lack of periocular pigmentation. Response to conventional treatments has been highly variable, though our recent work indicates that these tumors are highly responsive to local immunotherapy. In the present study, we extended our investigation of OSSN in horses to better und...
Hobbs KJ, Davis JL, Cooper BL, Ueda Y, Burke MJ, Sheats MK.Plasma cytokine adsorption has shown benefit as an adjunctive therapy in human sepsis but has yet to be investigated in horses. We hypothesized that ex vivo filtration of equine plasma with a novel cytokine adsorption device would significantly reduce concentrations of lipopolysaccharide-stimulated cytokines. We also hypothesized that the device would adsorb medications commonly used to treat sepsis. Methods: 8 horses owned by North Carolina State University. Methods: Four liters of heparinized whole blood was collected from healthy adult horses (n = 8) and stimulated with lipopolysaccharide (...
Rabelo AA, Maranhão RPA, de Miranda ALS, Ocarino NM, Amaral CI, Paes PRO, Monteiro NCC, Fantini P.A 25-year-old mixed-breed equine with separate nodular cutaneous lesions in the right thoracic limb (RTL) and right ventral abdominal region was admitted to a Veterinary Hospital in Belo Horizonte, Minas Gerais. Fine-needle aspiration cytology was performed on the RTL lesion and superficial cervical lymph node, and the results were suggestive of a malignant neoplasm known as myxosarcoma. Due to the unfavorable prognosis, the animal was euthanized. Based on the macroscopic and microscopic findings, the diagnosis of metastatic cutaneous myxosarcoma was confirmed. Although rare, this tumor should...
Martabano BB, Dow S, Chow L, Williams MMV, Mack MK, Bellone R, Wotman KL.To determine the safety and efficacy of perilesional human recombinant interferon alpha-2b (IFNα2b) for treatment of periocular squamous cell carcinoma (PSCC) in horses. Methods: Eleven horses (12 eyes) with PSCC were enrolled in this prospective clinical study with owner consent. Methods: Systemically healthy horses were included in the study following confirmation of PSCC via biopsy. Every two weeks for a maximum of six treatments, horses were sedated and perilesional injection of IFNα2b (10 million IU) was performed. Tumors were measured prior to each injection and at one, three, and 12 m...
Brown KA, Gregorio EN, Barot D, Usimaki A, Linardi RL, Missanelli JR, You Y, Robinson MA, Ortved KF.To determine the effects of a single dose of the NSAIDs phenylbutazone, firocoxib, flunixin meglumine, and ketoprofen on concentrations of growth factors and cytokines in autologous protein solution (APS) and platelet-rich plasma (PRP). Methods: 6 adult university-owned horses. Methods: For the first phase, 6 horses were randomized to receive ketoprofen (1,000 mg) or flunixin meglumine (500 mg) IV. Blood was obtained and processed for APS (Pro-Stride) and PRP (Restigen) before and 6 hours after administration of NSAIDs. Horses underwent a 2-week washout period, after which the protocol was rep...
Gao Y, Packeiser EM, Wendt S, Sekora A, Cavalleri JV, Pratscher B, Alammar M, Hühns M, Brenig B, Junghanss C, Nolte I, Murua Escobar H.Malignant melanomas (MMs) are the abnormal proliferation of melanocytes and are one of the lethal skin cancers in humans, equines, and canines. Accordingly, MMs in companion animals can serve as naturally occurring animal models, completing conventional cancer models. The common constitutive activation of the MAPK and PI3K pathways in MMs has been described in all three species. Targeting the related pathways is considered a potential option in comparative oncologic approaches. Herein, we present a cross-species comparative analysis exposing a set of ten melanoma cell lines (one human, three e...
Fesmire CC, Peal B, Ruff J, Moyer E, McParland TJ, Derks K, O'Neil E, Emke C, Johnson B, Ghosh S, Petrella RA, DeWitt MR, Prange T, Fogle C, Sano MB.Integrated time nanosecond pulse irreversible electroporation (INSPIRE) is a novel tumor ablation modality that employs high voltage, alternating polarity waveforms to induce cell death in a well-defined volume while sparing the underlying tissue. This study aimed to demonstrate the in vivo efficacy of INSPIRE against spontaneous melanoma in standing, awake horses. Unassigned: A custom applicator and a pulse generation system were utilized in a pilot study to treat horses presenting with spontaneous melanoma. INSPIRE treatments were administered to 32 tumors across 6 horses and an additional 1...
