Canine and feline oral tumors: Earlier is better

Author's note: This is the first of two articles that will address the most common canine and feline oral tumors. This article will discuss canine melanoma and squamous cell carcinoma. The second article will discuss fibrosarcoma and benign tumors in dogs as well as SCC and fibrosarcoma in cats.

Oral tumors are the fourth most common cancer in dogs and represent 6 percent of all canine cancers. The most common malignant tumors in dogs are melanoma, fibrosarcoma, SCC and osteosarcoma. Benign tumors include the epulides (ossifying, fibromatous and acanthomatous) and other odontogenic tumors. In cats, oral tumors make up 3 percent of all feline cancers. SCC is the most common malignant tumor followed by fibrosarcoma. Benign oral tumors are much less common in cats.

Photo 1: Dog with an oral melanoma. Note that this tumor is not pigmented.

Unfortunately, due to the location, these tumors are frequently not diagnosed until they are advanced, leading to a poorer prognosis. Early detection through client education and thorough oral examinations as well as aggressive intervention may improve the prognosis for our patients.

Photo 2: At necropsy, this 10-year-old Pug had widespread metastasis including the heart (pictured), as well as the lung and intestinal tract.

Canine oral tumors

Melanomas make up 30 to 40 percent of all oral tumors in dogs. They are typically friable pigmented tumors that occur most frequently along the gingiva, buccal and labial surface of the lip, on the hard or soft palate, and rarely the tongue (Photo 1). There are some melanomas that do not contain any pigment (amelanotic melanoma) so they may appear as friable fleshy lesions.

Photo 3: Metastasis to the adrenal gland.

Melanomas in the oral cavity should always be considered malignant regardless of the histology. They are locally invasive, and bone involvement is not uncommon. Metastasis to the local or regional lymph nodes or lungs is common although patients can present with widespread metastasis (Photos 2 and 3). It can be difficult to diagnose a melanoma if the cells are poorly differentiated or amelanotic (Photo 4). Melanomas can be misdiagnosed as round-cell tumors, epithelial tumors or anaplastic sarcomas. Immunohistochemistry could be helpful in confirming a diagnosis of melanoma although is not infallible. The most commonly employed markers include S-100 and Melan-A. However, sarcomas can be S-100 positive. The absence of Melan-A still does not rule out the potential for melanoma. Amelanotic melanomas do not appear to have a more aggressive behavior.

Photo 4: Cytology of a dog with oral melanoma. Note that several of the cells contain small pigmented granules, which is consistent with a melanoma.

Treatment of oral melanomas needs to take into consideration both local and systemic control. Staging should include three views of the thorax, preferably not under anesthesia, and aspirates of the draining lymph nodes. Options for local control would include surgical excision and/or radiation therapy. Given the potential for bone involvement and the need for wide margins, tumors on the gingiva generally require a mandibulectomy or maxillectomy. Tumors on the buccal surface should be excised with a full-thickness resection of the lip. A computed tomography (CT) scan, magnetic resonance image (MRI) or dental films prior to surgery may be helpful for surgical planning and to determine if the tumor is excisable. With surgery alone, local recurrence rates are around 25 percent with median survival times of eight months (MacEwen 2001). Dogs with tumors smaller than 2 cm have been reported to have a survival rate of 511 days while dogs that had tumors larger than 2 cm or with lymph-node involvement only had a survival time of 164 days (MacEwen 1986). It has also been reported that dogs treated for recurrent disease had a shorter survival time compared to those dogs that were treated aggressively at initial diagnosis (Harvey 1981).

Photo 5: Dog with an oral melanoma in the caudal maxilla. This photo was taken prior to starting radiation therapy.

For those cases where adequate margins cannot be obtained or surgery is not possible, radiation therapy is an option. Historically, melanomas have been considered resistant to radiation therapy; however, recent studies have shown that they are sensitive to the therapy.

Figure 6: Same dog three weeks later at time of final radiation treatment. Note the decrease in the tumor size seen following treatment.

An early study reported a partial and complete response rate of 83 percent when treating gross disease with three larger treatments of radiation therapy (0-,7-, 21-day schedule) (Bateman 1994) (Photos 5 and 6). The median survival time for this group of dogs was 7.9 months but the majority of dogs died due to systemic metastasis and not local recurrence. Additional studies found similar results (Bateman 1996, Proux 2003). As might be expected, dogs that had microscopic disease only fared better than those dogs with gross disease (Proux 2003). This underscores the need for early detection and initial aggressive treatment of these tumors.

Photo 7: Dog with a squamous cell carcinoma involving the rostral maxilla.

Given the high metastatic rate of these tumors, systemic therapy is indicated. However, similar to melanomas in humans, these tumors are relatively resistant to chemotherapy. Intravenous melphalan cisplatin and carboplatin all have been studied with limited success. Carboplatin was reported to have a partial and complete response rate of 28 percent in dogs with gross disease (Rassnick 2001); however several additional studies did not find any benefit. Chemotherapy has been used also for local control of melanomas. In one study, cisplatin in suspension was injected directly into the tumors. The complete and partial response rate was 70 percent with those dogs that achieved a complete response having a survival time of 51 weeks (Kitchell 1994). Keep in mind that the risk of personnel exposure to chemotherapy is higher with intralesional treatment.

