Skin cancer, or neoplasia, is the most common type of cancer diagnosed in horses, accounting for 45[1] to 80%[2] of all cancers diagnosed. Sarcoids are the most common type of skin neoplasm and are the most common type of cancer overall in horses. Squamous-cell carcinoma is the second-most prevalent skin cancer, followed by melanoma.[3] Squamous-cell carcinoma and melanoma usually occur in horses greater than 9-years-old,[3] while sarcoids commonly affect horses 3 to 6 years old. Surgical biopsy is the method of choice for diagnosis of most equine skin cancers,[1] but is contraindicated for cases of sarcoids.[4] Prognosis and treatment effectiveness varies based on type of cancer, degree of local tissue destruction, evidence of spread to other organs (metastasis) and location of the tumor. Not all cancers metastasize and some can be cured or mitigated by surgical removal of the cancerous tissue or through use of chemotherapeutic drugs.
Occult (hairless area at left) and nodular (large round bump at right) forms of equine sarcoids
Sarcoids account for 39.9% of all equine cancers and are the most common cancer diagnosed in horses.[3] There is no breed predilection for developing sarcoids and they can occur at any age, with horses three to six years old[5][6] being the most common age group and males being slightly more prone to developing the disease.[6] Sarcoids are also more prevalent in certain familial lines, suggesting that there may be a heritable component.[7] Several studies have found an association between the presence of Bovine papillomavirus-1 and 2 and associated viral growth proteins in skin cells with sarcoid formation, but the exact mechanism that controls or induces epidermal proliferation remains unknown.[8] However, high viral loads within cells are strongly correlated with more severe clinical signs and aggressive lesions.[9]
Clinical signs
The appearance and number of sarcoids can vary, with some horses having single or multiple lesions, usually on the head, legs, ventrum and genitalia or around a wound.[6] The distribution pattern suggests that flies are an important factor in the formation of sarcoids.[7] Sarcoids may resemble warts (verrucous form), small nodules (nodular form), oval hairless or scaly plaques (occult form) or very rarely, large ulcerated masses (fibroblastic form). The occult form usually presents on skin around the mouth, eyes or neck, while nodular and verrucous sarcoids are common on the groin, penile sheath or face. Fibroblastic sarcoids have a predilection for the legs, groin, eyelid and sites of previous injury.[10] Multiple forms may also be present on an individual horse (mixed form).[6]Histologically, sarcoids are composed of fibroblasts (collagen producing cells) that invade and proliferate within the dermis and sometimes the subcutaneous tissue but do not readily metastasize to other organs.[11] Surgical biopsy can definitively diagnose sarcoids, but there is a significant risk of making sarcoids worse. Therefore, diagnosis based solely on clinical signs, fine-needle aspiration or complete excisional biopsy are safer choices.[4]
Treatment
While sarcoids may spontaneously regress regardless of treatment in some instances,[12] course and duration of disease is highly unpredictable and should be considered on a case-by-case basis taking into account cost of the treatment and severity of clinical signs.[2] Surgical removal alone is not effective, with recurrence occurring in 50 to 64% of cases, but removal is often done in conjunction with other treatments.[10] Topical treatment with products containing bloodroot extract (from the plant Sanguinaria canadensis) for 7 to 10 days has been reported to be effective in removing small sarcoids, but the salve's caustic nature may cause pain and the sarcoid must be in an area where a bandage can be applied.[10] Freezing sarcoids with liquid nitrogen (cryotherapy)[13] is another affordable method, but may result in scarring or depigmentation.[10] Topical application of the anti-metabolite 5-fluorouracil[13] has also obtained favorable results, but it usually takes 30 to 90 days of repeated application before any effect can be realized.[10] Injection of small sarcoids (usually around the eyes) with the chemotherapeutic agent cisplatin and the immunomodulator BCG have also achieved some success.[13] In one trial, BCG was 69% effective in treating nodular and small fibroblastic sarcoids around the eye when repeatedly injected into the lesion and injection with cisplatin was 33% effective overall (mostly in horses with nodular sarcoids).[14] However, BCG treatment carries a risk of allergic reaction in some horses[10] and cisplatin has a tendency to leak out of sarcoids during repeated dosing.[14]External beam radiation can also be used on small sarcoids, but is often impractical. Cisplatin electrochemotherapy (the application of an electrical field to the sarcoid after the injection of cisplatin, with the horse under general anesthesia), when used with or without prior surgery to remove the sarcoid, had a non-recurrence rate after four years of 97.9% in one retrospective study.[15] There is a chance of sarcoid recurrence for all modalities even after apparently successful treatment.[5] While sarcoids are not fatal, large aggressive tumors that destroy surrounding tissue can cause discomfort and loss of function and be resistant to treatment, making euthanasia justifiable in some instances. Sarcoids may be the most common skin-related reason for euthanasia.[16]
Squamous-cell carcinoma
Squamous-cell carcinoma on the vulva of a gray mare, possibly arising from the clitoris. The tumor is ulcerated and has multiple necrotic areas (black spots).
