Bachata Rosa Flashcards

1
Q

Mutation and overexpression of what gene is present in both human and canine LSA?

What other TSG was also recently evaluated and found to be abnormal in both human and canine B-LSA?

A

p53 - lower remission rate and ST

Mutated in 16% and overexpressed in 22% of dogs with high-grade LSA

Hypermethylation of DAPK CpG islands - 45% of B-cell LSA; negative PI for survival in both humans and dogs

DAPK involved in IFN-y mediated apoptosis

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2
Q

What is the most common immunophenotype and cytomorphologic sub-classification of LSA in Boxers?

A

85% T-cell lymphoma
TCR ab+, CD4+
Lymphoblastic high-grade

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3
Q

What is the MST of Boxers and Boxer mix breeds when treated with the LOPP chemotherapy protocol? Prognostic indicators found?

A

MST - 3m (99d)

Boxers 6x more likely to develop PD
Boxer breed = negative PI for PFI

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4
Q

What is Ritcher’s syndrome and the MST* in dogs?

A

CLL -> lymphoma

Characterized by the presence of pleomorphic immunoblasts

Poor tx response and prognosis

MST 41d

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5
Q

What are the identified prognostic factors in dogs with CD21+ LSA (2)?

A

Large cell size = shorter remission duration and ST (HR: 2.77x more likely to die and 1.75x more likely to develop PD); also more likely to have lymphadenopathy and thrombocytopenia

MST: large cell 5m vs medium 9m vs small NR

Low MHC class II = shorter remission duration and ST (HR: 2.87x more likely to die and 3.49x more likely to develop PD)

MST: low 4m vs high 10.5m

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6
Q

What is the PFS* and MST in dogs with LSA treated with CCNU as a first line therapy? ORR? CR and PR?

A

PFS: 40d
MST 3.5m (111d)
ORR 52%, CR 35%, PR 17%

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7
Q

What is the PFS, and MST of dogs with LSA when treated with doxo/pred vs doxo/pred/CTX?

Main findings on this study?

A

Addition of CTX did NOT result in statistical improvement of ORR, PFS, or MST. Study was underpowered, however.

Doxo/pred/placebo - PFS 5 to 6m, MST 6 to 10m
Doxo/pred/CTX - PFS 8m, MST 14m

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8
Q

CR, PFI, MST with single agent doxo/pred in dogs with LSA of unknown phenotype?

ORR, CR, PFI, MST for B-cell?

ORR and CR* for T-cell?

A

Unknown: CR 78% PFS 4-6m, MST 5-10m

B-cell: ORR 100%, CR 70 to 86%, PFS 5-6m, MST 6-10m
Only chemo completion prognostic for PFS and ST; no diff when compared to historic controls that included T cell

T-cell: ORR 50%, CR 17%

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9
Q

CR to CHOP for T-cell vs B-cell canine multicentric LSA?

A

T-cell 88% (ORR 95%, PFI 5m, MST 8m)* largest study with specifically multicentric T-cell (no GI); 15% alive at 1 yr and 5% at 2 yr

B-cell 85 or >%

MOPP for T-cell: ORR 98%, CR 78%, PFI 6.3m, MST 9m)
25% alive at 2.5yrs

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10
Q

Main findings of RNA-loaded CD40-activated B-cells in dogs with spontaneous lymphoma?

A

Used CD40L transfected K562 cells to generate functional CD40-B cells from the peripheral blood of humans and dogs

It was administered to dogs in remission after induction of chemotherapy

Goal: Induce functional tumor-specific T cells in cancer patients

  • CD40 activated B cells are highly efficient antigen-presenting cells capable of priming naive T cells, boosting memory T-cell responses and breaking tolerance to tumor antigens
  • The use of tumor RNA as the antigenic payload allows for gene transfer without viruses or vectors and permits MHC-independent, multiple-antigen targeting

RESULTED IN:
-Higher % of dogs achieving a durable 2nd remission and improved lymphoma specific ST in relapsed dogs after rescue therapy

-Induced functional, antigen-specific T cells from healthy dogs and dogs with lymphoma

DID NOT affect: initial response, TTP, or ST compared to dogs tx with chemo alone

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11
Q

What is the ORR, CR, and PFI in dogs with NAIVE lymphoma when treated with alternating rabacfosadine/doxorubicin?

How does immunophenotype affect ORR?

Prognostic indicators (2)?

A

ORR 84% (CR 68%, PR 16%)
PFI 6.5m, if CR 7.2m

Immunophenotype predicted ORR:
95% - B cell
25% - T-cell

Substage and phenotype were associated with PFI; longer for B-cell

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12
Q

What is the ORR, CR, and PFI in dogs with B-cell LSA when treated with rabacfosadine in the RESCUE setting?

How does the PFI change for dogs with a CR or any response?

A

ORR: 74% (CR 45%, PR 29%)
PFI: 3.5m, 7m if CR, 6m with any response

No difference between doses used

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13
Q

What % of dogs with lymphoma vs myeloma develop dermatologic AE when treated with Tanovea?

A

Lymphoma: 25-37%
Myeloma: 50%

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14
Q

What is the most common phenotype, overall PFS and MST in dogs with colorectal lymphoma?

Does local therapy improve outcome?

A

B-cell, high-grade
PFS 3.6yrs
MST: 4-5yrs

Addition of local therapy to chemotherapy DOES NOT improve outcome

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15
Q

ORR, CR, PR to chemotherapy in dogs with colorectal LSA?

A

100% ORR
95% CR
5% PR

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16
Q

Prognostic factors in dogs with colorectal LSA (2)?

A

Younger dogs (<7yrs) = longer PFS (NR) and dz-specific MST

Hematochezia/substage b = longer PFS (NR)

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17
Q

What is the most common intestinal location in cats with LGL?

Most common phenotype?

IHC used for granules?

What % is NK origin?

A

Jejunum

granzyme B+ for granules (seen on cytology but not H&E sections)

CD3+ CD8+, CD20-, TCR gene rearrangement - most common

CD103 (integrin) - 60%

10% are NK origin (CD57+) and negative for B and T cell markers; C

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18
Q

What % of cats with LGL experience clinical benefit and a response when treated with chemotherapy?

A

35% - clinical benefit

30% - ORR

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19
Q

What is the overall TTP and MST in cats with LGL when treated with chemotherapy? MST w/o chemo? What % survives >7m?

A

TTP 50d
MST 2m; CHOP 60d, CCNU 60-130d
MST w/o chemo 2w
7% >6m SR

CHOP/COP ORR 30%
CCNU/Elspar ORR 56%

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20
Q

Negative prognostic indicators in cats with LGL (4)? Positive (1)?

A
  • Substage b
  • Circulating neoplastic cells
  • Lack of chemo administration
  • Lack of chemo response

Positive: chemo administration

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21
Q

What are the negative (4) and positive (3) prognostic factors identified in cats with nasal LSA?

A

Negative:

  • Anemia
  • Cribriform plate lysis
  • Total RT dose of <32Gy
  • BW of <4kg

Positive:

  • Achievement of a CR
  • Total RT dose of >32Gy
  • Apoptotic index and Ki67 >40%
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22
Q

What is the overall MST in dogs with intermediate to high vs low-grade nasal LSA? Most common phenotype?

A

B-cell

Intermediate to high - MST 12.5m
Low - MST 2.3yr

No statistical difference in MST, but chemo alone had lowest MST of 5m vs RT + chemo MST of 15m

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23
Q

Most common primary and metastatic* intramedullary spinal tumor in dogs? Location?

A

Primary - ependymoma (neuroepithelial)
Metastatic- HSA and LSA per Withrow
HSA and TCC new paper; 33% each
T3-L3

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24
Q

Most common secondary brain tumor in cats vs dogs?