Photo 8: Cytology of a dog with oral squamous cell carcinoma.

Activating the immune system

Melanomas are highly immunogenic tumors in both humans and canines. There is considerable interest in immunotherapy and gene therapy for the treatment of melanomas and other cancers. The concept of treating melanomas with immunotherapy is not new. Immunotherapy can involve a non-specific activation of the immune system or a targeted activation of the immune system specific for tumor cells. Early attempts at immunotherapy included injection of bacterial toxins, such as BCG or Corynebacterium parvum injected either intralesionally or systemically. This approach incites a non-specific activation of the immune system. More recently, this type of approach has been employed by either the exogenous administration of immunomodulatory cytokines, such as IL-2, interferon alpha and GM-CSF or the use of gene therapy to introduce genes that generate endogenous production of these cytokines. Tumor-specific methods of immunotherapy include the production of vaccines that are able to induce an immune reaction against antigens that are specific to melanoma cells, such as gp-100 and tyrosine kinase. Both of these approaches have been used in canine melanoma patients with some promise. Immunotherapy may ultimately become part of the standard of care for not only oral melanomas but for other tumors as well.

Photo 9: Dog with a squamous cell carcinoma of the mandible prior to surgery.

Canine oral SCC

SCC is the second most common oral tumor in dogs (Photos 7 and 8, p. 8S). These tumors are most commonly found on the gingiva but can involve the tongue or tonsil. Tonsillar SCC has an aggressive biologic behavior and will not be covered in this article. Non-tonsillar SCC is a locally invasive malignancy with a 5 to 10 percent rate of metastasis, although SCC of the tongue may have a higher metastatic rate. Bone involvement is common with these tumors. Metastasis is most frequently associated with the lymph node and lungs so complete staging should involve three views of the thorax and aspirates of the regional lymph nodes if possible.

Photo 10: Immediate post-operative photo of the same dog.

Given the low metastatic rate, treatment is directed at achieving local control of these tumors. As with most cancers, surgery is the treatment of choice whenever possible. For those tumors involving the mandible, a partial or hemi-mandibulectomy can provide long-term control (Photos 9 and 10). In one study, the median disease-free interval for dogs treated with mandibulectomy was 26 months and local recurrence was infrequent (Kosovsky 1991). Maxillary tumors can be more challenging. Ideally, they would require either an MRI or CT scan to determine the extent of the tumor. It is more likely that an incomplete margin will be obtained for maxillary tumors resulting in higher rate of local recurrence. The median survival time of all dogs treated with surgery alone was 18 months with a local recurrence rate of 15 percent (MacEwen 2001).

Photo 11: CT scan of a dog with an invasive maxillary squamous cell carcinoma. Due to the extent of involvement, surgery was not an option.

For those tumors that are not resectable or that have microscopic disease following surgical excision, radiation therapy is an option. Full-course radiation therapy would involve 15 to 20 treatments given over a three- to six-week period depending on the institution. Acute reactions to radiation therapy can include mucositis, moist desquamation and keratitis, KCS or conjunctivitis (depending on the location of the eye to the radiation field). With the exception of KCS, these effects resolve within two weeks after the completion of radiation therapy. In one study, median progression-free survival time for all patients with SCC was 36 months when treated with radiation therapy. Patients with tumors less than 2 cm had a significantly longer progression-free interval (Theon 1997). Given this finding, it is expected that treatment of microscopic disease with radiation therapy would provide long-term control. A second study reported a median local control rate of one year. In this study, the median disease-free interval and survival times were significantly greater for dogs younger than 9 years of age (LaDue-Miller 1996).

Photo 12: Photo of the same dog seen in the CT scan one week after starting piroxicam. This dog had a complete response to this drug. Note that there is an oronasal fistula present following regression of the tumor.

Given the lower metastatic potential, chemotherapy is not typically recommended for SCC. However, in situations were metastasis is present or when radiation therapy is not an option for non-resectable tumors, chemotherapy can be considered. Both cisplatin and mitoxantrone have been reported to have efficacy against these tumors. Although not a chemotherapeutic, piroxicam has also been used in the treatment of SCC in dogs (Photos 11 and 12). The exact mechanism of action is not known but piroxicam is not directly cytotoxic to tumor cells. The response rate to piroxicam has been reported around 18 percent (Schmidt 2001). Response rates of 55 percent have been reported when piroxicam is used in combination with cisplatin but caution must be exercised when using piroxicam with cisplatin given a higher risk of renal failure (Boria 2004).

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Dr. Cronin earned her DVM degree from Cornell University in 1990. She completed an internship at the Animal Medical Center in New York and a medical oncology residency at North Carolina State University. She is a diplomate of the American College of Veterinary Internal Medicine in the specialty of oncology. After completing her residency, she was lecturer at the University of Pennsylvania Veterinary Teaching Hospital and a medical oncologist at Angell Memorial Animal Hospital in Boston. In 2001, she co-founded the New England Veterinary Oncology Group in Waltham, Mass.