Equine Sarcoids. A therapeutic challenge
MeSH keywords:horses, sarcoidosis, therapeutics
Equine sarcoids are the most common skin tumors of horses, representing 12.5% to 67% of all neoplasms (Taylor & Haldorson 2013). They are found in horses worldwide but also a wide variety of other Equidae including zebras, donkeys, and mules are affected (Jackson 1936, Reid et al. 1994, Martens & DeMoor 1996, Scott & Miller 2003, Lohr et al. 2005, Valentine 2006, Kidney & Berrocal 2008). The term “sarcoid” was first used to describe these tumors in 1936, in South Africa, to distinguish them from other fibroblastic skin tumors such as fibromas, fibrosarcomas, and papillomas (Jackson 1936). These tumors do not metastasize, but they can be invasive, are regarded as cosmetic defects, can become ulcerated and infected and, when occurring near the eyes or on the eyelids, can impair vision (Wobeser et al. 2010, Semik‐Gurgul 2021). The treatment of horses for equine sarcoids can represent a considerable expense for horse owners (Nasir & Campo 2008, Wobeser et al. 2010).
Equine sarcoids are associated with the presence of 2 types of bovine papillomaviruses (BPV), BPV-type 1 (BPV1) and BPV-type 2 (BPV2) (Teifke & Weiss 1990, Otten et al. 1993, Teifke et al. 1994, Carr et al. 2001, Wobeser et al. 2010, Semik‐Gurgul 2021).
Although there may be some pathological reasons why the name, “skin cancer” does not necessarily fit the equine sarcoid, there are several features that are consistent with the clinical principles of a genuine neoplastic disease. These include:
- the behavior of the tumors,
- the difficulties encountered in treatment,
- the tendency to recurrence,
- the spread across the body from site to site (Knottenbelt 2005).
The sarcoid is a tumor of fibroblasts (Taylor & Haldorson 2013). However, the sarcoid cell does not survive in organs other than the skin and the adjacent subcutis -it is restricted to fibroblasts in the skin itself (Yuan et al. 2010).
The basic recognized types are (Knottenbelt 2005, Taylor & Haldorson 2013:
- Occult. There are flat and alopecic with mild scaling (Figure 1).
- Verrucous. There are wart-like and have a raised, scaly, lichenified appearance with epidermal thickening (Figure 2).
- Nodular. There are firm, well defined, subcutaneous lesions (Figure 3).
- Fibroblastic. There are fleshy and ulcerated with local infiltration (Figure 4).
- Mixed sarcoids may include any, or all, of the aforementioned types and often become progressively more aggressive as fibroblastic transformation occurs (Figure 5).
- Malignant sarcoids are the most infrequent form and are aggressive, invasive tumors that proliferate rapidly and may spread along fascial planes and vessels (Figure 6).
It is worth mentioning that affected horses frequently have multiple types of sarcoids at the time of biopsy (Torrontegui & Reid 1994, Martens et al. 2001).
Treatment options and considerations
The various types have different treatment options and different long and short-term prognoses. In general, sarcoids are difficult to treat. Currently, there are around 40 different treatments that are used world-wide, which suggests that no single method is universally effective (Tamzali et al. 2012, Taylor & Haldorson 2013). Furthermore, the various treatments have variable effects; some can be very successful on some occasions and ineffective on others.Moreover, not all horses respond in the same way either to the presence of sarcoid tumors or to the treatment modalities. Some horses respond better to individual types of treatment and even some lesions on a particular horse respond differently to the same treatment. Treatment that may be well tolerated by one sarcoid may cause severe reactions on another. This means that treatment responses are entirely unpredictable with all treatment methods with the possible exception of radiation (Knottenbelt 2019). To make things worse, failure of any treatment method is usually accompanied by the reappearance of a more aggressive tumor -and often in increased numbers (Taylor & Haldorson 2013). It is therefore important to select the best possible alternative as the first treatment method.
As a rule, the treatment goal would be to destroy every single sarcoid cell, which is seldom achieved; therefore, prognosis is usually poor (Knottenbelt 2019). However, leaving sarcoids alone makes the prospect of treatment even less feasible so the philosophy should be to try to treat when they are small and few in numbers.