Smooth, raised plaque on upper eyelid of a Paint horse. This horse developed a carcinoma secondary to sunburn (termed solar keratosis carcinoma in situ).
Squamous-cell carcinoma (SCC) is the most common cancer of the eye, periorbital area[17] and penis,[18] and it is the second most common cancer overall in horses,[17] accounting for 12[3] to 20%[19] of all cancers diagnosed. While SCC has been reported in horses aged 1 to 29-years, most cases occur in 8 to 15-year-old horses, making it the most common neoplasm reported in older horses.[19] Carcinomas are tumors derived from epithelial cells and SCC results from transformation and proliferation of squames, epidermal skin cells that become keratinized. Squamous-cell carcinomas are often solitary, slow-growing tumors that cause extensive local tissue destruction. They can metastasize to other organs, with reported rates as high as 18.6%, primarily to the lymph nodes and lung.[19]
Clinical signs and predisposing factors
Tumors related to squamous-cell carcinoma (SCC) can appear anywhere on the body, but they are most often located in non-pigmented skin near mucocutaneous junctions (where skin meets mucous membranes) such as on the eyelids, around the nostrils, lips, vulva, prepuce, penis or anus. The tumors are raised, fleshy, often ulcerated or infected and may have an irregular surface.[5] Rarely, primary SCC develops in the esophagus, stomach (non-glandular portion), nasal passages and sinuses, the hard palate, gums, guttural pouches and lung.[19] The eyelid is the most common site, accounting for 40-50% of cases, followed by male (25-10% of cases) and female (10% of cases) genitalia.[20] Horses with lightly pigmented skin, such as those with a gray hair coat or white faces, are especially prone to developing SCC,[19] and some breeds, such as Clydesdales, may have a genetic predisposition.[20] Exposure of light-colored skin to UV light has often been cited as a predisposing factor,[19] but lesions can occur in dark skin and in areas that are not usually exposed to sunlight, such as around the anus.[20] Buildup of smegma ("the bean" in horseman's terms) on the penis is also linked to SCC[19] and is thought to be a carcinogen through penile irritation. Pony geldings and work horses are more prone to developing SCC on the penis, due to less frequent penile washing when compared to stallions.[21] Equine papillomavirus-2 has also been found within penile SCCs, but has not been determined to cause SCC.[22]
Treatment and prevention of SCC
Before treatment of squamous-cell carcinoma (SCC) is initiated, evidence of metastasis must be determined either by palpation and aspiration of lymph nodes around the mass or, in smaller horses, radiographs of the thorax. Small tumors found early in the disease process (most frequently on the eyelid) can be treated with cisplatin or radiation with favorable results. For more advanced cases, surgical removal of eye (enucleation), mass or penile amputation can be curative provided all cancerous cells are removed (wide margins obtained) and there is no metastasis.[23] However, young horses (usually geldings less than 8-years-old) that have a hard or "wooden" texture to SCCs on the glans penis have a very poor prognosis for treatment and recovery.[21]
Regular washing of the penis and prepuce in males as well as cleaning the clitoral fossa (the groove around the clitoris) in mares is recommended to remove smegma buildup, which also gives the opportunity for inspection for suspicious growths on the penis or on the vulva.[21]