Armando F, Porcellato I, de Paolis L, Mecocci S, Passeri B, Ciurkiewicz M, Mechelli L, Grazia De Ciucis C, Pezzolato M, Fruscione F, Brachelente C....Vulvo-vaginal epithelial tumors are uncommon in mares, and data on the epithelial-to-mesenchymal transition (EMT) and the tumor-immune microenvironment (TIME) are still lacking. This is a study investigating the equus caballus papillomavirus type 2 (EcPV2) infection state as well as the EMT process and the tumor microenvironment in vulvo-vaginal preneoplastic/ benign (8/22) or malignant (14/22) epithelial lesions in mares. To do this, histopathological, immunohistochemical, transcriptomic, hybridization, and correlation analyses were carried out. Immunohistochemistry quantification showed tha...
Schäfer J, Graubner C, Gerber V, Drögemüller C, Underberg J, Gurtner C, Unger L.This case series describes the clinical course of ocular and non-ocular squamous cell carinoma (SCC) in the Haflinger horse and is intended to raise awareness of the high recurrence rate and tendency to metastasize. Eight Haflingers with histologically confirmed SCC were included, five ocular and three non-ocular, who were presented at the Institut Suisse de Médecine Équine (ISME) Bern between July 2015 and January 2022. The ocular SCC cases were all presented because of an apparent mass, which in most cases was post-treatment recurrence. The occurrence of recurrences was observed between 3 ...
Risselada M, Worth DB.Tumors of various sizes and locations can create a treatment dilemma in achieving adequate surgical margins when sufficient free tissue is not available for closure. Extravascular local adjunctive chemotherapy has been investigated clinically to aid in achieving local tumor control in animals with naturally occurring neoplastic disease. Local chemotherapy can be an alternative primary or a local adjunctive treatment. This is a summary of relevant findings of in vitro and in vivo studies on local chemotherapeutic delivery through carrier media, together with a summary of outcomes of clinical us...
Tommasa SD, Roth SP, Triebe T, Brehm W, Lohmann KL, Stöckle SD.Granulosa cell tumors (GCTs) are the most common ovarian tumors in mares. The classical presentation of a GCT is a unilaterally enlarged ovary appearing as a multicystic honeycomb mass. In rare cases, GCTs cause hemoperitoneum as a result of the rapid growth of the tumor. The clinical diagnosis of GCT is usually based on history, rectal examination, ultrasonographic examination, and serum hormone analysis, and surgical removal of the affected ovary is the treatment of choice. The different surgical approaches are based on the dimension of the GCT. A 7-year-old mare was referred to the departme...
Hajimohammadi A, Ghane M, Ghari Tehrani M, Paravar B, Mirzaei A, Razavi S, Nikzad M.Sixty-one horses were enrolled in this study and divided into 3 different groups according to their severity of colic (heart rate, oral mucous membrane color, and abdominal distention): a strangulating colic (SC) group (n=21), non-strangulating colic (NC) group (n=20), and control group (n=20) consisting of randomly selected normal horses without signs of colic. The serum concentrations of haptoglobin, tumor necrosis factor-α (TNFα), nitric oxide (NO), malondialdehyde (MDA), zinc, iron, and copper were evaluated in all horses. The average concentration of TNFα in the SC group was higher tha...
Stutsel M, Gimeno M, Young A, Bell JW, Horadagoda N.A 2-year-old Standardbred gelding was referred for a mass on the palmaromedial right front pastern which was accompanied by progressively worsening lameness. The mass was firm to palpation and covered by normal skin. Ultrasonographically, a smooth encapsulated mass was present, medial to the flexor tendons and palmar to the neurovascular bundle. Because of a poor prognosis for future athletic performance without surgical or chemotherapeutic intervention and economic constraints preventing further diagnostics and treatment, the horse was euthanised. Post-mortem magnetic resonance imaging, histo...