The most common treatments are:
Tumors that are easily accessible and in a location such that skin closure is possible are often treated with conventional surgical excision. It is critical that wide margins (2-3 cm) are removed to prevent recurrence due to inadequate removal of all extensions of the sarcoid into surrounding tissue (Carstanjen et al. 1997, McCauley et al. 2002). Because this is often difficult to achieve, conventional surgical excision alone has yielded success rates of 30-50%, with most tumors recurring within 6 months (Genetzkyet al. 1983, McConaghy et al. 1994, Knottenbelt & Kelly 2000). Laser resection has a positive post-operative prognosis (Compstonet al. 2016), however, it is not simple to perform and is not widely available (Carstanjen et al. 1997).
Ligation (tying off wit h string / tail hair / rubber bands etc.)
This method is performed by applying a strangulating band around the base of the sarcoid (Figure 7). It could be applied to conveniently sized and situated nodular lesion and a few small pedunculated fibroblastic lesions (Knottenbelt & Walker 1994, Knottenbelt 2019). It is considered extremely dangerous, especially where there is a root structure. Still, it may be effective if the lesion has no roots. It is important to realize that the tumor will die slowly over some weeks and will eventually fall off leaving an open wound. This may in some cases be much larger than expected due to elastic recoil in the skin. Although simple, there is a strong recommendation against the use of this technique. There is a very high rate of recurrence following this method, usually with more aggressive sarcoids (Knottenbelt & Walker 1994).
Cryosurgery, using liquid nitrogen spray at -196oC, can be used either on its own or in conjunction with other methods, such as surgical excision of the bulk of the lesion (Taylor & Haldorson 2013). Each lesion must be frozen quickly and thawed slowly at least three times (cryosurgical cycle) (Hewes & Sullins 2009). It can be used for most sarcoid types (Taylor & Haldorson 2013). There are several drawbacks of the technique. It is very time consuming and tedious if many lesions are to be treated. The recurrence rate is a quite high. In order to be effective, cryosurgery needs to be aggressive, and it may cause extensive damage to surrounding structures and consequent extensive scarring (Taylor & Haldorson 2013).
Bacillus Calmette Guerin (BCG) Injection
These agents are thought to stimulate a local cell-mediated immune response when injected intratumorally and thus induce cytotoxic T cell and natural killer cell activity against tumor cells (Davies 1982, Misdorp et al. 1985). This method works reasonably well for nodular and fibroblastic lesions around the eyes but is much less effective elsewhere (Knottenbelt & Kelly 2000). It is recommended that intratumoural injections be repeated every 2-4 weeks until regression occurs; an average of 12 ml per treatment and 3.2 treatments were required to achieve regression of periorbital sarcoids (Lavach et al. 1985, Taylor & Haldorson 2013). It should not be used on sarcoids on the limbs, as it usually leads to the deterioration of the lesions. The method has significant risks and so careful supportive medication is required at the time of each injection. The risks relate to the chance that the horse will react adversely to the protein in the injection (Knottenbelt & Kelly 2000).
Injection of cytotoxic drugs, such as cisplatin or 5-fluorouracil, into the center of lesions is a useful method of treatment for most types. Two approaches are available for controlled-release administration: percutaneous injection of a viscous fluid and implantation of biodegradable beads (Taylor & Haldorson 2013). Cisplatin in arachid oil is proven effective as it leads to complete regression in 78% of the sarcoid cases, with no systemic side-effects encountered (Spoormakers et al. 2002). Still, although treatment is easy to perform, the ALARA (As Low As Reasonably Achievable) principle should be followed when using cytostatics (Spoormakers et al. 2002). The combined use of injecting a chemotherapeutic drug (cisplatin) into the sarcoid followed by the application of high-voltage electric pulses is called electrochemotherapy (ECT). ECT is a new anticancer therapy that utilizes electrical field pulses to induce increased cell membrane permeability to antitumor hydrophilic drugs, such as cisplatin (Tamzali et al. 2012). This increases the drug concentration into the cells of the sarcoid by 100 times thereby increasing its effect (Tamzali et al. 2012). Due to the electric shock the procedure is completed under a brief (usually 15 minute) general anesthetic (Tamzali et al. 2012). Intratumoural injections of 5-fluorouracil have also been used for the treatment of equine sarcoids. This treatment modality should be used in relatively smaller tumors as sarcoids smaller than 13.5 cm3 are significantly more likely to resolve with treatment than larger sarcoids (Stewart et al. 2006). In general, the success rate of intratumoral 5-fluorouracil climbs up to 61.5% (Stewart et al. 2006).
