1. The Five Most Common Feline Tumors
2. Staging Feline Cancer Patients
Dr. Greg Ogilvie recommends the TLC staging plan for cats.
Tissue Diagnosis: you need to know what you are up against. Fine needle aspirate or biopsy of the mass. Many round cell tumors exfoliate well. Sarcomas- least likely to exfoliate -may require a biopsy.
Location of the tumor: The location of the tumor (both locally and distant) is essentially the stage of the tumor. The basics are always the same. A good physical exam- metastatic lymph nodes, abdominal masses, respiratory pathology etc. Minimum database- complete blood count, chemistry panel and urinalysis. All cats CXR- 3 views. +/-Abdominal radiography or ultrasound. Occasionally other specific tests such as bone marrow aspirates , CT scans or MRI are needed.
Condition of the Patient: Any tumor can cause various paraneoplastic syndromes. cancer patients are geriatric- numerous underlying problems (highT4, CRF, CHF) Treat the underlying conditions. Dont blame everything on cancer. It is easy to say that the cat feels sick because it has cancer, but it is not always a true statement.
3. Tumor Types
2.Lymphoma - most common cancer in the cat. Incidence grown significantly since the 1950s with feline leukemia virus. Incidence of lymphoma has decreased with the incidence of FeLV over the past 15 years. Any age or any breed. Siamese and Oriental pure bred cats at higher risk. May have to do with the higher incidence of FeLV in catteries. Siamese may also have a predilection of developing mediastinal lymphoma. Male cats have predominated in several studies.
2.25% of all FeLV cats will develop lymphoma at some point in their lives. FeLV integrates into the myc oncogene and transduces it to form tumors in many cases. 5% of lymphomas in nonFeLV cats will have provirus in their tumors- may not be seropositive. PCR and IHC may be needed for dx. Cats with FeLV get mediastinal and multicentric lymphoma as well as extranodal sites.
3.FIV may cause lymphoma in cats, however, it often occurs with FeLV. In countries with far less FeLV (like Australia) FIV plays a much larger role in the incidence of lymphoma. In Australia 45% of cats with lymphoma are positive for FIV on a western blot.
4. Cats with FeLV are 60 times more likely to develop lymphoma, cats with FIV are 5 times more likely to develop lymphoma and cats with both viruses are 80 times more likely to develop lymphoma. (based on study of 353 cats)
1.Lymphoma is a heterogenous and can present in many different ways.
2. The 3 most common locations of lymphoma in the cat are alimentary, mediastinal and multicentric.
3. Well discuss the clinical presentation, staging, diagnosis and treatment of each of these individually. May very difficult to classify some cats based on their tumor locations. E.g. Some people classify renal lymphoma as Gastrointestinal, some classify it as multicentric and other consider it as its own entity.
6. Clinical Staging System:
Stage I is a single tumor (extranodal) or single anatomical area (node). Includes primary intrathoracic tumors.
Stage II: single tumor with regional lnn involvement, 2 or more nodal areas on the same side of the diaphragm, 2 single tumors with or without regional node involvement on the same side of the diaphragm, a resectable primary GIT tumor, usually in the ileocecal area, with or without mesenteric lnn involvement
Stage III: 2 single tumors on opposite sides of the diaphragm, 2 or more nodal areas above and below the diaphragm, all extensive primary unresectable abdominal disease, All paraspinal or epidural tumors regardless of other tumor sites or sites.
7. Alimentary Lymphoma
40-50% of all feline lymphoma cases. Average age-10-12 years. Involves the gastrointestinal tract as well as the lymph nodes of the mesentary. DSH most common breed - Siamese cats were the next most common breed. Rarely going to test positive for FeLV or FIV. If positive more likely to test positive on PCR than serology. FIV is rarely associated with alimentary lymphoma.
Clinical signs chronic and have been present for 1-3 months. Anorexia and weight loss. Vomiting may be less common. Depend on the histologic type of lymphoma as well as the distribution. Well differentiated (small cell) GI lymphoma- more superficial in the small intestinal mucosa.
Study of 39 cats with well differentiated lymphoma all but 4 presented with vomiting or diarrhea. Other signs -lethargy, depression, weakness, PU/PD (often with renal involvement), pica and abdominal swelling. Intestinal thickening and occasionally abdominal masses.
Lymphoblastic alimentary lymphoma is more severe. Abdominal masses are often palpable - may even perforate and lead to sepsis. Present with more severe signs of weight loss, anorexia, vomiting and diarrhea. More rapid onset and progression of clinical signs
Inflammatory bowel disease risk factor? In a study of 49 cats that had alimentary lymphoma only 6 had been previously treated for IBD. May require exploratory laparotomy and full thickness biopsies to rule out lymphoma. Small cell lymphoma can look like IBD on endoscopic biopsies. Full thickness biopsies demonstrate the effacement of gastrointestinal mucosa that is necessary to diagnose lymphoma.
