Sarcoids are the most common equine cutaneous tumour and continue to provide a clinical challenge. The majority of sarcoids are diagnosed based on their characteristic clinical appearance and locations, which is probably appropriate in most cases. Common locations for sarcoid lesions include the periocular region, axilla, inguinum and sheath, although they can occur anywhere, especially following a wound. However, it is important to recognise that other tumour types exist and can imitate sarcoids, especially nodular lesions. Where single nodular lesions are present and where lesions are in atypical locations, biopsy is strongly recommended to enable accurate diagnosis and appropriate treatment selection.
Is benign neglect a viable treatment option for sarcoids?
Benign neglect is most commonly employed with small occult or verrucose lesions. However, benign neglect may be a misnomer, as withholding treatment is not always a benign procedure. In a series of 42 periocular lesions that were not treated at the time of examination by a veterinary surgeon, all required treatment at a later stage and 64% of the horses were euthanised because the lesions were too extensive to treat at the time of referral (Knottenbelt and Kelly, 2000). However, in a series of 31 horses where some (but not all) of their sarcoid lesions were treated, some (but not all) of the untreated lesions spontaneously resolved regardless of the treatment used (Martens et al, 2001). Interestingly, in the same study, new lesions developed in 6 of the horses during the same time period (Martens et al, 2001). In a longitudinal study of 61 Franches-Montagnes horses, 38 horses had sarcoids documented at 3 years of age, but spontaneous regression occurred without any treatment in 65% of occult lesions and 32% of verrucose lesions (Berreux et al, 2016). It is not known if the same could be applied to other breeds, but the high prevalence of sarcoids in the Berreux et al (2016) study is surprising compared to the known owner-reported prevalence of 5.8% (Ireland et al, 2013). Although it is conceivable that many lesions are missed by owners, it is difficult to explain such a big discrepancy and to draw definitive conclusions. In one small placebo-controlled study, a complete or partial regression rate of 14% was reported in the placebo arm (Christen-Clottu et al, 2010), and in another study, 1.9% of small lesions spontaneously regressed (Pettersson et al, 2020), supporting the theory that some lesions may regress without specific therapy, albeit at a far smaller frequency than those reported in the Berreux et al (2016) study. Based on these data, benign neglect may be viable in a small number of early, small, occult or verrucose lesions, but regular monitoring is essential to ensure that lesions are not allowed to progress to the stage of being difficult to treat.
Updates on the treatment options for sarcoids
Despite advances in our understanding of the pathogenesis of sarcoids, there is still no consensus on the best treatment and because of their complexity and variability, different treatments are likely to be appropriate in different circumstances.
Topical treatments remain the mainstay of many protocols and some new products are available, although data on their use remains relatively limited. Acyclovir showed early promise in the treatment of small, superficial lesions (Stadler et al, 2011) but since then it has been associated with treatment failures (Haspeslagh et al, 2016) and a placebo-controlled study demonstrated no advantage of acyclovir over a placebo (Haspeslagh et al, 2017), so the author does not recommend its use. Topical bleomycin has recently become more popular for the treatment of superficial sarcoids but in general, its penetration is poor, limiting its use. A formulation of ultra-deformable liposomes containing bleomycin has been used, which is believed to have improved penetration, and had a reported success rate of 44.4% when used as a sole treatment (Knottenbelt et al, 2020). Tazarotene alone led to resolution in 17.1% of cases, and 5-fluoruracil alone led to resolution in 26.7% (Knottenbelt et al, 2020). When the bleomycin formulation was used in combination with either 5-fluoruracil or tazarotene, the success rates were markedly improved to 76.9% and 77.8% respectively, suggesting that a combination of these treatments may be useful for occult or verrucose sarcoids. All of these treatments require extended periods of application to have any chance of success, with the duration of treatment depending on the lesions.
Recently, a report suggested that topical imiquimod may lead to regression in 84% of lesions, with a recurrence rate of 7.3%, and that bloodroot ointment (sanguinaria canadensis plus zinc chloride) may be effective in treating 75% of lesions, with a recurrence rate of 21.4% (Pettersson et al, 2020). Although the authors reported that the treatments both worked more effectively in small lesions (Pettersson et al, 2020), the high recurrence rate following apparently successful treatment with bloodroot ointment suggests that it may not be particularly effective even in these cases. However, as both treatments are relatively cost-effective and can be applied by owners, they may provide useful alternative options, especially in cases with financial constraints. Imiquimod is usually applied every 3 days for up to 42 days, depending on the clinical response. There are no definitive guidelines for the use of blood-root ointment.