5-Fluorouracil cream can be effective for the milder forms of occult or verrucose sarcoid. It is particularly useful as a pre-treatment modality before another method, such as surgery, cryosurgery or AW4-LUDES is used.
AW4-LUDES (Liverpool cream) are compounded topical chemotherapy creams that contain 5% fluorouracil, heavy metals and thiouracil. They are caustic agents that are dispensed at varying concentrations and cause inflammation and necrosis of sarcoid tissue without harming normal skin. There are variations in the power, duration, and interval between treatments. Usually, application of the cream daily or every other day is recommended for 3-5 treatments with necrosis of the sarcoid expected 5-10 weeks after the final treatment (Newton 2000).
Imiquimod cream is available for topical human use, and it can be used in some areas of the body and on superficial sarcoids only. It requires very specialized management with prolonged applications that may last up to 32 weeks. According to a recent study (Nogueira et al. 2006), application of imiquimod 5% cream three times a week until complete resolution of the tumor or 32 weeks led to marked improvement (80%) or complete resolution of tumors (60%). Advantages of imiquimod therapy include convenient application by owners without special equipment and facilities, a noninvasive treatment protocol and a satisfactory cosmetic outcome. It may be the first therapy choice for tumors in certain locations, such as the limbs, perineal and periorbital areas where other treatments may be inappropriate. Common adverse effects include exudation, erythema, erosions, depigmentation and alopecia; these are usually limited to the tumor and adjacent areas (Nogueira et al. 2006).
Radiotherapy is considered the gold standard treatment, and high dose rate brachytherapy (HDRB) may represent a safer and more effective method of delivering radiotherapy in the standing sedated horse (Bradley et al. 2017, Hollis & Berlato 2018). Usually, radiation is limited to localized lesions at difficult sites such as around the eyes and over joints. There are several ways in which radiation can be applied. The common method is the use of interstitial brachytherapy (Bradley et al. 2017). In this method radiation sources are implanted into the tumor and left to deliver the calculated dose of radiation before either being removed or fading sufficiently to be insignificant (Taylor & Haldorson 2013). Most current radiation systems use sealed radiation sources in the form of pellets or wires of a radioactive material (usually radio-222, gold-198 or, more often, iridium-192) to deliver gamma radiation. However, iridium-192 implants and other radioisotopes are expensive and not widely available but may be the best option for recurrent aggressive lesions (Taylor & Haldorson 2013). Radiation gives by far the best results (both in cure rates and cosmetic effects) but it is very expensive and very restricted (Hollis & Berlato 2018).
European mistletoe, Viscum album austriacus aqueous extracts (VAE) are used in the treatment of human cancer. The antitumoral properties of the VAE are mainly attributed to mistletoe lectins, which are glycoproteins, and viscotoxins, a class of polypeptides. VAE proved effective for treatment of equine sarcoids. It can be recommended particularly when excision is not indicated as the primary therapy, tumors near the eye, and in cases with multiple sarcoids, where complete surgical removal or local medical treatment is impractical (Christen-Clottu et al. 2010, Felenda & Stintzing 2018).
A “herbal paste” for topical use known as XXTERRA is reported to be effective in some cases. It is an extract of Blood Root (Sanguineria canadensis)along with zinc salts. Apparently, XXTERRΑ affects sarcoids by altering the tumor antigens in vivo. This stimulates the immune system to recognize them as foreign and mount a response quite similar to the host vs. graft rejection. The tumor bed becomes lined with sensitized white blood cells and becomes inflamed causing it to slough off.
Recently, therapeutic vaccines composed of chimeric virus-like particles have resulted in tumor regression in approximately half of treated equids (Ashrafi et al. 2008, Mattil‐Fritz et al. 2008, Taylor & Haldorson 2013). Further research is needed in this field and attempts to circumvent virus-mediated immunosuppression are ongoing (Ashrafi et al. 2008, Mattil‐Fritz et al. 2008).
In clinical practice, it is usually easy to identify sarcoids, therefore biopsy should be avoided, as sarcoids tend to become more aggressive afterwards. Still, it is always tricky to decide which is the best therapeutic approach. The best treatment plan is to start treatment early, before the tumor increases substantially in size. If means of radiation are available, this would be the treatment of choice. In not, and the size of the mass is relatively small, surgical excision with wide margins is the most practical solution and the patient should be monitored closely for the following months. If a relapse occurs, then, a topical cream should be applied while the size of the mass is still small. Although imiquimod is good, according to our experience, XXTERRA gives better results.
