Lucky Dip Flashcards
(501 cards)
1
Q
What is the Warburg effect?
A
Cancer cells experience a metabolic shift from oxidative respiration to an energy efficient aerobic glycolytic profile.
2
Q
Activating mutations of the BRAF gene lead to constitutive activation of the MAPK pathway. The most common alteration in BRAF are point substitutions at
A
Valine 600 (V600). In dogs with iUC it is usually V595E
3
Q
Which JAK/STAT inhibitor is used in veterinary medicine?
A
Oclacitinib
4
Q
What is Knudson’s 2 hit hypothesis?
A
That most tumor suppressor genes require both alleles to be inactivated (recessively acting cancer gene), either through mutations or through epigenetic silencing, to cause a phenotypic change (cancer development). This was proven with the Rb1 locus (retinoblastoma tumor suppressor gene). Homozygous loss of the wild-type Rb1 locus correlated with retinoblastoma development.
5
Q
Which virus is associated with the development of Burkitt’s lymphoma?
A
Epstein-Barr virus (EBV)
6
Q
What is the Hayflick limit?
A
The eventual loss of replicative potential (cellular senescence). The time to the cessation of cell division correlates closely with critically eroded telomeres (called telomere signal-free ends).
7
Q
What is the name of the complex that degrades proteins that are tagged with ubiquitin?
A
26S proteosome
8
Q
List the stages of apoptosis
A
- Rounding up of the cell
- Plasma membrane blebbing
- Cytoplasm shrinkage
- Alteration of membrane asymmetry
- Condensation and fragmentation of the nucleus
Late stage: fragmented into apoptotic bodies that are eliminated by phagocytic cells without triggering inflammation.
9
Q
What is the action of RANKL
A
Receptor activator of nuclear factor kappa betta ligand (RANKL) is released by osteoblasts. It activates myeloid progenitor cells to differentiate into osteoclasts that can digest bone structures, creating space for establishment of metastasis. Denosumab is a monoclonal Ab targeting RANKL, approved for treating patients with bone metastasis.
10
Q
How many tumor cells necessary for 1g (1 cm) of tumor (smallest clinically detectable mass)
A
1 x 10^9
11
Q
What is the action of DNA methylation
A
Covalent addition of a methyl group at position 5 of a cytosine (C) nucleotide (5mC), typically positioned close to a guanine residue (G), occuring mostly in CpG islands (regions dense in adjacent C and G nucleotides) found at the promoter region of genes. Typically results in gene-SILENCING.
12
Q
What is the normal diffusion distance of oxygen from tumor blood vessels?
A
150-200 um
13
Q
Name for the novel hedgehog pathway inhibitor?
A
Saridegib
14
Q
What is the name of the most common HDAC inhibitor?
A
Vorinostat
15
Q
What is the name of the most common PARP inhibitor
A
Olaparib
16
Q
What are the markers for cancer associated fibroblasts?
A
a-smooth muscle actin (a-SMA), fibroblast specific protein-1 (FSP-1)/S100, neuron-glial antigen-2 (NG-2), PDGFR-beta.
17
Q
Which enzyme functions in alkylator-induced DNA repair
A
MGMT
18
Q
What are the solvents used for paclitaxel and docetaxel respectively that allow for IV administration?
A
Paclitaxel = Cremophor EL, Docetaxel + Polysorbate 80
These solvents cause severe hypersensitivity reactions in dogs and require significant pretreatment with antihistamines and steroids and prolonged infusion with continued monitoring.
New water soluble formulation of paclitaxel (Paccal Vet) may lead to increased use of this drug in vet med.
19
Q
Feline cutaneous MCT response to lomustine?
A
20 cats: 2 CR, 8 PR = 50% ORR
20
Q
Which drugs are radiation sensitizers
A
Doxorubicin, carboplatin, actinomycin D, gemcitabine
21
Q
What toxicity is associated with 5-FU in cats
A
Fatal CNS toxicity
22
Q
Which anthracycline may be administered orally?
A
Idarubicin
23
Q
Why is cyclophosphamide relatively platelet sparing?
A
High levels of aldehyde dehydrogenase in the bone marrow (which deactivates cyclophosphamide)
24
Q
What is the active metabolite of cyclophosphamide?
A
Phosphoramide mustard
25
Which chemotherapy agent must you give MESNA with?
Ifosfamide
26
Which drugs are severe vesicants?
Doxorubicin, vinca alkaloids, mechlorethamin, actinomycin D
27
What are the IHC markers for melanoma?
Melan-A, S-100, PNL2, tyrosinase
28
IHC marker for thyroid carcinoma (epithelial)
Thyroglobulin (+)
29
IHC marker for thyroid carcinoma (c-cell)
Synaptophysin (+), chromogranin (+), thyroglobulin (-)
30
IHC markers for MCT
Vimentin (+)
Tryptase and CD117 (KIT) (+)
+/- chymase, MCP-1, and IL-8 (+)
31
Which IHC stain can differentiate between canine urinary bladder transitional cell carcinoma and other carcinomas?
Uroplakin III
32
Which IHC marker can confirm a diagnosis of hemophagocytic histiocytic sarcoma?
CD11d
33
Which IHC markers are positive with hemangiosarcoma?
Factor 8 (vWF), CD31
34
GIST IHC markers
CD117(KIT), CD34, DOG-1, and S-100
35
Which IHC markers are used to distinguish pheochromocytoma from adrenocortical carcinoma?
chromogranin A and synaptophysin
36
Markers for feline progressive histiocytosis
CD1a, CD11c/CD18, CD5, Iba-I, CD204
37
Which type of radiation induced DNA damage is most important for cell killing caused by exposure to ionizing radiation?
DNA double strand breaks
38
The main mechanism of cell death after irradiation is
Mitotic catastrophe: cells with damaged DNA attempt to divide resulting in progeny with an incomplete genetic complement and are unviable.
39
What is the annual dose limit for radiation workers?
0.05 Sy = 50 mSv = 5 rem
40
Which radiolysis product of water is responsible for the molecular damage caused by the indirect action of ionizing radiation?
OH* (Hydroxyl radical)
41
Cells in which phase of the cell cycle are most sensitive to radiation?
G2/M phase
42
Cells in which phase of the cell cycle are least sensitive to radiation?
Late S phase
43
What is the most common site for canine chondrosarcoma?
Nasal cavity
44
Is canine gastrointestinal lymphoma more commonly T or B cell?
T cell 63% vs B cell 37%
45
Which exons are typically mutated with c-kit in feline mast cell tumors?
Exon 8 and 9 (extracellular domain)
65% of cats will carry this mutation (most were 8, more common with splenic MCT).
46
Which gene was recently associated with MCT development in golden retrievers?
GNAI2-associated with hyaluronic acid synthesis
47
How many dogs with MCT present with multiple tumors?
11-14%
48
In dogs, c-kit mutations appear to be associated with what percent of intermediate and high grade MCT?
25-30%
49
How many dogs with MCTs located in the muzzle present with regional metastasis?
50-60%
This does not necessarily indicate a worse long term prognosis, as the MST for dogs with metastatic disease was 14 months.
50
What is the reported MST for poorly differentiated MCT with the presence of LN metastasis?
194 d
vs 503d for dogs with no metastasis
51
What is the incidence of bone marrow involvement in canine MCT
2.8%
52
Which parasite has been associated with development of sarcoma in dogs
Spirocerca lupi
53
What is the most common paraneoplastic syndrome associated with thymoma in the cat?
Exfoliative dermatitis
54
What 3 abnormalities characterize a syndrome associated with mutation in the canine Birt-Hogg-Dube (BHD) gene in GSD?
1. Multiple uterine leiomyomas
2. Bilateral renal cystadenocarcinomas
3. Nodular dermatofibrosis
Mutation in FLCN-tumor suppressor gene coding for protein folliculin. Also seen in Alsatians.
55
Which gene expression is common in canine gastric carcinoma
Exon 11 of c-kit gene, HER-2 (58%)
56
Which testicular tumor is most often associated with hyperestrogenism?
Sertoli cell tumor
57
Which characteristics predict a worse outcome for dogs diagnosed with B cell lymphoma?
Large cell, low levels of class II MHC expression
58
What is the most common location of feline appendicular osteosarcoma?
Distal femur and proximal tibia
59
Which tumor location is most suitable for limb sparing surgery in dogs affected by OSA?
Distal radius or ulna
60
Which protein is necessary for metastasis in murine models of osteosarcoma and associated with shorter DFI in dogs with osteosarcoma?
Ezrin
61
Which breed is predisposed to bile duct carcinoma?
Labrador retrievers, sex predilection for females
62
Which monoclonal antibody targets HER-2 positive tumors in humans?