A

Cats - LSA #1, pituitary #2

Dogs - HSA #1, pituitary #2, LSA #3

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25
What is the most common secondary intra-ocular tumor in dogs and cats?
LSA
26
Up to what % of dogs with LSA have ocular involvement? Most common abnormality?
37% | Uveitis
27
What is the PFS and OST in dogs with primary intrao-ocular LSA? Phenotype? CS? What % can develop neuro signs?
B-cell; considered stage V Uveitis, endophthalmitis (inflammation of the anterior chamber), and 2/5 had abnormalities in contralateral eye PFS/OST 6m 100% in one study
28
What is the PFS and MST in dogs with conjunctival LSA? Prognosis? How does it present?
Good prognosis Considered stage I PFS 7.5m, MST 18m All unilateral, 2/4 had a discrete mass Some can be cutaneous epi T-cell LSA Some can develop LN involvement later on
29
What is the ORR and PFS of DTIC when used as a rescue in dogs with LSA?
ORR 35% | PFS 40d, if CR 144d
30
What population has been identified as having a higher risk for LSA development in Australia?
Neutered dogs (males and females)
31
What breeds are at higher risk for LSA development in Europe (4)?
Dobies, Rotties, Boxers, BMD
32
In Europe, what type of LSA do Rotties, Boxers, and dog de Bordeaux, most commonly develop?
Rotties - B cell | Boxers Bordeaux - T cell
33
In Europe, although Labs are not predisposed to developing LSA, what type do they most commonly get?
High grade T cell
34
What is the difference between Goldens in the USA vs Europe when it comes to LSA?
Unlike USA, they are not predisposed to LSA or TZL
35
What % of DLBCL and T cell LSA over-express PD-L1? What has this been associated with?
50% DLBCL 0% T cell Increased expression of PD1 and PD1L in TIL and chemotherapy resistant cell lines in both B and T cells
36
Dogs with LSA tend to have a higher serum concentrations of what 2 things when compared to healthy dogs?
Lactate | B-hydroxybutyrate
37
How does the GI microbiota differ in dogs with asymptomatic LSA vs healthy dogs?
Asymptomatic LSA dogs have lower GI microbial diversity and higher degree of dysbiosis vs healthy dogs
38
How is the agreement of digital slide assessment with flow cytometry vs that of traditional glass slide assessment?
Lower
39
An s-phase fraction of > than ___% is consistent with high grade LSA. Sensitivity and specificity? What is it strongly associated with?
>3.15% Sensitivity 98% Specificity 100% Ki67
40
A Ki-67 of > than ___% is consistent with high grade LSA. Sensitivity and specificity?
Ki67 > 12.2% 96% sensitive 100% specific
41
What is the ORR, PFS, and MST in dogs with DLBCL, substage a, when treated with CHOP chemotherapy?
ORR 100% (82% CR, 18% PR) PFS 8.5m MST 11.5m
42
What are some identified PF for achieving a PR vs CR in dogs with DLBCL, substage a, when treated with CHOP (3)?
Thrombocytopenia at dx Greater age at dx High serum globulin concentration
43
What are some identified PF for a shorter PFS in dogs with DLBCL, substage a, when treated with CHOP (4)?
Thrombocytopenia at dx Greater age at dx PR as best response Increased neutrophil count MST 93d or < in these dogs
44
What is the ORR, CR, PFI, and MST of UK dogs with centroblastic DLBCL when treated with CHOP chemotherapy?
ORR 94%, CR 75% | PFI 6m, MST 11m (10.7m)
45
What is an identified prognostic factor for achieving a CR vs a PR in UK dogs with centroblastic DLBCL when treated with CHOP?
Entire dogs more likely to achieve CR
46
What are some identified prognostic factor (2) for achieving a longer PFI in UK dogs with centroblastic DLBCL when treated with CHOP?
Absence of anemia at dx | Pre-treatment neutrophil:lymphocyte ratio <9.44
47
What are some identified prognostic factor (4) for achieving a longer ST in UK dogs with centroblastic DLBCL when treated with CHOP?
Lymphocyte:monocyte ratio >1.43 Neut:lymph ratio <11.44 Combination of induction and rescue therapy Increased number of doxorubicin doses
48
Upregulation, phosphorylation, and nuclear localization of what 2 TF have been noted in lymphocytes from dogs with DLBCL vs those from healthy LN?
STAT3 and ERK1/2
49
What is the ORR in chemotherapy naive lymphoma patients when given VBL? Doses used?
7% PR at 2 mg/m2 | 60% PR at 2.5 mg/m2 - 80% developed neutropenia 1 week post
50
What is the ORR and DFI of VBL when used as a rescue agent in dogs with LSA? Dose used?
VBL at 2.6mg/m2 ORR 26% (CR 8%, PR 18%) DFI 30d 6% grade III or IV neut
51
In dogs with B cell lymphoma tx with doxo + pred, what has been addociated with a longer PFS and MST?
Chemo protocol completion
52
ORR, CR, PFS/DFI, and MST in dogs with T-cell LSA treated with Morgan vs Brown LOPP? 2-yr SR?
Morgan: ORR 94%, CR 83%, PR 11% PFS 14.4m, MST 17m 54% 1-yr PFS, 29% 2-yr PFS Brown: ORR 97%, CR 90%, PR 7% DFI 6m, MST 8m 39% 1-yr SR, 25% 2-yr SR
53
AE to Morgan vs Brown LOPP in dogs with T-cell LSA?
Morgan: 86% overall (higher) 51% myelosuppression; grade 3+ neut/thrombo in 80% 74% GI; only 13% grade 3+ 23% overall hospitalized; 11% if not including post induction 40% required dose reductions Brown: 42% overall Only 18% required dose reduction
54
How do CSC behave in dogs with B and T cell LSA vs LN samples from a healthy dog?
% of tumour cells expressing CSC markers were significantly increased in dogs with BCL, compared with B cells from normal lymph nodes. Similar results in T-cell.
55
CSC flow cytometry markers in B vs T cell lymphoma?
B-cell: higher expression of CD117, CD90, CD34, Oct 3/4 vs normal B cells T-cell: higher expression of Oct 3/4 and downregulation of CD90 vs normal T-cells
56
What is the ORR and T-cell RR, TTP, duration of response and AE of verdinexor (KPT-335) in dogs with T-cell LSA (naive and progressive)? MTD?
ORR: 37%, T-cell 71% TTP 30d Response duration 18d AE: 95% grade 1-2 anorexia 45% weight loss 31% vomiting 26% Hepatopathy also reported 1.75mg/kg PO BID 2-3x per week
57
What is verdinexor?
Oral selective inhibitor of nuclear export (SINE) ; reversibly binds to XPO1, which is responsible for moving p53, p21, pRb, FOXO, NF-KB into the cytoplasm
58
Based on geographical location within the USA, which locations have the longest vs shortest PFS when treated with chemo?
North - 8m South - 6m West - 4m
59
Dogs with centroblastic polymorphic DLBCL have a higher chance of 2-yr survival if what 4 factors are present?
BW >10kg Normocalcemia No BM involvement No steroids
60
MST of dogs with Burkitt's LSA?
15d
61
When dogs with LSA are treated with LPP in the relapse setting, which ones are more likely to respond?
Those getting a higher procarb dose
62
In geriatric dogs (14 or>) with LSA treated with COP or CHOP, what is the ORR, CR, duration of response, MST, grade 3 AE? Negative PI (1)? Most common phenotype?
``` B-cell 95% CR Duration of response 6m MST 7m AE: 27% (similar to historic CHOP data) ``` NPI: Anemia shorter PFI
63
What are some negative prognostic indicators for PFI and MST in geriatric dogs with B-cell LSA?
PFI: shorter if anemia present MST: shorter if BW 13kg or >
64
American Golden Retrievers are more likely to have TZL vs BCL in which geographic locations?
North East | East North Central regions
65
How its T-zone (clear cell) lymphoma characterized?
A variant of PTCL-NOS characterized by clonal expansion of T-cells that lack expression of CD45, a pan-leukocyte antigen, within the paracortex and medullary cords of LN resulting in compression of germinal centres. The cells are small to intermediate in size with very rare mitoses. ``` Phenotype: high MHC class II, low-moderate CD21+, CD5+, CD45- Not always CD21+ but high % can be + ```
66
What % of older Golden Retrievers without clinical TZL have peripheral circulating TZ cells compared to non-Goldens?
Goldens - 31% | Non-Goldens - 14%
67
What % of older Goldens without clinical TZL that have circulating TZ cells also have clonal TCR gamma gene rearrangement vs Goldens without TZ cells?
Golden's WITH TZ cells and clonal TCR - 34% Golden's WITHOUT TZ cells and clonal TCR - 20%
68
In dogs with nodal marginal lymphoma, what % is substage b, what % has stage V dz, splenic, hepatic, and BM involvement? Most common extranodal site?
``` Substage b - 34% Stage V dz - 100% Spleen - 97% Hepatic - 80% BM involvement - 60% Extranodal site - lungs ```
69
How is the neoplastic lymphoid population described in dogs with nodal MZL?
Medium-sized CD21+ and +/- CD70a+ lymphocytes Low mitotic activity Histopath: diffuse growth, loss of follicle architecture, thinning of capsule
70
What is the ORR, CR, PR, TTP and lymphoma-specific MST in dogs with nodal MZL when treated with CHOP? Overall outcome?
Poor outcome ORR 100%, CR 80%, PR 20% TTP 5m MST 9m (260d)
71
Negative prognostic factors for ST in dogs with nodal MZL (2)?
Substage b | Elevated serum lactate dehydrogenase
72
What % of dogs with hypercalcemic LSA have mediastinal involvement?
43%
73
What % of dogs with multicentric T-cell LSA have mediastinal involvement?
54%
74
Mediastinal lymphoma is almost always exclusively T-cell and hypercalcemia is most commonly associated with this form of LSA. What % of dogs with mediastinal lymphoma are hypercalcemic at diagnosis?
68%
75
Most common phenotype and cytomorphology in dogs with mediastinal LSA?
T-cell | Lymphoblastic high-grae
76
What % of dogs with mediastinal T-cell LSA are substage b? Most common clinical signs?
85% - substage b 71% - lethargy Anorexia PU/PD
77
What % of dogs with mediastinal T-cell LSA have pleural effusion at diagnosis?
45%
78
In dogs with mediastinal T-cell LSA, what is the ORR, CR, PFS, and OST when treated with CHOP chemotherapy?
ORR 93%, CR 70% PFS 4.5m OST 6m
79
PPI in dogs with mediastinal T-cell LSA when treated with CHOP?
CHOP chemo - improved PFS and OST | Lack of pleural effusion - improved OST
80
Is there a difference in outcome in dogs with relapsed multicentric lymphoma when treated with TMZ vs TMZ + doxorubicin? Overall MST?
No; overall MST 40d TMZ alone: ORR 32%, TTP 15d, MST 40d TMX/doxo: ORR 60%, TTP 19d, MST 60d
81
Most common LSA in CNS in dogs?
DLBCL; usually an extension vs primary
82
CSF analysis in dogs with CNA LSA is diagnostic in what % of cases?
~70% Increased TNC from which 95-100% are atypical lymphocytes and increased TP
83
Overall MST in dogs with CNS LSA?
170d (5.6m)
84
Phenotype of epitheliotropic LSA in dogs?
CD8+
85
ORR, CR, remission duration if CR, and MST in dogs with CETCL treated with CCNU?
ORR 80%, CR 30% CR duration 4.5m (132d) MST 6m
86
Prognostic factors in dogs with CETCL?
Positive PI: - Mucocutaneous or mucosal lesions vs cutaneous - For cutaneous lesions, the use of chemo and the presence of solitary lesions - For mucocutaneous, younger age and presence of solitary lesions
87
Sensitivity of a moth-eaten spleen in cats with LSA on AUS?
13% sensitive | 85% specific
88
What is the ORR to Elspar in cats with LSA? How is it when compared to dogs?
30% ORR (CR 15%, PR 15%) Shorter duration of response; <7d
89
Sensitivity and specificity of flow cytometry for LSA diagnosis in cats? What needle gauge is preferred in order to provide a highly cellular sample?
92% sensitive 100% specific 21 gauge needle
90
What is the most common Hodgkin's like lymphoma in cats? Presentation? Immunophenotype? Prognosis?
Lymphocyte-histiocytic (RS cell variant); usually small to medium sized lymphocytes and large histiocytic looking lymphocytes Reactive CD3+ T cells in the background Lymphohistiocytic cells positive for BLA 36 and CD79a -> B-cell Lymphadenopathy of 1 or > enlarged LN in the head/neck region Prognosis: usually excellent W/sx - DFI 1yr W/o tx - MST 7m-4yr ST Can sometimes regress on its own and then come back Can become aggressive Usually cats older than 6 yrs
91
What is the ORR, CR*, DFI, and MST for cats with various anatomic forms of intermediate to high-grade LSA when treated with intraperitoneal L-COP? 1 and 2yr SR?
``` ORR 96%, CR 77%, PR 19% DFI 14m (421d) MST 13m (388d) 55% 1-yr SR 47% 2-yr SR ```
92
Which anatomic in cats with LSA location has the shortest DFI when treated with intraperitoneal L-COP?
GI 7.6m < Nasal 13m < Peripheral 14
93
Most common AE in cats with intermediate to high-grade LSA when treated with intraperitoneal L-COP?
Vomiting - 42% Also anorexia and weight loss
94
Prognostic indicators in cats with intermediate to high-grade LSA when treated with intraperitoneal L-COP (2)?
Younger age = more favorable response CR = long-term ST
95
Most common cause of febrile neutropenia in cats?
``` #1 CCNU #2 Vincristine ```
96
Most important PI in cats with GI LSA?
Response to therapy
97
ORR, PFS, MST in cats with intermediate to high grade LSA treated with DMAC in the rescue setting? AE?
26% clinical benefit (no CR) PFS 14d MST 17d 16% grade 4 neutropenia
98
What % of cats with GI LSA have concurrent IBD?
60%
99
When the human WHO classification system is applied to cats with alimentary LSA, what is the predominant form seen in the stomach, SI, mesenteric LN, and ileocecocolic junction, large intestine?
Stomach - DLBCL SI - EATL type I (48%) and II (42%) Mesenteric LN - T-cell Ileocecocolic - DLBCL Phenotype statistically associated with associated with location
100
When the human WHO classification system is applied to cats with alimentary LSA, what are the 3 most common forms of alimentary LSA in cats?
#1 EATL type I - 41%; transmural T-cell LSA, large cells; extension into submucosa and muscularis propia #2 EATL type II - 34%; mucosal T-cell LSA, confined to mucosa and lamina propia, minimal sumucosal invasion, monomorphic small to medium-sized cells that show strong epitheliotropism, also known as LGAL #3 DLBCL - 20%
101
What are the 2 most common alimentary forms of LSA in cats when using the feline classification system?
Mucosal - usually low grade, small-cell, T cell Transmural - usually high-grade, small (40%) or large (60%), B or T cell; LGL is a large cell subtype
102
What % of alimentary LSA in cats are T vs B cell? Which form of LSA is more common within the phenotypes?
T- cell: 80%, usually mucosal (80%) | B-cell: 20%, usually transmural (95%)
103
What % of cats with LGAL develop large cell GI LSA?
3.7%
104
Most common location for alimentary LSA in cats?
SI; rarely in stomach and LI
105
In cats with alimentary LSA, what immunophenotype is most commonly associated with solitary/multifocal vs diffuse dz?
T-cell diffuse | B-cell solitary or multifocal; multiple common
106
Most common locations for low grade alimentary LSA?
Jejunum and ileum
107
What % of cats with LGAL exhibit epitheliotropism?
40%
108
What has been recently noted in cats with LGAL and COX-2 expression (2)?
COX-2 protein expression is present in 1/3 of cats with LGAL, but no difference when compared to cats with IBD. COX-2 mRNA levels are higher in cats with LGAL vs IBD or healthy cats
109
What are the 2 most common subtypes of transmural large-cell LSA in cats?
LGL - most common one* | DLBCL
110
Most common subtype of large-cell transmural alimentary LSA in cats?
Large granular LSA - 82%
111
Overexpression of ____ mRNA has been noted in cats with LGAL vs IBD.
MDR1
112
What % of cats with discrete intermediate to high grade LSA develop intestinal perforation post chemotherapy induction?
17% (20-90d post)
113
What is the most common complication in cats with alimentary LSA that undergo full thickness biopsies? Prognostic indicators for complications?
Transient hypo or anorexia - 11% Other: hyperthermia, pancreatitis NO dehisence!! No identified prognostic variables Low albumin NOT prognostic (as opposed to dogs <2.5)
114
Besides flow cytometry, what test has the best sensitivity and specificity for differentiating small cell GI LSA vs IBD?
PARR - 90% sensitive | Histopath - 99% specific
115
How has abdominal RT been combined with chemotherapy in treatment naive cats with abdominal or multicentric lymphoblastic/large cell lymphoma? Response and outcome?
``` 6 week CHOP chemo 2-week holiday 1.5Gy x 10d (M-F) 5/8 had durable remission of >266d (9m) Overall, well tolerated ``` 2 cats relapsed 1 euthanized for unknown reasons
116
What is the MST in cats with different types of GI LSA when treated with abdominal RT in the rescue setting? Protocol? AE?
8Gy x 2d MST 7m Minimal RT SE, 1 cat had self-limiting loss of appetite
117
What % of cats with LGL have extra-intestinal involvement? Three most common locations?
85% LN>liver>spleen>kidneys>lungs>bone marrow Epitheliotropism common
118
LGAL accounts for what % of feline alimentary LSA?
60-75% Most common form
119
What % of cats with LSA have pulmonary involvement?
13%
120
In cats, to what forms of LSA is pulmonary LSA associated (3)?
Mediastinal Alimentary Multicentric
121
Most common pulmonary lesions in cats with LSA?
No gross lesions 56% Masses 25% Nodules 20%
122
Most frequent radiographic pulmonary pattern seen in cats with LSA and pulmonary involvement?
Peribronchial-vascular infiltrative pattern
123
Most common phenotype and subtype in cats with LSA and pulmonary involvement?
``` B cell (90%) DLBCL (60%) ```
124
What are the identified risk factors for feline intestinal carcinoma (3)?
Age (10-12 yrs) Males Siamese - 1.8x increased risk for intestinal neoplasia and 5x increased risk for ACA
125
What IHC markers are used for GISTs (5)? Most sensitive ones (2)?
``` CD117 - 95-100% DOG-1 CD34 VImentin SMA - 30% (usually negative) ``` CD117 and DOG1; will catch the ones negative for CD117 Discovered-on-GIST 1 (DOG1) is a Ca-dependent Cl channel involved in generation of slow waves from the interstitial cells of Cajal
