Squamous Cell Carcinoma
Primary squamous cell carcinoma is a common tumour in horses. It only occurs in areas where there are squamous cells which means the skin, mouth, nasal cavity/sinuses and stomach.
Penile carcinoma is probably the commonest form.
How malignant the tumour is can be determined by its appearance under a microscope. If the cells appear relatively normal and produce keratin then it is less aggressive. Highly malignant forms produce virtually no keratin and are aggressive with rapid spread via blood and lymphatics to the local lymph node (gland) or to internal organs
What causes Carcinoma?
Carcinoma is caused by exposure to carcinogens (cancer inducing agents) such as sunburn or smegma (in the case of penile or clitoral forms). There is greater risk in parts of the world where the sun is stronger (nearer the equator). This risk factor is similar to that form human skin cancers.
Types of Carcinoma
Three clinical forms are recognised.
- Proliferative: Form a growth which is the common form on the penis of older geldings and on the cornea (surface of the eye).
- Ulcerative/Destructive: The tumour results in tissue loss, erosions and ulcerations. This type are commonly found on the non-pigmented eyelids and third eyelids, around the anus or perineal area.
- Combined ulcerative/Destructive forms: Quite a common form which includes the vulvar or clitoral forms. Younger geldings are liable to developing this type and where the horse is under 10 years of age there is a high degree of malignancy.
Squamous cell carcinoma of the Eye
Squamous cell carcinoma occurs in the eyelids, the third eyelid and the outside corner (lateral limbus) of the eye and on the surface of the cornea.
Eyelid squamous cell carcinoma is usually extensive, highly destructive, and invasive.
Non-pigmented eyelids are much more liable to develop the destructive and ulcerative form, and certain breeds are at greater risk.
The least common ocular forms include a lateral limbal form that is proliferative, and a carcinoma in situ where the corneal epithelium is involved. Horses with the corneal form usually present with an eye discharge that can be cloudy or look like pus.
When the carcinoma is advanced it is easy to diagnose. The first sign of disease is usually excessive tear production, testing the tears with a urine blood dipstick usually reveals blood. Sometimes the tears may be visibly blood stained.
Cutaneous (Skin) Squamous Cell Carcinoma
Cutaneous forms of squamous cell carcinoma occur in the facial region, the ears and the perineal skin. The majority of these are ulcerative/destructive forms. The site and extent of tissue loss at the time of diagnosis will affect the prognosis.
Penile Squamous Cell Carcinoma
There are two major forms of penile squamous cell carcinoma.
- The common form occurs in older geldings – stallions are very rarely affected and this suggests that smegma may be a precipitating factor. The lesions may be proliferative or ulcerative/destructive or there may be a combination of the two. The glans (head of the penis) is most often affected while the skin of the shaft of the penis may sometimes be involved. Lesions may be multiple and may be ulcerated or proliferative.
- In younger horses (<10–14 years of age) there is a much higher malignancy rate and these cases are often to far gone by the time they present to the vet. Often the glans (head of the penis) is the primary lesion.
The more malignant forms and those that have a very chronic course may sometimes “seed” into the skin at the opening to the prepuce. These lesions are very aggressive and may occur independently of the penile forms. The prognosis for these cases is extremely poor. Removal of the whole penis and prepuce and moving the urethra up to under the tail is the only option. Tumours at this site can result in scarring and a narrowing of the urethra so the first signs of this complication may be difficulty in urinating.
Horses with preputial discharge (often containing some (stale) blood) may indicate a pre-cancerous change in the skin of the penis and the glans.
Vulvar or Clitoral Squamous Cell Carcinoma
Vulvar or clitoral forms occur in older mares and can occur on pigmented skin. The carcinogenic properties of smegma may be involved in the development of the clitoral form. Vulvar carcinomas are usually proliferative when they develop within the vestibule, and ulcerative when they involve the lips of the vulva. The clitoral form is proliferative. Treatment usually involves a combination of radiation and surgical excision.
Mucosal Squamous Cell Carcinoma
Squamous cells form the mucosal surface that lines the mouth, nose, sinuses and throat (pharynx). The main presenting signs include chronic blood stained or pus like nasal discharge or oral bleeding. Secondary signs can include nasal obstruction and difficulty in swallowing or eating (dysphagia). Early clinical signs may not however be obvious. Because these forms are usually proliferative facial distortions and swellings may be detected. Mucosal forms of Squamous Cell Carcinoma often have an aggressive destructive nature and so may be a large proliferative lesion with extensive surrounding destruction.
Gastric squamous cell carcinoma only occurs in the oesophageal (squamous) portion of the stomach. Recurrent gastric infestation with Habronema and Draschia spp. worms or Bots may cause cancerous changes. Many horses with high infestations of all these never develop any disease. There is no evidence of a bacterial carcinogen.
