Diagnosis and Treatment of Some Common Malignancies in the Scottish Terrier
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.
Cancer: An Overview
The types of cancer afflicting dogs, and some new methods in battling them.
By Moira Anderson Allen
Source: AKC Gazette, June 1990, pp 84-91.
In the waiting room of the clinic in Hermosa Beach, California, I noticed the usual assortment of patients. A sleek Doberman paced restlessly at the end of a short lead, ignoring the graying mixed-breed that trembled on the lap of her mistress. A black tomcat growled steadily from his cage on the floor. The coffee table was strewn with pet-care literature, magazines and styrofoam coffee cups.
But there was a subtle difference. The clients in this waiting room didn't have any of the "hurry-up-let's-get-it-over-with" attitude of owners waiting for routine vaccinations or checkups. They seemed lost in their own thoughts, or constantly touching their animals. Even the literature on the table was different; much of it discussed how to deal with bereavement. The woman with the mixed-breed quietly tucked one of the flyers into her purse.
The waiting room belonged to the AnimalCancerCenter, one of the few specialized cancer clinics in the country. The Doberman and the cat were waiting for their scheduled radiation treatments, while the elderly mixed-breed was there for a workup. She had just been diagnosed with breast cancer.
"He said I should put her to sleep right away," the woman said clearly close to tears. "He said there was nothing anyone could do," she added.
"My vet said the same thing," said the Doberman's owner. "But he's worked so hard - got his CDX, and then we did the therapy thing for a couple of years. It seemed like he deserved a decent retirement. My vet didn't think there was much hope, but he's doing fine!"
Hope - that was the word that had brought these clients to the AnimalCancerCenter, and as many as 2,000 like them every year. Hope that the dreaded word "cancer" was no longer synonymous with "euthanasia"; hope that a beloved companion could enjoy a few more months or even years of quality life.
Now, thanks to dramatic strides in the availability of expertise, equipment and treatment techniques over the last decade, that hope exists. Ten years ago, the life expectancy of a dog diagnosed with cancer was three weeks to six months. Now, with treatment, some dogs have lived five or six pain-free years, depending on the type of cancer.
Fifteen years ago, oncology - the study of cancer - was not even a veterinary specialty. Now clinics are able to hire specialists in the field. Equally importantly, they are able to obtain the vital equipment needed to treat various types of cancer - equipment that has been used in human hospitals for fifteen or twenty years and is now being discarded for modernized machinery and passed on to veterinary hospitals. Ironically, much of this equipment was originally tested on animals with cancer, and many of the treatments used on humans were pioneered on animals. At last, animals are reaping the benefits of the technology they helped create.
Cancer is a common disease in dogs as well as humans, with many parallels between the species - with the exception of lung cancer, according to Dr. Alice Villalobos, head of the AnimalCancerCenter, because "dogs don't smoke." Some breeds have been reported to develop particular types of cancer.
Dr. Villalobos speaks of cancer treatment in military terms, describing tumors as an aggressive enemy that wages a destructive battle at the cellular level. To win, or even conduct a successful holding action, it is necessary to know the nature of the enemy, get early "intelligence reports" on its presence and location, and apply the battery of modern weapons against it.
Arriving at a Diagnosis
Early discovery of any form of cancer is very important for treatment to be effective. It's not enough just to find a "lump"; it's necessary to determine what type of cancer is involved and how far it has spread through the animal's system. Once, this might have meant exploratory surgery or guesswork. Now, veterinarians have more sophisticated and less invasive tools at their disposal.
One of these is needle aspiration, which is used to "suck" samples of tumor cells or fluids for biopsy. I watched the monitor of an ultrasound machine as Dr. Villalobos handled a needle-aspiration biopsy of Suzy, a seven-year-old Poodle. A lump had been detected in the lymph nodes near the spine, a tricky place to probe. Thanks to the monitor, the veterinarian was able to watch the needle in motion, white against the dark fluid systems of the dog, and guide it precisely to the lump without risking damage to surrounding areas.
"The ultrasound machine has become one of our most important diagnostic tools," Dr. Villalobos told me. By bouncing sound waves off organs and tissue, ultrasound creates a moving, computer-enhanced image of what is going on inside the body, including organ function and blood flow. It can detect tumors where X rays can't, including in the liver, where they show up as black holes against the whitish mass of tissue.
"It's very important to determine whether tumors have spread to the liver," says Villalobos. "This means the cancer is well advanced, and surgery probably isn't going to do much good." Another benefit of ultrasound is that in most cases an animal does not have to be anesthetized or sedated. It does have to be shaved locally, as sound waves are absorbed by the hair.
Another useful tool is the use of fiberoptic instrumentation, including endoscopy, proctoscopy and bronchoscopy. This enables a veterinarian to look inside intestines, the esophagus, or the colon, to check for tumors or take tissue samples. This type of equipment is expensive but has become more readily available. CT (computerized tomography) scanners are also used to determine the location and size of tumors.
The dog owner is still the first line of detection, however. An alert owner performs a physical examination every time he washes, grooms or even pets his dog. The owner should also examine the dog's mouth periodically, looking under the tongue, inspecting the palate, and checking for any changes, swellings or ulcers. In dogs, one to two percent of all tumors occur in the mouth, and half of these are malignant. The owner is also familiar with the dog's routine and normal behavior, and can spot warning signs. (See the sidebar, ÍThe Twelve Warning Signs of CancerÎ) ÍBut the owner needs to be aware that dogs try to cover up problems, and will try to 'keep up with the group' as long as possible." Dr. Villalobos notes.
Many tumors are detected during a physical examination conducted by a veterinarian before routine vaccinations, and Dr. Villalobos points out that the cheaper route of vaccine clinics or home-administered vaccinations that bypass this regular physical can place dogs at a disadvantage. Obesity also makes cancer harder to detect and tumors harder to locate, and can mask other warning signs, such as shortness of breath.
"It's also extremely important to know all you can about the total health of the dog before going ahead with some form of treatment" says Dr. Villalobos, who recommends a full workup for any cancer patient. Such a workup studies the dog's entire system including blood and urine to determine not only the extent of the cancer but whether a dog has heartworm, kidney disease, or other problems that could interfere with treatment or make treatment especially risky. A workup may be expensive but can make a tremendous difference in the outcome and may also save the owner the cost of going ahead with costly but useless treatment.
Once the "enemy" has been detected, what then? A few years ago, surgical removal was about the only solution to cancer. Surgery removes the visible tumor. Unfortunately, a malignant tumor sends out cells microscopically beyond the primary tumor. These cells enter the circulation system either through the lymph system or the vascular system. In some types of tumors, the cells go to distant locations such as the lungs or the liver, others may remain concentrated in the local area. During aggressive surgery designed to be curative, a veterinarian will try to remove up to three centimeters of the surrounding tissue to catch these cells.
Radiation to the site of surgery can help destroy cells that have spread further . (See sidebar, ÍBNCT: Experimental Treatment for Brain TumorsÎ) Radiation treatment is prescribed in the number of "rads," usually between 4,000 to 6,000, to be administered to the patient. The prescription is "filled" by a radiation therapist, who administers a certain number of rads per treatment day.
The typical patient, according to Dr. Villalobos, will come in two to three times a week for a total of ten to twelve treatments. One side effect of radiation is a bad sunburn effect to the treated portion of the skin.
While I visited the AnimalCancerCenter, I met Dr. Villalobos' dog, Duncan, a Bernese Mountain Dog with a magnificent coat and a classic California laid-back personality. I would never have suspected that Duncan was there for his chemotherapy treatment.
Radiation is a localized treatment and is often combined with chemotherapy, which treats cancer at the systemic level. Chemotherapy is also used when cancer is too widespread to make surgery or radiation effective.
Chemotherapy involves the oral or intravenous administration of drugs to stop the reproduction of malignant cells anywhere in the body. Usually a combination of drugs is used to inhibit several different phases of growth. Anti-neoplastic drugs, for example, stop division of cancer cells by acting on different proteins in the DNA. An other drug stops the zonulas or strands the cells need to multiply; another inhibits certain molecular bondings; another will inhibit a certain reaction that is important in mitosis. "It's like sending in the Green Berets, the militia, the submarines and the air force," says Dr. Villalobos. "You're attacking the enemy from very different directions." Additional "clean-up" drugs are used to follow up.
Because intestinal and hair cells reproduce even faster than some tumor cells, chemotherapy interferes with them as well, which is why humans lose their hair and become nauseated when undergoing treatment. Dogs have an advantage here: except for a few breeds such as Poodle, Maltese and Lhasa Apsos, they don't have a continuous hair-growth cycle like humans. Poodles will lose their hair with some of the stronger drugs. Dogs also don't seem to become nauseated: after his treatment, Duncan was slobbering eagerly for his milk bone.
"It's not unusual for a dog to slow down during the day of treatment," says Dr. Villalobos. In addition, dogs don't have the emotional burden and mental feedback of fear and stress to aggravate the problem.
Before a dog is put on chemotherapy, the specialist will want to know as much as possible about the patient's organ functions and medical history. The condition of the dog's liver and kidneys, whether it has heart disease, whether it is diabetic or has pancreatic deficiency, and whether it is on other drugs, are all important variables in determining the impact of chemotherapy.
Another cancer treatment method is immunotherapy. In this form of therapy, agents are given that stimulate the patient's own immune system to fight the cancer. (See the sidebar, ÍAn Update on the Magic BulletÎ)
Hyperthermia involves bringing up the animal's body temperature to a point that is lethal to tumor cells. This can be done locally or involve the entire body. This treatment is still experimental (researchers are still determining the precise temperatures and exposure times), and requires anesthesia. It is difficult to perform on dogs, and is somewhat expensive and cumbersome. Another form of hyperthermia treatment, also known as thermomagnetic surgery, involves injecting a ferrosilicone fluid into the tumor and then heating the particles up to fifty-five to sixty degrees centigrade, temperatures cancer cells cannot survive. This is also a relatively uncommon treatment that is still being studied.