Equine melanoma results from abnormal proliferation and accumulation of melanocytes, pigmented cells within the dermis. Gray horses over 6-years-old are especially prone to developing melanoma.[24] The prevalence of melanoma in gray horses over 15 years old[25] has been estimated at 80%.[19] One survey of Camargue-type horses found an overall population prevalence of 31.4%, with prevalence increasing to 67% in horses over 15 years old.[26] Up to 66% of melanomas in gray horses are benign,[19] but melanotic tumors in horses with darker hair-coats may be more aggressive and are more often malignant.[27] One retrospective study of cases sent to a referral hospital reported a 14% prevalence of metastatic melanoma within the study population. However, the actual prevalence of metastatic melanoma may be lower due to infrequent submission of melanotic tumors for diagnosis.[28] Common sites for metastasis include lymph nodes, the liver, spleen, lung, skeletal muscle, blood vessels and parotid salivary gland.[28]
Clinical signs
The most common sites for melanotic tumors are on the under-side of the tail near the base, on the prepuce, around the mouth or in the skin over the parotid gland (near the base of the ear).[24] Tumors will initially begin as single, small raised areas that may multiply or coalesce into multi-lobed masses (a process called melanomatosis) over time.[3] Horses under 2-years-old can be born with or acquire benign melanotic tumors (called melanocytomas), but these tumors are often located on the legs or trunk, not beneath the tail as in older animals.[29]
Treatment of melanoma
Treatment of small melanomas is often not necessary, but large tumors can cause discomfort and are usually surgically removed. Cisplatin and cryotherapy can be used to treat small tumors less than 3 centimeters, but tumors may reoccur.[10]Cimetidine, a histamine stimulator, can cause tumors to regress in some horses, but may take up to 3 months to produce results and multiple treatments may be needed throughout the horse's life.[10] There are few viable treatment options for horses with metastatic melanoma. However, gene therapy injections utilizing interleukin-12 and 18-encoding DNA plasmids have shown promise in slowing the progression of tumors in patients with metastatic melanoma.[30]
Other types of skin cancer
Lymphoma
Lymphoma is the most common type of blood-related cancer in horses and while it can affect horses of all ages, it typically occurs in horses aged 4–11 years.[31]
1 2 3 4 Torrontegui, B.O.; S. W. J. Reid (1994). "Clinical and pathological epidemiology of the equine sarcoid in a referral population". Equine Veterinary Education. 6 (2): 85–88. doi:10.1111/j.2042-3292.1994.tb01098.x.
↑ Top, J. G. B.; Heer, N.; Klein, W. R.; Ensink, J. M. (2008). "Penile and preputial tumours in the horse: A retrospective study of 114 affected horses". Equine Veterinary Journal. 40 (6): 528–532. doi:10.2746/042516408X281180. ISSN0425-1644. PMID18487101.
↑ Knight, C.G.; J. S. Munday; J. Peters; M. Dunowska (January 31, 2011). "Equine penile squamous cell carcinomas are associated with the presence of Equine Papillomavirus Type 2 DNA sequences". Veterinary Pathology. 48 (6): 1190–1194. doi:10.1177/0300985810396516. PMID21282669. S2CID1366300.
Beuchner-Maxwell, Virginia (2009). "Chapter 151: Skin tumors". In Norman Edward Robinson and Kim A. Sprayberry (ed.). Current therapy in equine medicine (6ed.). St. Louis: Elsevier Health Sciences. pp.692–697. ISBN978-1-4160-5475-7. Retrieved 7 August 2011.
Giuliano, Elizabeth A. (2009). "Chapter 139: Ocular squamous cell carcinoma". In Norman Edward Robinson and Kim A. Sprayberry (ed.). Current therapy in equine medicine (6ed.). St. Louis: Elsevier Health Sciences. pp.639–644. ISBN978-1-4160-5475-7. Retrieved 7 August 2011.
Pascoe, Reginald R.; Derek C. Knottenbelt (1999). "Equine Sarcoids". Manual of equine dermatology. London: WB Saunders. pp.244–252. ISBN978-0-7020-1968-5. Retrieved 7 August 2011.
Rooney, James R.; John L. Robertson (1996). "Melanoma". Equine Pathology. Ames: Iowa State University Press. pp.304–305. ISBN9780813823348.