Trastuzumab
63
What percentage of HSA occur primarily in the liver?
4-6%
64
Which virus is associated with HCC in humans?
Hepatitis viruses B and C
65
Which cells do carcinoid cells arise from?
Neuroendocrine cells
Contain secretory granules that may contain substances such as 5-hydroxytryptamine (seratonin), secretin, somatostatin, and gastrin, among others.
IHC for cytokeratin and serotonin may be positive.
66
What histopathologic factors are associated with worse prognosis for canine SQ MCT?
Mitotic index greater than 4
Multinucleation
Invasiveness
67
What is the MST for dogs with perianal adenocarcinoma with LN or distant metastasis?
7 months, however aggressive treatment was not attempted in 5/6 dogs
68
What is the RR of AGASACA to Palladia
25% PR, 63% SD, total clinical benefit rate = 88%
69
What is the MST of dogs with nasal carcinoma without treatment?
95 days (3 months)
70
What is the MST of cats with lymphoma without treatment?
53 days
71
What % of cats treated with SRT for functional pituitary adenoma developed hypothyroidism?
14%
72
Which tumors are known to express ABCB1
Canine lymphoma, mammary tumors, feline primary pulmonary carcinoma
73
What percent of dogs with testicular tumors have bilateral tumors?
50%
74
What percent of dogs with sertoli cell tumors will present with signs of hyperestrogenism?
50%
75
What percent of dogs will have greater than 1 testicular tumor type?
4-20%
76
What percentage of dogs with prostat tumors, when treated with a total prostatectomy, will experience permanent urinary incontinence
35%
MST = 231 days (shorter in dogs with extracapsular invasion compared to intracapsular tumors)
77
What percent of prostatic carcinomas had COX-2 expression in dogs?
75-88%
78
What is the MST of dogs with prostatic carcinoma treated with NSAID alone?
6.9 months
79
What percent of dogs with iUC are reported to have urethral involvement?
56%
80
What is the MST of cats with iUC treated with a variety of treatments?
261
11 cats treated with meloxicam = 311 days. More than half were away from the trigone
81
What percent of dogs with iUC are reported to have prostatic involvement?
29%
82
What is the MST of dogs with renal HSA in a retrospective study of 14 dogs?
278 d
83
In a phase I clinical trial of intravesical mitomycin C, what were the most significant complications?
Marked myelosuppression and GI upset - indicating there was some systemic absorption occuring
84
Although neoplastic cells are often indistinguishable from reactive epithelial cells in the urine of dogs with TCC, neoplastic cells may be present in the urine in up to what percent of cases?
30%
85
What percent of cats with meningioma present with multiple tumors?
17% (Withrow page 583)
86
What is the most common type of glioma in dogs?
Oligodendroglioma (previously reported to be astrocytoma) (new Withrow)
87
What is the MST for dogs with CNS lymphoma treated with a variety of treatments?
171 days
88
What is the MST for dogs with presumptive glioma treated with CCNU?
178 days
89
What is the reported MST for cats with cerebral meningiomas treated surgically?
23-37 months
685 days in another study (2 years)
90
What proportion of cerebral meningiomas in cats will recur following surgical treatment?
20.6-25% (median TTR 285 days)
91
What is the MST of dogs with meningioma treated surgically with conventional techniques?
7 months
92
What percent of feline brain tumors are detected incidentally?
20%
93
What is the most common location for spinal meningiomas and malignant nerve sheath tumors? Options are:
a. Extradural
b. Intradural/extramedullary
c. Intramedullary
d. Mixed
B
94
Which breeds of dogs are predisposed to spinal nephroblastoma at a young age?
GSD and Golden retrievers
95
Which spinal cord segments do nephroblastomas arise from?
T9-L2
96
Which is the most common spinal nerve root affected by PNST?
Caudal cervical region (C6-T2)
97
What is the most common tumor of the canine conjunctiva?
Melanoma
Older, female, weimaraner and possibly GSD/large breed dogs may be predisposed
98
What is the most common tumor of the third eyelid in dogs and cats?
Adenocarcinoma (85%)
99
What is the average latency period for cats to develop ocular posttraumatic sarcoma?
5 years
67% are males or neutered males
100
In cats with orbital neoplasia, what percent had radiographic signs of orbital bone lesions?
59%
15% had pulmonary metastasis.
101
What is the average latency period for cats to develop ocular posttraumatic sarcoma
5 years
67% are neutered males
102
In cats with orbital neoplasia, what percent had radiographic signs of orbital bone lesion?
59%
15% had pulmonary metastasis
103
What percentage of canine anterior uveal melanomas demonstrate metastasis?
25%
104
What percent of conjunctival melanoma recur following excision?
55%
At least 17% of the dogs experienced orbital invasion or spread to the regional lymph nodes or lung
105
What percentage of dogs with large B cell lymphoma will have normal CBCs but exhibit bone marrow involvement when assessed via flow cytometry?
15%
106
What is the characteristic marker for T zone lymphoma
CD45-
107
What was the MST of T zone lymphoma in Seelig et al 2014
657 days
108
What percent of normal canine lymphocytes in peripheral circulation are T cell and B cell respectively?
T cell = 80%
B cell = 15%
NK and double negative T cell = 5%
109
In a retrospective study by Childress et al, what were the 4 negative prognostic factors identified in dogs with DLBCL undergoing CHOP chemotherapy?
1. Thrombocytopenia
2. Greater age at diagnosis
4. Higher neutrophil count
4. Higher serum globulin concentration
110
What is the sensitivity and specificity of AUS for detection of splenic involvement of lymphoma?
Sensitivity 100%, specificity 23%
111
Which breed has been described to have lymphocytic plasmcytic inflammatory bowel disease that progressed to GI lymphoma?
Basenji
112
Which dog breeds may be overrepresented in cases of alimentary lymphoma?
Boxers and Sharpei
113
What percent of dogs with lymphoma present with hypercalcemia?
10-40%
114
What is the name of the syndrome of cutaneous T cell epitheliotropic lymphoma progressing to circulating malignant cells in humans?
Sezary syndrome
115
What chromosomal aberration has been detected in dogs with naturally occuring lymphoma and appears to hold prognostic significance?
Chromosome 13
Gains of canine chromosomes 13 and 31 and loss of chromosome 14 have been documented as the most common aberrations in a group of 25 cases analyzed
- prognostic advantage in dogs with trisomy chromosome 13 has been identified
116
What percent of dogs with multicentric lymphoma have diffuse pulmonary infiltration?
27-34%
117
What percentage of dogs with multicentric lymphoma are expected to go into complete remission when treated with single agent doxorubicin as a first line therapy?
50-75%, MST 6-8 months
118
For dogs that have completed the CHOP chemotherapy protocol for lymphoma, what percentage of dogs will successfully be reinduced by the same protocol more than 2 months after completion of treatment?
80-90%
119
What is the most common lymphoma related paraneoplastic syndrome?
Anemia
120
What percent of dogs with lymphoma will have ocular involvement/uveitis?
33-50%
121
What percent of dogs with lymphoma are reported to have monoclonal gammopathies? Which type of lymphoma?
6%, usually B cell LSA
122
What are the B cell markers?
CD79a, CD20, CD21, Pax5
Although dogs with TZL can express CD21
123
What are the T cell markers?
CD3 (pan), CD4 (helper), CD8 (cytotoxic)
124
What classifies as a LARGE lymphocyte?
Greater than 2x an RBC or larger than a neutrophil
Intermediate = 1.5-2 x RBC, same size as neutrophil
125
What percent of dogs with multicentric lymphoma?
35% (response duration of 43 d)
126
PARR sensitivity and specificity for canine lymphoma?
70-90% sensitivity, 5% false positive rate (95% specificity). False positives occur in some infectious diseases (ehrlichiosis and leishmania)
127
What is the name of the monoclonal antibody against CD20 used in humans with B cell non-hodgekins lymphoma
Rituximab
128
What is the MST for colorectal lymphoma in dogs receiving chemotherapy and what is the dominant immunophenotype?
MST - 1845-2352
B cell
129
What is the reported MST of dogs with low grade GI lymphoma treated with chlorambucil and prednisone?
1.5-2 years
130
What is the response rate for cutaneous lymphoma to chemotherapy?
40-80% median remission duration is 3-6 months
131
What percentage of senior golden retrievers without evidence of lymphoproliferative disease have TZ cells (CD45- T cells) in peripheral blood when analyzed by flow cytometry?
31%
132
Approximately what percentage of dogs with T zone lymphoma have been reported to be Golden Retrievers?
40%
133
What is the median PFI and overall ST for canine nodal marginal zone lymphoma?
