A closer look at…Paraneoplastic Syndromes in Domestic Cats
Paraneoplastic syndromes (PNSs) are changes (anatomical, structural, or functional) caused by certain malignant tumors. Some feline PNSs are frequent, whereas others are rare. Most commonly, PNSs are associated with generalized clinical signs involving areas distant to the primary tumor. Classification of PNSs is often based on the anatomical location affected. Although more common in older cats, PNSs are not overrepresented in specific breeds or gender. PNSs are important for several reasons. Firstly, PNSs are often the first indicator an animal has cancer. Secondly, some PNSs are specific to particular tumor types, thus they can aid in diagnosis or monitoring of the cancer.
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Since PNSs can cause more serious symptoms than the tumor, prompt diagnosis and treatment initiation is important. In cases where PNSs are apparent, management includes supportive care and treatment of the primary tumor. Animals can be affected with multiple PNSs at the same time, so a thorough physical exam and detailed history are essential. Owners’ primary complaints do not always indicate cancer or a PNS exists. Therefore, as veterinary nurses, we can help the veterinarian and patient immensely by asking owners supplementary questions and making fewer assumptions about the pet, no matter why they originally present to the veterinary hospital.
Gastrointestinal related PNSs are common in cats. Cachexia and anorexia both result in malnutrition and wasting of the patient, however, by different mechanisms. Anorexia is caused by a lack of proper nutritional intake manifested by a loss of appetite. The appetite loss could result from general malaise (due to cancer), treatments (such as chemotherapy), or the cat is physically unable to eat. When a cat is feeling sick from systemic cancer or nauseous from cancer treatments, appetite stimulants and anti-nausea medications can be prescribed. In addition, nutritional support and treatment of the primary cancer are often necessary in these patients. When a cat physically cannot eat due to cancer (which can be common with oral tumors such as squamous cell carcinoma or fibrosarcoma), surgery to remove the tumor and post-operative use of a feeding tube is often the best course of treatment. When cancer has progressed past the point of initiating aggressive treatment such as surgery, it is not recommended to place a feeding tube. This is because force-feeding a cat (with a painful tumor) is not associated with a good quality of life. For these patients, other palliative care (such as pain control) and end-of-life discussions may be more important.
Cachexia is defined as weight loss or muscle wasting while eating an appropriate amount of food. The mechanism of cachexia is complex because it can be attributed to multiple factors (such as metabolic changes, impaired digestion, tumor dependency on glucose, nutrient loss in effusions or exudates related to the cancer, endocrine derangement, humoral factor imbalances, or any combination of the preceding). Importantly, increasing caloric intake of a cachectic patient often will not reverse the symptoms. This is because treatment of cancer itself (with symptomatic management) is often necessary to effectively reverse the symptoms of cachexia. Tumor cells have a tendency to selectively use carbohydrates (and occasionally proteins) as energy sources, so diets with a higher fat content may benefit these patients. Many cachectic patients have difficulty staying adequately hydrated, so a food with higher water content (ex. canned food or dry food with added water) is useful. The American College of Veterinary Nutrition (ACVN) has recommended multiple diets for cats with cancer, but ultimately a feline diet that the cat will eat is the best option.
When a cat has an endocrinologic tumor, the tumor can produce hormones of the originating tissue at an uncontrolled rate. For example, thyroid carcinoma can cause hyperthyroidism. Surgical removal of the tumor usually alleviates any clinical signs associated with hyperthyroidism. Close monitoring of thyroid hormone levels after surgery is important because cats may become hypothyroid. If the tumor recurs, thyroid hormone levels can rise. Thus, thyroid hormone levels can be an indicator of tumor recurrence and should be checked regularly. Hypoglycemia is another PNS that can be seen in cats. Most commonly, hypoglycemia is seen in cats with an insulinoma which produces excess insulin causing low blood glucose (< 60 mg/dl). Clinical signs may include increased hunger, muscle fasciculation, lethargy, weakness, collapse, and ultimately death. Treatment of hypoglycemia includes removal of the tumor and supportive care with IV dextrose. Monitoring the blood glucose levels before and after surgery is vital, as surgical removal of the tumor can cause insulin deficiency (type I diabetes mellitus).
Hypercalcemia is another PNS, which is sometimes idiopathic. Increased hormone (parathyroid hormone, vitamin D, calcitonin) production can cause an imbalance in calcium homeostasis. Hypercalcemia can be seen in tumors such as lymphoma (especially mediastinal lymphoma), thymoma, multiple myeloma, and squamous cell carcinoma. Adverse consequences of hypercalcemia may include inappetence, vomiting, weakness, bradycardia, renal disease, cardiac arrhythmias, and obtundation. If left untreated, severe hypercalcemia can result in permanent disease (such as renal failure) or death (due to arrhythmia etc.) so it should be considered a medical emergency. Treatment involves treating the tumor (ex. surgery), combined with supportive care including drugs such as diuretics, glucocorticoids, and bisphosphonates. While treating for hypercalcemia, veterinary nurses must monitor patients diligently as close monitoring can make a life and death difference. Felines with accompanying heart disease require even more intense observation while being treated for hypercalcemia, as fluid overload could push the patient into heart failure. Being knowledgeable veterinary nurses is exceptionally important for these cats.
