By E. Gregory MacEwen, V.M.D.
Associate Professor of Oncology
School of Veterinary Medicine
University of Wisconsin, Madison
As our understanding of the causes of cancer unfolds, it is becoming apparent that the majority of cancers are caused by environmental factors, and the minority of cancers are genetically fated to occur. Within the Scottish terrier breed; however, it would appear that genetics still plays a significant role in the development of cancer. Epidemiologic studies have shown that the Scottish terrier has a higher than expected incidence of lymphosarcoma, bladder carcinoma, oral melanoma, cancer of the skin (squamous cell carcinoma and mast cell sarcoma), and, to a lesser extent, nasal carcinoma and gastric carcinoma. Genetic susceptibility combined with environmental influences probably represent the major factors involved in cancer development in the Scottish terrier.
In this paper I will discuss how one might recognize or suspect a possible tumor and present the current approaches to treatment for that particular tumor. I think it is important to remember that cancer is frequently seen in the Scottie, and an early diagnosis can potentially lead to a successful course of treatment.
Lymphosarcoma is a common malignancy of the dog. It usually occurs in dogs between 5 and 7 years of age, although it has been seen in dogs less than I year of age. It is a cancer of the lymphatic system, usually originating in the lymph nodes located in the neck, shoulder, groin and back legs.
Lymphosarcoma can also originate in the chest cavity (thymus region), intestines, spleen, liver, skin, and bone marrow. The most common form involves the external lymph nodes; however, the disease can spread to the internal lymph nodes, spleen, and liver.
Among the earliest signs the owner might notice are "lumps" in the jaw or neck region. Some dogs show no signs of illness; others are lethargic, appear somewhat depressed, have a poor appetite, lose weight, run a fever, or drink a lot of water. If the chest cavity is involved, the dog might show signs of breathing difficulty or coughing. Gastrointestinal involvement is usually characterized by vomiting, diarrhea, abdominal enlargement, and weight loss. Involvement of the blood or bone marrow usually results in a progressive anemia, and the dog appears weak and lethargic.
Lymphosarcoma can be a very rapidly advancing disease, and early diagnosis is vital to successful therapy. Diagnosis is based on an evaluation of the hematological system, biochemical serum analysis, x-rays of the chest and abdomen, and a lymph node and/or bone marrow biopsy. Without treatment most dogs will die of this disease within I month after diagnosis.
This type of cancer can be effectively controlled with chemotherapy. Chemotherapy involves the use of drugs given both by injection and orally over a number of months or years. The drugs most commonly used are prednisone, cytoxan, vincristine, methotrexate, adriamycin, and L- asparaginase. The vast majority of dogs tolerate therapy very well with minimal serious side effects. Many dogs will develop some episodes of vomiting or diarrhea and loss of appetite within 24 to 48 hours after chemotherapy. This can usually be controlled with antivomiting medication and/or a subsequent reduction in the dose of that particular chemotherapeutic agent. There are no long-term debilitating effects of chemotherapy. Eighty percent of the dogs treated will undergo a complete remission (complete regression of the disease-not cure). The average dog will remain in remission for 10 to 12 months (with a range of 4 to 36-plus months), after which the disease becomes resistant to the drugs and reappears. Approximately 20 percent of treated dogs will survive 2 years or longer if multidrug combination chemotherapy is used. Recent studies have shown that females tend to have a better prognosis than males, surviving an average of 3 to 4 months longer. The reason for this is unknown (1).
In summary, canine lymphosarcoma is a fatal disease, and without treatment it will rapidly lead to death. The response to chemotherapy varies with each individual animal. Although chemotherapy is not curative, the life of many dogs can be prolonged with minimal side effects. The optimal chemotherapy protocol for lymphosarcoma has not been determined, but with appropriate chemotherapy one can expect an average survival time of 10 to 12 months after diagnosis.
Many studies in man and a few in the dog have revealed some known suspected causes of bladder cancer. Industrial chemicals, metabolites of foodstuffs, and polycyclic hydrocarbons have been associated with bladder cancer in man. Experimentally, beta-naphthylamine increases the incidence of bladder cancer in dogs. Other studies have shown that an increase in excretion of tryptophan metabolites may increase susceptibility to bladder cancer.