PFI - 5 months
Overal ST = 8.5 mo
134
What is the median PFS for cutaneous lymphoma treated with Tanovea?
38 days
135
What is the response rate and median remission duration for cutaneous lymphoma treated with CCNU?
80%, median remission duration = 3 months
136
What is the concordance rate of pre-treatment bx STS to final dx?
59%
29% underestimate, 12% overestimate
137
What was the MST for dogs treated with surgery and adjuvant carbo for oral melanoma (+/- RT)?
MSTS = 440 d, PFI = 259 days
138
What percentage of dogs with chronic lymphocytic leukemia were reported to develop Richter's syndrome?
5%, median survival = 41 days
139
Normalization of lymphocytes counts occur in what percent of treated CLL cases?
70%
140
In a study of metastatic cancer of unknown primary, what percent were diagnosed as carcinoma?
57%
MST = 30 days
Primary site not identified on full body CT in 95% of dogs
141
What proportion of telangiectatic OSA were reclassified as HSA of bone when stained with VWIII-related antigen or VWf?
20%
142
In a study of 40 dogs with systemic mastocytosis, which chemotherapy protocol provided the best outcome?
Lomustine + vinblastine + prednisone -- MST = 227 d
Palladia MST = 118 days
143
What was the MST for feline large granular lymphoma receiving a variety of treatments?
MST = 21 days, small subset (7.3%) survived greater than 6 months
MST was significantly shorter in the case of substage b, circulating neoplastic cells, lack of chemotherapy administration, and lack of treatment response.
144
Which chemotherapeutic drugs are inhibitors of ribonculeotide reductase?
Gemcitabine, cytarabine, hydroxyurea; reason for radiation sensitivity?
145
What percent of cats with renal transplant receiving cyclosporine developed neoplasia in Wormser et al 2014?
22.5% (56% of which were lymphoma -- 10-13%)
146
Compared to the control population, renal transplant cats have a _______ times higher odds of developing malignant neoplasia and a _____ times higher odds of developing lymphoma?
6x neoplasia
7x lymphoma
147
What percent of cats with T cell GI lymphoma exhibit epitheliotropism?
40%
148
What percent of cats with lymphoma have pulmonary involvement?
12.8%
2% had no gross abnormalities (peribronchial-vascular invasion most common histo abnormality)
5% were B cell vs T cell
5% + FeLV
149
What is the immunophenotypic classification for Hodgkin's like lymphoma in cats?
T cell rich B cell lymphoma
150
Nasal lymphoma in cats are primarily what phenotype?
68% B cell (20% T cell, 12% mixed)
151
Renal lymphoma in cats in Australia are primarily what phenotype?
B cell
152
What percent of cats with renal lymphoma will have extension to the CNS?
40-50%
153
What percent of CNS lymphoma are FeLV+ antigeneic?
17-50%
154
Which area of the spine most commonly affected by CNS lymphoma?
Thoracolumbar
155
What percent of hypercalcemic cats are diagnosed with lymphoma?
10%
156
What is the reported sensitivity of PARR for feline lymphoma?
80% specificity has not been established
157
What percent of cats with LGL (6/8 were treated with CHOP) were reported to live longer than 6 months?
7.3%
158
What is the rerported MST of cats with LGL treated with chemotherapy?
63 d (2 months)
159
Methylation of the promoter region of p16 has been identified in ______% of feline B cell lymphoid tumors
33%
160
What is the reported sensitivity and specificity of splenic ultrasonographic appearance (ie a moth eaten parenchyma) for the diagnosis of feline malignancies?
Sensitivity 13.2%, Specificity 84.8%
Splenic mass>1cm, Sensitivity 21%, specificity 94.7%
161
Post-chemotherapy bowel perforation has been reported in cats with high grade gastrointestinal lymphoma. Which variable was associated with increased risk of perforation?
Magnitude of weight loss within 15-28 days of diagnosis
162
What is the increased risk associated with FeLV cats in developing lymphoma?
62 x
FIV infection associated with 5 x risk
163
Mast cells can be seen in up to ______% of aspirations from thymoma?
50%
164
What percent of renal lymphoma will be bilateral?
>80%
165
What percent of renal lymphoma will have AUS evidence of other organ involvement?
33%
166
What percent of renal lymphoma will have AUS evidence of other organ involvement?
33%
167
What percent of cats who relapsed following COP based protocol subsequently responded to single agent DOX?
22%
168
What was the response rate for cats with lymphoma treated with Lspar?
30%, much shorter asparagine depleting effect in cats (lost by 7 days)
169
A bone marrow aspirate with greater than ______% abnormal blast cells is sufficient to make the diagnosis of acute leukemia in cats?
30%
27% CR to COP based protocol
170
In cats with suspected CLL, infiltration of the bone marrow with more than ________% mature lymphocytes helps confirm the diagnosis?
20%, most are of T cell lineage and most are FeLV negative
171
ALL in cats is primarily what phenotype?
T cell, about 60-80% FeLV positive
172
What phenotype is most common with mediastinal lymphoma?
T cell
Nasal = B cell
173
What is the reported MST of 20 cats with high grade GI LSA when treated with surgical resection and CHOP based chemotherapy?
420 days
174
Nasal lymphoma immunophenotype?
3/4 B cell
175
What is the median survival time for FeLV positive cats with mediastinal lymphoma?
2-3 months
Young FeLV negative siamese cats with mediastinal lymphoma had durable responses of ~ 9 months
176
What percent of cats with lymphoma will respond to Elspar?
30%
177
Missense mutations in what genes have been identified in dogs with AML?
FLT3, C-KIT, RAS
178
What is the tendency for the myeloid:erythroid ratio to be in Polychythemia vera?
Normal
179
What are the markers for megakaryocyte lineage in dogs and cats?
Acetylcholinesterase, vWF/fVIII platelet glycoprotein, CD41
180
What are the markers for neutrophils?
Peroxidase, sudan black B, chloracetate esterase
181
What are the markers for monocytes?
Nonspecific esterases (alpha-naphithyl acetate esterase or alpha-naphthyl butyrate esterase) especially if they are inhibited by sodium fluoride
182
What is the marker for basophiles?
Omega exonuclease, + for chloracetate esterase activity
183
What are the markers for myeloid cells?
MPO and CD11b
184
What is the most common type of DNMT3L (methylation) mutation identified in dogs with AML?
Missense mutation in exon 7
185
What disorders are known to cause secondary thrombocytosis?
Iron deficiency anemia, chronic inflammatory diseases, recovery from severe hemorrhage, rebound from ITP, and absence of a spleen
186
You are treating a dog with chronic myelogenous leukemia. After inducing with hydroxyurea (20 mg/kg BID), what hematologic parameter is used to gauge your dose reduction?
Leukocyte count falls to 15000-20000 cells/uL
187
Philadelphia chromosome or BCL-ABL translocation between chromosomes 9 and 22 in humans with CML. What are the equivalent chromosomes in dogs with CML?
Chromosomes 9 and 26
188
What percent of dogs with MM will have abnormal PT/PTT?
50%
189
Hyperviscosity syndrome occurs in what percent of dogs with multiple myeloma? Which immunoglobulin is most frequently associated with this?
20-40% (IgM)
190
What percent of dogs with multiple myeloma develop Bence Jones proteinuria?
25-40%
191
What are the known negative prognostic factors in dogs with MM?
Hypercalcemia
Bence Jones proteinuria
Extensive bony lysis
192
Which IHC stains are typically used for extramedullary plasmacytosis?
MUM-1, IRF-4, thioflavin T
193
When is staging most important for extramedullary plasmacytosis?
Cutaneous plasmacytosis, solitary osseus plasmacytoma, GI extramedullary plasmacytoma (higher risk of metastasis)
Less important for cutaneous, oral, and colorectal plasmacytoma
194
What percent of cases with cutaneous plasmacytosis had LN or abdominal visceral involvement?
30%
195
What is the recurrence and metastatic rate for solitary cutaneous and oral plasmacytomas following surgery?
5% and 2% respectively
196
What is the MST for colorectal plasmacytoma treated with surgery +/- chemo?
15 months
197
What is the MST for Waldenstroms macrogaammaglobulinemia (IgM) treated with chlorambucil?
11 months, 77% RR
198
What percent of dogs had concurrent splenic and right atrial HSA on echocardiogram in one study?
8.7%
Previous necropsy studies suggest about 25%
199
What are the IHC markers for hemangiosarcoma?
VWf/fVIII related antigen or CD31/platelet endothelial cell adhesion molecule
200
What percent of grossly abnormal livers in dogs with confirmed splenic HSA were confirmed to contain HSA metastasis in one study?
50%
201
What is the MST for primary renal HSA?