Hoikhman R, Molinková D, Pillárová D, Linhart P, Kopecká A, Jahn P.Equine sarcoids (ES) are known globally as the most frequent skin tumour affecting horses. These tumours affect the horse's monetary value, they can affect the horse's welfare and can be difficult and expensive to treat. Bovine papillomavirus (BPV) is considered to be the aetiological agent of this tumour, as BPV 1, 2 and 13 have been detected in ES. This is the only known natural cross species infection by a papillomavirus. The BPV genome can be divided into two coding regions: The early region E which encodes the transforming proteins E5, E6 and E7 as well as the replication and transcriptio...
Straticò P, Hattab J, Guerri G, Carluccio A, Bandera L, Celani G, Marruchella G, Varasano V, Petrizzi L.Owner complaints of estrus-related behavior in mares are a common cause of referral for laparoscopic ovariectomy. Granulosa cell tumors are a common neoplastic condition affecting the equine ovary, causing behavioral changes at rest and reduced performance. The reported success rate of ovariectomy in treating behavioral disorders is 64-86%. The aim of this study was to retrospectively evaluate the long-term follow-up of laparoscopic ovariectomy in mares in our case series, focusing on the owner's perspective of the behavior of the mares after surgery. In addition, the histopathological feature...
Pimenta J, Pires I, Prada J, Cotovio M.Melanocytic tumors are an important neoplastic disease in human and veterinary medicine, presenting large differences regarding tumor behavior between species. In horses, these tumors present a prolonged benign behavior, with rare invasiveness and metastases. In humans and small animals, invasion and metastasis have been associated with an Epithelial-Mesenchymal Transition, where the loss of E-cadherin expression plays a key role in tumor progression. This process and the role of E-cadherin have not yet been evaluated in equine melanocytic tumors. This study aimed to assess the immunolabeling ...
De Paolis L, Armando F, Montemurro V, Petrizzi L, Straticò P, Mecocci S, Guarnieri C, Pezzolato M, Fruscione F, Passeri B, Marruchella G, Razzuoli E.Vulvar squamous cell carcinoma (VSCC) has been recently associated with Equus caballus papillomavirus type 2 (EcPV2) infection. Still, few reports concerning this disease are present in the literature. Objective: To describe a case of naturally occurring EcPV2-induced VSCC, by investigating tumour ability in undergoing the epithelial-to-mesenchymal transition (EMT). Methods: Case report. Methods: A 13-year-old Haflinger mare was referred for a rapidly growing vulvar mass. After surgical excision, the mass was submitted to histopathology and molecular analysis. Histopathological diagnosis was c...
Dolin A, Schweiger P, Waselau M, Egerbacher M, Walter I.Sex cord-stromal tumors (SCSTs), generally referred to as granulosa cell tumors (GCTs) or granulosa-theca cell tumors (GTCTs) in equids, show complex compositions and variable numbers of hormone-producing cells. These tumors can be difficult to diagnose, especially in early stages. Therefore, we tested a panel of antibodies for vimentin, smooth muscle actin, laminin, Ki-67, E-cadherin, calretinin, moesin, p-ezrin, AMH, and aromatase, markers used for tumor composition and classification, progression, and prognosis in human SCSTs, on an exemplary grapefruit-size equine GCT within the left ovary...
Norton AM, McGilp D, Vasey JR.A 4-month old, 200 kg, grey warmblood colt presented for a firm, non painful mass on the distal medial aspect of the left third metatarsus. Excisional biopsy revealed a diagnosis of haemangiosarcoma. Equine haemangiosarcoma is uncommon and only limited reports of successful treatment are available. The prognosis for survival is therefore considered to be poor. After two separate incidences of recurrence with incomplete excision of the tumour, intralesional treatment with cisplatin without excision or debulking was performed on three separate occasions. Intralesional cisplatin injection was p...
