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Oncology Boards > MCT > Flashcards

MCT Flashcards

1
Q

What bioactive substances to MC’s contain?

A

Heparin, histamine, TNF-alpha and proteases

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2
Q

What can MCs rapidly produce when stimulated?

A

Chymase, tryptase, cytokines (TNF alpha, IL6) chemokines (CCL2, CXCL1) VEGF, basic fibroblast growth factor, prostaglindin D2, leukotriene C4

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3
Q

What was found to be a risk factor for golden retrievers with MCT?

A

polymorphisms in the GNAI2 gene and multiple genes assoc with hyaluronic acid synthesis

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4
Q

Alterations in expression of what cyclin-dependent kinase inhibitors have been identified in a many canine MCTs?

A

p21 and p27

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5
Q

What is KIT normally expressed on?

A

Hematopoietic stem cells, melanocytes and MCs

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6
Q

What does KIT bind and what does this cause?

A

SCF binds KIT –> KIT dimerization –> phosphorylation –> intracellular signaling –> proliferation, differentiation and maturation of normal MCs

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7
Q

What is essential for the differentiation of mature MC from CD34+ stem cells?

A

SCF (stem cell factor)

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8
Q

The juxtamembrane domains of kit are

A

exon 11-12

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9
Q

The extracellular domains of KIT are

A

exon 8-9

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10
Q

What do KIT mutations cause?

A

SCF-independent activation of KIT –> unregulated KIT signal transduction

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11
Q

c-kit mutations are associated with ____% of canine intermediate and high grade MCTS

A

25-30%

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12
Q

CNVs ( copy number variation) have been associated with (high/low) MCTs

A

High

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13
Q

MCTs with kit mutations showed aberrant CNVs involving what genes?

A

p53 and rB pathways

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14
Q

What drug metabolism and cell cycle pathways have been shown to correlated with cure from surgery vs. death from MCT?

A

solute carrier transporter and UDP glucuronosyltransferase gene families

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15
Q

What four stress response proteins are significantly upregulated in high-grade MCT

A

HSPA9 PDIA3 TCP1A TCP1E

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16
Q

Over expression of what micro-RNA was associated with MCT metastasis?

A

micro-RNA-9

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17
Q

What percent of dogs present with multiple MCTs?

A

11-14%

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18
Q

What is the behavior of primary GI MCT in dogs?

A

Aggressive - 40% alive at 30d , <10% alive at 6mo

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19
Q

GI ulceration has been documented in ____% of dogs undergoing necropsy

A

35-83% (may be selecting for higher grade tumors because necropsy)

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20
Q

What does histamine released from MCT act on?

A

H2 receptors on parietal cells –> increased HCl

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21
Q

In addition to high plasma histamine concentrations, dogs with MCT can also have decreased plasma ____ levels

A

Gastrin - normally released by antral G cells in response to increased gastric HCl

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22
Q

What mediates the hypotensive effects in humans with MC diseases?

A

Prostaglandins in the D series

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23
Q

What is the most consistent and reliable prognostic factor for canine MCT?

A

Grade

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24
Q

What is the long term survival rate for well-diffentiated and intermediate grade MCT after complete surgical excision

A

well-differentiated 80-90% Intermediate 75%

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25
Q

What is the metastatic rate for undifferentiated MCT

A

range 55%-96%

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26
Q

What locations are associated with high grade/worse prognosis for canine MCT

A

subungual, oral, mucous membranes scrotal and preputial visceral or bone marrow = grave

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27
Q

Microvessel density has been associated with what in canine MCT

A

Higher grade, higher degree of invasiveness, worse prognosis

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28
Q

What is the Bostock Grading system for canine MCT

A

Same as patnaik except numbers reversed (i.e. high grade = grade 1 on bostock, low grade = grade 3 on Bostok)

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29
Q

What stain can determine the AgNOR score?

A

silver colloid staining

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30
Q

What markers of proliferation have been associated with biologic behavior of MCT? Which is the least consistent

A

Ki67, AgNOR, PCNA PCNA least consistent

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31
Q

What mitotic index cutoff is associated with MST in dogs with MCT?

A

MI <5 MST >5 3mo; <5 80mo

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32
Q

What are the three distinct ckit patterns

A

membrane, focal/stippled diffuse cytoplasmic

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33
Q

The presence of c-kit activating mutations has been associated with what in canine MCT?

A

higher rate of local recurrence, metastasis, death from disease

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34
Q

What percent of dogs with MCT on the muzzle present with regional LN mets?

A

50-60% but doesn’t mean worse prognosis MST w/ mets = 14mo

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35
Q

What is associated with a more aggressive behavior for canine SQ MCT

A

MI >4, infiltrative growth pattern, presence of multinucleation

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36
Q

What is the prognosis for dogs with conjunctival MCT?

A

Good - no dogs in the study looking at this died from the MCT

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37
Q

What IHC are MCTs positive for?

A

Vimentin, tryptase CD117 (KIT) +/- chymase, MCP-1 and IL-8

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38
Q

How does ultrasound or CT analysis of either MCT or STS change tumor margins planned at surgery?

A

Ultrasound upgraded tumor margins in 19%, CT upgraded margins in 65%

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39
Q

What other conditions can cause a peripheral mastocytosis (1-90MCs/uL)?

A

acute inflammatory disease (parvo), inflammatory skin disease, regenerative anemia, neoplasia other than MCT and trauma; may be more dramatic in other diseases than in MCT

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40
Q

What was the incidence of bone marrow involvement at the time of diagnosis in dogs with MCT?

A

2.8%

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41
Q

What was the incidence of bone marrow involvement and mastocytosis in dogs with visceral MCT?

A

Bone marrow 56% mastocytosis 37%

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42
Q

Adjuvant RT is associated with what 2-yr control rates for stage 0, low or intermediate grade MCT

A

85-95%

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43
Q

What is the general rate of recurrence for incompletely excised MCT? what may be associated in predicting likelihood of recurrence?

A

10-30%; proliferation indicies Ki67/PCNA

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44
Q

Is adjuvant steroid or antihistamine therapy beneficial for cases of intermediate MCT that have been excised or treated with RT?

A

Nope

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45
Q

What are the three distinct syndromes for feline MCT?

