Principles of Neoplasia Flashcards
(80 cards)
1
Q
• New, abnormal growth of tissue
– E.g. granulation tissue is new “normal” reparative growth
• Growth rate exceeds and is uncoordinated with the rest of the body
• Growth continues at the expense of the host
A
Neoplasm
2
Q
– the study of tumors
– the diagnosis and treatment of cancer
A
Oncology:
3
Q
: A hamartoma, not a true neoplasm
A
Hemangioma
4
Q
Do most cancer cells grow faster than normal cells?
A
No
5
Q
= the organ specific neoplastic cells – determines the neoplasm’s biologic behavior = the component from which the tumor derives its name
A
Parenchyma
6
Q
= the connective tissue and blood vessels – Crucial to the growth of the neoplasm, since it carries the blood supply and provides support for the growth of parenchymal cells.
A
Stroma
7
Q
• Abnormal cell growth that is uncontrolled, with the potential to invade or spread
to other parts of the body.
– Cause often lies in structural changes of DNA
A
Cancer
8
Q
- Generates own growth signals
- Ignores signals not to grow
- Evades apoptosis: normal cells die when their time is up
- Limitless replication potential
- Angiogenesis: allows the tumor to sustain itself
- Invasion/metastasis: ultimate goal of cancer cells
A
Cancer cell
9
Q
• The term means “to form backwards” •implies dedifferentiation, or loss of the structural and functional differentiation of normal cells • is the most extreme disturbance in cell growth
A
anaplasia
10
Q
• Disorderly, but non-neoplastic proliferation • Encountered primarily in epithelium • A loss in the uniformity of individual cells and in their architectural orientation • Typically implies a precancerous condition, however, all do not necessarily progress to cancer
A
dysplasia
11
Q
Which Type of cancer most commonly metastasize via lymphatic route to regional lymph nodes?
A
Carcinoma
12
Q
Which Type of cancer most commonly metastasize via hematogenous route to lungs?
A
Sarcoma
13
Q
Carcinomas metastasize via ____ route
A
Lymphatic
14
Q
Sarcomas metastasize via ____ route
A
Hematogenous
15
Q
Which type of cancer is mesenchymal?
A
Sarcoma
16
Q
Which type of cancer is epithelial?
A
Carcinoma
17
Q
____ is the development of tumor blood supply
A
Angiogenesis
18
Q
Mixed tumor (pleomorphic adenoma) of parotid gland implanted during surgery
A
Transplantation:
19
Q
Benign tumor of blood vessels
A
Heamngioma
20
Q
WHich germ layer forms skin, oral mucosa, and adnexa?
A
Ectoderm
21
Q
WHich germ layer forms muscle, fat, and bone?
A
Mesoderm
22
Q
WHich germ layer forms lining of respiratory tract, GI, GU tracts, and liver and pancreas?
A
Endoderm
23
Q
Carcinomas and adenomoas arise from what 2 germ layers?
A
Ecto and endoderm
24
Q
Sarcomas arise from what germ layer?
A
Mesoderm
25
Osteomas and osteosarcomas arise from what germ layer?
Mesoderm
26
____ is a neoplasm
Tumor
27
A malignant neoplasm
Cancer
28
= a benign neoplasm of glandular epithelial origin
Adenoma
29
= a malignant neoplasm of glandular epithelial origin
Adenocarcinoma
30
= a malignant neoplasm of mesodermal tissue origin (connective tissue) –
bone, cartilage, smooth muscle, skeletal muscle, nerve, adipose tissue
Sarcoma
31
Tumors of lymphocytes
Burkitt lymphoma
32
Primitive tumor of kidney
Wilm's tumor
33
Primitive tumor of bone
Ewing sarcoma
34
Do benign neoplasms transform into malignant?
Rarely
35
Are sarcomas more frequent in young or old?
Young
36
Are carcinomas more frequent in young or old?
