Withrow Flashcards
1
Q
True or false - cats can develop perianal adenoma/perianal adenocarcinoma
A
False - don’t have perianal sebaceous glands
2
Q
Development and progression of perianal adenomas is _____ with growth stimulated by ______ and suppressed by _____
A
Sex hormone-dependent androgens estrogens
3
Q
Perianal adenomas in female dogs occur almost exclusively in ______
A
spayed animals - have low estrogen = no tumor suppression
4
Q
T/F: Perianal adenocarcinomas are hormonally dependent?
A
False
5
Q
Rate of metastasis for perianal adenocarcinomas
A
Low, <15%
6
Q
Most frequent sites of mets from perianal adenocarcinomas? Less frequent?
A
Regional LN and lungs; liver, kidney, bone
7
Q
What five things are increased histologically/molecularly in perianal adenocarcinomas compared to adenomas?
A
Increased proliferating cell nuclear antigen (PNCA), apoptotic corpuscles, Ki67, VEGF, serum magnesium levels
8
Q
What is needed to definitively tell perianal adenoma from adenocarcinoma?
A
Incisional bx
9
Q
What IHC can help differentiate perianal adenoma from adenocarcinoma?
A
Monoclonal Ab against carcinoma-associated Ags 4A9, 1A10; PCNA, Ki67
10
Q
What can help differentiate a perianal adenocarcinoma from AGASACA?
A
cytokeratin expression patterns
11
Q
What margins can perianal adenomas be removed with?
A
Minimal margins, <1cm
12
Q
Other than surgical removal of the primary tumor, what else is recommended for treatment in dogs with perianal adenomas?
A
Castration
13
Q
What if a perianal adenoma is diffuse or too large to be removed? Treatment?
A
Surgical staging - castration first, may shrink tumor Cryosurgery CO2 laser ablation Hyperthermia RT ECT
14
Q
What is the repoarted response rate for perianal adenomas treated with ECT
A
>90%, 65% CR
15
Q
Do perianal adenocarcinomas respond to castration?
A
Nope
16
Q
What has a significant influence of DFI and OSTs for dogs with perianal adenocarcinoma?
A
Stage of tumor - T2 tumors (<5cm) do better
17
Q
2-year control rate for T2 perianal adenocarcinoma treated with surgery? Also, what is a T2 tumor?
A
<5cm >60%
18
Q
MST for dogs with LN or distant mets from perianal adenocarcinoma
A
7mo (but aggressive therapy not pursed for most dogs)
19
Q
What breeds have an increased risk of AGASACA?
A
Spaniels (particularly English cocker spaniels) German Shepherds Alaskan malamutes Dachshunds
20
Q
Gender/neuter status assoc. with risk of AGASACA?
A
Neutering may be associated with increased risk for males
21
Q
What are the three histologic patterns of AGASACA?
A
Solid Tubules/Rosettes/Pseudorosettes Papillary
22
Q
Which are the most common histologic patterns of AGASACA
A
solid and tubules/rosettes/pseeudorosettes in 95%
23
Q
What is the rate of bilateral AGASACA (simultaneously or temporally separated)
A
up to 14%
24
Q
Rate of paraneoplastic hypercalcemia in dogs with AGASACA?
A
16-53%
25
Mediator of hypercalcemia in canine AGASACA?
PTHrp from neoplastic tissue
26
Overall rate of mets for dogs with AGASACA? LN? Distant?
Overall: 26-96% LN 26-89% Distant 0-42%
27
What are the less common sites of AGASACA mets?
heart, omentum, stomach, adrenal glands, panc, kindeys, Ubladder, mediastinum
28
What has been associated histologically with risk of metastasis at diagnosis for canine AGASACA?
Marked peripheral infiltration into surrounding tissue, LV invasion, solid pattern
29
Does high or low levels of E-cadherin expression in AGASACA correlate with a better survival time?
Higher
30
Rate of mets from AG melanoma in dogs?
4/8 sublumbar LN, 1/11 pulmonary
31
Rate of mets from regional LN for feline AGASACA?
20%
32
Have bilateral AGASACA been reported in cats?
Nope
33
What percentage of dogs have an AGASACA be an incidental finding?
up to 47%
34
What is the most common clinical sign for cats with AGASACA?
Perineal ulceration or discharge
35
What IHC staining can confirm AGASACA dx if needed?
Cytokeratin pattern CK7+/CK14-
36
What was shown to be the only consistently abnormal feature of abdominal malignant LNs?
Size
37
What three LN centers can be involved in AGASACA
medial and internal iliac, sacral
38
What is the complication rate after local surgery for AGASACA and what is the most common complication?
5-24% wound dehisence, rectal perforation, rectocutaneous fistulation, incisional infection, transient fecal incontinence
39
What can help limit the complications of surgical removal of AGASACA
Smaller anoplasty - previous studies showed 40-60% rate of fecal incontinence when 120-270 degree anoplasties performed
40
Complication rate of LN extirpation for dogs with AGASACA?
0-12% - hemorrhage, uncresectable LN, LN rupture and abdominal wall dehisence
41
T/F: treatment of recurrent AGASACA or progressive nodal mets is not recommended for dogs as it does not improved survival
False
42
When can you pursue splenectomy for AGASACA?
If confirmed mets to spleen + context of slowly progressive dz and no other mets
43
What drugs have demonstrated antitumor activity in gross disease setting for AGASACA in dogs
carbo, cisplat, actinomycin D
44
Measurable response rates for dogs with AGASACA with bulky disease treated with RT (hypofx or fx protocols)?
38-75%
45
Over what radiation dose per fraction are late radiation side effects more likely to occur?
3Gy
46
Palliative RT protocols result in an improvement in clinical signs in up to \_\_\_\_\_\_, including resolution of\_\_\_\_
up to 63% Obstipation
47
Palliative RT protocols can resolve \_\_\_\_% of hypercalcemic dogs with AGASACA. What improves this %?
RT alone 31% RT + Pred + bisphosphonate = 46% additional
48
Reported PFIs and MSTs for dogs treated with palliative RT for AGASACA?
PFI 10-11 mo MST 8-15mo
49
Is rate of local recurrence for dogs treated with AGASACA related to the completeness of excision?