Staging and diagnosis- most commonly the small intestine is involved. Occasionally cecum and colon involved. Stomach is rarely involved. Lymphoma - associated with one segment of small intestine. Rarely surgically resectable because of wide spread involvement, nodal involvement, infiltration of other organs such as kidney, liver, spleen, bone marrow and other sites. Staging determines prognosis. A minimum database- CBC, Chem panel, UA, FeLV/FIV testing, T4 testing and CXR.
Diagnosis and staging: Abdominal ultrasonography - determining other organ involvement, thickening of intestines, loss of layering in the intestinal wall, enlarged lymph nodes, and free abdominal fluid. Guide fine needle aspirates. Abdominal radiographs- organ enlargement and barium studies. However, barium studies take a long time and are labor intensive.
Endoscopy is limited in its ability to diagnose lymphoma. Diagnostic efficacy as low as 32-36% with this modality. The biopsy samples small and shallow. They can miss the lymphoma underneath. Endoscopy is also unable to evaluate and biopsy the jejunum, ileum and cecum. Lymphoma often occurs in these areas of the gastrointestinal tract.
8. Alimentary Lymphoma
Supportive care very important! These patients are often thin and anorexic. Chemo can make anorexia and vomiting worse. Feeding tubes may be warranted. TPN must be considered if cannot feed enterally. Oral appetite stimulants-valium and cyproheptadine. Many feel better once respond to tx.
Monitor weight loss in these patients. Can lose a significant amount of their body weight in short period of time. Cats that are losing weight require intervention immediately.
Surgery alone is not enough to treat intestinal lymphoma. May require surgical intervention in order to relieve an obstructio. Almost never a solitary lesion in the intestinal tract. Chemotherapy is the best modality for treatment. At the VMTH we use Chlorambucil at 20 mg/m2 once every 2 weeks for small cell gastrointestinal therapies as our first line of therapy. Cytoxan at 250 mg/m2 by mouth every 2 weeks is used as a rescue therapy for those cats that no longer respond to chlorambucil. Prednisone is used with both protocols at 1-2 mg/kg by mouth once daily. If the cat does not tolerate the prednisone very well or is difficult for the owner to pill then an every other day therapy can be instituted. For large cell gastrointestinal lymphomas we typically use the CHOP protocol. (end of notes) This is a combination of vincristine, cytoxan, adriamycin and prednisone given over 25 weeks. We substitute mitoxantrone in place of adriamycin for cats with renal insufficiency. Multidrug therapies are more effective than a single agent approach.
Cats with small cell lsa- long remission times. MST >1 year w/ chlorambucil and prednisone (range 16-23 months). CRs have longest remissions. They stay on chemotherapy for the rest of their lives. Very well tolerated. Initially need CBCs done every 2 weeks. After a response to therapy - CBCs can be done every 4-6 weeks. See resolution in clinical signs as well as weight gain.
Large cell GI LSA-much worse prognosis. MST 4-6 months. Cats that achieve a complete remission may live up to 7 months. Responses range from 60-70%. CRs range from 11-54%. CHOP protocol- most CRs but MST the same.
9. Mediastinal Lymphoma
Once the most common form of lymphoma in the cat. 1980s -20-40% of all feline lymphomas in the United States. Now only about 15% of feline lymphoma cases. The median age < 5 years. Siamese and oriental breeds- highest risk. Feline Leukemia virus -etiology of this disease. 75% are FeLV positive.
Dyspnea-most common presenting sign. O may not notice- One study of 30 cats with mediastinal lymphoma only 13 of the owners recognized respiratory difficulty present in their cats. An additional 9 cats were noted to be dyspneic by the veterinarian upon presentation. Coomon other signs regurgitation, dysphagia, anorexia, weight loss, enlarged lymph nodes, cough and ptyalism. Usually acute onset. PE dull lung and heart sounds ventrally. Not normal compressibility and occasionally a palpable mass is present at the thoracic inlet. 30-40% have peripheral lymph node enlargement (head, axilla and neck). Pleural effusion is common. Dyspnea and can become life threatening. Grow very fast. One report of a cat with a tumor weighing 250 gm in the chest that was not detectable 3 weeks earlier.
MDB- CBC, biochemistry profile, urinalysis and FeLV/FIV test. CXR. The mass may be obscured by pleural effusion. CXR can be repeated after thoracocentesis to evaluate the size of the mass. Cytologyof pleural effusion diagnostic, large lymphoblasts Thoracic ultrasound- fine needle aspirate or tru-cut biopsy of the mass. Patient should be stabilized before performing this or any diagnostics. Main differentials: mediastinal mass: lymphoma, thymoma, ectopic thyroid tissue and a branchial cyst. Lymphoma - younger cats, thymoma tends to be in older cats with a prevelance in somalies and abbysinians. Difficult to differentiate a thymoma from small cell lymphoma with FNA. Biopsy may be required. Thymoma - often cystic and biopsy or a fine needle aspirate without ultrasound guidance can be nondiagnostic. Damage vital structures when doing these tests blindly. Thyroid tissue- vascular, start with a fine needle aspirate. Thyroid tissue looks different from thymoma or lymphoma. Branchial cysts- large fluid filled structures. Aspirates -cystic fluid with no neoplastic cells. Draining with ultrasound guidance can provide relief for cats with clinical signs.