126
Where are mutations in the c-kit gene located in dogs with GIST?
Exon 11 of juxtamembrane domain of KIT Results in constitutive activation Mutations: deletions, ITD, and point mutations
127
What techniques can be used to detect c-kit mutations in dogs with GIST (2) and which one is more likely to detect a mutation?
RT-PCR: 72.4% detected Conventional PCR: 32.6%
128
What is the most common KIT staining pattern in dogs with GIST? Is it associated with c-kit mutation status?
Diffuse cytoplasmic - 70% partial/focal stippled cytoplasmic - 30% NOT associated with c-kit mutation status
129
Why can females develop perianal gland adenomas after being spayed? What is another reason?
Loss of estrogenic inhibition Testosterone-secreting adrenal tumor
130
What are some negative prognostic indicators in dogs with AGASACA (10)?
Tumor size: > 9cm2 or >2.5cm LD Any mets: LN and distant Advanced clinical stage Lack of sx Lack of chemo Tx with chemo alone LN mets and extirpation Tx with platinums (shorter DFI, another study showed it decreases risk of local recurrence) Hypercalcemia (newer studies say its not) Some histopath changes (see next index card)
131
What are some negative histopathologic PI in dogs with AGASACA (7)?
Decreased E-cadherin expression Solid growth pattern Moderate or marked peripheral infiltration Necrosis Lymphovascular invasion Cellular pleomorphism MI 8 or >
132
What is the TTP and MST in dogs with early stage (<3.2cm) AGASACA w/o mets when treated with sx alone? Recurrence rate and later metastasis?
TTP 2.4yrs MST 3.4 yrs RR 20% Mets in 26% at 1yr or later
133
What is the MST in dogs with AGASACA that develop local recurrence and are treated with a 2nd surgery?
Overall 2 yrs After 2nd sx 9.5m
134
What is the TTP and MST in dogs with AGASACA when treated with sx and 4 doses of carboplatin? Did chemotherapy make a difference in ST?
TTP 13m MST 2 yrs Chemo did not make a difference
135
What is the MST in dogs with AGASACA when treated with sx and melphalan?
20m
136
What is the MST in dogs with AGASACA treated with sx, carboplatin, and hypofractionated RT?
19m
137
What is the PFI and MST in dogs with stage 3b AGASACA when treated with sx vs hypofractionated RT?
Sx - PFI 5.3m, MST 6m RT - PFI 11.5m, MST 15m IIIb - T any size, nodal mets >4.5cm (vs a, <4.5m)
138
Dog with AGASACA, no nodal metastasis, hypercalcemic – what is the best treatment? Pamidronate and fluids, sx alone, sx and hypofractionated RT to the node bed, Sx and Palladia
How to treat?
139
What % of AGASACAs express PDGFRa and b? VEGFR2 cytoplasmic staining?
Alpha - 100% Beta - 17 to 19.5% VEGFR - 80%
140
What are late SE that can occur with adjuvant RT for AGASACAs? How can this be minimized?
Rectal stricture or perforation | Minimize by using <3Gy per fraction
141
A study evaluating an IMRT theoretical 3.8 Gy x 12 protocol for dogs with stage IIIb AGASACA determined that in almost half of the patients, there was a ___% risk of late spinal cord toxicity. There was ___% risk of ____ in 33% of patients.
5% or > of late spinal cord toxicity >15% risk of myelopathy in 33% of patients
142
In dogs with GIST treated with Palladia, what is the median PFI when used in the gross vs microscopic dz setting? Biological response rate in dogs with gross disease?
Biological response 71% (2 CR, 1 PR, 1 SD) PFI in gross dz 2.3yrs (for responders) PFI in microscopic 1.3yrs
143
Negative PI for a shorter PFI in dogs with GIST treated with Palladia?
Metastasis at dx | High mitotic index (<5, 5-10, >10)
144
What is the TTP and MST in cats with salivary gland carcinoma when treated with RT and +/- surgery? Negative PI (2)?
TTP: 5m ST: 2-19m Advanced clinical stage Compared to dogs, cats have a higher metastatic rate and poorer long term prognosis
145
What is the most common exocrine pancreatic tumor in cats? Metastatic rate at diagnosis? Most common clinical signs at presentation?
Pancreatic adenocarcinoma 32% have mets at dx Weight loss (68%), anorexia (53%), vomiting (41%), palpable abdominal mass (41%)
146
What paraneoplastic syndrome can be seen in cats with exocrine pancreatic carcinoma?
Alopecia Acute, progressive, non-scarring, bilaterally symmetric; predominantly involves the limbs, but can include the ventrum, head, and trunk
147
What is the most common comorbidity in cats with pancreatic carcinoma?
Diabetes mellitus - 15% Other: Heart dz or murmur (21%) Hyperthyroidism (18%)
148
Overall MST in cats with pancreatic carcinoma? What is the MST in cats with pancreatic carcinoma treated with sx and chemo? 1-yr SR? What type of surgery is performed?
Overall 3m MST w/sx and chemo 5.5 to 10.5m *10.5 if no mets 8.8% 1-yr SR Complete pancreatectomy or Whipple’s procedure (pancreaticoduodenectomy)
149
Negative PI in cats with pancreatic carcinoma (3)?
Peritoneal effusion (30d) Tx with NSAIDs alone (26d) Lack of sx and/or chemo (improves ST, 165d) MST <1m
150
What chemotherapy has been shown to have clinical benefit in cats with pancreatic carcinoma?
Gemcitabine - 82%
151
Most common gastric mass in lesser curvature/antrum of stomach in dogs? CS: GI bleed, high BUN.
Gastric ACA - #1 gastric tumor in dogs (80%) Most common location: lesser curvature and antrum
152
Metastatic rate of gastric ACA in dogs? Locations?
70-80% metastatic rate lymph nodes #1, liver #2, lungs #3
153
Gastric ACA in dogs are more common in what sex and breeds (2)?
Males | Belgian Shepherd and Rough-Coated Collie
154
Ulcers and bleeding can occur in ___% of dogs with gastric ACA. Because of this, what is a common CBC finding?
50% Microcytic hypochromic anemia
155
What is the 2-week and 3-month SR in dogs with gastric neoplasia (benign and malignant) undergoing pylorectomy and gastroduodenostomy (Billroth 1)? What % of dogs undergoing this surgery survive to discharge? MST?
75% 2-week survival rate 60% 3-month survival rate 88% survived to discharge MST 1-2m (generally <6m) Billroth 1 - resection of pyloric antrum (pylorectomy) and gastroduodenal anastomosis (gastroduodenostomy)
156
Three most common complications in dogs with gastric neoplasia undergoing pylorectomy and gastroduodenostomy (Billroth 1)?
``` hypoalbuminemia (63%) anemia (58%) transfusion (33%) hypotension (17%) hypoglycemia (17%) aspiration pneumonia (13%) pancreatitis (13%) sepsis due to dehiscence (8%) ```
157
Negative PI (on univariate) in dogs with gastric neoplasia undergoing pylorectomy and gastroduodenostomy (Billroth 1) (2)?
Preoperative weight loss | Malignant cancer
158
Most common GIST location?
Cecum
159
Second most common gastric tumor in dogs? Location? Signalment?
LMA Stomach cardia, grow into lumen, discrete, pedunculated Always focal Commonly seen in older dogs ~15yr; Beagles
160
According to CT findings in dogs with gastric tumors, what tumor is most likely associated with larger LN?
Gastric LSA
161
According to CT findings in dogs with gastric tumors, is LSA more likely to be segmental or diffuse?
Segmental 60% | Diffuse 40%
162
According to CT findings in dogs with gastric tumors, is ACA more likely to be segmental or diffuse?
50:50
163
What are the intraoperative and perioperative mortality rates in dogs with massive HCC undergoing sx?
intraoperative 4.8% | perioperative 8-12%
164
What is the perioperative mortality rate in cats with massive liver tumors undergoing sx?
22%
165
In cats with massive liver tumors undergoing sx, what % survives to hospital discharge and what % lives >40d?
78% 61% lived >40d (multiple liver tumors)
166
Complication rate in dogs and cats undergoing liver sx for massive tumor removal? Most common complication?
Dogs - 30% Cats - 22% Hemorrhage; 17% of dogs and 44-61% of cats undergoing liver lobectomy need a blood transfusion
167
What are some identified prognostic factors in dogs undergoing sx for massive HCC (8)?
Surgical excision vs palliative care (MST >1460d vs 270d); non-surgical cases 15.4x more likely to die Increased ALT and AST Increased ALP to AST ratio Increased ALT to AST ratio Side of liver involvement; higher risk of intra-op complications for R-sided tumors, but no difference in ST Lethargy or tachypnea at presentation Experiencing an anesthetic complication Requiring a blood transfusion associated with failure to survive to discharge
168
What are some prognostic factors in cats with liver tumors treated with sx (3)?
Abdominal effusion Preoperative anemia Need for transfusion Shorter MST
169
What is the most common primary hepatobiliary tumor in cats overall?
Bile duct adenoma (biliary cystadenoma) - 52% of all liver tumors
170
How do bile duct adenoma (biliary cystadenoma) loos grossly? Sex predisposition? CS?
Cystic appearance Even distribution between focal vs multifocal Male Typically asymptomatic until mass effect occurs
171
What is the most common primary malignant hepatobiliary tumor in cats? Metastatic rate and locations?
Bile duct carcinoma (cholangiocarcinoma) 67-80% metastatic rate; LN, lungs, carcinomatosis, etc PNS alopecia reported (and with HCC)
172
What is the second most common malignant hepatocellular tumor in cats?
Hepatocellular carcinoma
173
Metastatic rate and MST with and w/o sx in cats with HCC?
Met rate - 0% | MST: w/o surgery 1.4yrs vs w/sx 2.4yrs
174
What are the most common chemistry abnormalities in cats with HCC (4)?
AST elevated in >90% ALT and ALP elevated in >70% Hyperbilirubinemia in >40%
175
What viruses are associated with HCC in humans?
Hepatitis B and C | Woodchuck: Woodchuck hepatitis virus
176
In dogs vs cats, are primary vs metastatic tumors more common?
Dogs - metastatic Cats - primary (usually benign)
177
Recently, upregulation of ___ mRNA was noted in dogs with HCC.
MET
178
In dogs with concurrent splenic and hepatic masses, what % had malignancies in both organs? Of those with concurrent malignant lesions, what % had the same malignancy? Most common malignancy?
48% - malignant in both organs 93% - same in both organs HSA - 77%
179
ORR of Palladia in dogs with non-resectable liver tumors?
50% (PR) in 3/6 dogs
180
What % of dogs with HCC develop tumor reduction post trans-catheter arterial embolization?
100%
181
What is an identified predisposition for intestinal tumors in both dogs and cats?
Male sex
182
Of dogs with inflammatory intestinal polyps that underwent a 2nd biopsy, what % developed adenoma and ACA?
36% adenoma | 20% ACA
183
In the study of dogs that developed adenomas and carcinomas after an initial diagnosis of polyps, what was also noted?
Inactivation of APC gene | Accumulation of B-catenin in cytoplasm -> translocation to nucleus -> promotion of Wnt associated genes
184
Most common sited for GIST in dog?
Cecum #1 | Colon
185
What drug is used in humans with GIST?
Imatinib (Gleevec) Can rescue with Sunitinib when Imatinib fails
186
In dogs, what are the most common locations for intestinal lymphoma?
Equal distribution between stomach and SI (LI less likely)
187
What dog breeds are predisposed to developing intestinal T-cell LSA (7) according to a Japan study?
Shiba dogs, German shepherds, Cairn terriers, Boston terriers, Papillons, Pugs and Maltese
188
What is the most common phenotype for intestinal T cell lymphoma in Shiba dogs in Japan?
CD3+, granzyme B+ Regardless of small or large cell
189
What is the most common phenotype and lesion distribution in dogs with small cell intestinal LSA?
T-cell Diffuse - 38% Discrete/multifocal - 23%
190
What is the most common clinical sign in dogs with small cell T-cell intestinal lymphoma?
Diarrhea #1 | Weight loss
191
What are the 3 most common US abnormalities in dogs with small cell T-cell intestinal lymphoma? What % of dogs have a normal AUS?
Abnormal wall layering - 54% Hyperechoic mucosal striations - 54% Thickened muscularis - 34% Normal - 38% Mild lymphadenopathy - 46%; only 1 had LSA confirmed
192
What % of dogs with with small cell T-cell intestinal LSA exhibit epitheliotropism?
60%
193
What is the overall MST and MST of chemotherapy treated dogs (14/17) with with small cell T-cell intestinal LSA?
Overall MST 9m Chemo tx dogs MST 14-21m
194
Identified prognostic factors in dogs with small cell T-cell intestinal LSA (4)?
Anemia = shorter ST Weight loss = shorter ST Tx with steroids + alkylator = longer ST vs steroids alone Response to therapy = longer ST
195
What is the ORR to chemotherapy in dogs with small cell T-cell intestinal LSA?
70%
196
What % of canine small cell T-cell intestinal LSA co-express CD20?
48%
197
2 common chemistry abnormalities in dogs with small cell T-cell intestinal LSA?
Hypocobalaminemia -71% | Hypoalbuminemia - 69%
198
Most common intestinal location in dogs with small cell T-cell intestinal LSA?
Duodenum
199
Histopathologic description of dogs with smal-cell T-cell intestinal LSA?
Lymphocytic infiltrates within the intestinal villous lamina propria and epithelium. Infiltrates were often more pronounced in the villous tips
200
Most common phenotype in dogs with large-cell intestinal LSA?
T-cell
201
What % of dogs with large cell intestinal LSA have intestinal + LN involvement vs intestinal involvement alone?
Intestinal + LN 48% (94% had LSA confirmed on LN) Intestinal alone 40%
202
MST in dogs with large cell intestinal LSA when treated with multiple therapies?
2-2.5m Dogs tx with CCNU have a numerically longer MST, but not statistically significant No differences in outcome based on tx
203
Most common AUS abnormalities in dogs with high-grade intestinal LSA (4)?
``` #1 Thickened intestinal wall with loss of layering #2 presence of ≥ 1 discrete mass #3 ulceration ```
204
What are some negative prognostic indicators in dogs with high-grade intestinal LSA (4)?
Diarrhea Anorexia Septic peritonitis Dz outside of intestines alone
205
What are the 3 most common causes of hypercalcemia in cats?
``` #1 idiopathic #2 kidney disease #3 neoplasia ```
206
What % of hypercalcemic cats have cancer?
1/3 or 33%
207
What are the most common causes of hypercalcemia of malignancy in cats?
Lymphoma and SCC PTHrp mediated
208
What % of cats vs dogs with MM are have hypercalcemia?
Cats: 10-25% Dogs: 15-20%
209
What is the main MOA for hypercalcemia in dogs and cats with MM?
IL-1B (osteoclast activating factor)
210
Expected BW abnormalities in dogs with primary hyperparathyroidism?
iCa and Tca - high PTHrp - zero PTH - normal or high Ph - low (if neoplastic too)
211
What non-neoplastic infectious dzs can cause a monoclonal gammopathy (8)?
``` Babesia Ehrlichiosis Leishmaniasis FIP Coccidioides Heartworm Bartonella henselae Strep zooepidemicus in cats Chronic pyoderma Amyloidosis ```
212
Clinical case of TCC with hypertrophic osteopathy. What to do next?
Tumor excision Can consider anti-inflammatory steroids, NSAIDs and/or bisphosphonates
213
What % of tumor bearing dogs have thrombocytopenia prior to therapy?
36% prior to therapy | Highest with lymphoproliferative disorders - 58%
214
Thrombocytopenia is higher in dogs with which class of tumors?
Lymphoproliferative disorders - 58%
215
What % of dogs and cats with MM have thrombocytopenia?
Cats 50% | Dogs 33%
216
Most common cause of thrombocytopenia in cats?
Lymphoma
217
What % of dog with HSA have thrombocytopenia?
75-97%
218
DIC cause of consumptive thrombocytopenia in ___% of dogs with cancer.
40%
219
What % of dogs with HSA and cats with splenic MCT have an abnormal coagulation profile?
Cat splenic MCT = 90% | Dog HSA = 50%
220
What is the most common PNS in dogs and cats with LSA?
Non-regenerative anemia
221
Non-regenerative anemia can be present in what % of dogs and cats with MM?
Dogs: 70% Cats: 50-65% Anemia more common than thrombocytopenia in MM*
222
What is the most common cutaneous tumor in cats? Biologic behavior and metastatic rate?
Basal cell tumor - 23% overall (10 to 26%) Usually benign. A study of 97 feline BCT had 10% categorized as malignant based on stromal invasion, vascular invasion, necrosis, high MI, LN mets (1 cat); another study had 1 cat with pulmonary mets
223
What is the most common malignant ear canal tumor in dogs and cats?
Ceruminous gland adenocarcinoma
224
In dogs and cats, are malignant vs benign tumors of the ear canal more common?
Dogs - uncertain | Cats -malignant
225
What canine breeds are at increased risk for developing ear canal ceruminous gland ACA (2)?
Cocker Spaniels and GSD
226
How is the metastatic rate in dogs and cats with ear canal ceruminous gland ACA?
Low and uncommon, but increases over time Dogs - LN 3.3%, lungs 8.5% Cats - LN 9%, lungs 0%
227
What is the TOC in dogs and cats with ear canal ceruminous gland ACA? Why?
TECA and BO Recurrence is lower vs LECA
228
What are negative prognostic factors in dogs with ear canal ceruminous gland ACA (1)?
Extension beyond ear canal (cartilage invasion) MST 6m vs w/o (confined) 30m
229
What are negative prognostic factors in cats with ear canal ceruminous gland ACA (4)?
MI of ≥ 3 (MST 12m vs 180m) Neurologic CS (MST 15.5m vs 1.5m) Histology (ACA MST 49m vs SCC 3.8m) Extension beyond ear canal/cartilage invasion (MST 4m vs w/o 22m)
230
What are negative prognostic factors in dogs with digital melanoma (8)?
- Mitotic index ≥ 3 - Ki67 index ≥ 15 - ≥ 20% nuclear atypia - Distant mets - Degree of pigmentation (scale 0-2, 2 is favorable) - Junctional activity - Level of infiltration/extension beyond dermis - Ulceration
231
What % of dogs with digital melanoma have metastasis at presentation?