Nope
50
What is associated with a shorter median DFI for dogs with AGASACA treated with surgery (across multiple studies)
LN mets: 134-197d vs. 529-760d if not
51
Est. 1 and 2 yr survival rates for dogs with AGASACA
65%, 29%
52
Poor prognostic factors for AGASACA in dogs (10)
Primary tumor size, presence of clinical signs, presence of LN mets, size of LN mets, distant mets, no surgery, tx with chemo alone, E-cadherin expression, solid histo type; hypercal in some.
53
PFI and OST for dogs treated for AG melanoma with a variety of treatments?
3mo, 3.5mo
54
MST for cats with AGASACA treated with surgically +/- chemo and/or RT?
260d
55
Poor prognostic factors for survival in cats with AGASACA
local tumor recurrence Increased nuclear pleomorphic score (2 or 3)
56
What bioactive substances to MC's contain?
Heparin, histamine, TNF-alpha and proteases
57
What can MCs rapidly produce when stimulated?
Chymase, tryptase, cytokines (TNF alpha, IL6) chemokines (CCL2, CXCL1) VEGF, basic fibroblast growth factor, prostaglindin D2, leukotriene C4
58
What was found to be a risk factor for golden retrievers with MCT?
polymorphisms in the GNAI2 gene and multiple genes assoc with hyaluronic acid synthesis
59
Alterations in expression of what cyclin-dependent kinase inhibitors have been identified in a many canine MCTs?
p21 and p27
60
What is KIT normally expressed on?
Hematopoietic stem cells, melanocytes and MCs
61
What does KIT bind and what does this cause?
SCF binds KIT --\> KIT dimerization --\> phosphorylation --\> intracellular signaling --\> proliferation, differentiation and maturation of normal MCs
62
What is essential for the differentiation of mature MC from CD34+ stem cells?
SCF (stem cell factor)
63
The juxtamembrane domains of kit are
exon 11-12
64
The extracellular domains of KIT are
exon 8-9
65
What do KIT mutations cause?
SCF-independent activation of KIT --\> unregulated KIT signal transduction
66
c-kit mutations are associated with \_\_\_\_% of canine intermediate and high grade MCTS
25-30%
67
CNVs ( copy number variation) have been associated with (high/low) MCTs
High
68
MCTs with kit mutations showed aberrant CNVs involving what genes?
p53 and rB pathways
69
What drug metabolism and cell cycle pathways have been shown to correlated with cure from surgery vs. death from MCT?
solute carrier transporter and UDP glucuronosyltransferase gene families
70
What four stress response proteins are significantly upregulated in high-grade MCT
HSPA9 PDIA3 TCP1A TCP1E
71
Over expression of what micro-RNA was associated with MCT metastasis?
micro-RNA-9
72
What percent of dogs present with multiple MCTs?
11-14%
73
What is the behavior of primary GI MCT in dogs?
Aggressive - 40% alive at 30d , \<10% alive at 6mo
74
GI ulceration has been documented in \_\_\_\_% of dogs undergoing necropsy
35-83% (may be selecting for higher grade tumors because necropsy)
75
What does histamine released from MCT act on?
H2 receptors on parietal cells --\> increased HCl
76
In addition to high plasma histamine concentrations, dogs with MCT can also have decreased plasma ____ levels
Gastrin - normally released by antral G cells in response to increased gastric HCl
77
What mediates the hypotensive effects in humans with MC diseases?
Prostaglandins in the D series
78
What is the most consistent and reliable prognostic factor for canine MCT?
Grade
79
What is the long term survival rate for well-diffentiated and intermediate grade MCT after complete surgical excision
well-differentiated 80-90% Intermediate 75%
80
What is the metastatic rate for undifferentiated MCT
range 55%-96%
81
What locations are associated with high grade/worse prognosis for canine MCT
subungual, oral, mucous membranes scrotal and preputial visceral or bone marrow = grave
82
Microvessel density has been associated with what in canine MCT
Higher grade, higher degree of invasiveness, worse prognosis
83
What is the Bostock Grading system for canine MCT
Same as patnaik except numbers reversed (i.e. high grade = grade 1 on bostock, low grade = grade 3 on Bostok)
84
What stain can determine the AgNOR score?
silver colloid staining
85
What markers of proliferation have been associated with biologic behavior of MCT? Which is the least consistent
Ki67, AgNOR, PCNA PCNA least consistent
86
What mitotic index cutoff is associated with MST in dogs with MCT?
MI \<5 MST \>5 3mo; \<5 80mo
87
What are the three distinct ckit patterns
membrane, focal/stippled diffuse cytoplasmic
88
The presence of c-kit activating mutations has been associated with what in canine MCT?
higher rate of local recurrence, metastasis, death from disease
89
What percent of dogs with MCT on the muzzle present with regional LN mets?
50-60% but doesn't mean worse prognosis MST w/ mets = 14mo
90
What is associated with a more aggressive behavior for canine SQ MCT
MI \>4, infiltrative growth pattern, presence of multinucleation
91
What is the prognosis for dogs with conjunctival MCT?
Good - no dogs in the study looking at this died from the MCT
92
What IHC are MCTs positive for?
Vimentin, tryptase CD117 (KIT) +/- chymase, MCP-1 and IL-8
93
How does ultrasound or CT analysis of either MCT or STS change tumor margins planned at surgery?
Ultrasound upgraded tumor margins in 19%, CT upgraded margins in 65%
94
What other conditions can cause a peripheral mastocytosis (1-90MCs/uL)?
acute inflammatory disease (parvo), inflammatory skin disease, regenerative anemia, neoplasia other than MCT and trauma; may be more dramatic in other diseases than in MCT
95
What was the incidence of bone marrow involvement at the time of diagnosis in dogs with MCT?
2.8%
96
What was the incidence of bone marrow involvement and mastocytosis in dogs with visceral MCT?
Bone marrow 56% mastocytosis 37%
97
Adjuvant RT is associated with what 2-yr control rates for stage 0, low or intermediate grade MCT
85-95%
98
What is the general rate of recurrence for incompletely excised MCT? what may be associated in predicting likelihood of recurrence?
10-30%; proliferation indicies Ki67/PCNA
99
Is adjuvant steroid or antihistamine therapy beneficial for cases of intermediate MCT that have been excised or treated with RT?
Nope
100
What are the three distinct syndromes for feline MCT?