Old
37
```
• Developmental, non-neoplastic
overgrowth of normal tissue at a site
where the tissues are normally
expected to be found
– Vs. Choristoma:
• Developmental non-
neoplastic overgrowth of
normal tissue at an abnormal
site abnormalities
```
Hamartoma
38
• A developmental, non-neoplastic overgrowth of normal tissue at a
site where the tissues are NOT normally expected to be found
• Heterotopic tissue
Christoma
39
```
• A tumor containing tissues from all three
germ layers
• Generally arise in gonadal tissues
• Ovary most common
• “Dermoid cyst” of the ovary
– Benign cystic teratoma
– May contain a variety of tissues
including hair, teeth, bone, cartilage,
thyroid, etc.
```
Teratoma
40
Using grading, is a well differentiated tumor grade 1 or 4?
1
41
Using grading, is a poorly differentiated tumor grade 1 or 4?
4
42
_____ is a measure of how localized or spread a malignant neoplasm is
-most important predictor of prognosis
Staging
43
Stage ____
| – Single lymph node region
Stage 1
44
Stage ______
– Multiple lymph node regions
– Same side of diaphragm
Stage 2
45
Stage ______
| – Disseminated disease
• Stage IV
46
Stage ______
– Multiple lymph node regions
– Both sides of diaphragm
• Stage III
47
A ____ grade tumor behaves aggressively
High grade
48
A ____ grade tumor behaves in an indolent manner
Low grade
49
What are the 2 groups of genes controlling growth?
Proto-oncogenes and TSG
50
At what point of the cell cycle do TSGs act?
G1 checkpoint
51
– normal function is to suppress cell proliferation
Tumor suppressor genes
52
– normal function is to promote cell proliferation
Proto-oncogenes
53
Is TSG dominant or recessive?
Recessive
54
Is proto oncogene, dominant or recessive?
Dominant
55
________ act as brakes on
cell proliferation
• Mutations must
create a loss-of-function if they are to have
an effect on cell proliferation
• Two copies of each gene, one paternal, one
maternal
• A loss-of-function mutation in one copy
leaves one functional copy
• A loss-of-function mutation in both copies
results in loss of all braking power, allowing
the cell to undergo unrestricted
proliferation
• act in a recessive
manner
Tumor suppressor genes
56
act as
accelerators for cell proliferation
• Mutations in must create
a gain-in-function if they are to have an
effect on cell proliferation
• There are two copies of each gene, one
paternal, one maternal
• A gain-in-function mutation in one copy is
all that is required to promote cell
proliferation
• A gain-in-function mutation in one copy
accelerates the cell cycle, allowing the cell
to undergo unrestricted proliferation
• act in a dominant manner
• Proto-oncogenes / oncogenes
57
The following are _______:
– P53
– Rb
TSG
58
```
The following are ______:
– RAS: MEN IIb
– cMYC: Burkitt lymphoma
– bcr/abl fusion gene (Philadelphia chromosome): Chronic Myelogenous
Leukemia (CML)
– Neurofibromin: Neurofibromatosis
```
Protoncogenes
59
```
• No role in the normal cell
cycle
• DNA damage causes a
rapid rise in protein
• cell cycle arrest in G1,
allowing time for DNA
repair by binding the
cyclin/CDK complex via
p21
• If the DNA damage
cannot be repaired, the
cell is instructed to
undergo apoptosis
```
p53
60
```
•___ gene codes for a
protein that acts as a
brake, creating a
checkpoint near the end
of G1
• G1 checkpoint is a pause
that assures DNA is
repaired and the cell is
prepared to enter the S
phase
• Mutations inactivate the
protein
loss of function and
loss of a brake
```
Rb
61
Are TSGs or proto-oncogenes 2 hits to cause oncogenic activity?
TSGs
62
```
• Germ-line mutation in p53 (first hit)
• A second hit eliminates all p53
activity
• 25x the risk of cancer at usual sites as
general population (lung, colon,
breast ...)
• Arise at earlier age and in multiple
organ systems
• Same cancers as the general
population
```
Li-Fraumeni Syndrome
63
```
• Malignant neoplasm of retina
• Familial form: multiple tumors in retinas
of both eyes occurring in first few weeks
of infancy
– Germline mutation of one Rb allele
(first hit) plus a somatic mutation of
the second allele (second hit)
• Sporadic form –single tumor in one eye
sometime in early childhood
– Both inherited alleles normal.