Gastric carcinomas are usually a combination of proliferation and destruction and this is probably the most aggressive form in horses. There is a high rate of direct spread to the liver and secondary spread to the lungs. Initial signs are often subtle and so on presentation these cases are usually clinically ill with recurrent colic, weight loss, inappetance and a harsh dry coat. The horse may also be slightly anaemic. As these signs can be associated with many other conditions cases are often presented late in the course. Use of a long endoscope is required for diagnosis. A tentative diagnosis can sometimes be obtained from gastric washings (containing both blood and abnormal squamous cells) or from abdominal fluid (containing blood, protein and abnormal squamous cells).
Treatment of Carcinoma
Squamous cell carcinoma management relies upon surgical or cryosurgery removal, or the application of various cytotoxic chemicals. Squamous cell carcinoma is usually locally aggressive and the prognosis is poor if the eye or area around the eye has been invaded. Although laser surgery has been attempted in some cases it is too early to confirm if this technique provides long term success.
Radiation therapy is considered the gold standard in suitable sites where surgical removal cannot be contemplated, or where the margins of the tumour are poorly defined making total removal challenging.
Radiation treatment is probably the best treatment option for all forms of squamous cell carcinoma of the skin in horses as the tumour is very sensitive both gamma and beta radiation. However the damaging effect of radiation on the eye itself means that some tumours in or around the eye cannot be treated in this way.
Both forms of radiation treatment use a radiation source that is implanted at the lesion. Gamma radiation from linear iridium192 wire is used for the treatment of eyelid carcinoma. Beta radiation from a Strontium90plaque is used on lesions at the corners of the eye and on the third eyelid or eye surface.
The cosmetic effects of radiation treatment are remarkably good with a relatively rapid resolution and minimal secondary complications even in severely destructive eyelid cases.
As beta radiation only penetrates about 1–2 mm deep into the tissue, it may be necessary to perform debulking surgery before the radiation treatment. Your vet should submit any tissue removed for histopathology (examining under a microscope) as this can determine the best course of action.
Surgical removal is the treatment of choice for all defined types of carcinoma at all sites but the criteria for selection of this method are strict. Surgical removal should not be considered if the tumour has already invaded the local lymph node or the margins of the tumour cannot be fully defined.
Surgery can be used for tumours of the third eyelids and conjunctiva (lining of the eyelid) and for most cases of early penile carcinoma.
Surgical removal of carcinoma on the surface of the eye (corneal carcinoma in situ) is extremely difficult, requiring microsurgical techniques involving removing part of the eye surface with a margin of 1-2 mm around the tumour. If not performed correctly the eye can rupture.
Eyelid tumours are generally not treated with surgical excision, unless they are very small and localised. The size of the tumour will determine if the eye lid can be preserved or reconstructed. Inadequate eyelid function is a serious complication and can lead to severe pain and eventual loss of the eye altogether.
Surgical amputation of the penis in horses with penile carcinoma is curative and recurrences are rare provided that all the tumour tissue is removed and the surgeon employs the principles of smart surgery to limit the risk of cross contamination of the wound site.
Removal of large aggressive carcinomas act as a temporary salvage procedure and the prognosis is poor.
Clitoral and some vulvar forms of carcinoma can be surgically removed with a reasonable prognosis.
Cryosurgery is rarely effective but can be considered for small lesions on the eyelid and other sites. The secondary effects of the freeze cycle can be very serious so sites needs to be chosen with great care. Nasal lesions and some oral lesions may be managed with cryosurgery but the results depend upon total tumour destruction. Lesions that are ulcerated and which bleed significantly may be managed by careful cryosurgery. However there are areas where its use is totally impossible and potentially dangerous. .
This chemotherapy agent is applied in a cream to the surface of the tumour and requires persistent application over several weeks and highly invasive or aggressive lesions do not seem to respond effectively in the time available.
The use of 5-Fluoro-uracil has been described for oral carcinomas (Patterson, 1997) but there are no reports of its use in the eyelids or for ocular lesions.
Cisplatin has to be injected into the carcinoma as an emulsion with almond or sesame oil (intralesional injection). It is effective in some cases although there are relatively few reports of success compared to other standard methods. The volume and concentration of cisplatin are critical (1 mg cisplatin needs to be delivered to 1 ml of tumour).
BCG has been used with success on cattle with carcinoma of the eye or area around the eye. It appears to work by stimulating the immune system to attack the cancer cells. It does not work in any other sites in cattle and does not appear to be successful in horses.
The prognosis for squamous cell carcinoma is dependent on:
- The site of the carcinoma and its suitability for effective therapy
- How malignant the carcinoma is.
- How long the carcinoma has been present and how many failed treatments have been attempted.
- How extensive the secondary effects of the carcinoma have become
Squamous cell carcinoma is less malignant in the horse than in other species. However gastric carcinoma, oropharyngeal carcinoma, and penile carcinoma in younger geldings are usually more malignant than other forms.
An early diagnosis and treatment improves the prognosis so any suspicious signs such as blood in the tears or other discharges should be actively investigated as soon as possible.