Semik-Gurgul E, Szmatoła T, Gurgul A, Pawlina-Tyszko K, Gałuszka A, Pędziwiatr R, Witkowski M, Ząbek T.DNA methylation is a key mechanism in transcription regulation, and aberrant methylation is a common and important mechanism in tumor initiation, maintenance, and progression. To find genes that are aberrantly regulated by altered methylation in horse sarcoids, we used reduced representation bisulfite sequencing (RRBS) accompanied by RNA sequencing (RNA-Seq) for methylome (whole genome DNA methylation sequencing) and transcriptome profiling, respectively. We found that the DNA methylation level was generally lower in lesion samples than in controls. In the analyzed samples, a total of 14,692 d...
Jindra C, Hainisch EK, Brandt S.Horses and other equid species are frequently affected by bovine papillomavirus type 1 and/or 2 (BPV1, BPV2)-induced skin tumors termed sarcoids. Although sarcoids do not metastasize, they constitute a serious health problem due to their BPV1/2-mediated resistance to treatment and propensity to recrudesce in a more severe, multiple form following accidental or iatrogenic trauma. This review provides an overview on BPV1/2 infection and associated immune escape in the equid host and presents early and recent immunotherapeutic approaches in sarcoid management.
Curnow B, Rich AF, Ireland J, Correa DC, Dunn J, Jenkins D, Carslake H, Ressel L.Although the equine sarcoid is the most common skin neoplasm in domesticated horses, histopathological characteristics have not previously been evaluated for association with recurrence. The aim of this retrospective cohort study was to investigate clinical and histopathological features of excised equine sarcoids and to evaluate their association with recurrence at the original surgical site and at new sites. Clinical records and excisional biopsies from 106 equine sarcoids from 64 horses referred to Leahurst Equine Hospital, University of Liverpool, between March 2010 and February 2015 were ...
Roxon C, Slack J, Bender S, Burns H, Turner R.A 12-year-old Standardbred stallion presented with a 5-month history of a growing mass in the left testis as well as an overall decrease in left testicular size. Palpation and ultrasonography of the left testis revealed a firm, hypoechoic, clearly delineated soft tissue mass in the craniolateral portion of the testis that measured 2.5 × 2.3 × 1.9 cm. Two smaller, hypoechoic regions also were visible ultrasonographically in the left testis, suggesting the presence of multifocal/multicentric neoplasia. The affected testis was very small (testicular volume of 40.3 cm). The right testis was ...
Walsh M, Fais S, Spugnini EP, Harguindey S, Abu Izneid T, Scacco L, Williams P, Allegrucci C, Rauch C, Omran Z.The treatment of cancer presents a clinical challenge both in human and veterinary medicine. Chemotherapy protocols require the use of toxic drugs that are not always specific, do not selectively target cancerous cells thus resulting in many side effects. A recent therapeutic approach takes advantage of the altered acidity of the tumour microenvironment by using proton pump inhibitors (PPIs) to block the hydrogen transport out of the cell. The alteration of the extracellular pH kills tumour cells, reverses drug resistance, and reduces cancer metastasis. Human clinical trials have prompted to c...
Dixon PM, Tremaine WH, Pickles K, Kuhns L, Hawe C, McCann J, McGorum BC, Railton DI, Brammer S.Of 400 horses referred because of dental disorders, 349 cases were diagnosed as suffering from primary disorders of their cheek teeth. Details of 104 of these cases are presented, including 44 cases with abnormalities of wear, 26 cases with traumatic damage, 24 cases with idiopathic fractures and 10 cases with miscellaneous cheek teeth disorders including oral tumours. The long-term response to treatment was excellent in most cases, even in cases with residual secondary periodontal disease.
van der Weyden L, Brenn T, Patton EE, Wood GA, Adams DJ.In contrast to other cancer types, melanoma incidence has been increasing over the last 50 years, and while it still represents less than 5% of all cutaneous malignancies, melanoma accounts for the majority of skin cancer deaths, due to its propensity to metastasise. Whilst melanoma most commonly affects the skin, it can also arise in mucosal surfaces, the eye, and the brain. For new therapies to be developed, a better understanding of the genetic landscape, signalling pathways, and tumour-microenvironmental interactions is needed. This is where animal models are of critical importance. The ...