Somatic mutation in both alleles
(double hit)
```
Retinoblastoma
64
How many alleles must be mutated to turn a proto oncogene to an oncogene?
1 hit
65
```
• Normal function of ____
protein: receive a growth-
promoting signal from cell
surface receptors and forward
the it through the cytoplasm to
the nucleus
• After the signal is sent by the
active GTP form of it, it
normally flips back to the
inactive GDP form ending the
signal
• Mutations that abolish the
ability to flip back to the
inactive state result in a
continuous signal to proliferate
when no signal has been
received from the cell surface
```
RAS
66
• _____ gene and its protein play an active role in shepherding the cell
through G1
• Cells lacking it will not progress to S phase
• Overexpression of it promotes inappropriate cellular
proliferation
– Burkitt lymphoma
c-myc
67
• Novel (new) protein (bcr/abl) formed with tyrosine kinase activity
• False signal sent to nucleus instructing it to enter the cell cycle and proliferate
• Acts as an oncogene
• Created by a 9 to 22 translocation that places the abl gene (chromosome 9) next
to the bcr region (chromosome 22)
Chronic myelogenous leukemia (Philadelphia chromosome)
BCR/ABL gene
68
```
• Translocation t(9:22)
• Proto-oncogene abl on long arm
chromosome 9(q34)
• Transposed to bcr region (breakpoint
cluster region) on chromosome
22(q11)
Results in bcr-abl fusion gene
Gene product is abnormal bcr-abl
tyrosine kinase
• Induces cell proliferation
• Therapeutic intervention:
– Gleevec (Imatinib mesylate)
binds to the site of the tryosine
kinase activity (tyrosine kinase
```
Philadelphia Chromosome –Chronic Myelogenous Leukemia (CML)
69
```
• Translocations, t(8:14) is the
most common
• c-myc proto-oncogene on
chromosome 8 has a role in cell
cycle progression
• Immunoglobulin gene
promoters cause overexpression
of c-myc
• Overexpression of c-myc
oncogene promotes
inappropriate cellular
proliferation
```
Burkitt's lymphoma
70
```
Normal function of ____
protein: receive a growth-
promoting signal from cell
surface receptors and forward
the it through the cytoplasm to
the nucleus
```
RAS
71
```
_______ facilitates
conversion of RAS from active
to inactive state
• Loss of its function
RAS tagged in active, signal-
emitting state
```
Neurofibromin
72
```
______ proto-oncogene codes for
a tyrosine kinase receptor
– mis-sense mutation of the
receptor causes activation
of the receptor protein
causing the receptor
monomers to dimerize
• Mimicks the effect caused by
binding of ligand
• Activating (gain-in-function)
mutation that sends a
continuous signal to the
nucleus to transcribe cyclins in
the absence of growth factor
```
RET
73
Is cancer itself inherited?
No
74
Is an increased risk for cancer inherited?
Maybe
75
Autosomal recessive inherited mutations of
DNA repair genes
• Predisposition to UV-B associated
malignancies of the skin (Squamous cell
carcinoma, Basal cell carcinoma, Melanoma)
• Cancer not inherited, but susceptibility to
cancer is inherited
Xeroderma pigmentosum (XP)
76
• Chemicals: Polycyclic hydrocarbons
• Viruses
– Epstein-Barr Virus
– Human Papilloma Virus ***
– Must be transcriptionally active
• Carcinoma of uterine cervix: high risk strains inactivate p53, Rb TSGs
• Oropharyngeal squamous cell carcinoma
• Medical/dental diagnostic radiation: Thyroid shielding
• Nuclear radiation: Nuclear weapons, nuclear accidents
• Actinic (UV) radiation: Skin cancer
Carcinogens
77
– Symptoms/disease due to the presence of cancer in the body, but not due to
the local presence of cancer cells
Paraneoplastic syndrome
78
: Parathyroid hormone-related protein (PTHRP)
Hypercalcemia
79
: verrucous hyperkeratosis of skin
Acanthosis nigricans
80
– A pathologic state characterized by weight loss and anorexia that
accompanies some infections and neoplastic diseases
– weakness and wasting of the body due to severe chronic illness
– sustained production of tumor necrosis factor contributes to Cachexia
Cachexia:
