1. 3 factors that cause cancer (with examples)
    • Genetic susceptibility: breed predilection, individual susceptibility
    • Physiologic influences: hormones, inflammation/trauma, obesity
    • Environment: diet (no data), substances in air/water/soil? Tobacco smoke, pesticides/herbicides, radiation (therapy!), infectious agents
  2. Clinical considerations in Onco: history/anamnesis
    • How long has it been there?  
    • Is it growing/changing?
    • Does it have previous dx of cancer?  Previous sx?
  3. Clinical considerations in onco: PE and notation
    PE should include rectal. MEASURE lesions with calipers!  Characterize: fixed vs mobile, haired or ulcerated. Use body maps!
  4. Diagnostics in onco: cytology
    • Help to give preliminary or definitive dx. Helps plan dx and tx strategies, px, detect recurrence, monitor response to tx
    • BIOPSIES HELP PLAN DEFINITIVE THERAPY (make sure bx tracts removed with tumor, no drains)
  5. histology report with tumor biopsy
    • gives you dx, margins, grade (if available—some tumors donb’t have grading systems)
    • Submit the WHOLE SAMPLE so you know if it’s complete.
  6. Grading of tumors
    • help determine biologic behavior
    • degree of differentiation, mitotic activity (index = # mitotic figures/10 hpf), invasiveness, percent necrosis (outgrow blood supply).  Likelihood of metastasis, other testing needed? Chemo?
  7. Tumor stage
    Extent of disease IN THE PATIENT (PE, lab data, imaging). Signs present or not, etc. Helps in planning, prognosis
  8. Response to therapy
    How you tell if it’s working!  Must have objective measurements — GET CALIPERS.  Be consistent
  9. Most common side effects of chemo
    Myelosuppression and GI upset
  10. Chemo works best with _________disease
    • Microscopic! Below the limits of clinical detection (not gross)
    • Gompertzian growth kinetics: best to tx during period of exponential growth before outgrows blood supply
    • fractional cell kill hypothesis: a PROPORTION of cells killed with each dose. Best to take out a bunch FIRST (sx)
    • drug resistance: will be acquired in response to tx - some cells will be resistant and more over time.
  11. Cell cycle phase in drug sensitivity (chemo)
    • Important!
    • Drugs can be cell cycle phase specific or non-specific
    • Cells in G0 are resistant to chemo.
  12. How chemo works
    • Cell death through direct and indirect DNA interactions
    • Actively dividing cells more sensitivity to DNA damage
    • rapid growth rates are more sensitive to chemo
    • Normal tissues with actively dividing cells are more sensitive
  13. Drugs commonly used to tx:
    Lymphoma (LSA)
    Osteosarcoma (OSA)
    Hemangiosarcoma (HSA)
    Mast cell tumors (MCT)
    • Lymphoma (LSA): CHOP (Cyclophosphamide, Doxorubricin, Vincristine, Prednisone)
    • Osteosarcoma (OSA): Doxorubricin, cisplatin, carboplatin
    • Hemangiosarcoma (HSA): doxorubricin
    • Mast cell tumors (MCT): lomustine vinblastine, prednisone, toceranib
  14. 2 fatal drugs in cats
    • 5-FU (neurotoxic)
    • Cisplatin (pulmonary edema)
  15. Mechanism of action, metabolism, excretion and toxicity of cyclophosphamide
    • MOA: alkylating agent, forms reactive intermediates that attack DNA. Cell cycle nonspecific.
    • Metabolism: metabolized to active form in the liver (p450)
    • excretion: in urine
    • Toxicity: myelosuppression, GI toxicity. Sterile hemorrhagic cystitis (mucosal damage, d/c and dilute)
  16. Mechanism of action, metabolism, excretion and toxicity of doxorubicin
    • MOA: inhibition of topoisomerase II, oxidative damage (generates ROS to damage, not stage-specific).
    • Metabolism: hepatic metabolism
    • excretion: biliary excretion, a little in urine
    • Toxicity: anaphylaxis, myelosuppression, GI toxicity, vesicant (perivascular slough!), cardiotoxicity, renal toxicity, alopecia
  17. Mechanism of action, metabolism, excretion and toxicity of vincristine
    • MOA: vinca alkaloid, prevents formation of mitotic spindle (M phase)
    • Metabolism: hepatic 
    • excretion: biliary 
    • Toxicity: vesicant, GI (paralytic  ileus!), minimal myelosuppression, peripheral neuropathy (rare)
  18. Mechanism of action, metabolism, excretion and toxicity of Carboplatin
    • MOA: reactive platinum binds DNA bases, forms crosslinks.  Cell cycle phase non-specific.
    • Metabolism: None?Water? 
    • excretion: renal
    • Toxicity: myelosuppression esp at 14d, small dogs increased risk of GI tox, safe in cats (dose based on GFR)
  19. Mechanism of action, metabolism, excretion and toxicity of Lomustine (CCNU)
    • MOA: alkylating agent, crosses BBB
    • Metabolism: hepatic
    • excretion: urinary 
    • Toxicity: myelosuppression, hepatotoxicity
  20. Appropriate PPE for chemo
    • Nitrile or “chemo-specific”  (not vinyl) gloves for PO or IV
    • disposable solid-front gown with cuffs
    • goggles or face-shield
    • respirators for mixing
    • Luer-lock syringes
    • ziplock bags for transport
    • absorbable liners everywhere
  21. Ideal setting and patient for chemo administration
    • Store separately from other drugs
    • administration in a separate area without drafts or traffic
    • trained personnel
    • Biological safety cabinet
    • closed handling systems
  22. Techniques to minimize occupational exposure
    • Respirators
    • luer-lock syringes
    • zip-lock bags to transport and store drugs
    • absorbable pads and liners on surfaces
    • PPE
    • mark hospital cages as contaminated and all waste for 48h . Wash, don't spray, and wear gloves. Double bag waste.
