Recent Advances in Diagnostic Techniques in Veterinary Oncology

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Recent Advances in Diagnostic Techniques in
Veterinary Oncology

• David Heller, DVM
• 07/27/06

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Overview

• Recent Diagnostic Advances in
• Canine Lymphoma
• Canine Mast Cell Tumor
• Canine Osteosarcoma
• Canine TCC
• Imaging

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Canine Lymphoma

• Neoplasms of lymphoreticular cells
• Incidence Kaiser 1981, Moulton et al 1990
• 7-24 of all neoplasms
• 83 of hematopioetic neoplasms
• Risk Factors
• Age Backgren 1965, Parodi et al 1968
• Breed Priester 1968
• Genetic Predisposition Teske 1993
• Gender? Priester, Parodi, Jarrett et al 1966

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Canine Lymphoma

• Common diagnostics
• CBC, chemistry profile, urinalysis
• Abdominal ultrasound, 3-view thoracic radiographs
• Confirmation of lymphoma by cytology or biopsy
• /- Bone marrow aspirate

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Canine Lymphoma

• Historically, a disease diagnosed by FNA and
  cytology
• Cytology indicates cell size (small,
  intermediate, large) but no indication of
  aggressiveness
• Biopsy gives information on tissue architecture,
  mitotic rate
• Both cytology and histopathology can give
  immunophenotype (B vs. T Cell)

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Indolent lymphoma

• Types follicular, mantle cell, marginal zone,
  and T-zone
• May have long survival times regardless of
  treatment
• 7 cases of Marginal zone LSA average survival
  18.8 months (Valli et al. Veterinary Pathology
  2005)
• Gastric lymphoma in humans
• Mucosa-associated lymphoid tissue (MALT)
• Reported in humans secondary to Helicobacter
  pylori infection

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Lymphoma New Diagnostic Tools

• Immunoglobulin rearrangement
• Clonal expansion of malignant lymphocyte
• PCR for TCR or BCR
• Lymphoid hyperplasia multiple clones
• Lymphoma single clone
• Telomerase activity
• Telomeres on 3 end of chromosomes
• Dictate proliferate capacity of cell
• Telomerase prevents reductions in telomeres

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Canine LSA Genomic Methylation

• Cytosine methylation is an epigenetic DNA
  modification necessary for cellular functions
  including gene transcription
• Methylation gene silencing
• Disruption can affect the cell cycle
• Hypomethylation gene activity
• PBLs from normal, lymphoma, leukemia and lymphoma
  LN evaluated (Pelham, Res vet sci, 2003)
• 2/3 of lymphoma (node) cases had evidence of
  hypomethylation compared to PBL of normal

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Canine Mast Cell Tumor

• Incidence
• Most common cutaneous tumor (dog)
• 16-21 of all cutaneous tumors
• Risk Factors
• Older dogs
• Breed
• No sex predilection
• Spontaneously regressing type

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The Great Imitator
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Canine Mast Cell Tumor

• Common diagnostics
• CBC, chemistry profile, urinalysis
• Abdominal ultrasound
• Fine needle aspirate of primary lesion, regional
  lymph nodes
• /- 3-view thoracic radiographs, bone marrow
  aspirate

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Canine Mast Cell Tumor

• AgNOR
• Ki-67
• PCNA
• C-kit
• Angiogenesis

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Canine MCT Proliferation Indices

• Ki-67, PCNA, AgNOR and C-kit scores evaluated
  with respect to grade and subgrade
• AgNOR prognostic for survival all indices
  associated with grade and subgrade, development
  of metastasis
• Important adjunctive diagnostics for canine MCT
  (Bergman PJ et al, VCS 2005)

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Canine MCT - Angiogenesis

• Angiogenesis formation of new capillary
  structures from existing vasculature
• Essential for tumor survival to gt2 mm

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Canine MCT - Angiogenesis

• Increased tumor microvessel density (MVD)
  associated with shorter survival
• Suggests that angiogenesis is essential for tumor
  invasion, progression
• Represents a therapeutic target

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Canine Osteosarcoma

• Dog species with highest incidence
• Model for OSA in human
• Breed large or giant
• Certain breeds overrepresented
• Median age 8 years
• Bimodal
• Possible causes

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Canine Osteosarcoma

• Routine diagnostics
• CBC, chemistry profile, urinalysis
• 3-view thoracic radiographs
• Abdominal imaging
• Radiographs of primary lesion
• Biopsy or cytology of primary lesion

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OSA - Diagnosis
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Canine Osteosarcoma

• Fine needle aspirate and cytology of primary bone
  lesions
• 18 G, 1.5 needle
• Aim for center of lesion
• Peripheral aspirate likely will only yield
  reactive bone

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Canine OSA - Cytology
Photo courtesy of Dr. Anne Barger
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Canine OSA ALP staining
Photo courtesy of Dr. Anne Barger
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Canine OSA Urine NTx
Lacoste et al, J Vet Intern Med. 2006
Mar-Apr20(2)335-41
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Canine OSA Gene Expression

• Expression profiling comparison of human, canine
  OSA samples
• Similarities in genes that encode for adhesion
  molecules, connective tissue (Khanna et al, VCS
  2006)

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Canine TCC

• Uncommon in dogs (lt1 of all malignancies)
• Females 21
• Scottish Terriers, Shetland Sheepdogs, West
  Highland White Terriers overrepresented
• Median age 10 years
• Risk factors cyclophosphamide administration,
  flea products, obesity?

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Canine TCC - Diagnosis

• FNA and cytology
• WARNING?!?!
• Nyland et al 2002
• Traumatic catheterization biopsy
• Surgical biopsy
• BTA test
• Screening test only
• Borjesson et al 1999, Billet et al 2002, Henry et
  al 2003

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Canine TCC

• Locally invasive
• Metastatic
• Loco-regional
• Pulmonary
• Staging
• Blood work
• Abdominal ultrasound
• Thoracic radiographs

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Canine TCC COX-2

• COX-2 expression detected in 21/21 samples
• No COX-2 expressed in normal urothelium
• COX-1 expressed in both normal and neoplastic
  cells (Knapp et al, AJVR 2000)

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Canine TCC - Survivin

• Anti-apoptotic protein
• Surrogate marker of disease remission status in
  humans
• Positive staining in 34/45 canine samples
• Trend towards shorter survival in positive tumors
  (Rankin et al, VCS proceedings 2005)

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Canine TCC - BTA

• Bladder Tumor Antigen test detects complex
  basement membrane proteins, immunoglobulins
• Sensitive but not very specific for TCC
• Excellent non-invasive screening tool positive
  test indicates need for further diagnostics

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Imaging

• Currently most useful for clinical staging of
  cancer patients
• Future use of modalities such as PET scan, in
  vivo optical imaging will aid in earlier
  detection
• Antibody internalization can detect therapeutic
  targets (Bryan JN et al, VCS Proceedings 2004)

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Imaging DEXA scan
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Imaging DEXA scan
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Imaging Nuclear Scintigraphy
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Questions/Comments

• Thanks to
• Deanna, Trish, Eric
• Andrea
• Tina