9 months
202
What is the MST for retroperitoneal HSA?
37.5 d
203
What is the MST for dogs treated with splenectomy + AC +LMTP-PE?
273 d (9 month)
204
What percent of dogs with thymoma are reported to have paraneoplastic syndromes?
67%
40% ME with associated aspiration pneumonia
205
What percent of dogs will have a concurrent second tumor with thymoma?
27%
206
Hypofractionated radiation therapy has been described as a treatment for non-resectable canine thymoma. What was the reported median time to response following treatment initiation?
22 d
207
What is the percent of perioperative mortality in dogs and cats undergoing excision of thymic epithelial tumors?
Dogs 20%
Cats 22%
208
Which histologic factors were more common with atypical thymoma and thymic carcinoma compared to thymomas?
Pleomorphism, mitotic figures, capsular invasion, and higher stage disease.
IHC (GLUT-1, CD5, CD117, CK8/18) was not useful
209
With TVT if regression is going to occur, at what time is this typically seen?
Within 3-9 months
210
What percent of TVT metastasize?
5-17%, to regional LN or elsewhere
211
hat are the IHC markers for TVT?
Vimentin, lysoszyme alpha 1 antitrypsin (AAT), macrophage specific ACM1
212
Oncogenesis of TVT involves which 2 genes?
LINE-c-myc and p53
213
What is a reported paraneoplastic syndrome of TVT?
Erythrocytosis
214
What is the reported metastatic rate for TVT?
<15% (but might be higher as many are not staged)
215
What is the recurrence rate of TVT following surgical removal?
30-75% (marginal surgical excision not effective)
216
TVT's are unlikely to spontaneously regress after how many months?
9 months
217
Which tumor suppressor genes are inactivated with mesothelioma?
Cyclin dependent kinase inhibitor 2A (CDKN2A), BRCA1 associated protein 1 (BAP1), and neurofibromin 2 (NF2)
218
Sclerosing mesothelioma is associated with what signalment?
Male GSD
219
Which gene is mutated with renal cystadenocarcinoma and nodular dermatofibrosis?
Birt-Hogg-Dube (BHD) gene
The BHD gene codes for the tumor suppressor protein folliculin and mutations in this gene are thought to lead to loss of function. This disease is primarily seen in GSD. Also see uterine leiomyomas.
220
Which mutation is most common with chronic myelogenous leukemia in humans?
Philadelphia chromosome or BCR-ABL translocation between chromosomes 9 and 22. The analogous chromosomes in dogs are chromosomes 9 and 26 and BCR-ABL translocation, termed "Raleigh chromosome" has been reported in several cases of CML in dogs
221
Most common mutation in canine and feline SCC
P53
222
Which of the following has been shown to be a negative prognostic factor for canine HS?
Palliative therapy, disseminated HS, and concurrent use of corticosteroids (Dervisis et. al, 2016, VCO)
223
Which drugs have been associated with radiation recall?
Doxorubicin, taxanes, gemcitabine
224
In the 2016 paper by Giuffrida et al, what percent of tumors were reclassified on the basis of FVII-RAg/yWE immunoreactivity, from an original diagnosis of telangiectatic OSA to HSA?
20%
225
What is the most common phenotype for canine CLL?
T cell origin (CD3+, CD21-)
CD3+, CD4-, CD8+ (73% in one study, 91% in another)
226
What percentage of cats with acromegaly were male in SRT paper for feline acromegaly? (Wormhoudt et al 2018)
80%
226
In a recent study on IHC for nasal carcinoma and lymphoma in cats, what percent of samples required IHC to differentiate carcinoma from lymphoma?
7%
227
Markers for feline progressive histiocytosis?
CD1a, CD!!c/CD18, CD5, Iba-1, CD204
228
Which IHC markers are used to distinguish pheochromocytoma from adrenocortical carcinoma?
chromogranin A and synaptophysin
229
GIST IHC markers?
CD117, Dog-1, CD34, and SMA (+/-)
Desmin and S-100 NEGATIVE
230
Which IHC markers are positive with hemangiosarcoma?
Factor VIII (vWF), CD31/PECAM-1
231
Which IHC marker can confirm a diagnosis of hemophagocytic histiocytic sarcoma?
CD11d
232
Which IHC stain can differentiate between canine urinary bladder transitional cell carcinoma and other carcinomas?
Uroplakin III- expressed in more than 90% of canine TCC
233
IHC markers for MCT?
Vimentin (+)
Tryptase and CD117 (KIT)+
+/- chymase MCP-1, and IL-8 (+)
234
IHC marker for thyroid carcinoma (c-cell)
Synaptophysin (+) chromogranin (+) thyroglobulin (-)
235
IHC marker for thyroid carcinoma (epithelial)
Thyroglobulin (+)
236
What are the IHC markers for melanoma?
Melan-A, PNL2, Tyrosinase-related protein (TRP)-1 and TRP-2 +/- S-100, human melanoma black 45 (HMB45)
237
Feline cutaneous MCT response to lomustine?
20 cats: 2 CR, 8 PR = 50% ORR
238
Which anthracycline may be administered orally?
Idarubicin
239
What toxicity is associated with 5-FU in cats
Fatal CNS toxicity
240
Why is cyclophosphamide relatively platelet sparing?
High levels of aldehyde dehydrogenase in the bone marrow (which deactivates cyclophosphamide)
241
Which chemotherapy drugs are severe vesicants?
Doxorubicin, vinca alkaloids, mechlorethamin, actinomycin D, Tanovea
242
What is the active metabolite of cyclophsophamide?
Phosphoramide mustard
243
Which drugs are radiation sensitizers?
Carboplatin/cisplatin, actinomycin D, gemcitabine, 5 FU, etanidazole, metronidazole (+/- DOX)
244
What are the solvents used for paclitaxel and docetaxel respectively that allow for IV administration?
Paclitaxel = Cremophor EL
Docetaxel = Polysorbate 80
245
Which enzyme functions in alkylator induced DNA repair (eg. temozolomide)
MGMT (O6 methylguanine DNA methyltransferase)
Removes adducts from the O-6 position of guanine and transfers the alkyl group to a specific cysteine residue (acceptor site) on the enzyme -- renders it inactive
246
What is the reported MST for dogs with stage IV MCT? (Pizzoni et al VCO 2018)
110 d
Tumor diameter >3 cm and more than 2 metastatic sites, BM infiltration, and lack of tumor control at primary site were negative px factors.
247
Which breed is predisposed to cutaneous langerhans cell histiocytosis?
Shar Pei (35%)
- Onset of regression can take up to 10 months
- 50% euthanized due to lack of regression
- LN metastasis - no regression
248
What are the markers for reactive histiocytosis?
CD1a, CD11c, MHC class II, Thy-1 (CD90), and CD4 but NEGATIVE for E-cadherin. Histiocytoma is NEGATIVE for Thy=1 and CD4 but POSITIVE for E-caherin CD1a, CD11b, CD11c, MHC class II can only be done on fresh smears or snap frozen tissues
249
What cell type or cytokine is thought to mediate the regression of cutaneous histiocytoma?
CD8+ T cells
250
Which tumor suppressor gene most commonly mutated with histiocytic sarcoma?
CDKN2A/B
Also RB1 and PTEN
251
Why is p53 often present in high concentrations in tumors that carry mutant, defective p53 alleles?
Mutant p53 loses its transcription activating powers, unable to induce Mdm2 transcription. In the absence of Mdm2, p53 escapes degradation and accumulates.
252
Genetic instability in patients with hereditary nonpolyposis colon cancer occurs because of a deficiency in which DNA damage repair pathway?
Mismatch repair (MMR)
253
What is the definition of Linear Energy Transfer?
The average energy lost by a particle over a given track length.
254
What percent of dogs with MCT had GI ulceration on necropsy?
35-83%
255
Prognosis for dogs with MCT with bone marrow involvement?
43 d
256
What are the markers for MCT?
Wimentin (+), CD117+, chymase, MCP-1, IL-8
257
What percent of tissue shrinkage will occur for cutaneous tumors following formalin fixation?
30%
258
What is the ORR for Paccal Vet for canine MCT?
59%
259
Negative prognostic indicators for feline splenic MCT?
Anorexia, significant weight loss, and male gender
260
What are the top 3 most common intestinal tumors in cats?
Lymphoma
Adenocarcinoma
Mast cell tumor
261
Tumor cells located further than approximately ________um from vessels experience "diffusion limited" hypoxia as oxygen is consumed by the tumor cells more proximal to the vessels.
150um (Tannock and Hill)
262
What are some of the markers of cancer stem cells?