Cutaneous, splenic/visceral and intestinal
101
What % of cutaneous and splenic/visceral feline MCT had c-kit mutations? What exons were these primarily present in
exons 8/9
102
Which subtype of feline cutaneous MCT may spontaneously regress?
Histiocytic MCT (vs. mastocytic MCT)
103
The histiocytic form of cMCT is more likely to occur in what signalment cat?
Young, siamese (male depending on study); usually presents with multiple masses that may be ulcerated (head/neck usually)
104
What are the two types of mastocytic cMCT in cats?
Compact (50-90% of cases) vs. diffuse (anaplastic)
105
Systemic mastocytosis does/does not occur in healthy or ill-from something other than a MCT in cats
does not
106
What percent of cats may present with positive buffy coats? What form of MCT is this usually associated with?
43%, usually splenic/visceral
107
What IHC markers are feline MCT usually positive for
Vimentin, alpha-1 antitrypsin and KIT
108
What other organs are frequently affected by splenic/visceral MCT?
liver (90%), LN (73%), bone marrow (40%), lung (20%)
109
What is the survival for cats undergoing splenectomy for splenic/visceral MCT
12-19mo even with bone marrow involvement
110
What are the 3 MC related diseases in people?
Cutaneous mastocytosis (benign, young children, spontaneous regression systemic mastocytosis - 4 subtypes extracutaneous MCT
111
What KIT mutation is most common in people with MC disease
point mutation in exon 17 - induces ligand-independent activation; exons 8 and 11 also identified
112
Are KIT inhibitors (imatinib, nilotinib, dasatinib) effective for treatin human MC diseases?
Not usually - inhibiting phosphorylation of KIT on exon 17 is challenging
113
The most common brain tumors in dogs are:
meningtiomas (45%), gliomas (40%) choroid plexus tumors (5%)
114
What gene locus is strongly associated with glioma in multiple breeds
CFA 26
115
Single nucleotide variants ____ \_\_\_\_ and ___ have been shown to be strongly associated with glioma
DENR, CAMKK2, P2RX7
116
What are the most common secondary brain tumors in cats?
LSA and pituitary
117
What is the most common clinical manifestation of intracranial neoplasia in dogs?
Seizures - 50% of dogs with forebrain tumors
118
What percentage of cats will present with seizures for brain tumors? Which tumor type is this more common for?
25%; glioma and LSA \> meningioma
119
What is the most frequently reported clinical signs in cats with brain tumors?
Behavior change - 16-67% of cats
120
What is the most common clinical manifestation of brain tumors affecting the brainstem?
central vestibular signs
121
What percent of cats with meningiomas present with multiple tumors?
20%
122
What is the unique method that choroid plexus carcinomas can metastasize via?
Drop metastases - cancer cells exfoliated into the subarachnoid space or ventricular system with distant implantation of tumor foci
123
What is the rate of dogs with simultaneous and unrelated tumors in dogs with primary brain tumors?
3-23%
124
Meningiomas are extra or intra axial
extraaxial
125
What is the overall sensitivity of MR to identify canine meningiomas
60-100%, but specific subtype and grade can't be determined
126
What pattern is associated with gliomas on MR?
"Ring enhancing" - circular ring of contrast enhancement surrounding nonenhancing abnormal tissue
127
What brain diseases can cause a ring enhancing pattern
GLIOMA, but also other neoplasia, vascular and inflammatory brain disease
128
What are the most common brain tumors in the intraventricular location
choroid plexus tumors and ependymomas
129
What is the overall safety and success rate for minimally invasive brain biopsy (MIBB)?
diagnostic yields ~95%, \<5% risk of serious AEs
130
Most feline meningiomas are grade ____ compared to grade _____ in dogs
grade 1 in cats; up to 40% atypical grade II in dogs
131
Nearly 50% of canine CPTs are found in \_\_\_\_\_\_
the fourth ventricular region
132
A CSF total protein concentration greater than ____ was exclusively associated with a diagnosis of choroid plexus carcinoma (vs. papilloma)
80mg/dL
133
Animals that have what feature on MRI are more likely to respond favorably to treatment with steroids?
Peritumoral vasogenic edema
134
What percent of canine and feline meningiomas are identified incidentally?
6-19%
135
Dogs with supra/infra- tentorial tumors have a better prognosis with palliative care than the other
Supratentorial = better, MST 25 wks w/ palliative treatment vs. 4wks for infratentorial
136
What is the current preferred primary mode of therapy for feline supratentorial meningiomas?
cytoreductive surgery
137
Survival time for cats with cerebral meningiomas treated surgically?
MST 23-27mo, usually over 2 yrs (but most recur)
138
Is surgery or RT better as a primary therapy for canine meningiomas
Trick question - both similar, one not superior to the other
139
The MST for dogs with VEGF expression of ____ had a longer MST than for dogs with VEGF expression of \_\_\_\_
≤75% of cells or fewer = 25mo \>75% of cells = 15mo
140
What spinal cord tumors are extradural
OSA, chondro, FSA, plasmacytoma, MM, LSA, HSA
141
What spinal cord tumors are intradural-extramedullary
Meningioma, PNS, nephroblastoma, HS, LSA
142
What spinal cord tumors are intramedullary
Astrocytoma, ependymoma, oligodendroglioma, gliomatosis cerebri, HSA, TCC, LSA
143
Extradural tumors account for ~\_\_\_\_\_% of spinal cord and frequently arise from the \_\_\_\_\_\_\_
50%; vertebrae
144
What is the most common spinal cord tumor diagnosed in dogs and cats?
Meningiomas
145
80-90% of cats diagnosed with CNS LSA were seropositive for _____ historically. Newer data suggests ~56%
FeLV p27 antigen
146
What breeds are predisposed to nephroblastoma
Young German Shep. and golden retrievers
147
What breed is overrepresented in intraspinal meningiomas?
Boxers
148
What % of dogs with intramedullary spinal cord tumors present with paraspinal hyperpathia
68%
149
Nephroblastomas almost always are found between ____ spinal cord segments because \_\_\_\_\_
T9 and L2 because of the embryologic origin of the metanephric blastema from which they arise
150
Approximately 80% of canine nephroblastomas will demonstrate immunoreactivity to\_\_\_\_
WT-1 (human nephroblastoma gene product)
151
What is the MST for palliative treatment of vertebral and spinal cord tumors?
0-105 d
152
What is the MST for dogs with intraspinal meningioma treated with surgery? What can increase this?
