Oral Tumors

Oral Tumors

Symposium on Clinical Veterinary Oncology Oral Tumors H. jay Harvey , D.V.M.* Oral tumors in dogs and cats present difficulties in clinical manageme...

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Symposium on Clinical Veterinary Oncology

Oral Tumors H. jay Harvey , D.V.M.*

Oral tumors in dogs and cats present difficulties in clinical management. They are frequently large and locally invasive by the time they are detected. In addition, some types of oral tumors, such as melanomas and tonsillar squamous cell carcinomas, metastasize early in their development. INCIDENCE Malignant oral tumors account for 5.4 per cent of all canine neoplasms and 6. 7 per cent of all feline neoplasms. 5 The incidence of oral tumors is 70.4 cases per 100,000 dogs in the population. 4 In cats, oral malignancies affect 45.4 cats per 100,000. 4 The most common oral malignancies in dogs are melanomas, squamous cell carcinomas, and fibrosarcomas. These tumors account for 52 per cent, 18 per cent and 9 per cent of canine oral malignancies, respectively. 5 Other malignant oral tumors that are seen more infrequently include adenocarcinomas (7 per cent), odontogenic tumors (5 per cent), and hemangiosarcomas (5 per cent). 16 Tumors may invade the oral cavity from contiguous tissues. Among these are osteosarcomas and chondrosarcomas arising from the bones bordering the oral cavity, mast cell tumors, and nasal cavity tumors. In cats, 69 per cent of malignant oral tumors are squamous cell carcinomas and 18 per cent are fibrosarcomas. 2 Benign oral tumors are common in dogs and rare in cats. Benign oral tumors are most commonly epulides, tumors of dental epithelium, and gingival hyperplasias. Benign oral tumors account for 3.4 per cent of all canine neoplasms. 5 Oral tumors arise most frequently in middle-aged and older animals. In one study, the mean age of dogs with melanoma was f~und to be 10.4 years. For dogs with gingival squamous cell carcinoma, the mean age was 8.4 years, and for dogs with fibrosarcoma, it was 7.9 years. 1 In another *Diplomate, American College of Veterinary Surgeons; Assistant Professor, and Chief, Section of Surge ry, New York State College of Veterinary Medicine, Cornell University, Ithaca, New York Veterinary Clinics of North America: Small Aninwl Practice- Vol. 15, No. 3, May 1985

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study, a marked increase in age-specific rates of canine and feline oral tumors after 9 years of age was reported. 3 The incidence of oral malignancies in different breeds of dogs has not been completely defined. It has been reported that German Shorthaired Pointers, Weimaraners, Golden Retrievers, and Boxers are at greater risk than other breeds. 3 Oral melanomas tend to affect breeds with pigmented mucous membranes, such as Scottish Terriers, Black Cocker Spaniels, and Boston Terriers. 9 In contrast, cutaneous melanoma in man, a tumor with malignant and biologic behavior similar to canine oral melanoma, tends to arise in light-skinned individuals. No breed susceptibility to oral -squamous cell carcinoma or fibrosarcoma has been noted, although fibrosarcomas tend to occur frequently in dolichocephalic breeds. 1 The incidence of canine oral malignancies is generally greater in male dogs than in female dogs. One study reported a male-female ratio of 6 to 1 for oral melanoma, a ratio of 3 to 1 for tonsillar carcinomas, and a ratio of 2 to 1 for fibrosarcomas.' Male and female dogs were equally affected by gingival squamous cell carcinomas. Oral malignancies occur with equalfrequency in male and female cats. 2 Siamese cats are disproportionately underrepresented in comparison to domestic shorthaired cats. 2

