Max's House

Understanding Cancer
&
Tumors

Introduction

Although its difficult for us to accept, the fact remains that the prevalence of cancer in cats (and dogs) is increasing. Prevalence simply implies an increased number of diagnosed cancer cases per year without documenting number versus population at risk (incidence). This prevalence is increasing for a variety of reasons but is at least in part related to animals living to older and older ages. Since cancer is generally a disease of the older animal, the price these animals pay for living longer is an increased likelihood of developing cancer. The greater life span is a result of better nutrition, vaccinations (preventing many previously fatal contagious diseases), better preventative and therapeutic medical practices, better understanding of the saftey of keeping cats (and dogs) indoors or supervised outdoors, and a deeper devotion (human-animal bond) to pet animals within the last few years. With this increasing prevalence, veterinarians will be called upon more frequently to diagnose and manage the pet with cancer.  The more we know about cancer, the better we will be able to work in partnership with our veterinarians to help provide our pets with the earliest (and best) possible treatments when it is likely to produce the best results.

Until a few years ago, a veterinarian facing an aged cat with cancer did not have many therapeutic options available because, when a neoplasm was not amenable to surgery, euthanasia was usually recommended or the owner was strongly discouraged from pursuing other treatment options. With a better understanding of tumor biology, effects of chemotherapy and radiotherapy on malignant and normal tissues, and management of therapeutic complications, clinical oncology has emerged as a distinct specialty in veterinary medicine. As a result, an increasing number of cats have benefited from different treatment regimens for both operable and inoperable cancers. These therapeutic regimens,  include surgery, chemotherapy, radiotherapy, hyperthermia, immunotherapy and cryosurgery (the controlled use of cold temperature to induce cellular death)..   It is important to understand that many tumors of domestic cats can be cured with the cat living a normal healthy, happy, life for years after treatment.

More open acknowledgment of the human-animal bond has elevated the importance of pet animals to the level of human beings in many owners' eyes. Some owners consider their pet more important than any human contact. Proper care of these animals are of increasing importance to many owners. In addition, its important for us as caretakers to understand cancer as a disease process and the concept that cancer is treatable (or even curable).   Therefore, we must learn to recognize the clinical signs and lesions associated with malignant neoplasms in cats. We owe it to our cats  to be well informed and up-to-date on current treatment methods for cancer and see to it that our cats receive the very best possible care.  Afterall, their health, welfare and lives are entrusted to us.

DEFINITION OF ONCOLOGY TERMS

Several terms need to be defined in order to achieve a better understanding of the subject. Cancer is defined as a malignant tumor or neoplasm. Neoplasms are classified as malignant if they can result in the patient's death. Within this context, the terms cancer and malignancy are used interchangeably. In addition, tumor and neoplasm are used as synonyms. The termination -oma is used to designate benign tumors of both epithelial and mesenchymal origin (e.g., perianal adenoma, fibroma, chondroma). Carcinoma refers to a malignant tumor of epithelial origin, while sarcoma refers to a mesenchymal malignancy. Adenocarcinomas are malignancies that affect the glandular epithelium (e.g., mammary adenocarcinoma). Mixed tumors are those in which both epithelial and mesenchymal components can be identified; mixed tumors can be benign or malignant and are rare in cats.

Metastasis refers to distant dissemination of a tumor by lymphatic or vascular routes; most malignant tumors result in the patient's death due to metastatic dissemination to vital organs. The most notable exception of a histologically benign tumor with biologically malignant behavior is a brain tumor that results in death secondary to local expansion and compression of normal tissue. The term paraneoplastic syndrome (or paraneoplasia) refers to the remote, indirect, noninvasive systemic effects of a tumor that are not directly related to metastatic lesions.

Response to therapy can be classified as complete response (CR), when there is complete disappearance of the primary and/or metastatic lesion(s); as partial response (PR) when there is at least 50 percent reduction in the size of the lesions; as stable disease (SD) when there is no appreciable change in the size of the lesions; and as progressive disease (PD) when there is progression of the lesions.

EPIDEMIOLOGY OF NEOPLASIA

The incidence of tumors in cats is roughly onehalf that in dogs, in cats it varies between 158 and 470 per 100,000 animals, while in dogs it varies between 381 and 1,126 per 100,000 animals. The discrepancy between these figures obtained from two different epidemiologic studies in defined feline populations may stem from artifact or from geographic reasons (i.e., cats are thought to be less popular in Oklahoma than in California, resulting in a lower number of visits to the veterinarian). Even though tumors in general are more common in dogs than in cats, the frequency of malignant tumors is considerably higher in the feline, mostly because of the high incidence of hematopoietic and skin and soft tissue tumors. In the cat, approximately 70 percent of tumors are malignant, while in the dog that percentage is approximately 35 percent.

The frequency of different histologic types and anatomic locations varies in different studies. When defined populations are studied, however, skin and soft tissue tumors represent approximately 35 to 45 percent of all tumors, while hematopoietic malignancies comprise approximately 30 to 40 percent of all tumors. .