Allen AL (2010) Epidemiology of equine sarcoids in horses in western Canada. Can Vet J 51, 1103-1108.
Ashrafi GH, Piuko K, Burden F, Yuan Z, Gault EA, Muller M, Trawford A, Reid SW, Nasir L, Campo MS (2008) Vaccination of sarcoid‐bearing donkeys with chimeric virus‐like particles of bovine papillomavirus type 1. J Gen Virol 89, 148‐157.
Bradley WM, Schilpp D, Khatibzadeh SM (2017) Electronic brachytherapy used for the successful treatment of three different types of equine tumors. Equine Vet Educ 29, 293-298.
Carr EA, Theon AP, Madewell BR, Griffey SM, Hitchcock ME (2001) Bovine papillomavirus DNA in neoplastic and nonneoplastic tissues obtained from horses with and without sarcoids in the western United States. Am J Vet Res 62, 741-744.
CarstanjenB, Jordan P, Lepage OM (1997) Carbon dioxide laser as a surgical instrument for sarcoid therapy – a retrospective study on 60 cases. Can Vet J 38, 773‐776.
Christen-Clottu O, Klocke P, Burger D, Straub R, Gerber V (2010) Treatment of clinically diagnosed equine sarcoid with a mistletoe extract (Viscum album austriacus). J Vet Intern Med 24, 1483-1489.
Compston PC, Turner T, Wylie CE Payne RJ (2016) Laser surgery as a treatment for histologically confirmed sarcoids in the horse. Equine Vet J 48, 451-456.
Davies M (1982) Bacillus Calmette‐Guerin as an antitumour agent. The interaction with cells of the mammalian immune system. Biochem Biophys Acta 651, 143‐174.
Felenda J, Stintzing F (2018) Mistletoe Preparations as an Option for Treatment of Equine Sarcoids – Results of an In vitro Investigation on Cell Proliferation in 2D and 3D Design. J Vet Med Res 5, 1169-1175.
Genetzky RM, Biwer RD, Myers RK (1983) Equine sarcoids, causes, diagnosis, and treatment. Comp Cont Educ Pract Vet 5, 416.
Hewes CA, Sullins, KE (2009) Review of the treatment of equine cutaneous neoplasia. Proc Am Ass Equine Practitioners 5, 386‐393.
Hollis AR, Berlato D (2018) Initial experience with high dose rate brachytherapy of periorbita sarcoids in the horse. Equine Vet Educ 30, 444-449.
Jackson C (1936) The mixed tumors. Onderstepoort J Vet Sci Anim Ind 345–385.
Kidney BA, Berrocal A (2008) Sarcoids in two captive tapirs (Tapirus bairdii): Clinical, pathological, and molecular study. Vet Dermatol 19, 380–384.
Knottenbelt DC (2005) A suggested clinical classification for the equine sarcoid. Clin Tech Eq Pract 4, 278-295.
Knottenbelt DC (2019) The Equine Sarcoid. Why are there so many treatment options? Vet Clin N Am Equine Pract 35, 243-262.
Knottenbelt DC, Kelly DF (2000) The diagnosis and treatment of periorbital sarcoid in the horse: 445 cases from 1974 to 1999. Vet Ophthalmol 3, 169‐191.
Knottenbelt DC, Walker JA. Topical treatment of the equine sarcoid (1994) Equine Vet Educ 6, 72-75.
Lavach JD, Sullins KE, Roberts SM, Severin GA, Wheeler C, Lueker DC (1985) BCG treatment of periocular sarcoid. Equine Vet J 17, 445‐448.
Lohr CV, Juan-Salles C, Rosas-Rosas A, Paras Garcia A, Garner MM, Teifke JP (2005) Sarcoids in captive zebras (Equus burchellii). Association with bovine papillomavirus type 1 infection. J Zoo Wildl Med 36, 74–81.
Martens A, De Moor A, Demeulemeester J, Peelman L (2001) Polymerase chain reaction analysis of the surgical margins of equine sarcoids for bovine papilloma virus DNA. Vet Surg 30, 460-467.
