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EV ACVD Study > Oncology (NAVDF 2023 LaPorte) > Flashcards

Oncology (NAVDF 2023 LaPorte) Flashcards

1
Q

Which proteins work by phosphorylating (activating) downstream tumor suppressor proteins.

A

Cyclins, cyclin-dependent kinases

Regulate the cell cycle

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2
Q

On which phase of the cell cycle do most chemotherapies work?

A

S phase (DNA replication)

(Can be M phase or signal transduction to start cell cycle)

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3
Q

In which phase of the cell cycle are cells most resistant to radiation

A

S phase

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4
Q

What are intrinsic causes of cancer development

A

Inherited gene, gene product abnormality

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5
Q

What are extrinsic causes of cancer development

A

Environmental factors

(UV, virus, ROS, chronic inflammation, trauma, chemicals, implants, radiation, magnetic field, hormones)

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6
Q

How does UV light cause cancer

A

Forms thymidine dimers

Nucleotide excision repair fails to fix them –> Cancer

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7
Q

Function of proto-oncogenes

A

Proto-oncogenes stimulate cell division, inhibit cell differentiation, inhibit cell death –> help make new cells, stay alive

When mutated to oncogene: Gas pedal stuck down!

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8
Q

Examples of oncogenes

A
  • c-KIT
    -Encodes tyrosine kinase protein; best known on mast cells tumors!
    *c-myc
    -Encodes TF that regulates cell cycle
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9
Q

Ligand for c-kit

A

c-kit binds stem cell factor (SCF) to increase signals for cell survival differentiation, proliferation

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10
Q

Function of tumor suppressor proteins

A

Slow down cell division. Induce apoptosis

TSP = Brake of the car

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11
Q

What is the most mutated protein in human cancer

A

p53– TSP

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12
Q

Name 2 tumor suppressor proteins

A

p53
pRB (E7 on papillomavirus binds, inhibits pRb –> uncontrolled cell cycling and cancer)

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13
Q

Function of DNA repair genes

A

Fix DNA mistakes around cell division. If can’t fix it -> trigger cell death

DNA repair gene = car mechanic

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14
Q

Steps of the metastatic cascade (4)

A

1) Invasion and migration
-Break through BMZ
2) Angiogenesis and intravasation
3) Survival in circulation and Attachment to endothelium
4) Extravasation and Colonization

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15
Q

What is the difference between pre-cancerous neoplasia and malignant cancer

A

Invasion through the BMZ in malignant cancer

This the the “differentiating step”

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16
Q

How can immunosuppresive drugs cause cancer

A

Immune system can no longer surveil for cancer growth, so easier for neoplastic growth to occur

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17
Q

Cyclosporine inhibits which cell that is crucial for cancer immunosurveillance

A

CD8 T cells

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18
Q

How could Apoquel potentially be associated with increased risk of cancer

A

Suppresses JAK1 –> inhibits IL-2, IL-4 –> reduces stimulation of innate tumor immunosurveillance (gamma delta T cells, NK cells)

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19
Q

T or F: it is likely that higher doses of oclactinib and cyclosporine are more likely pro-neoplastic

A

True

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20
Q

Metastatic pathway of Sarcomas

A

Sarcoma to Lungs via BLOOD

CXR

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21
Q

Metastatic pathway of Carcinomas

A

Carcinoma to REGIONAL LN -> lungs, liver spleen via BLOOD AND LYMPHATICS

Regional FNA, CXR, AUS

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22
Q

Metastatic pathway of Round cell tumors

A

Tumor -> Regional LN -> liver, spleen via LYMPHATICS

Regional FNA, AUS

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23
Q

Neoplastic consequences of Feline papillomavirus

A

1) BISC
2) SCC
3) Feline sarcoid (BPV14)

4) Viral plaqu

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24
Q

How do papillomaviruses cause malignant transformation

A

Destabilize TSP p53 by E6
Inhibit pRb by E7

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25
Q

Cancers associated with Feline Skin Fragility Syndrome

A

Adrenal carcinoma
Abdominal carcinomas
Multicentric lymphoma

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26
Q

Cancer associated with Bilateral Ischemic Necrosis of the HIndpaws

A

Multicentric follicular lymphoma

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27
Q

IHC marker for T cells

A

CD3

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28
Q

IHC markers for B cells

A

CD20, CD79a, PAX5

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29
Q

IHC marker for epithelial cells

A

Cytokeratin

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30
Q

IHC marker for Mesenchymal cells

A

Vimentin

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31
Q

IHC marker for melanocyes

A

Melan A

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32
Q

Origin of melanocytic tumors

A

Mesenchymal. But can look like epithelial or round cell on cytology

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33
Q

Stains for mast cell granules (2)