CD34- AML
CD44- breast cancer
CD133- glioma
263
Dogs with melanoma caudal to PM3 are ________ times more likley to die from tumor related causes compaired to dogs with tumors rostral to PM3
4.3x
Dogs with incomplete histo margins 3.6 times more likely to die of tumor related causes.
264
What is the MST of dogs with melanoma of the digit without lymph nodes or distant metastasis treated with digit amputation?
12 months
265
What percent of dogs with oral malignant melanoma will experience a complete remission when treated with RT?
51-69% (up to 70% according to new Withrow)
ORR = 82-94%
Dogs with tumors less than 5 cubic cm are more likely to achieve a CR
266
What percent of dogs with normal size lymph nodes and oral malignant melanoma had lymph nodes mets?
40%
267
What percent of dogs with oral melanoma treated with RT will develop bone necrosis?
8%
268
What is the local recurrence rate of dogs with microscopic disease of oral melanoma after incomplete surgical resection and radiation therapy?
26%
vs. 45% for those treated with RT in macroscopic disease setting
269
What are the local recurrence rates for manibulectomy and maxillectomy of OMM respectively?
22% = mandibulectomy
45% = maxillectomy
MST with surgery alone = 150-318 days, with 1 year survival of less than 35%
270
Melanoma typically is considered to have a high or low alpha beta ratio?
LOW - higher dose/fraction
Tumors that may have a lower a/B ratio including melanoma, prostatic tumors, STS, TCC, and OSA. Withrow pg 183 (2013)
271
In a study of 5 cats treated with RT for oral melanoma, what was the ORR and MST?
ORR = 60%, MST 146 d
One cat treated with carboplatin, one with carboplatin and mitoxantrone, one with melanoma vaccine.
272
What is the sensitivity and specificity for Ki67>19.5% to identify tumor related death due to OMM at 1 year?
Sensitivity 87%, specificity 85%
273
White cats in California are ______ times more likely to develop SCC
13.4 x
274
When PCR is used to amplify papillomavirus DNA, up to what percent of UV-protedcted SCC are positive?
76%
42% in SCC in regions exposed to UV radiation
275
What breeds are associated with multiple digital SCC?
Large breed dogs with black skin and haircoat: Standard Poodles, Black Labradors, Giant Schnauzers, Gordon Setters, Rottweilers, +/- dachschunds and flat coated retrievers
276
Which breed is predisposed to digital melanoma?
Scottish Terriers
277
What is the reported disagreement rate between pathologists when evaluating digital masses?
20%
278
What percent of canine SCC were positive for p53 overexpression?
30%
47.5% in feline SCC
279
What mutation was found with 100% of trichoepithelioma and pilomatricomas?
B-catenin
280
What percent of canine and feline SCC were positive for cyclin A?
44% canine, 90% feline
Cyclin D was rarely expressed in skin tumors of any type
281
Which marker is highly specific for BCC and helps to differentiate it from SCC or cystic solid ductular tumors in the diagnosis of BCC in humans?
BerEP4 +/- Cytokeratin 8
282
Which breeds are at increased risk for BCC in one study?
Cocker spaniels, poodles
283
What are the 3 histo subtypes of BCC?
Sold, keratinizing, clear cell
284
Which drug has been shown to be effective in treating multiple papillomas?
Azithromycin
285
What is the name for when SCC in situ appears in multiple sites?
Bowen's carcinoma or
Bowenoid carcinoma in situ (BISC) or
Multicentric papillomavirus-induced SCC
286
What is the name used for SCC in situ that arises as a consequence of UV exposure?
Actinic keratosis
Occurs in lightly haired skin with UV exposure, can occur as a solitary lesion. It is typically accompanied by solar elastosis and fibrosis of the skin, consistent with the effects of chronic UV exposure.
Highly positive for p53 expression compared to Bowenoid carcinoma in situ (BISC).
287
Which chromosome and gene is the effector transcription factor of hedgehog signaling cascade and has been reported to be associated with canine basal cell carcinoma?
Chromosome 10, GLI1 gene
288
What percent of dogs with digital SCC have bone lysis on radiographs?
80%
8.8% have metastasis at presentation, 23.2% eventually develop metastasis
289
What are the 2 immunosuppressive molecules expressed by T-reg cells and activated T cells and are the targets of check point inhibitors?
CTLA-4 and PD1
290
Mechanism of action of Imiquamod?
Activates TLR7
Has been used to treat BISC in 12 cats with a 42% CR
291
What percent of grade III PNST will invade the spinal cord?
50%
292
What percent of dogs develop recurrnece following hypofractionated RT for incompletely excised STS?
21%
293
What histologic subtype of rhabdomyosarcoma has a predilectionfor the urinary bladder in young, female, large breed dogs
Botryoid
St. Bernard possibly overrepresented. Grapelike appearance. In humans alveolar histotype has the worst prognosis and botryoid has the best.
294
What percent of dogs with GI leiomyosarcoma will have intestinal perforation with localized to diffuse peritonitis
50%
50% metastatic rate
295
What is the signalment and location most commonly seen with GI leiomyoma?
Male, predilection for the stomach
296
Three paraneoplastic syndromes seen with GI leiomyoma and leiomyosarcoma
Hypoglycemia
Nephrogeneic diabetes insipidus
Secondary erythrocytosis
297
Which histologic type of liposarcoma has the highest metastatic rate?
a. Well differentiated
b. Mysoid
c. poorly differentiated (round cell)
d. pleomorphic
e. dedifferentiated
Pleomorphic
298
What are the IHC that help differentiate lymphangiosarcoma from hemangiosarcoma?
LYVE-1 and PROX-1
299
MST of liposarcoma with wide excision?
1188 days
300
MST of liposarcoma with marginal excision?
650 days
301
ST of dogs with GIST or leiomyosarcoma with metastasis?
21.7 months (37.4 months without)
However other reports found metastasis signficantly decreases survival time to much less than 21.7 months
302
MST ofr dogs with splenic leiomyosarcoma
8 months
303
In one retrospective study of dogs with incompletely resected STS who underwent re-excision, how many had histologic evidence of residual tumor?
22%
304
What is the recurrent rate for grade II incompletely excised STS?
34% (7% for grade 1 and 75% for grade III)
305
Cumulative doses higher than _______Gy are recommended for incompletely excised STS and local tumor control is better with higher cumulative doses.
50 Gy
306
What is the median time to local recurrence for STS in dogs?
1 year (368 days)
307
In a study of 39 dogs with incompletely excised STS treated with orthovoltage and doxorubicin as a radiation sensitizer, what MI was associated with higher risk of local tumor recurrence and shorter survival time?
Mitotic rate greater than 9/10 HPF
308
What is the median time to metastasis for dogs with STS?
1 year (365 days)
309
What is the MST for dogs with STS MI>20?
236 days (5 x more likely metastasis, 2.8 x more likely tumor related death
310
What are some of the markers for FISS?
PDGRF, EGF, TGF-B, C-jun, p53
311
What percent of cats with FISS will have grade 3 tumors?
60% (only 5% grade 1)
312
What is the bluish gray foreign material that has been identified in the macrophages in peripheral inflammatory cell infiltrates assocaited with FISS?
Aluminium and oxygen
Aluminium hydroxide is one of several adjuvants used in currently available feline vaccines
313
With FISS, how much does the volume of tumor increase based on contrast enhanced CT compared to calipers on physical exam?
TWICE
314
What percent of FISS will recur following surgery and RT?
28-45%
315
Hi-low oral FSA tends to occur in what anatomical location?
Hard palate and maxillary arcade between the canine and carnassial teeth
Large breed dogs
316
How much of the cortex needs to be destroyed before bone lysis is evident on radiographs?
40%
317
What is the overall reported metastatic rate for MTB?
58%
318
Which breeds is canine oral eosinophilic granuloma suspected to be heritable in?
Siberian Husky and Cavalier King Charles
319
What is the MST of dogs with oral melanoma <2cm with no evidence of metastasis treated with surgery?
511 days
320
What are 3 main negative prognostic indicators for dogs with oral melanoma?
Non-rostral location
Bone lysis
Macroscopic disease
No risk factors MST = 21 months, 1 risk factor MST = 11 months, 2 risk factors MST = 5 months, All risk factors MST = 3 months
321
What is the most common location for oral SCC in dogs?
Rostral mandible
322
What paraneoplastic syndrome has been reported with Spirocerca lupi associated esophageal sarcoma?
Hypertrophic osteopathy
Usually affects the caudal thoracic esophagus, can be associated with thoracic spondylitis, microcytic hypochromic anemia and a neutrophilia
323
Which test may aid in the diagnosis of spirocerca lupi associated esophageal sarcoma?