30-40%
232
Picture of cytology (SCC) lab with lysis of P3. What is the metastatic rate at diagnosis and later on? What % has lysis on xrays?
At dx 9% Later on 23% 80% have lysis on xrays
233
What are identified prognostic factors in dogs with oral melanoma (14)?
- Ki67 index ≥ 19.5% (shorter DFI and MST) - MI ≥ 4/10 hpf - ≥ 30% nuclear atypia - Co-expression of PDGFR a/b (37%, shorter DFI and MST) - Higher % of intratumoral Tregs - Stage of dz - Size of tumor - Lymphatic invasion - Distant mets - Degree of pigmentation - Female sex - Adjuvant therapy - Intralesional excision - >12yrs of age
234
What are the negative prognostic indicators identified in dogs with lip melanoma (7)?
- Mitotic index ≥ 4/10 hpf - Ki67 index ≥ 19.5% - ≥ 30% nuclear atypia - Distant mets - Degree of pigmentation - Junctional activity - Level of infiltration/deep with bone involvement
235
Cutaneous melanomas are often benign if they are not in a mucocutaneous location. What are the negative prognostic indicators for this location in dogs (8)?
- Ki67 index ≥ 15% - MI ≥ 3/10 hpf - ≥ 20% nuclear atypia - Extension beyond dermis/level of infiltration (Breslow thickness: >0.75cm = risk of recurrence/mets, >0.95cm = unfavorable outcome) - Ulceration - Distant mets - Lymphatic invasion - Degree of pigmentation
236
What combination of IHC markers is the most sensitive and specific when trying to differentiate an amelanotic from a STS (3)? What is the sensitivity and specificity of this combination? What other markers (2) and what other histologic characteristic (1) can be used to help dx melanoma? What markers are 100% specific, but have a low sensitivity (3)?
Melan A, PNL2, tyrosinase (TRP1/2): 93% sensitive and 100% specific S-100, MITF: highly sensitive, but less specific (will also stain sarcomas) Others: vimentin, NSE - positive for both 100% specific, but low sensitivity: HMB-45, tyrosinase, tyrosinase hydroxylase Presence of junctional activity = proliferation of neoplastic cells at the dermoepithelial junction NOT ALL WILL STAIN WITH MELAN A
237
What IHC marker can be used to differentiate a malignant melanoma from a melanocytoma and how does the expression of this marker differs between them?
RACK1 (receptor for activated C kinase 1) Malignant melanomas stain homogeneously and benign ones heterogeneously Correlates with cell and nuclear size
238
What 2 transcription factors haven been associated with increased risk of death in dogs with melanomas? Which one was of prognostic significance on multivariate analysis?
FOXP3, IDO (indoleamine 2,3-dioxygenase) Increased risk of death associated with higher: - # FOXP3/HPF - % of FOXP3+ infiltrating lymphocytes - # IDO+ cells/HPF Only #IDO+ cells/HPF prognostic on multivariate
239
What is the overall MST and PFS in dogs with anal sac melanoma treated with a combination of therapies?
``` MST 3.5m (107d) PFS 3m (92.5d) ```
240
What ICC stain has been shown to be 100% sensitive and specific for the diagnosis of amelanotic melanoma? How does this differ when compared to routine cytology stains?
Melan A Routine cytology: 67% sensitive, 86% specific
241
When evaluating histopathology LN samples in dogs with melanoma and trying to differentiate malignant melanocytes from melanophages, the addition of Melan A has been reported to change the final diagnosis in what % of samples?
47% 14 from metastatic to reactive 1 from reactive to metastatic
242
What is the reported range of complete agreement between cytology and histopathology for the diagnosis of metastatic LN in dogs with melanoma?
30- 50% POOR
243
What are the reported ranges for ORR, CR, PR, and PFI, in dogs with OMM when treated with hypofractionated RT? Time to metastasis?
ORR 83-100% CR 50-70% PR 25-30% Time to mets 310d
244
What is the reported overall PFS and MST in dogs with OMM when treated with RT? 1 and 2 yr SR?
PFS 5-8m MST 4-12m (stage dependent) 1-yr SR 35-50% 2-yr SR 20%
245
What is the reported rec | OMM when treated with RT in the microscopic vs gross dz setting?
Microscopic 25% | Gross 45%
246
What is the MST for stage I, II, III, and IV oral MM in dogs when treated with RT and adjuvant sx or chemo? Any prognostic factors identified?
Stage I: 2yrs (758d) Stage II: 9m (278d) Stage III: 5.5m (163d) Stage IV: 2.5m (80d) Stage
247
What has been shown to affect prognosis in dogs with OMM treated with different forms of RT (6)? These dogs were also +/- treated with sx and chemo.
- Stage; stage I dz vs higher and stage III dz tx with orthovoltage (shorter MST) - Tumor volume/size (>5cm3 shorter MST) - Bone involvement (shorter TTP and MST) - High VEGF (shorter TTP and MST) - Location (rostral better) - RT in the microscopic dz setting (better)
248
What % of dogs with OMM is reported to develop oronasal fistulas and bone necrosis when tx with RT?
5.4% oronasal fistula | 7-8% bone necrosis
249
When combining chemotherapy with RT for the treatment of OMM, what drug has been shown to be effective and how did it affect prognosis?
Temozolamide: 60mg/m2 x 5 days then q1 month RT: 6 Gy x 5 Dogs tx with TMZ had a longer TTP vs RT alone; 205d vs 110d No difference in ORR or MST
250
Dogs with OMM of what tumor volume are more likely to achieve a CR and longer MST when treated with RT?
<5cm3
251
Dogs with OMM have elevated ____ plasma values when compared to normal dogs. What are 2 ways this can affect prognosis in dogs when treated with RT?
VEGF; shorter TTP and MST
252
Expression of ___ by tumor infiltrating lymphocytes has been documented in dogs with OMM. In what other tumors has this been documented (5)?
PD-L1 Also in OSA, HSA, MCT, CMT, prostatic ACA
253
A mutation in the KIT gene has been detected in exon ___ in ___% of dogs with MM. All samples with a mutation were KIT+ on IHC, but what was the difference in staining? How does the mutation affect prognosis?
Exon 11, C -> T mutation 10% of dogs with MM Strongly positive in 56% Weakly positive in 44% Significantly associated with dz recurrence
254
How does the Oncept melanoma vaccine work? In what % of dogs is a cell-mediated immune response produced?
Encodes human tyrosinase gene, which is inserted into pING plasmid vector. Plasmid vector contains cytomegalovirus promoter, kanamycin resistance selection marker, and a CpG sequence (which signals through TLR9). Tumor Ag is taken up by DCs -> presented via MHC class II (less commonly, class I) -> incites cell-mediated immune response in ~1/3 of dogs -> production of Ag-specific IFN-y T-cells CpG sequences also augment TH1 response
255
What is the overall MST in dogs with stage I-III OMM and either adequate or inadequate locoregional control when treated with all available xenogenic vaccines?
Adequate locoregional control > 3yrs Inadequate locoregional control 18m
256
In vitro, high-dose of what substance have induced apoptosis in melanoma cell lines? How does it induce apoptosis?
High-dose ascorbate | activation of Bax?
257
What is the overall metastatic rate in cats with malignant melanoma (excluding ocular)?
30.7%
258
What extra-ocular malignant melanoma site in cats has the shortest MST vs the longest when treated with multiple therapies?
Oral MST 4 Cutaneous MST 6 Auricular MST not reached
259
What are 2 identified prognostic indicators in cats with MM and how do they affect prognosis?
Amelanotic melanoma - negative prognosis | Surgical therapy - longer MST
260
What % of cats treated with the Oncept vaccine develop adverse events? Is the incidence higher or lower in dogs?
12% - pain on administration, brief muscle fasciculation, transient inappetence, depression, nausea, mild increase in pigmentation at injection site Incidence of AE higher in dogs
261
How are SCC categorized according to their degree of invasiveness?
In situ Superficial (<2mm deep) Infiltrative
262
ORR, recurrence rate, and ST in cats with IN SITU nasal planum SCC in situ when treated with Strontium?
ORR 100% RR 0% ST > 3000d
263
ORR, PR, CR, recurrence rate, PFI, and OST in cats with SUPERFICIAL nasal planum SCC when treated with Strontium? What % developed new lesions at a different location?
ORR 98% (CR 88%, PR 10%) RR 20% at median time of 308d only in cats with T1+, but no in situ ST > 3000d; better for those with a CR vs PR New lesions 33%
264
ORR, CR, RR in cats with all degrees of invasive nasal planum SCC when treated with strontium?
ORR 100% (CR 87%, PR 13% ) RR 13% - only in the 2 cats that had a PR which also had T2 dz at 81 and 141d
265
A study in cats with all degrees of invasive nasal planum SCC evaluated the use of fractionated vs single dose strontium. Was there a difference on ORR, DFI, or MST between the tx groups? Positive prognostic factors identified? (4)
No difference in ORR or MST, but DFI of cats tx with fractionated protocol significantly longer ORR 96%, CR 74%, PR 22%, RR 17% at median of 251d DFI 780d OST 1040d ``` PF: CR = longer ST No comorbidities = longer ST Early stage dz (T1-2) = longer ST Fractionated protocol = longer DFI ```
266
What % of dogs with nasal SCC that undergo nasal planectomy with bilateral labial mucocutaneous rotational flap experience complications? Most common complications (2)? What % required revision surgery? Clean margins were obtain in what % of dogs? Pulmonary metastatic rate?
73% overall complication rate Complications: 50% dehiscence 20% narrowing of nasal orifice 35% revision surgery 88% obtained clean margins 18% pulmonary mets at ~1 yr post diagnosis
267
Most common clinical signs in dogs with nasosinal tumors? Others? What clinical signs could make you be more concerned about neoplasia vs non-neoplasia?
Unilateral epistaxis and/or mucopurulent discharge of 2 to 3 months duration Other: facial deformity, sneezing, unwillingness to open mouth, dyspnea or stertorous breathing, exophthalmos, ocular discharge (due to mechanical obstruction of nasolacrimal duct) Facial deformity, stridor -> cancer Systemic clinical signs -> non-neoplastic
268
What clinical sign in dogs with nasosinal dz is significantly noted to be more common with neoplasia, foreign bodies, and nasal mycosis? What about with cancer specifically?
Pure or mixed hemorrhagic discharge Stridor, facial deformity (can happen with fungal and angiomatous proliferation too)
269
What staging system for dogs with nasosinal neoplasia have been associated with prognostic significance when RT is used?
Adams | Modified Adams
270
Describe the modified Adams staging system
Stage I - confined to one nasal passage, paranasal sinus, or frontal sinus, with NO bone involvement beyond turbinates Stage II - ANY bone involvement beyond turbinates, BUT NO evidence of orbit/subcutaneous/submucosal mass Stage III - involvement of orbit and/or nasopharyngeal, subcutaneous, or submucosal mass Stage IV - cribriform plate lysis
271
How has the modified Adams' staging system been associated with prognosis in dogs with nasosinal tumors that are treated with RT?
Dogs with stage IV dz based on CT images have shorter DFI and ST when treated with definitive RT
272
What is the MST and DFI of dogs with stage I vs stage IV dz when treated with definitive RT?
Stage I - DFS 6.5m, MST 24m Stage IV - DFS 4m, MST 7m
273
What is the overall MST of dogs with untreated nasal carcinomas? 
3m (95d)
274
What is the MST in dogs with untreated nasal carcinoma that have epistaxis vs in dogs w/o?
Epistaxis - 3m (88d) Without - 7.5m (224d)
275
What is the MST of dogs with nasal tumors when tx with definitive RT alone?  1-yr and 2-yr survival rates? What % of carcinomas experience tumor volume reduction compared to sarcomas?
7 to 20 months 1-yr survival rate 40-70% 2-yr survival rate 10-45% Carcinomas - 70% Sarcomas - 20%
276
What RT boost technique were recently published in dogs with nasal tumors when treated with IMRT with the goal of administering a higher dose and decreasing side effects and what was the outcome?
Boost technique: GTV receives a higher dose (20% in the study) while maintaining same CTV Ocular changes were negligible 33% developed VRTOG grade 3 mucositis Late AE not evaluated Median PFI and ST not reached
277
What is the MST in dogs with nasal tumors when treated with palliative RT? What % of dogs have improvement of clinical signs? Median duration of response?
MST 5 to 10 months 65-100% improvement of CS Duration of response: 4 to 10m
278
What are some identified positive (2) and negative (5) prognostic factors in dogs with nasal tumors when tx with palliative RT?
Positive for complete resolution of CS: - Adams stage I dz - CS present for >90d Negative PF: - CS present for <90 days prior to dx associated with higher risk of relapse - Adams stage IV dz - MST ~4.8m - Age of <10yrs - Non-dolichocephalic breeds - Dyspnea
279
What are some acute SE from definitive RT and how long do they take to resolve?
Oral mucositis, KCS, blepharitis, rhinitis, skin desquamation Within 2-8 weeks after tx
280
What are some late SE from definitive RT? When do they usually develop?
Cataracts, corneal keratitis, corneal atrophy, KCS, uveitis, retinal hemorrhage and degeneration, neuronal tissue SE (brain necrosis causing neuro changes or seizures, optic nerve degeneration), skin fibrosis. Months to years after therapy; irreversible
281
What are the most common and clinically relevant late effects in dogs with nasal tumors treated with RT?
Ocular changes - usually occur 6 to 9 months after RT KCS, cataract formation, blindness
282
What is the overall MST and PFS in dogs with nasal tumors when treated with SRT (3 papers)? MST specifically for carcinoma, sarcoma, and OSA?
Overall MST 8.5- 19.5m PFS 1yr Sarcoma - 10.7m Carcinoma - 10.4m OSA - 3m (significantly shorter ST)
283
What is the overall response or clinical response rate in dogs with nasal tumors when treated with SRT?
95-100%
284
What % of dogs with nasal tumors treated with SRT develop acute and late side effects? What % of dogs are euthanized due to late AE?
Acute 23-32% Late 17-40%; highest with SRS single fraction (fistulas, osteonecrosis, seizures) 7% mortality rate
285
What is the 1 and 2 yr SR in dogs with nasal tumors treated with SRT?
1 yr - 70% | 2 yr 40%
286
In dogs with nasal tumors treated with SRS, what has been associated with increased acute AE?
GTV > 50cm3
287
When gemcitabine is used as a radiosensitizer in dogs and cats with nasosinal carcinoma that are treated with RT, what % requires dose reductions?
Cats 50% Dogs 80% Neutropenia or local acute tissue damage
288
What is the MOA for gemcitabine when used as a radiosensitizer?
Inhibits RNR -> depletion of dNTPs -> inhibition of DNA polymerase and decreased DNA repair Results in inhibition of sublethal damage repair; most evident in mismatch repair-deficient cells Most pronounced if administered 24-60 hours prior to RT
289
What is the MOA for cisplatin when used as a radiosensitizer?
Covalently binds to purine DNA bases, causing adducts, and causing dsDNA breaks; decreases ability of tumor cells to repair DNA damage caused by ionizing RT; inhibition of non-homologous end-joining Exposure to RT causes single and double strand DNA breaks Although cisplatin does not increase the number of DSB, having an adduct near a DSB results in complete abolition of NHEJ repair The presence of unrepaired ds breaks results in cell death
290
What patients are at risk for development of benign osteocartilaginous tumors? What are these composed of and where do they arise from?
Young px with active osteochondral ossification sites Tumors that grow from the cartilaginous rings and are composed of cancellous bone capped by cartilage; they grow at the same speed as the rest of the skeleton May reflect a malfunction of osteogenesis rather than true cancer and are benign Young px also at risk of oncocytoma development
291
What are oncocytes?
Epithelial cells characterized by an excessive number of mitochondria, resulting in an abundant acidophilic and granular cytoplasm. Can be benign or malignant
292
What are rhabdomyomas?
Benign tumor of skeletal muscle | Can be large, minimally invasive, and do not metastasize
293
How can rhabdomyomas be differentiated from oncocytomas?
Transmission electron microscopy and IHC Appear THE SAME with light microscopy - 3 laryngeal tumors dx initially diagnosed as oncocytomas by light microscopy were dx as rhabdomyomas after ultrastructural and immunocytochemical examination - Rhabdomyomas are different from oncocytomas, but require electron microscopy or IHC to be differentiated from oncocytomas because they appear identical on light microscopy - Same thing for rhabdomyosarcoma, diagnostic features of skeletal muscle differentiation may not be evident at the light microscope level and may only be recognized by IHC or transmission electron microscopy. TEM is the gold standard in both humans and dogs, but it cannot differentiate between the subtypes.
294
The majority of laryngeal tumors in dogs are malignant and very locally invasive, except which one?
Rhabdomyoma Can be large but are minimally invasive and do not metastasize
295
Most common primary lung tumor in dogs and cats? Humans?
Dogs - bronchoalveolar carcinoma 85% Cats - adenocarcinoma 60-70% Humans - small cell carcinoma 25% and non-small cell 85%
296
What % of dogs with pulmonary carcinoma have evidence of local vascular or lymphatic invasion and what is the distant metastatic rate?
Local vascular or lymphatic invasion - 70% Distant - 25%  Anaplastic CA >90%, SCC >50%
