Trans 10- Neoplasia Flashcards
1
Q
Neoplasia=
A
“new growth”
2
Q
o Abnormal mass of tissue
o Uncontrolled, uncoordinated growth with that of the
normal tissue
o Persists in the same excessive manner after
cessation of stimuli
A
Premolecular era
3
Q
o Disorder of cell growth that is triggered by a series of
acquired mutations affecting a single cell and its
clonal progeny
A
Modern era
4
Q
neoplastic cells → survival and growth
advantage (excessive proliferation independent of
physiological growth)
A
Mutations
5
Q
tumor cells arise from a single cell that has
incurred genetic changes (result to cells with the same
genetic makeup)
A
Clonal
6
Q
o Parenchyma
o Where the classification of the tumor is usually based
on
o Cells that gained mutation and proliferated
o Determines the course of biological behavior
A
Neoplastic cells
7
Q
o Connective tissue: serves as framework of the tumor
o Blood vessels: to supply nutrition
o Chronic inflammatory cells
o Surround the neoplastic cells
o Essential for growth and spread of the tumor
A
Stroma
8
Q
§ Abundant collagenous stroma as stimulated by
parenchymal cells
§ Ex: Schirrous (stony hard) in breast cancer
A
Desmoplasia
9
Q
- Localized and will not spread to other sites
- Can be surgically removed
- Name of cell type from which it originated ends in –oma
A
Benign neoplasms
10
Q
In mesenchymal tumors, fibrous tissue
A
fibroma
11
Q
In mesenchymal tumors, cartilage
A
chondroma
12
Q
In epithelial tumors, derived from glands
A
adenoma
13
Q
In epithelial tumors, finger-like projections from epithelial surface
A
papilloma
14
Q
In epithelial tumors, form large cystic masses like in the ovary
A
cystadenoma
15
Q
Exceptions:
these are malignant
A
melanoma and lymphoma
16
Q
• “cancers” • Invade and destroy adjacent structures • Spread to distant sites through blood vessels and lymphatic vessels (metastasis) • Can cause instant death
A
malignant neoplasms
17
Q
o Epithelial cell origin (from any of the three germ
layers)
A
carcinoma
18
Q
tumor cells resemble
stratified squamous epithelium
A
squamous cell carcinoma
19
Q
neoplastic epithelial cells grow in
glandular pattern
A
adenocarcinoma
20
Q
o Sar = “fleshy”
o Arise in solid mesenchymal tissues
A
sarcoma
21
Q
o Arise from blood-forming cells (literally WBCs) or
lymphocytes and their precursors
A
Leukemias or lymphoma
22
Q
- Divergent differentiation of a single neoplastic clone
* With two lineages
A
mixed tumors
23
Q
Contain epithelial components scattered within a
myxoid stroma with cartilage or bone
A
Mixed tumor of the salivary gland
24
Q
from a single clone
producing both epithelial and myoepithelial cells
A
pleiomorphic adenoma
25
• Mature or immature cells or tissues belonging to more
than one germ cell layer
• From totipotent germ cells normally present in ovary,
testis or abnormal midline embryonic rests
• May contain variety of tissue types in an unorganized
arrangement
Teratoma
26
cystic tumor
lined by skin full of hair, sebaceous glands and tooth
structure
ovarian cystic teratoma
27
disorganized but benign masses of cells
| indigenous to the involved site
Hamartoma
28
disorganized cartilage and
| blood vessels
pulmonary hamartoma
29
heterotropic rest of cells
choristoma
eg nodule containing pancreatic tissue found in the
stomach, duodenum or small intestine mucosa
30
4 criteria to distinguish benign from malignant tumors:
o Differentiation and Anaplasia
o Rate of Growth
o Local Invasion
o Metastasis
31
extent to which tumor cells closely
| resemble original cells.