Jiang L, Campagne C, Sundström E, Sousa P, Imran S, Seltenhammer M, Pielberg G, Olsson MJ, Egidy G, Andersson L, Golovko A.Constitutive activation of the ERK pathway, occurring in the vast majority of melanocytic neoplasms, has a pivotal role in melanoma development. Different mechanisms underlie this activation in different tumour settings. The Grey phenotype in horses, caused by a 4.6 kb duplication in intron 6 of Syntaxin 17 (STX17), is associated with a very high incidence of cutaneous melanoma, but the molecular mechanism behind the melanomagenesis remains unknown. Here, we investigated the involvement of the ERK pathway in melanoma development in Grey horses. Methods: Grey horse melanoma tumours, cell lines ...
Boone CW, Harell GS, Bond HE.Large-scale separation of mixtures of mammalian cells was obtained with the A-1X zonal centrifuge rotor and density gradients consisting of Ficoll dissolved in modified Eagle's MEM suspension-culture medium. The cells remained viable as tested by plating efficiency or by motility observed with time-lapse photography. Rabbit thymocyte and HeLa cell mixtures were separated with 99 and 89 per cent purity, respectively. Mixtures of thymocytes and suspension-cultured, human acute leukemia cells (Roswell Park strain LKID) were separated with 93 and 91% purity, respectively. HeLa cells were isolated ...
Knottenbelt DC, Kelly DF.OBJECTIVE: Diagnosis and management of periorbital sarcoids in horses is a significant clinical challenge for the practicing veterinary surgeon and pathologist. The purpose of this study was to investigate the response of various types of sarcoids to different therapeutic methods. Animals studied Medical records of 445 clinical patients. Procedures This paper retrospectively examines the clinical and histological features of periorbital sarcoids and the treatment of 445 cases. Treatment by surgical excision, cryosurgery, Bacillus-Calmette-Gaérin (BCG) immunomodulation, topical cytotoxic appli...
Equine sarcoids are benign fibroblastic skin tumours that are recognized throughout the world. Infection with bovine papillomavirus (BPV) types 1 and 2 has been implicated as a major factor in disease development; however, the cellular mechanisms underlying fibroblast transformation remain poorly defined. The present study further characterizes aspects of the association with BPV in 15 equine sarcoids. BPV DNA was demonstrated in 12/15 tumours collected from different areas of Italy. Nine of these 12 tumours expressed the BPV oncoproteins E5 and E7, but these oncoproteins were not expressed by...
Angelos J, Oppenheim Y, Rebhun W, Mohammed H, Antczak DF.The relationship between breed and the risk of developing sarcoid tumours or uveitis of unknown etiology was evaluated in a retrospective study of 16242 equine cases admitted between 1975 and 1987 to the New York State College of Veterinary Medicine Large Animal Hospital, and 3198 equine tissue samples sent to the New York State Veterinary Diagnostic Laboratory between 1977 and 1987. Of 120 sarcoid cases from the Large Animal Hospital, sarcoids were twice as likely to develop in Quarter Horses (odds ratio, OR = 1.8, P less than 0.05) relative to Thoroughbreds and less than half as likely to de...
Almeida J, Ball BA, Conley AJ, Place NJ, Liu IK, Scholtz EL, Mathewson L, Stanley SD, Moeller BC.Anti-Müllerian hormone (AMH), a member of the transforming growth factor β superfamily of growth and differentiation factors, is expressed in granulosa cells of preantral and small antral ovarian follicles. In humans, AMH appeared to regulate recruitment and growth of small ovarian follicles. Furthermore, circulating AMH concentrations were elevated in women with granulosa-cell tumors (GCT). In the horse, GCTs are the most common tumor of the ovary, and a variety of endocrine assays have been used to diagnose presumptive GCTs. The objectives of the present study were to validate a heterologo...