One of the most common feline PNSs is anemia. There are multiple causes for anemia including hemorrhage, red blood cell destruction, and decreased red blood cell production. Based on the cause, anemia is classified as regenerative or non-regenerative. Clinical signs of anemia may include lethargy, weakness, tachycardia, anorexia, and pale mucous membranes. Anemic cats commonly present to a clinic for other problems, thus, anemia is often found incidentally. There are many cancers associated with anemia. Examples include, but are not limited to lymphoma, multiple myeloma, hemangiosarcoma, mast cell tumor, and gastrointestinal tumors. Treatment is based on the cause of anemia. In all cases, the cancer should be removed or treated whenever possible. Blood transfusions and supplementation (ex. iron, erythropoietin, or immune modulators) may be indicated in some cats.
Multiple myeloma can cause hyperglobulinemia (excessive production of immunoglobulin). This PNS can also be seen in cats with lymphoma, and clinical signs are usually nonspecific. Treatment includes chemotherapy to address the cancer, and potentially plasmapheresis. Coagulopathies are another hematologic PNS seen is cats. Though the cause varies depending on the type of cancer, management involves treatment of the tumor and supportive care. Intravenous transfusions of whole blood or fresh frozen plasma may be needed. When a coagulopathy is present, it is important to handle the patient carefully (to avoid trauma and hemorrhage) and never draw blood from the jugular vein or perform any invasive procedures (ex. biopsy). Having a pressure bandage ready for venipuncture and aspiration sites is important. Patients with coagulopathies can decompensate quickly so experienced nursing practices are essential.
Cutaneous PNSs are rare in cats. When identified, however, they can aid in diagnosis of cancer (once other diseases have been ruled out). When cats present with a cutaneous PNS they are often systemically ill with no major abnormalities on bloodwork. Generalized exfoliative dermatitis is a PNS reported in cats diagnosed with thymoma. When the tumor is removed surgically, the dermatitis resolves. There are few studies reporting feline exfoliative dermatitis. If surgery is not a treatment option, chemotherapy and/or radiation therapy may be considered. Paraneoplastic alopecia (PA) is an infrequent and potentially diagnostic PNS seen in pancreatic and biliary carcinomas. The alopecia is acute and symmetrical with the skin often having an oily or glossy appearance. Hair along the edges of alopecia falls out easily. If the tumor is removed surgically, the alopecia may resolve. Unfortunately, by the time PA is diagnosed, the cancer has often progressed to a point where prognosis is poor. These cats are primarily treated with a palliative intent to decrease discomfort and any secondary bacterial or yeast infections in the skin.
A rare and painful PNS is hypertrophic osteopathy (HO). This syndrome is caused by uncontrolled proliferation of bone cells and patients often present lame or reluctant to move. Although HO can be seen with any tumor, it is commonly associated with primary lung tumors. It is important to distinguish HO from feline lung-digit syndrome (which is more commonly recognized). Lung digit syndrome is seen when a primary tumor metastasizes to a digit. Removal of the primary tumor often results in remission of HO. Remission can take weeks to months. Pain control is important to keep the patient comfortable until the HO is resolved.
Client communication with owners of cats suffering from a PNS is extremely important. Subtle changes during (or after) treatments can be signs of cancer recurrence or spread. It is unfortunate that many PNSs have generalized nonspecific clinical signs which makes them difficult to identify. This is why veterinary nurses must be attentive to any question an owner may have about their cat, regardless of the perceived urgency. A PNS can have a higher morbidity rate than the cancer itself, therefore the earlier a change is noted, the higher chance a patient has at a favorable prognosis. During treatments for cancer or PNSs there are a multitude of complications that may arise. Veterinary nurses are commonly the first to notice subtle changes before the onset of a crisis. PNSs can complicate the management of pets with cancer. It is important for veterinary nurses to be compassionate and attentive, especially for owners of cats with PNSs.
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J. M. Grierson*, C. A. Burton and M. J. Brearley
Davies White Veterinary Specialists, Manor Farm Business Park, Higham Gobion, Hertfordshire, UK
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Feline hypertrophic osteopathy associated with pulmonary carcinoma.
Author Affiliation : Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, 1008 West Hazelwood Drive, Urbana, IL 61801, USA.
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