Endocrine, GI, oral, nasal, MGT Flashcards
Do canine and feline pancreatic acinar cell carcinomas harbor KRAS mutatins?
No
A single pancreatic nodule >__?__cm is suggestive of neoplasia
2cm
What is the most common gastric tumor in dogs?
Gastric ACA - 70-80%
The carbohydrate antigen c2-O-sLex is upregulated in which canine tumor?
Gastric carcinoma - esp poorly differentiated
Are tumors with KRAS mutations more or less likely to respond to EGFR inhibition?
less likely - KRAS mutation represents downstream activation
Which is more sensitive for gastric neoplasia: ultrasound or endoscopy?
Endoscopy -95%
What is the most common Helicobacter species detected in cats, and which GI disease is it associated with?
H. heilmannii, associated with lymphoblastic lymphoma
Did use of adjuvant gemcitabine for canine HCC result in improved survival over historical controls undergoing liver lobectomy alone?
No
In canine GISTS, activating mutations occur in exon __?__ of c-kit.
Exon 11
**mutational status not found to correlate with staining pattern
What impact did the addition of adjuvant carboplatin have on outcome of dogs with surgically excised AGASACA (Wouda et al 2016)?
No improvement in survival in dogs tx’d with carbo vs surgery alone
Potanas et al 2015 reported DECREASED survival in pts treated with platinum drugs
For advanced (stage 3b) anal sac carcinoma, does surgery or hypofractionated RT result in better outcome (Meier et al 2016)?
RT – McQuown et al reported 38% PR, 63% improved clinical signs
FNA, FNI, and impression smear cytology were shown to have >90% diagnostic accuracy for oral lesions in cats and dogs. Which of these had the highest agreement (kappa) with histopath?
FNA/FNI = highest agreement in both dogs and cats
What was the strongest predictor of positive outcome in a retrospective case series of canine oral fibrosarcoma (Garder et al 2013)?
Combination of surgery + RT = best outcomes
In human SCC, p16/CDKN2A staining can be used to demonstrate papillomaviral origin. Did p16 staining support a role for PV in the development of canine OSCC? In feline OSCC?
No, no p16 was detected in canine OSCC
No PV DNA could be amplified from feline OSCC
What histological features is associated with increased risk of death in dogs with surgically treated OSCC?
Tumor-associated inflammation = increased risk of death (Fulton et al 2013)
In the most recent case series of 12 dogs with oral papillary SCC, were the majority of dogs > or <6yrs old? (Nemec et al 2014)
Majority (75%) were > 6yrs old
What impact does the presence of α-SMA-expressing fibroblasts have on survival in cats with OSCC?
α-SMA fibroblasts = cancer associated fibroblasts = decreased survival in feline OSCC.
Bmi-1 is an oncogene that suppresses cell cycle inhibitors. What impact did its expression have on outcome in feline OSCC?
High Bmi-1 expression = negative prognostic factor
18F-FDG PET/CT is likely to be most useful in defining tumor extent in feline OSCC with what characteristics?
Soft tissue invasive tumors
In cats undergoing SRT for OSCC, did increased keratinization impart improved or worse outcome?
More keratinized = worse
What is the prevalence of lymph node metastasis in feline OSCC, and is this prognostic for survival.
30% LN mets, 10% pulmonary mets, not prx for survival.
In dogs with histiocytic sarcoma, what two findings are associated with decreased survival (<1mo)?
Hypoalbuminema, thromboytopenia
Which of the following may serve as biomarkers for BMD with histiocytic sarcoma:
1) C-reactive protein
2) Fibrinogen
3) Monocyte chemotactic protein-1
All of the above (CRP, fibrinogen, and MCP-1)
Which IHC markers are expressed by feline progressive histiocytosis?
CD1a/c, CD18, MHC Class II
E-cadherin is expressed by what class of dendritic cells?
Langerhans cells
Interdigitating DC are present where?
Lymph nodes, spleen
Which breeds have the highest rate of homozygous mutant MDR1?
Collies (70%)
Australian shepherds, mini Aussies (50%)
Long-haired whippet (60%)
Other: McNab, silken windhound, sheltie, English shepherd, GSD, herding breed x, Old english sheepdog
What is the response rate of canine lymphoma to first line treatment with prednisone and lomustine?
CR: 35%, ORR: 52%
What is the response rate of relapsed canine lymphoma to L-spar, CCNU, and pred?
CR: 52%, ORR 87%
Does addition of Cytosar to CHOP-based protocols affect survival in patients with stage V lymphoma?