Lancaster WD, Olson C, Meinke W.Four of five spontaneous benign equine connective tissue tumors of unknown etiology and a bovine papilloma virus (BPV)-induced equine tumor contained BPV-specific DNA sequences as determined by DNA-DNA hybridization of DNA from tumors with BPV DNA labeled in vitro. Analysis of the kinetics of reassociation indicated that 20-75% of the BPV genome was present in the various tumors. The number of partial BPV genome equivalents ranged from 60 to 500 copies per diploid quantity of cellular DNA. Thermal denaturation profiles of duplexes formed between labeled BPV DNA and DNA from tumor cells indicat...
Ding Q, Bramble L, Yuzbasiyan-Gurkan V, Bell T, Meek K.Previously, spontaneous genetic immunodeficiencies in mice, Arabian foals, and recently in Jack Russell terriers have been ascribed to defects in DNA-PKcs (catalytic subunit of the DNA dependent protein kinase) expression. In severe combined immunodeficiency (SCID) foals, a 5 bp deletion at codon 9480 results in a frameshift and a 967 amino acid deletion from the C terminus (including the entire PI3 kinase domain) and an unstable mutant protein. In SCID mice, a single base pair mutation results in a premature stop codon and deletion of 83 amino acids; as in SCID foals, the mutant protein is un...
Cissell DD, Wisner ER, Textor J, Mohr FC, Scrivani PV, Théon AP.The computed tomography (CT) features of tumors involving the nasal cavity and/or paranasal sinuses of 15 horses were reviewed. The 15 tumors included five neuroendocrine tumors/neuroblastomas, two undifferentiated carcinomas, two myxosarcomas, and one each of nasal adenocarcinoma, hemangiosarcoma, chondroblastic osteosarcoma, anaplastic sarcoma, myxoma, and ossifying fibroma. All tumors except the ossifying fibroma were iso- or hypoattenuating relative to masseter muscle. Thirteen of the fifteen tumors exhibited moderate or marked osteolysis of adjacent cortical bone and 14/15 were characteri...
Ogłuszka M, Starzyński RR, Pierzchała M, Otrocka-Domagała I, Raś A.Equine sarcoid is the most common skin tumor of horses. Clinically, it occurs as a locally invasive, fibroblastic, wart-like lesion of equine skin, which has 6 clinical classes: occult, verrucose, nodular, fibroblastic, mixed, and malignant. Sarcoids may be single but multiple lesions are more frequent. The typical histological feature is increased density of dermal fibroblasts which form interlacing bundles and whorls within the dermis. Lesions are mostly persistent, resist therapy, and tend to recur following treatment. In general, sarcoids are not fatal but their location, size, and progres...
Ganbaatar O, Konnai S, Okagawa T, Nojima Y, Maekawa N, Minato E, Kobayashi A, Ando R, Sasaki N, Miyakoshi D, Ichii O, Kato Y, Suzuki Y, Murata S....Programmed death-1 (PD-1) is an immunoinhibitory receptor expressed on lymphocytes. Interaction of PD-1 with its ligand PD-ligand 1 (PD-L1) delivers inhibitory signals and impairs proliferation, cytokine production, and cytotoxicity of T cells. In our previous studies, we have developed anti-bovine PD-L1 monoclonal antibodies (mAbs) and reported that the PD-1/PD-L1 pathway was closely associated with T-cell exhaustion and disease progression in bovine chronic infections and canine tumors. Furthermore, we found that blocking antibodies that target PD-1 and PD-L1 restore T-cell functions and cou...
Head KW, Dixon PM.The normal gross and histological anatomy of the equine nasal and paranasal sinuses are reviewed and the relationships between the local anatomy, the occurrence of different tumour types, and of tumour spread are examined. The histological classification of the more common equine sinonasal tumours and tumour-like lesions are discussed. Clinical and pathological descriptions of 50 more recently recorded such tumours are separately tabulated. The literature shows that equine sinonasal tumours, both endemic and sporadic, are relatively uncommon in horses, with non-neoplastic growths such as maxil...
van den Top JG, de Heer N, Klein WR, Ensink JM.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. Objective: 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, part...