Staging- ~ ½ of cats will have evidence of lymphoma elsewhere. Peripheral lymph nodes, intra-thoracic and intra-abdominal lymph nodes. Less commonly - spleen, liver, bone marrow or kidney. Complete staging - abdominal ultrasound and a bone marrow aspirate also
10. Mediastinal Lymphoma
Surgery does not play a role in the treatment of mediastinal lymphoma. Radiation therapy - Increase response rates or treat those resistant to chemotherapy.The risk of pulmonary damage is high with high doses of radiation therapy. Lymphoma-very radiation responsive. Chemo is mainstay. Most chemotherapy responsive lymphomas in the cat. We use CHOP chemotherapy for these cats. Multiple drug therapy more effective than single agent therapy, esp w/ adriamycin. Response rates range from 50-90%.
Median survival times and prognosis varies depending on who you talk to. FeLV negative cats -longest MST- remissions of >1 year and up to > 11 years. FeLV positive cats MST 2-3 months up to 4-6 months. Anecdotally, many oncologists feel that these cats enjoy longer survival times then what has been reported. Some of these cats have been reported to have disease free intervals of years and often die of other causes related to their FeLV status. Cats with a single mediastinal site survive longer than cats with more diffuse disease.
11. Multicentric/Nodal Lymphoma
Study of 118 cats with lymphoma, about 40% (47 cats) were noted to peripheral lymph node involvement. 18 had single node involved, 13 regional lymphadenopathy (head, neck and axilla) and 16- generalized lymphadenopathy. 50% had other organ system involvement.
A group of young cats (1-4 years) generalized lymphadenopathy - low grade lymphoma. 50% Maine Coon cats. All alive 1-7 years whether or not they were treated. Now thought to be inflammatory condition as opposed to a lymphoma. Cats recover and their lymphadenopathy resolved within 5-120 days.
9 cats were diagnosed with a lymphoma of B-cell origin with histologically very variable cells difficult dx. The cats all had cervical or mandibular node involvement with a median age of 11 years. All FeLV/FIV negative by PCR and surgical excision of the affected nodes was curative in all cats except for one. This cat experienced recurrence twice at 6 month intervals and finally responded to COP.
Staging- MDB - CBC, biochemistry profile, urinalysis and FeLV/FIV test. Imaging: CXR, AUS. BMA also. FNA of the affected lymph nodes is often enough for diagnosis- but in tough cases a biopsy may be required diagnose lymphoma.
Treatment for a single node- surgical excision (staging!). Disseminated disease chemotherapy. CHOP protocol. Poor px FeLV/FIV positive cats that are sick on presention.
12. Extranodal Lymphoma
Common extranodal sites: nasal cavity, CNS and renal lymphoma. We will go over these briefly.
Nasal lymphoma -older FeLV negative cats. It has been reported in FeLV positive cats- more likely to have systemic disease and a poorer px. Clinical signs: nasal discharge, facial deformity, watering of the eyes, anorexia (due to inability to smell food) and weight loss. Diagnosis: nasal biopsy or fine needle aspirate through the face (usually in cats with boney destruction and facial deformity). Staging MDB, CXR, AUS, BMA and CT scan of the head for radiation planning. Treatment options: radiation therapy and chemotherapy- alone or in combination. Systemic disease = chemotherapy. Appetite stimulants and pain medications supportive care for radiation side effects. Cats do great with RT- the occular side effects can be quite severe. May result in blindness or even require enucleation. Cats have very large eyes and short noses making sparing the eyes impossible. Side effects : KCS, cataracts and retinal degeneration. Chemotherapy- CHOP protocol. At the VMTH we use radiation therapy first and save chemotherapy for those cats that fail. Anecdotally, there have been reports of cats that originally present with nasal lymphomas having recurrence in the kidneys. There have been no published reports supporting this.
3. True incidence is unknown. Not all cats with brain mass will have symptoms. Intracranial lymphoma -older FeLV negative cats, whereas spinal lymphoma- young FeLV positive cats. Clinical signs- brain involvement: seizures, cranial nerve deficits, ataxia, circling, blindness, disorientation, aggression, hyperesthesia, intention tremors, anorexia and lethargy. Clinical signs- spinal cord lesions: posterior paresis/paralysis that is typically bilateral. Diagnosis may be achieved about 50% of the time with a CSF tap. CT or MRI are very good at demonstrating a mass in the brain. Staging as previously discussed. Radiation therapy - treatment of choice for local disease, chemotherapy for diffuse disease. Chemotherapy drugs that cross the blood brain barrier such as CCNU, prednisone or cytosine arabinoside have been used. These drugs have little effect when used alone. Most cats with spinal lymphoma have involvement of other sites (the bone marrow is commonly affected) and require chemotherapy. Steroids alone provided some short term relief. Combination chemotherapy has provided the best responses. Most survival times < 20 weeks. Surgery has little role in the treatment of this disease.