Most dogs with bladder cancer will present with signs of bleeding in the urine or straining to urinate. These signs may be identical to cystitis (bladder infection) or bladder stones (calculi). The major difference between an infection and cancer is that bladder cancer tends to be unresponsive to any type of antibiotic therapy. It can be extremely difficult to differentiate clinically between chronic bladder infection, stones, and cancer. Any dog (usually older than 8 years of age) with a chronic bloody urine and/or straining to urinate should be evaluated for possible bladder cancer.
Diagnosis is usually based on radiologic dye studies (cystogram and intravenous urogram) of the urinary tract. These studies will reveal a mass lesion in the bladder or urethra. Further studies that must be done to establish a diagnosis absolutely include cytologic examination of the urine for cancer cells and surgical exploration of the urinary bladder to obtain tissue for pathologic analysis. The most common tumor type seen is the transitional cell carcinoma.
Treatment of bladder cancer depends on the location and extent of the tumor (2). A partial cystectomy (bladder wall removal) is the treatment of choice. Unfortunately, the results of surgical treatment have not been very successful because at the time of diagnosis most dogs have a very advanced disease in which the tumors are too extensive for complete surgical excision. The use of chemotherapy (cytoxan, thio-tepa, and adriamycin) has been very disappointing, and only very minimal tumor control can be expected. Radiation therapy has not yielded very encouraging responses either. The best chance for control with this type of tumor is early diagnosis and aggressive surgical removal.
Oral melanomas are very malignant tumors that most often arise in the gum, lips, and tongue. They occur more frequently in darkly pigmented dogs (such as the Scottish terrier) and in older dogs (8 to 10 years of age). Melanomas can also occur on the digits, in the eye, and any place on the skin; however, melanomas of the oral cavity are most common and also the most malignant. Digital melanomas tend to be malignant also, but they have a better prognosis than those that occur in the oral cavity. Most skin melanomas are benign and have a very good prognosis.
Melanomas are usually observed as firm, pigmented masses in the oral cavity. Some of these tumors are amelanotic, that is they lack pigment. Dogs with these tumors may show no signs whatsoever. Sometimes the owner will notice an odor from the mouth, which he or she associates with the teeth, and will assume the dog needs dentistry. Melanomas can bleed easily, and small amounts of blood may be noted after the dog chews on a hard object. It is very important that a thorough physical examination be done once a year with special attention given to the oral cavity. Many of these oral tumors are diagnosed at the time of dentistry.
Oral melanomas can spread (metastasize) readily via the veins and lymphatics. It has been estimated that 25 percent to 30 percent of affected dogs will have lymph node metastasis at the time of diagnosis (3). Before any major surgical procedure is performed, chest radiographs should be taken to rule out possible lung metastasis. Surgical excision is the best treatment for oral melanomas. Cryosurgery (freezing) and electrosurgery can also be used. If the tumor is located on the lower jaw, and there is no evidence of metastasis, then radical removal of the section of the jaw (mandibulectomy) is advised. Dogs do very well and cosmetically look fine after a mandibulectomy.
The single most important prognostic factor for oral melanoma is tumor size. In dogs with an early diagnosis and a tumor of 2 cm (less than one inch) in diameter or less, the average survival time after surgery is around 16 months. In dogs with tumors greater than 2 cm in diameter or with evidence of lymph node metastasis, the average survival time is around 5 months. The results using radiation and chemotherapy have not been very rewarding. We have just completed a study using immunotherapy combined with surgery in dogs with oral melanoma (4). Using an agent called corynebacterium parvum (an immune stimulant with very minimal side effects), we found that in dogs with advanced disease (tumor size of 2 cm or with lymph node metastasis), we were able to improve survival from an average of 5 months to an average of 9 months. In dogs with small tumors (2 cm), C. parvum had minimal beneficial effects on survival time. C. parvum is given intravenously at frequent intervals after surgery.
