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
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)
3
Q
In which phase of the cell cycle are cells most resistant to radiation
A
S phase
4
Q
What are intrinsic causes of cancer development
A
Inherited gene, gene product abnormality
5
Q
What are extrinsic causes of cancer development
A
Environmental factors
(UV, virus, ROS, chronic inflammation, trauma, chemicals, implants, radiation, magnetic field, hormones)
6
Q
How does UV light cause cancer
A
Forms thymidine dimers
Nucleotide excision repair fails to fix them –> Cancer
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!
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
9
Q
Ligand for c-kit
A
c-kit binds stem cell factor (SCF) to increase signals for cell survival differentiation, proliferation
10
Q
Function of tumor suppressor proteins
A
Slow down cell division. Induce apoptosis
TSP = Brake of the car
11
Q
What is the most mutated protein in human cancer
A
p53– TSP
12
Q
Name 2 tumor suppressor proteins
A
p53
pRB (E7 on papillomavirus binds, inhibits pRb –> uncontrolled cell cycling and cancer)
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
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
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”
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
17
Q
Cyclosporine inhibits which cell that is crucial for cancer immunosurveillance
A
CD8 T cells
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)
19
Q
T or F: it is likely that higher doses of oclactinib and cyclosporine are more likely pro-neoplastic
A
True
20
Q
Metastatic pathway of Sarcomas
A
Sarcoma to Lungs via BLOOD
CXR
21
Q
Metastatic pathway of Carcinomas
A
Carcinoma to REGIONAL LN -> lungs, liver spleen via BLOOD AND LYMPHATICS
Regional FNA, CXR, AUS
22
Q
Metastatic pathway of Round cell tumors
A
Tumor -> Regional LN -> liver, spleen via LYMPHATICS
Regional FNA, AUS
23
Q
Neoplastic consequences of Feline papillomavirus
A
1) BISC
2) SCC
3) Feline sarcoid (BPV14)
4) Viral plaqu
24
Q
How do papillomaviruses cause malignant transformation
A
Destabilize TSP p53 by E6
Inhibit pRb by E7
25
Cancers associated with Feline Skin Fragility Syndrome
Adrenal carcinoma
Abdominal carcinomas
Multicentric lymphoma
26
Cancer associated with Bilateral Ischemic Necrosis of the HIndpaws
Multicentric follicular lymphoma
27
IHC marker for T cells
CD3
28
IHC markers for B cells
CD20, CD79a, PAX5
29
IHC marker for epithelial cells
Cytokeratin
30
IHC marker for Mesenchymal cells
Vimentin
31
IHC marker for melanocyes
Melan A
32
Origin of melanocytic tumors
Mesenchymal. But can look like epithelial or round cell on cytology
33
Stains for mast cell granules (2)
Toludine blue
Giemsa
34
Stain for melanoma (melanin vs hemosiderin)
Fontana Masson
35
IHC marker for plasma cell tumor
MUM1
36
IHC marker for Mast cell tumor
C-Kit
CD117
37
IHC marker for histiocytoma
CD18, CD204, E cadherin, IBA1
NEGATIVE for CD4, CD90
(reactive histiocytoma is negative for E cadherin; positive for CD4, CD90)
38
IHC marker for hemangiosarcoma
Factor VIII related antigen
Claudin 5
CD31 (endothelial origin)
39
IHC for melanoma
Melan-A
PNL2
TRP-1
TRP-2
+/- S100
40
IHC for smooth muscle
Smooth muscle actin
Desmin
41
IHC for skeletal muscle
Myogenin D
Sarcomeric actin
Desmin
42
IHC for neuroendocrine tumor
Chromogranin A
Synaptophysin
43
Definition of sentinel lymph node
First lymph node to which cancers would spread from a primary tumor
44
Chemotherapeutic effect of imiquimod
SCC
Activates TLR7, secrete cytokines (IFNa, IL6, TNF-alpha)
activate LCs to go to LN and activate adaptive immunotherapy
45
Chemotherapeutic effect of prednisone
Inhibits DNA synthesis
Induces apoptosis
Mechanism not know
46
Acute AEs of radiation
Mucositis, erythema, alopecia, desquamation, lymphedema, changes in pigmentation
Usually SELF RESOLVING, RAPID RECOVERY
47
Severe Late AEs of radiation
Fibrosis, necrosis
RARE
48
Radiation recall
Return of acute radiation side effects once an animal receives chemo later on