Renal lymphoma - middle aged (median age 7.5 years) male cats. DSH and DLHs. Intially > 50% of affected cats were FeLV positive, however, recently only 25% of cats are positive for the virus. Clinical signs: acute renal insufficiency - cortical infiltration by lymphoma cells. Progress quickly. Renal lymphoma- always bilateral and renomegaly easily felt on abdominal palpation. Rare to have renal involvement w/o other organ involvement. Staging should be done as previously described. Diagnosis FNA of the kidney done blindly or with ultrasound guidance. Occasionally a biopsy sample is needed, especially in those cats with preexisting congenital malformations of the kidneys such as polycystic kidney disease. Therapy: chemotherapy - CHOP protocol. MST are longer for FeLV negative cats. The median survival times all cats- 3-5 months.
13. Squamous Cell Carcinoma
Incidence depends on location and distance from the equator ~ 20% of all cat tumors. DSH most common. Risk factors: White skin, thin hair, sun exposure. White cats 5xs more likely to get SCC Older cats, no known gender predilection. Outdoor cats at higher risk- increased exposure to the sunlight. Cats that sit in windows or bask in the sun indoors are also at risk.
SCC is much more likely to affect the face than any other place (80-90% of the time). Nasal plane most common site, 2 pinnae and 3 eye lids. Multiple cutaneous sites on the face. Eyelid lesions often have other lesions on their face. 1st dysplasia of the skin (carcinoma in situ)- waxy debris that reveals reddened skin underneath that does not bleed. 2nd begins to crust and ulcerate- destruction of normal tissue. May be present for a long time. In a study SCC lesions were present for 18 months before treatment was initiated. Oral SCC not due to sun exposure or coat color. Often found late in the disease. Clinical signs- oral SCC: dysphagia, blood tinged saliva, ptyalism, anorexia, halitosis and oral pain.
Metastasis- uncommon and occurs late. Undifferentiated SCC- more likely to met. Tumor stage is prognostic. Staging: palpation of the regional lymph nodes (FNA if possible) MDB and CXR. FeLV not a know risk factor. FIV may play a role. Outdoor cats are at risk for both diseases. FIV positive- shorter survival times. Retrovirus status should be evaluated in these cats.
14. Squamous Cell Carcinoma
15. Squamous Cell Carcinoma
T2 and T3 are regardless of size in depth factor
16. Squamous Cell Carcinoma
Precancerous actinic keratosis lesions that have not expanded past the basement membrane (Tis) may respond to retinoic acid derivitives/carotenoids. Use is controversial. ? carotene and canthaxanthin - responses in cats that had erythema, increased pinna hyperesthesia and hairloss w/o ulceration. Not very effective for cats with cartilage deformity (curling). Actutane not effective in a study of 7 cats with actinic epidermal dysplasia. Another 7 cats w/ SCC treated with acutane-1 had a partial response.
Photodynamic therapy - lesions < 1 cm in depth. A drug is given systemically that can only be activated by a certain wave length of light. After a certain amount of time (depending on the drug used), drug levels in the tumor are higher than surrounding tissue. The tumor and the surrounding normal tissue margin is exposed to a laser at the appropriate wave length to activate the drug and tumor cells are killed by oxygen free radicals. There is poor light penetration in tissues > 1 cm in depth. Most of the photosensitizers used are porphyrin derivatives. Durable complete responses have been reported for cats with Tis T2 tumors (7 of 9 cats). Complete responses are rare for tumors that stage T3-T4. Some cats may require more than one treatment. Side effects: scabbing of the affected area and sneezing. Generalized cutaneous sensitization has been reported with additional sunlight exposure. Acute hepatic necrosis and DIC have been reported in a small number of cats presumably as a reaction to the photosensitizing drug.
Cryosurgery: treat superficial lesions as well. Cryoprobe to two freeze thaw cycles. Good for pinnae and the eye lids. Margins of 3-5 mm had very impressive results. Nasal lesions did not have as good of a response. MST 26 months. Cats with more aggressive tumors that had invaded deeper into the basement membrane MDFI 8.5 months in the 8 of 11 cats that responded to therapy.
Surgery- good option if surgical margins can be obtained. The ear pinnae- most amendable to surgical resection with margins. The eyelid lesions can also be amendable to surgery. Nosectomies: nasal planum squamous cell carcinomas. With complete margins MST 16-20 months. Incomplete margins MST 5 months. Surgery great for T1-T2 lesions. Oral lesions may require mandibulectomies or maxillectomies. A better prognosis- more rostral lesions. Cats do not tolerate mandibulectomies as well as dogs do. More aggressive lesions will require more aggressive surgery and may require adjunctive therapies.
