Vaccine Associated Sarcomas by MikeJenny

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									Feline Retroviruses and

 Glenna Mauldin, DVM, MS
Diplomate, ACVIM (Oncology)
  Louisiana State University
Feline Retroviruses
Feline Retroviruses
 Common characteristics
  – single strand of RNA
  – presence of reverse transcriptase (RT)
 several subfamilies
   – Oncovirinae
      • i.e. Feline Leukemia Virus (FeLV)
   – Lentivirinae
      • i.e. Feline Immunodeficiency Virus (FIV)
Feline Retroviruses
 Incidence in North America
   – FeLV
     • overall: 1 - 3%
     • sick cats: 11.5%
  – FIV
     • overall: 1 - 2%
     • sick cats: 7 - 12%
Feline Retroviruses
 LTR - long terminal repeat
   – regulatory function
 GAG - group associated antigen
 POL - polymerase
   – reverse transcriptase
 ENV - envelope
Mechanism of Infection
 Virus binds to host cell receptor
 nucleocapsid enters cell
 RT produces DNA provirus from viral RNA
 provirus incorporates into host genome
 provirus transcribed by host cell
 viral RNA packaged and buds from cell
Feline Leukemia Virus
Pathogenesis of Infection
 Infective saliva
 oronasal exposure
 replication in pharyngeal tissues
   – epithelium, lymphoid tissue
 infected cells drain to mandibular lymph
 virus replicates in lymph nodes
Feline Leukemia Virus
Pathogenesis of Infection
 Viremia results from oral infection
  – amplified by systemic replication
  – bone marrow becomes infected
     • highly mitotic cell population
     • site that determines outcome of infection
  – salivary glands become infected
 exposure to viral shedding
   – 3 weeks to several months
Feline Leukemia Virus
Outcome of Exposure
 No evidence of infection (28%)
  – inadequate dose, age, immunity
 persistent viremia (30%)
   – FeLV-related disease
 transient infection (42%)
   – viremia of 4 to 6 weeks
   – successful host immune response to viremia
   – may result in latency or sequestration
Feline Leukemia Virus
Outcome of Exposure
 Latent infection
  – usually follows transient infection
      • lasts 4 to 9 months
   – proviral DNA remains in lymphoid or marrow
   – not detectable by IFA or ELISA
   – not contagious
   – recrudescence may occur
      • steroids, stress
Feline Leukemia Virus
Outcome of Exposure
 Sequestration
   – infection confined to local tissues
   – usually glandular
      • mammary
      • salivary
   – not viremic (IFA negative) but core antigen P27
     circulates (ELISA positive)
      • “discordant” test results
          – 50% eventually ELISA (-), 25% eventually IFA (+)
Feline Leukemia Virus
 Disease varies with viral strain or subgroup
  – lymphoma and leukemia: 20%
  – immune system dysfunction: 80%
     • immunodeficiency
        – lymphoid atrophy, T-cell suppression
     • anemia
        – aplastic vs. regenerative
            » hemolysis or Hemobartonellosis
     • myelodysplasia
     • reproductive failure
Feline Leukemia Virus
Diagnostic Testing
 ELISA (enzyme-linked immunosorbent
  –   detects P27 core antigen in body fluids
  –   100 times more sensitive than IFA
  –   may detect sequestered infection
  –   will not detect latent infection
  –   retest positive cats monthly for 3 months
Feline Leukemia Virus
Diagnostic Testing
 IFA (immunofluorescent antibody test)
   – detects P27 core antigen in nucleated cells and
   – performed on peripheral blood or bone marrow
   – usually indicates persistent infection
      • marrow involvement
   – will not detect sequestered or latent infection
Feline Immunodeficiency Virus
Pathogenesis of Infection
 Virus primarily cell associated
 found in body fluids
   – typically low concentration
   – highest concentration in saliva
 common route of transmission: cat fights
 other routes possible
   – transfusions
   – nursing
Feline Immunodeficiency Virus
Pathogenesis of Infection
 T cell function compromised
 CD4 lymphocyte: helper/inducer T cell
 CD8: suppressor/cytotoxic T cell
 infection produces  CD4:CD8 ratio
   – both decline immediately after infection
   – CD8 cells rebound
   – CD4 cells remain low and continue to decline
   – terminally total lymphocytes <300
Feline Immunodeficiency Virus
Outcome of Exposure
 Two phases of infection
  – asymptomatic phase
     • exposure
