Exam 3 Flashcards
1
Q
Meningioma
A
- ‘benign’ tumor arising from meninges
- often can compress brain
2
Q
Sarcoma
A
- tumor arising from connective tissue
- malignancy of mesenchymal tissue (e.g. fat, bone, cartilage, muscle, endothelium)
3
Q
carcinoma
A
- tumor arising from epithelial cells
4
Q
types of acquired growth disorders
A
hyperplasia hypertrophy atrophy metaplasia dysplasia involution
5
Q
Hyperplasia
A
- increase in number of normal cells in a tissue/organ
- occurs in dividing cells
- can be physiologic (compensatory) or pathologic (adrenal gland hyperplasia in ferrets)
6
Q
Hypertrophy
A
- increase in size of cells in a tissue/organ
- occurs in dividing and non-dividing cells
- can be physiologic (gravid uterus) or pathologic
- causes: increased nutrient inflow, structural protein synth, calcium or water accumulation
7
Q
Atrophy
A
- Decrease in cell number or size (shrinking organ)
- Causes: disuse, loss of innervation, decreased blood supply, poor nutrition, loss of endocrine signals, pressure (space occupying lesion)
8
Q
Metaplasia
A
- change from 1 differentiated cell type/tissue to another
- benign, usually reversible, not pre malignant
- can occur secondary to tissue damage (e.g. smoker’s lung)
9
Q
Dysplasia
A
- abnormal growth or development
- can involve congenital or acquired abnormalities
- often occurs in metaplastic epithelium
- often considered a pre-neoplastic/malignant change but is reversible
10
Q
Histological features of dysplasia
A
- loss of cellular uniformity and architecture
- cells are variable in size, pleomorphic, increased cytoplasm
- increased mitotic activity
11
Q
Involution
A
decrease in tissue/organ size due to apoptosis of cells
e.g. uterus involutes after birth
12
Q
Developmental (congenital) growth disorders
A
hypoplasia aplasia agenesis atresia ectopia
13
Q
Hypoplasia
A
incomplete or under development of a tissue/organ
likely decreased in function too
14
Q
Aplasia
A
rudimentary development of a tissue/organ
will see remnant tissue of the organ
15
Q
Agenesis
A
complete absence of a tissue/organ - never developed
16
Q
Atresia
A
absence or abnormal narrowing of an opening or passage in the body
17
Q
Ectopia
A
- organ in an abnormal location
- can be congenital or acquired
- uncommon
18
Q
Neoplasia
A
- abnormal growth of tissue exceeding and uncoordinated with normal tissue
- persists after inciting stimulus is stopped (non-reversible)
- benign or malignant
- irreversible genetic changes
19
Q
neoplasm
A
abnormal mass resulting from neoplasia
can be benign or malignant
20
Q
Characteristics of benign neoplasms
A
- demarcated, encapsulated
- restricted to 1 tissue
- often slow growing
- well differentiated cells
- few mitotic figures
- easier to successfully completely surgically remove
- does not metastasize
21
Q
Characteristics of malignant neoplasms
A
- poorly demarcated, un-encapsulated
- infiltrative growth into other tissues
- often rapidly growing
- moderate to poorly differentiated cells
- numerous mitotic figures
- able to metastasize
22
Q
Benign neoplasia vs. hyperplasia
A
Hyperplasia
- well define stim with predictable effect
- purposeful course with limited progression
- diffuse
Benign neoplasia
- broad stim, variable effect
- meaningless course with unlimited progression
- single mass
23
Q
anaplastic tumor
A
- malignant, without indications of original tissue
- poorly differentiated cells
- often have loss of function
24
Q
Pathways of metastasis
A
Hematogenous
Lymphatic
Transcoelomic
25
Hematogenous pathway of metastasis
most common pathway for sarcomas
| targets: liver, lungs
26
Lymphatic pathway of metastasis
most common pathway for carcinomas
| target: regional lymph nodes
27
Transcoelomic pathway of metastasis
direct seeding throughout body cavities
| target: serosal surfaces
28
Use of cytology for neoplasms (fine needle aspirate)
Helps differentiate between neoplasm & inflammation
| Helps ID epithelial, mesenchymal, and round cell tumors
29
Epithelial neoplasm
basal cell tumor
very cellular sample
cohesive, homogenous groups of cells
30
Mesenchymal tumor
soft tissue sarcoma
less cellular sample
spindle-shaped cells arranged in sheets
31
round cell tumor
tumors involving leukocytes and melanocytes
histiocytoma common, other terms used
very cellular sample but no cohesive groups
no neutrophils or other signs of inflammation
32
Histopathology and neoplasms
most definitive diagnosis
33
4 classes of regulatory genes that when affected, cause neoplasia
- Proto-oncogenes (promote growth)
- Tumor suppressor genes (inhibit growth)
- Genes regulating apoptosis
- Genes involved in DNA repair
34
Tumor progression by mutations