Radiation therapy: Strontium 90 - no deeper than 3-5 mm (Tis to T1 tumors). High dose of radiation used successfully on nasal planum lesions as well as eyelid lesions. MDFI 34 months. Orthovoltage radiation - more advanced tumors. Very high doses - little to no significant side effects. Good responses with durable remissions w/ low stage tumors. Higher stages did not do as well. MST- lower stage tumors were ~ 2 years (up to 53 months for T1 tumors). High grade tumors MST 15-18 months. FIV positive-more likely to have cutaneous side effects.
Megavoltage radiation -cobalt-60 source is what we use at the VMTH. RT penetrates deeper into tissues- little benefit with a superficial tumor like SCC. Better for higher grade tumors. MDFI ranged from 3.5-12 months. Pretreating a tumor with radiation in order to shrink it for surgery may be useful tool for more aggressive tumors.
Chemotherapy rarely used for lower stage tumors. Low metastatic rate and relative chemoresistance. In humans and dogs cisplatin and 5FU have been used with some success. Both cause fatal reactions in cats. Carboplatin- drug of choice. Intralesional carboplatin can be done. It is important to infuse the margins around the tumor in order to prevent recurrence. MST> 1 year have been reported for at least 2 cats treated this way.
Pain management - discomfort associated with the therapy or the tumor. Cats with normal kidney function may benefit from NSAIDs or may require stronger medications such as tramadol or opiods.
17. Squamous Cell Carcinoma
Indoor/outdoor cats should have limited exposure only in the early morning and late afternoon avoiding the sun during its most intense time in the afternoon.
Cats that sunbathe in a favorite window can be protected by using UV light blocking film on the windows.
Owners with high risk cats should be educated on the causes as well as early recognition of these lesions. The sooner these lesions are treated the better these cats do.
Regular physical exams on feline patients including good oral exams and dental cleanings can help to identify oral lesions sooner.
18. Soft Tissue Sarcomas
Many histologic types including: fibrosarcoma, rhabdomyosarcoma, liposarcoma, leiomyosarcoma, hemangiopericytomas, nerveofibrosarcoma, Schwannoma, myxosarcomas, myxofibrosarcomas, malignant fibrous hitiocytoma, hemangiosarcoma and undifferentiated sarcoma. All have similar biologic behavior (with the possible exception of malignant fibrous histiocytomas and hemangiosarcomas). DSH (2 xs) Middle aged cats. Trunk and limbs are most common sites. Other common locations head, neck, pinnae and tail. Some rhabdomyosarcomas- thought to be actinically induced on the ears of white cats. Injection site sarcomas will be discussed separately.
Can occur anywhere on the body, tend to be dermal, not well demarcated and rarely ulcerated. Ulceration - large masses w/ pressure necrosis in the skin. Firm, may be cystic or mucinous. Slow growing and may have been present for a while according to the owner. Invade underlying bone -pain or lameness - affecting peripheral nerves can cause pain, weakness and neurologic deficits. These tumors can become large enough to impair ambulation depending on location.
19. Soft Tissue Sarcomas
STS tend to invade the tissues far beyond what one can feel on physical exam. CT scan or MRI to help to delineate the margins. Allows for all options to be explored. Metastasis is uncommon and late. Recent papers (20-26%). Mets to lungs 1st, other locations - skin, kidneys, lymph nodes and spleen have been reported. MDB-CBC, biochemistry profile, urinalysis, FeLV/FIV test, local lymph node aspirates and CXR. Diagnosis: fine needle aspirate. Cover the hub of the needle. Som require bx. A histologic grade and type can also be achieved with a biopsy.
Surgery: large margins > 2 cm in all planes (including deep). Hard in small animal, especially when dealing with a recurrence. May require removal of dorsal spinous processes, areas of the scapula, muscle and body wall. Tumors on the distal extremities that can be removed with amputation. It is also important to try to remove the tumor en block without cutting into the tumor tissue itself. Pseudocapsule that can give the impression that they are encapsulated but they are not! Excisional biopsy is not ideal. It is better to get a punch, wedge or trucut biopsy-then refer to a boarded oncologist and surgeon for planning and therapy. Recurrence rates of 80-90% with surgery alone within 3-5 months. Except for tumors removed by amputation.
Radiation therapy: Pre or postoperative radiation therapy. Several methods for the delivery of radiation therapy can been employed. Dr. Lawrence will discuss these options in more detail in her lecture on soft tissue sarcomas. Key point is that preoperative radiation therapy is preferred over post operative radiation therapy. Post operatively the scars too large - cannot safely treat w/o radiating important structures such as the kidneys, spinal cord or lungs. Higher dose required post operatively, increase side effects.