  23. at-home precautions for owners with pets on chemo
    double bag waste, wear gloves, walk frequently.  Scoopable, flushable litter for cats.  Also wear gloves.
  24. five stages and two substages of clinical lymphoma
    • I: confined to a single node
    • II: involvement of LN in a region
    • III: generalized LN involvement
    • IV: Liver and spleen involvement
    • V: involvement of blood, bone marrow or other extranodal sites
    • a: without systemic signs
    • b: with systemic signs
  25. Plan to diagnose and stage canine lymphoma
    • FNA and cytology: differentiates neoplastic from reactive process (not helpful for cutaneous or alimentary)
    • Tissue biopsy with histopathy
    • Stage: multiple nodes? All or regional? Liver and spleen?  Blood, marrow or other extranodal?  Systemic signs?
    • PE, US, thoracic rads/met check, blood smear, bone marrow aspirate.  Immunocytochemistry/immunohistochemistry for B vs T cell.
  26. 5 prognostic factors associated with outcome in canine lymphoma
    • immunophenotype: B or T? B has better prognosis
    • substage: no clinical signs (a) has better px
    • stage: lower stages (I and II) have better px.  V and primary extranodal have worse. 
    • pretreatment with prednisone
    • hypercalcemia
    • response to tx
  27. Name the most common and effective multidrug chemotherapy protocol and the most effective single agent chemotherapy protocol for the treatment of canine lymphoma
    • CHOP - cyclophosphamide, doxorubicin, Vincristine, prednisone
    • doxorubicin singly. 
    • Pred can be rewarding if against chemo
  28. Name two feline viruses that are known to contribute to the etiology of feline lymphoma
    • FeLV: 60x greater risk, usu T cell
    • FIV: 5x greater risk, usu B cell
  29. Describe a diagnostic plan to diagnose and stage cats with lymphoma
    • CBC, chem, UA, thoracic rads, abd U/S, BM aspirate, bx of affected organ.  FNA often not diagnostic or not possible dep on location. 
    • FeLV and FIV test!  
    • T4?
  30. Describe approaches to therapy and prognosis for feline lymphoma, depending on anatomic type
    • depends on anatomic site and diffuse/localized
    • High-grade lymphoma: CHOP, 70% response, 6-9mo
    • low-grade/lymphocytic intestinal lymphoma: chlorambucil and prenisolone. 2yrs.
    • Radiation for localized. Also good for palliative
    • Px: nasal do well.  Low grade GI, substage a, FeLV negative, multi-drug protocol, response to chemo are best px indicators.  B vs T/immunophenotype not prognostic.
  31. Compare and contrast: most common presentation and location between feline and canine lymphoma
    • Canine: LN, liver, spleen, BM, blood, extranodal (GI, cutaneous, CNS).  Swollen LN, weight loss, anorexia, lethargy, v/d, PUPD, febrile, tachypnea, stertor
    • Feline: alimentary, Mediastinal, extranodal (renal, nasal, CNS, ocular, cutaneous), peripheral LN
  32. Compare and contrast between canine and feline lymphoma: response to therapy
    Dogs tend to respond better than cats
  33. Palliative radiation protocol
    • Larger dose per fraction and lower total dose of radiation.  
    • Tumor control is less good, but intent is not to prolong survival. Great for dz that is impacting QOL. Fewer acute adverse though higher risk of late radiation effects. (expect 2-6mo of survival)
    • 8Gy/fraction, once/week, 3-4fractions
    • vs
    • 4Gy/fraction, daily for 5 consecutive days
    • vs
    • 3Gy /fraction, daily (M-F) for 2 weeks
    • 3.5-4Gy/fraction, BID for 2 consecutive days (repeat on monthly basis, quad shot x 2

    DEFINITIVE IS 2.5-3Gy/fraction, daily, 15-20 fractions
  34. acute radiation side effects occur in
    • renewing tissues: oropharyngeal, nasal, colonic mucosa (oral mucositis, rhinitis, colitis), skin (moist desquamation, alopecia), ocular (conjunctivitis corneal ulceration). 
    • tx with magic mouthwash (lidocaine), local nerve blocks, etc.  Side effects that WILL resolve in time, manage until then. 
    • late are in non-renewing tissues.
  35. Teletherapy
    • radiation is applied from a distance from the patient (as opposed to plesiotherapy)
    • Orthovoltage equipment: lower energy, only superficial. 
    • Megavoltage equipment: higher energy. Linear accelerator, cyberknife, etc.
  36. most common cutaneous tumors of dog and cat
    • Dermal and SQ tumors are most common in dogs (33%, 20-30% are malignant).  
    • Dogs: MCT, perianal adencarcinoma, lipoma, sebaceous hyperplasia/adenoma, histiocytoma, etc.
    • 2nd most common in cats (25% of all feline tumors, 50-65% are malignant). 
    • Cats: basal cell tumor, MCT, fibrosarcoma, SCC, sebaceous hyperplasia/adenoma
  37. diagnostic plan for a cutaneous mass in a SA
    • Hx: duration/changes, other masses? Travel/vax
    • meaure/topography: calipers
    • FNA: can be dx, but could be misleading, non-informative (grade, not exfoliative). 