differentiation
32
malignant tumors exhibit
anaplasia (total disarray of tissue architecture)
33
- lack of differentiation
| - hallmark of poor differentiated malignancies
anaplasia
34
anaplasia is characterized by
```
§ Pleomorphism
§ Abnormal nuclear morphology
§ Abundant mitoses
§ Loss of polarity
§ Others: tumor giant cells, necrosis
```
35
replacement of a mature cell type with
another mature cell type
o normally reversible but may progress to neoplasia
metaplasia
36
Disordered growth
o premalignant condition (not yet a tumor, might be precedent to the pre-invasive cancer, carcinoma in situ, but may be reversible)
o loss of uniformity of individual cells and architectural orientation
o exhibits pleomorphic, hyperchromatic nuclei, and frequent mitoses, loss of polarity
dysplasia
37
are cohesive, expansile and form a connective tissue capsule making surgical enucleation
easy
benign tumors
38
are invasive, infiltrating and lacking of
| well-defined capsule and plane of cleavage
malignant tumors
39
spread of tumor to other sites that are physically discontinuous with the primary tumor
metastasis
40
Unequivocally marks a tumor as
malignant
41
Almost all malignant tumors have the ability to
metastasize (Exception: glioma, basal cell carcinoma of the skin)
42
lymphatics invasion is most common in
carcinomas
43
hematogenous spread is most common in
sarcomas
44
§ favored by carcinomas originating from the kidney
§ Venous or arterial (more frequently through
veins)
§ Lung and liver are common sites because they
receive the systemic & venous outflow
Hematogenous spread
45
Differentiation: well-differentiated; typical structure
Rate of growth: gradual
local invasion: no
metastasis: no
benign
46
Differentiation: anaplastic; atypical structure
Rate of growth: rapid, erratic
local invasion: yes
metastasis: yes
malignant
47
Incidence of cancer in males
prostate > lung > colon/rectum
48
Incidence of cancer in females
breast >lung > colon/rectum
49
deaths in males
lung > prostate > colon/rectum
50
deaths in females
lung > breast > colon/rectum
51
Environmental factors that cause cancer
```
o Infectious agents (ex. HPV)
o Smoking – single most important factor
o Alcohol consumption
o Diet
o Obesity – higher death rates
o Reproductive history
o Environmental carcinogens
```
52
Carcinomas predominate in the
elderly
§ accumulation of somatic mutations
§ decline in immune competence
53
primitive malignancies in children
Wilms tumor retinoblastoma
| acute leukemias rhabdomyosarcomas
54
§ Proliferation of cells to repair the damage
§ Increase in pool of tissue stem cells susceptible
to transformation
§ Activation of immune cells – reactive oxygen
species
§ ex. H. pylori – lymphoma
chronic inflammation
55
Gastric and colonic metaplasia
Barrett esophagus
56
Squamous metaplasia
bronchial and
| bladder mucosa
57
Colonic metaplasia
pernicious anemia
58
presenc e of hyperplasia
endometrial hyperplasia
59
benign neoplasms
villous adenoma
| -> 50% may progress to colonic adenocarcinoma
60
those with deficient T cell immunity
- oncogenic viruses
| - lymphomas, sarcomas, carcinomas
61
Genetic predisposition and interactions between
| environmental and inherited factors examples
BRCA1
| BRCA2
62
Four basic principles of the molecular basis of cancer
non-lethal genetic damage
regulatory genes are involved
carcinogenesis is a multi-step process
monoclonal tumors
63
Genetic damage/mutation may be acquired by
the action of environmental agents (chemicals,
radiation and viruses) or it may be inherited
non-lethal genetic damage
64
These normal regulatory genes are the principle
| targets of genetic damage.
Regulatory genes are involved
65
§ Cancer is a multi-step process at both the
phenotypic and genetic levels resulting from the
accumulation of multiple mutations
§ Cancer does not develop right away because
numerous processes are involved.
carcinogenesis is a multi-step process
66
§ Are monoclonal wherein they arise from one
clonal cell
§ A tumor is formed by the clonal expansion of a
single precursor cell that has incurred genetic
damage.