49
Are dogs or cats more likely to have MALIGNANT skin tumors
Cats
50
Most common skin tumor in dogs
1) MCT
2) Lipoma
3) Histiocytoma
51
Most common skin tumor in cats
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
52
Which species develops cutaneous plasmacytosis
Dogs only
53
Which cancer should you may particular attention to iCa and Renal Function
Plasma cell tumors --> Multiple myeloma
54
IHC for plasma cell tumors
MUM1/Interferon regulatory factor4
55
T or F: Cutaneous plasmacytosis has a high metastatic rate
TRUE
Staging is important. Multiple myeloma also has high metastatic rate
56
Where on the body are you most likely to find a plasmacytoma
Head (ears), limbs
57
Breeds predisposed to plasmacytoma
Airedale terrier
Boxer
Cocker Spaniel
GSD
WHWT
Yorkshire terrier
58
Treatment plasmacytoma dogs
Surgery is usually curative. Normal lifespan
Local recurrence 5%
59
In cats with plasmacytoma, what should you monitor for
Progression to systemic myeloma-related illness
May be benign though! Just monitor
60
Treatment plasmacytoma cats
Surgery and chemo (check local LNs)
Usually benign in dogs, but may progress to multiple myeloma in cats
61
Treatment for cutaneous plasmacytosis (only dogs get this! Like MM)
Chemotherapy: Melphalan!
62
What is M component
Multiple myeloma
Accumulation of immunoglobulin (IgG or IgA) or Ig components (like Bence Jones protein)
63
Clinical signs of cryoglobulinemia (multiple myeloma)
Extremities have:
Erythema
Purpura
Ulcerations
Punched out necrosis
64
Prognosis of multiple myeloma in dogs
Good survival with Melphalan chemo; but rarely have CR
65
Prognosis multiple myeloma in cats
Poor. Visceral involvement with limited BM infiltration
MST 4-13 months
66
T or F: Multiple Myeloma in cats is oftentimes viral associated
FALSE.
Can be familial though!
67
4 types of cutaneous mast cell neoplasms
1) Mast cell tumor
2) Urticaria pigmentosa
3) Diffuse cutaneous mastocytosis
4) Systemic mastocytosis with cutaneous involvement
68
T or F: Mast cell tumors in cats are USUALLY benign
True
69
T or F: MCT can spontaneously regress
True, it is reported
70
Name the mediators in Mast Cell granules
1) Heparin
2) Chondroitin sulfate
3) Biogenic amines (histamine)
4) TNFa
5) Proteases (chymase, tryptase)
6) Acid hydrolases
7) Cathepsin G
8) Carboxypeptidase
71
Which growth factor binds to KIT on mast cells --> MC activation, decrease apoptosis
Stem cell factor (SCF)
KIT is a tyrosine kinase receptor
72
Which receptor on MCTs is associated with increased risk of local recurrence, metastasis, and death
c-kit ongogene
(Intermediate and high grade MCTs!)
73
What class of chemotherapy may be effective in MCTs with c-kit mutations
Tyrosine kinase inhibitors
(Palladia, toceranib)
74
Most common body sites for MCTs in dogs
Trunk, perineal, limbs > head/neck
75
T or F: Chronic inflammation may be related to MCT development
True
Also likely genetics (p53, cyclin-dependent kinases like p21 & p27, estrogen & progesterone receptor expression, c-kit)
76
Genes involved in MCT development (probably!)
**GAIN OF FUNCTIOn MUTATION IN EXON 8, 11 of C-KIT !!!**
* p53
* cyclin-dependent kinases like p21 & p27
* estrogen & progesterone receptors
77
T or F: MCTs REQUIRE a c-kit mutation
False
78
Breed predilection for MCT (Dogs, cats)
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
T or F: MCT in bulldogs are less likely to be aggressive
True
80
T or F: MCT in Shar Peis are less likely to be aggressive
FALSE. MORE AGGRESSSIVE. And happens at a younger age
81
Which breed has more aggressive MCTs
Shar Pei
82
T or F: SC MCTs are less aggressive than dermal
True
83
What is a Darier Sign in MCTs
Degranulation of the tumor from touching it --> surrounding wheal and flare
84
What causes GI ulceration in MCTs
MCT histamine acts on H2 in parietal cells of GI --> increased acid secretion --> GI ulceration
85
True or False: binding of histamine to H2 on GI may have negative feedback on gastrin
True
Gastrin normally decreases HCl, so MORE ulcers without it!
86
Why do MCTs cause coagulation abnormalities
Heparin released from MC granules
Rarely systemic hemorrhage
87
Why do MCTs cause delayed wound healing/dehiscence
Vasoactive amines and proteolytic enzymes --> suppress FGF --> less fibroplasia
88
Why do MCTs cause hypotension
Vasodilation from histamine or prostaglandin D
89
Stains, IHC for MCT
1) Giemsa
2) Toludine blue
3) Vimentin
4) Tryptase
5) KIT
6) Chymase
7) MCP-1
8) IL-8
90
T or F: LN aspirate is not important in MCT staging if they are normal size
False
91
T or F: AUS of the abdomen is sufficient for identifying liver/spleen metastasis
False. Need to FNA or biopsy to confirm metastasis
92
What grading system is best for subcutaneous MCT: Patnaik or Kiupel?
Neither
Use those for dermal only
93
Options for Patnaik grading
Grade 1, 2, 3
94
Options for Kiupel grading
Low, High grade
95
What percent of undifferentiated MCTs are metastatic
55-96%
Most dogs die within 1 year
96
What body locations of MCTs are associated with worse prognosis
Subungual
Oral
Mucus membranes
Also scrotal, preputial
97
T or F: Males have a shorter MST than females when treated with chemo for MCT
True. Men are weak, obvi
98
T or F: c-kit mutations in MCT are associated with a worse prognosis
True
99
Treatment for low, intermediate grade MCTs
Wide surgical excision
Marginal excision may be acceptable and may not recur
100
Treatment for high grade MCTs, MM MCTs, or LN mets
Refer to onco (Sx + Chemo)
101
MOA of prednisone for MCTs
* Inhibit MC proliferation
* Induce tumor cell apoptosis
* Decrease edema, inflammation
102
MOA of Tyrosine Kinase inhibitors for MCTs
Block tyrosine kinases on surface of MCs, which is crucial for growth/survival
Toceranib (Palladia), mastinib (Masivet), imatinib (Gleevec)
103
MOA of Stelfonta
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
Ancillary therapy for MCT when systemic signs are present
Antihistamines
Antacids
GI protectants (Sucralfate, misoprostol if GI ulcers)
105
What is the most common form of MCT in cats overall
Mastocytic MCT
Single nodule
Head, neck near base of pinnae
+ Darier sign
106
What is the most common type of MCT in young, Siamese cats
Histiocytic MCT
Multiple nodules
Majority of cells are histiocytes, only 20% are MCs
107
T or F: the Kiupel and Patnaik grading systems are used for dermal MCT in cats
False. Does not predict biologic behavior in cats
Use mitotic index instead
108
Which is more likely to be aggressive in cat MCTs: Compact or diffuse forms
Diffuse (anaplastic); but CAN still act benign
Compact form = more common
109
T or F: the histiocytic form of MCT (siamese, young) may spontaneously regress than ma
True
110
Other name for Urticaria Pigmentosa
Maculopapular Cutaneous Mastocytosis
111
Clinical signs of urticaria pigmentosa
Erythematous papules, plaques
112
Age of onset of urticaria pigmentosa in dogs and cats
Young animals (<1 yr old)
113
Treatment for urticaria pigmentosa in dogs
Excellent prognosis
Oral GCs
H1 blockers
H2 blockers
Possible spontaneous regression
114
Biologic behavior of urticaria pigmentosa in dogs, cats
Dogs: Excellent prognosis, lack of progression
Cats: Variable. Can spontaneously regress of be highly aggressive. Need long term tx usually
115
Urticaria pigmentosa breeds (cats)
Devon rex
Sphynx
116
3 clinical presentations of urticaria pigmentosa
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
T or F: there are many eosinophils on histopath of urticaria pigmentosa in cats
True
118
Easy clinical way to differentiate MCT from urticaria pigmentosa in cats
MCT is nonpruritic. Urticaria pigmentosa is usually pruritic
119
Are most cases of NONepithelioptropic cutaneous lymphoma B or T cell
T cell!