BIOLOGIC BEHAVIOR Melanomas Oral melanomas are nearly always malignant. 1 The most frequent sites of occurrence are the gingiva, lip, and palate. 1• 9 Melanomas are usually first observed as firm, pigmented masses that infiltrate regional soft tissues and bone. Necrosis and secondary infection are common, and it is frequently the odor of the necrotic tumor that causes pet owners to seek veterinary attention. Melanomas metastasize readily via veins and lymphatics; enlarged, firm, or fixed regional lymph nodes may have prognostic significance in a dog with oral melanoma. In one report of 23 necropsied dogs, 74 per cent had nodal metastasis and 65 per cent had lung metastasis.' Due to the rapid growth, invasiveness, and early metastasis of oral melanomas, the prognosis is poor. The median survival time after diagnosis for untreated dogs was 65 days in one report. 12 Squamous Cell Carcinoma Oral squamous cell carcinomas most commonly affect the gingiva and tonsils of dogs and the gingiva and tongue of cats. These tumors are usually reddened, friable, and bleed easily. Invasion of surrounding tissues is common. Extension into contiguous bone produces morphologic changes that may be either destructive or productive. In early stages, gingival carcinomas are often mistaken for localized gingivitis. Loosening of teeth is a common historical feature, and many clients believe there is a cause-andeffect relationship between tooth extraction and developme nt of tumor. Tonsillar carcinomas are usually unilateral, a feature that can be useful in

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differentiating them from benign conditions such as tonsillitis and from generalized neoplasms such as lymphosarcoma. 17 The biologic behavior of oral squamous cell carcinoma depends partially on location. Gingival carcinomas, although locally invasive, rarely metastasize until late in the course of disease, whereas tonsillar carcinomas have frequently spread by the time they are diagnosed. Dogs with tonsillar carcinomas are often presented for treatment of cervical masses that are subsequently diagnosed as metastatic sites in lymph nodes, muscle, or subcutaneous tissue. Tonsillar carcinomas also spread by direct extension through the pharyngeal wall. Curative treatment of tonsillar carcinoma is rare . In contrast, gingival carcinomas tend to remain localized, and aggressive regional therapy may effect long-term control or even a cure in favorable circumstances. Gingival squamous cell carcinomas appear to be more aggressive locally in cats than they are in dogs. Ulceration and secondary infection occur early. The incidence of metastasis of feline oral squamous cell carcinoma may be artificially low, because cats are frequently euthanatized because of associated infection and dysphagia. 2 Tonsillar carcinoma is rare in cats, whereas tongue carcinomas are more common in cats than in dogs. Fibrosarcoma Oral fibrosarcomas in dogs and cats are usually firm, relatively slowgrowing tumors that ulcerate less frequently than other types of oral tumors. Fibrosarcomas rarely metastasize to distant sites, but they may exhibit massive local growth with invasion into surrounding hard and soft tissues. Dogs will occasionally survive for months to years with an incurable oral fibrosarcoma provided that the primary tumor can be controlled. In the cat, oral fibrosarcoma is also a localized disease, but like oral carcinoma, it appears to be more aggressive and destructive than in dogs. In general, lymph node status in animals with sarcomas is of little prognostic value, because sarcomas usually spread via the blood stream rather than the lymphatics. Information on the behavior of less common oral malignancies is limited predominantly to what can be derived from clinical observation. Adenocarcinomas arise from minor salivary gland tissue located in most of the oral mucosa. These tumors are invasive, friable , metastasize slowly, and tend to cause discomfort. Osteosarcoma affecting the oral cavity, and the skull in general, seems to have a very low metastatic rate and can often be treated successfully if wide local resection is possible. Benign Oral Tumors Benign oral tumors, by definition, do not metastasize, although they may attain large size. Some benign tumors will destroy contiguous bone either by invasion or by pressure necrosis. Epulides (tumors of peridontal ligament stroma) are common in dogs and rare in cats. 6 The epulides have recently been classified into the fibromatous epulis, the ossifying epulis, and the acanthomatous epulis. 6 Fibromatous epulis and ossifying epulis are benign, noninvasive, and are cured by surgical removal. Acanthomatous epulis contains an epithelial component that may invade regional tissues. 6 Ameloblastoma is a behaviorally benign tumor that arises from dental