In cyrosurgery, liquid nitrogen in sprayed onto the tumor, and an instrument records the temperature. This is especially useful for skin and oral tumors, which turn black and drop off two weeks after being frozen. When a larger tumor is frozen, devices are used to monitor it at several different points, and surgeons also keep track of the animals's general body temperature. One must be careful not to freeze and damage normal tissues.
Many veterinarians still don't refer cancer patients to oncologist. Some feel that prolonged, expensive treatment that may buy no more than a year of additional life for an animal isn't worth the client's time and money.
Dr. Villalobos emphasizes that this is the owner's decision to make. Many owners, offered the choice of keeping a cherished companion for an additional year or more or saving money, adopt the "It's only money" attitude or find other ways to compensate for the costs. And cancer treatment isn't cheap: radiation treatments alone average around $75 per visit, for ten to twelve visits. A course of treatment combining radiation, chemotherapy, or other methods can cost $1,200 to $2,000, or more. Some pet insurance programs will cover a portion of the costs.
Nor is treatment foolproof. According to Dr. Villalobos, "Sometimes it's pure luck. You put all the right ingredients together, and sometimes it works, sometimes it doesn't." The basic health and age of the animal are also important factors. But dogs actually have an advantage over humans: They do not experience emotional trauma and stress and so their recovery rate is likely to be better.
There are only twenty-seven schools of veterinary medicine in the U.S., and only a handful of veterinary oncologists and specialty clinics, though more are opening every year. To locate a treatment center, ask your veterinarian, check with your nearest school of veterinary medicine or contact the local chapter of the Veterinary Medical Association.
The Most Common Cancers in Dogs
Cancer isn't an independent entity that invades the body, but a normal body cell gone berserk. Dr. Alice Villalobos of the AnimalCancerCenter in California describes it as war on a cellular level, and a malignant cell is very aggressive. Every cell has a special function. When a normal cell divides; it stops next to its neighbor. But when a cell becomes malignant, it begins to bread all the rules. It ceases to function as a kidney cell or blood cell; its only remaining function is to divide rapidly. It grows and laterally eats anything around it, killing other cells and even dissolving bone cells, to get them out of the way and take their place.
The type of cell that began the abnormal dividing will determine where the cancer will be located, how far it will spread and to what body systems, and what the chances of treatment are. Following are the more common types of cancer in dogs:
Skin is the most common site for tumors in the dog. However, not all skin tumors in the dog are malignant. Malignant melanomas start in the pigmented cells in the skin. In humans, this is the most common form of fatal skin cancer, usually appearing where pigmented cells cluster, such as in moles or freckles. Although malignant melanoma is the most common form of fatal skin cancer in humans, most dermal or skin melanomas in the dog are benign. On the other hand, melanoma in the mouth of dogs is a highly malignant disease. One to two percent of all dog tumors are in the mouth, of which fifty percent are malignant melanomas. Malignant melanomas spread through the circulation and lymph systems and will usually spread to the lungs if not caught early.
Another skin cancer, squamous cell carcinoma, is caused by excessive sun exposure. This type of skin cancer can appear as small or large ulcers that appear to be nonhealing, crusted sores. Squamous cell carcinomas also occur in the oral cavity and can metastasize as well.
Mast cell is a common skin tumor in dogs but rare in man. Mast cell tumors can appear anywhere on the body and are unpredictable; potentially, but not invariably, malignant. Therapy with corticosteroids and/or radiation therapy may be needed in addition to surgical removal. Mast cell tumors are generally not sensitive to chemotherapy, so newer methods of treatment are being explored.
Lymphoma or lymphosarcoma is a malignancy of lymphocytes involving the lymph nodes and any other organ. As this system extends throughout the body, the entire animal can become involved. These cancers generally stay in the lymph system in the early stages and don't attack bones or organs. In more advanced disease, they can enter the bone marrow, spleen and liver. Chemotherapy or chemoimmuotherapy is used to treat lymphomas.
Breast cancer is very common in dogs. Fifty percent of breast tumors become malignant, and may spread to other body systems, especially the lungs. though some veterinarians may feel comfortable leaving a small breast tumor in place for observation for a few months, Dr. Villalobos recommends that all such tumors be surgically removed immediately to be on the safe side.
Unspayed, unbred bitches are the most likely to develop breast cancer. Spaying before the first heat reduces the risk of breast cancer to almost zero, as well as the risk of uterine or ovarian cancer, because hormones sensitize breast tissues to malignant tumors. Spaying up until two and one-half years can still greatly reduce the risk.
Hemangiosarcomas occur in the spleen, especially in larger, older dogs. These often go undetected until rupture of the spleen causes the dog to bleed to death internally. Tumors such as this are often detected by abdominal palpation on routine vaccination physical. Hemangiosarcomas may spread through the bloodstream to the heart, lungs or liver. Ultrasound can help determine whether surgery for this tumor type will be effective. If the tumor has already spread, a splenectomy may not be that helpful. After surgery, chemotherapy is recommended to extend survival.
Osteosarcomas, or bone cancers, can spread throughout the entire body system. They are more common in large-breed males over five years old. Usually they appear first in one leg. The common treatment is amputation for pain control, followed by chemotherapy.
Testicular cancer, cancer of the prostate, and tumors (both benign and malignant) around the anus are common in intact male dogs, and tend to remain localized. Neutering greatly reduces the incidence of these malignancies in male dogs in their senior years.-MA
BNCT: Experimental Treatment For Brain Tumors
Brain tumors develop in dogs as frequently as in people. The most common types of canine brain tumor are gliomas and meningiomas. Gliomas are the result of uncontrolled division of the supportive cells within the brain tissue, while meningiomas stem from cells of the meningeal layers external to the brain.
Canine brain tumors occur more often in middle-aged or older animals. Certain breeds have predilections for different brain tumor types. Gliomas commonly occur in bracycephalic (broad-skulled) breeds of dogs, while meningiomas are found more frequently in dolicocephalic (long-snouted) breeds. Clinical signs exhibited by affected dogs depend on the region of brain affected by the abnormal growth. Common symptoms associated with canine brain tumors include onset of seizures late in life, behavior changes, difficulties in coordination or balance, visual defects, loss of function of nerves supplying the head or endocrine abnormalities.
Under ideal circumstances, diagnosis of and treatment for canine brain tumors is similar to that for people. Brain tumors in certain locations can be approached surgically. Success of surgery is limited due to difficulties in completely eradicating tumor tissue, and tumor recurrence is common. X-radiation therapy is available for the treatment of canine brain tumors at a limited number of veterinary medical centers. Radiation therapy for dogs with brain tumors can alleviate clinical signs for a variable time period, but it is difficult to draw conclusions on survival rates following treatment due to the small number of dogs that have been treated to date. When surgery or radiation therapy is not available, medical management using anti-inflammatory medications may alleviate symptoms for a limited time.
Boron Neutron Capture Therapy (BNCT) is an experimental form of radiation therapy that may offer advantages over conventional radiation techniques for people and animals with brain tumors and other forms of cancer. An initial series of companion dogs with brain tumors have been treated with BNCT through a Department of Energy-funded pilot study at Washington State University College of Veterinary Medicine and Surgery. Most of the treated dogs have been returned home and are being monitored for tumor recurrence and post-treatment effects.
BNCT involves the administration of a drug containing 10 Boron (10B). This is followed by radiation therapy using a specialized neutron beam. The neutrons interact with the 10 B atoms, causing a fission reaction which releases high-energy short-range particles that damage tissues only in the immediate vicinity (about the distance of an average cell width). Significant highly damaging radiation is produced only where the neutrons interact with the nonradioactive 10B atoms. BNCT, therefore, may represent a means to selectively treat a tumor with highly effective radiation while sparing normal surrounding tissues.
A treatment program for dogs with brain tumors will be continued if results in the initially treated group are favorable. In addition, studies evaluating the pharmacokinetic of 10B-containing compounds and studies on the radiation effects of BNCT continue. Owners with dogs having symptoms suggestive of the presence of a brain tumor are encouraged to have their referring veterinarian contact personnel of the WSU research program if they are interested in further information. In Washington, call (800) 345-3047; out-side Washington, (800) 537-3647.-Susan Kraft, D.V.M.; Patrick Gavin, D.V.M., Ph.D., Constance De Haan, D.V.M.
The authors are with WashingtonStateUniversity's College of Veterinary Medicine.
The Twelve Warning Signs of Cancer
1. Abnormal swellings that continue to grow, especially in the lymph glands
2. Sores that do not heal
3. Bleeding or discharge from the mouth, nose, urinary tract, vagina or rectum
4. Offensive odor
5. Difficulty eating and/or swallowing
6. Difficulty breathing
7. Difficulty urinating or defecating
8. Hesitation to exercise, or loss of energy
9. Loss of appetite, weight loss
10. Persistent lameness or stiffness of movement
11. Lump in the breast area
12. Abnormality or difference in size of testicles
(Courtesy of the AnimalCancerCenter)
An Update on The Magic Bullet
In February 1986, the GAZETTE published an article entitled "Speeding Towards the Magic Bullet" on the ongoing studies in cancer research at the University of Pennsylvania funded by the American Kennel Club. Canine lymphoma has remained one of our prime targets for new treatment approaches.