A

Cutaneous, splenic/visceral and intestinal

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46
Q

What % of cutaneous and splenic/visceral feline MCT had c-kit mutations? What exons were these primarily present in

A

exons 8/9

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47
Q

Which subtype of feline cutaneous MCT may spontaneously regress?

A

Histiocytic MCT (vs. mastocytic MCT)

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48
Q

The histiocytic form of cMCT is more likely to occur in what signalment cat?

A

Young, siamese (male depending on study); usually presents with multiple masses that may be ulcerated (head/neck usually)

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49
Q

What are the two types of mastocytic cMCT in cats?

A

Compact (50-90% of cases) vs. diffuse (anaplastic)

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50
Q

Systemic mastocytosis does/does not occur in healthy or ill-from something other than a MCT in cats

A

does not

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51
Q

What percent of cats may present with positive buffy coats? What form of MCT is this usually associated with?

A

43%, usually splenic/visceral

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52
Q

What IHC markers are feline MCT usually positive for

A

Vimentin, alpha-1 antitrypsin and KIT

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53
Q

What other organs are frequently affected by splenic/visceral MCT?

A

liver (90%), LN (73%), bone marrow (40%), lung (20%)

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54
Q

What is the survival for cats undergoing splenectomy for splenic/visceral MCT

A

12-19mo even with bone marrow involvement

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55
Q

What are the 3 MC related diseases in people?

A

Cutaneous mastocytosis (benign, young children, spontaneous regression systemic mastocytosis - 4 subtypes extracutaneous MCT

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56
Q

What KIT mutation is most common in people with MC disease

A

point mutation in exon 17 - induces ligand-independent activation; exons 8 and 11 also identified

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57
Q

Are KIT inhibitors (imatinib, nilotinib, dasatinib) effective for treatin human MC diseases?

A

Not usually - inhibiting phosphorylation of KIT on exon 17 is challenging

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58
Q

What percent of feline MCT are kit positive on IHC (Mallett Vet Path 2012)

A

69% cutaneous

35% splenic

33% GI

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59
Q

What was found to be correlated with worse outcome in cats with MCT? What was the strongest predictive variable? (Sabattini VetPath 2010)

A

Multiple lesions, pleomorphic phenotype, KIT score, MI and Ki67 indicies

MI strongest

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60
Q

Other than MCT, what other disease can cause mastocythemia in cats? (Piviani Vet Clin Path 2013)

A

LSA, HSA, CKD

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61
Q

For low grade MST with tumor free margins on histopath (radial), what margin cutoff is concerning for incomplete excision based on tangential sections? (Dores VCO 2018)

A

<10.9mm

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62
Q

What was the percent overall shrinkage for excised canine cMCT? (Upchurch AJVR 2018)

A

17.7%

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63
Q

Was the amount of shrinkage in normal skin or the cMCT larger for excised canine cMCT? When did most of the shrinkage occur?

A

Larger for grossly normal skin (24.42%) compared to tumor (4.45%); most occurred immediately after excision

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64
Q

What was the overall risk of metastasis for grade 3 MCT (Patanaik) vs. high grade (Kiupel) (Stefanello JAVMA 2015)

A

OR for Patanaik = 5.46

OR for Kiupel = 2.54

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65
Q

What was the rate of mets from MCT for grade 1 and 2 tumors compared to low grade tumors (Stefanello JAVMA 2015)

A

Patanaik: grade 1 (5.8%) grade 2 (16.5%)

Kiupel 14.9% low grade had mets

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66
Q

Expression of what IHC marker was expressed in canine MCT but not normal MC and had lower expression in high grade MCT than low grade MCT? (Meyer Vet Path 2012)

A

CD 25 (subunit of IL-2 receptor)

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67
Q

What is the rate of abberant KIT staining in horses?

A

12%

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68
Q

What was the agreement between 28 vet pathologists for grade 3 MCT vs grade 1/2 MCT? (Kiupel Vet Path 2011)

A

High grade 75%, grade I/2, < 64%

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69
Q

What are the crieteria for high grade MCT on the two-tier system? (Kiupel Vet Path 2011)

A

Any 1 of the following:

MI ≥ 7

3 or more multinucleated (3 or more) in 10hpf

3 or more bizarre nuclei/10hpf

Nuclear diameters of at least 10% vary by at least 2-fold

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70
Q

What was the prognosis for low vs. high grade MCT on the two tier system? (Kiupel Vet Path 2011)

A

<4mo for high grade

>2yrs for low grade

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71
Q

An HN score > 0 was associated with what size cutaneous MCT? (Ferrari VCO 2018)

A

>3cm

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72
Q

What percent of dogs with non-palpable or normal sized LN had LN mets when the LN was extirpated? (Ferrari VCO 2018)

A

Almost 1/2 (HN2 28%, HN3 21%)

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73
Q

What was the tumor specific survival (TSS) for dogs with grade II stage II MCT treated with surgical removal vs not of the metastatic LN? (Marconato VCO 2018)

A

TSS LN extirpation: 2213d

W/o: 360d

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74
Q

For dogs with grade 2 stage 2 MCT, the risk of tumor progression was ___ higher without LN removal and the risk of tumor related death was ____ higher without LN removal (Marconato VCO 2018)

A

5x, 3.5x

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75
Q

What prognostic factors were associated with tumor progression for dogs with grade 2 stage 2 MCT? (Marconato VCO 2018)

A

Age >9

Head/neck

lymphadenopathy

no LN extirpation

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76
Q

What prognostic factors were associated with tumor related death for stage 2 MCT (marconato VCO 2018)

A

Head/neck, high grade no LN extirpation

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77
Q

What was the overall expression of fibroblast activating protein in canine MCT? (Giuliano J Comp Path 2017)

A

90% - 16 low to intermediate, 14 high

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78
Q

What was fibroblast activating protein correlated with in canine MCT

A

FAP positiviely correlated with Patnaik and Kiupel grade, MI and Ki67 expression - FAP may be negative prog factor in MCT

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79
Q

What defines HN0 for MCT? (Weishaar J Comp Path 2014)

A

0-3 scattered or individual MC in sinues and/or arenchyma per 400x field

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80
Q

What defines HN1 for MCT? (Weishaar J Comp Path 2014)

