Skin, MCT, STS, OSA Flashcards
What is the sensitivity of ultrasound-guided FNA for diagnosis of OSA in dogs?
97%
Increased to 100% when ALP staining was used
Is feline sarcoma virus transmissible between cats?
No
Requires FeLV co-infection to replicate
Regional lymph node metastasis is documented in ?% of dogs with appendicular OSA at amputation and ?% at necropsy.
- 4% at amputation
6. 1% at necropsy
What is the recurrence rate following incomplete excision of maxillary OSA?
100%
Which histologic subtype of axial OSA carries the highest risk of metastasis?
Telangiectatic – 100% metastatic rate when occurs at axial sites
Up to ?% of feline OSA are extraskeletal.
40%
What is the reported metastatic rate for feline OSA?
5-10%
What impact does increased monocyte count have on disease free interval in dogs with OSA?
Decreased disease-free interval with monocyte count >0.4 x10^3 cells/uL
**does NOT need to be outside the reference range
Expression of which RTK was more common in lung tumors from dogs with pulmonary anthracosis than those without notable anthracosis?
EGFR
p53 has been related to what clinical outcome measure in cats with ISS?
recurrence
altered p53 sequence or cytoplasmic location related to recurrence
What is the recurrence rate in cats with ISS following radical surgery with 5cm margins
14%
20% met rate
11% major complication rate
What dose of CYC resulted in decreased number and percentage of circulating T-regs and tumor MVD?
15mg/m2 SID
12.5mg/m2 only decreased absolute T-reg #
What clinical factors are associated with malignant versus benign hepatic tumors in cats?
Elevated ALT, AST, and Tbili
Age at presentation
Clinical signs at presentation
Name two negative prognostic factors for feline exocrine pancreatic carcinoma.
Effusion
NSAID use
Which of the following is prognostic for outcome in feline lung tumors?
Presence of effusion
Tumor size
Histologic grade
What is the survival time following ulnectomy for telangiectatic OSA of the ulna?
7mo
Telangiectatic subtype was negative prognostic factor; dogs 7x more likely to die. Other subtypes had MST >1yr
What impact does increased monocyte and lymphocyte count have on OSA prognosis?
High monocyte or lymphocyte count = poor prognosis
Aside from morphologic subtype and IHC, what histologic factor is prognostic for fibrohistiocytic nodule?
lymphocyte %
<40% = grade 3
What percentage of mast cell tumors of the muzzle have metastasized at presentation?
59% to regional LNs
What changes in ISS demographics were seen following the recommendations of the VAS Task Force?
Significant decrease in intrascapular and thoracic tumors
Increased occurrence in right forelimb, both hindlimbs and caudolateral abdomen
COX-2 expression has been detected in what % of MCT?
78-92%
What clinicopathologic factors have been correlated with COX-2 staining intensity in canine MCT?
higher grade (2 studies) higher Ki67, MI, and MVD (1 study) decreased survival (conflicting results)
Which RTK expression characteristics were associated with decreased MST/DFI in canine MCT?
Phospho-KIT
VEGFR2 staining (MCT>skin)
Diffuse cytoplasmic KIT staining
What did the use of COLD-PCR and DHPLC demonstrate regarding the rate of kit mutational status?
Conventional methods of detection likely underestimate mutational status
What types of activating mutations are identified in Kit juxtamembrane and extracellular domains, respectively?
juxtamembrane: ITDs (11 and 12)
extracellular: activating point mutations (8 and 9)
What was the concordance in mutational status and sequence between primary and metastatic MCT lesions?
100%
What impact did mRNA expression of Kit and SCF have on survival in canine MCT?
none
Which pathologic features were significantly associated with recurrent/metastatic subcutaneous MCT?
MI, Ki67, Ki67+AgNOR, kit pattern
Characterize the sensitivity and specificity of Ki67 vs MI for predicting death due to MCT.
Ki67 = sensitive (87%) but poorly specific (58%) MI = poorly sensitive (32%) but highly specific (96%)
Which of the following parameters carried the highest hazard ratio for risk of death in canine MCT: high histologic grade, MI, Ki67?
high histologic grade - HR = 45.6
What impact did Bcl-2 mRNA expression have on survival in canine MCT?