Valentine, Beth A. (2006). "Chapter 13: Neoplasia". In Joseph Bertone (ed.). Equine geriatric medicine and surgery. St. Louis: Elsevier Health Sciences. pp.147–167. ISBN978-0721601632. Retrieved 6 August 2011.
Related Research Articles
Skin cancers are cancers that arise from the skin. They are due to the development of abnormal cells that have the ability to invade or spread to other parts of the body. It occurs when skin cells grow uncontrollably, forming malignant tumors. The primary cause of skin cancer is prolonged exposure to ultraviolet (UV) radiation from the sun or tanning devices. Skin cancer is the most commonly diagnosed form of cancer in humans. There are three main types of skin cancers: basal-cell skin cancer (BCC), squamous-cell skin cancer (SCC) and melanoma. The first two, along with a number of less common skin cancers, are known as nonmelanoma skin cancer (NMSC). Basal-cell cancer grows slowly and can damage the tissue around it but is unlikely to spread to distant areas or result in death. It often appears as a painless raised area of skin that may be shiny with small blood vessels running over it or may present as a raised area with an ulcer. Squamous-cell skin cancer is more likely to spread. It usually presents as a hard lump with a scaly top but may also form an ulcer. Melanomas are the most aggressive. Signs include a mole that has changed in size, shape, color, has irregular edges, has more than one color, is itchy or bleeds.
Penile cancer, or penile carcinoma, is a cancer that develops in the skin or tissues of the penis. Symptoms may include abnormal growth, an ulcer or sore on the skin of the penis, and bleeding or foul smelling discharge.
Cutaneous squamous-cell carcinoma (cSCC), also known as squamous-cell carcinoma of the skin or squamous-cell skin cancer, is one of the three principal types of skin cancer, alongside basal-cell carcinoma and melanoma. cSCC typically presents as a hard lump with a scaly surface, though it may also present as an ulcer. Onset and development often occurs over several months.
Anal cancer is a cancer which arises from the anus, the distal opening of the gastrointestinal tract. Symptoms may include bleeding from the anus or a lump near the anus. Other symptoms may include pain, itchiness, or discharge from the anus. A change in bowel movements may also occur.
Bovine papillomaviruses (BPV) are a paraphyletic group of DNA viruses of the subfamily Firstpapillomavirinae of Papillomaviridae that are common in cattle. All BPVs have a circular double-stranded DNA genome. Infection causes warts of the skin and alimentary tract, and more rarely cancers of the alimentary tract and urinary bladder. They are also thought to cause the skin tumour equine sarcoid in horses and donkeys.
An eye neoplasm is a tumor of the eye. A rare type of tumor, eye neoplasms can affect all parts of the eye, and can either be benign or malignant (cancerous), in which case it is known as eye cancer. Eye cancers can be primary or metastatic cancer. The two most common cancers that spread to the eye from another organ are breast cancer and lung cancer. Other less common sites of origin include the prostate, kidney, thyroid, skin, colon and blood or bone marrow.
Vulvar cancer is a cancer of the vulva, the outer portion of the female genitals. It most commonly affects the labia majora. Less often, the labia minora, clitoris, or Bartholin's glands are affected. Symptoms include a lump, itchiness, changes in the skin, or bleeding from the vulva.
Nasopharyngeal carcinoma (NPC), or nasopharynx cancer, is the most common cancer originating in the nasopharynx, most commonly in the postero-lateral nasopharynx or pharyngeal recess, accounting for 50% of cases. NPC occurs in children and adults. NPC differs significantly from other cancers of the head and neck in its occurrence, causes, clinical behavior, and treatment. It is vastly more common in certain regions of East Asia and Africa than elsewhere, with viral, dietary and genetic factors implicated in its causation. It is most common in males. It is a squamous cell carcinoma of an undifferentiated type. Squamous epithelial cells are a flat type of cell found in the skin and the membranes that line some body cavities. Undifferentiated cells are cells that do not have their mature features or functions.
Transitional cell carcinoma is a type of cancer that arises from the transitional epithelium, a tissue lining the inner surface of these hollow organs. It typically occurs in the urothelium of the urinary system; in that case, it is also called urothelial carcinoma. It is the most common type of bladder cancer and cancer of the ureter, urethra, and urachus. Symptoms of urothelial carcinoma in the bladder include hematuria. Diagnosis includes urine analysis and imaging of the urinary tract (cystoscopy).