- multiple mutations accumulate independently in different cells
- get subclonal populations with varying abilities to grow, invade, metastasize, and resist therapy
- morphologically same cell type, but a genetically heterogenous population
35
Types of mutations involved in neoplasia
- point mutations (substitute 1 base pair)
- translocations (hybrid chrom)
- amplification
- deletions
36
changes that determine transformation into malignancy
- self sufficiency in growth signals
- insensitive to growth-inhibitory signals
- evasion of apoptosis
- limitless replicative potential
- sustained angiogenesis
- ability to invade and metastasize
- defects in DNA repair
37
multicentric
- distribution term used to describe malignant neoplasms
| - same neoplasm growing at multiple sites at the same time
38
mesenchymal tumor naming
pattern: streams, bundles, whorls
B: ____oma
M: ___sarcoma
39
Types of mesenchymal tumors
- vascular endothelium
- odontogenic ligament
- meninges
- bone
- fat
- smooth m
- cutaneous/SQ soft tissue
40
tumors of vascular endothelium
- most common mesenchymal neoplasm
- Hemangioma/hemangiosarcoma
- cutaneous
- visceral (R atrium, liver, spleen, highly metastatic)
41
tumors of odontogenic ligament
B: peripheral odontogenic fibroma
M: none
Rare in cats, hard to excise
42
meninges tumors
B: meningioma
M: malignant meningioma (doesn't metastasize, but compresses)
43
bone tumors
B:osteoma
M: osteosarcoma
locally aggressive, highly metastatic in 3-6 mo to reg. LN & lungs
44
fat tumors
B: lipoma
M: liposarcoma
locally invasive, rarely metastasize (lungs, liver)
45
Smooth m. tumors
B: leiomyoma
M: leiomyosarcoma
uterus, skin, spleen, liver
46
Cutaneous/SQ soft tissue tumors
B: multiple names (fibroma, etc. rare)
M: soft tissue sarcoma
47
Types of epithelial neoplasms
```
mammary glands
thyroid glands
odontogenic epithelium
epidermis
urothelium
hepatocytes/bile duct epithelium
resp epithelium
pancreas
stomach/GI
adrenal, salivary glands etc.
```
48
Epithelial neoplasms
Pattern: lobules, acini, nests, trabeculae
B: ____(aden)oma
M: ___carcinoma
49
thyroid gland tumors
B: thyroid adenoma -cats
M: thyroid carcinoma - dogs, metastasize to lungs
50
odontogenic epithelium tumors
B: acanthomatous ameloblastoma
M: none
51
Epidermis tumors
B: papilloma
M: squamous cell carcinoma
52
Urothelium tumors
B: adenoma/papilloma
M: transitional cell carcinoma (freq, common with cystitis, metastasize to sublumbar LN >femur>skin
53
stomach/GI tumors
B: none
M: adenocarcinoma
54
Round cell neoplasm types
```
mast cell tumors
melanocytic tumors
histocytic tumorsytic tumors
lymphocytic tumors
plasma cell tumors
Transmissible venereal tumo (TVT)
CNS tumors
```
55
Mast cell tumors
B: cutaneous mc tumors in ferrets, cats
M: cutaneous mc tumors in dogs, visceral commonly malignant (GI, spleen)
See lots of eos on histo
56
teratoma
tumor with cells/tissue from different germ layers
| gonads, abdominal viscera
57
What's special about mixed mammary tumors
usually benign but poorly differentiated
58
anisocytosis
wide variation in cell size
59
megalocytosis
giant tumor cells
60
pleomorphism
variation in cell shape
61
Cell cycle parts
```
G1 - presynth
S-DNA synth
G2- premitotic
m - mitotic division
G0- quiescent
```
62
cell groups based on proliferative activity
- labile - continuously dividing cells (all the epitheliums)
- quiescent - stable cells that can enter cycle at low levels (organs, fibroblasts, osteocytes, etc)
- permanent - terminally differentiated, non dividing (neurons, skeletal, cardiac m)
63
p53 gene
- oncogene
- initiates cell cycle arrest
- gives cell time to repair DNA damage (senescence) or triggers apoptosis
64
Tissue size/cell population determined by...
- rate of proliferation (due to microenvironment signals)
- rate of differentiation (once differentiated, usually quiescent)
- rate of cell death
65
Mechanisms of cell death
- senescence
- apoptosis
- autophagy
66
What do pathways trigger to cause apoptosis
cytochrome C release from mitochondria
| also caspases to degrade DNA, organelles
67
How do tumor cells avoid apoptosis
inactivate p53 gene
activate survival signal pathways
inactivate death signaling pathways
68
Neoplastic transformation steps
pre-neoplastic change
dysplasia, metaplasia
anaplasia (now getting irreversible)
69
Transformation into carcinogenesis
- initiation - genetic irreversible change to just 1 cell
- promotion - increasing mutations, decreased response to stimuli (preneoplastic lesions)
- progression to benign tumors
70
Latency period
time before a tumor is clinically detectable (usually long time)
71
Why are tumors able to proliferate in an unlimited way?
