Topic:Melanoma
Melanoma in horses is a type of skin tumor commonly observed in gray horses, although it can occur in horses of any color. These tumors are typically found in areas such as the under-tail region, perineum, and around the lips and eyes. While many melanomas remain benign, some can become malignant and metastasize to other parts of the body. The underlying causes of melanoma in horses are not fully understood, but genetic factors and coat color are known to influence their development. Diagnosis often involves clinical examination and, in some cases, biopsy or imaging techniques. This page compiles peer-reviewed research studies and scholarly articles that explore the prevalence, diagnosis, progression, and management of melanoma in equine populations.
The Impact of Excision Interval on Equine Melanoma Progression: Time Matters? 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...
White horses – non-coding sequences drive premature hair greying and predisposition to melanoma. The Grey allele in horses is causing premature hair greying and susceptibility to melanoma. The causal mutation is a 4.6 kb tandem duplication in intron 6 of the Syntaxin 17 gene. A recent study demonstrated that the most common allele at the Grey locus (G3) involves three tandem copies of this sequence, whilst a more rare allele (G2) has two tandem copies and the wild-type allele (G1) only one copy. The G3 allele is causing fast greying and high incidence of skin melanoma, whereas the G2 allele is causing slow greying and no obvious increase in melanoma incidence. Further somatic copy number ...
Cross-Species Comparison of the Pan-RAF Inhibitor LY3009120’s Anti-Tumor Effects in Equine, Canine, and Human Malignant Melanoma Cell Lines. 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...
Investigation of integrated time nanosecond pulse irreversible electroporation against spontaneous equine melanoma. 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...
Horse Herd Optimization with Gate Recurrent Unit for an Automatic Classification of Different Facial Skin Disease. The human body's largest organ is the skin which covers the entire body. The facial skin is one area of the body that needs careful handling. It can cause several facial skin diseases like acne, eczema, moles, melanoma, rosacea, and many other fungal infections. Diagnosing these diseases has been difficult due to challenges like the high cost of medical equipment and the lack of medical competence. However, various existing systems are utilized to detect the type of facial skin disease, but those approaches are time-consuming and inaccurate to detect the disease at early stages. To address var...
Equine Melanocytic Tumors: A Narrative Review. Adult grey horses have a high incidence of melanocytic tumors. This article narratively reviews the role of some genetic features related to melanoma formation in horses, such as STX17 mutation, ASIP or MITF alterations, and the link between the graying process and the development of these tumors. A clear system of clinical and pathological classification of melanocytic tumors in naevus, dermal melanoma, dermal melanomatosis and anaplastic malignant melanoma is provided. Clinical and laboratorial methods of diagnosing are listed, with fine needle aspiration and histopathology being the most re...
From Keratoma to Anaplastic Malignant Melanoma in a Horse’s Hoof. Melanomas in horses are most often associated with gray, older horses with an average age of over 16 years. Anaplastic malignant melanoma, however, can very rarely affect non-gray horses. Herein, we report a case of a 16-year-old Wielkopolski gelding with a chronic lameness caused by a mass in the hoof. The first resection of the lesion and histopathological examination confirmed the presence of a keratoma. The regrown mass and persistent lameness resulted in another mass resection. The second histopathological examination result suggested a neoplastic growth of melanocytic origin with a low h...
Caecal dysfunction following standing surgical procedures. The aim of this study is to report cases of caecal dysfunction following surgical procedures in the standing horse. The study design is retrospective. Six client-owned horses developed caecal dysfunction following a variety of surgical procedures undertaken in the standing sedated horse. Medical records were reviewed for caecal dysfunctions that had occurred in horses within 2 weeks of standing surgical procedures. Signalment, details of the original standing surgery and medications administered were recorded. Short-term outcome was obtained from clinical records. Long-term outcome was obtain...
Viscum album L., a Therapeutic Option for Neoplastic Diseases in Companion Animals? A Systematic Review. Cancer is a common disease in humans and in companion animals and treatment is challenging. The aim of this systematic review was to identify and assess the potential use of Viscum album L. extracts (VAE) for treatment of neoplastic diseases in companion animals. Peer-reviewed animal, in vivo and in vitro studies were included, considering the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and A Measurement Tool to Assess Systematic Reviews (AMSTAR). Overall, 6,148 references were identified. Following a predefined protocol, 114 full-text references were ...
Faecal Proteomics and Functional Analysis of Equine Melanocytic Neoplasm in Grey Horses. Equine melanocytic neoplasm (EMN) is a common disease in older grey horses. The purpose of this study was to examine the potential proteins throughout EMN stages from faecal proteomic outlining using functional analysis. Faecal samples were collected from the rectum of 25 grey horses divided into three groups; normal group without EMN ( = 10), mild EMN ( = 6) and severe EMN ( = 9). Based on the results, 5910 annotated proteins out of 8509 total proteins were assessed from proteomic profiling. We observed differentially expressed proteins (DEPs) between the normal group and the EMN group, and 1...
