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Onco Board Review > LSA, Histiocytic, HSA, Melanoma > Flashcards

LSA, Histiocytic, HSA, Melanoma Flashcards

1
Q

How does Yunnan Baiyao induce cell death in HSA cells in vitro

A

Caspase-mediated apoptosis

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2
Q

Can serum VEGF aid in distinguishing hemangiosarcoma from splenic hematoma?

A

NO - elevated in both compared to normal dogs

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3
Q

Which IHC markers can help distinguish HSA?

A

c-kit, CD31 (PECAM-1), VEGFR-3, vWF, CD44

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4
Q

What % of nontraumatic hemoabdomen in cats is neoplastic in origin? What is the most common underlying neoplasia?

A

44% neoplastic

most common = hepatic neoplasia

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5
Q

What is the metastatic rate at diagnosis of feline visceral HSA?

A

33% mets to lungs @ dx

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6
Q

What conditions can result in acanthocytosis (spiculated RBCs)?

A

HSA (ie microangiopathic - also expect schistocytes)
liver disease
hypercholesterolemia

spherocytes –> zinc, IMHA

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7
Q

Name two positive prognostic indicators for cutaneous HSA?

A

Predisposed breed with ventral abdominal location

Histologic solar changes

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8
Q

In a whippet with multiple ventral cutaneous HSA, what is the prognosis?

A

Higher risk for recurrence – predisposed breed with multiple ventral masses

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9
Q

What clinical factors are associated with poor prognosis in cutaneous hemangiosarcoma?

A

Non-predisposed breed with invasive tumors

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10
Q

In dogs that received allogenic HSA tumor vaccines, which of the following were observed: antibody production, fever, vasculitis

A

Antibodies

Strong humoral response

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11
Q

Which of the following is higher in feline HSA: multicentric disease at diagnosis or mets to lungs at diagnosis?

A

Multicentric in 77%

Mets to lungs in 33%

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12
Q

What was the ORR and MST for dogs with presumptive cardiac HSA treated with DOX?

A

ORR=41%

MST = 120d

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13
Q

What is the response rate to DOX treatment in dogs with SQ HSA?

A

38.8%

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14
Q

What is the MST for dogs with B-ALL treated with multiagent chemotherapy?

A

120d

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15
Q

Flow cytometry from a dog with a mediastinal mass shows >10% CD4+CD8+ cells. What is the diagnosis?

A

Thymoma

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16
Q

What is the flow cytometric phenotype for LGL lymphoma? What is the survival time?

A

CD3+/CD8+

MST = 57d

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17
Q

What effect did CD40L vaccination have in dogs with lymphoma?

A

Improved SECOND remission duration and OST

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18
Q

What drug increases sensitivity of mast cells to chemotherapy but is limited by toxicity?

A

Calcitriol

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19
Q

What % of patients with digital melanoma have mets detected at diagnosis?

A

30-40%

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20
Q

What is the reported ORR of melanoma to RT?

A

82-94%

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21
Q

Which radiation protocol reported to date has resulted in the longest MST for dogs with oral melanoma?

A

6x6Gy

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22
Q

What is the recurrence rate reported by Proulx et al for dogs treated with RT for oral melanoma in the setting of microscopic disease? Macroscopic disease?

A

Microscopic - 26%
Macroscopic - 45%

MST 7mo

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23
Q

What is the reported ORR of melanoma to platinum-containing drugs?

A

18-28%

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24
Q

To which canine chromosome has p53 been mapped?

A

CFA 5

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25
Q

What is the function of p21/Waf-1?

A

universal CDK inhibitor

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26
Q

What is the function of p16?

A

CDK 4/6 inhibitor

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27
Q

What is L-MTP-PE? What was the conclusion of a randomized placebo-controlled trial using L-MTP-PE as an adjunct to surgery in patients with oral melanoma?

A

liposomal muramyl tripeptide phosphatidylethanilamine

–> induces proinflammatory cytokines

improved survival in canine OMM

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28
Q

For which types of melanoma is ulceration prognostic?