Schöniger S, Summers BA.In humans, neurofibroma and schwannoma are distinct entities within the group of benign peripheral nerve sheath tumors. In the veterinary literature, these tumors are often classified together simply as benign peripheral nerve sheath tumors, and diagnostic criteria for their subclassification are not well established. We describe peripheral nerve sheath tumors with microscopic, immunohistologic, and ultrastructural features similar to those in subtypes of human neurofibroma in 12 dogs, 2 horses, and 1 chicken. Dogs were of different breeds and were aged 2 months to 15 years. The canine tumors ...
Kafarnik C, Rawlings M, Dubielzig RR.To describe the pathomorphological features of corneal stromal invasive squamous cell carcinoma (CSI-SCC) in horses. Methods: A total of 87 equine SCC in the Comparative Ocular Pathology Laboratory of Wisconsin database were retrieved. The signalment and anatomical distribution were summarized. Ten CSI-SCC out of 87 SCCs were further investigated focusing on pathomorphological description. All 10 cases were stained with H&E, periodic acid-Schiff stain and Verhoeff's elastic stain. Results: Four Appaloosas, two Quarter horses, two American Paint, one Pinto and one Thoroughbred horse were affect...
Bogaert L, Martens A, Kast WM, Van Marck E, De Cock H.Bovine papillomavirus (BPV)-1 and -2 is linked to equine sarcoids, a commonly observed skin tumor in horses that is of considerable veterinary importance. Previous studies using in situ hybridization have detected BPV DNA only in fibroblasts and not in keratinocytes of sarcoids. In contrast, normal equine skin latently infected with BPV shows a dysplastic epithelium without dermal changes, similar to lesions induced by other papillomavirus types infecting the epithelium. The first goal of our study was to describe the epidermal and dermal characteristics of several stages in sarcoid developmen...
Bergvall KE.Sarcoids are the most common skin tumors seen in horses worldwide. The pathogenesis of sarcoids is multifactorial, including an association with bovine papillomavirus types 1 and 2 and a genetic susceptibility to tumor development. Clinical manifestations vary and include occult, verrucous, nodular, fibroblastic, mixed, and malignant (malevolent) types. The tumor is nonmetastasizing but can become very aggressive locally. Multiple tumors are common. All clinical types can be present in the same horse. No treatment protocol is universally effective. The tumor has a high risk of recurrence. Recu...
Martano M, Corteggio A, Restucci B, De Biase ME, Borzacchiello G, Maiolino P.Equine sarcoids are locally invasive, fibroblastic benign skin tumors. Bovine papillomavirus type-1 (BPV-1) and/or Bovine papillomavirus type-2 (BPV-2) are believed to be the causative agent of sarcoids, although the mechanisms by which the virus induce the tumor are still poorly understood. We hypothesized that in genetically predisposed equines latent BPV infection may be reactivated by immunosoppression and/or mechanical injury leading to a form of pathologic wound which may transform into a sarcoid. In this study, we investigated in 25 equine sarcoids and in five normal skin samples the hi...
Dugan SJ, Roberts SM, Curtis CR, Severin GA.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 c...
Fleury C, Bérard F, Balme B, Thomas L.The clinical and pathological characteristics of cutaneous melanomas occurring in Camargue-type gray-skinned horses are reported. Examination of 83 tumor-bearing horses revealed that the tumors occurred most frequently underneath the tail (93.9%) and at high rates in the peri-anal region (43.0%), the lips (33.0%), and the eyelids (24.0%), but rarely in the vulva (3.8%). Tumorous lesions were characterized by the presence of either hemispheric nodules or large infiltrated plaques, or their combinations. Microscopic examination indicated that tumorous lesions were composed mostly of melanocytes ...
Nogueira SA, Torres SM, Malone ED, Diaz SF, Jessen C, Gilbert S.Imiquimod is an immune response modifier with potent antiviral and antitumour activity. The objective of this pilot study was to evaluate the efficacy of an imiquimod 5% cream (Aldaratrade mark: 3M, Saint Paul, MN, USA) as a topical treatment for equine sarcoids. Fifteen horses with a total of 19 tumours were enrolled, including mixed (7), fibroblastic (5), flat (3), verrucous (2), and nodular (2) types. Baseline data included history, physical examination, tumour location, measurement and digital photography. Imiquimod was applied by the owners three times a week until complete resolution of ...