     • followed by prolonged low-grade virus replication
  – symptomatic phase
     • lymphadenopathy
     • AIDS-related complex (ARC)
     • AIDS: infections, weight loss, neurologic disease,
Feline Immunodeficiency Virus
 Hematopoietic neoplasia
 severe lymphoplasmacytic stomatitis
 chronic enteritis
 chronic upper respiratory disease
 neurologic disease
 immune-mediated disease
 chronic renal failure
Feline Immunodeficiency Virus
Diagnostic Testing
 Infection diagnosed by presence of FIV
     • convenient, cost effective and sensitive
        – false positives common
             » maternal antibodies (gone by 12 weeks)
             » 33% negative on Western blot
  – Western blot
     • more specific but costly
Feline Retroviruses
 Primary therapy nonspecific
   – nutritional support
   – blood products
   – antimicrobials
 specific therapies largely ineffective
   – reverse transcriptase inhibitors
   – oral interferon
Feline Retroviruses
 FeLV positive
   – persistently viremic cats: 2 year mean survival
   – 83% of FeLV positive cats dead within 3.5
 FIV positive
   – 50% of FIV positive cats dead within 5 years
   – 20% one year survival if symptomatic

Administration of chemical reagents which
 have a specific and toxic effect on
 neoplastic cells.
Basic Principles
 Greatest efficacy against cycling cells
 high growth fraction =  chemosensitivity
   – neoplastic cells
   – gastrointestinal mucosa
   – bone marrow
 low growth fraction =  chemosensitivity
   – plateau phase of growth
   – cells in G0
Basic Principles

   Systemic disease  Systemic therapy

       Local disease Local therapy
Basic Principles
 Indications for chemotherapy
   – most effective treatment for some tumors
      • lymphoma
   – adjuvant therapy for highly metastatic tumors
      • osteosarcoma
   – shrinkage of large masses prior to surgery
   – radiation sensitization
   – palliation of very large or painful tumors
Basic Principles
 Combination chemotherapy protocols
  – proven efficacy
  – complementary mechanism of action
  – balanced toxicity
  – scheduling of administration
 multimodality therapy
  – surgery, radiation therapy, immunotherapy
Chemotherapy Drug Classes
1. Alkylating agents
   – cause interstrand DNA binding
   – non-cell cycle specific
   – i.e. cyclophosphamide, chlorambucil, melphalan
2. Antimetabolites
   – structural analogues of metabolites required for
     nucleotide biosynthesis
   – cell cycle specific
   – i.e. methotrexate, cytosine arabinoside, azathioprine
Chemotherapy Drug Classes
3. Mitotic inhibitors
   – bind microtubular proteins leading to mitotic arrest
   – cell cycle specific
   – i.e. vincristine, vinblastine, taxol
4. Antitumor antibiotics
   – form complexes with DNA, free radical formation
   – non-cell cycle specific
   – i.e. doxorubicin (AdriamycinR), mitoxantrone, dauno-
     mycin, actinomycin-D
Chemotherapy Drug Classes
5. Miscellaneous
   – numerous mechanisms of action
   – glucocorticoids
      • lympholytic, immunosuppressive
   – L-asparaginase
      • enzymatic depletion of amino acid asparagine
   – platinum analogues
      • covalent binding to DNA
      • cisplatin, carboplatin
 Commonly utilized for treatment of
  lymphoma, leukemia, carcinomas and soft
  tissue sarcomas in both dogs and cats
 alkylating agent - crosslinks DNA
 cell cycle nonspecific
 must be biotransformed to active form by
  hepatic mixed function oxidase system
 absorbed orally (>75% bioavailability)
 Myelosuppression
  – nadir of leukopenia 7 to 10 days
  – platelet sparing
 vomiting and diarrhea
 alopecia
 carcinogenic, teratogenic and mutagenic
   – second tumors
 Sterile hemorrhagic cystitis
 difficult to treat
   – antibiotics, corticosteroids, DMSO
 administer drug in morning, free access to
  water, frequent opportunities to urinate
   – furosemide 2.2 mg/kg IV
 substitute chlorambucil in severe cases
 rare in cats
 Used to treat wide variety of neoplastic
  diseases in dogs and cats
  – lymphoma, leukemia, carcinomas (mammary,
    thyroid), sarcomas (bone, soft tissue)
 multiple potential mechanisms of action
  – intercalates with DNA
  – altered membrane function
  – free radical generation
 Extensive hepatic metabolism
  – reduced dose with hepatic disease?