Squamous Cell Carcinoma
Squamous cell carcinoma is a common cancer of the skin in Scotties, which occurs at an average age of 9 years. The most common sites are the digits, scrotum, lips, nose, and oral cavity. These tumors usually appear as solitary, proliferative, ulcerative or erosive lesions. The proliferative types may give the appearance of a cauliflower type of growth. The surface tends to ulcerate easily and bleed. The erosive tumors tend to appear as shallow, crusted ulcers that can become deep and crater-like. Squamous cell carcinomas tend to be invasive, and when metastasis occurs, it usually involves the lymph nodes and sometimes the lungs (5).
Surgical excision is the best treatment. The prognosis will depend on the location of the tumor, degree of invasiveness, and the histopathologic degree of malignancy. For those tumors that cannot be removed surgically, show evidence of invasion, or recur after surgery, radiation therapy should be performed.
MAST CELL SARCOMA
One of the most common types of skin cancer is the mast cell sarcoma. Despite the frequency of its occurrence; however, we lack a basic understanding of its cause and behavior. It is one of the most perplexing forms of cancer with which a veterinarian must deal.
Mast cell sarcomas usually arise from the skin or subcutaneous area. The most common tumor appears as a well circumscribed, raised, firm mass with a reddish appearance. Ulceration of the tumor with frequent bleeding is not uncommon. Another type usually appears as a soft, poorly cir- cumscribed mass, which rarely ulcerates. Mast cell tumors may vary from a very small solitary lesion (1 cm in diameter) to very large masses or multiple skin masses located either in one area or all over the body. These tumors frequently metastasize to the lymph nodes.
A complicating factor with mast cell tumors is that they can elaborate an excessive amount of histamine. The histamine can then stimulate the stomach to secrete an inordinate quantity of gastric acid. Thus, dogs with mast cell tumors are prone to gastric ulcers. The owner must be aware of this because dogs with long-standing tumors may start to vomit, lose weight, and pass blood into the intestinal tract. A bleeding ulcer leads to chronic anemia and dark tarry feces. If a dog has a mast cell tumor, a veterinarian should be consulted regarding the use of special antihistamines (cimetidine) to prevent this complication (6).
The best treatment for mast cell tumors is complete surgical excision (7, 8). The single most important prognostic factor associated with this type of tumor is the degree of malignancy. This is determined by a veterinary pathologist after the tumor is removed and submitted for analysis. Dogs with what is termed poorly differentiated cancers have an average survival of less than 4 months. Dogs with well differentiated cancers have a very good prognosis, and the vast majority will be cured with surgery alone. Dogs with intermediate differentiated cancers hdv-8@an average survival of 8 months after surgery.
Radiation therapy can be used very successfully to afford long-term control in at least 50 percent of the mast cell tumors treated. Radiation can be used as the primary treatment or in conjunction with surgery. The results of evaluating the response to radiation based on the histopathologic degree of malignancy has not been studied. Chemotherapy can be used, but this serves only for temporary control or to shrink the tumor prior to surgical excision. The drug most commonly used is the corticosteroid prednisone. Prednisone is given in very high doses, and some of the side effects include increased water intake, excessive urination, and a voracious appetite. Other chemotherapy drugs, such as vincristine and L-asparaginase, can also be used.
Nasal tumors occur more commonly in dogs of middle age (8 to 10 years old) and in medium to large breeds. The cause is unknown. Most dogs will have signs of chronic nasal discharge and sneezing. The discharge tends to be bloody and may have a mucoid component. The discharge is usually from one side, but, if both nostrils are affected, it may be bilateral. As the disease progresses, nasal and oral deformities may develop as a result of tumor invasion beyond the nasal cavity. Sometimes the tumor extends behind the eye, and the eye appears to deviate outwardly. When these deformities are noted, the prognosis is very poor.
It is very easy to confuse a nasal tumor with chronic bacterial and fungal infections or a possible foreign body in the nasal cavity (9). Most dogs with this disease are initially treated with antibiotics for a presumed infection or with antihistamines for sneezing. Any dog that does not respond to prolonged antibiotic therapy should have further diagnostic testing. The most informative diagnostic procedures include x-rays of the nasal cavity under anesthesia and a nasal flush procedure to obtain tissue samples for culture or pathologic analysis. Sometimes it is necessary to surgically explore the nasal cavity to obtain a diagnosis.