    • Bx: for firm fixed and painful or difficult location. Excisional vs surgical. Tru-cut (core-needle) vs punch vs scalpel. Mark excision!
    • Regional LN eval, blood work, thoracic rads, abd u/s, tumor imaging.
  38. Which cutaneous tumors in SA will regress spontaneously?
    • papillomas
    • Histiocytoma
    • histiocytic type of MCT
  39. Tx of dermal and SQ tumors
    • Surgical excision! 
    • Dep on size, location, type. 
    • Cryotherapy for small superficial on face. 
    • Ensure this isn't a metastasis of dz somewhere else!
  40. MCT
    • dogs: usu solitary skin mass, raised, dermal, possibly erythematous.  Can be SQ and feel like a lipoma (aspirate). Grading. 
    • cats: can have multiple, can't grade.
  41. canine perianal adenoma
    • male dogs, esp intact (androgens). 
    • Can sometimes be cured by castration
    • raised masses, ulcerated, on hairless perianal skin.
    • There are malignant adenocarcinomas, too
  42. Canine Lipoma
    • benign fatty tumors, common in dogs. Often multiple. Aspirate to differentiate from MCT. 
    • Sx if causing problems or if infiltrative (looks like fat but infiltrates). These need aggressive resection and radiation.
  43. Canine sepaceous hyperplasia/adenoma
    • solitary or multiple wart-like growths that are <1cm. 
    • sx! Rarely recur
  44. Feline Basal cell tumor
    • Benign
    • Usu solitary, well-circumscribed, firm, hairless, elevated masses, freely moveable, usu head neck and shoulders, sometimes trunk. 
    • Surgical resection or cryotherapy
    • There are malignant versions
  45. Feline SCC
    • SOLAR usu (white, thin hair, etc) 
    • nasal planum, eyelids, temples, pinnae. 
    • Progress from actinic keratosis to SCC in situ (not broken through basal membrane), then SCC
    • Locally invasive but rarely metastatic (but often in multiple places from exposure). 
    • tx: excision, cryotherapy, photodynamic therapy, plesiotherapy/radiation, intralesional chemo
    • Bowen's Disease in non-sun SCC, bleed when you touch them. Exise or irradiate.
  46. Fibrosarcoma
    • aggressive infiltrative masses, unlikely to metastasize. Often SQ but can grow and cause skin ulceration. Fixed. 
    • Imaging necessary. Often caused by injections in cats. 
    • Tx: wide surgical resection. combo sx and radiation, +/- chemo. 
    • Hemangiopericytomas in dogs are rarely metastatic but recur after local resection.
  47. Equine sarcoid behavior
    3 causes
    classification (5)
    • fibroblastic neoplasm with epidermal proliferation. MOST COMMON NEOPLASM OF HORSES
    • Histologically benign but act malignant. Irritating, hard to tx, recur. 
    • factors leading to sarcoids: bovine papilloma virus (spread by insects?), genetic predisposition (MHC, breed), local trauma/wounds
    • presentation: usu 3-6yo. usu on head, limbs, ventrum. 
    • classification: no typical appearance. flat, verrucuous (wart-like/scaly), fibroplastic (nodular or ulcerated), mixed verrucuous and fibroplastic, malevolent (malignant).
    • dx: histo to a VET PATHOLOGIST (no human equivalent) 
    • tx: benign neglect, sx (recur), cryo, immunotherapy (autologous vax or topical to stim immune), local chemo, laser excision, electrochemotherapy, local radiation, hyperthermia.
  48. Melanocytic tumors recognition and tx in horses
    • common, esp in older grey horses. Anywhere on the body
    • usu benign at first but become malignant. Variable appearance
    • esp in ventrum of tail and perineum, but anywhere. Guttural pouch?
    • tx: sx excision or cryotherapy.  Could ignore, intralesional chemo, immunotherapy (autologous, new vax?), gene therapy, cimetadine (H2 antag to stim immune?)
  49. SCC in horses
    • 2nd most common equine tumor
    • risks: age (9-15y), white skin, excessive sun, draft horses
    • location: mucocutaneous junctions (eye, genitalia, mouth), integument (esp post-trauma), epidermal laminae of hoof
    • Etiology: from precancerous lesions? Chronic irritation, UV light, maybe Equine papilloma-2 virus. 
    • Appearance: small superifical nodules with normal skin.  Later solitary lesions that are proliferative or erosive.
    • Behavior: slow to metastasize, usu to local LN
    • dx: histopath, cytology from FNA. 
    • Tx: WIDE EXCISION.  Cryotherapy, intralesional chemo, systemic piroxicam (unproven), radiation, BCG therapy for eye
  50. Papillomatosis recognition and tx in horses
    • EPV-1: juvenile warts (puppy warts!)
    • EPV-2: ocular and genital SCC
    • EPV-3, 4: aural plaques. Leave them alone. They'll go away. 
    • rest are uncommon
  51. Bovine/farm animal papillomas
    • BPV, 6 types in cattle. VERY Contagious, 2mo incubation.  Young animals.  Lesions on head and neck, occasionally genitalia. 
    • Spontaneously regress but can take a year. 
    • Commercial or autologous vaccine (auto better)
    • Also in sheep and goats, less often.
  52. bovine/farm animal SCC
    • usu white hair and lightly pigmented ksin. 