Monoclonal tumors
67
o Non-lethal genetic damage at the heart of
carcinogenesis
o May be caused by environmental agents or
spontaneously occur
Mutation
68
Four classes of genes that are targets of genetic damage
- Proto-oncogenes and oncogenes
- Tumor suppressor genes (anti-onco genes)
- Apoptosis genes
- DNA-Repair genes
69
§ Normal function is to PROmote cell PROliferation
§ Activation to oncogenes->excessive cell
proliferation
Ø Over-expression of proteins
Ø Gene amplification
Ø Constitutive activation
Ø Ex. eRB-2, ras, abl, mvc
Proto-oncogenes and oncogenes
70
Normal function is to INHIBITcell proliferation
§ Damage (“inactivation”) leads to inability to
suppress cell division
§ P-53- involved in tumor formation
§ Rb-13- associated with retinoblastoma
§ APC- adenomatous polypoid gene- polyp in GI
tract
Tumor suppressor genes (anti-onco genes)
71
involved in tumor formation
P-53
72
associated with retinoblastoma
Rb-13
73
adenomatous polypoid gene- polyp in GI
| tract
APC
74
§ Genes that regulate apoptosis
§ Bcl-2 (anti-apoptosis gene); overexpression leads
to tumorigenesis, involved in gastric lymphoma
§ Bax, bud (pro-apoptosis gene): inactivation leads
to tumorigenesis
Apoptosis genes
75
-anti-apoptosis gene
-overexpression leads
to tumorigenesis, involved in gastric lymphoma
Bcl-2
76
-pro-apoptosis gene
-inactivation leads
to tumorigenesis
Bax, bud
77
is a multi-step process: present on both
| the phenotypic and genotypic level.
Carcinogenesis
78
are needed to produce a
malignant cell (the more defects, the more
malignant/aggressive the cell)
Multiple genetic alterations
79
8 key changes associated with cancer:
1. Self-sufficiency in growth signals
2. Insensitivity to growth-inhibitor signals
3. Altered cell metabolism
4. Evasion of apoptosis
5. Limitless replicative potential
6. Sustained angiogenesis
7. Ability to invade and metastasize
8. Ability to evade host immune response
80
tumor cells undergo a metabolic
switch -> Synthesis of macromolecules and
organelles
Warburg effect
81
Increased glucose leads to increased lactose
| conversion
glycolytic pathway
82
o Inactivation of P-53
| o Activation of anti-apoptotic genes
evasion of P-53
83
Continuous expression of
| telomerase
Evasion of mitotic crisis
84
ability to continually produce stem cells
self-renewal
85
Biological hallmarks of malignant tumors
ability to invade and metastasize
86
Two steps in the ability to invade and metastasize
§ Invasion of basement membrane
| § Vascular dissemination, homing and colonization
87
Invasion of basement membrane
downregulation of E-cadherin
| activation of proteinases
88
loosening up of
| tumor cells
downregulation of E-cadherin
89
degradation
| of basement membrane
MMP’s, cathepsin D,
| urokinase, plasminogen activator)
90
3 Types of DNA repair systems
§ Mismatch repair
§ Nucleotide excision repair
§ Recombination repair
91
o Familiar cancer: cecum and proximal colon
o Defect in DNA mismatch repair system (“proofreader”)
o Hallmark: microsatellite system instability (also 15% of sporadic cancers)
Hereditary Non Polyposis Cancer Syndrome
92
mismatch repair genes
MSH2, MLH1
93
o Increases risk for skin cancer after UV exposure
(formation of pyrimidine dimers)
o Defect in nucleotide excision repair
Xerdoerma Pigmentosum
94
developmental defects and multiple tumors
Bloom syndrome
95
neural symptoms
ataxia telangiectasia
96
bone marrow aplasia
fanconi anemia
97
chromosomal changes:
| Translocation and inversion
Lymphomas, Leukemias, Sarcomas, Carcinomas
98
chromosomal changes:
| deletions
Rb gene: Retinoblastoma
99
Malignancy: Chronic Myeloid Leukemia
Translocation:
BCR / ABL
100
Malignancy: Burkitt Lymphoma
Translocation:
C-MYC / IGH
101
Malignancy: Mantle Cell Lymphoma
Translocation:
CCND1 / IGH
102
Malignancy: Follicular Lymphoma
Translocation:
IGH / BLC2
103
Malignancy: Ewing’s Sarcoma
Translocation:
EWSR1 / FLI1
104
Multiple copies of proto-oncogene à protein
| overexpression
gene amplification
105
N-MYC gene
neuroblastoma
106
HER2 gene
breast cancer
107
o Reversible heritable changes in gene expression without mutation or change in DNA sequence
o Silencing of the gene by methylation or histone
modification
Epigenetic Changes
108
carcinogenic agents
- chemical
- radiation
- viruses