Yes, addition of Cytosar improved survival.
What is the response rate of relapsed lymphoma to to single-agent DTIC?
35%
What is the response rate of relapsed lymphoma to to DMAC?
65%
What is the expression of the following markers in feline Hodgkin’s-like lymphoma?
CD40L
CD3
CD79a
- will have both CD3+ and CD79a+ cells
- Reed-Sternberg cells do not stain with any typical markers, but are positive for BLA36
Name 3 factors associated with poor prognosis in canine multiple myeloma.
Hypercalcemia
Bence-Jones proteinuria
Extensive bony lesions (ie path frac)
Azotemia
What is the most common M component in feline myeloma?
IgG
Name 3 negative prognostic factors in feline myeloma.
Pathologic fracture
Anemia
Bence-Jones proteinuria
Azotemia
Name two prognostic factors for lingual hemangiosarcoma.
Tumor size (smaller = better) Lack of clinical signs = better
What are the two most common tumors of the canine tongue?
SCC
Melanoma
What proportion of dogs with oral mucosal mast cell tumors have evidence of local lymph node metastasis at diagnosis?
55%
What is the most notable difference between extramedullary plasmacytoma in humans and dogs?
Humans - 1/3-1/2 have associated hypergammaglobulinemia or convert to MM
Dogs - rarely associated with systemic signs or MM
What impact did EGFR expression have on survival in feline OSCC?
Decreased survival in one study (no effect in other studies)
Which histologic subtypes of canine nasal tumor are associated with an unfavorable prognosis?
Carcinoma, esp squamous or undifferentiated
Which biopsy technique (blind, image-guided, or rhinoscopy) is most likely to give a diagnosis of nasal neoplasia?
All - proportion of diagnostic biopsies was not different between all 3 techniques
What is the rate of acute and late toxicity following SRS for nasal tumors in dogs?
Acute: 23%
Late: 40%
Tumor type was the only prognostic variable in a study evaluating SRS for nasal tumors. Which tumor type was associated with significantly decreased survival?
OSA - decreased survival following SRS
COX-2 expression has been demonstrated in __?__% of canine nasal tumors. Did addition of firocoxib to radiation therapy result in significantly increased survival?
71-95% COX-2 +
No difference in DFI/survival when firocoxib added to RT, but QoL measures improved
What was the clinical ORR of dogs with nasal tumors treated with a 5x4Gy daily protocol? What proportion of these constituted clinical CR?
ORR = 95% CCR = 78%
In dogs re-irradiated with a hypofractionated protocol following PRT, what was the clinical response rate to the second course of RT?
70%
Belshaw et al demonstrated positive immunostaining for COX2 in 90% of canine nasal tumors. How did COX2 expression correlate with survival?
COX2 expression had no impact on survival
In reviewing 140 cases of feline nasal neoplasia with IHC, Nagata et al calculated an initial diagnostic error rate of 6.5%. Was lymphoma or carcinoma more likely to be underdiagnosed?
Lymphoma was more commonly misdiagnosed as carcinoma.
What was the recurrence rate of feline nasal planum SCC treated with curettage and diathermy?
<10%
What complications of full thickness GI biopsies can be expected in cats with alimentary lymphoma?
Anorexia, hyperthermia, pancreatitis, constipation
**even when albumin <2.5, no leak or dehiscence was noted
What proportion of cats developed neoplasia following renal transplantation?
22% - lymphoma most common
6.6X increased risk of neoplasia
ST did not differ between cats that developed neoplasia and those who did not
What are the diagnostic features of myelodysplastic syndrome?
<30% blasts
Dysplastic changes in 1 or more cell lines
What was the ORR and PFS for dogs with measurable MCT treated with toceranib, prednisone, and hypofractionated RT?
75%, PFS 300d
What criteria define a high-grade MCT in the two-tiered grading scheme (Kiupel)?
At least 7 mitotic figures/10hpf
At least 3 multinucleated cells/10hpf
At least 3 bizzare nuclei/10hpf
Karyomegaly
Name 3 histopathologic features associated with a worse prognosis in canine subcutaneous MCT.
MI >4
Infiltrative growth pattern
Presence of multinucleation
Also: Age at dx
What is the survival time for canine appendicular chondrosarcoma with amputation alone?
2.5 yrs (979d)
Expression of which of the following was prognostic for survival in canine osteosarcoma: Ezrin Met VEGF COX2
Ezrin
In dogs with osteosarcoma, what impact does a decreased circulating CD8:Treg ratio have on survival?