Based on the available data, the author uses laser surgical excision for the majority of first-line treatment of equine sarcoids. It appears to be a consistently successful therapeutic modality, with 83% of lesions having no recurrence following laser surgical excision (Compston et al, 2016). In the majority of cases, only one treatment is required and the lesions heal slowly but completely with minimal aftercare, making it a practical option for most owners.
Radiotherapy has consistently been reported to have very high success rates and may currently be administered via strontium plesiotherapy (Hollis, 2017, 2020), high dose rate brachytherapy (Hollis and Berlato, 2017), electronic brachytherapy (Bradley et al, 2017) or teletherapy (Henson and Dobson, 2004). Electronic brachytherapy and teletherapy both require general anaesthesia, making them less practical than approaches using strontium plesiotherapy and high dose rate brachytherapy, which can usually be administered under routine standing sedation (Henson and Dobson, 2004; Bradley et al, 2017; Hollis and Berlato 2017; Hollis, 2017, 2020). The very limited availability of any form of radiotherapy restricts its use and it is usually only recommended for periocular lesions or those in difficult locations such as over joints (Figures 1 and 2). Radiotherapy can be administered via a variety of protocols, but is most effectively performed using multiple fractions rather than as a single treatment. This approach improves the success rate and reduces the risk of adverse side-effects.
Interestingly, electrosurgery has been reported to have an impressive success rate of 86.8% (Haspeslagh et al, 2016). Although, to the author's knowledge, this technique is not yet widely available, if these results are replicated in further studies it represents a simple and relatively cost-effective alternative to laser surgical excision. The wounds were routinely closed following rinsing with a chlorhexidine solution (Haspeslagh et al, 2016), avoiding the open wound management and slow healing following laser surgical excision, making it an appealing alternative.
Electrochemotherapy is another useful treatment that is gaining popularity in the UK. Reported success rates of this technique range from 94-100% in a relatively large number of cases (Rols et al, 2002; Tamzali et al, 2012; Tozon et al, 2016). The technique is based on the intralesional injection of chemotherapeutic compounds (most commonly cisplatin). followed by the application of specialised electrodes to increase the penetration of the chemotherapeutic compound. Unfortunately, general anaesthesia is a prerequisite for treatment and multiple treatments are recommended, which presents a significant disadvantage compared to other modalities. However, its combination with other methods, such as laser surgical excision, is also being used in practice, and this may enable a single treatment under general anaesthesia which becomes a much more attractive prospect. The health and safety implications of the intralesional chemotherapy should not be underestimated, especially where cisplatin or carboplatin are used, and appropriate personal protective equipment of individuals handling the compound and the horse after treatment is essential.
Intralesional injections of Bacillus Calmette-Guerin have long been used in the treatment of periocular sarcoids (Knottenbelt and Kelly, 2000), but reduced availability has restricted its use. A related product has been developed, which is a Mycobacterium cell wall fraction marketed as Immunocidin Equine®, which has been used in lesions any location. This can be accessed via special import and its use in any location led to a complete resolution rate of 52.9%, with a further 17.6% showing improvement but not complete resolution at the time of follow-up (Caston et al, 2020). It is important to remember that these treatments are only likely to be effective where the lesion is readily accessible and of a type that is amenable to intralesional injections (verrucose and occult lesions are generally not suitable for intralesional injections). The reported protocol for use of Immunocidin Equine® is as an intralesional injection every 2 weeks until the tumours are resolved (Caston et al, 2020).
Recently, an interesting new intralesional therapy has been reported in the treatment of equine sarcoids. Tigilanol tiglate is licensed for the treatment of mast cell tumours in dogs and has been reported to be successful for the treatment of a single sarcoid in one horse (De Ridder et al, 2020). The treatment causes oncolysis, an acute inflammatory response, as well as increased tumour vasculature permeability which leads to haemorrhagic necrosis and the development of an eschar which sloughs off, leaving a wound that heals via secondary intention. The necrosis occurs extremely rapidly (Figure 3) and the resulting wounds are simple to manage, requiring minimal intervention. The author has used this in a small number of cases to good effect. Although, in one case, abscessation of the local lymph nodes occurred following treatment and a very wide slough has also been seen, so it is not without potential complications. Further work is required before its use could be routinely recommended.
