Neoplasia Flashcards
1
Q
tumor also known as
A
neoplasm
new growth/swelling
2
Q
what did galen do? 167 AD
A
natural-pregnant uterus
unnatural-pus, bone callus
contrary to nature-neoplasms
3
Q
what are tumors?
A
attempt by body (under a stimulus) to make a new, useless organ
4
Q
what do tumor cells arise from?
A
a single cell
- usually due to mutation
- can also be due to chromosomal abnormalities
- wrong shape, wrong place, etc.
5
Q
tumors similarities to normal
A
- functional (parenchyma) and supporting (stroma) tissues
- cells look similar (usually) to those of organ in which tumor arose
- cells continue to perform some same functions
- cells continue to produce some same proteins
6
Q
tumors differences from normal
A
- don’t contribute to maintenance of homeostasis
- grow more rapidly (usually) than surrounding normal origin
- some benign and all malignant tumors never stop growing
7
Q
what types of cells are tumors?
A
overgrowths of cells bearing cumulative genetic injuries
8
Q
Nowell’s law
A
each mutation confers a growth advantage over the neighbors
9
Q
what are tumors a failure of?
A
division control
senescence (immortalization)
proper apoptosis (cell suicide)
(at least some of these have already gone bad in the seemingly-normal cells from which tumors arise)
10
Q
what is the great acquired genetic disease of humans?
A
cancer
11
Q
benign tumors characteristics
A
- cells resemble normal cells and tumor architecture resembles parent organ
- usually spherical (grossly) and compress surrounding tissues
- have a surrounding capsule
- grow slowly
- never metastasize
12
Q
malignant tumors characteristics
A
-cells differ from normal and tumor architecture disorganized
-tumor bears tendrils (crab claws) and grows into surrounding tissue
-grow more rapidly than benign
-will eventually metastasize (some exceptions)
malignant=cancer
13
Q
what gives a tumor its name?
A
cell of origin
14
Q
differentiation
A
degree of resemblance to normal cell counterpart
15
Q
examples of differentiation terms
A
well, moderate, poorly
basis for “grading” malignant tumors
16
Q
what are cancers of epithelium called?
A
carcinomas
17
Q
what are cancers of mesenchyme called?
A
sarcomas
18
Q
anaplasia
A
ugly cells, a marker for cancer or “pre-cancer”
19
Q
dysplasia
A
ugly cells in epithelium with no invasion
20
Q
other terms for dysplasia
A
carcinoma in-situ
intraepithelial neoplasia
pre-cancer
intraepithelial lesion
21
Q
where do squamous carcinomas arise?
A
where stratified squamous is normal or metaplastic
- skin, esophagus, mouth, anal canal, others
- cervix, bronchi
22
Q
what do pathologists see in squamous carcinomas?
A
- keratin
- pearls (little hairs)
- desmosomes (intracellular junctions)
- single-cell apoptosis (cells think they’re at the top of the epidermis)
23
Q
where do adenocarcinomas arise?
A
anywhere there are glands, even single-cell glands
24
Q
what are the most common cancers?
A
adenocarcinomas
25
what do pathologists see in adenocarcinomas?
-lumens (intercellular, intracellular)
-"glands within glands" or even "glands inside-out" glands ("papillary growth)
-mucin (intercellular or intracellular "lakes)
-other secretory products, depending on gland of origin
-cells sticking to one another
-signet-ring cells (distended with a product), alone or in clusters
microvilli
26
adenomas
many features of adenocarcinomas but appear benign
no invasion
often functional
27
can adenomas show dysplasia?
yes without invasion
| pre-malignant
28
appearance of benign tumors
typically spherical
29
appearance of malignant tumors
exophytic-"lump" with a cauliflower-like surface
endophytic-appears as an ulcer
infiltrating-diffuse spread through organ without change in shape
often will have areas of hemorrhage and necrosis
30
exophytic
"lump" with a cauliflower-like surface
31
endophytic
appears as an ulcer
32
infiltrating
diffuse spread through organ without change in shape
33
why do malignant tumors have areas of hemorrhage and necrosis?