Urethral cancer is a rare cancer originating from the urethra. The disease has been classified by the TNM staging system and the World Health Organization.
Vaginal cancer is an extraordinarily rare form of cancer that develops in the tissue of the vagina. Primary vaginal cancer originates from the vaginal tissue – most frequently squamous cell carcinoma, but primary vaginal adenocarcinoma, sarcoma, and melanoma have also been reported – while secondary vaginal cancer involves the metastasis of a cancer that originated in a different part of the body. Secondary vaginal cancer is more common. Signs of vaginal cancer may include abnormal vaginal bleeding, dysuria, tenesmus, or pelvic pain, though as many as 20% of women diagnosed with vaginal cancer are asymptomatic at the time of diagnosis. Vaginal cancer occurs more frequently in women over age 50, and the mean age of diagnosis of vaginal cancer is 60 years. It often can be cured if found and treated in early stages. Surgery alone or surgery combined with pelvic radiation is typically used to treat vaginal cancer.
Wolfram Samlowski is an American medical oncologist with Comprehensive Cancer Centers of Nevada (CCCN) and a member of the Research Developmental Therapeutics and Genitourinary Committees for US Oncology. His research interests include translational research and development of novel cancer immunotherapy agents, translational drug development as well as gene therapy. His clinical interests are in developing more effective treatments for advanced stages of melanoma and non-melanoma skin cancers, and renal cancer.
Nivolumab, sold under the brand name Opdivo, is an anti-cancer medication used to treat a number of types of cancer. This includes melanoma, lung cancer, malignant pleural mesothelioma, renal cell carcinoma, Hodgkin lymphoma, head and neck cancer, urothelial carcinoma, colon cancer, esophageal squamous cell carcinoma, liver cancer, gastric cancer, and esophageal or gastroesophageal junction cancer. It is administered intravenously.
Conjunctival squamous cell carcinoma and corneal intraepithelial neoplasia comprise ocular surface squamous neoplasia (OSSN). SCC is the most common malignancy of the conjunctiva in the US, with a yearly incidence of 1–2.8 per 100,000. Risk factors for the disease are exposure to sun, exposure to UVB, and light-colored skin. Other risk factors include radiation, smoking, HPV, arsenic, and exposure to polycyclic hydrocarbons.
Pembrolizumab, sold under the brand name Keytruda, is a humanized antibody, more specifically a PD-1 Inhibitor, used in cancer immunotherapy that treats melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, stomach cancer, cervical cancer, and certain types of breast cancer. It is administered by slow intravenous injection.
Squamous-cell carcinoma (SCC) of the lung is a histologic type of non-small-cell lung carcinoma (NSCLC). It is the second most prevalent type of lung cancer after lung adenocarcinoma and it originates in the bronchi. Its tumor cells are characterized by a squamous appearance, similar to the one observed in epidermal cells. Squamous-cell carcinoma of the lung is strongly associated with tobacco smoking, more than any other forms of NSCLC.
Atezolizumab, sold under the brand name Tecentriq among others, is a monoclonal antibody medication used to treat urothelial carcinoma, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), hepatocellular carcinoma and alveolar soft part sarcoma, but discontinued for use in triple-negative breast cancer (TNBC). It is a fully humanized, engineered monoclonal antibody of IgG1 isotype against the protein programmed cell death-ligand 1 (PD-L1).
An equine melanoma is a tumor that results from the abnormal growth of melanocytes in horses. Unlike in humans, melanomas in horses are not thought to be caused by exposure to ultraviolet light. Melanomas are the third most common type of skin cancer in horses, with sarcoids being the first most prevalent and squamous-cell carcinoma being second. Melanomas are typically rounded black nodules that vary in size and are usually found underneath the dock of the tail, in the anal, perianal and genital regions, on the perineum, lips, eyelids, and sometimes near the throatlatch.
Squamous-cell carcinoma (SCC), also known as epidermoid carcinoma, comprises a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the lining of the respiratory and digestive tracts.
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