Adjunctive Chemotherapy at recurrence or diagnosis of metastatic disease. Some studies- no survival advant. Recent paper- advantiage with carboplatin. May save chemotherapy until there is recurrence or metastatic disease instead of using everything up front. Drugs that have been used to treat soft tissue sarcomas in cats include: adriamycin, cytoxan, CCNU, carboplatin, bleomycin, methotrexate, vincristine, and mitoxantrone. Adriamycin and carboplatin seem to have the most promise as adjuvant chemotherapies for these tumors.
Prognosis: Mitotic rate - mitotic index of < 4 had a median survival time of 128 weeks (even with a 62% recurrence rate)- mitotic index of 5 or more had a median survival time of 16 weeks and a recurrence rate of 75%. The degree of histologic differentiation - higher grade tumors having a shorter survival. Histologic type may also play a role a recent paper published in JAVMA indicated that malignant fibrous histiocytomas may have a worse prognosis than other types of soft tissue sarcomas.
20. Vaccine Associated Sarcomas
The incidence increased significantly over the past 20-25 years. Coincides with wide spread rabies and FeLV vaccines. DSHs that are 6-7 years old. Fibrosarcomas msot common, but can be any type of sarcoma. Sarcomas have been reported with feline panleukopenia, herpesvirus and calicivirus vaccinations in countries that dont often vaccinate for FeLV and rabies. Also at sites of SQ fluid injections, antibiotic injections, Program 6 months and long acting corticosteroid injections. Incidence ranges from 1 in a 1000 to 1 in 10,000. Most of the data is based on estimates of cats truly vaccinated and sarcomas in injection sites.
2. Etiology- Inflammatory reaction caused by the vaccine. 1st macrophage response (frequently contain foreign blue material). Occasionally giant cells area seen as well. Aluminum has been reported to be associated with VAS when used as an adjuvant. However, other adjuvant material can also lead to inflammation. One study in 36 cats found that aluminum adjuvanted vaccines caused more inflammation than other adjuvants and that nonadjuvanted vaccines did not incite an inflammatory response. They also found that rabies vaccines cause more inflammation than FeLV vaccines. IM injections can have the same inflammatory reaction and sarcomas have been reported at IM injection sites- less common. Even though rabies vaccines cause more inflammation FeLV are more likely to lead to VASs. Cats receiving FeLV are 3 times more likely to develop VAS while cats receiving rabies vaccines are 2 times more likely to develop a VAS as compared to non vaccinated cats. Risk increases with # of Vacc in a certain spot. Feline sarcoma virus does not appear to be associated with the development of VAS. This virus requires the help of FeLV in order to cause sarcomas. In most studies only a very small number of cats have been FeLV positive and even fewer have been found to have both viruses.
21. Mast Cell Tumors
2nd most common skin tumor in cats. Account for 20% of cutaneous tumors in cats. 2 main forms in the cat. 1. mastocytic form-similar to MCTs found in dogs. 2. histiocytic form resemble histiocytic mast cells. Histiocytic - in younger cats (mean age 2.4 yrs) and mastocytic MCTs- older cats mean age 10 years old. Siamese predisposed to both histologic forms. Multiple spontaneously regressing tumors have been reported in the dog, cat, pigs, horses and human. This occurs in young animals- may be a hyperplastic or dysplastic syndrome rather than a true neoplasia.
4.Etiology is unknown- There has been no association with retroviruses and feline MCTs. There may be a genetic predisposition in siamese cats.
2. The grading system used in dogs does not apply to cats.
MCT rarely spread to the lungs. Visceral mast cell more common in the cat than the dog. Up to 50% of cats can have visceral involvement- more likely to spread than cutaneous forms. Metastatic rates for cutaneous tumors in cats are variable from 0-22% in different studies. Diffuse tumors are thought to have higher metastatic rates than others. The histiocytic types often regress on their own within 4-24 months.
In the feline visceral form the spread is most often to the liver first, then visceral lymphnodes, bone marrow, lung and intestine. Cats more likely to have mastocytosis than the dog.
2.Histologically anaplastic mast cell tumors look like only round cell tumors. Mast cell granules stain with Toluidine blue. This stain may be helpful in picking up small granules that are difficult to see with H&E staining. Mast cell tumors are also vimentin positive and often alpha-1-antitrypsin positive (true in cats and dogs). There are two main types of mastocytic: well differentiated (compact) and anaplastic (diffuse). Well differentiated tumors are the most common comprising 50-90% of feline MCTs- less aggressive. Anaplastic tumors are thought to be more aggressive. The histiocytic MCTs look similar to histiocyte-like cells with granules. There may also be lymphoid aggregates and eosinophils present. Not all of these tumor have granules. Some feline mast cell tumors are phagocytic and erythophagia may be seen.