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laminar epithelium in dogs. 6 These tumors have been characterized as "expansile tumors occurring deep within bone. " 7 Although the term adamantinoma has been used interchangeably with ameloblastoma, one author deplores the term adamantinoma as antiquated and confusing, and suggests eliminating it from medical nomenclature. 6 DIAGNOSIS The most important factor in the prognosis of oral tumors in dogs and cats is the biologic behavior of the tumor, which in turn depends on the type of tumor. However, it is reasonable to assume that length and quality of survival might improve if the tumor was detected and treated at an early stage. Unfortunately, oral tumors often do not cause clinical abnormalities until they are advanced in size and degree of invasiveness. In other cases, oral tumors observed in early stages are commonly diagnosed as gingivitis, gingival hyperplasia, epulis, tonsillitis, or cheilitis. Especially in older dogs and cats, localized oral lesions should be investigated histologically, particularly if the animal must be anesthetized for examination or dental care. Clinical signs associated with advanced oral tumors include salivation, pain, bleeding, dysphagia, and odor. When oral neoplasia is suspected, general anesthesia is usually necessary to facilitate a detailed examination. General anesthesia is preceded by an evaluation of the patient that includes a physical examination, the determination of hematologic and blood chemistry values, and electrocardiography. Thoracic radiographs are always indicated to rule out overt metastasis. Such an evaluation helps determine the extent of tumor involvement and identifies any concurrent metabolic or degenerative diseases that may need attention. To avoid multiple anesthetic episodes in old animals, all procedures requiring anesthesia should be done in one session, if possible. Radiographs of the oral cavity are desirable to detect the presence and degree of bony invasion. Biopsy, either excisional or incisional, should be performed. When complete excision is not possible, incisional biopsies should be deep and include a margin of normal tissue, if possible. Tumor growth is most active at the junction between normal and abnormal tissue, and cellular characteristics are most likely to be identifiable where growth is most pronounced. Regional lymph nodes should be palpated and biopsied if they enlarged, firm, or fixed to surrounding tissues. In this manner, nodes with tumor metastasis may be differentiated from those that are reactive or hyperplastic. Complete systematic evaluation of the animal allows accurate staging of the disease. Staging, in oncologic terms, is a shorthand description of the tumor and patient that allows anyone familiar with the nomenclature to instantly determine the extent of tumor involvement. Beyond being a common language, staging allows the prospective and retrospective study of comparable groups of patients and their prognoses. A staging system based upon the TNM classification has been adopted by the World Health Organization (Table 1).

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Table I. Clinical Stages (TNM) of Canine and Feline Tumors of the Oral Cavity (Buccal Cavity) Case number . . . . . . . . . . . . . . . . . Name of owner . . . . . . . . . . . . . . . Date ... . . . . . ..... . . . Cat/Dog . . . . . . Age . . . . . . . . . . Sex . . . . . . . . . . Breed . . . . . . . . Body weight . . . . . . lb (l kg = 2.2 !b) ............. kg This classification applies to the anterior two thirds of the tongue, floor of mouth, buccal mucosa, the alveoli, and the hard palate. The following are the minimum requirements for assessing the T, N, and M categories. (If these cannot be met, the symbols TX, NX, and MX should be used.) T categories: Clinical and surgical examination N categories: Clinical and surgical examination M categories: Clinical and surgical examination, radiography of thorax CIRCLE APPROPRIATE CATEGORY

T: Primary Tumor Tis Preinvasive carcinoma (carcinoma in situ) TO No evidence of tumor Tl Tumor < 2 em maximum diameter Tla without bone invasion Tlb with bone invasion T2 Tumor 2-4 em maximum diameter T2a without bone invasion T2b with bone invasion T3 Tumor > 4 em maximum diameter T3a without bone invasion T3b with bone invasion The symbol (m) added to the appropriate T category indicates multiple tumors. N:

M:

Regional Lymph Nodes (RLN)* NO No evidence of RLN involvement Nl Movable ipsilateral nodes Nla Nodes not considered to contain growtht N2 Movable contralateral or bilateral nodes N2a Nodes not considered to contain growtht N3 Fixed nodes

Nlb

Nodes considered to contain growth**

N2b

Nodes considered to contain growth**

Distant Metastasis MO No evidence of distant metastasis Ml Distant metastasis (including distant nodes) detected-specificy site(s):

STAGE GROUPING

I II III:j: IV

T Tl T2 T3 AnyT AnyT AnyT

N NO,Nla or N2a NO,Nla, or N2a NO,Nla, or N2a Nlb Any N2b or N3 Any N

Comments

*The RLN are the cervical, submandibular, and parotid nodes. t(-) = histologically negative, ( + ) = histologically positive. :j:Any bone involvement.