 biliary excretion
 minimal urinary excretion (<5%)
 does not cross blood brain barrier
 allergic reactions during infusion
   – diphenhydramine (30 mg/m2 IV) in dogs
   – dexamethasone (0.1 mg IV) in cats
 Cardiotoxicity is dose limiting in dogs and
  – maximum cumulative dose 180 mg/m2 in dogs,
    550 mg/m2 in humans
 irreversible dilated cardiomyopathy
 fibrosis and electrical conduction
  abnormalities long term
 clinical cardiac toxicity not reported in cats
 Myelosuppression
  – nadir at 10 to 14 days
 severe tissue necrosis with extravasation
 radiation recall effect
 anorexia, vomiting and diarrhea
 alopecia
 nephrotoxicity in cats?
 Indicated primarily for treatment of canine
  and feline lymphomas and lymphoid
 curative in >90% of canine transmissible
  venereal tumors
 used occasionally for treatment of
  carcinomas and soft tissue sarcomas
 Binds tubulin and prevents nuclear
  microtubule formation
  – causes metaphase arrest
  – stops chromosome segregation
 cell cycle specific
 hepatic metabolism with biliary excretion
   – dose modification with liver disease
 Vomiting and diarrhea
 necrosis with perivascular administration
 peripheral neuropathies
   – sensory impairment
   – motor weakness
 paralytic ileus
 myelosuppression
  – mild when administered alone
Fun Chemotherapy Facts
 L-asparaginase may cause anaphylaxis
 cisplatin causes pulmonary edema in cats
 cisplatin causes renal failure in dogs
 carboplatin causes  platelets in dogs
 5-FU causes severe neurotoxicity in cats
 carmustine and lomustine (BCNU and
  CCNU) cross the blood brain barrier
Canine Lymphoma
 Commonly diagnosed malignancy in dogs
  – 5 to 7% of canine tumors
 etiology uncertain
   – genetic predisposition
      • Boxer, Golden Retriever, Bull Mastiff
   – environmental toxins
      • 2,4-dichlorophenoxyacetic acid (2,4-D)
   – possible retrovirus
Canine Lymphoma
 Relatively homogeneous presentation
  – disease of middle aged dogs
     • average age 6 to 9 years
  – multicentric involvement in 84% of dogs
     • profound peripheral lymphadenopathy
     • most common presenting complaint
  – frequently no systemic signs of disease
  – other organs may be involved
     • spleen, liver, thymus, bone marrow
Canine Lymphoma
 Well established clinical staging system
  – clinical stages I through V
     • stages I through III: increasing LN involvement
     • stage IV: liver and/or splenic involvement
     • stage V: bone marrow involvement or atypical
  – clinical substages a and b (not sick vs. sick)
 paraneoplastic syndromes common
     • hypercalcemia most common (20% of dogs)
        – also anemia, fever, DIC, IMHA/ITP, cancer cachexia
Canine Lymphoma
 Chemotherapy is most practical and
  effective treatment
   – canine lymphoma is a systemic disease
 median survival from 6 to 14 months
  – longest with protocols containing doxorubicin
 combination protocols preferred
   – maximize efficacy