Increased Bcl-2 associated with increased mortality
What are minichromosome maintenance proteins, and in which malignancy has expression of MCM7 been shown to be prognostic?
Marker of cell proliferation (expressed throughout all cell cycle phases but not G0)
MCM7 >0.18 is prognostic for decreased survival in canine MCT
Using a cytologic grading scheme
that classified MCTs as high grade if they were poorly granulated or had at least 2 of 4 findings: mitotic figures, binucleated or multinucleated cells, nuclear pleomorphism, or >50% anisokaryosis, what was the Sn and Sp relative to histologic grading?
88% Sn
94% Sp
In a study evaluating cytologic grading of MCT, dogs with high histologic grade were ___X more likely to die of MCT within 2 year, those with a high cytologic grade were ____X more likely to die.
histologic - 39X
cytologic - 25X
Application of the 2-tiered/Kiupel grading criteria to cytologic grading resulted in a sensitivity, specificity, and accuracy of:
Sn - 85%
Sp - 97%
Accuracy - 94%
In a study comparing the two- and 3-tiered grading schemes for MCT, what was the 1-year survival probability for Grade II high/low grade?
Grade II/high - 46%
Grade II/low - 94%
In a blinded study assessing concordance in grade between 28 pathologists using the Patnaik scale, what was the concordance for Grade III and Grade I/II
Grade 3 - 74%
Grade 1/2 - <64%
What is the rate of BM involvement in dogs with cutaneous and visceral MCT, respectively?
cutaneous < 3%
visceral 56%
Plasma histamine levels are elevated in appx what % of dogs with MCT?
75%
Polycythemia vera is most commonly associated with a mutation in which gene?
JAK2
How do Sertoli cell tumors and seminomas lead to thrombocytopenia?
ectopic estrogen production
What was the prevalence of glomerular abnormalities detected by renal biopsy in dogs with mammary CA?
78%
31% had UPC >0.5
Which 3 cytokines are thought to be primarily involved in cancer cachexia?
TNFa
IL-1B
IL-6
Consumption of which omega-3 fatty acids may decrease loss of lean body mass and decrease tumor growth?
EPA and DHA
Is bone lysis more common with digital SCC or melanoma?
SCC - 80%
melanoma only 21%
What is the 1yr survival rate for dogs with subungual SCC?
95%
What drives mast cell differentiation from bone-marrow derived precursors?
SCF (stem cell factor)
Which juxtamembrane and extracellular domains of kit may harbor mutations?
Juxtamembrane - 11 and 12 (ITD)
Extracellular - 8 and 9 (point mutations)
What histologic features predicted aggressive behavior in subcutaneous MCT?
MI >4
Infiltrative growth
Multinucleation
Which 3 chemotherapy protocols carry the highest reported response rates for MCT?
Pred/VBL/CCNU - 57-64%
Pred/VBL/Cytoxan - 63%
COP-HU - 59%
What is the response rate of measurable MCT to the following drugs: CCNU Calcitriol Hydroxyurea Chlorambucil/Pred
CCNU - 44%
Calcitriol - 40%
Chlorambucil/pred - 38%
Hydroxyurea - 28%
In the initial placebo-controlled trial of Palladia for canine MCT, what was the ORR and biological activity rate?
ORR - 37-43%
ORR + SD - 60%
What was the MTD of VBL when combined with toceranib EOD to treat MCT? What was the ORR?
MTD = 1.6mg/m2 q14d ORR = 71%
What was the clinical benefit rate of dogs with MCT treated with the humanized anti-KIT mAb KTN0158?
100% (PR + SD)
Was not dependent on kit mutational status
In a study regarding the utility of staging in canine MCT, what was the rate of local and distant metastasis detected on routine staging of dogs presenting to a referral clinic for evaluation of MCT?