Fecal flotation test
324
Loss of which protein expression is associated with pancreatic carcinoma (especially poorly differentiated)
Claudin 4 and Claudin 5
325
Which breeds are predisposed to gastric cancer?
Belgian shepherds
Norweigian lundehunds
Dutch Tervueren shepherds
Males are more commonly affected
326
Which tumor has been reported to metastasize to the tests?
Gastric and intestinal adenocarcinoma
327
What is the reported rate of metastasis at necropsy for gastric adenocarcinoma?
70-80%
328
Where do gastric leiomyomas occur most commonly?
Cardia
329
Where do gastric adenocarcinomas most commonly occur?
Lesser curvature and pyloric antrum
330
What percent of dogs with HCC have additional tumors?
20% - most were benign and endocrine in origin
331
Which signalment may be overrepresented for HCC?
Male, mini schnauzers
332
What is the metastatic rate for massive HCC?
0-37%
333
What cells do neuroendocrine tumors arise from?
Neuroectodermal cells
334
What histochemical stain is used to differentiate neuroendocrine tumors (carcinoids) from carcinomas?
Silver stain (Withrow pg 407)
335
What is the most common type of primary liver sarcoma in dogs? Cats?
Dogs = leiomyosarcoma
Cats = hemangiosarcoma
336
Which tumor can be identified with the Grimelius histochemical stain?
Neuroendocrine tumor (Pascual's Grimelius, Sevier-Munger)
337
What percent of dogs and cats undergoing liver lobectomy require blood transfusion?
Dogs 17%
Cats 44%
Hanson et al JAVMA 2017
338
Which cat breed is 8 x more likely to develop intestinal adenocarcinoma?
Siamese
339
Most commonly reported signalment for intestinal MCT in the dog?
Male maltese
340
Which tumors are most likely to develop in the cecum?
Leiomyosarcoma or GIST
341
What cells do GIST arise from?
Multipotent stem cells phenotypically similar to interstitial cells of Cajal
342
What percent of previously diagnosed leiomyosarcomas in the dog were reclassified as GIST using IHC for CD117/KIT?
66%
and only 7% of GIST metastasized
343
Where do leiomyomas most commonly occur?
Stomach
344
Which tumor was reported in association with paraneoplastic alopecia and Cheyletiella infection?
Intestinal carcinoma with abdominal carcinomatosis
345
What paraneoplastic syndrome is seen in dogs and cats with intestinal T cell lymphoma? What is the proposed cause?
Hypereosinophilia and eosinophilic tumor infiltrates
Suggested cause is IL-5 secretion by the neoplastic lymphocytes
346
Which GI tumor was associated with a paraneoplastic syndrome of erythrocytosis and erythropoietin mRNA protein production by tumor cells?
Cecal leiomyosarcoma
347
What clinicopathologic abnormality is detected in up to 85% of cats with nonlymphomatous intestinal tumors?
Elevated ALP
348
What paraneoplastic syndrome has been reported in dogs with rectal tumors?
Neutrophilic leukocytosis
349
What breeds may be predisposed to perianal adenoma?
Cocker Spaniels, Beagles, Bulldogs, and Samoyeds
350
Which breed may be predisposed to anal sac adenocarcinoma?
English Cocker Spaniel
In male dogs -- neutering may increase risk
351
What is the rate of metastasis for perianal adenocarcinoma?
15%
Possibly occurs later in the course of disease?
352
What is the overall incidence of bilateral anal sac adenocarcinoma (either simultaneous or temporally separated)
14%
353
What is the overall incidence of hyperclacemia with AGASACA?
27%
354
In a study of dogs with splenic mass based on body weight, which were more likely to be diagnosed with HSA?
Greater than 27.8 kg
355
What is the most common immunophenotype for canine chronic lymphocytic leukemia?
CD8+ T cell
356
What percent of normal lymphocytes are CD8+ T cell?
25-35% (compared to 5-20% for B cell)
357
Which bacterial infection can result in expansion of a phenotypically homogenous population of lymphocytes, making it difficult to distinguish from neoplasia?
E canis - expansion of CD8+ T cells that have LGL morphology
Anne Avery, VCP 2004, molecular methods to distinguish reactive and neoplastic lymphocyte expansions
358
Which molecular test has been developed to identify differences between chromosomes in different cells by detecting amplifications or deletions of segments of DNA (eg. gains and losses in chromosome number)?
Comparative genomic hybridization
359
Which assay is most often used to identify HER2 status of breast cancers and N-myc amplification in neuoblastoma?
FISH
360
After a certain number of population doublings cells undergo senescence and cease dividing although generally retaining viability. This is referred to as _______?
The Hayflick Limit
361
What is the name of the statistical adjustment that helps alleviate the risk of detecting a deifference due to chance alone (type 1 error) when analyzing large numbers (eg 10000 genes in 20 patients) by dividing the threshold p-value by the number of tests to be performed?
Bonferroni correction
362
What is the name of the statistical adjustment that controls the percentage of tests that will be expected to be false positives and provides an adjusted p-value (q-value)?
False discovery rate
363
What is the name for the descriptive epidemiology term that refers to the number of new cases of a disease observed in a defined population in a specific time period divided by the population size?
Incidence rate
364
What is the name for the descriptive epidemiology term that refers to the number of deaths caused by the disease during a specific time period divided by the population size?
Mortality rate
365
Which term is used to describe the number of deaths caused by a specific disease in a defined population divided by the number of individuals who have been diagnosed with that particular disease in a fixed time interval?
Case fatality rate
366
What is the term used to describe the proportion of a population that has a disease at a specific time point, (cases divided by population size) where cases include both new cases of disease and the number of previously diagnosed cases who are still alive in a population?
Prevalance
Prevalance is affected by the mortality of the disease, for example: although lung cancer is one of the most common cancers, its prevalence ranks lower then that of prostate or breast cancer because lung cancer is such a lethal disease. Cancer incidence may better reflect how common cancer develops in a population.
367
What is the term used to describe the risk in a group exposed to a potential disease related factor and compares it to the risk in a group that is not exposed (or has lower exposure) to the factor
Relative risk
368
What is the most probably cellular outcome following DNA damage?
Repair the damage by DNA repair enzymes
369
During which phases of the cell cycle does homologous end recombination work?
S and G2
370
In which type of DNA repair is BRCA1 and BRCA2 important?
Homologous end recombination
371
Which DNA repair pathway typically suppresses micro satellite instability?
Mismatch repair
Mutations in MMR associated with hereditary nonpolyposis colon cancer typically causes microsatellite instability
372
Which phosphorylated protein has been shown to be a reliable surrogate marker for DNA double strand breaks (DSBs) in cells?
Histone yH2AX
373
RAD52 is associated with which DNA repair pathway?
Homologous recombination
374
KU70/80 proteins are associated with which DNA repair pathway?
Nonhomologous end joining (NHEJ)
375
What is the approximate agreement rate between MRI and CT for staging dogs with nasal tumors?
5/6 were in agreement (83%)
Though MRI resulted in a higher tumor volume (median 18%) in 5/6 dogs and greater likelihood of detgecting meningeal involvement
376
Which cytokine is believed to be involved in inducing radiation fibrosis?
TGF - beta
377
Which 2 rare paraneoplastic diseases have been reported with nasal tumors in dogs?
Erythrocytosis and hypercalcemia
378
Bilateral carotid artery ligation can palliate the symptoms in dogs with nasal tumor related epistaxis for up to _______ months or longer
greater than 3 months
379
What percent of dogs will develop late effects when treated with SRT for nasal tumors?
30-40%
380
What is the most common lung tumor in dogs?
Bronchoalveolar carcinoma (84%)
381
What is the most common lung tumor in cats?
Adenocarcinoma (60-70%)
382
What percent of canine pulmonary malignant tumors had evidence of local vascular or lymphatic invasion?
71%
383
What percent of dogs with pulmonary tumors have tumors found in multiple lung lobes?
37.1%
384
What percentage of cats with primary lung tumors show GI signs on presentation?
20%
385
What percent of cats had evidence of pulmonary metastasis of primary pulmonary tumor on CT?
53%
386
Which of the followin gchemotherapy protocols has proven to have a greater than 50% reduction in gross pulmonary adenocarcinoma in dogs?
Vindesine + cisplatin
387
What is the complication rate for CT guided lung biopsy?
43% (pulmonary hemorrhage and pneumothorax)
388
Which mutation has been identified in p53 of canine OSA?
Missense mutation of exons 4-8 in 25-47%
389
Which antibiotic has been shown to reduce canine OSA cell viability in vitro?
Enrofloxacin - regardless of p53 mutational status or downstream activity
390
What is the metastatic rate of OSA affecting the head (mandible, maxilla, and skull)
37%
391
What is the MST for rib OSA following rib resection with and without chemotherapy?