Decreased CD8/Treg ratio = decreased survival
What is the MST for parosteal OSA?
a) 3mo
b) 1 yrs
b) 33mo
33mo
What is the 3-year control rate for STS treated with surgery and hypofractionated RT?
a) 30%
b) 50%
c) 70%
d) 90%
70% control at 3 yrs
Which of the following is prognostic for outcome in canine pituitary tumors treated with RT?
a) tumor size
b) ACTH
c) baseline cortisol
d) brachycephalic breed
Tumor size - pituitary to brain height ratio and pituitary to brain area ratio
What clinical factor was most predictive of complications following stent placement for urogenital tumors?
Duration of stranguria prior to stenting
Which of the following has the highest reported response rate in treating canine TCC?
a) piroxicam
b) deracoxib
c) firocoxib
Firocoxib - 20% PR
***but, piroxicam has a 6% CR rate + 12% PR rate
__?__% of renal tumors are bilateral at diagnosis.
4% of renal tumors are bilateral at diagnosis
What is the MST following surgery for renal cell carcinoma?
16mo
What two factors have a positive impact on survival for canine inflammatory mammary carcinoma?
- lack of coagulopathy
- medical treatment
What criteria are used to grade canine mammary carcinomas?
Tumor type, nuclear/cellular pleomorphishm, MI, necrosis, lymphatic invasion, and LN metastasis
What is the response of canine MLO or osteosarcoma of the skull to treatment with 153-Samarium?
20%
What are the most common bloodwork abnormalities seen with hypertrophic osteopathy?
Anemia, neutrophilia, elevated ALP
What labwork findings are expected in cases of ATLS?
Hypocalcemia Metabolic acidosis Hyperphosphatemia Hyperkalemia Decreased bicarb
RT for ameloblastoma resulted in sarcoma in __?__% of dogs treated.
3.5%
Tonsilar SCC is associated with living in what kind of environment?
Tonsillar SCC- urban environoment
What impact does Wnt/B-catenin signaling have on telomerase?
Wnt/B-catinine regulates telomerase by increasing TERT subunit; without B-catenin telomeres are shorter
True/False: Mice have longer telomeres than humans.
True - mice telomeres are 5-10x longer
What is the TRAP assay?
Telomeric Repeat Amplification Protocol
Detects telomerase activity using a primer and amplification; 92% sensitivity for malignant tumors in dogs
What are the cellular features of senescent cells?
Senescent cells are larger and more morphologically diverse
B-galactosidase is a commonly used marker
p16INK4a also a marker
What is considered the most important histologic predictor of outcome in human and canine mammary carcinoma?
LN status
Which of the following was shown to be prognostic for survival in canine mammary carcinomas (Diessler et al)? Histologic Grade LN status Vascular Invasion PCNA MVD VEGFR2
LN status
Vascular invasion
trend towards shorter survival in high-VEGFR2 tumors
What does a CD44+/CD24- phenotype in canine mammary tumor cells imply?
CD44+/CD24- = cancer stem cell
Associated with higher grade of malignancy
What is unique about the sensitivity of CD44+/CD24- canine mammary tumor cells to metformin?
CD44+/CD24- = cancer stem cell
Highly resistant to DOX but susceptible to metformin
Compare the degree of malignancy, frequency of vascular invasion, and age of onset in canine mammary carcinoma in overweight/obese dogs versus those in good body condition.
Obese dogs had higher degree of malignancy, more frequent vascular invasion, and younger age of onset than those in good body condtion
In canine mammary carcinoma, frequency of copy number aberrations and LOH increase or decreases with histologic grade of malignancy?
frequency of copy number aberrations and l.o.h. INCREASES with histologic grade of malignancy
In canine mammary carcinoma, which of the following copy number aberrations was more common: amplification or deletion?
Deletion
Copy number aberrations frequently identified in canine mammary carcinoma include gain/loss of:
1) MYC
2) PTEN
MYC - frequently increased
PTEN - frequently lost
What is the significance of detection of MAC387+ cells in canine mammary tumor samples?
MAC387 = tumor-associated macrophage marker
TAMs were associated with decreased survival, malignant > benign tumors, VEGF+ tumors, presence of infiltrative growth and LN mets
How are tumor-associated macrophages thought to contribute to angiogenesis?
Production of VEGF
FOXP3 expression in canine mammary tumors correlates with…?