A

> 3 individualized MC in sinuses and/or parenchyma in a minimum of 4 400x fields

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81
Q

What defines HN2 for MCT? (Weishaar J Comp Path 2014)

A

Aggregates (clusters) of MCs (≥3 assoc cells) or sinusoidal sheets of MCs

HN2 = early metastasis

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82
Q

What defines HN3 for MCT? (Weishaar J Comp Path 2014)

A

Disruption or effacement of normal nodal architecture by MCs

Overt metastasis

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83
Q

What was MST for HN0/HN1 MCT vs. HN2/3 MCT (Weishaar J Comp Path 2014)

A

HN0/1 = 1824d

HN2/3 = 804d

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84
Q

What percentage of canine MCT have TP53 mutations? Associated with grade? (Vozdova VetJ 2019)

A

15%; mutation not associated with grade

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85
Q

How did the average extracellular vesicle concentration compare in dogs with MCT vs. healthy dogs? (Simundic VCO 2019)

A

Higher in MCT dogs than in healthy dogs

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86
Q

What is ibrutinib and how does it work?

A

Bruton’s tyrosine kinase (BTK) inhibitor; blocks IgE dependent activation and histamine release in human basos and MCs

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87
Q

What was the effect of ibrutinib on MCT cell lines? (Gamperl VCO 2019)

A

Suppressed phosphorylation of BTK and downstream STAT5

Induced apoptosis in cells at higher doses

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88
Q

High levels of what apopototic intrinsic pathway proteins was associated with a higher mortality rate and shorter ST? (Barra VCO 2018)

A

BAX

BCL2 lower in high grade tumors

Higher APAF1 = lower risk of death

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89
Q

Mean plasma CK18 was/was not a predictor of development of GI tox from TOC in dogs (Kovac JVIM 2018)

A

was not

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90
Q

What Jak2 and Stat5 inhibitors had efficacy in MCT lines

A

**Both MCT lines had JAK2 and STAT5 detected**

Jak2: R763, TG101348, AZD1490, ruxolitinib

Stat5: pimozide, piceatannol

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91
Q

What STAT 5 inhibitor has synergistic effects with KIT-targeting drugs for treatment of canine MCT (in cell lines) (Keller VCO 2018

A

Pimozide

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92
Q

Immuno expression of HSP32 was highest or lowest in high grade MCT? What does this suggest? (Romanucci Vet Path 2017)

A

Highest, suggests loss of immunosiganling in poorly differentiated MCT

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93
Q

Dogs with cMCT with loss of genomic copy numbers of ____ and gain of copy numbers in ____ had shorter survival and worse prognosis (Jark, ResVetSci2017)

A

Loss: PTEN, FAS

Gain: MAPK2, WNT5B, FGF, FOXM1, RAD51

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94
Q

What c-KIT mutation was detected in a MCT from a dog with resistance to imatinib? Nakano Vet Immuno 2017

A

c.2006 C-T in exon 14

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95
Q

Mutant kit with both _____ and _____ mutations caused ligand independent phosphorylation that was not suppressed by _____. (Nakano Vet Immuno 2017)

A

c.1663-1671del on exon 11

c.2006 C-T

Imatinib

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96
Q

What was the first mechanism of imatinib resistance identified in a clinical case of canine MCT? (Nakano Vet Immuno 2017)

A

c.2006 C-T in exon 14

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97
Q

What was associated with decreased MST/DFI and increased met rate in dog SQ and cMCT? (Thompson Vet Path 2016)

A

Phosphorylated KIT, VEGFR2, KIT cellular localization

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98
Q

What was associated with an increased rate of local recurrence in dogs with SQ or cMCT? (Thompson Vet Path 2016)

A

Expression of VEGFR2 and KIT diffuse cytoplasmic staining

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99
Q

What was the KIT expression pattern for most equine MCTs (Ressel JCompPath 2015)

A

low grade with KIT pattern 1 and low proliferation (2/3)

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100
Q

What is the expression of COX-2 in MCT, HS and HSA? (Heller Vet Path 2005)

A

Not expressed

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101
Q

What was the rate of ITD mutations in exon 11 and 12 of c-kit in cMCT? (AJVR 2002)

A

Grade 1 8%

Grade 2 35%

Grade 3 35%

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102
Q

Describe the mismatch repair protein expression in K9 MCT (Munday Vet Path 2009)

A

All expressed MLH1, MSH2 and MSH6

No difference in old dogs or nonpredisposed breeds

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103
Q

What is p62/sequestosome-1

A

Stress-inducible “hub” protein found in all cell types

Shuttles b/w nucleus and cytoplasm

Regulates NFkB

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104
Q

What p62 patterns were associated with MCT tumor grade? (Rich Vet Path 2014)

A

P62 nuclear - 100% low grade

P62 cytoplasmic - 93% high grade

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105
Q

What was the rate of phosphorylated KIT in canine MCT treated with TOC or VBL? what was it associated with? (Thamm VCO 2019)

A

pKIT in 66%

Associated with aberrant KIT localization, high MI and high grade

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106
Q

On multivariate analysis, what predicted MST and PFI for dogs with cutaneous MCT treated with TOC or VBL (Thamm VCO 2019)

A

MST - phosphorylated kit

PFI - MI

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107
Q

What breeds were more likely to have high grade MCT vs. those that weren’t (Reynolds VCO 2019)

A

More likely: Sharpeis

Less: goldens, pug

108
Q

What location of MCT was more likely to have a high grade MCT? (VCO 2019 Reynolds)

A

Inguinal

109
Q

What was correlated with response to glucocorticoid therapy in dogs with MCT and what was the response rate?

A

PR 63.3%

no response: 36.7%

Lower stage of disease, lower grade, lower KITr expression and Ki67 score

110
Q

What was the MST for dogs with stage IV cMCT? (Pizzoni 2018)

A

MST 110d.