This form of lymph node cancer is one of the most common and yet treatable in the dog. The conventional treatment for lymphoma has been systemic chemotherapy since the malignant cell is a lymphocyte and can circulate throughout the body. However, with chemotherapy alone, the peak median survival times are six to ten months. The goal in our research has been to use immunotherapy with agents called biological response modifiers (BRMs) to improve the prognosis of canine lymphoma, that is, prolong remission durations off chemotherapy and improve overall survival times.
BRMs are aimed at stimulating the dog's own immune system to fight the cancer and are generally associated with fewer side effects than chemotherapy drugs.
We initially reported on the effectiveness of using tumor vaccines made from each dog's individual lymph nodes, but continued to look for improved methods of stimulating the immune system. In addition, there was always the limitation of needing a laboratory to prepare vaccines. Thus, we embarked on our studies of nomoclonal antibodies (Mabs) as a more sophisticated and easily producible BMR. To develop a monoclonal antibody, one takes a tumor from a patient, a dog in this case, and immunizes a mouse that has myeloma. Myeloma is a form of a cancer in animals and humans that affects the cells that make antibodies. If you give a tumor cell from a patient to a mouse with myeloma, the mouse will then make large quantities of antibody against the patient's tumor cell antigens. Through hybridoma technology, each mouse will make a specific antibody, or a monoclonal antibody, that can later be made in large quantities. Some of those monoclonal antibodies may be capable of killing tumor cells.
In the previous article, we had only produced and characterized the first Mabs against canine lymphoma. We have now completed our Phase I clinical studies which have investigated potential side effects and have preliminary clinical results in our Phase II studies aimed at looking at the effectiveness of Mabs in dogs with lymphoma. We observed no significant side effects in fifteen dogs treated with Mab.
Following those results, we initiated a study to compare the effectiveness of Mabs in the same treatment protocol we had used with our tumor vaccine following remission induction with chemotherapy. Following a complete diagnostic medical workup, dogs were started on eight weeks of low-dose chemotherapy followed by a three week rest from all therapy. This is to allow the immune system to recover from the effects of the chemotherapy. We then administer Mab therapy for five days via an intravenous injection. The dogs do not need to be hospitalized during this time.
We have recently compared the ongoing results of our Mab trail with our previously published results with tumor vaccine. With over forty dogs treated with Mab, they appear to have longer remission durations off all therapy and longer survival times than previously reported with chemotherapy alone. We are currently comparing the efficacy of Mab to that of tumor cell vaccine. The median survival time of dogs treated with chemotherapy and monoclonal antibody is currently 591 days. Eighteen percent of the 57 dogs on the Phase I study are Golden Retrievers.
The majority of owners who are referred with their dogs to Penn choose to treat their dogs and elect to use the chemoimmunotherapy. The reasons for owners' preference for the combined therapy are several. First, we stress the primary goal of therapy of cancer in dogs as being normal quality of life for the patient. Since the dogs are off chemotherapy much of the time, the dogs feel much better. Additionally, economics obviously play an important role in an owner's ability to treat his dog. The major expense in the lymphoma patient is the cost of the chemotherapy drugs and support care for resulting side effects. Naturally, if the dogs are off chemotherapy more of the time, the costs will be less. Even when the Mab becomes commercially available, we anticipate that the cost of the Mab will still be less than that of continuous chemotherapy.
An additional observation we have made in the dogs treated with chemoimmunotherapy is that they appear to remain sensitive to the chemotherapy drugs longer than dogs treated with the cytotoxic drugs alone. Treating tumor cells is similar to therapy of infections with antibiotics. The bacteria will become resistant to chronic use of the same antibiotics. The same phenomena occurs with chronic bombardment of tumor cells with the same chemotherapy drugs. Since control of lymphoma is dependent on responsiveness to chemotherapy drugs, drug resistance results in relapse, progressive disease and potentially death. Since dogs on immunotherapy are off chemotherapy for varying periods of time, chemotherapy remain effective if and when the dog relapses. Additionally, we suspect that the immune system itself may have a role in preventing drug resistance. Further studies will include using the magic bullet or Mab to target chemotherapy drugs or radionuclides to the tumor site.
Although our speeding bullet has been moving along at a rapid pace in canine lymphoma, we have been continuing to seek and pursue new methods of treatment for cancers in dogs that are not as responsive as lymphoma to chemotherapy. Those tumors include mast cell tumors, malignant melanoma, mammary adenocarcinoma and squamous cell carcinoma. Although progress has been made in humans with these cancers, the aggressive type of chemotherapy utilized would be very compromising to a dog's quality of life. Again we have turned to immunotherapy with BRMs for innovative therapy approaches, trying to treat the disease effectively with minimal compromise of quality of life.
In 1988, we started a clinical trail, funded in part by the Cetus Corporation, using interleukin-2 (IL-2) and tumor necrosis factor (TNF) as stimulants of the immune system. IL-2 and TNF are substances known as cytokines, meaning that they are naturally produced by the immune cells of our bodies. Through recombinant technology these cytokines can now be synthesized in the laboratory. The cytokines are biological factors that produce a variety of normal physiological responses including fever.
Fever has been shown to be an important response of the immune system in fighting cancer. Therefore, when we attempt to treat cancer with cytokines we expect to see some side effects including fever and a flu-like syndrome. This indicates that the immune system is able to respond to these factors. to date, we have seen encouraging responses in mast cell tumors and breast cancer, two of our most common and problem diseases.
Dogs are actively being sought for these trials. Through our continuing AKC support, we will be able to continue these very important explorations. -K. Ann Jeglum, V.M.D.
Dr. Jeglum is the staff oncologist at the University of Pennsylvania's School of Veterinary Medicine.
Any breed of dog can develop any type of cancer. The two most common malignant tumor types (excluding tumors of the skin) in the canine species are breast cancer and lymphatic cancer (lymphoma). However, there are certain breed-tumor relationships that are seen fairly consistently.
The following is a partial list of some of the more common malignant tumors seen in dogs. This information is from a variety of articles and texts, as well as from the case files of the AnimalMedicalCenter in New York.
Lymphoma - Boxer, Basset Hound, Scottish Terrier, Airedale Terrier, Bulldog, Golden Retriever, Labrador Retriever, Old English Sheepdog
Leukemia - Golden Retriever, Labrador Retriever
Oral Cancer - Cocker Spaniel, Boxer, Golden Retriever, Weimaraner, German Shorthaired Pointer
Bone Cancer - St. Bernard, Great Dane, Irish Wolfhound, Golden Retriever, Irish Setter, Doberman Pinscher
Pancreatic Cancer - Airedale Terrier
Hemangiosarcoma (tumor of the blood vessels of liver, spleen and heart) - German Shepherd Dog
Nasal sinus tumors - Airedale Terrier, Basset Hound, Old English Sheepdog, Scottish Terrier, West Highland White Terrier, Collie, Shetland Sheepdog
Dr. Mauldin is a staff oncologist with the Donaldson-Atwood Cancer Clinic of the AnimalMedicalCenter in New York.
Where To Go For Help
"It's a good idea to seek a second opinion when your dog is diagnosed with cancer," says Dr. Ralph Richardson, head of Veterinary Clinical Sciences at the VeterinaryMedicalSchool at PurdueUniversity. "Proceed very cautiously, as you would with any family member."
The following universities' schools and colleges of veterinary medicine offer a comprehensive program of radiation, chemotherapy, surgery and other forms of cancer treatment. All have board-certified oncologist on their staffs: AuburnUniversity; University of California, Davis; ColoradoStateUniversity; University of Florida; University of Illinois; University of Minnesota; North CarolinaStateUniversity; OhioStateUniversity; OhioStateUniversity; University of Pennsylvania; PurdueUniversity; University of Tennessee; TexasA&MUniversity; TuftsUniversity and the University of Wisconsin.
The AmericanCollege of Veterinary Internal Medicine has available a list of its twenty-eight Diplomates who are board-certified oncologist. It can be obtained by contacting the ACVIM at Suite C-1A, 620 North Main St., Blacksburg, VA 24060; (800) 245-9081.
The Veterinary Cancer Society can provide information on oncologist working in specific types of treatment (for example hyperthermia, chemotherapy or immunotherapy). The Society's address is P.O. Box 370450, San Diego, CA92137; (619) 295-6347.Several options exist for owners of dogs afflicted with cancer. Many more are being developed.-Dominique Davis.
The author is an assistant editor at the GAZETTE.
Moira Anderson Allen is a freelance writer and frequent contributor to the GAZETTE whose previous article, "Being of Sound Mind..." appeared in the February 1988 issue.
Original Doc: cancer02.doc
Neoplasms And Neoplasm-Like Conditions Of The Skin
The skin is the most common site of occurrence of neoplasms in the dog (about 30% of the total), and the second most common site in cats (about 20% of the total). Although variable from report to report, canine skin neoplasms are approximately 55% mesenchymal and 45% epithelial in origin.
The skin is the most common site of neoplasia in horses (mostly mesenchymal and benign) and goats (mostly epithelial and malignant), the second most common site in swine (mostly epithelial and malignant), and the second or third most common site in cattle (mostly epithelial and benign) and sheep (mostly epithelial and malignant).
The clinical key to appropriate management and accurate prognosis of skin tumors is specific diagnosis, which can only be achieved by biopsy and histologic examination (and then sometimes only with great difficulty).
Fine-needle aspiration or impression smears are easily performed in a clinical setting, and often provide very valuable information about cell type and degree of differentiation, but give no information about local invasion into surrounding tissues or potential metastatic involvement. When push comes to shove, a "lump is a lump" until it is evaluated histologically.