Decreased survival
Negative FOXP3 expression was correlated with positive ER and PR expression
Is expression of phospho-mTPR considered a prognostic factor in dogs with mammary carcinoma?
No, p-mTOR expression did not correlate with survival or histologic grade in Delgado et al 2015
What impact do VEGFR-2 and VEGF expression have on survival in canine MGTs?
Both VEGFR-2 and VEGF expression correlated with decreased survival in canine mammary tumors
High expression of COX2 and EGFR in canine mammary carcinoma corresponds to what clinicopathologic features
COX2 and EGFR co-expression in canine MGTS ==> higher histologic grade, presence of LN metastasis
Name two circulating antigens investigated as potential biomarkers in canine mammary carcinoma.
Carcinoembryonic antigen (CEA) and cancer antigen (CA 15-3)
CA 15-3 was more sensitive for detecting disease
Certain haplotypes/SNPs of what three gene have been associated with increased risk of mammary carcinoma in both humans and dogs?
ESR1 (estrogen receptor)
BRCA1 & BRCA2
A female dog presents with two mammary tumors. One is biopsied as benign. Is the other more likely to be malignant or benign, or is the chance equal?
More likely to be benign
Gunnes et al 2015: Simultaneous tumours within dogs more often had equal diagnoses and neoplastic level (benign or malignant) than would be expected by chance alone.
What is the risk of mammary tumor in dogs spayed before their first, second, and third heat cycles, respectively
0.05% before 1st heat
8% before 2nd heat
26% before 3rd heat
Dogs with BRCA1 and BRCA2 mutations have a _?_X higher risk of mammary tumor development.
4X higher
What percentage of HAC cases are PDH?
85%
What were the two most prevalent dopamine and somatostatin receptor subtypes expressed in canine pituitary adenomas?
Type 2
D2 + SST2
What percentage of pituitary tumors in dogs are adenocarcinomas?
6%
Differentiated by presence of metastasis, not infiltration
Plasma levels of ___?____ may help select PDH patients for brain imaging, as they can be correlated with tumor size.
Pro-opiomelanocortin
Pro-ACTH
Which of the following adrenal tumors is most common in cats?
- Adrenocortical tumors
- Pheochromocytoma
- Metastatic lesions
Metastatic lesions
next most common = adrenocortical
The most common metastatic adrenal neoplasia in both dogs and cats is:
lymphoma
What is the sensitivity and specificity of abdominal ultrasound and contrast-enhanced CT for the detection of vena cava invasion?
AUS - 80-100% sensitive, 90% specific
CT - 92% sensitive, 100% specific
Adrenal tumors larger than ___cm are more likely to be carcinomas than adenomas.
> 2cm
What % of adrenal tumors locally invade the phrenicoabdominal vein?
20%
How is Conn’s syndrome diagnosed?
Plasma aldosterone:renin ratio
Pheochromocytoma has a metastatic rate of ____% and vascular invasion is observed in ____%
40% met, 82% invade
Which IHC marker most accurately identifies medullary thyroid carcinoma?
Calcitonin
- Which of the following is the most sensitive for detection & localization of canine insulinoma?
a. Abdominal ultrasound
b. CT
c. SPECT with 111‑In-DTPA-D-Phe1-octreotid
d. 111‑Indium penetreotide scintigraphy
SPECT with 111‑In-DTPA-D-Phe1-octreotid
What is the response rate of dogs with insulinoma to diazoxide therapy?
70%
Diazoxide is a nondiuretic benzothiadizine that supresses insulin release from B cells and stimulates gluconeogenesis
What is the response rate of dogs with insulinoma to octreotide?
~50%
Besides gastrinoma, what conditions can lead to elevation of gastrin levels?
renal, hepatic, and gastric disease; tx with antacids
Activating mutations of which of the following genes were detected in canine adrenocortical tumors?
a. PI3K
b. GNAS
c. MC2R
GNAS - activating mutations
there was evidence of increased PI3K/AKT signaling, but no mutations identified
What was the accuracy of cytology in differentiating adrenocortical vs. medullary tumors?
90-100%
Is hisotpathology a reliable determinant of behavior in adrenocortical tumors?
No, although lymphovascular invasion and ki67 may predict malignancy
Is serum inhibin concentration higher in patients with adrenocortical or medullary tumors?