It is important to emphasize that for nasal cancer early diagnosis and aggressive treatment is paramount to long-term control and good quality of life. The best treatment for nasal cancer is the use of radiation therapy. At veterinary schools or institutions where orthovoltage radiation therapy is used, surgery should be done first to remove the tumor. At schools or institutions where cobalt therapy is available, surgery is not necessary. The average survival time for dogs with nasal tumors treated with radiation, with or without surgery, has ranged from 8 to 18 months (10). Most treatment failures result from local recurrence or the spread of tumor to the local lymph nodes. Dogs treated with surgery alone live only 3 to 5 months. There have been no studies to evaluate the effectiveness of chemotherapy in treating this type of cancer.
Gastric cancer occurs in dogs ranging in age from 3 to 13 years. The cause is unknown, but in humans gastric cancer has been associated with exposure to nitrates in the diet, use of highly salted and seasoned food, and low intakes of vitamins C and A.
The signs of gastric cancer are usually vomiting (sometimes with blood), loss of appetite, weight loss, and abdominal pain. An animal with gastric cancer typically shows chronic deterioration with a gradual onset of vomiting. Many dogs are treated with antivomiting medications and dietary changes. Usually at the time of diagnosis the disease has progressed to the point where effective treatment is hopeless.
Diagnosis is based on a barium series, which may show evidence of a mass lesion in the stomach wall; direct visualization of the stomach wall using a flexible fibroptic scope (gastroscopy); or exploratory surgery and direct visualization of the cancer. Confirmation of the diagnosis requires a biopsy and pathologic analysis. Most gastric tumors are carcinomas, and these are usually too extensive for surgery and have an extremely poor prognosis. Chemotherapy has not been helpful.
Some tumors that occur less commonly in the stomach include lymphosarcoma and benign leiomyoma. Lymphosarcoma can be treated with chemotherapy, with or without surgery; leiomyoma is treated with surgery alone (11).
In summary, the treatment of gastric tumors is difficult even for the most experienced surgeon. The potential complications are great, and recurrence is extremely common. In the vast majority of dogs, diagnosis is all that can be performed; very little can be done to treat these cancers.
1. MacEwen EG, Brown NO, Patnaik AK, et al.: Cyclic combination chemotherapy of canine lymphosarcoma. J Am Vet Med Assoc. 178:1178-1181,1981.
2. MacEwen EG, and Harvey HJ Urinary tract neoplasia in dogs and cats. In Pathophysiology in Small Animal Surgery (ed MJ Bojrab). Lea & Febiger, Philadelphia, 1981, pp 276-284.
3. Harvey HJ, MacEwen EG, Braun D, et al.: Prognosis after surgical excision of canine melanoma. J Am Vet Med Assoc 178: 580-582, 1981.
4. MacEwen EG, Patnaik AK, Harvey HJ, et al.: Canine oral melanoma: comparison of surgery versus surgery plus Corynebacterium parvum. Cancer Invest, 1986 (In Press).
5. Bevier DE, and Goldschmidt MH: Skin tumors in the dog. Part 1. Epithelial tumors and tumor-like lesions. Compend Contin Ed 3:389, 1981.
6. Macy DW: Canine mast cell tumors. Vet Clin NA 15:783-803, 1985.
7. Bostock DC: The prognosis following surgical removal of mastocytoma in dogs. J Small Anim Pract 14:27-40, 1973.
8. Patnaik AK, Ehler WN, and MacEwen EG: Canine cutaneous mast cell tumor: morphologic grading and survival time in 83 dogs. Vet Pathol 21:469-474, 1984.
9. MacEwen EG, Withrow SJ, and Patnaik AK: Nasal tumors in the dog: retrospective evaluation of diagnosis, prognosis and treatment. J Am Vet Med Assoc 170:45 -48, 1977.
10. Beck ER, and Withrow SJ: Tumors of the canine nasal cavity. Vet Clin NA 15:521-533,1985..
11. Crow SE: Tumors of the alimentary tract. Vet Clin NA 15:577-596, 1985.
Original Doc: cancers.doc
Source: Scottish Terrier Club of America’s 1986 Handbook, pages 152-158.