    • at mucocutaneous junctions
    • solar injury largest risk (photosensitizing plants!)
    • also at injury sites, like brands or ear tags
  53. Bovine/farm animal cutaneous lymphosarcoma
    • non-fatal tumor in young adults (NOT BLD+)
    • nodular lesions in dermis or SQ fat, often ulcerated. Esp in neck or trunk. 
    • Spontaneous regression in a few weeks, rarely recur. No tx.
  54. bovine/farm animal melanoma
    • Cattle: Rare. young (<2), black or red hair most. May be congenital, anywhere on body. 
    • Swine: durcos - red. Inherited
    • Sheep: rare, suffolks. Anywhere but esp base of horn. COngenital
    • goats: rare, older angoras. Coronary band and udder.
  55. Three most common oral tumors in dogs and their metastatic potential
    • Malignant melanoma: VERY aggressive, both local and metastatic, poor px
    • fibrosarcoma: locally aggressive but low metastatic potential
    • squamous cell carcinoma: locally invasive but low metastatic potential.  Worse if tonsillar or lingual
  56. two most common oral tumors in cats and their metastatic potential
    • Squamous Cell Carcinoma: Locally invasive, low metastatic potential, poor px.
    • Fibrosarcoma: locally invasive but low metastasis. Fair to good px.
  57. strategy for diagnosis of oral tumors
    • PE including hx of behavior/pytalism/halitosis/weight loss
    • palpation of regional LN, retropulse eyes
    • oral exam - use a dental map and take pictures!
    • obtain a sample - FNA? Hard to get a good sample due to inflammation or infection. Incisional biopsy esp if taking teeth.  Excisional biopsy okay for small, superficial.
  58. Staging a dog/cat with oral tumors
    • MDB: CBC/Chem/UA, FeLV/FIV, T4.  Paraneoplasic hypercalcemia!
    • regional LN FNA with cytology: Not just palpation — FNA or resect them!
    • thoracic rads: met check since varied metastasis.
    • abdominal US: metastasis dep on tumor type.  maybe neck, too, for regional LN.
    • oral rads: lysis etc helps with dx
    • advanced imaging: sx or radiation planning. MRI is less common than CT. 
    • SIZE is very prognostic
  59. biologic behavior and prognosis of epulides
    • Tumors that arise from periodontal ligament. Locally invasive, but pretty benign.  Don’t return or spread usu. Younger or middle aged dogs. 
    • Fibromatous 
    • ossifying
    • giant cell 
    • acanthomatous: aggressive locally, no metastasis, looks like SCC.  Need to take bone, maybe radiation (sensitive)
  60. indications of mandibulectomy or maxillectomy in dogs with oral tumors and complications
    • Lesions that involve bone but have not spread, no metastasis
    • Can hemorrhage intra-op
    • pain, difficulty eating, dehiscence,epistaxis in maxillectomies, increased salvation, malocclusions, mandibular drift.  
    • O is usually pretty happy.
  61. c-kit mutation in MCT
    • 30% of high-grade MCT have mutation that cause receptor to be constantly on, telling MCT to proliferate. NOT inherited. Certain axons have mutations.
    • Higher chance of local recurrence and metastasis = shorter survival.
  62. 5 ddx for round cell tumor
    • MCT
    • lymphoma
    • histiocytoma
    • TVT
    • Plasma cell tumor
  63. common clinical presentations of MCT in a dog (3)
    • average 9 years
    • breed: boxer, pug, boston, EBD, lab, schnauzer, shar pei
    • dermal: 1-10cm, well-circumscribed,raised,firm. +/- erythematous, ulcerated. Gets bigger and smaller. 
    • SQ: soft, ill-defined mass, feel like lipomas. Normally overlying skin. 
    • Systemic: rare or advanced
    • 14% have multiple MCT at once, more likely to get MORE. Solitary can too, but less likely.
  64. Paraneoplastic syndromes of MCT
    • Gastric ulceration: histamine causes HCl secretion
    • Coagulopathies: usu local, systemic can cause DIC
    • delayed wound healing: inhibition of fibroplasia and re-epithelialization
    • anaphylactoid reaction: hypotensive shock (vasodilation, increased capillary permeability), respiratory distress (bronchoconstriction/spasm, pharyngeal/laryngeal edema), V/D. Manipulation of tumor can cause degranulation leading to anaphylactoid.  Usu large tumors. 
    • Can be pruritic, cause self-mutilation
  65. where do MCT metastasize?
    • Regional/draining  LN first
    • then spleen, liver, BM in advanced disease
  66. Staging tests for a dog with MCT
    • CBC/Chem,UA
    • aspirate regional LN: few MC okay if not clustered. Can be subjective, but the less obvious the better px
    • Thoracic rads: rarely pulm metastasis, look at heart/lung and image regional LN or primary tumor.
    • US: evaluate regional LN, liver, spleen
  67. MCT surgery
    • If no signs of metastasis...
    • Plan, wide margins, minimize tumor manipulation or tension on the wound. 
    • place hemoclips to  mark tumor bed so you can set up radiation fields.
  68. main prognostic indicators for MCT in dog
    • C-KIT MUTATION (PCR, Staining pattern)
    • location
    • growth rate/size
    • breed
    • systemic signs
    • recurrence
    • proliferation markers (Ki-67, AgNOR count, PCNA)
  69. Tx options for MCT in d/c and when to use each
    • Surgery: non-metastatic, grades 1 or 2
    • radiation therapy: after incomplete resection or regional LN (prophylactic or metastasis).   Also non-resectable small tumors. 