111
Q

What were negative prognostic factors for dogs with stage IV cMCT? (Pizzoni VCO 2018)

A

>3cm, >2 metastatic sites, bone marrow involvement, lack of primary tumor control

112
Q

Combining MI and Ki67 score with ____ showed improved accuracy of predicting death in dogs with cMCT (Berlato VCO 2018)

A

minichromosome maintenance protein 7 (MCM7)

113
Q

What are ckit mutations associated with in cMCT in dogs? (Thamm VCO 2019)

A

higher grade, increased recurrence rate, decreased ST

May NOT be an independent factor

114
Q

Are dogs getting RT + VBL/pred for MCT more likely to get neutropenic than dogs without RT? (Stiborova JSAP 2019)

A

No increased risk - RT group 18% risk, chemo alone 23%

115
Q

What were the randomized groups for Weishaar’s ckit vbl/toc study? (JVIM 2018)

A

Prospective randomized tiral - 88 dogs

TOC (2.75mg/m2 EOD) or VBL (2.5mg/m2 weekly x4 then EOW)

Randomized by KIT localization and c-kit mutation status using an adaptive randomization scheme

116
Q

For dogs treated with toceranib for MCTs in a randomized study (Weishaar), what percent had c-kit mutations and what was the ORR for these dogs? (JVIM 2018)

A

20% had kit mutations, ORR 46%

117
Q

What was the mPFS and OST of dogs treated with toceranib in a randomized trial looking at the influence of c-kit mutations (Weishaar JVIM 2018)

A

mPFS 95.5d (14-990)

OST 159 (20-990)

118
Q

What percentage of dogs had kit mutations in Weishaars toceranib vs. vbl study and what was the ORR rate to vbl? (JVIM 2018)

A

30% had kit mutations

ORR 30%

119
Q

What was the mPFS and OST for dogs treated with vbl randomized by kit mutation status? (Weishaar JVIM 2018)

A

mPFS 78d (7-1521)

OST 241.5d (10-1521)

120
Q

Did c-kit mutation status predict the response to toc vs. vbl? Also, were PFS or OS different between these groups? (Weishaar JVIM 2018)

A

No difference in treatment response (c-kit mutation status was no different between groups)

No difference in OS or PFS

121
Q

What was the response rate for intralesional triamcinolone treatment for MCTs in dogs? (Case JAVMA 2018)

A

ORR 67% - 4/24 CRs, 12/24PRs

122
Q

What was the response rate to a single dose of intralesional tiramcinolone for MCT in dogs? (JAVMA 2018)

A

1/5 CR, 3/5 PR, 1/5 SD

123
Q

What were the characteristics for inclusion for the study examining triamcinolone intralesionally for MCT in dogs (Case JAVMA 2018)

A

MCT ≥0.5cm treated with at least 1 IL tx

124
Q

What AEs were reported for dogs with MCT treated with at least one intralesional triamcinolone tx? (Case JAVMA 2018)

A

3 dogs AEs: 1 local bleeding and 2 suspected GI ulceration

125
Q

What rapid dose escalation was used for treatment of dogs with MCT? How was it tolerated? (Serra Varlera, VetM&Sci 2016)

A

2.3, 2.6, 3, 3 then 3 EOW

70% tolerated 3mg/m2 q7d at d 14 and 21

126
Q

How many dogs had a DLT and d/c treatment due to toxicity in the study looking at rapid VBL escalation for MCT? (Serra Varlera VetM&Sci 2016)

A

30% DLT

8% d/c

**2 dogs died from febrile neutropenia**

127
Q

How was the combination of toc and CCNU tolerated when used for treatment of non-resectable or recurrent MCT? (Bavcar VetJ 2017)? What were the doses used?

A

Doses: Toc 2.7mg/kg EOD, CCNU 60mg/m2 q3wk)

Severe AEs in all dogs (10 dogs), all needed protocol changes

**3 dogs died or were euthanized**

128
Q

What waws the ORR for dogs treated with a combination of toc and CCNU for non-resectable or recurrent MCTs? (Bavcar VetJ 2017)

A

ORR 50%; long term response (>1yr) in 2

129
Q

What does Masitinib target?

A

c-kit

Possibly PDGF receptor alpha and beta; lyn and FGFR receptor 3; focal adhesion kinase pathway

130
Q

What was the ORR for dogs with macroscopic MCT treated with masitinib (Grant, JSAP 2016)

A

ORR 82% (by RECIST, 61% by WHO)

43% CR, 39% PR

131
Q

What was the TTP and MST for dogs treated with masitinib for macroscopic MCT? (Grant JSAP 2016)

A

TTP 79d (longer if in CR)

MST 5mo

132
Q

What was the rate of AEs/what grade for dogs treated with masitinib for gross MCT (Grant JSAP 2016)

A

AEs in 64% (25% grade 3/4)

Most common = ALT and vomiting

133
Q

What was the protocol for pulse toc + CCNU for unrescetable MCT (Burton, JVIM 2015)?

A

TOC d 1, 3 and 5 of 21 d. cycle (2.75mg/kg)

CCNU d 3 of each cycle at 50mg/m2

134
Q

What was the ORR and mPFS for dogs treated with pulse TOC + CCNU for unrescetable MCT? (Burton 2015)

A

ORR 46%

mPFS 53d

135
Q

What was the response rate to a dose of vinorelbine for dogs with MCT?

A

13% response (CR or PR)

83% SD

136
Q

What was the protocol for alternating CCNU and high dose VBL for dogs with MCT? (Rassnick VCO 2010)

A

CCNU 70mg/m2 alt EOW with VBL 3.5mg/m2

137
Q

What was the ORR for dogs treated with CCNU/high dose VBL for MCT? (Rassnick VCO 2010)?

A

ORR 65%

138
Q

What was the median PFS for dogs treated adjuvantly with CCNU/high dose VBL for MCT? (Rassnick VCO 2010)

A

mPFS = 489d

139
Q

What was the PFS for dogs with grade 3 MCT vs. metastatic grade II MCT treated with CCNU/high dose VBL? (Rassnick VCO 2016)?

A

Grade 3 190d

metastatic grade II 954d

140
Q

What was the confirmed ORR (CORR) for dogs treated with water soluble micellar paclitaxel (Paccal Vet) for nonresectable grade 2 or 3 MCT? (Vail JVIM 2012)

A

CORR 7% (150mg/m2)

141
Q

What was the outcome for dogs treated with adjuvant CCNU/pred for incompletely excised grade 2 MCT? (Hosoya JAAHA 2009)?

A

12 nogs, non developed local recurrence or mets

2 dogs died from liver failure

142
Q

What were the 1- and 2-yr PF rates for dogs treated with CCN/pred for incompletely excised grade 2 MCT? (Hosoya JAAHA 2009)

A

1yr 100%, 2yr 77% (n= 12 dogs)

143
Q

What was the remission rate for dogs treated with oral calcitriol for MCT? (Malone VCO 2010)

A

40% (1 CR, 3 PR)

144
Q

How was high dose calcitriol (DN101) tolerated for dogs with MCT? (Malone VCO 2010)

A

Poorly - majority needed d/c because of tox - hyperCa, GI, azotemia

145
Q

What was the ORR for dogs treated with chlorambucil and pred for inoperable MCT? (Taylor JSAP 2009])

A

ORR 38%

146
Q

What was the PFI for the dogs that responded to chlorambucil and pred for inoperable MCT? What was the MST for all dogs? (Taylor JSAP 2009)

A

PFI for 8 responders = 533d.

overall MST = 140d

147
Q

What was the response rate to vinblasine + pred vs. pred alone for treatment of MCT? (Rungsipipat Comp Clin Path 2009)

A

Vibl 78.2% vs. 50% pred alone

148
Q

What proliferative markers were shown to decrease after treatment (vbl and/or pred) for dogs with MCT? (Rungsipipat CompClinPath 2009)

A

AgNOR, PCNA, Ki67

149
Q

What was the MST for dogs treated with vbl/pred vs. pred alone for MCT? (Rungsipipat Comp clin path 2009)?

A

MST vbl 101d, pred alone 175d

150
Q

ORR and median duration of response for dogs with microscopic or macroscopic MCT treated with alternating CCNU/VBL q2wks (Cooper VCO 2009)

A

ORR 57%, median duration 52wks

151
Q

PFST and OST for dogs with macroscopic MCT treated with alternating CCNU/VBL q2wks (Cooper VCO 2009)

A

PFST 30wks, OST 35wks

152
Q

PFST and OST for dogs with microscopic MCT treated with alternating CCNU/VBL EOW (Cooper VCO 2009)

A

PFST 35wks, OST 48wks

153
Q

What was the response rate to imatinib for dogs with MCT (Isotani JVIM 2008)

A

48% w/in 14d

154
Q

All dogs with exon ____ mutations had a response to imatinib (Isotani, JVIM 2008)

A

exon 11

155
Q

What was the response rate for dogs with grade II or III nonresectable MCT treated with 2mg/m2 or 3.5mg/m2 without prednisone? Rassnick JVIM 2008

A

VBL 2.0 = 12% pr for 77d

VBL 3.5 = 27% ORR

156
Q

Rate of grade 4 neutropenia after treatement with 3.5mg/m2 vbl for dogs with unresectable grade II or III MCT? (Rassnick JVIM 2008)

A

46%

157
Q

What was the 1- and 2-yr survival rate for dogs treated for nonrescetable grade 2 or 3 MCT with masitinib? What was the dose of masitinib used?

A

12.5mg/kg/d

1yr 62.1% vs 36% for placebo

2yr 39.8% vs 15%

**treatment significantly prolonged survival rates**

158
Q

Median OST for dogs with nonrescetable grade II or III MCT treated with masitinib (Hahn AJVR 2010)

A

617d. vs. 322d for placebo

159
Q

What was found to have high or poor predictive value for tumor control for dogs treated with masitinib for nonresectable grade II or III MCT? (Hahn AJVR 2010)

A

High predictive value: tumor control at 6mo

Poor predictive value: short-term tumor response (6wks)

160
Q

What was the rate of recurrence and median time to recurrence for dogs treated with ECT with cisplat for MCT? (Spugnini JVIM 2011)

A

recurrence 16% (6/37)

median time to recurrence 1200d

161
Q

What was the ORR for metastatic and non-metastatic MCT treated with Masitinib (Smrkovski VCO 2013)

A

50%

162
Q

What was the MST for responders vs. nonresponders in dogs treated with Masitinib for metastatic and nonresectable MCT? (Smrkovski VCO 2013)

A

Responders 630d

Nonresponders 137d

163
Q

What was the rate of AEs and what were they in dogs treated with Masitinib for nonresectable or metastatic MCT? (Smrkovski VCO 2013)

A

Toxicity in 61.5% - most mild and self-limiting

ALT, proteinuria, heme (neutropenia) GI

164
Q

What was the RR for dogs treated with Masitinib as a first-line vs. rescue treatment for nonresectable or metastatic MCT? (Smrkovski VCO 2013)

A

First line RR 57%; rescue 25%

165
Q

What was the most common side effect for dogs treated with 12.5mg/kg/day Masitinib for nonmetastatic recurrent or nonresectable grade 2 or 3 MCT? (Hahn JVIM 2008)

A

GI upset - grade I/II diarrhea or vomiting

166
Q

What was the TTP for dogs with nonmetastatic recurrent or nonresectable grade 2 or 3 MCT treated with masitinib? How did it compare if it was first line therapy?

A

TTP 188d overall

if first line TTP 253d (vs 75d for placebo)

167
Q

What was the protocol for dogs treated with single-agent hydroxyurea for MCT? (Rassnick VCO 2010)

A

60mg/kg PO q24 x14 then 30mg/kg PO q24

168
Q

What was the response rate for dogs treated with single-agent hydroxyurea for MCT? (Rassnick VCO 2010)

A

28%

169
Q

What were the AEs for single agent hydroxyurea for treatment of dogs with MCT (Rassnick VCO 2010)

A

Primary AE = anemia (median drop in HCT 10%)

Neutropenia, thrombocytopenia

170
Q

What was the PFS for dogs treated with VBL/CTX/pred for measureable disease vs. incomplete excision or high risk of mets (Camps-Palau VCO 2007)

A

Measurable: 74d

Incomplete or high risk of mets 865d

171
Q

Did hypotonic water as adjuvant therapy for incompletely excised MCT affect survival time or rate of local recurrence (Brocks Vet Surg 2008 - mentioned in new withrow chapter)

A

Nope - not recommended for use

172
Q

What % of MCT were not diagnosed with rapid stain compared with Giemsa? How about LN mets? (Sabattini VCO 2018)