Both for epitheliotropic and nonepitheliotropic
120
What is a risk factor for cutaneous lymphoma
Chronic inflammation
121
T or F: Dogs with cAD may be at increased risk fo CETL
True
122
What infectious agent MAY be associated with cutaneous lymphoma in cats
FeLV. NOT seropositive actively, but may be from PREVIOUS infection (no longer seropositive)
123
Is epitheliotropic or nonepitheliotropic lymphoma more often associated with disseminated disease
Nonepithelotropic
Full staging is highly recommended
124
What subtype of cutaneous lymphoma is associated with a more aggressive behavior in cats
Nonepitheliotropic lymphoma of the TARSUS
125
What type of T cell is most common in epitheliotropic T cell lymphoma in dogs
CD8 (85%)
Gamma/delta (62%)
126
Which cytokines are higher in CETL skin?
Th1 cytokines:
IL-12, IFNg
127
What T cell markers are higher in CETL skin
Perforin
Granzyme B
Associated with CD8 T cells
128
What defines CETL as "Mycosis fungoides" form
Lesions in the epidermis AND DERMIS (unlike PR)
129
What defines CETL as "Pagetoid reticulosis" form
Lesions in the epidermis and adnexa ONLY. NOT IN THE DERMIS (like in MF)
130
What defines CETL as "Sezary syndrome" form
Leukemia of neoplastic lymphocytes
131
T or F: IL-31 is increased in nonpruritic forms of CETL
False. (No studies to see if it is elevated in pruritic CETL)
132
CETL lesions on the ______ (body region) are associated with a LONGER survival time
Mucus membranes
MM longer MST than skin lesions
133
Which type of lymphocytic neoplasm is more common in CATS (and less common in dogs)
Cutaneous NONepitheliotrophic Lymphoma
134
Which cell type most commonly is found in Cutaneous NONepitheliotrophic Lymphoma
T cells, usually CD8+
135
Histopathology of Cutaneous NONepitheliotrophic Lymphoma
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
Clinical lesions of Cutaneous NONepitheliotrophic Lymphoma
Deep dermal to SC nodules
Can mimic panniculitis
Typically rapidly progressive with metastasis to LNs
Possible paraneoplastic hypercalcemia
137
Do B or T cell lymphomas have a longer MST in cats
T cell
(opposite in dogs)
138
What clinical presentation of Cutaneous NONepitheliotrophic Lymphoma is associated with a worse prognosis
Panniculitis-type T cell non-epitheliotropic lymphoma in dogs
Very aggressive
139
Which species is more likely to have cutaneous lymphocytosis
Cats
140
Biologic behavior of cutaneous lymphocytosis
Acts like an indolent, slowly progressive cutaneous lymphoma
Can metastasis after years of stability
141
What type of cell is most common in cutaneous lymphocytosis in dogs
Alpha/beta T cells
(half CD8, half CD4-CD8-)
142
T or F: cutaneous lymphocytosis is commonly pruritic in dogs
FALSE. Usually nonpruritic in dogs (dif than CETL)
BUT IT IS PRURITIC IN CATS
143
What type of cell is most common in cutaneous lymphocytosis in cats
CD18+, CD3+, CD5+ T cells
144
Signalment of cutaneous lymphocytosis in cats
Older, FEMALE cats
No breed
145
Cell types in Lymphomatoid granulomatosis
Large atypical lymphocytes (mixed B and T) and plasma cells and histiocytes
146
Location of metastasis common in Lymphomatoid granulomatosis
Lungs
147
Prognosis Lymphomatoid granulomatosis
Poor. MST 2 months
148
Unusual clinical manifestation of extranodal lymphoa with cutaneous manifestation in cats
Otitis media/interna
T cell origin. Poor prognosis
149
Diagnosis: a localized lesion that LOOKS like cutaneous lymphoma on histopath BUT has polyclonal PARR
Lymphoid hyperplasia