   – minimize toxicity
Canine Lymphoma
 Chemotherapy usually well tolerated
 potential toxicities
   – gastrointestinal toxicity most common
      • anorexia, nausea and vomiting
      • diarrhea/colitis
   – alopecia
   – perivascular necrosis
   – sterile hemorrhagic (Cytoxan®) cystitis
Canine Lymphoma
 Life-threatening toxicity uncommon
  – myelosuppression and infection or sepsis
      • gram negative organisms typical
   – doxorubicin-induced cardiotoxicity
      • dose limiting toxicity of doxorubicin in dogs
         – maximum cumulative dose 180 to 240 mg/m2
      • irreversible dilated cardiomyopathy
      • close cardiac monitoring necessary
Canine Lymphoma
 Factors affecting prognosis
   – clinical stage of disease
     • worse for stages IV and V
  – clinical substage of disease
     • worse for dogs with systemic signs of illness
     • includes hypercalcemia
  – prior treatment with corticosteroids
     • induces multiple drug resistance
  – response to therapy
Feline Lymphoma
 Incidence of lymphoreticular neoplasia in
  the cat highest of any species
  – one third of feline malignancies
 caused by the feline leukemia virus (FeLV)
   – young, FeLV (+) cats with thymic lymphoma
     most common in early studies
   – fewer FeLV (+) cats in recent studies
     • geriatric, FeLV (-) cats with GI lymphoma
Feline Lymphoma
 Presentation and clinical signs vary widely
   – multiple anatomic sites
     •   cranial mediastinum/thymus
     •   gastrointestinal
     •   renal
     •   multicentric
     •   nasal
     •   miscellaneous/atypical
  – peripheral lymphadenopathy uncommon
Feline Lymphoma
 Most common presenting complaints
  – anorexia and lethargy
  – weight loss
 specific signs related to anatomic site
   – dyspnea
   – vomiting and diarrhea
   – polyuria and polydipsia
Feline Lymphoma
 Most common physical exam findings also
  – dehydration and weight loss
  – pallor
 specific abnormalities vary with site
   – abdominal masses
     • intestine, lymph node, spleen, liver, kidneys
  – decreased compression of anterior thorax
Feline Lymphoma
 Optimal treatment is chemotherapy
  – feline lymphoma is a systemic disease
 median survival approximately 7 months
  – not as well defined as canine lymphoma
 combination protocols recommended
   – maximize efficacy, minimize toxicity
   – doxorubicin increases remission duration
Feline Lymphoma
 Potential toxicities associated with
  chemotherapy for lymphoma in cats
  –   anorexia
  –   nausea and vomiting
  –   diarrhea
  –   coat changes and whisker loss
  –   perivascular necrosis
 may tolerate therapy better than dogs
Feline Lymphoma
 Less common toxicities
  – diabetes mellitus
  – immunosuppression with infection or sepsis
      • significant leukopenia less common than in dogs
      • consider Salmonella
   – doxorubicin nephrotoxicity
   – doxorubicin cardiotoxicity?
   – sterile hemorrhagic (Cytoxan®) cystitis?