Distinguishing features of benign and malignant neoplasms
Limited, cicumscribed, encapsulated
Mode of growth
Recurrence after removal
Invasion of vesels and other structures
Nearly normal amount
Large, may be multiple
Cytomorphologic features suggestive of malignancy
q Pleomorphism (variable cell forms)
q Variable nucleus:cytoplasm ratios
q Variable staining intensity
q Marked variation in size
q Coarsely clumped, sometimes jagged chromatin
q Nuclear molding
q Peripheral displacement by cytoplasmic secretions or vacuoles
q Prominent, occasionally giant, or angular nucleoli
q Variable staining intensity, sometimes dark blue
q Discrete, punctate vacuoles
q Variable amounts
Breed predilections for cutaneous neoplasms in the dog (Table 1)
Breed Predilections for Cutaneous neoplasms in Large Animals (Table 2)
Cutaneous papilloma / Papillomatosis
These are neoplasms caused by a DNA papovavirus. They are common in dogs, cattle, and horses (and humans), to rare in other domestic species. Individual species are afflicted by their own specific viruses.
Canine viral papillomatosis, equine viral papillomatosis, and bovine viral papillomatosis affect younger animals, with no breed or sex predilection. The disease is contagious, with an incubation period of about one month. Papillomatosis almost always occurs as multiple lesions, varying from white, flat, smooth papules and plaques to gray-white, pedunculated or cauliflower-like masses up to 2 cm in diameter. In the dog, lesions commonly affect the mouth, lips, skin of the face, conjunctiva or cornea. In the horse, lesions commonly affect the skin of the face and lips, in cattle, the lesions commonly affect sites of epithelial damage such as ear-tag holes, or the penile mucosa. There is a rather nebulous connection between bovine papillomavirus and equine sarcoid, a locally invasive neoplasm of horse skin.
Cutaneous papillomas occur in older animals. In dogs, there are breed and sex predilections, as noted in the table above. In dogs and cats they may be single or multiple, occur mainly on the head, eyelids, and feet. They are usually pedunculated or cauliflower-like, firm to soft, well circumscribed, alopecic, smooth to keratinous, and usually 0.5 cm in diameter.
Histologically, papillomas may be classified as squamous, characterized by papillated epidermal hyperplasia and papillomatosis, with ballooning degeneration and variable basophilic intranuclear inclusions; or fibropapilloma, with a proliferation of collagen-producing fibroblasts and an overlying hyperplastic epidermis.
Although both viral papillomatosis and cutaneous papillomas are benign lesions, transformation into squamous cell carcinoma has been recognized in a few cases.
Common benign neoplasm of the dog, thought to arise from the epidermis between hair follicles. Usually occur in dogs 5 years old, and more commonly in males. See the breed predilection table for specifics about predisposed breeds. These are usually solitary lesions, presenting as 0.5 to 4 cm dermal or subcutaneous masses, with a variably-sized pore opening to the skin surface. The pore may not be present, lending to confusion of
these lesions with "cysts", discussed later. Histologically, these are typically keratin-filled intradermal crypts lined by thick, complex, folded, well-differentiated stratified squamous epithelium, with columns of epithelial cells projecting peripherally from the basal surface of the wall and forming small epithelial nests.
Although these are benign neoplasms, in the generalized form, affected dogs tend to develop additional tumors throughout their lives.
Squamous cell carcinoma
Common malignant neoplasms of the dog, cat, horse, and cattle arising from squamous epithelial cells. May be a correlation between UV light exposure and development of squamous cell carcinoma, especially in white cats, humans, sunbathing dogs, and eyes of cattle. In sunbathing dogs and horses, this has been associated with actinic skin damage. Rarely may arise from scars (brand carcinoma in cattle). Has been an association in dogs with papillomavirus in a few cases, and squamous cell carcinoma has been induced by injection of papillomavirus vaccines. These generally occur in older animals. Canine breed predilections are listed in the above chart. In cats, there is no breed predilection, just an association with white coats. In cattle, Herefords most commonly develop squamous cell carcinoma of the eye.
These are usually solitary tumors, and may be ulcerative or proliferative. The proliferative types are papillary masses of varying sizes, often assuming a cauliflower appearance. Surfaces are often ulcerated and tend to bleed easily. The ulcerative types begin as shallow, crusted, non-healing ulcers that eventually become deep and crateriform. Histologically, these appear as irregular masses or cords of epidermal cells that proliferate downward and invade the dermis. Frequently there are whorled masses of
keratin (keratin pearls) within the tumor, visible intercellular bridges, mitoses, and moderate to marked cellular atypia (anaplasia). Generally, they are locally invasive, with metastasis occurring late in the course of the disease.
Basal cell tumor
These are common neoplasms of the dog and cat, and rare in other domestic species. They are thought to arise from the basal cells of the epidermis, hair follicles, sebaceous glands and sweat glands. There is some controversy as to the malignant potential of these tumors, although historically they have been classified as benign tumors. They generally occur in older animals.
They are usually solitary tumors, firm, rounded, elevated, well-circumscribed, and located dermoepidermally. They are frequently alopecic, and may become ulcerated. They may become cystic.
Histologically, they are described as solid, cystic, ribbon (garland), adenoid, basosquamous, and medusoid, depending on the microscopic arrangement of the neoplastic cells.
Hair follicle tumors
These are relatively common in dogs to rare in cats and other domestic animals. They are thought to arise from keratinocytes in the hair follicle outer root sheath or the hair matrix, or both. Usually they occur in older animals (> 5 yr in dogs). They are similar in gross appearance to basal cell tumors, and, along with other hair follicle tumors, are classified as types of "basal cell tumors" by some. Are almost always benign tumors, however, there have been a few cases where there was metastatic involvement of local lymph nodes.
Histologically, there is marked variability, depending on the degree of differentiation and the exact site of origination (hair follicular sheath or hair matrix. Frequently, there are horn cysts, lack of intercellular bridges (differentiating them from squamous cell carcinoma), formation of rudimentary hair follicle-like structures, and formation of hairs.
Uncommon neoplasms that arise from keratinocytes of the outer root
sheath of hair follicles. Occur in middle-aged to older dogs, most
commonly on the head and neck, and are usually firm, ovoid, and 1-7 cm
Histologically, these are characterized by a nodular proliferation of clear,
PAS-positive keratinocytes. Tumor nodules are surrounded by a distinct,
often thickened basement membrane zone.
Rare benign neoplasms of dogs that essentially amount to hamartomas of the pilosebaceous unit. They are usually domed, firm papules or nodules, often containing a central depression or pore that may exude sebaceous material or contain a tuft of hair.
Histologically, they are characterized by a large dilated or cystic follicle, with peripheral radiating follicles or follicle-like structures.
These uncommon (dogs) to rare (cats) neoplasms are thought to arise from the hair matrix. They occur in dogs that average 6 years of age. Usually they are solitary, with site predilections of shoulders, back, flanks, and legs. They are usually firm, rounded, elevated, well-circumscribed and dermoepidermal in location. As with basal cell tumors, they can become alopecic, ulcerated, and occasionally cystic.
Histologic characterization included a variable proliferation of cells resembling hair matrix cells, and central shadow or ghost cells. There is abrupt keratinization (no stratum granulosum), and the keratin is homogenous, relatively amorphous, and nonfibrillar (tricholemmal keratin). There may be mineralization within foci of ghost cells.
Sebaceous gland tumors
These are common in dogs to rare in cats. They are epithelial neoplasms that arise from sebaceous gland cells. Generally occur in older animals. See chart for breed predilections. They may be single or multiple, and may occur anywhere on the skin, with the head being the most common site. Nodular sebaceous hyperplasia is the most common type of sebaceous gland proliferation, and is usually firm, elevated, well circumscribed, and dermoepidermal in location. They are usually alopecic, shiny, lobulated, pink to yellow, and small (2-10 mm). Sebaceous adenomas tend to be larger (up to 2 cm), and less lobulated. Sebaceous epitheliomas are similar to basal cell tumors in appearance. Sebaceous carcinomas tend to be larger than 2 cm, firm, poorly circumscribed, and ulcerated. Sebaceous carcinomas are usually locally invasive and rarely metastasize.
Histologically, these are composed of foamy to finely vacuolated cells, and are classified into the above categories based on the degree of overall glandular organization and cellular atypia.
Sweat gland tumors
There are uncommon tumors arising from epithelium lining the apocrine and eccrine sweat glands. Apocrine tumors are usually solitary, and may be predilected to occur on the back and flank. They must be differentiated from apocrine cysts, which may be multiple, and more frequently occur on the head and neck. They are elevated, round, fluctuant, well circumscribed, dermoepidermal in location, and may be light blue to
purple. They may range from benign adenomas to malignant carcinomas. The malignant tumors are often highly invasive, and frequently metastatize.
Histologically, they are classified based on pattern of growth into apocrine cyst, cystadenoma, papillary syringoadenoma, spiradenoma, cylindroma, hidradenoma papilliferum, adenocarcinoma (papillary, tubular, solid, signet ring), or clear-cell hidradenocarcinoma.
Perianal gland tumor
These neoplasms, common in the dog, arise most frequently from the perianal glands (hepatoid or circumanal glands) and less commonly from apocrine anal glands or anal sac glands. The hepatoid gland tumors are known to modulated by the presence of sex hormones, and are more common in the male. They occur in older dogs, and must be differentiated from nodular hyperplasia of these glands.
Apocrine neoplasms of anal sac origin are most common in aged female dogs and are often associated with pseudohyperparathyroidism due to production of PTH-like substances. These are usually not classified as a "true" perianal gland tumor, since they arise from apocrine glands found within the anal sac.
Histologically, perianal gland tumors are classified into two basic types: perianal or hepatoid gland tumors (hyperplasia, adenoma, adenocarcinoma); and apocrine anal gland tumors. Apocrine tumors of anal sac origin are a separate type.