6-47mo Post-op Rt - MST 45mo
153
MST of cats treated with surgery for spinal meningiomas
6-17mo
154
Cats have a higher proportion of benign or malignant PNSTs than dogs?
benign
155
What is the most frequently affected cranial nerve for PNST in dogs?
Trigeminal nerve
156
What is the most common spinal nerve roots affected by PNSTs in dogs?
Caudal cervical (C6-T2) followed by lumbar intumescence
157
What are the signs of trigeminal PNSTs?
Severe, unilateral masticatory mm atrophy, diminished jaw tone, decreased facial sensation, Horners
158
What % of brachial plexus tumors will have a palpable mass on PE?
33%
159
Up to 50% of PNST will display only what on MRI
Only nerve thickening (w/o a discrete mass)
160
What are negative prognostic indicators for dogs with PNST?
proximity to and invasion of the vertebral canal (occurs in 45% of tumors) and incomplete margins after surgery
161
What is the overall MST for dogs with paraspinal and plexus PNST?
6mo
162
What is the prognosis for cats with PNST
better - only low low percent recur after surgery
163
What is the prognosis for dogs with trigeminal PNST treated with SRS or SRT
745d/441d
164
What are the four most common skin and SQ tumors in cats?
Basal cell tumors, MCT, SCC and fibrosarcoma
165
Papillomaviruses are only able to replicate in _____ cells
terminally differentiated cells
166
What are the two main viral proteins from papillomavirus that lead to neoplastic transformation? What do that interact with?
E6 - destabalizes p53 E7 - inhibits pRB
167
Disruption of p53 by papillomavirus protein can cause increased levels of ____ which is detectable with IHC
p16
168
Canine papillomavirus has been associated with the development of \_\_\_\_\_\_
SCC - usually cutaneous
169
What are PPVs associated with in cats?
Viral plaques - aka feline sarcoids
170
PPV can be detected with IHC in most feline plaques - as the plaques progress to SCC, the ability to detect PPV ag increases/decreases
Decreases
171
PPV is detected in more UV-protected or UV exposed areas of SCC in cats
UV-protected - up to 76% vs. 42% of UV exposed
172
Basal cell carcinoma in people is thought to arise from critical mutations in what signaling pathway
Hedgehog
173
What aberrant karyotypes have been found in feline basal cell tumors
Trisomy E2 and monosomy E2 - unknown significance
174
\_\_\_\_ staining is considered fairly specific for human BCC and was detected in 23/24 BCC in cats in one study
Bcl-2
175
The presence of detectable ____ with IHC indicates mutations in the coding sequence and has been associated with what cutaneous tumor in cats and dogs
p53; SCC
176
What does p27 do? What cancer type has lower levels of this compared to benign tumors?
protein thought important in maintaining cells in G0 SCC
177
Nuclear activation of beta-catenin was detected in 100% of what skin tumor(s)
trichoepitheliomas and pilomatricomas
178
Which cyclin is expressed in the majority of feline SCC and just under half of canine SCCs
cyclin A
179
What is the causative mutation causing renal cystadenoma and nodular dermatofibrosis?
Birt-Hogg-Dube (BHD) gene
180
What does the BHD gene code for?
Tumor suppressor protein folliculin
181
What TKI has been associated with the rapid development of actinic keratosis and invasive SCC in people? What does this TKI inhibit?
Sorafenib - inhibitor of RAF and VEGF/PDGFR
182
What markers are used to differentiate BCC from SCC in people
epithelial membrane protein BerEP4
183
What dog breeds are at an increased risk for BCC
cocker spaniels, poodles
184
What are the three histologic subtypes of BCC in dogs
solid, keratinizing and clear cell
185
What is the behavior of BCC in dogs?
Low-grade malignancy; can recur but no reports of mets
186
Where does BCC most commonly occur on cats?
Head and neck - can be pigmented, too!
187
In patients with multiple papillomas, what drug may be effective
azithromycin
188
What is actinic keratosis in cats?
SCC in situ that arises as a consequence of UV exposure (different from Bowens based on location and histo)
189
Median DFI and MST for cats treated with surgery for a single nasal planum or pinna SCC?
DFI 594d, MST 675d
190
What cream can be used to treat Bowens in cats?
Imiquimod 5%
191
What topical cream was NOT effective for Bowens in cats
13-cis-retinoic acid
192
For cats treated with photodynamic therapy for bowens, what is the response rate and what is prognostic?
RR up to 100% (used in people too) Clinical tumor stage
193
What breeds of cats are at a DECREASED risk of SCC
Siamese, Himalayan and Persian
194
What dog breeds have a predisposition for nasal planum SCC?
Labs and goldens
195
what dog breeds are predisposed to cutaneous SCC
Poodles, bassets and blood hounds
196
What paraneoplastic syndrome has been associated with cutaneous SCC in cats?
Hypercal - two had ear canal tumors, the other had multiple cutaneous tumors
197
ECT with bleo for cats with cutaneous SCC has what CR rate and what survival range?
CR in 82%; survival 2mo - 3yrs
198
What breeds of dogs are more likely to ket infundibular keratinizing acanthomas (IKAs)
Nordic breeds - Norwegian elkhouds, belgian sheepdogs, Lhasa apso, German Shep
199
Surgery is the treatment of choice for IKA but what is an alternative option?
Isotretinoin (vitamin A derivative)
200
Malignant trichoepitheliomas are also called\_\_\_\_
matrical carcinoma
201
What is the behavior of malignant trichoepithelioma?
Rare and only case reports but reports = highly metastatic to regional LN and lungs
202
What breeds are more likely to get pilomatricomas
Kerry blue, soft-coated wheatens, Bouvier, poodles, sheepdogs, bichons, Airedales
203
What is the behavior of malignant pilomatricoma
High metastatic potential - mets to lungs, bone, LN, mammary gland or skin in 11/12 dogs in one report
204
What cutaneous tumors have adenxal differentiation? What does this mean
Arise from hiar follicle IKAs, tricholemmoma, trichoblastoma, trichoepithelioma, malig. trcihoepithel (matrical carcinoma), pilomatricoma/malignant pilomatricoma
205
Where is the most common site for apocrine gland carcinoma in dogs?