- don't need growth signals
- insensitive to growth-inhibiting signals
- aka don't go into G0, continuously proliferating
- don't express functional p53
72
2 ways a tumor can develop
- dedifferentiate mature cells
- arise from resident stem cells (multipotenet/pluripotent neoplastic progenitor than totipotent)
- totipotent = teratoma
73
Components of tumor microenvironment
Stroma = fibroblasts, normal ECM, blood vessels, inflammatory & immune cells
74
Tumor secretes PDGF and TGFalpha. what happens
- stroma gets more fibroblasts to build collagen (PDGF)
| - fibroblasts turn into myofibroblasts (more primitive) TGFalpha
75
How do tumors initiate angiogenesis
VEGF
FGF
downregulate anti-angiogenic factors (thrombospondin)
release ECM-bound angiogenic and antiangiogenic factors
76
Paraneoplastic syndromes
indirect effects on body caused by tumor products, not tumor itself
(e.g. hypocalcemia in dogs with gastrolymphoma because lymphomas produce PTH)
77
Common PNP syndromes
- Cachexia
- endocrinopathies
- skeletal syndromes
- vascular and hematologic syndromes
- neuro syndromes
- other
78
common PNP endocrinopathies & their effects
- functional thyroid follicular adenoma (= hyperthyroidism in cats)
- functional pituitary tumor (=hypoadrenocorticism aka cushing's)
- pancreatic islet beta-cell tumors (= hyperinsulinemia --> hypoglycemia, neuro syndrome)
79
If a dog has adenocarcinoma, what are you likely to see?
increased PTH, PTHrP causing hypercalcemia
| rare in cats
80
If a dog has hemangiosarcoma, what are you likely to see?
anemia
| DIC
81
Neuro syndromes are usually related to what?
hypercalcemia
hypoglycemia
hyperviscosity
seizures, PNS dz
82
What do tumor grades indicate
degree of differentiation
(poor, moderate, well differentiated)
give some idea of predicted biological behavior
83
What does tumor stage indicate
extent of tumor growth and spread
-malignant tumors only
TNM system
84
TNM system
T - size of primary tumor
N - lymph node involvement
M - metastasis
85
Ways to treat neoplasia
surgery
radiation
chemo or immunotherapy
genetic manipulation
86
Passive vs. active immunotherapy
P - gives patient mature effector cells or AB's that recognize & destroy tumors
A - simulate host IR against tumor
87
Mutagen vs. carcinogen
Mutagen - damages DNA, creates mutations
| Carcinogen - causes cancer, sub-group of mutagen
88
3 broad classes of stromal cells in the tumor microenvironment
Cancer-associated fibroblasts (CAFs)
Angiogenic vascular cells (endothelial cells, pericytes)
Infiltrating immune cells (macrophages)
89
CAF activities
- induce angiogenesis
- promote cancer cell migration, invasion
- fibroblasts help maintain stem cell niches
- increase mitochondrial respiration by making environment use aerobic glycolysis
90
Immune promotion of tumor growth by macrophages
- make immunosuppressive cytokines (PD-L1, not IL-12)
| - enzymatically deplete essential nutrients for anti-tumor T cells (Arginine, tryptophane)
91
Non-immune promotion of tumor growth by macrophages
- make VEGF to simulate angiogenesis
- make mitogenic growth factors to sustain proliferative signaling
- make growth factors that trigger invasion
- evade growth suppression by enzymes
92
Key locations in the cancer immunity cycle
blood vessels
tumor
tumor-draining lymph node
93
key players in the cancer immunity cycle
tumor cells
APC’s
T cells
94
3 phases of cancer immunoediting
Elimination
Equilibrium
Escape
95
Elimination
mutated cells are eliminated by IS via innate and adaptive components
-NK cells, Macrophages, neutrophils, DC's, CD8 & CD4 T cells, B cells
96
Equilibrium
tumor cells incompletely eliminated by IS
| poorly/non-antigenic cells selected for and continue to divide
97
Escape
- tumor pop escapes IR, begins to grow unchecked
| - via immunoselection and silencing tumor-Ag expression
98
How do NK cells ID can cause tumor cell death?
- loss of MHC expression, or upregulation of stress-induced ligands
- Kill by perforin-granzyme mediated, FAs-ligand mediated killing, or AB-dependent cell-mediated cytotoxicity (ADCC)
99
Passive mechanisms by which tumor cells escape immune attack
Become less immunogenic (immunoselection, Ag-expression silencing)
Become invisible to IS (downregulate MHC I expression)
100
Active mechanisms by which tumor cells escape immune attack
Secrete suppressive molecules (TGF beta, IL-10)
Express immune cell co-inhibitory proteins (PD-L1 - decreases IR, keeps T cells from activating)
101
adenoma vs. oma
```
oma = non-glandular
adenoma = glandular
```