A

5% of MCT - majority high grade tumors

7-18% of nodal mets

173
Q

Did cytologic grading accuracy differ between aqueous stains vs. Giemsa? (Sabattini VCO 2018)

A

Nope - 85% accuracy

174
Q

What was the CT appearance of the liver in 5 dogs with confirmed cytologic mets from MCT? (Hughes VRU 2018)

A

4/5 normal - CT not good for detecting liver mets

175
Q

What CT finding were significantly associated with MCT mets in the spleen? (Hughes VRU 2018)

A

Heterogenous or nodular spleen

176
Q

Was FDG-PET-CT better for staging MCT in dogs compared to traditional methods? Anything associated with high grade? (Griffin VRU 2018)

A

Nope

Higher median SUVmax correlated with high grade (5.63, range 3.92-23.73) vs low grade (2.7, 1.8-5.7)

177
Q

What was the diagnostic accuracy for pre-treatment bx of cMCT in dogs? (Shaw, VCO 2017)

A

Overall agreement 96% on Patnaik, 92% on Kiupel; lowest for wedge bx

178
Q

If bx of cMCT did not match the overall grade after surgical removal, did bx over or underestimate grade? (Shaw VCO 2017)

A

Under

179
Q

What was significantly associated with stage 2 grade 2 MCT? (Krick JAAHA 2017)

A

AgNORs/nucleus (OR 2.8)

Recurrent tumors(OR 8.8)

180
Q

What was the sensitivity and specificity of AgNORs/cell in predicting stage of canine MCT? What was the cutoff value? ( Krick JAAHA 2017)

A

AgNORs/cell ≥1.87

sensitivity 93.3

specificity 27.4%

181
Q

What was the AgNOR cutoff value that reliably predicted LN metastasis for canine MCT? (Krick JAAHA 2017)

A

Trick question - cutoff NOT determined

182
Q

What were the cytologic characterisitics used to grade cMCT cytologically for dogs? (Scarpa VCO 2016)

A

number of mitoses

multinucleated cells

bizarre nuclei

presence of karyomegaly

183
Q

What was the accuracy, sensitivity and specificity for cytologic grading of canine cMCT? (Scarpa VCO 2016)

A

Accuracy 94%

Sensitivity 84.6%

Specificity 97.3%

184
Q

What criteria classified a MCT as high grade based on cytology (Camus VetPath 2016)

A

Poorly granular

OR at least two of the following:

Mitotic figures, nuclear pleomorphism, binucleated or multinucleated cells, >50% anisokaryosis

185
Q

What was the sensitivity and specificity of the Camus cyto grading scheme compared to histopathology (Vet Path 2016)

A

88% sensitivity

94% specificity

186
Q

What was the overall agreement, sensitivity, specificity and kappa score for two teir cyto grading for MCT? (Hergt VetClinPath 2016)

A

Agreement in 113 cases, 87% sens; 97 spec; kappa 0.853

187
Q

Of the 8 cases that disagreed between cyto and histo grading for MCT, how many were cyto low/histo high vs cyto high/histo low? (Hergt Vet Clin Path 2016)

A

5 low on cyto, high on histo

3 high on cyto, low on histo

188
Q

What percentage of c-kit mutations matched between primary and metastatic lesions for MCT? (Marconato 2014)

A

100%

189
Q

What were the MR imaging characteristics of MCT **exam committee**

A

T2: 7/9 = hyperintense to mm, 2/9 iso

T1: 8/9 isointense, 1 iso

All strongly contrast enhancing (homogenous 5, heterogenous 4)

190
Q

Incidence of bone marrow mets from MCT at diagnosis vs. in overall study? (Enicott VCO 2007)

A

At dx: 2.8%

All: 4.5%

191
Q

Survival for dogs with liver/spleen mets from MCT compared to w/o? (Stefanello JVIM 2009)

A

34d vs. 733d

192
Q

What breeds are predisposed to get maculopapular cutaneous mastocytosis? Ngo JFMS 2019

A

Sphynx, Devon Rex

193
Q

What were the three types of feline maculopapular cutaneous mastocytosis described? (Ngo JFMS 2019)

A

Polymorphic

Monomorphic

Pigmented

194
Q

Stem cell factor was expressed in what percent of feline cutaneous MCT? Where in tumor was this expressed and what other markers were/were not associated with it?(Sakurai J Comp Path 2018)

A

43% (10/23) expressed at margins of feline cMCT

8/10 co-expressed Kit, not near Ki-67 expressing cells

195
Q

What was the MST for cats with GI MCT? (Barrett VCO 2018)

A

531 d.

196
Q

What was associated with a prolonged survival times in cats with gastrointestinal MCT? (Barrett VCO 2018)

A

Treatment - chemo (CCNU/chlorambucil most commonly), sx+chemo, steroids + sx, steroids alone

197
Q

What was found to significantly prolong survival in cats with splenic MCT? (Evans VCO 2017)

A

Splenectomy - 856d vs. 342d w/o

198
Q

What was the survival time for cats terated with chemo alone vs. supportive care for cats with splenic MCT? (Evans VCO 2017)

A

Chemo alone 244d, supportive care 365d

199
Q

What was the survival time for cats treated with splenectomy vs. splenectomy + surgery for splenic MCT? (Evans VCO 2017)

A

Splenectomy: 856d, +chemo: 853d.

Role of chemo for treatment = unknown

200
Q

What was the overall clinical benefit for cats treated with TOC for MCT (various locations) (Berger JFMS 2017)

A

80%

86% cutaneous

80% visceral

76% GI involvement

201
Q

Median duration of treatment for cats with clinical benefit from TOC for MCT? (Berger JFMS 2017)

A

36wks for cutanoues, 48 for visceral and 23 for GI

202
Q

What was the median dose/schedule for cats treated with TOC for MCT? (Berger JFMS 2017)

A

2.5mg/kg PO 3 days/wk

203
Q

What was the rate of AEs for cats treated with TOC for MCT? (Berger JFMS 2017)

A

60% rate of AE, jaority low-grade GI or heme

204
Q

What was the rate of KIT expression for feline intestinal MCT? (Sabattini JFMS 2016

A

overall 12/17 70.5%

membranous (33%), focal paranuclear (33%), diffuse cytoplasmic (13%)

205
Q

What KIT staining pattern was associated with less differentiated intestinal MCT in cats? (Sabattini JFMS 2016)

A

Diffuse cytoplasmic

206
Q

What breed of cats is overrepresented for feline cMCT? (Melville FJMS 2015)

A

Siamese, Burmese, Russian Blue, Ragdoll

207
Q

What was the most common location for cMCT in young vs. older cats? (Melville JFMS 2015)

A

Young: head

Older: trunk

208
Q

What was or was not associated with survival time in cats with cMCT? (Melville JFMS 2015)?