A

Digital, cutaneous

NOT oral

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29
Q

Name 5 factors that are prognostic for melanoma regardless of the site.

A 
Distant mets
Nuclear atypia
Mitotic index
Ki67
Degree of pigmentation
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30
Q

What is the prognostic Ki67 threshold for oral melanoma? For cutaneous/digital?

A

Oral - >19.5

Digital - >15%

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31
Q

Name two breeds in which melanocytic neoplasms are more likely to be benign.

A

Dobbies, mini Schnaz

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32
Q

What is the prognostic mitotic index threshold for oral melanoma? For cutaneous/digital?

A

Oral - >/= 4

Digital - >/=3

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33
Q

What effects did celecoxib have in COX-2 expressing melanoma cell lines?

A

Decreased PGE2
Decreased cell viability, increased activated caspase 3
Cell cycle arrest, decreased cyclin D1

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34
Q

In which melanocytic tumors was COX2 expression higher? Did COX2 expression correlate with survival?

A

Oral tumors, MI >3, high Ki67 –> higher COX2

Higher COX2 = decreased survival

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35
Q

What impact did KPT335, an XPO1 inhibitor, have on melanoma cell lines?

A

induced apoptosis and inhibited proliferation

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36
Q

Were CSCs (identified by CD133, CD24, CD34, CD44, and Oct3/4 expression) more common in melanoma tumors or cell lines?

A

Tumors

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37
Q

What are the most frequent chromosomal aberrations in melanocytic tumors?

A

gain of CFA 13 & 17

loss of CFA 22

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38
Q

Despite the rare presence of BRAF and NRAS mutations in canine melanoma, evidence of constitutive activation of which pathways was similar between human and canine cell lines?

A

MAPK

PI3K/AKT

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39
Q

What impact did decreased expression of miR-203 have on overall survival in dogs with melanoma? What impact did ectopic expression of miR-203 in melanoma cell lines?

A

Decreased survival

Ectopic expression –> inhibited cell growth

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40
Q

What % of melanoma cell lines investigated expressed alpha-3 integrin, a protein associated with increased motility and metastatic behavior?

A

100%

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41
Q

Mutations in kit exon 11 were detected in what % of canine melanoma? Did kit mutation/expression correlate with outcome?

A

0 - 10% mutation rate, 51 - 100% kit expression

NO correlation with outcome (2 studies)

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42
Q

What % of canine OMM showed co-expression of PDGFRa/B, and what impact did this have on prognosis?

A

37.5%

associated with poor prognosis

43
Q

What were the staining patterns of canine melanoma and melanocytoma for receptor of activated c-kinase 1 (RACK1)?

A

melanomas - 100% homogenous staining

melanocytomas - 100% heterogenous staining

44
Q

Increased expression of which genes was detected in metastatic canine uveal melanoma (compared to nonmetastatic)?

A

HTR2B, FXR1, LTA4H, CDH1

45
Q

PNL2 is an antigen of unknown function identified on what two cell types?

A

Melanocytes, granulocytes

46
Q

What is the sensitivity and specificity of an IHC cocktail of PLN2, Melan-A, and TRP-1/TRP-2 for diagnosis of canine oral amelanotic melanoma?

A

100% Sn, 94% specific

47
Q

High tyrosinase expression (compared to normal tissue) has been documented in both canine and equine melanomas. Does tyrosinase expression correlate with degree of pigmentation?

A

No

48
Q

What impact did the expression of actin-bundling protein fascin-1 have on survival in canine melanoma?

A

Associated with higher stage and decreased survival

49
Q

Microvessel density and endothelial area were found to be higher in oral melanomas than cutaneous melanocytomas. Were these features prognostic for survival?

A

No- no correlation with survival

50
Q

Which of the following markers is most sensitive for detection of melanocytic tumors?
PNL2, Melan-A, tyrosinase

A

PNL2

51
Q

What % of melanoma stained + for VEGF?

A

95%

52
Q

What correlation did plasma VEGF levels have with melanoma disease status and survival?