Effects of Topically Applied Betulinic Acid and NVX-207 on Melanocytic Tumors in 18 Horses. The naturally occurring betulinic acid (BA) and its derivative NVX-207 induce apoptosis in equine melanoma cells in vitro. After topical application, high concentrations of the substances can be reached in healthy equine skin. With the aim to investigate the effect and safety of topically applied BA and NVX-207 in horses with melanocytic tumors, the longitudinal, prospective, randomized, double-blind, placebo-controlled study protocol included eighteen Lipizzaner mares with early-stage cutaneous melanoma assigned to three groups. Melanocytic lesions were topically treated either with a placebo...
DPF3, A Putative Candidate Gene For Melanoma Etiopathogenesis in Gray Horses. Melanoma prevalence in gray horses reaches up to 50% and more. Several studies have documented a genetic melanoma predisposition which is referred to the 4.6 kb duplication in intron 6 of STX17 and its surrounding haplotype. However, the genetic background and mechanisms responsible for differences in etiopathogenesis of equine dermal melanomatosis still remain unknown. In the current study, we performed a genome wide association analysis in 141 Lipizzan horses and subsequently identified one candidate gene on chromosome 24 putatively involved in melanoma pathogenesis in gray horses. The assoc...
The equine graying with age mutation of the STX17 gene: A copy number study using droplet digital PCR reveals a new pattern. The equine graying with age causative mutation in the syntaxin-17 gene (STX17) has been known for over a decade, but proper genotyping of this variant remains challenging due to its molecular character (4.6-kb tandem duplication). Precise information on gray mutation status is important for horse breeders and veterinarians, since gray homozygous horses are more prone to developing aggressive melanoma tumors than heterozygotes. Since recent studies have confirmed that droplet digital PCR is a valuable technique for copy number analysis, we decided to investigate whether this method can be used ...
Expression of the Wilms’ tumour gene and its association with PPARβ/δ in healthy skin and melanoma of horses. The Wilms' tumour gene (WT1) has previously been described as an oncogene in several neoplasms of humans, including melanoma, and its expression increases cancer cell proliferation. Recent reports associate the expression of the PPARβ/δ gene (peroxisome proliferator-activated receptor beta/delta) with the downregulation of WT1 in human melanoma and murine melanoma cell lines. The aim of this work was to analyse the expression of WT1 and its association with PPARβ/δ in samples of healthy and melanoma-affected skin of horses by immunohistochemistry. WT1 protein expression was detected in hea...
Circulating melanin-containing cells and neutrophils with phagocytized melanin granules in a horse with disseminated melanoma. An 18-year-old, grey, Thoroughbred Cross gelding was referred to the Cummings School of Veterinary Medicine at Tufts University following a 3-week history of low-grade fever of unknown origin, distal limb swelling, and weight loss. Clinical examination identified a few black, round, smooth nodules along the ventral aspect of the proximal tail. Transabdominal ultrasound showed a markedly enlarged heterogenous spleen, hyperechoic liver nodules, and evidence of peritonitis with fibrin deposition. A mature neutrophilia was noted on complete blood count with variable numbers of phagocytized granule...
Spontaneously occurring melanoma in animals and their relevance to human melanoma. 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 ...
Genetics of Skin Disease in Horses. Equine skin diseases are common, causing increased costs and reduced welfare of affected horses.Genetic testing, if available, can complement early detection, disease diagnosis, and clinical treatment and offers horse breeders the possibility to rule out carrier status. The mechanisms of complex disease can be investigated by using the latest state-of-the-art genomic technologies. Genome-based strategies may also serve as an efficient and cost-effective strategy for the management of the disease severity levels, with particular interest in complex traits such as insect bite hypersensitivity, c...
Bleaching melanin in formalin-fixed and paraffin-embedded melanoma specimens using visible light: a pilot study. In fluorescence microscopy, light radiation can be used to bleach fluorescent molecules in formalin-fixed and paraffin-embedded (FFPE) samples, in order to increase the ratio between signal of interest and background autofluorescence. We tested if the same principle can be exploited in bright field microscopy to bleach pigmented melanoma FFPE sections together with cell morphology maintenance. After dewaxing and rehydration, serial FFPE sections of a feline diffuse iris melanoma, a canine dermal melanoma, a gray horse dermal melanoma and a swine cutaneous melanoma were irradiated with visible ...
Treatment of Infiltrative Superficial Tumors in Awake Standing Horses Using Novel High-Frequency Pulsed Electrical Fields. 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...
Treatment Options for Melanoma of Gray Horses. All gray horses inherited a single gene mutation, STX17G, that unbalances melanocyte behavior to cause graying and propensities to develop vitiligo and melanoma. The coat color genes ASIPa and MC1RE add risk such that relative likelihood of melanoma based on pregraying coat color is black > bay > chestnut. Melanomas begin at about 4 years. Locoregional control of melanoma masses depends on surgical removal and/or intralesional chemotherapy (possibly with adjunctive hyperthermia or electroporation). Systemic treatment is not evidence based but immunomodulators (cimetidine, levamisole) and ...
Genetic and environmental risk factors for vitiligo and melanoma in Pura Raza Español horses. Vitiligo and melanoma are relatively common disorders in grey Pura Raza Español horses and other horse breeds with grey-coloured coats. Objective: To determine the breed prevalence, environmental risks factors and estimate the genetic parameters for vitiligo and melanoma in Pura Raza Español horses. Methods: Retrospective cohort study. Methods: We analysed data from a large worldwide population of Pura Raza Español horses. The database included the vitiligo and melanoma scores, on either a four- or six-point linear scale, of 11,436 horses. Genetic parameters were estimated using a Bayesian ...
The use of a combined sliding skin graft and a free labial mucocutaneous graft for reconstruction of the equine upper eyelid after full-thickness excision of a melanoma. A melanoma of the upper eyelid was resected in a gray warmblood gelding. A full functional eyelid could be obtained by completion a sliding skin graft with a free labial mucocutaneous graft transplantation to restore the mucocutaneous junction and to decrease the risk of postoperative trichiasis.
[A case of leptomeningeal melanomatosis with acute paraplegia and multiple cranial nerve palsies]. A 62-year-old man with acute paraplegia was transferred to our hospital. He had flaccid paraplegia and multiple cranial nerve palsies, such as mydriasis of the left pupil, abduction palsy of the left eye, hoarseness and dysphagia, but no meningeal irritation signs. MRI of the spinal canal showed swellings of the conus medullaris and the cauda equine, and also contrast enhancement of the spinal meninges. The cerebrospinal fluid (CSF) showed pleocytosis and protein increment. The lymph node was swollen in his right axilla. The biopsy specimen from the right axillary lymph node revealed metastasi...
Regulatory pathway analysis of coat color genes in Mongolian horses. Studies on the molecular genetics of horse skin pigmentation have typically focused on very few genes and proteins. In this study, we used Illumina sequencing to determine the global gene expression profiles in horses with white-colored coats and those with black-colored coats, with the goal of identifying novel genes that could regulate horse coat color. Results: Genes encoding ribosomal-associated proteins were highly expressed in horse skin. We found a total of 231 unigenes that were differentially expressed between horses with white coats and horses with black coats; 119 were down-regulate...
Utilization of polarized microscopy to differentiate deep penetrating nevus from equine type melanomas. Equine type melanoma can mimic deep penetrating nevus (DPN), making histologic diagnosis challenging. We sought to investigate if the pattern of collagen polarization could be helpful in this setting. A total of 52 specimens were reviewed with polarized microscopy to determine whether refractile collagen was present within melanocytic nests vs. surrounding but not within the nests. Seven of eight (87.5%) equine type melanomas demonstrated refractile collagen within melanocytic nests in part or all of the lesion. In contrast, DPN showed no refractile collagen within the melanocytic nests. Inste...
COMPUTED TOMOGRAPHIC APPEARANCE OF MELANOMAS IN THE EQUINE HEAD: 13 CASES. Melanomas are one of the most common neoplasms in the horse and are frequently found in the head region. There is a genetic predisposition in horses with a gray hair coat. Computed tomography (CT) is frequently used in referral practice to evaluate the equine head but there are few reports describing the CT appearance of melanomas in this location. The aim of this retrospective, case series study was to describe characteristics in a group of horses with confirmed disease. Case records from two referral hospitals were reviewed, and 13 horses were identified that had undergone CT of the head, wi...
In vitro anticancer activity of Betulinic acid and derivatives thereof on equine melanoma cell lines from grey horses and in vivo safety assessment of the compound NVX-207 in two horses. Betulinic acid, a pentacyclic triterpene, and its derivatives are promising compounds for cancer treatment in humans. Melanoma is not only a problem for humans but also for grey horses as they have a high potential of developing melanoma lesions coupled to the mutation causing their phenotype. Current chemotherapeutic treatment carries the risk of adverse health effects for the horse owner or the treating veterinarian by exposure to antineoplastic compounds. Most treatments have low prospects for systemic tumor regression. Thus, a new therapy is needed. In this in vitro study, Betulinic acid a...
What’s New in Old Horses? Postmortem Diagnoses in Mature and Aged Equids. 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...
A systematic review and meta-analysis of animal-type melanoma. Animal-type melanoma is a rare subtype of melanoma with heavily pigmented dermal epithelioid and spindled melanocytes. Its classification as a subtype of melanoma versus a borderline melanocytic tumor is debated. Objective: Our primary objective was to characterize the demographics, clinical presentation, histopathology, management, and outcomes of patients with animal-type melanoma. Methods: We performed a systematic review and meta-analysis of the English-language literature on animal-type melanoma. Results: We identified 190 cases of animal-type melanoma. They occurred equally in men and wo...
Local and systemic effect of transfection-reagent formulated DNA vectors on equine melanoma. Equine melanoma has a high incidence in grey horses. Xenogenic DNA vaccination may represent a promising therapeutic approach against equine melanoma as it successfully induced an immunological response in other species suffering from melanoma and in healthy horses. In a clinical study, twenty-seven, grey, melanoma-bearing, horses were assigned to three groups (n = 9) and vaccinated on days 1, 22, and 78 with DNA vectors encoding for equine (eq) IL-12 and IL-18 alone or in combination with either human glycoprotein (hgp) 100 or human tyrosinase (htyr). Horses were vaccinated intramuscularly, a...