There is no significant association between sex and the development of tumors in cats, with the exception of mammary cancer, which as anticipated is more prevalent in the intact female than in the spayed female or the male.

Although certain tumors such as lymphosarcoma have a bimodal age of presentation,   most tumors affect cats over 5 years of age. Other factors such as breed may exert a positive or a negative effect in the development of tumors (i.e., Siamese cats have
high incidence of intestinal adenocarcinomas but low incidence of cutaneous squarnous cell carcinomas). Finally, skin pigmentation has a definitive influence on the development of cutaneous squamous cell carcinomas, since white cats are 13 times more susceptible to developing this type of tumor than are nonwhite cats.


ETIOLOGY OF NEOPLASIA

It is generally accepted that tumors are not caused by a single agent (with the possible exception of tumors caused by oncogenic viruses), but rather by a multitude of factors, among which genetic, environmental, nutritional, traumatic, and hormonal factors predominate.

The occurrence of lymphoid and myeloproliferative neoplasia is associated with feline leukemia virus (FeLV) infection in cats. However, the development of FeLV-induced neoplasms depends on several factors, including type of exposure and mainly the ability of the cat's immune system to overcome or suppress the FeLV infection.

Feline immunodeficiency virus (FIV) also has been implicated as a cause of lymphoid malignancies and possibly myeloproliferative disease and squamous cell carcinoma.   Feline immunodeficiency virus infection is associated with only a 5-fold increased risk of developing lymphoma as compared to a 62-fold relative risk for cats infected with FeLV.' Concurrent infection with both retroviruses results in a relative risk of 77-fold indicating synergistic activity between the two viruses. The mechanism of oncogenesis by FIV remains to be elucidated but may be associated with the imumnosuppressive condition induced by the virus. Lymphoma occurs with increased frequency in humans infected with human immunodeficiency virus, and the use of immunosuppressive drugs has also been associated with an increased frequency of lymphoma and squamous cell carcinoma.

Genetic factors may predispose animals to the development of neoplasia, although no specific ones have been identified in the cat. However, it is well recognized that certain breeds of cats have a higher (or lower) incidence of neoplasia than the average cat population. For example, Siamese cats have a significantly higher incidence of intestinal adenocarcinoma than does the general cat population, while the incidence of squamous cell carcinoma in this breed is significantly lower. In addition, genetic factors governing the amount of skin pigment in cats determine the greater relative susceptibility of white cats to the development of cutaneous squamous cell carcinoma.  A familial tendency to develop lymphoma has also been reported in cats; however, this report was published before FeLV testing became available, and it might have represented clustering due to FeLV infection.

Many environmental factors have been implicated in the causation of neoplasia, including chemical carcinogens, ionizing radiation, and sunlight exposure (ultraviolet [UV irradiation). However, of them, only UV irradiation has been definitively identified cause of cutaneous squamous cell carcinoma in cats on the basis of both epidemiologic and experimental studies, to the point that avoidance of sunlight exposure in white cats prevents the development of these tumors.

Certain food additives and carcinogenic substances may be important nutritional factors involved in the pathogenesis of feline neoplasms. However, the effect of specific diets on the development of tumors in cats is unknown.

Trauma has been implicated in the development of neoplasia in dogs and cats. It is well established that repeated trauma from orthopedic devices may result in the development of bone neoplasia. In addition, trauma may result in the development of cutaneous and subcutaneous feline sarcoma virus (FeSV)-related sarcomas in cats. A number of posttraumatic ocular sarcomas have been reported in the cat. Of 25 cats, 16 had a history of trauma and 6 had a history of chronic uveitis. The interval between trauma and diagnosis of neoplasia may be as short as several months but is typically more than 5 years. The trauma or uveitis is commonly severe enough to result in the development of a plithisical eye. Tumor types reported include fibrosarcoma, osteosarcoma, and anaplastic sarcoma. The mechanism underlying the development of sarcomas secondary to trauma is unknown.

Hormonal factors may influence the development of tumors in cats. The fact that spayed female cats have a lower risk of developing mammary cancer than intact queens has been known since the late 1960s. In addition, several reports document a strong association between the use of progestins and the development of mammary masses in cats. These factors are discussed in more detail under Neoplasms of the Mammary Gland.

An increase in the number of sarcomas in cats arising from sites commonly used by veterinarians for subcutaneous and intramuscular vaccination has led to the suggestion that this may be a vaccine-related phenomenon. The increased incidence appears to correlate with the enactment of required rabies vaccination in cats in several states .

Focal, necrotizing, granulomatous panniculitis has been recognized for years by veterinary pathologists as an adverse reaction to vaccination. Frequently, the macrophages would contain bluish material interpreted as residual vaccine or adjuvant. Macrophages containing similar material have been found in association with the sarcomas. Electron probe x-ray microanalysis has revealed this material to be composed of aluminum. Aluminum hydroxide and aluminum phosphate are frequently used as adjuvants in vaccines.