M MO MO MO

MO Ml

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TREATMENT Conventional surgical excision is the basis for treating nearly all oral tumors in dogs and cats. In addition to or in place of conventional blade excision, cryosurgery and electrosurgery may be used, although there is no evidence that either of these methods is superior to conventional excision in prolonging survival times. u The choice and aggressiveness of treatment will depend on the extent of tumor involvement (localized or metastatic), tumor type, and the physical status of the patient. These are the factors determined by staging. For certain patients, the prognosis may be so poor that therapy is not warranted. Palliative therapy should not be overlooked. For example, certain gingival squamous cell carcinomas and fibrosarcomas, because of their low metastatic potential, can sometimes be locally controlled for long periods of time merely by resecting recurrent foci as they develop. Results of treatments adjuvant to surgery, such as chemotherapy or immunotherapy, are largely unreported in the veterinary literature. Adjuvant treatments are unlikely to be effective unless the majority of the tumor can be surgically removed. Oral melanomas are treated by wide local excision that may require mandibulectomy or partial maxillectomy. Encouraging results are being reported using these methods of aggressive local excision. 22 • 23 Every effort should be made to eliminate the possibility of regional or distant metastasis before subjecting dogs to these extensive and potentially mutilating operations. Thoracic radiographs and regional lymph nodes should be unequivocally free of metastatic tumor. Electrocautery and cryosurgery are alternatives to conventional surgery, although cryosurgery was found to be inferior to surgical excision in one study. 12 Radiation therapy of melanomas is controversial but is usually considered ineffective. 21 Melanomas are resistant to chemotherapy, although partial response to dacarbazine has been reported. 18 Immunotherapy of oral melanoma is still experimental, although cutaneous melanoma in man shows a predictable response to intralesional bacille Calmette Guerin (BCG). 15 One report describes successful use of BCG in a dog with melanoma. 1° Corynebacterium parvum has also been used in dogs. 13 The overall prognosis for dogs with oral melanoma is poor. Aggressive surgery may control local disease, but the incidence of metastasis is high. Gingival squamous cell carcinoma is also treated initially by surgical excision. Aggressive surgical removal offers a more reasonable hope for long-term control or cure with this disease than with other oral malignancies in dogs. Radiation therapy has been advocated as primary or adjuvant therapy for oral carcinomas, and favorable response rates have been reported. However, the author's experience is that the response rate of squamous cell carcinoma is considerably less than the 50 per cent reported in the literature .8 The treatment used at the New York State College of Veterinary Medicine is 4000 rads delivered by an orthovoltage unit in ten fractions. Local control of tonsillar squamous cell carcinoma for periods ranging from 51 to 631 days was achieved by use of a Cobalt-60 teletherapy unit in one studyY However, most tonsillar carcinomas have metastasized