Rib resection alone = 3 months
Rib resection + chemo = 8 months
392
What is the MST for OSA of the canine scapula treated with subtotal scapulectomy surgery and chemotherapy?
8.2 months (246 days) (DFI = 210 days)
393
What is the MST of OSA distal to the antebrahciocarpal or tarsocrural joints?
MST = 466 days = 15.5 months
394
What is the MST for vertebral OSA treated with surgery, RT, and chemo?
4 months (8.7 mo in another study)
Sx alone = 42 days, Sx + chemo = 82 days
Dixon et al 2019 VCO
395
What is the MST for mammary gland OSA treated with surgery alone?
3 months. Most died of pulmonary metastasis (62.5%)
396
What gene mutation has been detected in BMD with histiocytic sarcoma?
PTPN11 (MAP Kinase pathway) -- 36.67%
397
In a study by Barrett et al VRU 2014 what percent of dogs with histiocytic sarcoma with pulmonary involvement had internal air bronchograms?
57% (12/21)
398
In a study by Barrett et al VRU 2014, which lung lobes were most commonly affected by HS?
Right middle and left cranial
399
In a study by Marlowe et al 2018 VCO regarding primary pulmonary histiocytic sarcoma in dogs, how many were found incidentally?
25%
400
What are the 4 negative prognostic indicators with histiocytic sarcoma?
Anemia, thrombocytopenia, splenic involvement, hypoalbuminemia
401
Which region of bone is most suitable for limb spare?
Distal radius and ulna
B/c function following carpal arthrodesis is good
402
Which anatomical location for OSA is typically seen in young dogs (mean age 4.5-5.4 years)
Rib
403
What type of fluid should be given for diuresis with cisplatin and why?
NaCl
B/c in a low chloride environment such as urine, cisplatin undergoes aquation and attacks renal epithelium. Maximizing chloride content with NaCl will help reduce aquation and thereby prevent renal damage.
404
What is the mechanism of action of bisphosphonates?
Inhibits Farnesyl diphosphate (FPP) synthase. FPP prenylated proteins are required for osteoclast function and survival
405
What is the MST for dogs with telangiectatic OSA (confirmed via IHC) undergoing surgery +/- chemotherapy?
7 months (213 days)
406
What percentage of telangiectatic osteosarcomas were reclassified to hemangiosarcoma after IHC with factor VIII-RA/vWF?
407
Which type of OSA carries the best prognosis?
Parosteal
408
Primary appendicular HSA primarily affects which bone?
Tibia
409
What disease is commonly associated with MCE in cats?
FeLV/FIV
410
What is the MST of cats with OSA treated with surgery alone?
24-44 months
Low metastatic rate (5-10%) so chemotherapy not recommended
411
NF-kappaB is inactivated and sequestered in the cytoplasm by?
IkappaB
412
NFkappaB is made up of which 2 proteins?
RelA (p65) and p50
413
c-KIT exon 11 is located in which part of the chromosome?
Juxtamembrane domain
This domain is responsible for preventing the kinase from being activated - therefore with mutations in exon 11 of this domain such as internal tandem duplications seen with MCT, there is a loss of autoinhibitory activity of the juxtamembrane domain and the kinase becomes constitutively activated
414
Which 2 markers are primarily used to identify T-reg cells?
FoxP3 and CD25
T-regs are an immunoregulatory subset of CD4+ T cells
415
Which two cytokines are secreted by iTregs and responsible for most of their immunosuppressive action?
TGF-beta and IL10
416
Which cytokine can act as a tumor suppressor AND promoter?
TGF-beta
417
Tyrosinase is an example of which type of tumor associated antigen?
Differentiation antigen
418
HER-2/neu is an example of which type of Tumor Associated Antigen?
Overexpressed antigen
419
V600 BRAF mutation is an example of which type of Tumor Associated Antigen?
Mutation antigen
420
What is the overall diabetic remission rate in cats with pituitary tumors and uncontrolled diabetes mellitus when treated with SRT?
32%
421
Which clinicopathologic finding is common in cats with hepatobiliary tumors?
Azotemia
422
Which protein can be found in the serum of up to 75% of dogs with HCC and 55% of dogs with bile duct carcinoma?
Alpha fetoprotein (differentiation antigen)
However it has limited value in the diagnosis and treatment of canine HCC as serum levels are also increased in other types of liver tumor such as bile duct carcinoma and lymphoma, and nonneoplastic hepatic disease.
423
In a study of 19 dogs undergoing US guided FNA of an adrenal lesion, what percent had side effects?
5% (1/19) = ventricular tachycardia consistent with pheochromocytoma
424
What is the most common clinical sign associated with Conn's Syndrome in cats?
Muscle weakness secondary to hypokalemia
Aldosterone secreting adrenal tumor
425
What is the mortality rate for cats undergoing adrenalectomy for neoplasia?
20%
20/26 cats (77%) survived in one study, and 8/10 (80%) in another (Holt et. al JVIM 2014)
426
What is the most common intraoperative complication in a retrospective of 86 dogs undergoing adrenalectomy? Barrerra et. al 2013 JAVMA
Hypotension (62%) followed by blood loss requiring transfusion (26%)
On multivariate analysis of risk factors for short term survival, extensive invasion was the most important risk factor
427
In a study of 52 dogs undergoing adrenalectomy for adrenal tumor, what factors were significantly associated with shorter survival time?
Major axis length >5 cm
Metastasis
Vein thrombosis
428
In dogs undergoing VMAT SRT for adrenal tumors with vascular invasion, what was the MST?
1030 days (34 months = 2.8 years)
The endocrine profile normalized in 2/3 dogs with cortisol secreting tumors. Radio-toxicities were mild and self-limiting. All dogs experienced progressive shrinkage of the tumor (mean reduction 30%)
429
What percent of dogs developed hypothyroidism following RT for thyroid carcinoma?
47%
Development of hypothyroidism was not associated with the radiation protocol used, and median time to diagnosis of hypothyroidism was 6 months
430
What is the sensitivity and specificity of CT for determining histopath invasion of thyroid carcinoma?
Sensitivity 70%
Specificity 100%
430
Which activating missense mutation has been identified in dogs with thyroid carcinoma and has also been described in humans?
K-RAS
431
What is the MST of dogs with bilateral thyroid tumor undergoing thyroidectomy?
38 months
432
What is the MST of dogs with sublingual ectopic thyroid carcinoma treated with various modalities (surgery and/or I-131)
19 months (562 days)
Compared to other locations, these dogs were significantly younger (9 years) and less likely to have metastasis (15%-30%)
433
Mineralization of the kidney occurs when the calcium x phosphorus product exceeds ______?
70
434
What percent of dogs developed hypocalcemia following surgical excision of parathyroid carcinoma?
47%
435
What percent of canine insulinomas metastasize?
50%
436
What is the reported metastatic rate of gastrinoma?
85%
437
What disease is associated with glucagonoma?
Necrolytic migratory erythema (NME)
438
Which treatment for insulinoma acts by inhibiting secretion of insulin?
Octreotide
439
Tumors of which organs are associated with multiple endocrine neoplasia type 2 (MEN2)?
Medullary thyroid carcinoma
Pheochromocytoma (adrenal medulla)
+/- parathyroid tumor
440
Inhibin alpha is a sensitive and specific marker for which female reproductive tumor?
Granulosa-theca cell tumor (GTCT)
Inhibin-a is a glycopeptide synthesized in gonadal cells of the ovaries, and inhgibits pituitary secretion of follicle stimulating hormone (FSH)
441
What is the most common ovarian tumor in cats?
Granulosa-theca cell tumor
442
What is the most common ovarian tumor in dogs?
Ovarian adenocarcinoma
443
Which breeds have been shown to overexpress BRCA1 mutations with mammary carcinoma?
English springer spaniels, shih-tzu
444
What are the risk factors for canine bladder cancer? List 5.
1. Older generation flea control products and lawn chemicals
2. Obesity
3. Cyclophosphamide exposure
4. Female sex
5. Breed associated risk (Scottish Terrier)
445
In a study by Hanazono et. al., what was the expression of p63, B-catenin, and Ki67 in TCC compared to normal urinary bladder and polypoid cystitis?
p63 - significantly lower in TCC
B-catenin - significantly lower in TCC
Ki-67 - significantly higher in TCC
In TCC, low p63 expression was significantly related to the presence of vessel invasion, metastasis, as well as short survival time
446
What is the MST for dogs undergoing partial cystectomy and daily piroxicam for urothelial carcinoma, with or without chemotherapy?