A

Was associated: MI

Was not associated: number of tumors

209
Q

What percent of cats died from cMCT? (Melville FJMS 2015)

A

17.4%

210
Q

What was the overall MST for cats treated with splenectomy for splenic MCT? (Kraus JAAHA 2015)

A

390d.

211
Q

What were negative prognostic factors for cats undergoing splenectomy for splenic MCT? (Kraus JAAHA 2015)

A

Admin of blood product, mets to regional LN, concurrent or historic neoplasia

212
Q

What was associated with improved survival time for cats treated with splenectomy for splenic MCT? (Kraus JAAHA 2015)

A

Response to chemo

213
Q

What was the dose of CCNU given to cats for treatment of MCT? (Rassnick JAVMA 2008)

A

50-60mg/m2

214
Q

What was the ORR and median response duration to CCNU for feline MCT? (Rassnick JAVMA 2008)

A

ORR 50%, median duration 168d

215
Q

What were the primary toxicities associated with CCNU given to cats with MCT? (Rassnick 2008(

A

Neutropenia and thrombocytopenia

216
Q

What were the predominant staining patterns for feline MCT (Rodriguez-Carino VetPath 2009)

A

diffuse cytoplasmic (8/19) and membranous (7/19)

217
Q

Atypical feline MCT typically have which KIT pattern? (Rodriguez0Carubi Vet Path 2009)

A

diffuse cytoplasmic

218
Q

What was the rate of metastasis (and hwere was it) for felline intestinal sclerosing MCT (Halsey, VCO 2010)

A

66%, LN and hepatic

219
Q

What was the outcome for feline intestinal sclerosis MCT? (Halsey VCO 2010)

A

23/25 died/euth w/in 2 mo

220
Q

What four TKIs were tested in felline MCT with systemic mastocytosis with what exon internal tandem duplication? (Hadzijusufovic Vet Immuno/Immunopath 2009)

A

imatinib, midostaurin, nilotinib, and dasatinib

Exon 8

221
Q

What were the results of the 4 TKI’s tested on feline MCT in vitro? (Hadzijusufovic Vet Immuno and immunopath 2009)

A

All four showed dose-dependent growth inhibition, growth inhibition associated with morph signs of apoptosis

222
Q

What was the rate of metastasis for oral mucosal MCT in dogs? (Elliot VCO 2016)

A

55% at time of diagnosis

223
Q

What was prognostic for dogs with oral mucosal MCT (Elliot VCO 2016)

A

Nodal mets (w/ = MST 276d vs. not reach if not)

MI >5 MST 120 vs. not reached if <5

Inadequate local control (OST 242 vs. not reached)

**site not prognostic - lip, gingiva, other**

224
Q

Dogs with high grade/grade II MCT did better with vinblastine/pred compared to ______? (Miller VCO 2014)

A

Masitinib (369d) vs. vbl/pred 1946d

225
Q

What was associated with outcome for dogs with MCT on the pinna that were treated surgically? (Schwab JAAHA 2014)

A

Grade - MST grade 1-2 not reached

MST of grade3 = 10mo

226
Q

What was the affect of LN mets on dogs with grade 2 MCT treated with surgery to remove the primary tumor +/- LN? (baginski JAAHA 2014)

A

No difference in survival time, but dogs that had metastatic LN removed did to better than those that did not

227
Q

What was the MST for high-risk MCT treated with adjuvant vbl/pred? (Thamm 2006)

A

Grade II MST not reached

Grade III MST 1374d

228
Q

In canine MCT, a Ki67 index cutoff value of ____ was correlated with aggressive behavior

A

> 1.8% = more likely to be aggressive (lower 1- 2- and 3-yr survivals)

229
Q

What prognostic factors are associated with SQ MCT? (Thompson Vet Path 2011)

A

MI >4 strongly predictive of mortality

others - infiltrative growth pattern, presence of multinucleation

230
Q

What was the MST for SQ MST with an MI > 4 + other poor prognostic factors (infiltrative growth, multinuc) vs. those with an MI >4 w/o other poor prognostic factors (Thompson vet path 2011)

A

W/ other poor = mst 140d

w/o = mst 950d

231
Q

What KIT and IHC proliferation indicies were associated with tumor regrowth or metastasis for canine SQ MCT? (Thompson Vet Path 2011)

A

Recur: AgNOR >2.71

Recur or met: MI >4, Ki67 >21.8 Ag67 (AgNOR x Ki67) > 55, cytoplasmic kit localization

232
Q

Increased ____ and ____ were significantly associated with decreased survival and increased local mets for canine SQ MCT (Webster Vet Path 2007)

A

Ki67 > 23

Ag67 (AgNOR x Ki67) >54

233
Q

SQ MCT with aberrant KIT localization or c-kit mutations were associated with ____ (Webster Vet Path 2007)

A

increased cellular proliferation

234
Q

What was the MST for dogs with multiple cutaneous MCTs (Mullins JAVMA 2006)

A

MST not reached

2-5yr survival 85%

235
Q

What was the rate of metastasis for dogs with multiple cutaneous MCTs (Mullins JAVMA 2006)

A

15%

236
Q

What was prognostic for DFI in dogs with multiple cutaneous MCTs? (Mullins JAVMA 2006)

A

Clinical signs at time of dx

237
Q

What factors were prognostic for DFI and OS in dogs with MCT treated with VBL/pred (Webster BMC 2008)

A

Grade 3, c-kit mutation, increased cytoplasmic KIT, increased Ki67 and AgNOR

238
Q

Bcl-2 expression was higher in what grade MCT and was associated with what? (Vascellari Vet Path 2013)