    • chemotherapy: metastatic tumors, grade 3 tumors, non-resectable.  WITH resection where possible. Prednisone, vinblastine, lomustine, tyrosine Kinase inhibitors (palladia)
  70. common locations for visceral MCT in cats and general prognosis for each location
    • VIsceral MUCH more common as primary tumor in cats - in dogs it’s usu a metastasis.
    • Spleen: ~12mo with splenectomy. Poorer if anorexic.
    • Intestinal: <4mo even with sx resection (chemo?). Often metastasis. High risk of dehiscence.
  71. prognostic factors for MCT in cats
    • Mitotic index >5 maybe worse.
  72. Differentials for splenic mass in a dog
    • non-neoplastic: hematoma, hemangioma, extramedullary hematopoiesis, nodular hyperplasia
    • neoplastic: HSA, histiocytic sarcoma, leiomyosarcoma, others (lymphoma, metastasis)
  73. clinical signs of visceral hemangiosarcoma in dogs
    • acute collapse
    • weakness
    • inappetance
    • weight loss
    • abdominal distension
    • exercise intolerance
    • dyspnea
    • wax and wane
  74. hematologic abnormalities that you may see in a dog with HSA and WHY you see them
    • anemia: regen or nonregen dep on when you catch it. 
    • thrombocytopenia: >75% from consumption
    • Schistocytes: shearing from tortuous blood vessels
    • leukocytosis (neutrophilia): stress? Inflammation?
    • Panhypoproteinemia: bleeding
    • Coag: abnormalities, often DIC
  75. Diagnostics to stage a dog with visceral HSA
    with cutaneous HSA
    • vital signs, ECG, BP, PCT/TS, A-FAST, fluid sample analysis
    • Peritoneal fluid analysis rarely helpful because sarcomas don't exfoliate well
    • thoracic rads: check lung fields for mets!  Cardiac silhouette, too (globoid for pericardial effusion)
    • abdominal imaging: cranial abdominal mass, fluid
    • +/- echo: can't always see the mass, mass may not be HSA, often unrewarding
    • ECG: VPCs common, electrical alternans from PE
    • FNA or surgical biopsy for definitive. Usu FNA doesn't exfoliate, blood contamination. usu bx is splenectomy, but do a FULL EXPLORATORY
    • Cutaneous: requires biopsy, an aspirate will just be blood. Also required for staging.
  76. Staging system for cutaneous HSA and how stage affects outcome
    • Stage I: involvement restricted to dermis, complete excision is pretty good px. Sx only. 
    • Stage II: involvement/invasion of SQ tissues, sx + chemo
    • Stage III: involvement/invasion of muscle layer, sx + chemo
    • II and III have metastatic rate of 60%. significant decrease in MST
  77. Tx for HSA (visceral or cutaneous)
    • no tx: supportive. It will happen again
    • sx: part of definitive dx, also primary tx. Stabilize, splenectomy, pericardectomy or resect cardiac masses?
    • chemo: ALWAYS indicated because highly metastatic. Doxirubicin best. + combo doesn't seem to help
    • radiation: usu not indicated. hard to irradiate visceral organ tumors. Maybe for excised stage I or II cutaneous?
  78. Cats with visceral HSA, cutaneous/SQ HSA
    clinical behavior
    • visceral: splenic, behaves like dogs. anorexia, vomiting, lethargy, collapse, dyspnea, distended abdomen. 
    • tx: sx. no info about chemo in cats. 
    • px: poor
    • Cutaneous: older cats with poorly pigmented skin. Small red lesions, less aggressive than dogs but stages II, III behave like other sarcomas. 
    • sx: no info about chemo in cats. 
    • px: 60-80% recurrence.
  79. Steps to diagnose soft tissue sarcomas in a dog or cat
    • FNA: mesenchymal cells don't exfoliate well and hard to differentiate from fibroblasts (reactive). negative FNA does not rule out a sarcoma. 
    • histopath: incisional vs excisional biopsy
    • interpreting biopsy: diagnosis (grouped by managment strategies/biologic behavior. STS, atypical or non-soft tissue like osteo, hemangio, histiocytic (macrophage)). Feel good that your "lump" will follow certain behaviors. 
    • more bx info: sure it's soft tissue? R/O hemangio, round cell, etc with extra tests?. Details that direct local therapy--MICROSCOPIC margins and invasiveness.  Details that direct systemic therapy--tumor grade and mitotic index.
  80. common histologic types of soft tissue sarcoma
    • fibrosarcoma
    • peripheral nerve sheath tumor (hemangiopericytoma, schwannoma, neurofibrosarcoma)
    • liposarcoma
    • myxosarcoma
    • mesenchymoma
    • pleomorphic sarcoma
    • malignant fibrous histiocytoma
    • Atypical: leiomyosarcoma, rhabdomyosarcoma, synovial cell sarcoma
  81. staging tests for a dog or cat diagnosed with soft tissue sarcoma or injection site sarcomas
    • MDB for systemic health
    • 3-view thoracic rads
    • LN
    • rads of limb if applicable
    • consider CT or MRI for sx planning, body wall tumors, aggressive resection, large tumors
  82. Contrast biologic behavior, treatment and px for low, intermediate and high grade canine soft tissue sarcoma
    • low: ~10% metastatic risk, good to excellent px with sx or + radiation
    • Intermediate: ~20% metastatic risk, good to excellent px with sx or + radiation
    • high: ~40% metastatic risk.  add chemo? Not sure what helps. Doxyrubicin? Metronomic?
    • tx: sx!  wide margins with aggressive resection. Don't just "pop out" the pseudocapsule, you need 3cm around to get tendrils. Include bx tract. Mark the margins to ensure localizing if margins aren't clean.
  83. features/characteristics suggestive of an injection site sarcoma in a cat
    • lumps in younger cats (8-10). Can be asymptomatic, painful or ulcerated. 
    • often rapid growth rate. Can be firm and attached or soft and moveable. Recur!
    • In injection sites, esp FeLV and rabies, worse with 3-4vax at same time! 3mo-10yrs after.
    • Early detection is important, watch injection sites!
    • histo: increase in mitotic index, pleomorphic, granulation tissue, stroma variable (collagen, osteoid, chondroid, myxomatous), inflammation, necrosis
    • Grades don't really direct treatment - cat STS more aggressive than dogs
  84. surgical recommendations for injection site sarcomas and impact of adjuvent radiation therapy and chemo on outcome
    • Incisional biopsy ALWAYS recommended, not excisional (higher growth rate--don't open up avenues for the tumor!). Ensure tract will be removed with tumor
    • 1-2-3 rule: 1 month after injection, larger than 2cm, persists for 3 months
    • SURGERY is key, but inadequate alone. Even clean margins get 50% recurrence. Take HUGE margins, amputate limb if possible. 3-5cm and 2 fascial/muscle planes deep. 
    • recommend radiation after. Getting better, but still 40% recurrence but 3yrs. 
    • not much info about chemo. We offer but hard to know.
  85. Mammary gland tumors in dogs
    risk factors
    clinical presentation
    staging tests
    • risk factors: female, no OHE or after 3rd estrus, breeds? Obesity, esp at 9-12mo. Diet? Exposure to exogenous progestins/estrogen
    • clinical presentation: discrete mass, moveable or fixed, one or multiple, esp caudal 2 glands. Size correlates with px? LN may be metastatic. Systemic illness rare, more common in carcinoma. Aspiration doesn't tell you benign/malignant. 
    • staging tests: Measure tumor, aspirate LN, MDB, 3-view thoracic rads (lungs common metastasis), abd U/S esp for LN
    • treatment: ~75% cured by sx with clean margins. Could be lumpectomy to simple or regional mastectomy. Remove and submit ALL tumors - can be dif. Spay may help here? chemo for high-risk, but large randomized studies don't prove efficacy.  Doxo, cisplatin, carboplatin, taxanes.
    • prognosis: benign vs malignant, degree of differentiation (grade), evidence of lymphatic/vascular invasion, tumor size (BIGGER HAS WORSE PX, INCREASE METASTASIS), LN metastasis (SIGNIFICANT PX FACTOR, PULM MOST COMMON), completeness of excision.
  86. Mammary gland tumors in cats
    risk factors
    clinical presentation
    staging tests
    • risk factors: DSH, siamese, Early OHE (before 2y). 
    • clinical presentation: PE - mass in mammary chain, often just one, variable mvmt or ulceration. 
    • staging tests: 85% malignant. Measure, 3-view thoracic rads for lung mets, abd US, LN eval, MDB
    • treatment: Sx - radical mastectomy, frequently recur. Chemo?
    • prognosis: studies don't concur! Range is huge. >3cm tumor is much worse. Higher stage, histo types and differentiation/grade (well-differentiated is much better).
  87. bovine leukemia virus basic info
    • lymphotrophic, deltaretrovirus (retrovirus). Provirus that integrates itself into host DNA, so remains latently integrated into B lymphocytes. spread by infected lymphocytes.
    • up to 50% of all adult dairy cattle are infected, 89% of herds. Fewer in beef.  Sudden rise in infection at 15-30mo
    • Causes lymphoma, loss, restriction of sales, public perception, detrimental effect on immune status, herd longevity and milk production even with disease +, tumor -.
  88. Persistent lymphocytosis
    • no cause except bovine leukemia virus in a population of cattle. 
    • familial predisposition, polyclonal B lymphocyte proliferation.  
    • highly contagious cows - 50% of lymphocytes infected!  these are the cows doing the transmission (via flies or needles)
    • May be more likely to get lymphoma?
  89. Diagnosis of BLV infection (3)
    • AGID: Sn 80-90%. False - in late gestation (concentrate Ab in colostrum). 
    • ELISA: Sn 97%
    • PCR: little advantage over serologic
  90. Transmission of BLV
    • ONLY by lymphocytes.
    • In utero - uncommon, mostly in persistent lymphocytosis/high previral load or lymphoma cows. Warn O!
    • Horizontal: 0.0005-1mL of blood, often needles, rectal sleeves, dehorning. Insects, tattoos? Milk and colostrum are controversial.
  91. Bovine lymphoma and common sites (4), dx (2), tx.
    • Almost all adults
    • clinical signs vary dep on location. Often peripheral lymphadenopathy. - retrobulbar, prescap, mesenteric, mammary
    • Retrobulbar! Common!  Heart (RA), abomasum, uterus, kidney, spinal, thoracic, intestinal etc.  ANY lymphoid tissue can be involved. 
    • abomasal: bleeding/obstruction
    • Cardiac: RA, pericarial effusion or atrial fibrillation
    • Diffuse intestinal is more a horse thing. 