Updates on the treatment options for melanoma
Melanomas remain ubiquitous in the grey horse population, and present a unique treatment challenge. They are believed to be benign in the majority of cases and treatment is therefore frequently sought at a late stage, when they begin to cause problems as a result of local invasion. Xenogeneic DNA vaccination against melanoma-associated antigens such as tyrosinase may provide a systemic therapy against multiple lesions, an attractive option if the therapy is successful. Tyrosinase is over-expressed in equine melanoma cells (Phillips et al, 2012). A product based on this concept has been licensed for use in canine melanomas in the USA, marketed as Oncept®. Using a standard protocol, this has been demonstrated to lead to the development of antibodies in horses, and it appears to be safe and well tolerated (Lembck Perez Prieto, 2013). There is limited data to suggest that this treatment may lead to stabilisation of the disease, with 28 treated horses showing no progression of their lesions, compared to progression of lesions in 20 untreated Lipizzaner stallions over the same time frame (Echelmeyer et al, 2020). Unfortunately, the control group was different to the treated group, as the control group consisted of a single breed and gender kept under similar conditions, as opposed to the treatment group which consisted of client-owned horses of varying breeds and genders kept under varying conditions, so drawing firm conclusions from these data is difficult. Oncept is administered as an intradermal injection via a specialised applicator every 2 weeks for four doses, and then one dose every 6 months thereafter. In the author's experience, the administration of Oncept appears to be associated with stabilisation of the disease in the majority of horses with melanomas, but it has little or no utility in end-stage cases where stabilisation alone is not sufficient. In these cases, treatment options beyond surgical resection and/or intralesional chemotherapy are difficult, and there is limited evidence for any one approach.
Update on treatment options for squamous cell carcinoma
Surgical excision with wide local margins remains the mainstay of treatment for the majority of cases of squamous cell carcinoma in any location. Where available, radiotherapy is the gold standard and is especially useful in suitable sites where surgery is not feasible or where margins are poorly defined. Prior to any treatment, staging should be performed to rule out the possibility of metastasis. Metastatic squamous cell carcinoma has a poor prognosis, unless all locally involved structures (such as lymph nodes) can also be resected. Intralesional tigilanol tiglate has also been reported to be successful in the treatment of one squamous cell carcinoma in a horse (De Ridder et al, 2020), and this is an interesting option that would be more widely accessible than radiotherapy in the majority of cases. Further work is required to fully assess its use but it may prove to be a useful and practical treatment option.
Other cutaneous tumours in horses
Other cutaneous tumours are occasionally seen in horses. There are limited treatments for these less frequent tumour types. Cutaneous lymphoma, basal cell carcinoma and mast cell tumours are all occasionally diagnosed, and each has their own recommended treatment protocol. In general, where surgical excision is possible, this is the recommended treatment for cutaneous lymphoma, but it may also respond to progesterone therapy in some cases, or to systemic corticosteroid administration. Mast cell tumours can be treated via surgical excision or intralesional injection with sterile water or corticosteroids, and are typically benign lesions in horses. In contrast to the same tumour type in dogs, systemic anti-histamine administration prior to treatment is not generally considered necessary, as significant histamine release from these lesions appears to be rare in horses. Basal cell carcinomas are benign lesions that frequently look like sarcoids, although they are most commonly located on the distal limb and tail. They are generally successfully treated via surgical excision.
KEY POINTS
- Biopsy should be performed to establish a diagnosis, especially in atypical lesions.
- Benign neglect may be an appropriate approach in early, small, occult or verrucose lesions, as spontaneous regression has been reported. However, early treatment at the first sign of progression is strongly recommended to avoid the lesions becoming advanced and more difficult to treat.
- Laser surgical resection is an appropriate first-line treatment for the majority of sarcoids, but other options include electrochemotherapy, electrosurgery, and new topical and intralesional treatments.
- Xenogenic DNA vaccines may be useful for the management of melanomas in horses.
- New intralesional treatments are available for the treatment of squamous cell carcinoma, which may provide a practical alternative to surgical excision.