A

Higher plasma/serum VEGF in dogs with melanoma than controls

Higher VEGF correlated with higher stage and decreased survival

53
Q

What was the sensitivity and specificity of ICC using cytokeratin, vimentin, and melan A for the cytologic diagnosis of amelanotic melanoma? How does this compare to routine cytology?

A

100% Sn/Sp

better than routine cyto (67% Sn, 85% Sp)

54
Q

Which pathologic feature was prognostic for cats with non-ocular melanoma?

A

Lack of pigmentation

55
Q

What were the ROC cutoff values identified for predicting death due to melanoma at 1 year for the following parameters: Ki67, nuclear atypia, MI

A

Ki67 > 19.4
Nuclear atypia score > 4
MI > 4

56
Q

What was the mPFI and MST following curative-intent surgery for oral melanoma?

A

508d PFI

723d MST

57
Q

Which factors were predictive of disease progression following curative-intent surgery for oral melanoma?

A

administration of adjuvant therapy
presence of mets at dx
higher tumor stage, increased size (>3cm)
sexually intact female dogs

58
Q

What is the ORR of melanoma to carboplatin?

A

28%

59
Q

What outcome parameters were significantly different in dogs receiving RT + temozolomide vs RT alone?

A

Temo group had longer TTP and lower failure rate (distant + local)

Met rate was not significantly different

60
Q

What was the rate of AEs observed in cats recieving Oncept?

A

11.4%

61
Q

What was the 1-year survival rate for dogs with digital melanoma treated with a murine tyrosinase DNA vaccine?

A

63%

MST =476d

62
Q

What % of canine malignant melanoma express CSPG4?

A

57%

63
Q

What was the affect of CSPG-4 electovaccination on MST and antibody formation in dogs with OMM?

A

significantly longer DFS

all dogs developed antibodies

64
Q

What are the B2 integrins?

A

CD11(a-d) and CD18 – adhesion molecules differentially expressed by all leukocytes

65
Q

Which cell types express CD11c and CD11d, respectively?

A

CD11c - LCs and interstitial DCs/most histiocytic diseases

CD11d - macrophages/hemophagocytic HS (also CD11b in some settings)

66
Q

In which species are the characteristic Birbeck’s granules lacking from Langerhans cells?

A

dogs

67
Q

Which breed is predisposed to multiple cutaneous histiocytomas?

A

Shar pei

68
Q

Abnormalities in which tumor suppressor genes have been implicated in the formation of histiocytic sarcoma in BMD and flat-coated retrievers?

A

CDKN2A/B
Rb1
PTEN

69
Q

In hemophagocytic HS, where is the primary tumor?

A

Spleen (splenic red pulp)

70
Q

Which joints are most commonly affected by periarticular HS? Which breed is predisposed?

A

stifle and elbow

Rotties

71
Q

Name 3 negative prognostic factors for canine histiocytic sarcoma identified by Dervisis et al (2016).

A

Use of corticosteroids
Disseminated disease
Palliative treatment

72
Q

What is the odds ratio for development of PAHS in BMD with previous joint disease vs. those without?

A

5.4

73
Q

Which diseases resulted in the highest levels of hyperferritinemia?

A

IMHA
Histiocytic sarcoma
Liver dz

Degree of elevation allowed differentiation from LSA and inflammatory disease

74
Q

Name two factors associated with decreased survival in dogs with periarticular histiocytic sarcoma.

A

Use of prednisone

Mets at diagnosis

75
Q

What was the ORR of histioctytic sarcoma to a combination protocol using DOX and CCNU?

A

58%

76
Q

Copy number aberrations in histiocytic sarcoma were recently investigated in BMD and flat coats. Did identified CNAs differ between these breeds?

A

No, the CNAs were shared between the two breeds

77
Q

Is CD204 more sensitive, specific, or both than CD18 or MHC II for detection of histiocytic sarcoma?

A

More specific

Sn = 100% for all 3, CD18/MHC II are much less specific

78
Q

What % of histiocytic sarcoma are + for CD204 on IHC? on ICC?