Thoracic limbs
206
What is the prognosis for apocrine gland carcinoma
Highly invasive, but cure rates high with surgery alone
207
What is an eccrine adenoma/carcinoma
tumors of the sweat glands of the footpads
208
What is the other name for neruoendocrine carcinoma
Merkel cell carcinoma
209
What is the behavior of Merkel cell tumors in people? How does this compare to dogs and cats?
Highly malignant in humans; case reports in cats and dogs suggest more benign clinical course
210
Loss of expression of what proteins is linked to a more aggressive behavior in humans for Merkel cell tumors has also been found in dogs
E-cadherin, beta-catenin
211
What do most dogs with nodular dermatofibrosis die from and how long does this usually take?
Renal failure from renal cystadenocarcinoma, average 3 years
212
What breeds are at an increased risk of ceruminous gland adenocarcinoma (dogs
german shep, cocker spaniels
213
Skull rads for dogs with malignant tumors of the ear cnala showed what primary features
Lysis of the bulla (13/27), sclerosis of the bulla (8/27)
214
Is metastasis from ear canal tumors common in dogs and cats?
No - 1/30 dogs had LN + distant mets, 3/35 had pulmonary, one lytic bone lesion; cats only regional LN
215
What is the MST for dogs and cats treated with a TECA-LBO for malignant ear canal tumors?
42-50mo (cats), not reached at 36mo for dogs (Better than lateral ear canal resection)
216
What is the staging scheme for primary tumors of the ear canal
T1 = confined to external or horizontal ear canal T2 = extending beyond TM T3 = extending beyond middle ear/bone destruction
217
What prognostic factor was identified in dogs with malignant ear canal tumors
Extension beyond ear canal (no MST = 30mo, yes MST = 5.9mo)
218
Cats with SCC of the ear canal have an MST of ____ compared to an MST of \_\_\_\_for ceruminous gland
SCC = 3.8mo, ceruminous = 49
219
What mitotic cutoff is associated with MST in cats with primary tumors of the ear canal?
≤2 mst = 180mo ≥3 MST ~24mo
220
What percent of dogs with digital SCC have involvement of multiple digits
~3%
221
What dog breeds are predisposed to having multiple digital scc?
large breed with black coats - standard poodles, black labs, giant schnauzers, gordon setters, rotties, beaucerons, briards
222
Are the thoracic or pelvic limbs more commonly affected by digital SCC?
Thoracic limbs
223
What breed of dog is overrepresented for digital melanoma?
Scotties
224
What was the % disagreement amongst pathologists for histo from digital tumors? How often was this clinically significant?
20% of cases, clinically significant differences in 75% of these
225
What is another term for lung digit syndrome?
Acrometastasis
226
What was the rate of primary lung tumors in 64 cats with digital carcinoma
88%
227
What is the MST for cats with lung digit vs. primary digital SCC
lung-digit: 4.9 weeks primary SCC 29.5wks
228
What digit tumor does bone lysis have prognostic significance for in dogs?
melanoma
229
Dogs with digital SCC have what rate of metastasis at diagnosis and what rate develop it subsequently?
6-13% at dx additional 9-17% develop it
230
What location of digital SCC may carry a better prognosis?
Subungual
231
What is the rate of mets at the time of diagnosis and what additional percent develop it for digital melanoma
32-40% at dx (local LN or distant) additional 10-26% develop after definitive treatment
232
What are the 1 and 2-year survival rates for dgital SCC treated with surgery alone in dogs?
1yr 50-83% 2yr 18-62% Better for subungual lesions
233
What are the 1- and 2-yr survival rates for dogs with digital melanoma treated with surgery alone?
1yr 42-57% 2yr 13-36%
234
Is there a survival benefit from adding chemo to surgery in dogs with digital melanoma?
Not for carbo - 1 and 2 yr survival : 89 and 67% vaccine - 1 and 2 yr 63% and 32% (but 28% had mets at treatment)
235
What is the survival time for cats with digital melanoma? how many developed mets?
0-\>577d (helpful information, I know) 4/5 developed mets
236
What two changes in the mid-1980's in vaccines correlate with FISS development in cats?
Development of a killed rabies and killed FeLV vaccine - both have strong association with FISS development
237
What is the estimated prevalence of sarcoma development at sites of vx admin
1-4/10,000 up to 13-16/10,000 cases
238
What is the time from vaccine to tumor development for FISS?
Anywhere from 4wks up to 10yrs
239
Are adjuvanted vs. nonadjuvanted vx more likely to cause fiss?
No one knows - though it adjuvanted increases inflammation and therefore increases risk of FISS, but 3 large studies showed no evidence that aluminum-containing vx had more risk
240
What IHC markers are FISS positive for that non-FISS FSA's are not (or are only weakly positive for)
PDGF, epidermal growth factor, TGF-beta
241
Lymphocytes in FISS are positive for ____ while lymphocytes in non-injection-site FSA and normal LN are negative this
PDGF (macrophages, too)
242
What proto-oncogene was strongly positive in ISS and not expressed in non-FISS FSA? What does it code for?
c-jun, codes for AP-1
243
FeLV and feline sarcoma virus are/are not involved in FISS pathogenesis?
Are not
244
Non FISS FSA typically arise from the ____ compared to FISS which typically arise from the \_\_\_\_
non-FISS FSA: skin FISS: SQ
245
What subtypes of tumors are included in FISS
FSA, rhabdoymyosarcoma, MFHs (malignant fibrous histiocytomas), undifferentiated sarcomas, extraskeletal OSA and chondrosarcomas
246
What do macrophages in the peripheral inflammatory cell infiltrates of FISS often look like/contain
bluish-gray foreign material - aluminum and oxygen
247
How should CT imaging be performed for intrascapular FISS
postcontrast CT with thoracic limbs extended cranially and caudally along body to better determine the association with the FISS and the adjacent tissue
248
What is the preferred surgical approach to FISS
5-cm lateral margins and two fascial layers deep for gross palpation 3cm lateral and one fascial layer deep for cats with CT to characterize extent of disease
249
What is the rate of complete excision for FISS when a 3cm/1 layer deep approach is used based on palpation vs. 5cm/2 layers?
3cm/1 layer = 50% complete 5cm/2 layer = 95-97%
250
What is the median DFI for marginal resection, wide resection and radical surgery for FISS
marginal 79d wide 325d radical 419d
251
What is the time to first recurrence for FISS when first surgery was at a nonreferral vs. referral practice
nonreferral 66d referral 274d
252
T/F wide surgical resection of FISS in the interscapular area usually requires removal of the dorsal spinous processes
T
253
Has preoperative RT been shown to reduce rate of recurrence in FISS treated with surgery?