Yuan Z, Gault EA, Campo MS, Nasir L.Equine sarcoids represent the most common skin tumours in equids worldwide, characterized by localized invasion, rare regression and high recurrence following surgical intervention. Bovine papillomavirus type 1 (BPV-1) and less commonly BPV-2 are now widely recognized as the causative agents of the disease. Fibroblasts isolated from sarcoids are highly invasive. Invasion is associated with a high level of viral gene expression and matrix metalloproteinase upregulation. However, it remains unclear to what extent BPV-1 proteins are involved in the transformation of equine cells. To address this ...
Brandt S, Haralambus R, Shafti-Keramat S, Steinborn R, Stanek C, Kirnbauer R.Bovine papillomavirus type 1 or 2 (BPV-1, BPV-2) are accepted causal factors in equine sarcoid pathogenesis. Whereas viral genomes are consistently found and expressed within lesions, intact virions have never been detected, thus permissiveness of sarcoids for BPV-1 replication remains unclear. To reassess this issue, an immunocapture PCR (IC/PCR) was established using L1-specific antibodies to capture L1-DNA complexes followed by amplification of the viral genome. Following validation of the assay, 13 sarcoid-bearing horses were evaluated by IC/PCR. Samples were derived from 21 tumours, 4 per...
Staiger EA, Tseng CT, Miller D, Cassano JM, Nasir L, Garrick D, Brooks SA, Antczak DF.The common equine skin tumors known as sarcoids have been causally associated with infection by bovine papillomavirus (BPV). Additionally, there is evidence for host genetic susceptibility to sarcoids. We investigated the genetic basis of susceptibility to sarcoid tumors on a cohort of 82 affected horses and 270 controls genotyped on a genome-wide platform and two custom panels. A Genome Wide Association Study (GWAS) identified candidate regions on six chromosomes. Bayesian probability analysis of the same dataset verified only the regions on equine chromosomes (ECA) 20 and 22. Fine mapping us...
Christen-Clottu O, Klocke P, Burger D, Straub R, Gerber V.Equine sarcoids (ES) are common, difficult to treat, and have high recurrence rates. Viscum album extracts (VAE) are used in human cancer treatment. Objective: That therapy with VAE (Iscador P) is effective in the treatment of ES. Methods: Fifty-three horses (444 ES); 42 were treated with VAE or placebo as monotherapy; 11 were treated with VAE or placebo after selective excision of ES. Methods: Prospective, randomised, blinded, clinical trial. Horses were randomly assigned to treatment (VAE; n=32) or control group (Placebo; n=21). One milliliter of VAE (Iscador P) in increasing concentrations ...
Klein WR, Bras GE, Misdorp W, Steerenberg PA, de Jong WH, Tiesjema RH, Kersjes AW, Ruitenberg EJ.A total of 30 horses with single or multiple sarcoid tumors of the skin were randomly divided into three treatment groups: (i) cryosurgical treatment, (ii) intralesional immunotherapy with a live BCG vaccine, (iii) intralesional immunotherapy with a BCG cell wall preparation. Complete tumour regression was obtained in all 10 cryosurgically treated horses, in 6 of 10 live BCG treated horses, and in 7 of 10 BCG cell wall treated horses. One live BCG and 2 BCG cell wall treated horses showed partial tumour regression of more than 50% of the tumour area. Eleven horses with sarcoid tumours were not...
Marchetti B, Gault EA, Cortese MS, Yuan Z, Ellis SA, Nasir L, Campo MS.Bovine papillomavirus type 1 is one of the aetiological agents of equine sarcoids. The viral major oncoprotein E5 is expressed in virtually all sarcoids, sarcoid cell lines and in vitro-transformed equine fibroblasts. To ascertain whether E5 behaves in equine cells as it does in bovine cells, we introduced the E5 open reading frame into fetal equine fibroblasts (EqPalF). As observed in primary bovine fibroblasts (BoPalF), E5 by itself could not immortalize EqPalF and an immortalizing gene, such as human telomerase (hTERT/hT), was required for the cells to survive selection. The EqPalF-hT-1E5 c...