297
What is the metastatic rate in cats with pulmonary carcinoma?
Overall 75% (LN 30%, intrathoracic 30%, extrathoracic 15%) 88% of cats with digital carcinoma have metastasis from a primary pulmonary carcinoma; MST 1m with digital amputation alone; not recommended as other lesions cn pop up
298
How can you confirm pulmonary metastasis on a digital lesion?
IHC with TTF-1 and the presence of ciliated epithelial cells (thyroid transcription factor 1)
299
Prognostic factors in dogs with pulmonary carcinoma (8)?
``` CS at diagnosis Tumor size >100cm3 TNM stage (>T1N0M0) LN involvement Involvement of entire lung lobe Gross dz post-operatively Histologic type (papillary has best prognosis vs. SCC and undifferentiated Ca) Histologic grade (well differentiated best progn) ```
300
Prognostic factors in cats with pulmonary carcinoma (8)?
``` CS at diagnosis (dyspnea, especially) TNM stage (>T1N0M0) LN enlargement Pulmonary metastasis Histologic type Histologic grade Degree of differentiation Pleural effusion ```
301
MST in dogs with T1, T2, T3, N0, and N1 pulmonary carcinoma when tx with surgery? Statistically, which one has the best ST?
``` T1 (solitary): 12-26m T2 (multiple): 2.5-7m T3 (invasive into adjacent tissue): 23d-3m N0: 6-15m N1: 1 to 2m ``` T1N0M0 tumors of papillary type MST 18.5m (555d) vs 72d for others
302
MST in dogs with pulmonary ACA vs SCC vs papillary* adenocarcinoma when treated with sx?
Papillary - 18.5m ACA - 19m SCC - 8m All other tumor types 2.4m
303
What is the MST in cats with well-differentiated bronchogenic carcinoma when treated with sx?
23-24m Some studies say shorter ST
304
What are the surgical approaches for lung lobectomies? What approach is required for removal of lesions in multiple lobes? What approach is associated with higher morbidity?
Lateral (intercostal) thoracotomy and median sternotomy Median sternotomy needed for multiple Median sternotomy - more likely to have increased fluid production from chest tube, hypoxia, prolonged hospital stay For hilar LN biopsies - easier to perform via lateral thoracotomy
305
What is the TTP and MST in dogs with advanced pulmonary carcinoma when treated with sx vs metronomic chemotherapy with CTX, thalidomide and piroxicam vs no therapy? Main findings?
Metronomic chemotherapy: TTP 5.7m MST 4.6m Surgery: TTP 3m MST 3m No therapy: TTP 20d MST 2m Significantly longer TTP and MST with MC vs sx and MTD groups.
306
Breeds predisposed to develop pulmonary histiocytic sarcoma (2)?
Pembrook Welsh Corgis, Min Schnauzers
307
When compared to other pulmonary tumors, what imaging characteristics do pulmonary HS have in dogs (3)?
- Significantly larger - Right middle (43%) and left cranial (38%) most common locations - More likely to invade entire lobe
308
What % of dogs with localized HS have the pulmonary form?
31%
309
What is the overall PFI and MST of dogs with pulmonary HS?
PFS 7m | MST 4.5-8m
310
What is the PFS and MST of dogs with pulmonary HS treated with CCNU chemo alone?
PFS 3m | MST 4m
311
What is the PFS and MST of dog with pulmonary HS treated with surgery and CCNU?
PFS 9m | MST 12.5m
312
What prognostic factors (3) in dogs with pulmonary HS negatively affect PFI and MST?
Clinical signs - PFS only Intrathoracic mets - PFS & MST Tx with sx alone Tumor size NOT prognostic
313
ORR of dogs with pulmonary HS to chemotherapy?
44%
314
In Norway, what breeds are at increased risk for developing testicular tumors? Which ones?
Shelties and Collies have a 5x increased Shelties - majority (80%) are Sertoli Collies - majority (70%) mixed Sertoli/seminoma Norweigan elkhounds - 2x increased risk of seminoma
315
What breeds (3) most commonly get seminomas?
German Shepherds Belgian Malinois Norweigan elkhounds (2x increased risk)
316
With what frequency do the different types of testicular tumors occur in dogs within the USA?
Equal frequency
317
What testicular tumor most commonly secretes estrogen?
Sertoli 50% produce estrogen and signs of feminization; 17% if scrotal
318
What testicular tumor is most likely to cause feminization signs? Is it affected by location? How can estrogen be measured?
Sertoli (>50% if cryptorchid and 15% if scrotal) Estraidol 17-B - usually higher when compared to normal dogs; not all dogs have elevated estraidol Testosterone/estraidol ratio - usually lower; feminization signs occur secondary to disruptions in this ratio, may be better
319
What are the clinical signs associated with feminization syndrome?
Bilateral symmetric alopecia, cutaneous hyperpigmentation, thinning of skin, galactorrhea, gynecomastia, atrophy of prepuce, atrophy of contralateral testicle, squamous prostatic metaplasia, bone marrow suppression
320
What effects can hyperestrogenism have on the bone marrow?
BM suppression/hypoplasia: may be irreversible Transient increase in granulopoiesis with peripheral neutrophilia followed by progressive neutropenia, thrombocytopenia, and nonregenerative anemia
321
Which testicular tumor can sometimes be associated with perianal gland hyperplasia?
Interstitial cell tumor
322
What % of dogs with a testicular tumor have a contralateral testicular tumor or a primary tumor elsewhere?
50% Therefore, COMPLETE STAGING is recommended
323
What % of dogs with prostatic carcinoma have COX-2 expression vs normal prostate?
75-88% express COX-2 (vs 0% normal prostate tissue)
324
Dogs with prostatic carcinoma have an improved ST when treated with what?
NSAID; MST 7m vs 0.7m if no nsaid A 2018 study NSAID MST 1.7m Piroxicam or carprofen
325
What % of dogs with prostatic carcinoma have a BRAF mutation?
85%
326
What is the benefit of systemic chemo for prostatic carcinomas?
Unclear
327
What is an identified risk factors for prostatic carcinoma development in dogs?
Castration; OR 2.3:4.3 Also tend to develop more aggressive tumors
328
What % of dogs with prostatic carcinoma have metastasis at the time of diagnosis and at the time of death?
40% at diagnosis; SLLN most commonly | 80% at death
329
What % of canine prostatic carcinoma develops metastatic disease to bone? Most common site? Mediated by (3)?
22 to 42% Lumbar vertebrae and pelvis May be mediated by TGF-B, PTH-rP, endothelin  More commonly osteoproductive, but can also be osteolytic Skeletal metastasis most commonly OSTEOBLASTIC in nature
330
Unlike humans, in dogs with prostatic carcinoma, downregulation or hypermethylation of what gene has not been detected? Like humans, dogs exhibit loss of ___ and gain of ___.
APC gene Loss of NKX3.1 Gain of c-MYC
331
When compared to BPH, dogs with prostatic carcinoma have increased nuclear expression of what 2 things?
Survivin | Sox9 (stem cell marker)
332
What % of dogs with prostatic carcinoma have a concurrent UTI?
33-36%
333
Mineralization in the canine prostate can be due to what?
In intact dogs - prostatitis, BPH, cysts | In neutered dogs - 100% PPV for neoplasia
334
Prostatectomy should be considered in which dogs?
Dogs with early stage dz and no capsular involvement
335
What % of dogs undergoing total prostatectomy develop major complications, transient incontinence, and permanent incontinence?
Major complications - 16%: dehiscence, uroabdomen, prepubic herniation 60% transient - resolved within 4 weeks 35% permanent incontinence
336
In the VSSO study where dogs were treated with prostatectomy, did the addition of chemotherapy prolong ST?
No
337
What is the DFI and MST in dogs with prostatic carcinoma when treated with prostatectomy, NSAIDs, and chemo? Negative PI in the VSSO study (1)?
DFI 3m (2.7m) MST 8m (7.7m) 1-yr SR 32% and 2-yr SR 12% Histologic extracapsular extension MST 4.6m
338
Overall clinical response rate and MST of dogs with TCC and prostate involvement when treated with chemo and an NSAID?
Clinical response 33% | MST 3.5m
339
Negative PI in dogs with prostatic carcinoma when treated with chemo + NSAID? (4)
- Intact male status - shorter MST - Presence of CS - shorter MST - Metastasis to sites other than lungs - shorter MST - Tx with NSAIDs alone (TTP/MST 1.7m vs addition of chemo 3.5m)
340
Survival time of dogs with prostatic lymphoma? How does it usually present? US characteristics? Most common phenotype? Breed?
Mean ST 2m; 2 dogs tx with chemo survived for 1 and 10m 56% had LN involvement and all appeared to have multicentric intra-abdominal dz US: hypoechoic lesions, ABSENCE of mineralization T-cell most common 1/2 were Labs
341
How can you use PCR to diagnose a TVT?
TVT cells all share a c-myc oncogene rearrangement - a long interspersed nuclear element (LINE-1) is present 5’ to the first exon LINE-1 can disrupt transcriptional regulation of downstream genes, potentially initiating oncogenic activity LINE-c-myc sequence is used to confirm a diagnosis with PCR
342
How does the karyotype change in dogs with TVT?
Highly conserved karyotypic changes Normal dogs have 78 chromosomes and all but 2 are acrocentric (the 2 sex chromosomes) TVT cells have a rearranged karyotype consisting of 57-59 chromosomes, including 15-17 submetacentric (resulting from fusion) chromosomes and 40-42 acrocentric chromosomes TVT cells are aneuploid but exhibit stable and similar karyotypes in samples from different regions
343
How does TVT influence the immune system?
TVT cells downregulate MHC class I B2 microglobulin and MHC class II expression; this occurs secondary to TGF-B1 production by the tumor and allows for immune system evasion and decreased NK cell activity Tumor infiltrating lymphocytes produce IFN-y, which promotes MHC expression and counteracts TGF-B1 actions from tumor cells; TIL then secrete IL-6 which is synergistic with IFN-y -> MHC expression and NK function is restored, allowing for tumor regression This occurs during P phase, but expression of IL-6 triggers R phase
344
Why do females develop hepatoid gland adenomas when spayed?
They lose estrogenic inhibition
345
What is the most common intraocular tumor in cats?
Anterior uveal melanoma
346
What is the metastatic rate of anterior uveal melanomas in cats? Locations?
50% | Lungs or liver
347
When do anterior uveal melanomas metastasize in cats?
1 to 3 years post enucleation
348
How do anterior uveal melanomas progress in cats?
Slowly progressive over months to years : iridial hyperpigmentation -> glaucoma
349
What are identified prognostic risks for metastasis in cats with anterior uveal melanomas (4)?
More common with high MI Larger tumors Tumor invasion into ciliary body stroma Invasion into scleral venous plexus
350
What are prognostic factors for ST identified in cats with anterior uveal melanomas (4)?
Tumor confined to iris stroma and trabecular meshwork = longer ST, decreased MR Enucleation after invasion to ciliary body (but NOT sclera) = MST 5 yrs Enucleation after scleral invasion = MST 1.5yrs Glaucoma
351
What can increase the risk of SCC development in cats (4)?
Flea collars 5x Canned tuna 4.7x Canned food 3x Household smoke 2.5x
352
The risk of tonsillar SCC is ___x higher in dogs living in urban
10x
353
What oral tumors are known to be responsive to RT (3)?
Melanoma Canine oral SCC Acanthomatous ameloblastoma
354
What oral tumors are considered to be RT resistant (2)?
Feline SCC | Fibrosarcoma 
355
Canine papillary oral SCC: - Age of dogs? - Most common location? - What % have T2 or T3 dz at diagnosis? - Overexpression of what protein? - Met rate? - Therapy, prognosis, and MST? - Histopathology?
Very young dogs; 2-5m; 1 study 75% >6yrs 70% rostral; arise from gingiva of dentate jaws 92% are advanced T2-T3 at dx; seem large and invasive p53 Complete excision or reduction + RT: all dz-free at >4yr 0% metastatic rate Excellent prognosis Histopath: -Exophytic superficial papillary portion that lacks criteria of malignancy and can be confused with papilloma - Deep invasive portion extends into gingival stroma or bone can be confused with SCC or ameloblastoma - Papillomavirus has not been detected
356
What was recently published about intratumoral T cells in cats with oral SCC (3)?
- CD3+ T cell infiltrates in 92% of samples - T-regs within the neoplastic epithelium and stroma in 60% - Increased total frequency of circulating Tregs compared to healthy controls (but proportion of T regs compared to other lymphocytes unchanged)
357
As opposed to high COX2 expression in dogs with oral SCC, what % of oral SCC in cats express COX2?
18% - therefore COX2 likely not beneficial
358
What is the significance of MVD and EGFR expression in cats with oral SCC?
High MVD = shorter MST | EGFR expression inversely related to ST
359
MVD is higher in which location in cats with oral SCC?
Higher in TONGUE vs mandibular and maxillary regions
360
What negative prognostic factors (3) have been identified in cats with oral SCC when treated with SRT? How do they affect prognosis?
Higher MVD, more keratinized SCC, male sex = shorter PFI and ST
361
Negative PI in cats with oral SCC (8)?
Anorexia at dx Location: - Tonsillar/cheek - improved prognosis with accelerated RT/carbo (mean ST 725d vs other locations) - Mandible with sx -improved Complete response to accelerated RT/carbo (MST 375d) Male cats High bmi-1% expression (protein involved in self-renewal) High MVD High EGFR (inversely related to ST) More keratinized SCC
362
Palladia ORR/biological response and MST in cats with SCC? Prognostic indicators? Toxicity %?
ORR 57% (biological response rate) MST 4m NPI: Anorexia at dx 17% had AE (grade 1-2GI, 1 grade 4 ALT)
363
Fatty acid synthase is over expressed in humans and cats with what type of cancer? What medication has been shown to reduce cell viability in vitro?
SCC | Orlistat - FASN inhibitor
364
Recently, ___ was shown to decrease canine SCC cell growth in vitro in tumors that over-expressed ___.
``` YM 155 (a survivin inhibitor) Survivin ```
365
With surgery for oral melanomas, the disease is usually controlled in ___% of the cases.
75%
366
What factors affect prognosis in dogs with oral melanoma when treated with sx (3)?
Tumor size: <2cm vs >2cm Stage - mets vs no mets Ability of the first sx to achieve local control
367
Sensitivity of CT for identifying metastatic LN in px with oral tumors?
Poor | 10-12%
368
What % of dogs and cats with facial/oral tumors have metastasis to the mandibular LN vs other regional LN? When retropharyngeal LN metastasis is present, what LNs are also ALWAYS involved according to one study? What % has ipsilateral vs contralateral metastasis?
55% Mandibular LN Ipsilateral 90% Contralateral 60%
369
What is the MST in dogs with oral MM when treated with sx alone for stage I-III dz?
I: 17-18m (PFI 19m) II: 5-6m III: 3m
370
What is the most common intra-operative complication in dogs with oral tumors undergoing a partial maxillectomy?
Intraoperative bleeding - 53% 43% required blood transfusion
371
Complications like IO bleeding and requirement of a blood transfusion in dogs with oral tumors undergoing a partial maxillectomy are significantly associated with what 4 things?
- tumor size - location (caudal) - maxillectomy type (complete, caudal, and if involving orbit) - surgical approach (dorsolateral combined with intraoral)
372
What are the 3 most common short-term complications in dogs with oral tumors undergoing a partial maxillectomy?
Lip trauma 13% | Dehiscence and fistula 11%
373
Most common post-op complications in dogs with oral tumors undergoing a partial maxillectomy (3)?
Minor epistaxis Facial swelling Difficulty eating
374
What % of dogs and cats with tonsillar SCC have systemic dz at diagnosis? What % of dogs develop LN and pulmonary mets?
90% 70% LN 10-20% pulmonary mets at diagnosis
375
What % of dogs with tonsillar SCC have bilateral dz as per CT?
50%
376
Canine tonsillar SCC and surgery?
Rarely curative and if performed, it should be bilateral due to high % of dogs with bilateral dz
377
Control rate with radiation therapy alone and 1-yr SR in dogs with tonsillar SCC? Can this be improved?
75% control rate <10% 1-yr survival Yes; with chemotherapy - improved RR and ST
378
Overall MST of dogs with tonsillar SCC treated with sx, RT, and/or chemotherapy?
6m *Significantly improved ST*
379
Negative PI in dogs with tonsillar SCC (3)?
Anorexia Lethargy Lack of RT/chemo
380
Urban environments are associated with increased risk of what types of cancer in urban dogs?
Canine LSA Tonsillar SCC Nasal tumors in dolicocephalic breeds
381
Recent literature suggest an improved overall MST for oral FSA in dogs of what?
8m to 2 years | Likely due to improved sx technique
382
Overall MST, recurrence rate, and 1-yr SR of dogs with oral FSA treated with surgery alone? What is prognostic (1)?
MST 10-12m RR 30-50% 1-yr SR of 20-50% MST lower with conservative vs aggressive sx; MST 300d vs 526 days
383
DFI and MST of incompletely excised oral FSA in dogs?
DFI 13m MST 19m 50% of maxillary tumors incompletely excised
384
MST of dogs with oral FSA when tx with RT alone? What is prognostic (1)?
MST 7m Definitive RT longer PFS vs palliative; PFS 470d vs 170d
385
PFI, MST, recurrence rate, and 1-yr PFS in dogs with oral FSA when treated with sx and adjuvant RT? What is prognostic (1)?
PFI 10m MST 18-26m (1.5 to 2.2yrs) 24-32% recurrence 1-yr PFS of 76% Tumor size: T1 and T2 improved PFS and ST vs T3
386
Prognostic factors in dogs with oral FSA (7)? Strongest predictor of survival?