    • Spinal: extradural, esp in lumbosacral area. Ataxic in rear, lose tail tone, bladder dysfunction. Reach up on rectal on either side of aorta, caudal iliac LN is usu enlarged. Often contaminates CSF taps and makes you think it's intradural. 
    • dx: clinical signs, serology (high Sn, low Sp, only neg predictive value, so only neg helpful), CBC not helpful. Cytology (FNA, effusion, wedge bx* best). 
    • tx: pretty much just euthanasia. Salvage with pericardectomy, chest drain, steroids (usu cause abortion, isoflupredone acetate didn't?). L-asparaginase eats up aa that cells can make themselves, probably illegal in cows but great in other species.
  92. Control of BLV
    • remove Persistent Leukosis cows from herd! to prevent spread
    • remove cows with double line AGID (genes)
    • limit possibility of blood transmission
    • colostrum and milk transmission?
    • genetic selection. There may be a resistant gene.
  93. Sporadic lymphosarcoma in cows
    • only type of bovine lymphoma that isn't BLV related.  
    • Calf form - usu B cell
    • Thymic - T cell. 
    • skin - T cell
    • juvenile -  T cell
  94. Biologic behavior of osteosarcoma
    • MOST COMMON PRIMARY BONE TUMOR in middle-older dogs, breeds, appendicular skeleton (long-bone pain)
    • More in forelimb than hindlimb.  Distal radius, proximal humerus, distal femur, tibia
    • Malignant mesenchymal tumor of primitive bone cells (osteoblasts), produce ECM. 
    • Grade helps predict behavior (but >75% are high grade). 
    • From multiple minor trauma? Definitely implants, chronic infection, radiation (3-5y later). 
    • Lameness and swelling, can be acute and severe (pathologic fracture) or chronic
  95. ddx of osteosarcoma
    • Other primary bone tumor: chondrosarcoma,hemangiosarcoma, fibrosarcoma, multilobular osteochondrosarcoma (MLO)
    • Metastatic bone tumor: diaphysis is common
    • multiple myeloma or lymphoma (very lytic, multi-focal)
    • Osteomyelitis: fungal, bacterial
  96. staging/dx tests of osteosarcoma
    • Image primary tumor: rads show moth-eaten lysis, cortical destruction, periosteal proliferation,sunburst new bone, subperiosteal bone formation, soft tissue swelling with calcification, indistict zone of transition
    • Cytology: from lytic bone lesion (painful!), use alkaline phosphatase to differentiate form other sarcomas
    • Histopathology: DEFINITIVE dx, from bx/amputation. Bone biopsies can be open incisional, closed needle (Jamshidi - one cortex) or trephine. Take post-bx rads!!!  
    • STAGING: MDB, thoracic rads (lungs, rarely at initial dx), regional LN eval (rare), careful orthopedic to check for other bone involvement (rare)
  97. tx of osteosarcoma
    • Two-armed approach: tx primary tumor and metastatic disease!  
    • Amputation!  Can even be palliative — OSA is PAINFUL. Complete forequarter or coxofemoral disarticular vs hemipelvectomy
    • Amputation alone: just palliative, MST = 4-5mo due to metastasis (LUNGS)
    • Limb-sparing techniques: O won’t amputate, distal tumor with no metastasis, little soft tissue involvement or not a good candidate.  Stereotactic Radiation Therapy. No change in MST. 
    • Stereotactic Radiation Therapy: large doses of radiation in precise site. Spares normal tissue, lots of biologic effect on that site, but can cause pathologic fractures. MST ~10mo with chemo. 
    • Chemo: systemic. Carboplatin.  Maybe doxo or cisplatin. Extend MST, NOT CURE. Doesn’t help if we can SEE the dz. 
    • working on a VACCINE as part of tx, HUGE improvement in MST
  98. px of ostesarcoma
    • Factors: metastasis at dx, elevated serum alkPhos (due to size?), size of lesion, tumor grade, younger age, location (prox humerus is worse)
    • MST with pulm metastasis: 59 d.
    • MST 76d once metastatic.
    • Longest with aggressive local control. Sx, radiation, chemo (platinum or doxo)
  99. Axial Osteosarcoma
    • mandible and maxilla most common
    • Metastatic potential prob the same (but can’t control local dz as well).
    • Mandibular OSA has a better outcome = 71% alive at 1 year! Often lower grade, too.
  100. Osteosarcoma palliative care
    • For everyone! It’s a painful tumor!
    • Doesn’t extend survival. 
    • Medical: NSAID, Opioids, gabapentin, prefab, NMDA antagonist.
    • Radiation: once a week for 3-4wks with a high rad dose, not as good in large/lytic tumor. Lasts 2-4mo
    • Bisphosphonates: pamidronate. Inhibits bone resorption, anti-tumor effects?
    • watch for pathologic fractures!
  101. equine Lymphoma basics
    • Neoplasia of lymphoid origin, rarely secondary leukemia
    • infrequent (most common malignant neoplasia but only 3%)
    • 50% can happen in YOUNG adult horses.  An aborted fetus had it!
    • No strong virus association (unlike bovine). Maybe EHV-5?