772 days (26 months, 2.1 years)
76% had local recurrence within the bladder
11% had abdominal wall mets (median 150d later)
447
In a study by Blackburn et al., 2013 on urethral stent placement for canine iUC what was the only variable signficantly associated with extent of urinary incontinence?
Duration of stranguria before SEMS placement
448
In a study by blackburn et al 2013, on urethral stent placement for canine iUC, what was the MST after SEMS placement?
78 days
Treatment with NSAIDs before and chemo after SEMS placement increased MST to 251 days
64.3% developed incontinence (26% severe)
449
In a study by McMillan et al 2012 on self expanding nitinol urethral stent placement for canine iUC in 19 dogs, what percent of dogs developed incontinence?
39% (7/18, in 1 dog stent placement was unsuccessful)
MST = 78 (same as the Blackburn study)
450
What percent of iUC are positive for HER2?
56-61%
HER2 expression was not associated with any clinical factors
451
In a study of dogs with presumed primary renal lymphoma, what was the MST?
12 days (47 days for those that responded to chemotherapy - 50% PR seen). Erythrocytosis in 51%, azotemia in 86%.
452
What is the most common site of bone mets in dogs with iUC?
Lumbar vertebrae (47% of dogs with boney mets)
Charney et al 2016 Vet Path
9-14% of dogs evaluated had bone mets
453
What percentage of canine urothelial carcinomas exhibit a BRAF mutation (V595E)?
>80% (Withrow)
75% on ddPCR 83% of both iUC and PC in free catch urine, Mochizuki et al 2015 Plos One
454
What percent of dogs with transitional cell carcinomas are reported to develop a urinary tract infection during chemotherapy?
55%, primarily staphylococcus and e coli
455
What is the median PFI for dogs with RCC undergoing partial cystectomy +/- various nonsurgical treatments? (Marvel et al 2017)
235 days
Overall MST =348 days
MST for dogs treated with sx + piroxicam (w/or without chemo = 722 days)
Prognostic factors significant for PFI were full thickness excision and frequency of piroxicam administration.
456
What percentage of dogs with DIC are diagnosed with underlying neoplasia?
40%
457
Which enzyme is inhgibited by zoledronate to produce its anti-osteoclast activity?
Farnesyl diphosphate synthase
458
What percent of cats with thrombocytopenia will have a diagnosis of neoplasia?
20%, most commonly associated with lymphoma
459
Other than PTH-rp, what are mediators of hypercalcemia of malignancy?
IL-1B, TGF-B, receptor activator of nuclear factor kappa-B (RANKL), tumor associated prostaglandins (PGE1/2)
460
Whichu mutation has been associated with polycythemia vera in canine patients?
JAK2
5/6 dogs
461
Paraneoplastic eosinophilia is suspected to be a result of overproduction of which cytokines?
IL5, IL13, IL17, GM-CSF and eotaxins
462
What tumor is associated with hepatitis B virus in humans?
HCC
463
Which protein associated with papillomavirus targets p53 for degradation in the ubiquitin pathway?
E6
464
Which protein associated with papillomavirus binds to and inhibits pRB?
E7
465
The pathogenesis of PNS fever is predominantly due to excessive production of which cytokines?
IL1, IL6, TNF-a and interferons
466
Which virus is associated with Burkitt's lymphoma in humans?
Epstein Barr virus
Also associated with some types of Hodgkin Lymphoma, gastric carcinoma, and nasopharyngeal carcinoma
467
DNA base damage due to endogenous oxidative processes or exogenous DNA damage (ionizing radiation) is repaired by?
Base excision repair pathway
468
Which species of animal has been linked to a viral (hepadnavirus) etiology of hepatocellular carcinoma?
Woodchuck
469
What is the name of the paraneoplastic syndrome in humans, (primarily seen with lung tumors), similar to myasthenia gravis, but instead is a result of calcium channel autoantibody formation causing poor calcium influx from the presynaptic neuromuscular junction?
Lambert Eaton Syndrome
470
In humans, human herpes virus 8 (HHV-8) is associated with which vascular tumor of endothelial cells?
Kaposi sarcoma
Most common in HIV patients
471
Which cells are affected by HIV?
CD4+ T cells
472
Chronic tumor retroviruses do not contain viral oncogenes but transform infected cells through a mechanism known as __________?
Insertional mutagenesis
473
FIV/HIV is what type of virus?
Retrovirus - classified as a lentivirus
474
What percent of intact female dogs present with more than one mammary tumor at diagnosis?
70%
475
What is the reported cytologic sensitivity and specificity for a malignant mammary tumor diagnosis?
Sensitivity = 88%, Specificity = 96%
476
What percent of canine malignant mammary tumors have been found to be HER2 positive (according to withrow 5th edition)
17-29% (using HercepTest scoring system used in human medicine)
Overexpression of HER2 seen in 20-25% of human BC patients.
477
Increases of which cytokine are related with an increased risk of death from canine mammary tumors?
IL10
Estela et al 2016 VCO
478
Paget's disease?
Carcinoma with epidermal infiltration of the nipple in women. Paget like disease exists in the dog as well.
The carcinoma is present within the mammary gland, and carcinoma cells, either as individual cells or small aggregates, are present within the epidermis of the nipple.
479
What 3 criteria make up the Elston and Ellis Mammary Tumor Grading for dogs?
1. Tubule formation (>75%, 10-15%, <10%)
2. Nuclear pleomorphism (mild, mod, marked)
3. MI (0-9, 10-19, >20)
Grade 1 = 3-5
Grade 2 = 6-7
Grade 3 = 8-9
(Withrow pg 543)
480
What are the 3 factors that are most consistently reported to be associated with prognosis for canine mammary tumors?
Tumor size, lymph node involvement, WHO stage (Withrow page 543)
481
Which of the following features have the highest level of evidence to support the addition of chemotherapy for dogs with mammary carcinoma?
Lymph node metastasis
Size >3 cm/40cc
Withrow pg 547, table 27-5
482
What was the most common alteration seen on kidney biopsies of dogs with mammary carcinoma?
Focal glomerular mesangial matrix seen in 60%
483
What are the 3 main risk factors for mammary tumors in dogs and cats?
Age, breed, hormonal influence
484
Which drug when given perioperatively, significantly prolonged the disease free survival and overall survival in bitches with grade 2-3 carcinomas compared to controls?
Desmopressin (DDAVP)
485
What percent of cats with mammary tumors have more than one tumor at diagnosis?
60%
486
What Ki-67 index has been established as prognostic in feline mammary carcinoma?
>14%
Significantly associated with large tumor size, poor differentiation, presence of necrosis, estrogen receptor negative, HER2-negative, and shorter overall ST
Ki-67 expression also strongly and positively correlated with both regional and distant metastasis
487
What is the reported MST of feline mammary carcinoma treated with unilateral radical mastectomy and doxorubicin based chemotherapy?
1988 days (vs 414 days with chain mastectomy alone)
488
How does ovariohysterectomy decrease the risk of mammary tumor development in cats? Compare the decrease in risk when OHE is performed <6 months, between 7-12 months, and between 13-24 months of age
91%, 86%, 11%
489
What is the most common complication in dogs following hypophysectomy?
Diabetes insipidus (53%)
490
Which tumor in humans can be caused by loss of tumor suppressor gene von hippel lindau (VHL)?
Renal cell carcinoma
Loss of the VHL protein leads to constitutive activation of HIF, as VHL, in the presence of oxygen, ubiquinates the alpha subunit of HIF, targeting it for degradation
491
What is the most common B-RAF mutation in humans? What is the canine equivalent?
V600E substitution in the kinase activation loop (90%), the equivalent in dogs (eg iUC) is V595E
492
What is the target of vemurafenib?
BRAF
493
Which guanine nucleotide exchange factor (GEF) is important in the MAP kinase pathway and promotes GTP loading of RAS?
Son of Sevenless (SOS)
Works together with adaptor protein GRB2 at the ligant activated receptor on the cell membrane.
494
Which viral particle was involved in the discovery of p53?
SV40 viral T antigen
495
Which protin binds to and induces ubiquitination of HIF-a?
Von Hippel Lindau protein (VHL)
496
True or false: Insulinomas in ferrets rarely metastasize
True. Long term survival seen with surgical resection, though recurrence is relatively common
497
What are the 2 most common tumors in ferrets?
Pancreatic islet cell tumor (insulinoma)
Adrenal cortical carcinoma
498
What are the clinical signs of adrenal tumor in ferrets?
Cutaneous - bilateral truncal alopecia and patchy hair loss
Behavioral - return to intact sexual behaviour such as mounting, urine marking, and aggression
Reproductive - Vulvar swelling in up to 90% of neutered Jills. Prostatic cysts in males resulting in dysuria
499