A

100%

79
Q

Which of the following is likely to be a therapeutic target in feline histiocytic disorders? PDGFR-B, Kit

A

PDGFR-B

Kit expression negative in all tumors investigated

80
Q

What is the OR for development of histiocytic sarcoma in BMD and FCR compared to other breeds?

A

BMD - 45.0

FCR - 62.0

81
Q

What is the ORR and duration of HS to CCNU?

A 
ORR = 46%
MPFI = 85d
82
Q

Which gene locus has been identified as a germline susceptibility locus for histiocytic sarcoma in BMD?

A

MTAP

83
Q

Which CD11 isoforms are expressed by macrophages?

A

CD11b; CD11d (BM and splenic mphages)

84
Q

Which CD11 isoform is expressed by interstitial DCs?

A

CD11c

85
Q

Which histiocytic cells express E-cadherin?

A

Langerhans cells

86
Q

Which histiocytic cells express Thy-1 (CD90)?

A

Dendritic cells

87
Q

What is the response rate of histiocytic sarcoma treated with CCNU at 70 and 90 mg/m2, respectively?

A

70mg/m2 - 46%

90mg/m2 - 29%

88
Q

VEGF and MMP-9 were highest in dogs with which types of lymphoma?

A

T-cell > B-cell
High grade > Low grade
Stage 5 > other

89
Q

What Ki67 cutoff value (determined by FC) distinguished high grade from low grade lymphoma?

A

12.2%

90
Q

Was neutrophil/lymphocyte count prognostic for survival in dogs with lymphoma?

A

NO

91
Q

Was VEGF expression or MVD prognostic for survival in dogs with lymphoma?

A

NO

92
Q

MRD status at which timepoints has been shown to be prognostic in dogs with lymphoma?

A

CHOP week 11

completion of CHOP

93
Q

Which of the following flow cytometric characteristics are associated with poor prognosis in canine lymphocytosis? CD34+, CD4-CD8-CD5+, large cell size, lymphocytosis >30K

A

CD34+
lymphocytosis >30K for CD8+ subset
large cell size for CD21+ subset

94
Q

Which features were common to the 10% of canine lymphoma patients living >2years

A 
BW >10kg
B-cell centroblastic phenotype
No hypercalcemia
No BM involvement
No steroids
95
Q

In a study of lymphoma stage migration by Flory et al, what impact did stage have on remission rate and duration and overall survival?

A

None

“There was migration between all of the staging methods. However, the stage was not a predictor of remission rate, remission duration, or survival, regardless of staging method used.”

96
Q

Human Burkitt lymphoma is characterized by a chromosome 8:14 translocation, juxtaposing which two genes? What is the corresponding recombination in dogs?

A

Myc-IgH

Dogs - CFA 8:13

97
Q

What was the odds ratio for neutered male dogs to develop TCC of the bladder and prostate?

A

bladder - 3.6
prostate - 8.0 !!!

*** increased risk for TCC, prostate CA, any prostatic tumor. Hypothesis = increased estrogen efx on tissue, epigenetic changes due to loss of androgen-R signaling

98
Q

What was the rate of high grade prostatic intraepithelial neoplasia (HGPIN) and prostatic inflammatory atrophy (PIA) in prostatic samples from dogs?

A

HGPIN - 24%

PIA - 19%

99
Q

Anti-Mullerian hormone is a useful IHC marker to detect what tumor?

A

Sertoli cell tumor

100
Q

Which breeds have an increased incidence of BCL?

A

Cockers and Bassets

101
Q

Which breeds have the highest incidence of TCL?

A

Irish wolfhounds
Huskies
Shih Tzus

102
Q

Which IHC marker is useful in equine melanoma: S-100, PNL2, MelanA?

A

PNL2 - sensitive and specific

MelanA was not expressed in equine melanomas

103
Q

What were the most common subtypes of lymphoma in horses?

A

T-cell–rich large B-cell lymphoma = most common
Peripheral T-cell lymphomas
diffuse large B-cell lymphomas

Onco Board Review (6 decks)

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