Mesenchymal (dermal and subcutis) neoplasms
These are uncommon benign tumors of the domestic animals that arise from subcutaneous fibroblasts. They are usually neoplasms of older animals, usually solitary, well circumscribed dermal to subcutaneous nodules, and may be soft (fibroma molle) to firm (fibroma durum). Histologically, these appear as whorls and interlacing bundles of well-differentiated fibroblasts and collagen.
Fibrovascular papilloma (Acrochordon, Skin tags)
Common benign tumors of fibrovascular origin in dogs. Large and giant breeds may be predisposed. They may be solitary to multiple, filiform to pedunculated, smooth or hyperkeratotic, soft, and small (less than 1 cm in length). They occur most commonly on the proximal extremities and ventral thorax. There are relatively common in humans on the eyelids, and occasionally in the axillae.
Histologically, they are characterized by a fibrovascular core exhibiting papillomatosis and irregular hyperplasia of the overlying epidermis.
Common malignant neoplasms of the dog and cat arising from dermal or subcutaneous fibroblasts. They are uncommon in large domestic animals. Some feline fibrosarcomas are virus-induced, caused by the C-type retrovirus FeSV. Although fibrosarcomas typically occur in older animals, the viral-induced feline tumors occur in younger animals.
Histologically, these are characterized by interlacing bundles of immature fibroblasts and moderate collagen fiber deposition. Mitotic figures are common, and cellular atypia is often pronounced.
This is a unique, locally aggressive fibroblastic skin tumor of horses. It may affect any age horse, but approximately 70% of cases are in animals younger than 4 years of age. This neoplasm is thought to be caused by a papovavirus (not bovine papovavirus types 1 and/or 2, but another papovavirus). The lesions frequently occur in areas subjected to trauma, and there may be a history of an injury to the development site several months prior to tumor development. They can occur at any body site, especially on the head, and may be multiple.
Histologically, these are characterized by fibroblastic proliferation with an attendant marked epidermal hyperplasia and dermoepidermal activity. A characteristic of these tumors is perpendicular orientation of neoplastic fibroblasts along the dermoepidermal junction in a "picket-fence" pattern.
Myxoma and Myxosarcoma
These are neoplastic proliferations of fibroblasts, and are rare in all domestic animals. They are soft, slimy, poorly circumscribed masses often without definite shape. Both may recur following surgical excision due to their locally infiltrative pattern of growth.
Both are characterized histologically by stellate to fusiform cells distributed in a vacuolated, basophilic, mucinous stroma that may be partitioned by connective tissue septae.
Leiomyoma and Leiomyosarcoma
These are extremely rare skin neoplasms in domestic animals. They are neoplastic proliferations of smooth muscle cells of arrector pili muscles or of cutaneous blood vessels. They are usually solitary, firm, well circumscribed, dermoepidermal in location, and variable in size.
Histologically, these are characterized by interlacing bundles of smooth muscle fibers that tend to interact at right angles. Cell nuclei are usually cigar-shaped, with rounded, blunt, ends. There may be a slightly wrinkled appearance to nuclear membranes due to cell contraction.
Lipoma and Liposarcoma
Lipomas are common in dogs to uncommon in other domestic animal species. They arise from subcutaneous lipocytes (adipocytes). They usually occur in older animals. They may be single or multiple, and occur most commonly on the ventral trunk and proximal limbs. They are usually domed to pedunculated, well circumscribed, soft to flabby, variable in size, often multilobulated, and subcutaneous in location. There may be some firmness due to presence of fibrous tissue and/or inflammation within the tumor.
Histologically, lipomas are characterized by well circumscribed masses composed of adipocytes. Liposarcomas are characterized by a cellular, infiltrative proliferation of anaplastic adipocytes, with abundant, eosinophilic, finely vacuolated cytoplasm. Liposarcomas tend to be locally aggressive, and rarely metastasize.
Mast cell tumor
These are common tumors of the dog and cat and range in biological behavior from benign to malignant. They have been described in horses. Occur in animals of any age, but tend to occur in older animals. In the horse, there is no breed predilection, but a preponderance of occurrence in males. See chart for breed predilections. Canine mast cell tumors occur most commonly on the trunk, perineum and limbs, and may be domed,
nodule, or pedunculated; sell to poorly circumscribed, firm to soft, dermoepidermal to subcutaneous in location, and variable in size. They may be "pinfeathered", edematous, ulcerated, and may be melanotic. Feline mast cell tumors occur most commonly on the head and neck and may present as variable plaques and dermal masses fixed to the overlying skin, to papules and nodules, to discrete domed masses. Noncutaneous
clinical signs occasionally observed with mast cell tumors include gastric and duodenal ulcers (thought to be histamine induced), and defective blood coagulation (thought to be heparin induced).
Equine mast cell tumors appear to be hyperplastic rather than neoplastic lesions. They occur most commonly on the head or legs. Spontaneous remission may occur in young animals, and metastases are not known to occur.
Histologically, these are composed of a diffuse to multinodular proliferation of mast cells, with ancillary findings including foci of eosinophil infiltration and collagenolysis in association with the mass, edema. Neoplastic mast cells tend to percolate between collagen fibril at the tumor periphery, occasionally making surgical excision difficult. This in one tumor in which a presumptive diagnosis can be made with confidence by examining a Wright’s-stained (or Diff-Quick) smear of a fine needle aspirate of the mass. Mast cells are typically round, with intracytoplasmic metachromatic granules.
Schwannomas are uncommon to rare neoplasms of domestic animals arising from dermal to subcutaneous Schwann cells (nerve sheath). Usually occur in older animals with no sex predilection. They are usually solitary, and are firm, well- to poorly-circumscribed, variable in size, and dermoepidermal to subcutaneous in location. There may or may not be obvious nerve involvement. Most of these in dogs appear to be benign, but frequently recur after surgical excision. A condition of multiple schwannomas (neurofibromatosis) in cattle has been likened to von Recklinghousen’s disease in humans. In this particular disease, lesions are usually multiple, firm, round to flat, subcutaneous, and up to 8 cm in
diameter; occurring most commonly on the head and trunk. Affected cattle often have extracutaneous lesions as well, involving the heart, brachial plexus, and intercostal nerves.
Histologically, these are characterized by one of two patterns: (1) neurofibroma—faintly eosinophilic, thin, waxy fibers lying in loosely textured strands that extend in various directions, with spindle cells that may exhibit nuclear palisading (Verrocay bodies), and (2) neurilemmoma—areas of spindle shaped cells exhibiting nuclear palisading and twisting bands or rows (Antoni type A tissue), alternating with an edematous stroma containing relatively few haphazardly arranged cells (Antoni type B tissue).
These are benign, haphazard proliferations of Schwann cells and nerve fibers in areas of trauma, especially tail docking. They will often be excoriated to ulcerated due to self trauma.
Histologically these are characterized by irregular axonal sprouting, with secondary remyelination in a bed of fibrous connective tissue.
These are benign to malignant tumors arising in cells of neural crest origin (melanocytes) They are relatively common in dogs and horses (gray) to rare in other species. They occur in older animals. See chart for breed predilections in dogs. In cats there is no breed or sex predilection, and in horses it is usually associated with gray coats. Melanomas are usually
solitary in the dog to multiple in the horse, and vary in appearance from brown to black macules and plaques or firm, domed nodules. Malignant melanomas are usually larger than 2 cm, and frequently ulcerated. Remember, malignant melanomas can be non-pigmented if the neoplastic melanocytes are so poorly differentiated that they produce no pigment. Biologic behavior is very difficult to judge from histopathologic characteristics. However, up to 90% of canine oral melanomas are malignant; up to 25-50% of cutaneous melanomas may be malignant, especially if they arise from the digits, or scrotum. In the older gray horse, these typically arise within or associated with the perineum, and may metastasize to regional lymph nodes, to internal organs to the spinal cord.
Histologically, these vary from masses of pigmented melanocytes within the dermis exhibiting junctional activity with the overlying epithelium to bizarre, poorly circumscribed masses of epithelioid to spindled to dendritic and whorled patterns of cells that range from deeply pigmented to non-pigmented.
This is a rare cutaneous of dogs and humans, that appears to arise from cutaneous Merkel cells. Remember, Merkel cells show dual epithelial and neural differentiation. Most commonly occurs in older animals. May vary from benign to malignant in biologic behavior.
Histologically, these are characterized by sheets, solid nests, or anastamosing trabeculae of uniformly round tumor cells with abundant amphophilic cytoplasm, hyperchromatic and vesicular nuclei, and frequent mitoses. Electron microscopy or imunohistochemistry is needed to differentiate from other round cell tumors.
These are uncommon in dogs to rare in other domestic species. They usually occur in older animals, and arise from vascular endothelial cells. They usually present as well circumscribed, firm to fluctuant, rounded, bluish to reddish black dermoepidermal to subcutaneous masses. They may rarely appear as blood filled cysts.
Histologically, they are characterized by masses composed of blood-filled, endothelium-lined spaces within a variable fibrovascular stroma. The vascular spaces are lined by a single layer of flattened, well-differentiated endothelium. These may be subdivided as cavernous or capillary, depending on the size of the vascular spaces and amount of intervening fibrous connective tissue.
These are uncommon in dogs and cats to rare in other domestic species. As in hemangiomas, these arise from vascular endothelial cells. They are usually solitary, rapidly growing, poorly circumscribed, soft, and friable, and dermoepidermal to subcutaneous in location. They often undergo necrosis, ulcerate, and bleed. They are highly invasive and malignant in dogs.
Histologically, these are characterized by an invasive proliferation of atypical, anaplastic endothelial cells, with variation from formation of vascular spaces lined by atypical endothelial cells to solid sheets of large, plump spindle to fusiform cells.