Feline Lymphoma
 Radiation therapy often beneficial
  – combined with chemotherapy for anatomically
    confined forms of lymphoma
     • incorporated into induction therapy
  – palliation of chemotherapy resistant lymphoma
  – central nervous system lymphoma
     • brain or spinal cord
 localized disease more common than dogs
Feline Lymphoma
 Factors affecting prognosis
   – FeLV status
     • median survival of FeLV (+) cats 3 to 4 months
  – clinical stage of disease
     • improved prognosis for stages 1 and 2
  – clinical substage of disease
     • improved prognosis for substage a
  – response to therapy
     • prognosis better if response rapid and complete
Soft Tissue Sarcomas
Soft Tissue Sarcomas
 Tumors arise from primitive mesenchyme
  – numerous cell types
  – similar biologic behavior
 occur in both dogs and cats
 no breed or sex predilection
 disease of middle-aged to older animals
   – average age at diagnosis 8 to 12 years
Soft Tissue Sarcomas
 Common biologic features
  – arise from any anatomic location
  – pseudocapsule
  – poorly defined margins
  – local infiltration through and along fascial
  – metastasis in only 10 to 25% of cases
      • hematogenous route when present
Soft Tissue Sarcomas
 Clinical presentation
  – firm subcutaneous mass
  – adherent to deep structures
  – any body location
  – locally invasive, poorly defined margins
      • may appear discrete or encapsulated
   – growth rate generally slow
   – lymph node involvement rare
Soft Tissue Sarcomas
 Cytology unreliable in identifying sarcoma
  – small, nonrepresentative sample obtained
  – exfoliate poorly
  – areas of tumor necrosis often present
  – reactive fibrosis and low grade tumor have
    similar cytologic appearance
 may differentiate inflammation and tumor
 histopathology essential for diagnosis
Soft Tissue Sarcomas
 Surgery is central to successful therapy
   – metastasis infrequent
   – survival depends on local control
 plan surgery carefully
   – include all biopsy sites in resection
   – consider maximal possible scope of resection
     including margins
   – be prepared to place markers for RT
Soft Tissue Sarcomas
 Aggressive resection necessary for control
  – wide and deep - 3 cm margins
  – en bloc removal with dissection through normal
    tissue planes only
  – never “shell” or “peel” out - leaves
 submit all tissues for histology
   – ink or tag suspect margins
Soft Tissue Sarcomas
 Adjuvant therapy indicated in some cases
 radiation therapy if resection incomplete
   – consider second surgery first
 high total cumulative dose necessary
   – 21 fractions of 3 Gy each (total 63 Gy)
 excellent results in canine patients
 fewer studies in feline patients
   – median survival one year
Soft Tissue Sarcomas
 Chemotherapy alone unlikely to provide
  long term control
  – systemic therapy for localized disease
 shrink primary tumor, delay or treat
  metastasis, radiation sensitization
 Adriamycin® most often recommended
  – single agent or in combination
 carboplatin also reported to have activity
Soft Tissue Sarcomas
 Consider palliative radiation for advanced
  stage or nonresectable tumors
  – improves quality of life but not survival
     • relieves pain, improves function
  – less complex than definitive radiotherapy
     • short course of large dose per fraction
        – 8 to 10 Gy days 0, 7 and 21
     • cross-sectional imaging may be required
  – more effective than chemotherapy
Soft Tissue Sarcomas
 Prognosis depends primarily on surgeon’s
  ability to achieve complete resection
 factors associated with favorable prognosis:
  –   small size
  –   superficial lesion
  –   location on extremity
  –   noninvasive, mobile mass
  –   low histologic grade
Vaccine Associated Sarcomas
 Rabies vaccination first linked with
  development of sarcomas in 1991 a
 strong epidemiologic support in 1993 b
     – increased risk of sarcoma at vaccine sites
     – increased risk of sarcoma with FeLV and rabies
     – increased risk with multiple vaccinations
aHendrick.   JAVMA 1991:199;968.
bKass et al. JAVMA 1993:203;396.