    • effects: mass effects, changes function of organs/cells, obstructs venous and lymphatic flow
    • px: grave, death within 6mo
  102. signs of equine lymphoma
    • Depression
    • inappetance
    • weight loss
    • poor performance
    • intermittent fever
    • ventral edema (mass effect on drainage)
    • lymphadenopathy
    • resp distress, cough
    • GI colic/diarrhea
    • secondary: anemia (IM due to type II hypersensitivity, chronic inflamm, blood loss from tissue damage), thrombocytopenia (IM), pancytopenia, neutrophilia, hyperfibrinogenemia (inflamm), hypoalbuminemia (PLE, malabsorption, inflamm), hyper- (B cell) or hypo-(T cell) gammaglobulinemia, hypercalcemia, hypophosphatemia, pseudohyperparathyroidism (secreted by tumor)
  103. 4 anatomic categories of equine lymphoma
    • generalized or multicentric:most common, most malignant. Lymphadenopathy, adults. Spinal, pelvic, ocular, mandibular etc. May see fever
    • intestinal or alimentary: diffuse infiltration of intestine. Young horses, weight loss, could be fast or slow. Can be d, colic. Hypoalbuminemia from malabsorption, PLE. Could cause pseudodiverticula. Oral glucose absorption test - deficiencies can show diffusion of tumor cells. 
    • mediastinal or thoracic: adult horse. Primary of lymph tissue like thymus or thoracic/mediastinal LN. Mass effect = dysphasia, jugular distension, serosanguinous pleural effusion, ventral edema, muffled heart sounds, resp distress, tachycardia/arrhythmia. 
    • cutaneous: 4-9yo, lymphadenopathy in some, normal blood work, rarely metastasize. Dermal or subdermal nodules, always covered by hair (unlike sarcoids). Well-circumscribed, not painful, very firm. Anywhere on integument, often ventral. Most benign form. Can appear, diseappear, reappear. Fast or slow - hormones?  Can be a LOT, large lesions can cause necrosis etc. 
    • also can be overlapping
  104. dx of lymphoma in Horses And most common type
    • excisional biopsy and impression smear vs aspirate (often not enough, inflammatory cells) 
    • cytology, histology, immunophenotyping on fresh-frozen tissue for T or B cell.
    • Most common type of lymphoma in horse: T-cell rich B-cell lymphoma (surrounded by reactive T cells)
  105. lymphocytic leukemia in eqine
    • cancer of blood-forming tissues including BM and lymphoid system.  Acute is blast cells and chronic are small cells. 
    • primary: origin in BM, rare, causes myelophthisis (anemia,thrombocytopenia, neutropenia)
    • secondary to lymphoma: chicken or the egg? Tumor cells circulate in blood and may or may not infiltrate bone marrow. RARE to have both but can happen, either from lymphoid tissue s to BM or BM to lymphoid tissues
  106. Treatment of equine lymphoma and/or leukemia
    • Prednisolone
    • doxorubicin
    • cyclophosphamide
    • vincristine
    • L-asparaginase
    • Surgical removal
    • Often initially responsive but frequently recur in a few months
    • Poor px because hard to tx successfully. 
    • Intestinal or cutaneous much more likely to respond to immunosuppressive
  107. appropriate diagnostic steps and decision making process for animals presenting with cutaneous/SQ masses
    • anatomical location of mass and 3D measurements recorded in tumor map on medical record
    • Palpation to ID fixation etc.
    • palpate local LN (poor prediction!)
    • pull PE including rectal to ID concurrent dz
    • FNA!!  

    • staging tumors: looking for METASTASIS (chest rads). Only needed for tumors likely to metastasize
    • grading tumors: aggressiveness of cytology of tumor itself, likelyhood of local recurrence and systemic spread. 
    • can it be removed? Can I even GET big margins? 
    • Px
    • First cut is the BEST CHANCE of surgical cure, 
    • CT: if VERY fixed - may have invaded deeper tissues and we need to know just what our deep fascial plane is.
    • Take FNA of regional LN even if not enlarged!  Aggressive hunt for mets.
  108. Why and how to appropriately perform a surgical biopsy of cutaneous/SQ masses
    • Incisional: small cut from CENTER of tumor.  Better to start here with minimal tissue to work with etc. Anything that will require extensive reconstruction after 3cm margins are taken. 
    • Excisional: Anywhere that large margins are of minimal morbidity to P - can take lots of skin twice!

    • wide margin incision (3cm lateral, one fascial plane deep) 'en bloc' with sharp dissection, never touching tumor (suture skin to fascia to make a sandwich). Spare muscles if possible, and avoid coning.
    • ink margins of removed tumor for pathologist. Esp focus on muscle junctures etc.
    • lavage
    • Change gloves/instruments after resection to close!  
    • Avoid drains in tumor beds
    • leave the "dog ear" in case you need to re-cut (smaller tumor bed and you need the skin!)
    • re-cuts need 3cm from scar and a fascial plane. More likely to remain dirty than first incision. Drains make it worse.
  109. indications and differences of technique between local excision and curative intent wide margin excision
    • Local excision: 0.5cm margin laterally, no "fascial planes" required. Can use blunt dissection and "shell out" tumor by undermining. Ellipse to avoid "dog ear". Fine for benign, encapsulated tumors. Still submit. 
    • Curative intent wide margin excision: 3cm lateral margin and 1 fascial plane deep (suture skin to fascia so all comes out as a block with tumor locked into the middle). Remove 'en bloc' to prevent seeding. All SHARP dissection. Muscle-sparing if you can. Skin will retract - avoid 'coning'.  May require graft, DON'T use drains
  110. How to prepare a sample (of a SQ/cutaneous tumor) for margin assessment by pathologist
    • Skin-to-fascia sutures maintain orientation and prevent tissue slippage. 
    • ink margins (1 deep, 4 lateral, blue) so you know where to re-cut (though it doesn't much matter) and the pathologist knows where to look
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