These are common benign neoplasms of dogs, with only rare reports of occurrence in cats. There are no descriptions of this tumor in other domestic animals. They occur in older dogs, with breed predilections as listed in the chart. They are usually solitary, and occur most commonly on the limbs. They are usually firm, multinodular, well circumscribed, and dermoepidermal to subcutaneous in location. They rarely metastasize.
Histologically, these are characterized by interlacing bundles and whorls of spindle to ovoid cells, often around blood vessels.
Histiocytomas are common benign neoplasms the dog, arising from histiocytes. They are very rare in the other domestic animals. They characteristically arise in young dogs (under 2 yrs old), however, this is not a hard and fast rule. There is no sex predilection, but several breed are predisposed (see chart). They are usually small, domed or button shaped (hence the terminology "button tumor"), well circumscribed, dermoepidermal in location, and frequently ulcerated.
Histologically, these are characterized by uniform sheets of pleomorphic histiocytes infiltrating the dermis and subcutis and displacing the collagen fibers and adnexae. There are usually abundant mitoses present. Lymphocytic infiltration and foci of necrosis develop in regressing tumors, and may make histologic diagnosis difficult in cases of advanced regression.
This is a rare, malignant neoplasm of histiocytic origin in dogs. Mostly older animals are affected. It has been recognized in several breeds of dogs. Cutaneous lesions are rarely seen and are typified by multiple, firm, dermal to subcutaneous nodules anywhere on the body. Lesions may be alopecic or ulcerated. The disease course is rapidly progressive and
invariably fatal. Histologically, this disease is characterized by nodular to diffuse, deep dermal and subcutaneous infiltration, with cytomorphologically atypical histiocytes exhibiting cytophagocytosis and a high mitotic index. Additionally, numerous internal organs may be have similar neoplastic infiltrates.
This is a histiocytic proliferative disorder of dogs. It has been described in closely related Bernese Mountain dogs of 2-8 yrs of age, with males predominating. The disorder is rare in other breeds of dogs. It may present as multiple cutaneous papules, plaques, nodules, and ulcers over the entire body, especially the face. The course of the disease varies from
prolonged, with alternating periods of exacerbation and remission, or rapidly progressive and fatal.
Histologically, systemic histiocytosis is characterized by superficial and deep perivascular, nodular, or diffuse dermal and subcutaneous infiltration of cytologically normal histiocytes. Cutaneous histiocytosis
This is a benign histiocytic proliferative disorder of dogs. There is no apparent age, breed, or sex predilection. Lesions are multiple, erythematous, dermal or subcutaneous plaques or nodules, 1 to 5 cm in diameter, anywhere on the body. Lesions may wax and wane, and appear in new sites. Systemic involvement does not occur in this condition.
Histologically, this is characterized by nodular to diffuse dermal or subcutaneous infiltration of cytologically normal histiocytes. Transmissible venereal tumor
This is an uncommon benign to malignant neoplasm of the dog. The cell of origin is unknown. It is a naturally occurring allograft with transmission occurring by transplantation of viable neoplastic cells to a susceptible host. Tumor cells contain 59 chromosomes, compared to the normal complement of 78 in the dog. The neoplasm is typically transmitted coitally, but may be inoculated into susceptible sites by licking, biting, and scratching. A viral origin was suspected, but not verified. These occur in sexually active dogs, there is no breed or sex predilection. Neoplasms occur commonly on the genitalia, and skin of the face and limbs, and may be single or multiple, nodular, pedunculated, multilobular, or cauliflower-like. They may be firm or friable, and dermoepidermal to subcutaneous in location. There may be frequent ulceration.
Histologically, TVT is characterized by compact masses or sheets of uniform round to polyhedral neoplastic cells, often growing in rows in a delicate stroma. There are usually many mitoses. Tumors undergoing spontaneous regression display necrosis, increasing numbers of infiltrating leukocytes (especially lymphocytes), and increased collagen deposition.
These are uncommon in dogs to rare in cats and other domestic animals. In dogs, they occur most commonly in 2-4 year old animals. They are usually multiple and occur most commonly on the face. They are usually firm, well circumscribed, and dermoepidermal in location. The overlying skin may be normal or alopecic. Histologically identical lesions may occur on the cornea, with or without concurrent skin lesions.
Histologically, these are characterized by a poorly circumscribed cellular infiltrate permeated by a swirling stroma. The majority of cells are recognizable as fibroblasts and histiocytes. Collagen formation is minimal. There may be lymphoplasmacytic infiltrates, especially at the periphery of the lesions.
Malignant fibrous histiocytoma
They have been given various other names such as extraskeletal giant cell tumor or giant cell tumor of soft parts. They are rare malignant neoplasms of the cat and dog and horses. They are believed to arise from undifferentiated mesenchymal cells. They occur in older animals with no breed or sex predilection. They are usually solitary, firm, poorly circumscribed, variable in size and shape, and dermoepidermal and subcutaneous in location. There may be a predilection for limbs and the neck in dogs and cats. These neoplasms are locally invasive and slow to metastasize.
Histologically, these are characterized by an infiltrative mass composed of varying mixtures of pleomorphic histiocytes, fibroblasts, and multinucleated giant cells. Numerous mitotic figures and a "storiform" (cartwheel) arrangement of fibroblasts and histiocytes are common features.
This is a rare malignant neoplasm of the dog, cat, horses and cattle to extremely rare in sheep, goats and swine. In cats, FeLV has been implicated as a cause, although most cats with cutaneous lymphoma are FeLV-negative. The neoplasm occurs in older dogs, with no sex predilection, but with a breed predilection as noted in the chart. In dogs and cats, the neoplasm is usually generalized or multifocal and has a variety of manifestations, including dermoepidermal and subcutaneous nodules, plaques, ulcers, erythroderma, and exfoliative dermatitis. Cutaneous malignant lymphoma can be divided into epitheliotropic and nonepitheliotropic, depending of involvement of and interaction with the overlying epidermis. Epitheliotropic (also known as mycosis fungoides) are
usually T cell in origin, while non-epitheliotropic are usually B cell in origin. Nonepitheliotropic malignant lymphomas are characterized by diffuse dermal and subcutaneous infiltration by malignant lymphocytes.
In horses and cattle, cutaneous malignant lymphoma as usually multiple dermoepidermal to subcutaneous nodules, and may occur anywhere on the body, especially the trunk. Lesions may be firm or soft, and the overlying skin is usually normal. Older horses are usually affected. In cattle, there is an association with bovine leukemia virus, a retrovirus, and the neoplasm typically arises in young adult animals, with no breed or sex predilection.
Multiple myeloma with cutaneous involvement is rare. Primary cutaneous plasmacytomas are more common. They may be solitary rounded, soft,
erythematous subepidermal masses, often involving the digits or interdigital spaces; or may involve the oral cavity of dogs.
Histologically, they are characterized by dermal and subcutaneous or submucosal infiltration of normal-appearing to pleomorphic, atypical plasma cells.
These are common in dogs to uncommon in other domestic animals. They are benign non-neoplastic lesions characterized by an epithelial wall, with keratinous to amorphous contents. They are subdivided into six types based on histologic appearance.
Epidermal Inclusion cysts
Thought to be acquired lesions arising from displaced fragments of epithelium or occluded pilosebaceous follicles. They may be single to multiple, and there is no age, breed, or sex predilection. The lesions are round, smooth and well circumscribed, firm to fluctuant, and up to 5 cm in diameter, often bluish, and dermoepidermal to subcutaneous in location. They may open and exude a gray to white-brown, cheesy material. In the horse, they most commonly occur at the base of the ear, and may discharge a mucoid material, or unilaterally in the false nostril.
Histologically, they are characterized by an epithelial lining that undergoes maturation and keratinization typical of epidermis, but contains no adnexal structures.
Usually hereditary or congenital lesions, which may be single or multiple. Breed predilections are listed in the chart. There is no sex predilection, and the lesions are seen in young animals. Dermoid sinus, pilonidal sinus of Rhodesian ridgebacks is this type of cyst, and is seen along the dorsal midline of the neck and sacrum.
Histologically, dermoid cysts are characterized by a stratified epithelial lining that contains adnexae (hair follicles, sebaceous glands, etc; and central keratinaceous material.
Follicular cysts (milia)
Develop be retention of follicular glandular products, due to congenital or acquired loss or obliteration of follicular ostia. They are usually small, and white to yellow, and may resemble pustules or calcinosis cutis.
Histologically, they are characterized by a greatly enlarged, dilated, keratin-filled hair follicle with sebaceous or apocrine sweat glands or atrophic secondary hair follicles entering the base of the cyst.
Trichilemmal (pilar) cysts
These are seen in dogs. Grossly, they resemble other cysts.
Histologically, they are greatly enlarged and dilated hair follicles with a proliferative wall exhibiting trichilemmal keratinization, and homogenous keratin filling the cyst cavity. Squamous eddies are frequently present
Also known as conchal fistula, cyst, or sinus; dentigerous cyst, temporal teratoma or odontoma; ear fistula or ear tooth). They occur in the horse, and are thought to represent developmental defects. Lesions are solitary and occur at or near the base of the ear or in relationship to the zygomatic process. They may discharge a grayish mucoid material.
Histologically, they may be epidermoid, dermoid, or dentigerous (containing a tooth or teeth).
These occur in the wattles of goats, most commonly Nubian and Nubian crossbreeds. They are believed to be developmental abnormalities, possibly arising from branchial clefts. They contain a clear fluid, and if aspirated, with reform.
Histologically, they are characterized by a cyst wall composed of a single to double layer of cuboidal to columnar epithelial cells that often exhibit the apical budding typical of apocrine sweat gland secretory epithelium.
A nevus is a circumscribed developmental defect of the skin. They may arise from any skin component or combination thereof.
Recognized in many breeds of dogs as solitary or multiple cutaneous lesions, especially involving the skin of the head, neck, and proximal extremities. Most collagenous nevi are firm, well circumscribed, and up to 5 cm in diameter. The lesions may be alopecic, variably hyperpigmented, and have pitted surfaces. There can be continued growth and recurrence following surgical removal of these, and in this sense, they may behave as
a locally aggressive neoplasm.
Histologically, the lesions are characterized by nodular areas of "collagenous hyperplasia". Think about this: collagen does not divide or otherwise proliferate, how can this be "hyperplasia"? Perhaps these would better be described as foci of nodular collagen deposition.
Reported in dogs and cats. The lesions are single or multiple, firm to mushy, 3 mm to 3 cm in diameter, and domed to pedunculated. They occur primarily on the rostral half of the body.
Histologically, they are characterized by hyperplasia of hair follicles, sebaceous glands, and, rarely, apocrine sweat glands.
These most commonly occur on the scrotum of older dogs. They are more common in breeds of dogs with pigmented skin. The lesions appear as single or multiple, slowly enlarging and hyperpigmented plaques on the scrotum, which may periodically hemorrhage. They may occasionally occur at other anatomic sites.
Histologically, they are characterized by cavernous dilation (telangiectasia) of blood vessels and epidermal melanosis.
These are seen in the dog and cat. The lesions may be single or multiple and occur most commonly on the trunk. They vary from brown to black, and from macular (junctional nevi) to papular or pedunculated. Malignant transformation has not been recorded.
Histologically, they are characterized by intraepidermal and/or dermal nests (theques) of benign, hyperplastic melanocytes.
These are firm, elevated, circumscribed areas of excessive keratin production. They are uncommonly reported in domestic animals.
These are elevated plaques or nodules with a hyperkeratotic, often greasy surface.
Histologically, they are characterized by hyperkeratosis, hyperplasia (basaloid and squamoid), and papillomatosis
These have been recognized in dogs, cats, horses, sheep and cattle. They are caused by excessive exposure to ultraviolet light. They may be single or multiple, appear in lightly haired and lightly pigmented skin, and vary in appearance from ill-defined areas of erythema, hyperkeratosis, and crusting to indurated, crusted, hyperkeratotic plaques.
Histologically, they are characterized by atypia and dysplasia of the epidermis, hyperkeratosis (especially parakeratotic) and occasionally by solar elastosis of the underlying dermis. These are premalignant lesions capable of becoming invasive squamous cell carcinomas.
These have been recognized in dogs. Generally, they present as solitary lesions of the pinnae. Lesions are well circumscribed, erythematous, and scaly to markedly hyperkeratotic plaques or papillomas.
Histologically, an irregular to papillated epidermal hyperplasia with overlying hyperkeratosis overlies a subepidermal lichenoid band of inflammation.
These have been recognized in dogs, cats, cattle, sheep and horses. They may originate from other epidermal lesions. They may be single or multiple horn-like projections up to 5 cm long.
Histologically, they are characterized by extensive, compact, laminated hyperkeratosis.
These are benign, post-traumatic proliferation of fibrous tissue in humans. The veterinary literature is unclear on their occurrence in domestic animals.
These are benign granulomatous lesions associated with increased concentrations or composition of plasma lipids. The lesions vary from yellow to erythematous, having the gross appearance of pustules.
Xanthomatosis has been reported in cats with a presumed hereditary hperlipoproteinemia.
Histologically, they are characterized by an infiltration of foamy macrophages (xanthoma cells) with or without concurrent granulomatous inflammation and fibroplasia.
This is an uncommon disorder of dogs. Widespread calcinosis cutis can occur with either natural or iatrogenic hyperglucocorticoidism. Lesions consist of papules, plaques, and nodules that are firm, often gritty, frequently ulcerated and secondarily infected, and yellowish to pink.
Histologically, calcium salts are deposited along collagen and elastin fibers of the dermis and basement membrane zones and are frequently surrounded by a granulomatous inflammatory response. This is though to be a dystrophic calcification.
Localized foci of calcinosis cutis (calcinosis circumscripta) are seen most commonly in young dogs of either sex. The cases are more numerous in large breed dogs. Lesions are usually domed, fluctuant or firm, and 1-10 cm in diameter. As lesions age, they can become superficially ulcerated, and discharge a chalky white, pasty to gritty material. They are most frequently seen near pressure points
Histologically, the localized type of calcinosis cutis is characterized by multiple foci of granular amorphous material surrounded by a zone of granulomatous inflammation and separated by fibrous trabeculae.
A heterogenous group of skin disorders due to excessive accumulation or deposition of mucin (acid mucopolysaccharide) in the dermis and or epithelial structures. In dogs, it may be seen with hypothyroidism lupus erythematosus, dermatomyositis, mycosis fungoides, and as a normal finding in the Chinese Shar Pei
Breed Predilections for Cutaneous Neoplasia in Dogs
Cocker spaniel, Kerry blue terrier
Intracutaneous cornifying epithelioma
Norwegian elkhound, Collie, German shepherd, Keeshond
Effect Of Fish Oil, Arginine And Doxorubicin Chemo-Therapy On Remission And Survival Time In Dogs With Lymphoma: A Double Blind, Randomized Placebo Controlled Study
By GK Ogilvie, MJ Fettman, CH Mallinckrodt, JAWalton, RA Hansen, DJ Davenport, KL Gross, KL Richardson.
Colorado State University, Ft. Collins, CO 80523, Hill's Science and TechnologyCenterTopeka, KS
Source: Emailed to ScottiePhile from Carole Owen, 19 December 2001.
Polyunsaturated n-3 fatty acids have been shown to inhibit the growth and metastasis of tumors. One previously reported study demonstrated that a diet supplemented with n-3 polyunsaturated fatty acids improved the disease free interval and survival time and lowered lactate and insulin levels in 32 dogs with lymphoma. The double blind, randomized study reported here was designed to evaluate the hypothesis that polyunsaturated n-3 fatty acids can improve metabolic parameters, decrease chemical indices of inflammation, enhance quality of life, and extend disease-free interval in dogs treted for lymphoblastic lymphoma with doxorubicin chemotherapy.
Seventy one dogs with lymphoma were randomized to receive one of two diets. The experimental diet was supplemented with menhaden fish oil and arginine while the otherwise identical control diet was supplemented with soybean oil. Diets were fed prior to and after remissions were attained with up to 5 dosages of doxcrubicin. Parameters examined included blood concentrations of glucose, lactic acid and insulin in response to glucose and diet tolerance tests, alpha-1 acid glycoprotein, tumor necrosis factor, interleukin-6, metalloproteinase levels, body weight, amino acid profiles, platelet aggregometry, resting energy expenditure, disease-free interval (DFI), survival time (ST), and clinical performance scores.
Dogs fed the experimental diet had significantly (P<0.05) higher mean serum levels of the n-3 fatty acids docosahexaenoic acid (C22:6) and eicosapentaenoic acid (C20:5) when compared to controls. Dogs fed the experimental diet had significantly higher levels of arginine than those in the control group. Higher serum levels of C22:6 and C20:5 were associated with lower (P<0.05) plasma lactic acid and insulin responses to intravenous glucose and diet tolerance testing. Interleukin 6 and TNF alpha levels were lower in dogs fed the experimental diet. Interleukin 6 levels were increased in dogs fed the control diet. Resting energy expenditure was lower in dogs fed the experimental diet compared to controls. The percentage of dogs with increased toxicity was significantly lower in the dogs fed the experimental diet compared to controls. Increasing C22:6 levels were significantly (P<0.05) associated with longer DFI and ST for dogs with lymphoma.
We conclude that fatty acids of the n-3 series normalize elevated blood lactic acid and insulin in a dose dependent manner, result in an increase in DFI, ST and improved quality of life in dogs with lymphoma.
Original Doc: Abstract On Lymphoma Treatment.doc
Promising New Treatment For Malignancies
By Carole Fry Owen¸
Source: The Bagpiper, 1993 Number 3.
A new treatment for canine malignancies is available. Piroxicam, a non-steroidal, anti-inflammatory drug, is now in the treatment arsenal of veterinarians. Sold under the trade name Feldene, piroxicam is a popular prescription familiar to many as a human arthritis medication.
The interesting point for STCA members is that prioxicam is showing an effectiveness in treating maliganancies to which Scotties seem to have a greater risk than some other breeds. Quoting the 1986 Scottish Terrier Club of America Handbook article Diagnosis and Treatment of Some Common Malignancies in the Scottish Terrier, "it would appear that genetics 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." (1)
These are the same malignancies which recently have been treated with good results in piroxicam studies at Purdue University School of Veterinary Medicine. This new therapy has meant a much improved quality of life in a 10-year-old female Scottie of mine. She was diagnosed with transitional cell carcinoma of the bladder in September 1992. Surgery, radiation and chemotherapy all give quite disappointing results with this type of bladder cancer, indicates the above 1986 STCA cancer review. We are pleased with the results of piroxicam therapy.
Lucky, our old C.D. obedience dog, started having accidents in winter, 1991, at 9 years old. Urinalyses on several occasions revealed no infection, though there were microscopic traces of blood. Our local veterinarian, Dr. Scott Burt, Big Spring, TX, suggested diethylstilbesterol (DES), an estrogen therapy that can help female incontinence caused by weakening of the muscles that control bladder action. But he cautioned that the accidents and straining to urinate might be evidence of early bladder malignancy. Routine blood work not long after had shown elevation of the serum alkaline phosphatase enzyme which sometimes indicates presence of malignancy. Cancer ws a distinct possibility. And, affirmed the 1986 STCa cancer article, "It can be extremely difficult to differentiate clinically between chronic bladder infection, stones and cancer."