Not in the literature - local recurrence with complete margins = 42% compared to incomplete for 32% of cats treated with pre-op RT + surgery
254
When should post-op RT start for FISS?
10-14 days post-op; DFI and ST decreases as the interval between surgery and RT increases
255
What is the rate of recurrence for FISS with multimodal treatment with surgery (2-3cm margins) + RT
28-45%
256
What was the response rate to hypofx rt (5x4gy) + liposomal DOX as a radiation sensitizer for cats with gross disease FISS?
90% ORR - 7 PR, 2 CR; problem = not durable (117d)
257
What was the median PFI and MST for cats treated for gross disease FISS with 4x8Gy RT?
PFI 4mo, MST 7mo
258
What is the response to SRT for gross disease FISS
Variable protocols (most 3x10Gy), 8/11 response (3CR, 5PR), median PFI 242d, MST 301d
259
What is the rate of metastasis for FISS?
0-26%
260
T/F cats treated with gross residual disease after surgery for FISS with post-op RT and chemo had an improved MST compared to those only treated with surgery + RT
True - MST 29mo vs. 5mo (all chemo = doxo except 1 cat had doxo + cytoxan)
261
\_\_\_\_ Has been shown to result in inhibition of the PDGF/PDGFR pathway and results in chemosensitiaztion in FISS cell lines
Imatinib
262
\_\_\_\_\_ has been shown to inhibit PDGFR in FISS cell lines (but in concentrations higher than readily achieveable) and was/was not found to be a radiation sensitizer
Masitinib, was not a radiation sensitizer
263
What was the median time to local recurrence for FISS treated with surgery vs. intraop vs. post-op ECT with bleo?
Surgery only 4mo intraop bleo ECT = 12mo post-op bleo ECT = 19mo
264
T/F it is safe to treat cats with FISS with cisplatin ECT?
True - minimal systemic toxicity (pulmonary, renal, cutaneous); local recurrence 29%
265
What were the rates of recurrence for cats with FISS treated with surgery + iridium-based brachytherapy and IL-2
Human IL-2 w/ vaccina virus vector: 39% at 1yr Feline IL2 w/ canary pox vector: 28%
266
Intratumoral feline IL-2 has been combined with what other therapies in a phase I trial?
IFN-gamma and granulocyte-macrophage colony-stimulating factor + preop magnetofection
267
What is the 3-yr disease free rate for FISS when removed with 5cm lat margins or compartmental resections
86%
268
What are prognostic factors for local recurrence for FISS
Tumor size, surgical dose, completeness of histologic excision, histologic grade
269
What are the metastatic rates for grade I, II and III FISS
I: 0-17% II 15-19% III: 22-100%
270
What is the overall MST for radical surgery with 4-5cm/2layer deep for FISS?
804-901d
271
What are prognostic factors for survival in cats with ISS
PCV\<265%, tumor size (\<2cm vs. 2-5 vs \>5cm; or \<3.75cm in another study), treatment type, histologic subtype, mitotic rate (20) local tumor recurrence and mets
272
Where does the VAFSTF recommend feline vaccines be administered?
Rabies RHL FeLV LHL Other vaccines: right shoulder none interscapular
273
Is SQ or IM vaccine recommended by VAFSTF?
SQ because masses are easier to detect earlier
274
When should a mass at vaccination sites be investiaged further?
Mass is evident 3 or more months after vx If the mass is larger than 2 cm If the mass is increasing in size more than 1 month after vaccination
275
What is the rate of local recurrence for nasal SCC in cats treated surgically? What is the DFI?
\<10% recurrence, median DFI 594d for isolated, 426d for SCC in multiple locations
276
What is the MST for cats with either isolated nasal planum SCC treated with surgery or SCC in multiple locations treated with surgery?
isolated: 673d multiple: 530d
277
What is the median time to recurrence for dogs treated with external beam RT for nasal planum SCC?
2-3mo, RT not generally used
278
What was the 1-yr PFS rate for cats with nasal planum SCC treated with orthovoltage?
60%
279
What is the median DFI and MST for cats treated with megavoltage RT for nasal planum SCC?
DFI 361-916d MST 902d
280
What was the CR rate for cats treated with intralesional carbo for nasal planum SCC?
73%
281
What % of oral melanomas are amelanotic?
38%
282
What antiboides hawve been found to have 100% specificity and 94% sensitivity for dx'ing melanoma?
PNL2, Melan A, TRP-1 and TRP-2
283
What is the metastatic rate for dogs with OMM?
Stage dependent, can be as high as 80%
284
What are the five histologic subtypes of SCC in dogs?
conventional, papillary, basaloid, adenosquamous and spindle cell
285
What is the common case presentation for oral papillary SCC in dogs?
Young dogs (usually \<9mo) in the rostral oral cavity
286
What location of oral SCC has a higher rate of metastasis vs. lower?
Higher: tongue and tonsil Lower: rostral oral cavity
287
What has been shown to increase the risk of oral SCC in cats?
flea collars and high intake of either canned food or canned tuna, household tobacco smoke
288
Mutations in what gene are significantly increased in SCC lesions in cats with smoke exposure compared to those w/o smoke exposure
p53
289
Increased tumor expression of ____ in cats with oral SCC may play a role in bone resorption and tumor invasion
parathyroid hormone-related protein (PTH-rp)
290
What is the rate of metastasis for cats with oral SCC?
31% mandibular LN, 10% lungs
291
Where do hi-low fibrosarcs usually occur in dogs?
hard palate and maxillary arcade b/w canine and carnassial teeth
292
What are peripheral odontogenic fibromas?
benign gingival proliferations arising from the periodontal ligament (previous name = epulides)
293
Where are peripheral odontogenic fibromas more likely to occur in the mouth?
Maxilla rostral to the 3rd premolars
294
Where is the most common location for acanthomatous ameloblastoma?
Rostral mandibule (51%)
295
What was the diagnostic accuracy of FNA and impression smear cytology for cats and dogs with oral tumors?
FNA: dogs 98%, cats 96% impression: dogs 92%, cats 96%
296
Bone lysis is not evident on radiographs until \_\_\_\_% of the cortex is destroyed
40% or more
297
How did CT vs. radiographs compare for diagnosing invasion into surrounding structures for maxillary masses in dogs?