Martens A, DeMoor A (1996) Equine sarcoid. 1. Clinical types, prevalence, epidemiology, aetiology and pathogenesis. Vlaams Diergen Tijds 65, 10-17.
Mattil‐Fritz S, Scharner D, Piuko K, Thones N, Gissmann L, Muller H, Muller M (2008) Immunotherapy of equine sarcoid: dose‐escalation trial for the use of chimeric papillomavirus‐like particles. J Gen Virol 89, 138‐147.
McCauley CT, Hawkins JF, Adams SB, Fessler JF (2002) Use of a carbon dioxide laser for surgical management of cutaneous masses in horses: 32 cases (1993‐2000). J Am Vet Med Ass 220, 1192‐1197.
McConaghy FF, Davis RE, Reppas GP, Rawlinson RJ, McClintock SA, Hutchins DR, Hodgson DR (1994) Management of equine sarcoids: 1975‐93. N Z Vet J 42, 180‐184.
Misdorp W, Klein WR, Ruitenberg EJ, Hart G, de Jong WH, Ruitenberg PA (1985) Clinicopathological aspects of immunotherapy by intralesional injections of BCG cell walls or live BCG in bovine ocular squamous cell carcinoma. Cancer Immunol Immunother 20, 223‐230.
Nasir L, Campo MS (2008) Bovine papillomaviruses: their role in the aetiology of cutaneous tumors of bovids and equids. Vet Dermatology 19, 243-254.
Newton SA (2000) Periocular sarcoids in the horse: three cases of successful treatment. Equine Vet Educ 12, 137‐143.
Nogueira SA, Torres SM, Malone ED, Diaz SF, Jessen C, Gilbert S(2006) Efficacy of imiquimod 5% cream in the treatment of equine sarcoids: a pilot study. Vet Dermatology 17, 259-265.
Otten N, von Tscharner C, Lazary S, Antczak DF, (1993) DNA of bovine papillomavirus type 1 and 2 in equine sarcoids: PCR detection and direct sequencing. Arch Virol 132, 121-131.
Reid SW, Gettinby G, Fowler JN, Ikin P (1994) Epidemiological observations on sarcoids in a population of donkeys (Equus asinus). Vet Rec 134, 207–211.
Scott DW, Miller WH (2003) Neoplastic and non-neoplastic tumors. In: Equine Dermatology. St. Louis, Missouri, Saunders, pp. 719-731.
Semik‐Gurgul Ewelina (2021) Molecular approaches to equine sarcoids. Equine Vet J 5, 221-230.
Spoormakers TJ, Klein WR, van Weeren PR (2002) Treatment of equine sarcoids with cisplatin in arachid oil: a useful alternative. Tijdschr Diergeneeskd 127, 350-354.
Stewart AA, Rush B, Davis E (2006) The efficacy of intratumoural 5-fluorouracil for the treatment of equine sarcoids. Aust Vet J 84,101-106.
Tamzali Y, Borde L, Rols MP, Golzio M, Lyazrhi F, Teissie J (2012) Successful treatment of equine sarcoids with cisplatin electrochemotherapy: a retrospective study of 48 cases. Equine Vet J 44, 214‐220.
Taylor S, Haldorson G (2013) A review of equine sarcoid. Equine vet Educ 25, 210-216.
Teifke JP, Hardt M, Weiss E (1994) Detection of bovine papillomavirus DNA in formalin-fixed paraffin-embedded equine sarcoids by polymerase chain reaction and non-radioactive in situ hybridization. Eur J Vet Pathol 1, 5-10.
Teifke JP, Weiss E (1991) Detection of bovine papillomavirus DNA in equine sarcoids using the polymerase chain reaction (PCR). Berl Munch Tierarztl Wochenschr 1104, 185-187.
Torrontegui BO, Reid SWJ (1994) Clinical and pathological epidemiology of the equine sarcoid in a referal population. Eq Vet Educ 6, 85-88.
Valentine BA (2006) Survey of equine cutaneous Neoplasia in the Pacific Nortwest. J Vet Diagn Invest 18, 123-126.
Wobeser BK, Davies JL, Hill JE, Jackson ML, Kidney BA, Mayer MN, Townsend HG,
Yuan Z, Gobeil PAM, Campo MS, Nasir L (2010) Equine sarcoid fibroblasts over-express matrix metalloproteinases and are invasive. Virology 396, 143-151.
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