Inhibin is higher in cortical tumors
What is the preferred method for differentiation of pheochromocytoma?
a. Urine epinephrine:creatinine ratio
b. Urine normetanephrine:creatinine ratio
c. Plasma free normetanephrine
d. Plasma total metanephrine
Urine normetanephrine:creatinine ratio
What was the most imported predictor of short term survival in dogs undergoing adrenalectomy?
Extent of vena caval invasion/thrombus
Does extent of caval invasion influence long-term survival in dogs with adrenocortical tumors?
No, only short term survival
Only tumor type was predictive of longterm survival
Are metastatic or primary tumors more common in the kidney?
Metastatic
Renal cell carcinoma accounts for ____% of primary renal tumors in dogs.
50-60%
Which of the following renal tumors has the highest metastatic rate: carcinoma, sarcoma, nephroblastoma
Sarcoma - 88%
Nephroblastoma - 75%
Carcinoma - 69%
What is the most significant histological predictor of survival in canine renal cell carcinoma?
Mitotic index (<10, 10-30, >30)
Name 3 clinical negative prognostic factors at diagnosis for canine RCC?
age <6yrs
cachexia
hematuria
What presenting complaint is more common in primary renal sarcomas compared with other primary renal tumors?
Pain
What percentage of renal tumors in BHD heterozygous GSD had a mutation in the wild-type FLCN gene?
71% – indicates likely “second-hit” as underlying the pathogenesis of this disease
OHE at the time of benign mammary tumor removal reduces risk of new tumor formation by ?%
50% reduced risk
What is the MST for dogs with nasal tumors treated with robotic radiosurgery?
399d
What is the most common laryngeal tumor in cats?
SCC
Which of the following canine nasal tumor histologies is associated with a worse prognosis?
SCC
Adenocarcinoma
SCC
Ki67 >____% indicates a malignant adrenal tumor.
Ki67 >2.4 = ACA not adenoma
What factor is prognostic for outcome in cats undergoing adrenalectomy for tx of Conn’s syndrome?
Anesthetic time >4hrs
Treatment of thyroid carcinoma in cats requires I-131 dosing ____X higher than thyroid adenoma.
5-10X
Which canine breeds are predisposed to thyroid carcinoma?
Beagle, Husky, Golden retriever
What % of thyroid carcinoma will lose the ability to accumulate radioactive iodine? Can these secrete thyroglobulin?
20-30%
Can still secrete Tg even if don’t concentrate iodine
What impact does EGFR expression have on canine mammary CA?
EGFR overexpression = poor prognosis
What was the age and neuter status of male dogs with mammary tumors?
Avg age = 11.5yrs
50% neutered vs intact
What was the clinical behavior of mammary tumors in male dogs?
Benign - treated with surgery only
ER receptor expression high, PR expression present
In which species is HER2 immunovaccination more likely to be useful?
Cats
HER2 is expressed in 95% of K9 MGTs but it is also expressed in normal tissue. Cetuximab was not successful in dogs.
BRCA mutation has been detected in what breed?
English Springer Spaniel
What is the response rate for feline nasal planum SCC treated with strontium?
88% RR
Recurrence - 20%
What is the response rate of feline nasal planum SCC to PDT with 5-ALA?
> 95%
What is the complication rate for intrathoracic biopsies?
40%
Which tumor subtype of canine lung tumors has the longest MST?
Papillary adenocarcinoma - T1, Stage I = 555d survival time
What percentage of AGASACA express PDGFRa? PDGFRb?
100% PDGFR-alpha
10% PDGFR-beta
What is the MST of AGASACA following treatment with surgery, radiation, and MTX?
960d
What feature of LN ultrasound is reliable for detecting AGASACA metastasis?
size
What % of canine malignant melanomas expressed KIT, and what % harbored mutations?
100% weak to strong staining
~10% exon 11 mutation
What % of GISTs have kit mutation?
35%
What % of GISTs have PDGFR-alpha mutation?
0%
What is the outcome of gastric tumors treated with gastroduodenectomy?
25% mortality rate
MST = 33d
What factors are prognostic for outcome in lingual tumors?
Size
LN mets
tumor subtype (melanoma vs SCC) did NOT impact outcome
What is the most likely diagnosis of a 2.5cm ulcerated mass on the ventral aspect of the tongue?
SCC
What is the most important predictor of outcome in both human and canine MGT?
LN status
What were the transcript levels of ATM in canine mammary CA and benign MGTs compared to normal tissue?
ATM was lower in benign/neoplastic tissue than normal
What impact did loss of autophagy-related protein Beclin-1 have on behaviour of canine mammary tumors?
more aggressive behavior