40%
LN mets - 31%
Distant mets - 6.8%
**all dogs with distant mets also had LN mets
What % of canine STS expressed fibroblast growth factor 23 (FGF23). What paraneoplastic syndrome is FGF23 responsible for in humans?
31% expressed FGF23
causes osteomalacia in humans due to renal phosphate wasting and subsequently decreased VitD
What is the sensitivity and specificity of palpation for LN metastasis of MCT?
71% Sn, 54% Sp
In a study evaluating surgically planned vs histologically measured tumor margins for dogs with MCT, how much smaller than surgical margins were histologic margins?
35-42%
In a study evaluating histologically safe margins for MCT, what were the recurrence rates for high and low grade tumors?
High - 36%
Low - 4%
A modified proportional margin technique for removal of cutaneous MCT resulted in complete excision of what % of tumors?
85%
What was the ORR of MCT to neoadjuvant prednisone?
70%
**no difference in response rate between 1mg/kg vs 2.2mg/kg
Following incomplete or close surgical excision of MCT, what was the recurrence rate for untreated, reexcised, and irradiated tumors?
Untreated - 38%
Re-excised - 13%
Radiation - 8%
In dogs with completely excised, high Ki67 Grade II MCT, which treatment results in statistically improved survival: VBL/pred or masitinib?
VBL/pred statistically superior to masitinib
What was the CR rate of canine MCT folowing electrochemotherapy and periturmoal IL-2?
72% CR rate
What is the ORR to masitinib for measurable MCT?
50 - 82%
Lowe study: 39% CR, 44% PR
What is the MTD of CCNU when given with pulse-dose toceranib? What is the ORR to this combination for canine MCT?
50mg/m2
46% RR
What is the rate of febrile neutropenia following 3.5mg/m2 VBL?
8% in 2 studies
What is the ORR of canine MCT to alternating CCNU and high dose (3.5mg/m2) VBL?
65%
What percentage of dogs experienced grade 3-4 AEs at 2.67-3.0 mg/m2 vinblastine?
5.9-9.5%
What is the ORR of canine MCT to single agent vinblastine at 2.0 and 3.5 mg/m2, respectively?
- 0mg/m2 –> 12% (all PR)
3. 5mg/m2 –< 27% (1 CR)
What was the rate of grade IV neutropenia following VBL 3.5mg/m2?
46%
What was the ORR to Paccal Vet in dogs with measuarble Grade II-III MCT?
59%
What was the ORR in the initial placebo-controled trial of Palladia in MCT?
42.8%
What is the most common gain of function mutation in KIT in canine MCT?
ITD in exon 11
What is the ORR of MCT to toceranib + pred + hypofractionated RT?
76%
59% CR!
What is the rate of metastasis to local lymph nodes for oral and perioral MCT in dogs?
59%
For MCT of the pinna, did cartilage infiltration impact outcome?
No
What was the ORR in the initial placebo-controled trial of Palladia in MCT?
42.8%
What is the most common gain of function mutation in KIT in canine MCT?
ITD in exon 11
What is the ORR of MCT to toceranib + pred + hypofractionated RT?
76%
59% CR!
What is the rate of metastasis to local lymph nodes for oral and perioral MCT in dogs?
59%
For MCT of the pinna, did cartilage infiltration impact outcome?
No
Were nuclear morphometric features such as mean nuclear area and mean diameter prognostic in canine ceruminous gland ACA?
yes
What % of canine STS expressed fibroblast growth factor 23 (FGF23). What paraneoplastic syndrome is FGF23 responsible for in humans?
31% expressed FGF23
causes osteomalacia in humans due to renal phosphate wasting and subsequently decreased VitD
Which of the following pathways were highly expressed in the majority of canine perivascular wall tumors? VEGF, PDGFB, bFGF, TGFB, COX2
VEGF
PDGFB
bFGF in 47%, cox2 in only 35%
Compare the incidence of OSA in dogs and humans?
14X higher in dogs
Which of the following is more similar to human TP3: canine or murine TP3?
canine (>90%)
What is the most frequent genetic alteration observed in both canine and human OSA?
amplification of Myc and c-kit
karyotypes of both are complex and chaotic