Whether the aluminum is oncogenic or simply a marker of the inflammatory reaction, and whether vaccinal viruses are oncogenic remains to be determined. It has not yet been possible to identify a specific vaccine or adjuvant as the inciting agent; however, vaccination site fibrosarcomas are associated statistically with prior rabies and FeLV vaccination, especially when vaccines are given repeatedly at the same site.  Further studies are necessary to identify the precise risk factors and to eliminate the offending agent. It is important to note that routine vaccination has improved the quality of life for cats and should not be discontinued.

In summary, until further evidence becomes available, it should be considered that most feline neoplasms (with the possible exception of FeLV-, FIV-, and FeSV-associated malignancies) are the result of a multitude of factors. In specific cases, however, owners should be advised to avoid exposing their cats to known predisposing factors (e.g., avoiding exposure to sunlight in white cats, early spaying of female cats).



DIAGNOSTIC APPROACH TO THE
CAT WITH NEOPLASIA


In general, there are three categories of oncologic patients: cats in which the diagnosis of cancer has been confirmed by means of a biopsy; cats in which neoplasms are highly suspected on the basis of the history and clinical signs; and finally those in which the diagnosis of neoplasia is made incidentally during a routine physical examination. In the latter group of patients, the diagnosis is usually made when the tumor is relatively small and the patient is asymptomatic; in these cats, the prognosis is more favorable than in those with advanced disease. This is yet another reason why routine yearly physical examinations should be encouraged for all pets and semi-annually for cats over ten years old.

History and Physical Examination

Clinical signs in cats with cancer are usually nonspecific; they include weight loss, anorexia, depression, vomiting, diarrhea, bleeding, chronic nonhealing lesions, halitosis, and the finding of "lumps" or "bumps" by the owners. Except for the rapid clinical course seen with myelo- and lymphoproliferative neoplasia, the signs in most cats with cancer are chronic. Anorexia, weight loss, and depression usually result from the systemic effects of the tumor on the host (tumor cachexia). Vomiting and/or diarrhea are common signs in cats with G1 neoplasia, such as adenocarcinoma and lymphoma. Bleeding is a common presentation in cats with hematopoietic neoplasms (e.g., lymphoma, myeloproliferative disorders), since bone marrow infiltration commonly results in thrombocytopenia in these patients. Chronic nonhealing skin lesions are commonly the result of cutaneous /subcutaneous malignancy; neoplasms commonly associated with chronic nonhealing ulcers in cats include mainly squamous cell carcinoma and basal cell tumor. Halitosis is the most common complaint in cats with oropharyngeal neoplasms, of which the most common is squamous cell carcinoma. Because cat owners usually attribute halitosis to periodontal disease, these cats are presented to the veterinarian when the tumors are extremely advanced. Finally, lumps and bumps are the most common complaint of owners of cats with cutaneous /subcutaneous tumors and generalized lymphadenopathy due to lymphoma or leukemia. In addition to these clinical signs, organ failure can result from neoplastic infiltration of any parenchymal organ (e.g., hepatic failure due to primary or metastatic liver neoplasia). The Veterinary Cancer Society in conjunction with the American Veterinary Medical Association has published an educational pamphlet on Cancer in Animals for pet owners. 72

Physical examination is the mainstay of tumor diagnosis. A complete physical examination   should always be performed for any cat in which neoplasia is suspected, with particular attention to lymph node and splenic palpation, since cats have a high incidence of hematopoietic malignancies. Palpable lymph nodes in the cat include the submandibular, prescapular or cauda] cervical, superficial inguinal, axillary, and popliteal. Retropharyngeal, mesenteric, and mediastinal lymph nodes may become palpably enlarged when affected by pathologic processes. Palpable masses should be characterized as accurately as possible, trying to determine their size (in centimeters), consistency, regularity, and mobility, as well as the presence or absence of pain. Palpable features are extremely useful in limiting the number of differential diagnoses. For example, an irregular, firm, mobile, nonpainful, 2 X 3-cm, mid-abdominal mass, not associated with the small intestine in a 3-year-old cat with lethargy, anorexia, and weight loss, and absence of GI signs limits the differential diagnoses mainly to mesenteric lymphadenopathy (e.g., lymphoma, feline infectious peritonitis). If therapy is being contemplated, the tumor should be measured bidimensionally with calipers or a ruler as accurately as possible, as this will give the clinician an objective parameter with which to determine whether the patient is responding favorably to therapy.

After a presumptive diagnosis of neoplasia has been made on the basis of the history and physical examination, additional evaluation is warranted. Laboratory tests should initially be limited to a complete blood count (CBC, serum biochemistries, and urinalysis). Plain radiographs of the affected area, if indicated, and of the thoracic and abdominal structures are helpful in determining the extent of the tumor (i.e., evaluation of metastatic disease). Abdominal ultrasonography is also helpful. Hematologic, serum biochemical, and radiographic features of cats with suspected cancer are all essential in the proper diagnosis and treatment. 

It is important to understand that with early detection, proper diagnosis,  and immediate treatment, many tumors of domestic cats can be cured with the cat living a normal healthy, happy, life for years after treatment.

 

Modalities of Cancer Therapy
(Currently Under Construction)

 

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