A

Toludine blue
Giemsa

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34
Q

Stain for melanoma (melanin vs hemosiderin)

A

Fontana Masson

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35
Q

IHC marker for plasma cell tumor

A

MUM1

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36
Q

IHC marker for Mast cell tumor

A

C-Kit
CD117

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37
Q

IHC marker for histiocytoma

A

CD18, CD204, E cadherin, IBA1

NEGATIVE for CD4, CD90

(reactive histiocytoma is negative for E cadherin; positive for CD4, CD90)

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38
Q

IHC marker for hemangiosarcoma

A

Factor VIII related antigen
Claudin 5
CD31 (endothelial origin)

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39
Q

IHC for melanoma

A

Melan-A
PNL2
TRP-1
TRP-2

+/- S100

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40
Q

IHC for smooth muscle

A

Smooth muscle actin
Desmin

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41
Q

IHC for skeletal muscle

A

Myogenin D
Sarcomeric actin
Desmin

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42
Q

IHC for neuroendocrine tumor

A

Chromogranin A
Synaptophysin

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43
Q

Definition of sentinel lymph node

A

First lymph node to which cancers would spread from a primary tumor

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44
Q

Chemotherapeutic effect of imiquimod

A

SCC

Activates TLR7, secrete cytokines (IFNa, IL6, TNF-alpha)

activate LCs to go to LN and activate adaptive immunotherapy

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45
Q

Chemotherapeutic effect of prednisone

A

Inhibits DNA synthesis
Induces apoptosis

Mechanism not know

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46
Q

Acute AEs of radiation

A

Mucositis, erythema, alopecia, desquamation, lymphedema, changes in pigmentation

Usually SELF RESOLVING, RAPID RECOVERY

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47
Q

Severe Late AEs of radiation

A

Fibrosis, necrosis

RARE

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48
Q

Radiation recall

A

Return of acute radiation side effects once an animal receives chemo later on

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49
Q

Are dogs or cats more likely to have MALIGNANT skin tumors

A

Cats

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50
Q

Most common skin tumor in dogs

A

1) MCT
2) Lipoma
3) Histiocytoma

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51
Q

Most common skin tumor in cats

A

1) Basal cell tumor
-Basal cell carcinoma
-Basal cell epithelioima
-Trichoblastoma
-Solid-cystic ductular sweat gland adeno(carcino)mas
2) MCT
3) Fibrosarcoma
4) SCC

*Collectively, account of 70% of all feline skin tumors

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52
Q

Which species develops cutaneous plasmacytosis

A

Dogs only

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53
Q

Which cancer should you may particular attention to iCa and Renal Function

A

Plasma cell tumors –> Multiple myeloma

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54
Q

IHC for plasma cell tumors

A

MUM1/Interferon regulatory factor4

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55
Q

T or F: Cutaneous plasmacytosis has a high metastatic rate

A

TRUE

Staging is important. Multiple myeloma also has high metastatic rate

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56
Q

Where on the body are you most likely to find a plasmacytoma

A

Head (ears), limbs

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57
Q

Breeds predisposed to plasmacytoma

A

Airedale terrier
Boxer
Cocker Spaniel
GSD
WHWT
Yorkshire terrier

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58
Q

Treatment plasmacytoma dogs

A

Surgery is usually curative. Normal lifespan

Local recurrence 5%

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59
Q

In cats with plasmacytoma, what should you monitor for

A

Progression to systemic myeloma-related illness

May be benign though! Just monitor

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60
Q

Treatment plasmacytoma cats

A

Surgery and chemo (check local LNs)

Usually benign in dogs, but may progress to multiple myeloma in cats

61
Q

Treatment for cutaneous plasmacytosis (only dogs get this! Like MM)

A

Chemotherapy: Melphalan!