Vaccine Associated Sarcomas
 Estimated prevalence 1 to 3 in 10,000
  vaccines administered
   – as high as 1 in 1000 vaccines administered
 aggressive biologic behavior
   – rapid growth and extensive local invasion
   – late metastasis
 sarcoma development typically seen within
  3 to 12 months of vaccination
Vaccine Associated Sarcomas
 Most tumors are fibrosarcomas
  – other sarcomas reported
 tumors composed of spindle cells, multi-
  nucleate giant cells, and histiocytic cells
  – inflammatory cell infiltrates
  – granulation and fibrosis
 intracytoplasmic material consistent with
  adjuvant in adjacent macrophages
Vaccine Associated Sarcomas
 Tumors appear to develop secondary to
  chronic local inflammatory response
  – fibroblastic proliferation
  – vaccine adjuvant implicated
 interaction between inflammatory cells,
  environment, and individual genome
  – intracellular oncogenes
  – cytokine response induced by vaccine antigen
Vaccine Associated Sarcomas
 Aggressive multimodality therapy required
 confirm diagnosis with incisional biopsy
 complete surgical excision ideal
   – difficult anatomic locations
   – include all biopsy sites
   – 3 centimeter margins recommended
   – radiodense markers to facilitate RT
 consider specialist referral
Vaccine Associated Sarcomas
 Preventing vaccine associated sarcomas
   – minimize dose of adjuvant administered
     • use nonadjuvated products
     • use single dose vials to standardize adjuvant dose
     • do not administer 3 year products annually
  – do not give multiple vaccines in same location
  – administer FeLV vaccine only to cats at risk
  – excise and biopsy palpable masses persisting at
    vaccine sites longer than 2 months
Mammary Gland Tumors
Canine Mammary Tumors
 Most common tumor of unspayed bitch
 average age at diagnosis 10 to 11 years
 clear hormonal dependency
   – tumor risk varies with timing of spay
      • 0.05% if spayed before first heat
      • 8% if spayed before second heat
      • 26% if spayed after second heat
   – 40 to 60% estrogen receptor positive
Canine Mammary Tumors
 Highly heterogeneous disease
 many histologic types
  – benign (50% of tumors)
     • fibroadenoma, simple adenoma
  – malignant (50% of tumors)
     • solid carcinoma, tubular adenocarcinoma, papillary
       adenocarcinoma, anaplastic carcinoma, sarcoma,
       mixed mammary tumor (carcinosarcoma)
 biologic behavior varies widely
Canine Mammary Tumors
 Physical examination findings
   – firm, well defined mammary gland nodule
     • single mass in 75% of dogs
  – local invasion and ulceration if malignant
  – evidence of metastasis possible
     • axillary or inguinal lymph nodes
     • internal iliac lymph nodes
     • dyspnea
        – pulmonary parenchyma
Canine Mammary Tumors
 Surgery is treatment of choice
   – least aggressive surgery that controls disease
      • often lumpectomy or mammectomy
      • routine radical mastectomy does not increase
         – increased cost and morbidity

 simultaneous OHE may be helpful
   – many tumors estrogen receptor positive
 chemotherapy has no proven benefit
Canine Mammary Tumors
 Prognosis excellent for benign tumors
 widely variable for malignant disease
  – prognostic factors
     •   size and ulceration
     •   presence of metastasis
     •   histologic type
     •   local invasion
     •   degree of histologic differentiation
  – survival times from months to many years
Feline Mammary Carcinoma
 Third most common feline neoplasm
 average age at diagnosis 10 to 12 years
 hormonal influences important
  – more common in unspayed cats
  – megestrol acetate induces tumor
 some differences from dogs
  – estrogen receptors rare (10% or less)
  – progesterone receptors demonstrated
Feline Mammary Carcinoma
 Homogeneous disease
  – majority malignant
      • 80 to 85% adenocarcinoma
 biologic behavior consistent
   – locally invasive
   – early metastasis to local lymph nodes
   – distant metastases also common
      • distant lymph nodes, pleura, lung, viscera
Feline Mammary Carcinoma
 Physical examination findings
   – multiple masses in two thirds of cats
   – suggestion of malignancy often present
      •   mass fixed to skin, subcutis, or body wall
      •   ulceration
      •   palpable lymphadenopathy
      •   tachypnea, dyspnea, or cough
Feline Mammary Carcinoma
 Surgery is primary therapy for most cats
   – aggressive resection recommended
   – “radical” mastectomy on affected side
     decreases local recurrence rate
   – bilateral mastectomy often necessary
   – resect all involved lymph nodes
 simultaneous OHE of unknown benefit
   – concurrent ovarian or uterine disease?