A

Higher in grade 2 than 1 (but not different in high vs. low)

increased Bcl-2 associated with increased mortality

239
Q

____% of cutaneous MCT were positive for IHC for PGE2 and VEGF and ____ grade MCT had higher PGE2 than grade ______. (Amorim VCO 2010

A

100% expressed both; grade II and III had higher PGE2 than grade I

240
Q

A mitotic index of ____ was found to be prognostic in 148 dogs with cutaneous MCT (Romansik Vet Path 2007)

A

<5 MST 70mo

>5 MST 2mo

241
Q

What was the PFS and OST for dogs with grade 3 MCT (Hume JAAHA 2011)

A

PFS 133d, OS 257

Mix of treatments (21/32 had adequate local control)

242
Q

What was prognostic for PFS and MST for dogs with grade 3 MCT treated with a variety of treaments (Hume JAAHA 2011)

A

PFS: tumor size (>3cm), LN status

MST: treatment of LN mets (240d. vs 89d)

243
Q

What was the overall rate of recurrence and rate of developing a new MCT for dogs with incompletely excised grade 2 cMCT? (Seguin JVIM 2006)

A

Recurrence 23.3%

39.3% developed another MCT

244
Q

Dogs presenting with metastatic disease from MCT benefited from what treatment? (Miller VCO 2016)

A

surgery to remove the pimary + chemo - MST 278d vs. 91d w/o surgery

245
Q

Which KIT staining pattern was associated with local MCT recurrence and shorter survival? (Kupel Vet Path 2004)

A

Diffuse cytoplasmic

246
Q

Tumor suppressor in lung cancer 1 (TSLC1) had what relationship with Ki67 and tumor grade for MCTs? (Taylor VCO 2010)

A

TSLC1 inversely correlated with tumor grade and Ki67

Lower TSLC1 in intermediate MCT = more likely to die from MCT related disease

247
Q

What signalment dog had increased overall risk of developing MCT? (White, JAAHA 2011)

A

Spayed females (OR 4.11)

Boxers (6.09)

Large (2.1) and giant (5.44) breeds

248
Q

For dogs with MCT on the head treated with RT, where was the highs grade toxicity? (Blackwood VCO 2018)

A

Mucosa or nasal planum

249
Q

What was associated with an increased frequency of grade 2 or 3 RT toxicityf at 1st recheck for dogs treated with RT for MCT? (Blackwood 2018)

A

increased frequency in patients using prednisolone prior to RT

250
Q

What was the RT/Palladia protocol for hypofx RT + TOC for gross MCT in dogs? (Carlsten JVIM 2012)

A

Toc 1 week prior to RT

RT 24Gy in 3-4fx

251
Q

What was th ORR for dogs treated with hypofx RT + TOC for gross disease MCT? (Carlsten JVIM 2012)

A

ORR 76.4%

CR 58.8%

PR 17.6%

**higher response rate than Palladia as single agent**

252
Q

What was the median time to best response for dogs treated with hypofx RT + TOC for gross disease MCT (JVIM 2012 Carlsten)

A

32d

253
Q

What was the median PFI and MST for dogs with gross disease MCT treated with hypofx RT + TOC? (Carlsten JVIM 2012)

A

mPFI 316d, MST not reached

254
Q

What was the rate of tumor recurrence for incompletely excised grade II MCT treated with cobalt RT? What effect did prophylactic nodal irradiation have? (Poirier JAAHA 2006)

A

Rate of recurrence 6.7%

No difference in mets when dogs had or didn’t have prophy. RT to LN

255
Q

What was the clinical benefit to treatment with diphenhydramine in dogs undergoing excision of MCT? (Sanchez JAVMA 2017)

A

None found - histamine higher during max tumor manipulation and surgery prep in diphenhydramine group; higher in control for surgical dissection

256
Q

How did histological margins compare to surgical margins measured in dogs with MCT? (Risselada JAVMA 2015)

A

histo 35-42% smaller than lateral surgical margins

BCS did not influence this

257
Q

Did a low AgNOR and Ki67 score for grade II MCT surgically removed influence rate of recurrence? (Smith VCO 2015)

A

Sort of - only 7% rate of recurrence for dogs, no difference in complete vs. incomplete margins

Authors conclusion - second surgery may not be necessary for incomplete sx in grade II MCT with low Ki67/AgNOR scores

258
Q

What was the MST for dogs with incompletely exicsed MCT treated with a second surgery vs. RT vs. no additional therapy? (Kry Vet Surg 2014)

A

Recut: 2930d

RT 2194d

No additional therapy: 710d (significantly shorter)

259
Q

T/F: adjunctive chemo was associated with improved survival or local control in dogs with narrow or incompletely excised MCT (Kry Vet Surg 2014)

A

False - no benefit found

260
Q

No MCT recurrence of mets after surgery were found for dogs with what histologic margins (for any grade MCT) (Schultheiss JAVMA 2011)

A

Lateral margins >10mm, deep margins >4mm

261
Q

What was the rate of achieving histo clean margins for dogs having MCT (SQ or dermal) removed with modified proportional margins? How many had local recurrence? (Pratschke JAVMA 2013)

A

85% complete, 15% incomplete

Local recurrence suspected in 1 dog (2%)

262
Q

What was the rate of complete excision and local recurrence for dogs with grade 1 or 2 MCT treated with 2cm lateral and 1 fascial plane deep margins? (Fulcher JAVMA 2006)

A

91% completely excised, no local recurrence

263
Q

What was the response rate to neoadjuvant pred prior to surger for MCT? What was the difference between dosing strategies for pred? (Stanclift JAVMA 2008)

A

70% response rate

No difference in size reduction b/w 1mg/kg and 2.2mg/kg

264
Q

What is tigilanol tiglate and how does it work (Miller Frontiers in Vet Science 2019)

A

Novel diterpene ester from Fontainea picrosperma seed

Modifies cell signaling processes and induces rapid hemorrhagic necrosis and activates protein kinase C

Mainly targets tumor vasculature

265
Q

What was found to be the best dosing for tiglanol tiglate in dogs with MCT (Miller Frontiers in Vet Science 2019)

A

Highest concentration used (1mg/ml) - 90% CT, majority AEs grade 1 (80%), rest grade II

Oncology Boards (26 decks)

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