62
Q

What is M component

A

Multiple myeloma

Accumulation of immunoglobulin (IgG or IgA) or Ig components (like Bence Jones protein)

63
Q

Clinical signs of cryoglobulinemia (multiple myeloma)

A

Extremities have:

Erythema
Purpura
Ulcerations
Punched out necrosis

64
Q

Prognosis of multiple myeloma in dogs

A

Good survival with Melphalan chemo; but rarely have CR

65
Q

Prognosis multiple myeloma in cats

A

Poor. Visceral involvement with limited BM infiltration

MST 4-13 months

66
Q

T or F: Multiple Myeloma in cats is oftentimes viral associated

A

FALSE.

Can be familial though!

67
Q

4 types of cutaneous mast cell neoplasms

A

1) Mast cell tumor
2) Urticaria pigmentosa
3) Diffuse cutaneous mastocytosis
4) Systemic mastocytosis with cutaneous involvement

68
Q

T or F: Mast cell tumors in cats are USUALLY benign

69
Q

T or F: MCT can spontaneously regress

A

True, it is reported

70
Q

Name the mediators in Mast Cell granules

A

1) Heparin
2) Chondroitin sulfate
3) Biogenic amines (histamine)
4) TNFa
5) Proteases (chymase, tryptase)
6) Acid hydrolases
7) Cathepsin G
8) Carboxypeptidase

71
Q

Which growth factor binds to KIT on mast cells –> MC activation, decrease apoptosis

A

Stem cell factor (SCF)

KIT is a tyrosine kinase receptor

72
Q

Which receptor on MCTs is associated with increased risk of local recurrence, metastasis, and death

A

c-kit ongogene

(Intermediate and high grade MCTs!)

73
Q

What class of chemotherapy may be effective in MCTs with c-kit mutations

A

Tyrosine kinase inhibitors

(Palladia, toceranib)

74
Q

Most common body sites for MCTs in dogs

A

Trunk, perineal, limbs > head/neck

75
Q

T or F: Chronic inflammation may be related to MCT development

A

True

Also likely genetics (p53, cyclin-dependent kinases like p21 & p27, estrogen & progesterone receptor expression, c-kit)

76
Q

Genes involved in MCT development (probably!)

A

GAIN OF FUNCTIOn MUTATION IN EXON 8, 11 of C-KIT !!!

  • p53
  • cyclin-dependent kinases like p21 & p27
  • estrogen & progesterone receptors
77
Q

T or F: MCTs REQUIRE a c-kit mutation

78
Q

Breed predilection for MCT (Dogs, cats)

A

CATS: SIAMESE

DOGS: Bulldog descendants
-Boston terrier
-Boxer
-English bulldog
-Pug

Labrador retriever
Golden retriever
Cocker spaniel
Schnauzer
Staffordshire bull terrier
Beagle
Rhodesian ridgeback
Weimaraner
Shar Pei

79
Q

T or F: MCT in bulldogs are less likely to be aggressive

80
Q

T or F: MCT in Shar Peis are less likely to be aggressive

A

FALSE. MORE AGGRESSSIVE. And happens at a younger age

81
Q

Which breed has more aggressive MCTs

82
Q

T or F: SC MCTs are less aggressive than dermal

83
Q

What is a Darier Sign in MCTs

A

Degranulation of the tumor from touching it –> surrounding wheal and flare

84
Q

What causes GI ulceration in MCTs

A

MCT histamine acts on H2 in parietal cells of GI –> increased acid secretion –> GI ulceration

85
Q

True or False: binding of histamine to H2 on GI may have negative feedback on gastrin

A

True

Gastrin normally decreases HCl, so MORE ulcers without it!

86
Q

Why do MCTs cause coagulation abnormalities

A

Heparin released from MC granules

Rarely systemic hemorrhage

87
Q

Why do MCTs cause delayed wound healing/dehiscence

A

Vasoactive amines and proteolytic enzymes –> suppress FGF –> less fibroplasia

88
Q

Why do MCTs cause hypotension

A

Vasodilation from histamine or prostaglandin D

89
Q

Stains, IHC for MCT

A

1) Giemsa
2) Toludine blue
3) Vimentin
4) Tryptase
5) KIT
6) Chymase
7) MCP-1
8) IL-8

90
Q

T or F: LN aspirate is not important in MCT staging if they are normal size

91
Q

T or F: AUS of the abdomen is sufficient for identifying liver/spleen metastasis

A

False. Need to FNA or biopsy to confirm metastasis

92
Q

What grading system is best for subcutaneous MCT: Patnaik or Kiupel?