Feline Mammary Carcinoma
 Adjuvant therapy often recommended
 chemotherapy may delay metastasis
   – doxorubicin at 1 mg/kg IV q3 wks for 5 to 6
     doses after surgical resection
   – response demonstrated in cats with advanced
   – preliminary reports indicate prolonged survival
     for early stage disease
Feline Mammary Carcinoma
 Guarded prognosis in affected cats
  – median survival 10 to 12 months
 factors affecting prognosis
   – tumor size
     • if >3 cm, median survival 6 months with surgery
     • if <2 cm, median survival > 3 years with surgery
  – presence of ulceration
  – clinical stage of disease
Mast Cell Tumor
Canine Mast Cell Tumor
 Possibly most common canine skin tumor
   – 16 to 21% of tumors
 certain breeds predisposed
   – Boxer, Boston Terrier, Golden Retriever,
     Labrador Retriever, Schnauzer
 disease of older dogs
   – average age 9 years
 primary visceral involvement very rare
Canine Mast Cell Tumor
 Clinical presentation
  – single skin mass most common
     • multiple masses in ~ 10% of dogs
     • present for weeks, months or years
  – rapid growth if malignant
     • ulceration, swelling, ecchymoses
     • metastasis to local lymph nodes, viscera, marrow
  – systemic illness uncommon but possible
     • may occur with release of granule constituents
Canine Mast Cell Tumor
 Histopathologic grade predicts prognosis
  – Grade I (10%) - benign
  – Grade II (80%) - intermediate malignancy
     • aggressive local invasion
     • low to moderate rate of metastasis
  – Grade III (10%) - highly malignant
     • aggressive local invasion and distant metastasis
 most dogs have localized disease
Canine Mast Cell Tumor
 Surgery is primary therapy
 complete resection curative for grade I mast
  cell tumors
 wide and deep excision necessary for local
  control of grade II and III tumors
  – extensive local invasion
  – 3 centimeter margins recommended
Canine Mast Cell Tumor
 ~ 50% of dogs with “resected” grade II mast
  cell tumors have regrowth in 1 year
 radiotherapy proven to significantly
  improve local control of grade II tumors
  – > 95% of dogs free of local recurrence 5 years
    after completion of therapy
  – 4 to 6 week course of definitive radiotherapy
     • local treatment - will not address metastasis
Canine Mast Cell Tumor
 Chemotherapy inappropriate for most dogs
  with mast cell tumor
  – ineffective systemic therapy for local disease
 consider for metastatic grade II or III
 prognosis poor with advanced disease
  – median survival < 6 months with grade III mast
    cell tumor
Feline Mast Cell Tumor
 Two forms of feline mast cell tumor
  – cutaneous
      • mastocytic vs. histiocytic
      • less than 10% of feline skin tumors
   – visceral
      • splenic vs. intestinal
 no breed or sex predilection
   – histiocytic cutaneous mast cell tumors more
     common in Siamese cats?
Feline Mast Cell Tumor
 Mastocytic cutaneous mast cell tumor
  – most common dermal form
  – typical mast cells on histopathology
  – older cats (average age 10 years)
  – raised, white to pink, hairless dermal nodules
      • head and neck
      • 25% of cats have multiple lesions
   – usually benign behavior
      • ~20% metastasize (lymph nodes, systemic)
Feline Mast Cell Tumor
 Histiocytic cutaneous mast cell tumor
  – less common
  – histiocyte-like cells with equivocal granules
       • may be misdiagnosed as inflammatory lesions
   – young cats (average age 2.5 years)
   – firm, pink, hairless subcutaneous masses
       • head and neck
   – benign disease
      • spontaneous regression over 4 to 24 months
Feline Mast Cell Tumor
 ~ 50% of feline mast cell tumors visceral
   – much more common in cats than dogs
 older cats (average age >10 years)
 splenic and intestinal forms
 more malignant than cutaneous MCT
  – spread to liver, lymph nodes, bone marrow
  – pleural or peritoneal effusion with mast cells
    and eosinophils
Feline Mast Cell Tumor
 Cats with visceral mast cell tumor often ill
  – signs over weeks to months
  – anorexia, weight loss, vomiting, diarrhea
 physical exam findings
   – massive splenomegaly
   – abdominal mass, abdominal effusion
   – lymphadenopathy
   – pallor
Feline Mast Cell Tumor