CT showed \>90% of dogs had invasion vs. only 30% on radiographs
298
What was the relationship of normal and enlarged LN and presence of metastasis in dogs with OMM?
40% of dogs with normal sized LN had mets 49% of dogs with enlarged LNs did not have mets
299
For cats and dogs with oral tumors with LN metastasis, what was the rate of the mandibular LN being affected?
55% - need to look at other nodes, too!
300
What is the one type of oral tumor that does not often invade the underlying bone?
peripheral odontogenic fibromas
301
How do cats tolerate mandibulectomy?
Not well - usually need to have reconstruction (compared to dogs which reconstruction is not recommended due to high rate of complications)
302
What are the most common complications from maxillectomy?
Blood loss and hypotension
303
What % of cats will never eat voluntarily after mandibulectomy?
12%
304
What is the overall rate of mets to the lungs for OMM
14-67%
305
What are known prognostic variables for dogs with OMM treated with surgery +/- other therapies
Tumor size, age, clinical stage, ability of 1st sx to achieve local control, degree of differentiation, MI, nuclear atypia score, pigment quant, COX-2 expression, PDGFR expression, Ki67 expression, c-kit expression
306
What is the overall rate of response of OMM to RT? What percent are CR?
81-100%, up to 70% CR
307
what is the overall ST for dogs with OMM treated with RT?
192-401d
308
MST for OMM T1 vs. T2 vs. T3
T1 19mo T2 or T3 \<7mo
309
MST for dogs treated with hypofractionated RT based on stage?
Stage I = 758d II = 278d III = 163d IV 80d
310
Result of phase I OMM vx trial? (Responses?, MST?)
Dog with lung mets at CR n=2 stage IV lived \>400d n=2 stage II or III lived 500d w/o evidence of melanoma at necropsy \*\*MST sig improved when primary site + LN treated with sx or RT\*\*
311
One study of the OMM vx showed that dogs under what wight did better
20kg
312
What locations may be associated with longer STs for OMM
Lip (MST 580d) Tongue (MST 551)
313
What is prognosis for dogs with well-differentiated OMM treated with surgery alone?
only 5% died of OMM, MST 34mo
314
Rate of metastasis for dogs with oral SCC?
Regional LN 10%, lungs 3-36%
315
What areas of the mouth are associated with a more aggressive behavior and higher rate of mets for canine oral SCC
tonsils and base of tongue - rate of mets 73%
316
What is the rate of local recurrence from oral SCC for dogs treated with mandibulectomy and what is the MST?
0-10%; MST 19-43mo
317
What is the rate of local recurrence from oral SCC for dogs treated with maxillectomy and what is the MST?
14-29%; MST 10-39mo
318
What are prognostic factors for dogs with OSCC?
Presence of tumor-associated inflammation and risk score of 2 or ≥ 3 (combination of tumor-assoc inflammation, lymphatic or vascular invasion and peripheral nerve invasion)
319
What molecular marker has been shown prognostic in dogs with surgically resected mandibular or maxillary OSCC?
proliferating cell nuclear antigen expression (PCNA) \>65% MST 155d ≤65% MAR not reached
320
What is the MST for dogs with OSSC treated with RT alone vs. surgery + RT
RT alone 15-16mo RT + surgery: 34mo
321
What was the response rate to piroxicam alone for dogs with OSCC?
17% - 1 CR and 2 PR
322
What was the CR rate for dogs with T3 oral SCC treated with carbo + piroxicam
57% - sustained in all dogs at median follow-up time of 534d
323
Recent molecular data suggests that HSA arises from ___ rather than from malignant transformation of mature peripheral endothelial cells
bone marrow progenitor cells that undergo dysregulated maturation
324
Mutations in ____ and ____ have been shown in the pathogenesis of angiosarcoma in mic and humans but are infrequent in canine HSA
p53 and Ras
325
What key growth and apoptosis regulating proteins are overexpressed in HSA compared to hemangiomas or normal tissues
pRB, cyclin D1, Bcl2 and survivin
326
Two large studies have shown _____ of dogs with splenic tumors have malignant disease and ______ of these are HSA
50%; 50-74%
327
What IHC can be used to support diagnosis of HSA and rule out other sarcomas
CD31/platelet endothelial cell-adhesion molecule von Willebrand's factor (factor VIII-related antigen)
328
What RBC changes are common in dogs and cats with HSA
schistocytes, acanthocytes and nRBCs
329
Thrombocytopenia is found in \_\_\_\_\_% of HSA
75-97%
330
Alterations in secondary coag parameters (PT and PTT, fibrin degradation product, fibrinogen and d-dimers) are found in nearly \_\_\_\_\_% of patients with HSA
50%
331
More than 50% of cats may have elevations in this chemistry value
AST
332
What are the "T" classifications for HSA
0 = no evidence of tumor T1 = tumor \<5cm diameter and confined to primary tissues T2 = tumor ≥5cm, or ruptured or invading into SQ tissues T3 = tumor invading adjacent structures including mm
333
What are the TNM stages for HSA
I = T0 or T1, N0, M0 II = T1 or T2, N0 or N1, M0 III = T2 or T3, N0, N1 or N2, M1
334
What is significantly elevated in dogs with cardiac HSA compared to HSA at other sites, dogs with other cancers, etc
cardiac troponin-1 also higher for HSA pericardial effusion vs. non-HSA pericardial effusion
335
What is the MST for dogs with cardiac HSA treated with hypofractionated RT?
MST 2.5mo + decreased frequency of cardiac tamponade
336
The original eBAT trial showed what?
MST 8.5mo, 6-mo survival of 70.6% (treatment before standard of care dox), six long term survivors All dogs were stage I or stage II
337
What is the MST for dogs with stage I splenic HSA treated with surgery + chemo?
MST 239-355d
338
What is the MST for dogs with stage II splenic HSA treated with surgery + chemo
MST 120-148d
339
Which form of asbestos is more likely to cause mesothelioma?
the amphibole (vs. chrysotile which is now 90% of what is used)
340
Mutations in what are common in humans with mesothelioma
tumor suppressor genes - CDKN2A, BRCA1, BAP1, neurofibromin 2 (NF2)
341
In what species do mesothelial tumors more commonly occur in young or new born animals
cattle and sheep
342
Mesothelial cells appear morphologically as ____ but their derivation is from \_\_\_\_\_
epithelial cells; mesoderm
343
Mesothelioma can be ruled out as a cause of pleural effusion in dogs and cats if \_\_\_\_levels are not increased
pleural effusion levels of fibronectin (sensitive but not specific)
344
What are the most useful IHC markers for mesothelioma in humans
calretinin, wilms' tumor gene (WT1), cytokeratin 5/6 and D2-40
345
What is the most common cardiac tumor in cats?
LSA - primary and secondary
346
What is the sensitivity of radiographs for detecting cardiac HSA
47%
347
What breeds of dog is OMM most commonly diagnosed?
Scotties, goldens, Chows, poodles and dachshunds
348
Canine OMM is most commonly found in what locations of the mouth in order of decreasing frequency
gingiva, lips, tongue and hard palate
349
WHat are the primary factors that determine the biologic behavior of an OMM in dogs
Site, Size, Stage and histo parameters
350
What cocktail of IHC Abs are used to diagnose melanoma
PNL2, tyrosinase, Melan A and S-100
351
BRAF is frequently mutated in which form of human melanoma?
Commonly mutated in cutaneous but not in oral (also uncommon for BRAF mutations in OMMs in dogs)
352
What IHC marker can more reliably predict potential malignant behavior compared to classical histology for cutaneous melanoma?
Ki67 (also prognostic in OMM)
353
What is the MST of dogs with melanoma of the digit w/o LN or distant mets treated with digit amp?
~12mo, 1yr survival 42-57%, 2yr 11-13%
354
What is the rate of metastasis at presentation for dogs with digital melanoma?
30-40%
355
What do most dogs with digital melanoma die from?
Metastasis - regional or distant
356
What are the T classifications for OMM based on WHO TNM staging
T1 ≤2cm T2 2-4cm T3 \> 4cm
357
What are the N classifications for OMM based on WHO TNM staging?
N0 = no regional nodes N1 = histo or cyto evidence of regional node involvement N2 = fixed nodes
358
What are the WHO TNM-based stages for OMM in dogs?
Stage 1 = T1N0M0 2 = T2N0M0 3 = T2N1M0 or T3N0M0 4 = Any T, Any N and M1
359
What is the MST for dogs with stage I OMM treated with surgery
511-874d
360
What is the MST for dogs with stage II OMM treated with surgery
160-818d
361
What is the MST for dogs with stage III OMM treated with surgery
168-207d
362
What % of enlarged vs normal LN have mets from OMM?
70% of enlarged LN have mets 40% of normal LN have mets
363
What margins are generally recommended for benign cutaneous melanomas?
1cm skin margins, 1 fascial plane deep
364
What margins are recommended for OMM
2-3 cm when possible
365
Dogs with incomplete histo margins from OMM are ____ times more likely to die of tumor-related causes compared with dogs with complete excision
3.6x
366
Dogs with OMM located where in the mouth are 4.3x more likely to die of tumor-related causes
Caudal to PM3 (compared to those rostral to PM3)
367
What is the radiosensitivity melanom
Generally radioresistant --\> need higher dose/fx to achieve local control
368
What is the overall response rate to RT for melanoma? PR vs. CR?
Overall 82-94% PR 25-67% CR 19-69%
369
What is the PFS for dogs treated with RT for gross disease melanoma?
3.6-8.6mo
370
What is the ORR and MST for cats with OMM treated with RT?
ORR = 60% (1 CR 2 PRs/5 cats) MST 146d
371
Does adding chemotherapy to RT improve outcomes for dogs with OMM?
No based on the largest study; may have a role as a chemosensitizer (low rate of recurrence 15% with cisplat or carbo)
372
For dogs treated for OMM with surgery + carbo +/- RT, what was the MST? How did RT influence this?
MST for sx/chemo/RT 440d vs. sx/chemo 387d (not stat sig), but lower rate of local recurrence for RT group (27% vs. 67%)
373
What was the difference in TTP and MST for dogs treated with RT alone vs. RT + temozolomide
PFS sig shorter for RT alone (110d vs. 205d), MST numerically different but not stat sig (RT alone 192d vs. 402d w/ chemo+RT)
374
When using the WHO TNM staging system, what is the PFS for OMM treated with 12x4Gy MWF RT protocol based on T?
T1 PFS 11.3mo T2 6.0 T3 6.7mo
375
Bony involvement has been reported in up to \_\_\_\_\_% of dogs with melanoma
92%
376
What is the ORR for dogs with measurable malignant melanoma to carbo? vs. cisplat + piroxicam
Carbo: 28% Cisplat + piroxicam: 18%
377
What happens after intradermal or intramuscular injection of a DNA vaccine (ex: melanoma vs)
APCs (dendritic cells) present the Ag on MHC
378
Collectively, the melanoma vx literature has showed what?
1. It's safe 2. It leads to development of antityrosinase Ab and T cells 3. potentially therapeutic 4. needs to be further investigated in adjuvant, minimal disease phase II setting
379
Other than the oncept vaccine, what other vaccine has been shown to be potentially beneficial for canine OMM
CSPG4 vx MST and median DFI longer for vx group
380
What are the T classifications for digital melanoma based on WHO TNM staging
T1: \<2cm + superficial or exophytic T2 = 2-5cm with minimal invasion T3 = \>5cm or invading the SQ T4 = invading into fascia or bone
381
What are the stages of digital melanoma in dogs based on WHO TNM staging
1 = T1N0M0 2 = T2N0M0 3 = T2N1M0, T3 or T4 N0 or N1 M0 4 = Any T, any N, M1
382
What was the MST for dogs treated with digit amp + oncept based on digital melanoma stage?
stage 1 = \>952d 2 = \>1093d 3 = 321d 4 = 76d \*\* Oncept sig improved outcomes compared to historic controls\*\*
383
What was the MST for dogs treated with digit amp + oncept for digital melanoma w/ vs. w/o mets
W/mets = 105d w/o = 533d
384
Most STS occur in middle-aged to older dogs with the exception of
rhabdomyosarcoma
385
What is the likelihood of local recurrence for STS after surgery dependent on?
tumor size, degree of infiltration, completeness of excision, grade
386
What is the likelihood of metastasis from STS primarily dependent on?
Grade