A

Neither

Use those for dermal only

93
Q

Options for Patnaik grading

A

Grade 1, 2, 3

94
Q

Options for Kiupel grading

A

Low, High grade

95
Q

What percent of undifferentiated MCTs are metastatic

A

55-96%

Most dogs die within 1 year

96
Q

What body locations of MCTs are associated with worse prognosis

A

Subungual
Oral
Mucus membranes

Also scrotal, preputial

97
Q

T or F: Males have a shorter MST than females when treated with chemo for MCT

A

True. Men are weak, obvi

98
Q

T or F: c-kit mutations in MCT are associated with a worse prognosis

99
Q

Treatment for low, intermediate grade MCTs

A

Wide surgical excision

Marginal excision may be acceptable and may not recur

100
Q

Treatment for high grade MCTs, MM MCTs, or LN mets

A

Refer to onco (Sx + Chemo)

101
Q

MOA of prednisone for MCTs

A
  • Inhibit MC proliferation
  • Induce tumor cell apoptosis
  • Decrease edema, inflammation
102
Q

MOA of Tyrosine Kinase inhibitors for MCTs

A

Block tyrosine kinases on surface of MCs, which is crucial for growth/survival

Toceranib (Palladia), mastinib (Masivet), imatinib (Gleevec)

103
Q

MOA of Stelfonta

A

Signals for rapid destruction by hemorrhagic necrosis or tumor sloughing

Activates Protein Kinase C

Skin heals be second intention

SC MCT on distal limbs, dermal MCT anywhere on body

104
Q

Ancillary therapy for MCT when systemic signs are present

A

Antihistamines
Antacids
GI protectants (Sucralfate, misoprostol if GI ulcers)

105
Q

What is the most common form of MCT in cats overall

A

Mastocytic MCT

Single nodule

Head, neck near base of pinnae

+ Darier sign

106
Q

What is the most common type of MCT in young, Siamese cats

A

Histiocytic MCT

Multiple nodules

Majority of cells are histiocytes, only 20% are MCs

107
Q

T or F: the Kiupel and Patnaik grading systems are used for dermal MCT in cats

A

False. Does not predict biologic behavior in cats

Use mitotic index instead

108
Q

Which is more likely to be aggressive in cat MCTs: Compact or diffuse forms

A

Diffuse (anaplastic); but CAN still act benign

Compact form = more common

109
Q

T or F: the histiocytic form of MCT (siamese, young) may spontaneously regress than ma

110
Q

Other name for Urticaria Pigmentosa

A

Maculopapular Cutaneous Mastocytosis

111
Q

Clinical signs of urticaria pigmentosa

A

Erythematous papules, plaques

112
Q

Age of onset of urticaria pigmentosa in dogs and cats

A

Young animals (<1 yr old)

113
Q

Treatment for urticaria pigmentosa in dogs

A

Excellent prognosis
Oral GCs
H1 blockers
H2 blockers

Possible spontaneous regression

114
Q

Biologic behavior of urticaria pigmentosa in dogs, cats

A

Dogs: Excellent prognosis, lack of progression

Cats: Variable. Can spontaneously regress of be highly aggressive. Need long term tx usually

115
Q

Urticaria pigmentosa breeds (cats)

A

Devon rex
Sphynx

116
Q

3 clinical presentations of urticaria pigmentosa

A

1) nonpigmented papules, wheals with pruritus on head, neck, axillae
2) nonpigmented maculopapular dermatitis with crusts and pruritus
3) Highly pruritic, bilaterally symmetrical on flanks

117
Q

T or F: there are many eosinophils on histopath of urticaria pigmentosa in cats

118
Q

Easy clinical way to differentiate MCT from urticaria pigmentosa in cats

A

MCT is nonpruritic. Urticaria pigmentosa is usually pruritic

119
Q

Are most cases of NONepithelioptropic cutaneous lymphoma B or T cell

A

T cell!

Both for epitheliotropic and nonepitheliotropic

120
Q

What is a risk factor for cutaneous lymphoma

A

Chronic inflammation

121
Q

T or F: Dogs with cAD may be at increased risk fo CETL

122
Q

What infectious agent MAY be associated with cutaneous lymphoma in cats

A

FeLV. NOT seropositive actively, but may be from PREVIOUS infection (no longer seropositive)

123
Q

Is epitheliotropic or nonepitheliotropic lymphoma more often associated with disseminated disease

A

Nonepithelotropic

Full staging is highly recommended

124
Q

What subtype of cutaneous lymphoma is associated with a more aggressive behavior in cats

A

Nonepitheliotropic lymphoma of the TARSUS

125
Q

What type of T cell is most common in epitheliotropic T cell lymphoma in dogs

A

CD8 (85%)
Gamma/delta (62%)

126
Q

Which cytokines are higher in CETL skin?

A

Th1 cytokines:
IL-12, IFNg

127
Q

What T cell markers are higher in CETL skin

A

Perforin
Granzyme B

Associated with CD8 T cells

128
Q

What defines CETL as “Mycosis fungoides” form

A

Lesions in the epidermis AND DERMIS (unlike PR)

129
Q

What defines CETL as “Pagetoid reticulosis” form

A

Lesions in the epidermis and adnexa ONLY. NOT IN THE DERMIS (like in MF)

130
Q

What defines CETL as “Sezary syndrome” form

A

Leukemia of neoplastic lymphocytes

131
Q

T or F: IL-31 is increased in nonpruritic forms of CETL

A

False. (No studies to see if it is elevated in pruritic CETL)

132
Q

CETL lesions on the ______ (body region) are associated with a LONGER survival time

A

Mucus membranes

MM longer MST than skin lesions

133
Q

Which type of lymphocytic neoplasm is more common in CATS (and less common in dogs)

A

Cutaneous NONepitheliotrophic Lymphoma

134
Q

Which cell type most commonly is found in Cutaneous NONepitheliotrophic Lymphoma

A

T cells, usually CD8+

135
Q

Histopathology of Cutaneous NONepitheliotrophic Lymphoma

A

Deep dermal and SC nodules of monomorphic lymphocytes

Bottom-heavy

“Grenz zone” seen. = area of unaffected superficial dermis

Adnexa are usually not affected

Oftentimes need PARR, IHC to differentiate from histiocytic diseases!

136
Q

Clinical lesions of Cutaneous NONepitheliotrophic Lymphoma

A

Deep dermal to SC nodules

Can mimic panniculitis

Typically rapidly progressive with metastasis to LNs

Possible paraneoplastic hypercalcemia

137
Q

Do B or T cell lymphomas have a longer MST in cats

A

T cell

(opposite in dogs)

138
Q

What clinical presentation of Cutaneous NONepitheliotrophic Lymphoma is associated with a worse prognosis

A

Panniculitis-type T cell non-epitheliotropic lymphoma in dogs

Very aggressive

139
Q

Which species is more likely to have cutaneous lymphocytosis

140
Q

Biologic behavior of cutaneous lymphocytosis

A

Acts like an indolent, slowly progressive cutaneous lymphoma

Can metastasis after years of stability

141
Q

What type of cell is most common in cutaneous lymphocytosis in dogs

A

Alpha/beta T cells

(half CD8, half CD4-CD8-)

142
Q

T or F: cutaneous lymphocytosis is commonly pruritic in dogs

A

FALSE. Usually nonpruritic in dogs (dif than CETL)

BUT IT IS PRURITIC IN CATS

143
Q

What type of cell is most common in cutaneous lymphocytosis in cats

A

CD18+, CD3+, CD5+ T cells

144
Q

Signalment of cutaneous lymphocytosis in cats

A

Older, FEMALE cats

No breed

145
Q

Cell types in Lymphomatoid granulomatosis

A

Large atypical lymphocytes (mixed B and T) and plasma cells and histiocytes

146
Q

Location of metastasis common in Lymphomatoid granulomatosis

147
Q

Prognosis Lymphomatoid granulomatosis

A

Poor. MST 2 months

148
Q

Unusual clinical manifestation of extranodal lymphoa with cutaneous manifestation in cats

A

Otitis media/interna

T cell origin. Poor prognosis

149
Q

Diagnosis: a localized lesion that LOOKS like cutaneous lymphoma on histopath BUT has polyclonal PARR

A

Lymphoid hyperplasia

EV ACVD Study (52 decks)

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