3. Mast cells release potent inflammatory mediators: histamine, proteases, chemotactic factors, cytokines and metabolites of arachidonic acid that act on the vasculature, smooth muscle, connective tissue, mucous glands and inflammatory cells. Gastric ulceration- common. Ulcers in 35-83% of necropsy specimens- perforation is rare. Histamine acting on the parietal cells via H2 receptors- increased hydrochloric acid secretion. High serum histamine levels and low serum gastrin levels as a result of the negative feed back. Hypotension- thought to be due to prostaglandin D release as a vasoactive substance (at least in humans). Heparin release -coagulation abnormalities- localized hemorrhage as opposed to systemic bleeding. Delayed wound healing after surgery- proteolytic enzymes and vasoactive amines released by the tumors.
22. Mast Cell Tumors
Small, solitary nodules, non-haired and ulcerated ~25% of the time. May appear as plaque like masses or subcutaneous masses. Multiple nodules occur in approximately 20% of cases. The histiocytic type often occur as multiples on the head and may be ulcerated, but often resolve on their own. Visceral or disseminated -clinical signs of depression, anorexia, weight loss, vomiting, diarrhea and melena. Most cats have been sick for several months. Abdominal effusions- distension of the abdomen and pleural effusions may cause respiratory distress. Cutaneous MCTs in the cat often occur on the head and neck, then the trunk and limbs. The visceral form is more common in cats than in dogs (up to 50%)
Splenic MCT is the most common splenic disease of cats. Intestinal MCTs are the 3rd most common intestinal tumor. There is a diffuse splenomegaly form (most common) and a nodular form - uncommon. Intestinal MCTs- affect the SI with only 15% affecting the colon. Cranial Mediastinal MCTs have also been described in the cat. Many will have palpable splenomegaly. Diarrhea is a common sign with intestinal MCT. Occasionally life threatening hemorrhage or respiratory distress can be noted, but is often episodic unless due to pleural effusion.
2. Dx FNA of the mass and local lymph nodes that are accessible. Rowmanovskys or rapid hematologic-type stains will usually suffice. MDB- CBC, biopchemistry panel and urinalysis in all cats. ~ 50% of all cats with visceral MCT are anemic and many animals may have abnormalities concurrent with GI ulcers such as low protein, anemia and increased BUN. Buffy coats are still warranted - mastocytosis.Rarely splenic MCT tumors have also been reported to have hyperglobulinemia - unknown etiology. A CBC can help you determine if you need a bone marrow aspirate. AUS for spleen and liver involvement. The spleen is most often diffusely affected but may be nodular.
23. Mast Cell Tumor
Surgery usually curative for cutaneous. Do not require same margins as dogs- less aggressive (which is good, because a lot of them are on the head). Cats often do not have recurrence (0-24%) and if they do they typically have it within 6 months. Cats with histiocytic MCT can be identified on biopsy and then watched. If do not regress in several months, then you can remove.
Splenic MCT usually disseminated but improve clinically with a splenectomy with survival of 12-19 months even in the face of bone marrow and peripheral blood disease. Intestinal MCT in the cat carry a worse prognosis. Require large surgical margins (if focal) of 5-10 cm of bowel on either side. They often have high spread rates and cats usually die or are euthanized soon afterwards.
Chemotherapy mostly untested- people have tried vinblastine, vincristine, cyclophosphamide and methotrexate. The first protocol we typically use is Vinblastine with prednisone. Vinblastine is typically dosed at 2 mg/m2 IV with 8 doses over 12 weeks. There is also an escalating protocol for gross disease starting with 2 mg/m2 and going up to 3 mg/m2 over 4 weeks and maintaining the higher dose for an additional 4 doses. Vinblastine is a vinca alkaloid derived from periwinkle. Well tolerated, mild to moderately immunosuppressive, minimal gastrointestinal side effects. CCNU has also been used. Dose of 60 mg/m2 by mouth every 3 weeks. An abstract in this years VCS conference indicated that CCNU may be a good choice for cats with intestinal MCT with a MST of around 240 days. Several of the cats also received vinblastine. Either one of these drugs seems to improve survival over surgery alone. Cyclophosphamide - alkylating agent used to treat mast cell tumors with prednisone as a rescue or with vinblastine as a first line therapy. Cytoxan is dosed at 250 mg/m2 IV or PO every 2 weeks. This drug is mildly to moderately immunosuppressive with minimal gastrointestinal side effects.
3.Radiation therapy is not very useful in cats because they tend have more systemic disease. However, if local disease were to be incompletely resected in an area such as the limb where further resection were not possible with out amputation and the cat staged clean else where, then radiation therapy may be a possibility.
4. Misc.- A study using Imatinib in 9 tumor bearing cats orally included 1 MCT (lachowicz, et al 2005, JVIM). The dose escalation ranged from 1-15 mg/kg orally with only 1 cat experiencing minimal GI upset. No CBC or chem abnormalities were noted.
5. Ancillary therapies. It can become cumbersome for the owner to give all of these medications, however, many animals feel better on one or a combination of these therapies.