 Prognosis excellent for cutaneous disease
 surgery is treatment of choice
   – curative in many cats
 submit all specimens for histopathology
   – no grading system for cats
   – anaplastic tumors have worse prognosis
     • aggressive resection recommended
     • efficacy of RT and chemotherapy unknown
Feline Mast Cell Tumor
 Splenectomy beneficial for splenic mast cell
 median survival 14 months
  – even with positive bone marrow or buffy coat
 anorexia, weight loss, male sex associated
  with worse prognosis
 benefit of chemotherapy unproven
  – consider corticosteroids, H1 and H2 blockers
Feline Mast Cell Tumor
 Resection and anastomosis recommended
  for intestinal mast cell tumor
   – wide 5 to 10 cm margins of normal bowel
 very poor prognosis
   – most cats die soon after surgery
 benefit of adjuvant therapy unknown
Canine Osteosarcoma
Canine Osteosarcoma
 Most common bone tumor of dogs
  – 85% of primary bone tumors
  – over 8,000 cases diagnosed yearly
 affects middle aged to older dogs
   – average age 7 years
 large and giant breeds predisposed
   – Great Dane, Irish Setter, Saint Bernard
 highly malignant biologic behavior
Canine Osteosarcoma
 Clinical presentation
  – lameness and swelling at primary site
  – poor response to analgesics
  – mild trauma often precedes lameness
      • bone weakened by tumor infiltration
      • minor injury may cause microscopic fractures
   – pathologic fractures possible
      • sudden, severe lameness
Canine Osteosarcoma
 Occurs most commonly at growth plates
  – “away from the elbow, toward the knee”
  – twice as common in fore limbs as hind limbs
      • distal radius or proximal humerus
          – distal radius is most common site
      • distal femur or proximal tibia
   – more rare in axial skeleton
      • skull, vertebrae, ribs
 consistent, rapid metastasis to lung
Canine Osteosarcoma
 Initial therapy involves surgical resection of
  primary tumor
  – amputation of affected leg
 provides palliation and prevents further
 median survival with amputation alone only
  3 to 4 months
  – occult pulmonary metastases at diagnosis
Canine Osteosarcoma
 Chemotherapy proven to significantly
  prolong survival
  – cisplatin, carboplatin and doxorubicin
     • as single agents or in combination
  – median survival 1 year
  – 25% of dogs survive 2 years
 radiotherapy occasionally indicated
   – incomplete resection or palliation
Canine Hemangiosarcoma
Canine Hemangiosarcoma
 Malignant tumor arising from endothelium
 common in middle aged to older dogs
   – average age 8 to 13 years
 some breeds predisposed
   – German Shepherd Dog
 may be caused by chemical exposure
  – arsenicals, vinyl chloride
Canine Hemangiosarcoma
 Spleen is most common site
   – rapidly growing, friable mass filled with spaces
     containing blood
   – easily traumatized
 other tissues often involved
   – liver, lung, heart (right atrium), brain
 metastasizes widely
Canine Hemangiosarcoma
Clinical Signs
 Often no clinical signs until tumor ruptures
  – sudden collapse or death due to blood loss
 intermittent bleeding may also occur
   – repeated episodes of weakness, pallor,
     distended abdomen
   – gradual recovery as blood is resorbed
 some symptoms due to metastases
   – cough, dyspnea, seizures
Canine Hemangiosarcoma
 Surgical biopsy required for diagnosis
   – many dogs have emergency abdominal
     exploratories and splenectomy
 full presurgical evaluation recommended
   – blood work with blood coagulation testing
   – chest radiographs, abdominal ultrasound
 diagnosis from radiographs not possible
   – 50% of splenic “masses” are benign
Canine Hemangiosarcoma
 Surgery is most effective single therapy
 primary tumor must be completely removed
   – splenectomy, liver resection
 surgery stops hemorrhage, relieves clinical
  signs temporarily
  – does not stop development of metastases
Canine Hemangiosarcoma
 Doxorubicin (Adriamycin®) chemotherapy
  may slow development of metastases
 prognosis still poor
  – average survival ~4 months with surgery alone
    after splenic rupture
  – average survival ~7 months with surgery and
    doxorubicin chemotherapy after splenic rupture

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