- Location: mandibular shorter PFS and MST vs maxillary - Size: MST not reached for T1 vs T2 and T3 - Grade - Tx with any type of RT longer PFS and MST, but definitive RT protocol better than palliative - Type of sx performed: no sx vs conservative vs aggressive - Complete sx excision vs incomplete - Sx + RT longer PFS and ST = STRONGEST
387
Most common lingual tumor in dogs and cats?
SCC
388
Possible predilection of lingual T-zone lingual lymphoma has been noted in what breed?
Golden Retriever
389
How does lingual T-zone lymphoma look grossly?
Multifocal to coalescing, raised, red, nodular mases RARELY ulcerated
390
What % of dogs with lingual T zone lymphoma have concurrent lymphadenopathy and lymphocytosis?
70% lymphadenopathy | 60% lymphocytosis
391
Most common immunophenotype of lingual T zone lymphoma?
CD8+ (majority) CD45- Lack epitheliotropism Expand within superficial submucosa and are separated from the dermis
392
CR and SD responses in dogs with lingual T zone lymphoma to any treatment?
CR 60% SD 30% 10/12 still alive 27 to 893d post diagnosis
393
What is the 4th most common tumor in the oral cavity of dogs?
OSA
394
Overall, what % of canine OSA is oral or maxillofacial?
12%
395
What % of axial canine OSA involves the mandible vs the maxilla?
Mandible 27% | Maxilla 16-22%
396
What is the overall metastatic rate of dogs with oral/maxillofacial OSA? What % of dogs have mets at diagnosis? Is the rate higher for the mandible or maxilla and if so, what is the metastatic rate? Time to metastasis?
35-40% overall 6% at diagnosis 58% mandibular 17-20 months
397
What type of OSA is most commonly seen in the mandible vs maxilla?
Mandible - osteoblastic | Maxilla - osteoclastic
398
Compare recurrence, metastasis, cause of death, and ST in dogs with mandibular vs maxillary OSA.
Maxillary - higher RR, local dz most common cause of death, no mets reported, shorter MST Mandibular - lower RR, metastasis most common cause of death in 35%, 58% met rate, longer MST
399
What is the MST, recurrence rate, MFI, metastatic rate, and 1-yr SR in dogs with MANDIBULAR OSA tx with maxillectomy and +/- chemo? Most common cause of death?
``` MST 17.5m RR 15-45% MFI 20m Metastatic rate 58% 1-yr SR 35-70% ```
400
Prognostic factors in dogs with mandibular OSA for metastasis and ST (2)?
- Grade: II/III tumors 2.4x increased risk of mets and shorter MST - Lack of adjuvant chemotherapy 2.6x increased risk of mets and shorter MST Overall, shorter MFI and MST
401
What OSA location in the canine head is most likely to recur after sx?
Calvarium MST 11m
402
Identified prognostic indicators in dogs with OSA of the head? Positive (4) and negative (5)
Positive: - mandibular location - smaller body weight - grade I - pure-bred dogs Negative: - Incomplete surgical margins - Grade II/III tumors - Lack of adjuvant chemo post op - Every 1,000-cell increase in monocyte count associated with a 76% increased hazard of death - MI >40 on univariate
403
Tx of choice for canine MLO?
Sx; poor responses to RT and chemo
404
Overall RR and RR for grade I, II, and III MLO in dogs? What is it dependent on (2)?
Overall 47-58% I - 30% II - 50% (47%) III - 80% (78%) Grade and margins
405
DFI in dogs with completely vs incompletely excised MLO?
Complete - 3.6 yrs | Incomplete - 11m
406
Overall metastatic rate and in grade I, II, and III in dogs with MLO? Incompletely vs completely excised tumors? Time to metastasis? What is it dependent on (2)?
Overall 60% to lungs I - 30% II - 60% III - 80% (78%) Complete - 25% Incomplete - 75% Late in dz Grade and margins dependent Slow growing tumor so can consider metastasectomy (>12m survival)
407
Overall MST and MST in grade I, II, and III MLO in dogs? What is it dependent on (2)?
Overall 21m I - 50m II - 22m III - 11m Location and grade dependent
408
What is the MST in dogs with MLO of the mandible vs other locations?
Mandibular MST 4yrs | Other: 1.5yr (590d)
409
What are the 2 types of feline epulides?
Fibromatous - 60% Giant cell epulis - 30%
410
How does GCE differentiate from fibromatous epulis in cats?
Significantly different and more aggressive behavior In dogs, these behave like fibromatous epulis and rarely recur post sx
411
Which IHC markers can be used for GCE and what cell origin are they suggestive of?
IHC suggestive of osteoclastic origin POS for: vimentin, TRAP, RANK NEG for: SMA, MIB-1, factor VIII In dogs, these behave like fibromatous epulis and rarely recur post sx
412
What % of AA invades bone?
80-100%
413
What is the most common site for AA in dogs?
Rostral mandible
414
What dog breeds are predisposed to developing AA?
Shetland and Old English sheep dogs
415
What 2 proteins are over-expressed in dogs with AA?
MMP9 | TIMP1
416
MST and recurrence rate for MANDIBULAR AA treated with mandibulectomy? 1yr SR?
MST not reached; >28-64m 0-3% recurrence 98-100% 1-yr SR
417
MST and recurrence rate for MAXILLARY AA treated with maxillectomy? 1yr SR?
MST not reached; >26-30m 0-11% recurrence 71-100% 1-yr SR
418
When hypofractionated RT is used to treat AA, what is the 3-yr PFS? Recurrence rate? Complications (2)?
80% 3-yr SR 8-18% recurrence; 8x higher risk in T3 tumors Transformation in 5-18% Bone necrosis 6%
419
Response rate of IL bleomycin in dogs with AA?
100% CR for > 1 yr in 4 dogs
420
What is the MST in dogs with incompletely excised non-tonsillar SCC that do not receive adjuvant therapy vs those that receive RT post operatively? Protocol used?
Sx alone - 6m Sx + RT - 5.6yrs 8-9 Gy x 4 (weekly) (In the case of FSA, did not improve outcome)
421
Compared to other oral tumors in dogs, what tumor is most likely to be incompletely excised after maxillectomy?
FSA | 50% incompletely excised
422
Why can't imatinib and masitinib be used in dogs with oral FSA?
In vitro, cell death requires doses unable to be achieved clinically Effects potentiated by doxorubicin.
423
What things are evaluated when determining the grade of a ST?
Degree of differentiation: normal M tissue [1], specific histo type [2], undifferentiated [3] Mitosis: 0-9 [1], 10-19 [2], 20 or > [3] Necrosis: none [1], 50% [2], >50% [3] Grade I: cum score of 4 or < Grade II: cum score of 5-6 Grade III: cum score of 7 or > LOOK AT GRADE TABLE!!
424
What are 2 stains that will help confirm a peripheral nerve sheath tumor?
S-100 - derived from cells of neural crest origin normally present in cells derived from the neural crest (Schwann cells, and melanocytes), chondrocytes, adipocytes, myoepithelial cells, macrophages, Langerhans cells, dendritic cells, and keratinocytes. Some FSA +. Vimentin - protein expressed in mesenchymal cells (all sarcomas positive)
425
What is the difference in histology between lipomas and liposarcomas?
Lipomas have INDISINCT nuclei and cytoplasm resembling normal fat. Liposarcomas are characterized by increased cellularity, DISTINCT nuclei, and abundant cytoplasm with one or more droplets of fat.
426
Where are intermuscular lipomas usually located?
Caudal thigh of dogs between the semitendinosus and semimembranosus
427
What is the most common complication seen with removal of intermuscular lipomas?
Seroma formation if a penrose drain is not used
428
What are infiltrative lipomas?
Uncommon tumors composed of well-differentiated adipose cells without evidence of anaplasia.  Cannot be differentiated from simple lipomas.  Considered benign and do not metastasize.  Commonly invade adjacent muscle, fascia, nerve, myocardium, joint capsule, and even bone. Aggressive treatment such as amputation may be needed.
429
What is a diagnostic challenge seen when using CT to evaluate infiltrative lipomas?
It cannot be distinguished from normal fat and DO NOT contrast enhance. They are, however, more likely to have an irregular shape. Liposarcomas, however, DO contrast enhance
430
What are liposarcomas?
Malignant tumors arising from adipoblasts They are locally invasive They DO CONTRAST ENHANCE!!
431
What is the metastatic potential of liposarcomas and what are the most common sites they metastasize to?
Low to moderate Lungs, liver, spleen, and bone
432
Metastasis in dogs with liposarcoma is more commonly associated with which histologic subtype?
Pleomorphic
433
Most common liposarcoma histologic subtype to metastasize to extrapulmonary soft tissue structures?
Myxoid
434
Is the prognosis in dogs with liposarcomas affected by the histologic subtype?
No
435
What is the MST for liposarcomas with wide resection, marginal resection, and incisional biopsy? 
MST 1200 days - wide surgical resection MST 650 days - marginal resection MST 180 - incisional biopsy  
436
CT characteristics of liposarcomas?
77% contained focal areas of fat attenuation 81% heterogeneous internal attenuation 38% lacked clearly defined capsule and were locally infiltrative 23% had foci of mineralization More likely to be heterogeneous, have a soft tissue component with irregular conglomerate appearance, mineralized, and have regional lymphadenopathy
437
How are rhabdomyosarcomas diagnosed?
Transmission electron microscopy IHC TEM is the gold standard in both humans and dogs, but it cannot differentiate between the subtypes.
438
What are the IHC stains and criteria used to diagnose rhabdomyosarcomas? What are some skeletal muscle specific markers?
At least 1 muscle specific marker and absence of smooth muscle markers is needed ``` Src-actin Myosin - mature SKM Myoglobin -mature SKM Myogenin - embryological nuclear TF MyoD - embryological nuclear TF ``` ALL are vimentin and desmin positive, but these lack specificity
439
How do lymphangiosarcomas look histologically and with what tumor can it be confused? What IHC (2)markers can be used to clear up confusion?
They resemble normal endothelial cells. May be confused with HSA because of the vascular channels, however, RBC are not seen within channels. Lymphatic and endothelial cells - both positive for factor VIII-RA and CD31 Lymphatic endothelial cells: PROX-1, LYVE -1 
440
What are dermal hemangiomas and HSA associated with?
UV light exposure in short-haired dogs with poorly pigmented skin
441
How are canine cutaneous HSA staged? What are the stages?
According to depth of involvement Stage I - confined to dermis Stage II - extending into SQ tissues (hypodermal) Stage III - involving underlying muscle (hypodermal)
442
What is the treament of choice fore cutaneous HSA?
Wide surgical excision +/- doxo (if stage II or III)
443
What is the ORR of doxorubicin for cutaneous HSA in the gross dz setting? Median duration of response?
ORR 40% 50d
444
What is the MST in dogs with stage I, II, and III dermal HSA when treated with surgery?
Stage I: 780 days (2yrs) Stage II-III: 5.5 to 10m (170-300d)
445
What is the metastatic rate for stage I, II, and III dermal HSA in dogs?
Stage I: 30% | Stage II-III: 60%
446
What is the locoregional recurrence rate in dogs with cutaneous HSA tx with sx? Most common in which breeds?
77%; pre-disposed breeds w/ventral location/multiple tumors 50-80% in cats
447
Prognostic factors in dogs with dermal (no SQ invasion) HSA?
Predisposed breeds = longer MST Ventral abdomen location = longer MST Solar changes = longer MST Mets or hemoabdomen = shorter MST
448
In dogs with SQ and IM HSAs treated with surgery, +/- radiation therapy, and doxorubicin, what is the median DFI and MST?
SQ - DFI/MST > 4yrs IM - DFI/MST 9m
449
What are the 2 different types of synoviocytes? 
Type A - phagocytic and resemble macrophages Type B - fibroblastic; produce glycosaminoglycan
450
From what type of synoviocytes do synovial cell sarcomas arise? What about histiocytic sarcomas? What is the exception?
Synovial cell sarcomas - Type B (fibroblastic) Histiocytic sarcoma - Type A (phagocytic macrophage resemblance) Periarticular histiocytic sarcoma - arises from dendritic cells; cannot use CD18 to differentiate between DC and type A macrophages
451
What immmunohistochemical cell marker, utilized to dx histiocytic sarcomas, cannot differentiate between macrophages (type A synoviocytes) and dendritic antigen presenting cells?
CD18
452
IHC markers to differentiate between synovial cell sarcoma, histiocytic sarcoma, and malignant fibrous histiocytoma?
SCS: vimentin+, pancytokeratin +/- (small population) Histiocytic sarcoma: vimentin+, CD18+ Malignant fibrous histiocytoma: vimentin+, SMA+
453
What is the metastatic potential of synovial cell sarcomas? What are the most common metastatic sites?
Moderate to high (higher risk vs STS) Regional LN, lungs
454
Up to ___ % of dogs with synovial cell sarcomas have evidence of metastasis at the time of diagnosis and ___ % by the time of euthanasia. 
30% - diagnosis 55% - euthanasia  
455
What is the typical signalment for synovial cell sarcomas in dogs? Common anatomic locations?
Large breeds Flat-coated and Golden retrievers No sex predilection Larger joints - stifle, elbow, shoulder
456
Most common presenting complaint in dogs with synovial cell sarcomas?
Lameness
457
What are some radiographic features of synovial cell sarcomas in dogs? How are these be different from OSA? How do these differ in cats?
Periarticular soft tissue swelling, bone invasion manifested as ill-defined periosteal reaction and/or multifocal punctate osteolyitic lesions, can involve sites on either side of the joint. Cats - bone involvement is rare in cats
458
What is the treatment of choice? Why?
Limb amputation Local recurrence is common and MST is better (850d vs 450 if marginal resection) Forequarter amputation, hemipelvectomy or coxofemoral diasrticulation - as much as possible
459
Prognostic factors in dogs with synovial cell sarcomas (4)?
Stage/presence of metastasis Histologic grade Extent of surgical treatment Pancytokeratin +
460
What is the MST in dogs with synovial cell sarcoma with metastasis vs without?
W/o mets >36m | With mets <6m
461
What is the MST in dogs with synovial cell sarcoma when treated with amputation vs marginal resection?
Amputation - 30m | Marginal resection - 15m
462
What is the MST for the different grades of canine synovial cell sarcoma?
> 48m - grade I > 36m - grade II 7m - grade III
463
What is the MST and metastatic rate for dogs with synovial sarcoma, myxoma, histiocytic sarcoma, and other types of synovial tumors?
Synovial - MST 32m, MR 30-55% Myxoma - MST 30m, MR 0% Histiocytic sarcoma - MST 5m, MR 90% Other types - MST 3.5m, MR 100% 
464
For surgery alone... Recurrence rate for grade I, II, and III STS after marginal/incomplete resection in dogs? Median time to recurrence and metastasis? MST?
Grade I - 7% Grade II - 35% Grade III - 75% 1yr to recurrence and mets 4yrs
465
How does adjuvant RT delay time to recurrence in dogs with incompletely excised STS? Control rates at 1 and 2 yr? MST?
Time to recurrence >700d 80-95% controlled at 1yr 70-90% controlled at 2 yr 6yrs
466
What is the 3-year PFS and 3-year local failure free* probability for 3 years in dogs with incompletely/marginally excised STS when treated with hypofractionated RT? Local recurrence rate? Time to recurrence? Acute AE? MST?
3-year PFS probability: 24% 3-year local failure free probability: 73% 21% recurrence rate at a median of 9m AE: 65% required treatment (dermatitis, mucostitis) MST not reached Protocol: 6-8Gy/weekly for a total of 24-32Gy using electrons
467
Incompletely excised STS in a dog, what to do next?
A 2nd surgery is ALWAYS the best choice For low grade (I-II) - active surveillance or staging sx (scar with 0.5-1cm margins) High grade - sx if possible, if not RT (cumulative doses of >50Gy rec for better control) or metronomic chemo Consider adjuvant chemo for high-grade tumors, those with high met rate, presence of mets
468
How do Tregs and MVD change in dogs with incompletely excised STS after metronomic chemotherapy? Doses?
A 15.0mg/m2/day dose resulted in decreased # and % Tregs along with decreased tumor MVD A 12.5mg/m2/day decreased Treg # only; no change in % Tregs or MVD
469
What is the median DFI in dogs with incompletely excised STS treated with metronomic chemotherapy vs those not treated?
DFI > 410d in treated dogs vs 210
470
How does MC affect prognosis in dogs with STS?
Prolongs disease free interval time
471
What is the overall % of agreement between pathologists for tumor grade in pre-treatment biopsies vs excisional biopsies in dogs with STS? What % of pre-treatment biopsies underestimate the grade vs overestimate it?
60% agreement 30% underestimate 12% overestimate No statistical difference in accuracy between various techniques (punch, needle core, wedge) Histologic subtype agreed for 89% of cases
472
What is the sensitivity and specificity of pre-treatment biopsies for high grade STS in dogs?
95% specific 33% sensitive -You can believe a high grade result, but not a low grade
473
What is the sensitivity of LN aspirates for sarcoma in dogs?
67%
474
Mutation or loss of which gene/protein has been associated to cats with injection site sarcomas? Most common mechanism by which it occurs? How does this affect prognosis?
p53 LOH most common Rapid tumor recurrence and reduced overall survival
475
p53 mutations have been identified in ___ to ___% of cats with VAS. What type of p53 staining pattern is negatively associated with prognosis?
60 to 80% Cytoplasmic staining in 44%; shorter time to recurrence and ST
476
Although Withrow states that FeLV has not been detected in ISS, a newer study found viral particles in ___% of the cases
43%
477
Mor than ___% of FISS are COX-2 positive.
>56%
478
In cats with FIIS, COX2 expression is highest vs lowest in what situations?
High - in tumors with greatest inflammatory infiltrates Lowest - in grade 3 tumors vs 1 and 2 *One study found no association between COX2 and grade
479
c-kit expression is present in what % of FIIS?
19-26%
480
Answer the following questions for cats with ISS treated surgically with 5cm lateral margins and 2 fascial planes deep. Completely excised in what %? Local tumor recurrence in what %? Major complications in what %? What was the overall MST?
97% complete excision rate 14% recurrence rate 11% major complications; dehiscence in interscapular tumors most common 11% metastatic rate MST 907 days (2.4 yrs)
481
CCNU ORR, CR, PR, median PFS, and duration of response in cats with ISS?
ORR 25% (1CR, 6PR) PFS 2m (60d) Duration of response 2.5m (80d)
482
What % FSA in cats are virally induced? How does this affect prognosis?
2% Poor prognosis
483
Feline sarcoma virus
Results from the rare recombination of FeLV DNA provirus and feline proto-oncogenes, resulting in a hybrid. FeLV incorporates into feline's DNA near a proto-oncogene and takes up the proto-oncogene into the FeLV provirus -> formation of FSV occurs. In the process, part of FeLV GAG gene, most of the envelope gene, and all of the pole genes are lost. The loss of these vital components makes FeSV dependent on FeLV as a helper virus for replication. Recombination results in transformation of fibroblasts and production of fibrosarcomas. Cats with FeSV always test positive for FeLV Natural transmission between cats does not occur
484
FOCMA and FSV
FOCMA = protein found on the surface of FeLV and FeLV-induced neoplasms but not on non-neoplastic feline cells. It is detected serologically when cells expressing it react to immunoglobulins produced in cats that have regressed FeSV-induced FSA or FeLV infection. Some cats are capable of rejecting transformed cells and producing FOCMA antibodies. This is important in the experimental response of cats to FeSV because FOCMA Ab administration has been associated with tumor regression and failure to develop tumors. Cats that fail to develop FOCMA die quickly of fast-growing sarcomas. Ab to FOCMA van protect against neoplastic and myeloproliferative disease. Some FeLV vaccines contain FOCMA and elicit an anti-FOCMA response. The importance of this in preventing dz in vaccinates is unknown.
485
What is the biologic behavior of FSV?
Rrapid growth with doubling times as short as 12-72 hours. Lesions typically occur at sites of previous bite wounds. Met rate 30% to lungs or other organs. Chemo and RT have been used and although RT is usually combined with sx in the case of solitary tumors, recurrence both within the RT field or outside is common
486
The vaccine associated feline sarcoma task force recommends treatment for masses after vaccination based on what?
3-2-1 rule If mass is still evident 3 months after vaccination If the mass is larger than 2cm in diameter If the mass increases in size 1 month after vaccination
487
VAFS Task Force recommends what minimal margins? Problem with this? Best margin recommendations?
Minimal: 2cm lateral and 2cm deep Problem: <50% completely excised 5cm lateral and 2 fascial planes deep
488
Task Force BULLSHIT; studies to determine if recommendations made a difference
- Implementation of of task force changed tumor locations - Significant decrease in interscapular and lateral thoracic wall tumors - Significant increase in tumors of the right thoracic limb (but not left), the R/L pelvic limbs, abdominal wall - # tumors cranial to the diaphragm decreased and # of tumors caudal to it increased
489
What are risk factors for the development of TCC in dogs (7)? What has been found to help reduce the risk?
``` Older generation flea/tick control products Lawn chemicals (ex. 2,4-D) Female sex Obesity in females Cyclophosphamide exposure Neutered status Breeds ``` Scottish Terriers that ate vegetables at least 3 times per week had reduced risk (OR 0.3). Carrots were most commonly used. Green leafy veggies or yellow orange veggies. NOT cruciferous. Overweight females exposed to flea products 28x risk vs normal weight males w/o exposure
490
What breeds are at increased risk for TCC development (8)?
``` Scotties (OR 18-21) Eskimo dogs (OR 6.5) Shelties (OR 6) Westies (OR 5.8) Keeshonds (OR 4.2) Samoyed (OR 3.4) Beagle (OR 3) Dalmatian (OR 2.4) ``` Scottish Terriers that ate vegetables at least 3 times per week had reduced risk (OR 0.3). Carrots were most commonly used. Green leafy veggies or yellow orange veggies. NOT cruciferus Ses Shel Wee Kee Sam Begged Dan
491
In dogs with renal cell carcinoma, what is the overall MST and MST post nephrectomy*? 1 and 2 year survival rates? Time to recurrence or metastasis?
MST 480-530*d 1-yr SR 45% 2-yr SR 25% 8. 5m * use of adjuvant therapy did not improve prognosis, but 6 dogs with distant mets were treated with chemo and had an MST of 14m*
492
What are the negative prognostic factors for ST identified in dogs with renal cell carcinoma (10)?
Age <6yrs Hematuria Cachexia Metastasis at dx (MST 4.5m vs 18m) Clear cell subtype (MST 3m) Histologic vascular invasion Fuhrman nuclear grade (grade IV MST 3m, grade III MST 1yr, grade II MST 3yr) 14-3-3o IHC protein expression; 38% of RCC; associated with poorly differentiated tubular subtype and MI of >30 High COX-2 expression; present in 76%; MST 14m vs 40m **MI (>30 MST 4-6m [HR 12], 10-30 MST 15m, <10 MST 3.2yrs)
493
What is Sanguer sequencing?
Gold standard for detecting a single nucleotide substitution, but requires a 10-20% fraction of mutated allele for reliable detection - therefore low sensitivity leading to false negatives. Can be used in tissue or urine.
494
BRAF mutations are present in what % of dogs with urothelial and prostatic carcinoma? Overall?
Overall - 80% (20% do NOT posses the mutation) Urothelial - 67% Prostatic - 80%
495
Describe the BRAF mutation in dogs with urogenital TCC. What is the equivalent mutation in humans?
BRAF gene in chromosome 16, exon 15, codon 450 or 595 Results in a T -> A transversion that causes aa substitution of valine for glutamic acid Leads to constitutive activation of the MAPK pathway Humans, V600E, chromosome 7 SOMATIC mutation
496
Sensitivity and specificity of Sanger sequencing and ddPCR for detecting BRAF mutations in tissue and urine samples from dogs with TCC?
Sanger sensitivity: Tissue - 71% (67% UC, 78% PC) Urine - 61% UC, 100% PC ddPCR sensitivity: Tissue: 79% (75% UC, 85% PC) Urine: 85% (83% UC, 100% PC) BOTH are 100% specific! ddPCR more sensitive than Sanger for both tissue and urine
497
Advantages of ddPCR over Sanger for BRAF mutation detection?
ddPCR much more sensitive; able to detect mutation when present at levels as low as 0.005% (1 in 10,000 alleles) Sanger requires a 10-20% fraction of mutated allele for reliable detection - therefore low sensitivity leading to false negatives.
498
What BRAF inhibitor is used in human patients with melanoma?
Vemurafenib BRAF mutation present in >90%
499
What % of dogs with TCC experience relief of UO with urethral stent placement?
98-100%
500
What % of dogs with TCC experience incontinence, UTIs, stranguria, and re-obstruction after urethral stent placement? Median time to re-obstruction?
Incontinence 37-64% (males more common); severe in 26% (equal sex) UTI 35% Re-obstruction 22% at median of 3m Stranguria 5%
501
What is the MST in dogs with TCC when treated with urethral stent? What has been shown to prolong the MST in these dogs (2)? MST?
MST 20d to 2.5m (therefore mostly palliative) Tx with an NSAID for >4 weeks prior to stent Chemotherapy post stent MST 8m
502
Most common cause of re-obstruction in dogs with urethral stents?
100% due to PD 10% due to intraluminal PD 90% due to PD cranial or caudal to stent
503
Duration of stranguria in dogs with urethral stents is significantly associated with what?
Degree of incontinence post stent placement Longer stranguria duration = increased risk of severe incontinence; 1.7x increased risk for every 2 weeks duration
504
ORR and MST of piroxicam when used as a single agent in dogs with urogenital carcinoma?
ORR - 18% (6% CR, 12% PR, 53% SD) MST 6m *non COX selective
505
ORR, PFS, and MST of deracoxib when used as a single agent in dogs with urogenital carcinoma?
ORR 17% (PR 17%, SD 71%) PFI 4.5m MST 10.7m GI toxicity in 19% *COX 2 selective inhibitor
506
ORR, PFS, and MST of firocoxib when used as a single agent in dogs with urogenital carcinoma?
ORR: 20% (20% PR, 33% SD) PFI 3.5m MST 5m COX-2 selective*
507
Identified prognostic factors in dogs with TCC (6)?
- TNM stage - Tumor location: urethral (worse prognosis) and prostatic involvement - Dogs receiving 3+ chemo drugs had a longer MST compared to those receiving 1-2 chemo drugs - Daily piroxicam had a longer PFS and MST - Sx - trigonal location shorter MST, improved MST when combined with doxo and piroxicam - AUS findings: dogs with wall involvement, heterogenous mass, and trigone location - shorter MST
508
What factors are associated with a higher TNM stage in dogs with TCC (3)?
young age (increased risk of nodal mets) prostate involvement (increased risk of distant mets) higher T stage (increased risk of nodal and distant mets).
509
Dogs with TCC and higher # of ___ have an improved MST.
Granzyme B+ TIL CTL and NK are granzyme B+ DFI unaffected
510
___ overexpression is documented in 56% of TCC. Treatment with what TKI results in cell cycle arrest and decreased cell growth of all TCC lines in vitro?
HER-2 Iapatinib - TKI of HER2, EGFR
511
What is the MST in dogs with TCC according to the different TNM stages?
``` T1-2: 7m T3: 4m N0: 8m N1: 1.5-2m M0: 7m M1: 3.5m ```
512
What is the diagnostic yield of US-guided kidney FNAs in dogs and cats? Sensitivity and specificity for neoplasia?
70% (dogs 72%, cats 68%) Dog: 80% sensitive and 90% specific for cancer; highest for LSA Cat: 100% sensitive and specific for neoplasia
513
Expression of what 2 IHC markers by the majority of canine RCC suggests they arise from the distal convoluted tubule of the kidney?
Cytokeratin | VImentin
514
What IHC markers are used to diagnosed RCC in cats (4)?
CK7, CK20, KIT, CD10
515
What is the MST in px with brain tumors treated with palliative care? Is there a location that may do better with palliative care?
6d to 4m; generally 2m Supratentorial/forebrain tumors 6m Cats <1m
516
What are some positive prognostic indicators overall in dogs and cats with primary brain tumors (6)?
Solitary lesions (some w/ multiple meningiomas do well) Limited neurologic dysfunction Normal CSF analysis Tumor type Supratentorial/forebrain location Tx with RT or sx/RT combo
517
What are some negative prognostic indicators overall in dogs and cats with primary brain tumors (6)?
Multiple lesions Neurologic CS Palliative care Infratentorial/caudal brain lesions High VEGF High PCNA index
518
What is the MST in dogs with meningioma when tx with sx, HU/pred, conventional RT, SRT, and sx/RT combination? Hypofractionated RT with VMAT for intracranial and spinal M?
Sx: 7-10m Hydroxyurea/pred: 7m Conventional RT: 12-27m (gen 12m/351d) SRT: 17-19m Hypofractionatd RT with VMAT: 66% ORR 2 yrs post; 2-yr SR 74%, MST not reached Sx + RT: 17m
519
What % of dogs with intracranial meningioma treated with SRT experience AE? Suspect cause? Tx?
30-35% Subacute demyelination Most responsive to steroids
520
What is the mortality rate in dogs with intracranial meningioma treated with SRT? What was found to be predictive of death during the first 6m post therapy?
10% Volume of normal brain receiving 100% of SRT dose was predictive of death during first 6m Ideally <1cc of normal brain tissue should receive 100% of isodose
521
Meningioma-specific negative prognostic factors in dogs (6)?
Histotype (anaplastic = worse; psammomatous, meningothelial, and transitional better) High VEGF expression High PCNA index (shorter PFS), Longer MST with HU vs pred alone (7m vs 3.5m) Infratentorial location and high gradient index = shorter ST post SRT Volume of normal brain receiving 100% of SRT dose was predictive of death during first 6m
522
What are the 1 and 2 yr SR in dogs with intracranial meningiomas treated with SRT?
1-yr 60-65% 2-yr 24-33%
523
What is the MST in dogs with glioma when treated with sx (craniotomy), chemotherapy, conventional RT and SRS/VMAT +/- TMZ?
Sx: 6m CCNU chemotherapy: - glioma 4.5m - astrocytome 3-8m Conventional RT: 7-9m SRS VMAT, +/- TMX: 13-14m
524
What is the 1yr-SR of dogs with glioma when treated with sx vs SRT?
Sx 1-yr SR: 25%, 2-yr 6% | SRS 1-yr SR: 60-90%
525
Glioma-specific positive PI in dogs (5)?
Extra-axial longer ST vs intra-axial Ratio between target and brain volume <5% increased ST Normal mentation at dx increased ST CCNU longer ST vs palliative (35d) Tumor volume <5%
526
What is the MST in cats with intracranial meningioma when treated with sx and RT? % of neurologic improvement with RT?
Sx: 2-3yrs RT: 17m (combo of tumors); 96% improvement
527
What is the recurrence rate in cats with intracranial meningioma when tx with sx?
20%
528
What % of dogs with intracranial meningiomas tx with sx survive to discharge?
92% 8% overall mortality rate
529
What is the intraoperative and postoperative complication rate in dogs with intracranial meningiomas when treated with surgery?
Intraop 10% Postop 45%
530
What is the most common intraoperative complication in dogs with meningiomas treated with surgery?
Hemorrhage
531
What % of dogs with intracranial meningiomas tx with surgery experience neurologic vs non-neurologic postoperative complications?
45% transient neurologic deterioration 18% non-neurologic; aspiration pneumonia
532
Which intracranial tumor commonly has a contrast enhancing rim on MRI? Why?
Glioma Correlates with necrotic or cystic areas; not specific for G, seen best on T2 images
533
How do canine gliomas look on MRI?
Arise from intra-axial tissue and move outwards; infiltrative (as opposed to displacing tissue) Often lacks distinct margins Ring enhancement; seen best on T2 Hyperintense on T2W Hypo to isointense on T1W
534
How do canine meningiomas look on MRI?
Arise from periphery of brain and pushes brain inwards Broad base with extra-axial attachment -> dural or meningeal tail Distinct tumor margins Uniformly contrast-enhancing 25% have a cystic component Hyperintense on T2W Hypo to isointense on T1W
535
Most tumors are hyperintense on what MRI setting?
T2W
536
What is the relationship between gliomas and c-kit?
Gliomas - all negative for c-kit and COX-2 in one study c-kit expressed on vasculature of high grade gliomas 3 high grade tumors had intramural vascular expression of c-kit This suggests kit inhibitors may provide an anti-angiogenic effect in high grade gliomas In humans, expression of c-kit and COX is associated with a poor prognosis
537
What is the most common primary intradural spinal cord tumor in dogs?
Meningioma
538
What is the most common location for spinal meningiomas in dogs?
C1-C4 100% intradural and usually extramedullary
539
MST of dogs with spinal meningioma when treated?
17m (500d)
540
Most common metastatic intramedullary spinal cord tumor and location in dogs?
HSA and TCC T3-L3 Withrow says HSA and LSA, but recent literature says what above
541
Most common extradural spinal cord tumor in both dogs and cats?
OSA
542
Most common primary spinal cord tumor in dogs vs cats and location?
Dogs - meningioma; cervical Cats - LSA; thoracolumbar or lumbosacral Primary>metastatic
543
Most common metastatic brain tumors in dogs and cats?
Cats - LSA #1, pituitary #2 | Dogs - HSA #1, pituitary carcinoma #2, LSA #3
544
Most common phenotype of canine CNS lymphoma?
DLBCL >50%
545
What % of canine CNS lymphoma infiltrates the pituitary?
>70%
546
Most common clinical signs in dogs with CNS lymphoma (2)?
Weakness, ataxia
547
MST in dogs with CNS lymphoma when treated with multiple therapies?
6m (171d)
548
The majority of gliomas in dogs are what grade?
High grade - 94% Invasive and resistant to therapy
549
What is the most sensitive IHC stain for anaplastic oligodendryomas? What other tumor is also positive?
Olig; most sensitive, but astros also + Others: SOX10, PDGFRa, NG2, GFAP Astrocytomas
550
When RT is being pursued as a treatment modality, what is recommended for planning purposes? Why?
Combination of CT and MRI GTV measured on MRI typically 25% larger than CT If MRI not available, recommend using CT GTV + additional margin of 0.3cm to avoid geographic miss for 3D-CRT
551
What % of dogs with brain tumors experience shrinkage 3m after SRT?
60%
552
Clinical response to RT in dogs with brain meningiomas?
80%
553
Clinical benefit of SRS in dogs with meningioma?
60%
554
In dogs with primary or metastatic vertebral OSA when treated with SRT, what is the MST, and % that experienced improved pain control and neurologic score?
MST 4.5m 83% improved pain control 44% improved neuro score
555
Splenic fibrohistiocytic nodules is a term no longer used and has been reclassified to other dzs, with the most common ones being stromal sarcomas, HS, and complex nodular hyperplasia. What is the MST of splenic stromal sarcomas and splenic HS?
Stromal splenic sarcoma - 16m Splenic HS - 2.4m SFHN represents a heterogeneous group of diseases and the authors propose this term should no longer be used.
556
Splenic fibrohistiocytic nodules (SFHN) were previously classified as grades 1-3 based on what? What were the MSTs for the grade and what was prognostic (2)?
% lymphocytic infiltrate PI: Lymphoid:fibrohistiocytic ratio Grade Grade 3 significantly shorter MST (113 days) compared to grades 1 and 2 (MST not reached; mean 1,118 days)
557
What % of plasma cells should be present in a normal bone marrow? What % of plasma cells in the bone marrow is suggestive of MM in dogs and cats?
< 5% >20% is abnormal Can consider abnormal >10% in cats as they may not have extensive bone marrow involvement, so also consider cell morphology and visceral organ infiltration as they can be more commonly affected or of equal importance
558
What BM finding is a prognostic factor in cats with multiple myeloma?
Plasma cell morphology - well-differentiated (< 15% blasts) - intermediate (15-49% blasts) - poorly differentiated (>50% blasts) ~80% of cats exhibit abnormal plasma cell morphology
559
What are the negative prognostic factors identified in dogs with MM (5)?
Hypercalcemia Bence Jones (light chain) proteinuria Extensive bone lysis Presence of renal dz = shorter PFI and MST High neutrophil to lymphocyte ratio >4.28 = shorter PFI and MST In a newer study, hypercalcemia and bone lysis were not prognostic
560
What is the historic ORR, CR, median time to response, and MST in dogs with MM treated with melphalan?
92% ORR, 43% CR | MST 540d
561
A study evaluating pulse-dosed vs daily administered melphalan in dogs with MM was performed. ORR? Prognostic factors identified (2)? Which ones were not of prognostic significance (2)?
ORR 86% MST 930d Prognostic factors: Renal dz (MST 330d) Neutrophil to lymphocyte ratio of >4.28 (MST 330d) Not of significance: Hypercalcemia Lytic lesions
562
What is the ORR, CR, median time to response, and MST in cats with MM when treated with melphalan? DLT?
ORR 70% CR 30% Time to response 4.5m MST 8.5m (not SS diff from CTX) DLT: neutropenia; d/c in 63%
563
What is the ORR, CR, median time to response, and MST in cats with MM when treated with melphalan? DLT?
ORR 83% CR 50% Time to response 45d MST 13m (not SS diff from melphalan) Toxicity common but mild, none required d/c Authors recommend as first line therapy*
564
What is the ORR and CR in cats with MM treated with chlorambucil?
ORR/CR 50%
565
According to Withrow, what is the ORR and MST in cats with MM when treated with melphalan or COP? Compared to Europe study?
ORR 60% Most die within 4m Occasional long-term survivors >1yr Europe study: 9.5m
566
What % of cats with MM have hyperglobulinemia at dx? Monoclonal vs biclonal?
88% (most common BW abnormality in 1 study) 80% monoclonal 20% biclonal Biclonal gammopathies cats>dogs
567
Most common M component in cats vs dogs with MM?
Cats: IgG (more common in some studies) Dogs: IgG or IgA
568
What is referred to as the M component in patients with MM?
The presence of a malignant clonal protein (M-protein or M-spike) reflecting production of a single Ig
569
What % of cats with MM exhibit Bence Jones proteinuria?
50%
570
What chemistry abnormality in cats with MM is inversely correlated to globulin levels?
Cholesterol Hypocholesterolemia in 70% of cases
571
What would be the expected levels of EPO and blood oxygen in px with polycythemia vera vs PNS polycythemia?
PV: low or low-normal EPO and normal blood O2 PNS: increased EPO, normal O2
572
What has to be done in order to dx polycythemia vera?
Rule out everything else
573
Increased activity of what signaling pathway has been identified in neoplastic canine HSA cell lines vs normal endothelial cells?
NOTCH; necessary for maintenance of stem-cell properties Inhibition via y-secretase inhibitors suppresed cell growth
574
What red blood cell morphology has been associated with HSA (2)?
Shistocytes - seen with microangiopathic hemolysis Acanthocytes - 10% of dogs with them have HSA
575
Dogs with splenic masses that weigh more than ___kg are more likely to have HSA.
>27.8kg
576
When comparing the site and cause of spontaneous hemoabdomen, dogs weighing < ___kg were more likely to be bleeding from which organ vs dogs weighing > than ___kg. Bleeding from which organ was most commonly associated with HSA?
< 20kg liver > 20kg spleen Spleen
577
Although there is no difference in cytology of pericardial effusion in dogs with HSA vs other tumors, dogs with HSA have elevated levels of what when compared to dogs with idiopathic effusions?
Troponin I If > 0.25 ng/mL more likely to be cardiac HSA
578
What IHC stains can be requested to dx HSA?
Von Willebrand factor (factor VIII-related antigen CD31/PECAM) Other markers that could be used: - CD117 (KIT) - Claudin 5 - VEGFA and its receptor Flk-1 - no difference when compared to non-neoplastic endothelial cells - Ang 2 - may be useful - Tie 2 - less reliable
579
Why is an IHC panel more useful to dx HSA vs any marker on its own?
Poorly differentiated tumors may not express vWF CD31 is not a consistent marker as cross labeling can occur with other tumors (AGASACA, nodular hyperplasia, mammary Ca, plasmacytoma, RCC, cutaneous histiocytoma)
580
What % of dogs undergoing laparoscopy for splenic HSA have to convert to open laparotomy? What was significantly associated with conversion?
27% Heavier body weight Splenic mass, BCS, were NOT
581
What was recently shown to decrease MST when given concurrently with doxorubicin in dogs with splenic HSA?
Concurrent doxo and metronomic chemo with CTX = shorter MST
582
When used in a metronomic fashion combined with CTX and piroxicam, what drug has been shown to improve TTM and MST in dogs with HSA post splenectomy and doxo completion?
Thalidomide TTM and MST not reached *CTX alone has not been shown to increase anything after doxo*
583
What is the MST in dogs with HSA treated with single agent thalidomide post splenectomy? Prognostic indicators? 1-yr SR?
MST 6m (172d) PI: Stage II dz longer MST vs stage III (40d) 33% 1-yr SR (vs usual 10% 1-yr SR)
584
What has been demonstrated when Palladia is administered to dogs with stage I or II splenic HSA after doxorubicin (q2w) chemotherapy completion? What % of dogs receiving Palladia developed mets?
No improvement in ANYTHING over doxorubicin alone. Same numbers as with everything else. Overall DFI 140 Palladia DFI 160 Overall MST 170 Palladia MST 170 ~5.6m 80%
585
What chemotherapy drug has been shown to inhibit HSA cell migration and induce apoptosis in vitro?
Paclitaxel
586
What 2 chemical compounds have been shown to enhance cell kill when combined with doxorubicin vs doxo alone in cell lines?
Tetrathiomolybdate - Cu binding agent that may reduce resistance Resveratrol - naturally occurring polyphenolic compound in red wine; induces autophagy via activation of MAPK
587
What is allogenic LDC vaccination for dogs with HSA? In what did it result? AE?
Cationic liposome and DNA complex, which is an immune stimulant added to vaccines, combined with pooled cells from 2 HSA cell lines. 8 doses were administered along with doxorubicin chemo Vaccine elicited strong humoral immune response to a control antigen and most dogs also mounted an Ab response against canine HSA cell lines DFI 3m MST 6m 20% GI AE; diarrhea and anorexia most common
588
How does Yunnan Baiyao work for HSA (3)?
Increased activity of caspases 3 and 7 Increased clot strength on TEG Improved DFI in dogs with HSA
589
Identified negative prognostic factors in dogs with splenic HSA?
``` Sx alone Stage (I vs II-III) Mets at dx MI (<11 MST 10m, 11-20 MST 7m, >21 4m) Administration of allogenic blood products ```
590
Cutaneous HSA most common signalment, location, and predisposed breeds (9)?
Light pigmented dogs with thin coats Ventral abdomen and preputial region most common location Breeds: Whippets, Salukis, bloodhounds, beagles, white bulldogs, English pointers, Staffies, Italian greyhound Dalmatian
591
Histopathology consistent with UV-associated solar dermatosis is detected in what % of dogs with skin HSA?
70%
592
How is the location distribution of HSA in cats?
Equally distributed between visceral and cutaneous forms
593
In cats with visceral HSA, what % has multifocal disease at sx? Most common locations?
77% multifocal disease ``` Liver 35% Small intestine 31% Large intestine 31% Abdominal LN 31% Mesentery 27% Spleen 23% ```
594
With which form of HSA is the metastatic rate higher in cats?
Visceral (vs cutaneous/SQ)
595
What % of cats with visceral HSA have pulmonary mets at diagnosis vs extrathoracic mets?
33% pulmonary at dx 60% extrathoracic mets
596
When compared to dogs, how does cutaneous/SQ HSA behave in cats? Major concern with it?
Behaves similar to other STS Local recurrence in; 60-80% Cutaneous - MST not reached SQ - MST 384d (12.8m)
597
Negative PI in cats with HSA (3)?
SQ location (vs cutaneous) Visceral form (poor progn and high met rate) MI>3 (MST 2m) Incomplete tumor excision (MST 9m)
598
MST of cats with visceral HSA?
2.5m
599
MST of dogs with cardiac/pericardial mesothelioma when treated with a pericardiectomy?
10-15m; can be less, not a lot out there, usually palliative; IC chemotherapy can be beneficial
600
"Grossly", how does mesothelioma look? Cytologically, how do mesothelial cells look? Histologically, what are the 3 ways they can be classified and which one is most commonly seen?
Diffuse nodular masses that cover the surface of body cavities (depends on histo type) Similar to epithelial cells; CANNOT be diagnosed cytologically Epithelial, mesenchymal, biphasic (combination) Epithelial most common
601
What can cause an increase in proliferation of mesothelial cells?
Any sort of inflammation
602
What variant of the mesenchymal form of mesothelioma can be seen in male or German Shepherd dogs?
Sclerosing: resembles a sarcoma Causes restriction
603
What is the metastatic rate of mesothelioma?
True metastasis is rare. Fluid accumulation results in exfoliation and implantation of cells, which results in seeding and multiple tumor formation.
604
What is a CT finding that can be seen in px with mesothelioma?
Pleural thickening
605
How can you rule out mesothelioma in a px with pericardial effusion?
Normal fibronectin concentration; usually increased with MSA
606
Local penetration of IC chemotherapy?
2-3mm; consider debulking sx for large masses before IC
607
Overall MST of dogs with malignant thoracic effusions? MST with IC carbo or mitoxantrone vs no tx? Prognostic factors for response to therapy?
Overall 4-12m 11m w/chemo <1m if no therapy Tx dogs live longer than w/o tx NO PI identified; presence of effusion, thoracic disease, chemotherapy drug used, or metastasis did not affect MST
608
Infiltration of thymomas by which cell is positively correlated with improved survival in both dogs and cats?
Lymphocytes
609
What is the most common form of thymomas in cats and how does int influence prognosis?
Cystic; better prognosis
610
Metastatic rate of cystic thymoma in cats?
20%
611
How can you differentiate lymphoma vs thymoma using flow cytometry?
Thymoma - >10% of lymphocytes co-express CD4+ and CD8+ Lymphoma - <2% co-express Carcinoma <1% co-expression and samples usually have a low lymphocyte count (<40%)
612
Negative prognostic factors in dogs with thymoma (6)?
Presence of another tumor at dx; MST 282 vs 586d Lack of sx excision; MST 76 vs 635d Masaoka stage III+ MST 224 vs 1045d Presence of PNS (MG or hypercalcemia) Incomplete margins Tx with adjuvant chemo and/or RT *PNS did not influence outcome in a study*
613
What % of dogs with thymoma have a polyclonal PCR result?
92%
614
How do thymomas differentiate from lymphomas when contrast-enhanced CT are performed?
Thymomas - more likely to have heterogenous contrast enhancement LSA - more likely to be homogeneous
615
What is the ORR in dogs and cats with thymoma treated with adaptive RT (3Gy x 12)? What is the % of regression per day? GTV and PTV shrunk by how much?
100%; all achieved a PR 5% regression/day GTV and PTV 30% Why replanning may help protect organs at risk
616
Tasmanian facial tumor immune regulation, differences from TVT, metastatic rate, IHC, prognosis
Tumor highly conserved, as TVT They downregulate expression of MHC genes, but NOT through upregulation of TGF-B1 as TVT Downregulation of MHC can be restored by treating with IFN-y Metastatic rate 65% to LN, lungs, kidneys It is a PNST of Schuwann cell origin, so IHC positive for: S-100, vimentin, periaxin Periaxin 100% sensitive and the most specific marker No response to chemo Most die within 6 months of infection
617
Prognostic factors for <1m survival in dogs with HS (4)?
Anemia Thrombocytopenia Hypoalbuminemia Palliative therapy (12-40d)
618
Biomarkers for HS in BMD (3)?
High ferritin (not necessarily outside the reference range) - early in dz/asymptomatic Lower total WBC count - early in dz/asymptomatic High MCP-1 (monocyte chemoattractant protein); it is a chemokine produced by DCs and macrophages; serves to recruit mononuclear cells from the marrow to sites of inflammation
619
What is the most reliable IHC marker for HS?
CD204 Class A macrophage scavenger receptor, expressed on normal tissue macrophages. HS samples and normal macrophages will be CD204+. Lymphoid neoplasms, sarcomas, and cutaneous histiocytomas (Langerhans origin) will be CD204-. 50/50 HS samples were positive, including EHS
620
What dog breed is most commonly associated with pulmonary HS?
Min Schnauzer; OR 4.8 for HS
621
What breeds are predisposed to developing HS (6)?
``` Flat coated retreivers (OR 34) Bernese Mountain dog (OR 15) Sharpeis (OR 16) Miniature Schnauzers (OR 4.8) Golden retreiver (OR 3.9) Rottweilers ```
622
What IHC markers are used for feline progressive histiocytosis (7)?
Positive for: CD1a, CD1c, CD11b, CD18, MHC II +/-, E-cadherin 87% express PDGFR-b (of FPH and HS) Almost all cats surviving > 300d had high PDGFR-b expression
623
What is feline progressive histiocytosis? Most common locations?
Initially occurs in skin and progresses over time to involve multiple organs (LN, lungs, abdominal viscera) Multiple firm, haired or hairless, dermal papules or nodules, that can coalesce into plaques and become ulcerated Head, feet, legs Unresponsive to steroids, effective medical tx not available; can consider removal of solitary masses, but development of more is expected Disease progresses over months to years (median 13.4m)
624
What are the most common TSG mutations in BMD and FCR with HS?
CDKN2A/B deletions - 63% PTEN deletions - 40% RB1 - FCR 2x more likely to have deletions vs BMD TP53 - FCR 2x more likely to have gain of function mutations vs BMD
625
BMD with HS have a higher prevalence of a gain of function mutation in what gene, compared to other breeds?
PTPN11 gene - exon 3 BMD with HS had a higher prevalence of this mutation (37%) compared to other breeds with HS (9%)
626
Identified risk factors in BMD vs FCR
BMD: - 225x higher risk of HS - 17x more likely to die from tumor causes - 2x as likely as FCR to develop disseminated dz - FCR 7x more likely than BMD to have localized dz - Prev orthopedic dz increases risk of HS in BMD, but risk is lower in those receiving medications for >6m
627
What proteinases are expressed at the invasive front of HS and are produced by TAMS (4)?
MMP 2, 9, 14 | TIMP 1
628
Metastatic rate at dx of pulmonary HS?
16% pulmonary | 46% intrathoracic
629
Common MRI findings (4) in dogs with CNS HS?
Diffuse enhancement of meninges Forebrain most common location Solitary extra-axial mass with moderate to marked CE Iso or hypointense on T2 (vs meningioma, hyperintense)
630
Negative prognostic factors on multivariate analysis for dogs with histiocytic sarcoma (4)? On univariate (1)?
Multivariate: - Thrombocytopenia - Disseminated dz - Palliative therapy - Concurrent use of steroids Univariate: -Elevated survivin levels- also associated with chemoresistance
631
ORR of epirubicin in dogs with HS (alternating with CCNU, singe agent, rescue)? Rescue-specific ORR? Overall TTP and MST? What % required dose reductions? DLT?
ORR 29% Rescue specific ORR 19% TTP 2m MST 6m 30% due to GI toxicity primarily
632
Marker for erythrophagocytic HS?
CD11d (macrophages from the splenic red pulp and BM)
633
Blood work abnormalities that can be seen with EHS (4)? | MST?
Regenerative anemia - 94% Hypoalbuminemia - 94% Thrombocytopenia - 88% Hypocholesterolemia - 70% days to 1-2m
634
Describe the Philadelphia and Raleigh chromosomes
Philadelphia - BCR-abl 9 ->22 translocation - Chrom 9 encodes abl gene for a TKR involved in growth and differentiation - Chrom 22 encodes bcr gene - Abl gene moves close to the bcr gene (9->22 translocation) and a new fusion gene bcr-abl is formed; this allows for constitutive activation of the abl tyrosine kinase, which promotes CML; present in 90% of CML cases and occasionally AML and ALL Raleigh: BCR-ABL translocation affects chromosomes 9 and 26
635
Canine ALL phenotype?
Typically B-cell CD34+, CD21+, CD3-, CD4-, CD8- <10% T-cell: CD3+, CD4-, CD8-, CD21-
636
Canine AML phenotype?
CD45+, CD34+, CD11b+, CD11c+, CD14+, MPO+, CD4+ (+/- ) Granulocytes can sometimes express CD4 so it may be CD4+ Strong ALP (none in LSA or CLL); weak on some ALL Negative for B and T cell markers; 30% can express them
637
Canine CLL phenotypes? Which one is more common?
T-cell: CD8+ with large granular morphology . MOST COMMON. MST 930d B-cell: CD21+, CD34- SMALL BREED DOGS/Bulldogs MST 480d
638
What is different about Bulldogs and CLL?
Increased risk of CLL Median age of 6 yrs Low MHC class II and CD25 expression Higher % of hyperglobulinemia