DES seemed to improve the situation temporarily. Lucky headed for college as a bed-dog for our son Scott. Later, off at school, there were more accidents. This time blood was in the urine, obvious to the eye. Home Lucky came in June, 1992, for a recheck. Dr. Burt x-rayed for possible bladder stones or a malignant growth. There was no evidence of either.
By September, 1992, Lucky's puddles were centered with large spots of blood. Dr. Burt ran positive and negative cystograms, radiologic dye studies of the bladder. This time the news was defenite, and bad. There was a growth at the neck of the bladder. It was so obstructive to the pathway into the bladder that Dr. Burt could not use the usual French 8 catheter to insert dye into the bladder. He had to resort to the smallest French 3«. Cell studies at Texas Veterinary Medical Diagnostic Laboratory confirmed Dr. Burt's tentative diagnosis of transitional cell carcinoma of the bladder.
The options? Surgery, radiation, chemotherapy, or nothing. The nearest surgical specialist was 300 miles away. Even for a specalist, the tumor would be hard to reach and tricky to excise completely. Dr. Burt predicted that the tumor's location probably would require breaking Lucky's pelvis, and that the delicacy of operating at the narrow neck of the bladder would make it nearly impossible to remove all the malignancy. Prognosis, even with surgery, would not be good. There isn't much hope for transitional cell carcinomas.
Breaking her pelvis would guarantee Lucky would complete her life as a cripple, and the surgery also might leave her totally incontinent, instead of only partially. Our family decided we couldn't put a 10-year-old dog through such trauma. We opted to let our dog live out whatever time might be left as normally as possible at home.
The first two weeks after the cystogram were not good. There were more accidents than ever, with large quantities of blood. Lucky was listless. She lost a pound, a noticeable loss for a 15-pound Scottie that never misses a meal.
Sadly, we figured Lucky had only a very few weeks left and took her back down for a college weekend and a final farewell to Scott. That weekend was full of last photos. I investigated cremation. We expected the end soon.
Back in Big Spring, the nice surprise was that there was still something we could try. Dr. Burt had checked with oncologist at Texas A & M University College of Veterinary Medicine. Clinicians there were having some success with piroxicam cancer therapy pioneered by Purdue's vet school. Oncologist Dr. Claudia Barton suggested we use piroxicam with Lucky.
Dosage prescribed for a dog the size of a Scottie required me to reformulate the drug. I became something of a pharmacist. The 10 mg capsules are too strong for a Scottie. Recommended dosage is 0.3 mg/kg every 48 hours. For Lucky's 15 pounds, that means three doses per capsule. One capsule lasts six days. To prevent breakdown of the drug because of its possible instability in liquid, I mix one capsule at a time with pharmaceutical syrup. The mixture is split between three syringes (to be given orally) and refrigerated until used.
In the Purdue clinical trial reported in a 1992 issue of Cancer Chemotherapy and Pharmacology, piroxicam was given to 62 dogs. A fairly complete range of cancers was studied. Tumor types were 10 transitional cell carcinomas, 10 melanomas, 9 osteosarcomas, and smaller numbers of fibrosarcomas, hemangiopericytomas, squamous cell carcinomas, mammary adenocarcinomas, perianal gland adenocarcinomas, anal sac adenocarcinomas, lymphomas, mast-cell tumors, nasal carcinoma, mammary adenoma, transmissible veneral tumor, synovial cell sarcoma and lipoma. Though no complete remissions occurred, eight partial remissions were documented in 3 of the 10 dogs with transitional cell carcinoma of the bladder, in 3 of the 5 animals with squamous cell carcinoma, in 1 of 3 dogs with mammary adenocarcinoma, and in the one dog with transmissible veneral tumor.
Complete tumor remission in two dogs bearing malignant hemangiopericytoma and metastatic carcinoma was observed in an earlier Purdue study using piroxicam. A previous human clinical trial of piroxicam with 31 cancer patients having pulmonary metastasis also had shown one complete response and give "minor regressions" of malignancy.
Additionally, Purdue later reported use of piroxicam in 24 dogs, all with transitional cell carcinoma of the bladder. These tumor responses at 60 days were 0 complete remissions, 4 partial remissions, 11 stable diseases, and 8 progressive diseases. Preliminary analysis showed a median survival of 150 days (range 30 to 510 days) with 8 dogs alive at the time that the report was written.
Veterinarians at Texas A & M have used piroxicam therapy for about a year and have been pleased with the results. "the good thing about piroxicam therapy is that the dogs feel pretty good," said oncologist Dr. Barton. She notes, "We still recommend radiation followed by surgery, if the tumor is in a site where it can be reached."
Dr. Barton does not claim that piroxicam is a miracle drug. She describes results at Texas A & M which are similar to those at Purdue: about dogs responding with decreased tumor size, with stable disease, and with progressive disease. "But," she emphasizes, "that's better than other results we've had."
The results at Texas A & M have been obtained with half the dose originally used in the 1992 Purdue research, and patients have exhibited fewer gastrointestinal problems. Piroxicam can cause serious GI bleeding, according to Dr. Barton.
"We have tested the tumor size with sonography. It does appear tumors get a little smaller with piroxicam," indicates Dr. Barton. "There may be some chemotherapeutic benefit, but we're not particularly impressed with tumor shrinkage." She explains that improvement may be due to reduced edema and reduced inflammation rather that true tumor reduction.
"We feel like piroxicam gives comparable results to those we get with cisplatin chemotherapy or radiation," say Barton. The advantage, Dr. Barton repeats, is: "the dogs feel good, and they get to stay at home. " Disadvantages Barton ascribes to the common cisplatin chemotherapy include severe nausea, vomiting and kidney toxicity. And with radiation treatment, dogs must be hospitalized four to five weeks for the 12 to 15 treatments, according to Barton.
Purdue also compared its piroxicam results to similar cases treated with cisplatin, the currently used chemotherapy in canine transitional cell carcinoma. The tumor response and survival date of the two drugs were similar, but the toxicity of piroxicam treatment was much less that that of cisplatin treatment, according to Purdue.
From my own experience with a Scottie, piroxicam has been a bit of a miracle. We expected a steady deterioration and speedy demise of our pet. Instead, five months after beginning piroxicam therapy our dog acts like a 10-year-old puppy. Next month she will be 11. The first three months of treatment Lucky almost stopped having accidents, and the ones she had weren't bloody. The fourth month of treatment she did start having frequent accidents again, and they remain bloody. (2) However, Lucky feels good!
The only side effect of piroxicam therapy has been an occasional day with minor nausea and spitting up. There's an occasional time like the morning she tipped over her bowl of kibble and tried to bury the food disgustedly under her kennel rug. Two hours later her belly must have been back to normal. She knocked the same bown off a crate top to get at every crunchy bite and then scavenged a jar of throw-away bacon grease from the trash.
Lucky retains her great interest in food. She is active, can still work up a game of soccer. She delights in life and appears in no pain. What more could we wish for a cancer patient?
Without treatment of any kind, transitional cell carcinoma of the bladder can claim a dog's life in a very short time, as little as one to three months or less, according to Dr. Barton. With piroxicam therapy, Dr. Barton projects a more usual survial time of 9 months.
At this point, it's been about a year from what must have been Lucky's first signs of bladder cancer, and five months since diagnosis of cancer and beginning treatment with piroxicam. We still have milestones ahead with Lucky. We had our one more Christmas, now maybe one more birthday next month, perhaps even one more walk in the neighborhood 4th of July parade. The end has not changed, but piroxicam has been a gift of time, more importantly, a gift of quality time.
For future reference, please write the following addendum in your 1986 STCA Handbook following the article, "Diagnosis and Treatment of Some Common Malignancies in the Scottish Terrier".
CANCER UPDATE, 1993--
Piroxicam (Feldene) therapy is being used with good results in treatment of some canine malignancies. Recent suggested regimen: 0.3 mg/kg piroxicam every 48 hours.
Reference: Dr. Claudia Barton, Professor of Oncology, Texas A & M University College of Veterinary Medicine, College Station, TX.
"Piroxicam Therapy in 24 Dogs with Transitional Cell Carcinoma of the Bladder." D. W. Knapp, R. C. Richardson, et al. Proceedings of the 9th Annual ACVIM Forum, New Orleans, LA, May, 1991. p. 896.
"Phase I Trial of Piroxicam in 62 Dogs Bearing Naturally Occurring Tumors." D. W. Knapp, R. C. Richardson, et al. Cancer Chemotheraphy and Pharmacology. 29: 214-218, 1992.
(1) Of genetic interest is that one litter mate of our Lucky is known to have died with transitional cell carcinoma at about 9 years old. Lucky's breeder is deceased, so we do not know if these are the only two closely related dogs in that line to have had transitional cell carcinoma. Lucky is a spayed female, and was never bred, so implications in her own offspring are impossible to determine.
(2) During the first several months of her piroxicam therapy, Lucky received Vitamin C supplementation daily, unrelated to her cancer treatment and unprescribed by a veterinarian. About 1,000 mg ascorbic acid crystals were added to her evening meal. For no special reason, I stopped Vitamin C supplementation, then about two months later added it to Lucky's diet again. I noticed that, upon receiving Vitamin C again, Lucky almost immediately had few accidents and that there was much less blood in them. Thinking back, the time when Lucky stopped receiving Vitamin C was about the time she started having bloody and frequent accidents. I have no scientific evidence that Vitamin C is a hepful adjunct of piroxicam therapy, but I can't help but wonder. I have sent this information to Dr. Barton for her comment.
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