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at the time of diagnosis, and effective treatment is unlikely. Fibrosarcomas are treated almost exclusively by surgical excision that may include mandibulectomy and maxillectomy. Because of the low early metastatic rate of fibrosarcoma, adequate local excision has curative possibilities. Ap unmeasured clinical observation is that cryosurgery seems to enhance the metastatic potential of fibrosarcomas and should be avoided. This observation is supported by the relatively short survival times of dogs treated with cryosurgery for oral fibrosarcoma. 11 Fibrosarcomas are resistant to orthovoltage radiotherapy as well as to chemotherapy and immunotherapy. 19 Based on clinical observation, osteosarcomas and chondrosarcomas of the mandible and maxilla tend to behave like benign tumors. Extensive local resection with mandibulectomy and maxillectomy is justified, because such treatment may result in cure or long-term control. The same treatment methods used in: dogs can be used in cats. In the author's experience, however, feline oral fibrosarcomas and carcinomas exhibit more aggressive behavior than do similar tumors in dogs; successful treatment is correspondingly more uncommon. The epulides are treated by surgical excision. The fibromatous and ossifying types of epulis are cured by local excision, whereas the acanthomatous epulis may require adjuvant radiation therapy for control. 6 Squamous cell carcinomas have been noted to grow at the sites of irradiated acanthomatous epulides. 20 Ameloblastoma is best treated by complete excision of the bone of origin. Local excision or the use of cryosurgery is rarely effective. REFERENCES 1. Brodey, R. S.: A clinical a':ld pathological study of 130 neoplasms of the mouth and pharynx in the dog. Am. J. Vet. Res., 21:787-811, 1960. 2. Cotter, S. M. : Oral pharyngeal neoplasms in the cat. J. Am. Anim. Hosp. Assoc., 17:917- 920, 1981. 3. Dorn, C. R.: Epidemiology of canine and feline tumors. J. Am. Anim. Hosp. Assc., 12:307- 313, 1976. 4. Dorn, C . R. , and Priester, W. A.: Epidemiologic analyses of oral and pharyngeal cancers in dogs, cats, horses and cattle. J. Am. Vet. Med. Assoc., 169:1202- 1206, 1976. 5. Dorn, C. R., Taylor, D. 0. N. , Frey, F. L. , et al.: Survey of animal neoplasms in Alameda and Contra Costa counties, California. II. Cancer morbidity in dogs ar.d cats from Alameda County. J. Nat!. Cancer lnst., 40:307-318, 1968. 6. Dubielzig, R. R.: Proliferative dental and gingival diseases of dogs and cats. J. Am. Anim. Hosp. Assoc., 18:511-584, 1982. 7. Dubielzig, R. R., and Thrall, D . E. : Ameloblastoma and keratinizing ameloblastoma in , dogs. Vet. Pathol. , 19:596--607, 1982. 8. Gillette , E. L.: Radiation therapy of canine and feline tumors. J. Am. Anim. Hosp. Assoc., 12:359- 362, 1976. 9. Gorlin, R. J. , Clark, J. J. , and Chaudhry, A. P.: The oral pathology of domesticated animals. Oral Surg., 11:500-535, 1958. 10. Grier, R. L., et a!. : Regression of cutaneous melanocarcinoma following intralesional Mycobacterium bovis BCG injection: A case report. J. Am. Anim. Hosp. Assoc., 14:16--81, 1978. ll. Harvey, H . J. : Cryosurgery of oral tumors in dogs and cats. Vet. Clin. North Am. [Small Anim. Practs.]: 10:821- 830, 1980.

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12. Harvey, H . J.: Prognostic criteria of dogs with oral melanoma. J. Am. Vet. Med. Assoc., 178:580--582, 1981. 13. MacEwen, E. G.: Immunotherapy of cancer. Vet. Clin. North Am., 7:65-75, 1977. 14. MacMillan, R., Withrow, S. J. , and Gillette, E. L.: Surgery and regional irradiation for treatment of canine tonsillar squamous cell carcinoma: Retrospective review of eight cases. J. Am. Anim. Hosp. Assoc., 18:311-314, 1982. 15. Morton, D. L., Eilber, F. R., Malmgren, R. A. , et al.: Immunological factors which influence response to immunotherapy in malignant melanoma. Surgery, 68:158-164, 1970. 16. Piermattei, D. L.: Oral and pharyngeal neoplasia. In Proceedings of the American Animal Hospital Association, 40:729--732, 1973. 17. Ragland, W. L., and Gorham, J. R.: Tonsillar carcinoma in small dogs. Nature, 214:925-926, 1967. 18. Richardson, R. C., Jones, M. A. , and Elliot, G. S.: Oral neoplasms in the dog: A diagnostic and therapeutic dilemma. Compend. Conlin. Ed., 5:441-446, 1983. 19. Thrall, D. E.: Orthovoltage radiotherapy of oral fibrosarcomas in dogs. J. Am. Vet. Med. Assoc., 179:159--162, 1981. 20. Thrall, D. E. , Goldschmidt, M. H ., and Biery, D. N.: Malignant tumor formation at the site of previously irradiated acanthomatous epulides in four dogs. J. Am Vet. Med. Assoc., 178:127-132, 1981. 21. Thrall, D . E., and Biery, D. N.: Principles and application of radiation therapy. Vet. Clin. North Am., 7:35-49, 1977. 22. Vernon, F. F. , and Helphrey, M. : Rostral mandibulectomy: Three case reports in dogs. Vet. Surg., 12:2&-29, 1983. 23. Withrow, S. J., and Holmberg, D . L. : Mandibulectomy in the treatment of oral cancer. J. Am. Anim. Hosp. Assoc., 19:273-286, 1983. Section of Surgery New York State College of Veterinary Medicine Cornell University Ithaca, New York 14853