24. Malignant Mammary Tumors
Mammary epithelial tumors-most common mammary tumors in the cat. Adenocarcinoma and solid carcinomas are the most common. Mixed mammary carcinomas and sarcomas are rare. Mammary sarcomas in the cat tend to be slow to metastasize.
2. Older with a median age of 11 years. The risk for mammary tumors increases with age especially in intact female cats. No clear association between neutering and mammary carcinoma development in the cat. Some reports spayed cats were half as likely to develop mammary carcinomas as intact cats. Other studies ~50% of the affected cats were spayed, however, many were spayed late in life. Not completely clear spaying decreases the risk of developing malignant mammary tumors. Does not eliminate the risk. Parity is not a risk factor. Tricolored DSHs may be at an increased risk compared to other coat colors. Siamese cats appear to be at an increased risk. Exogenous progestins may increase the risk of tumor development. Estrogen and progesterone receptors have been found in feline mammary tumors. Not as common in malignant tumors as they are in benign tumors. Progesterone receptors more common than estrogen receptors- half of the cats in the study had been given progestins and this may have contributed to receptor upregulation. Mammary tumors are very rare in male cats (6 of 671 cats in seven studies) These male cats have often been treated with progestins for behavioral issues.
Often cats present to the veterinarian with advanced disease. In one study the time from owner detection of a mammary tumor to presentation to a veterinarian was 5 months. Educate cat owners that mammary masses in cats are very serious. Tumor can range from a few mm to > 10 cm on presentation. ½ ulcerated on presentation. 50% of cats present with multiple tumors. Entire mammary chains can be affected. This may be a result of lymphatic spread as oppose to synchronous tumor development. Caudal two mammary glands more likely (numbers 3 and 4) than other glands. The left and right sides equal. Lymphadenopathy rare, but a normal sized lymph node can still be affected. In 1 study only 6% had enlarged lymph nodes on presentation, but 27% of the same group had evidence of metastasis on histologic evaluation of the node. Wide spread metastasis can be a reason for presentation with lethargy, anorexia, dyspnea and cough may be the presenting complaint.
25. Malignant Mammary Carcinoma
26. Malignant Mammary Tumors
MDB- CBC, biochemistry panel, urinalysis and CXR should be performed in all cats. Careful assessment and palpation of all mammary glands and adjacent tissue should be performed before surgery. The local lymph nodes (axillary and inguinal) are commonly affected. In a paper of 129 cats that had been treated surgically for mammary carcinomas, 120 of them were found to have metastasis to a lymph node at post mortem. Pulmonary metastasis- more common than regional lymph node involvement. Miliary or a nodular pattern. Pleural metastasis is also common. Metastasis is just as common with the caudal mammary glands as it is in the cranial glands. Less commonly, these tumors can spread to liver and bone. Increases in liver enzymes or lameness may be present. Other metastatic sites that have been reported include the spleen, kidney, adrenal gland, peritoneal surfaces and heart.
Diagnosis surgical biopsy. Fine needle aspirates can be helpful, however, they are not as good at determining malignant from benign as a biopsy.
Aggressive surgery 1st. Spread via lymphatics as well as blood vessels. They can be very locally invasive and can spread to other mammary glands along the same chain. There does not appear to be a lymphatic connection across midline. Recommend radical mastectomy of the affected chain. A conservative approach of mammectomy has a much higher local recurrence rate. If only one side is affected then it is not necessary to take the other side. When mammary tissue is left behind there is always a risk of developing another tumor. Histology should be the final determining factor for completeness of incision. Small tumors that have not invaded the basement membrane (in situ) may be cured with surgery alone. Surgery should not be delayed for the results of a biopsy. Excisional biopsy in this case is warranted. MDFI surgery alone is 6 months. Cats with stage II and stage III tumors had significantly longer survival times than those of higher grades- MDFI of 10 months. Stage II tumors also did significantly better than stage III tumors. Surgery alone is often not enough for this disease. Chemotherapy -combined post operatively for metastatic disease control. Doxorubicin is the drug of choice for those cats that do not have renal insufficiency. Carboplatin can be used at a decreased dose if renal failure is present. Doxorubicin has improved survival in the microscopic and gross disease settings. MST 25-73 weeks. The main side effects: anorexia and a low white blood cell count. Appetite stimulants may be required.
Radiation therapy has not been widely studied because of the risk of side effects to important organs such as the lungs, kidneys, gastrointestinal tract and bladder. Shallow penetrating low energy radiation (such as a linear accelerator) would need to be used to safely treat these cats.
Prognosis- mets at time of dx. Tumors > 3 cm have a much worse prognosis than those that are < 3 cm in diameter. Histologic type- little significance prognostically, but the degree of differentiation was significant in one study. Studies have shown that high proliferating cell nuclear antigen (PCNA) as well as high mitotic rates and necrosis in the tumor are associated with a poor prognosis. These are all indicators of rapid growth.
28. Fibroepithelial hyperplasia