tumor invades its own blood supply
34
malignant tumors-potential for metastasis
spread of malignant tumor cells to distant sites
35
four routes of metastasis
carcinomas-typically spread via lymphatics
sarcomas-typically spread via blood vessels
seeding of serosal surfaces from pleural or peritoneal fluids
mechanical transplantation (rare, typically iatrogenic)
36
where do certain cancers go?
certain cancers have unexplained predilection for certain metastatic sites
37
common sites of metastasis
lymph nodes, liver, bone, brain
38
grading and staging
used to determine prognosis and treatment
| both usually represented by roman numerals (I=good; III, IV, V=bad)
39
grading
done by pathologists
requires tissue
reflects degree of differentiation (similarity to normal organ)
40
staging
done by clinicians
reflects size and extent of tumor spread
elaborate systems for each tumor type
41
TNM staging
T for tumor
N for regional lymph nodes
M for metastases
42
what determines stage?
TNM combination
43
what suffix for tumors?
end in -oma
| non-neoplasms also: hematoma, granuloma, gossypiboma, etc.
44
what do you add to a tumor name if malignant?
add carcin if epithelial
add sarc if mesenchymal
if benign, add nothing (just oma no middle)
45
additional roots
describe cell of origin
46
what to add to name for glandular epithelium
add adeno-
47
squamous or transitional epithelium and benign
add papill-
48
non-glandular epithelium and malignant, what do you add to the tumor name?
cell of origin
| ex. basal cell carcinoma, squamous cell carcinoma, renal cell carcinoma, choriocarcinoma
49
additional roots to describe cell of origin non-epithelial examples
```
fibr-fibroblasts
chondr-cartilage
oste-osteoblasts
lip-fat
leiomy-smooth muscle
rhabdomy-striated muscle
hemangi-blood vessels
lymphangi-lymphatics
mesotheil-mesothelium
meningi-arachnoid granulation
lymph-lymphocytes
```
50
malignant tumor with "benign" names
```
lymphoma
leukemia
melanoma
hepatoma (now hepatocellular carcinoma)
pheochromocytoma (adrenal medulla)
mesothelioma
myeloma ("multiple", plasma cell)
astrocytoma
glioma
ependymoma
seminoma
```
51
tumors or unknown (or used to be) origin have eponyms
Hodgkin's disease
Ewing's sarcoma
Wilm's tumor
52
non-tumors
hamartoma-tissue in right location but in wrong proportions
| choristoma-tissue in right proportion but in wrong location
53
hamartoma
tissue in right location but in wrong proportions
54
choristoma
tissue in right proportion bu t in wrong location
55
what causes cancer?
```
multiple genetic injuries conferring growth advantages
clones within clones within clones
less subject to growth controls
learn how to do things they shouldn't
grow faster than die off
carcinogenesis
```
56
things cancer cells learn to do but shouldn't
invade basement membrane
| induce own blood supply
57
carcinogenesis
events leading up to malignant phenotype
58
karyotype changes
many cancers have hallmark chromosomal abnormalities
| "genetic fingerprint"
59
t (9;22)
chronic myelogenous leukemia
| Philadelphia chromosome
60
t(8, 14)
Burkitt's lymphoma
61
del 3p
renal cell carcinoma (VHL) and almost all lung cancers
62
del 13q
retinoblastoma (Rb)
63
del 11p
Wilms tumor (WT1)
64
monosomy 22
meningioma (NF-2)
65
chemical carcinogenesis-initiator
induces genetic damage but not phenotype (yet)
mutagen "genotoxic carcinogen"
avoid these as much as possible
66
chemical carcinogenesis-promotor
```
causes initiated cells to become tumors
only "work" after initiation
stimulate cell division, promote Nowell's law
"non-genotoxic carcinogen"
lots of common substances
```
67
which carcinogens are genotoxic?
initiators
| avoid these
68
complete carcinogen
acts as both initiator and promoter
69
chemical carcinogens-scoot
scrotal cancer "chimney sweep's cancer"
70
chemical carcinogens-chemotherapy
acute leukemias (promoters)
71
chemical carcinogens-polycyclic hydrocarbons (stuff in tobacco smoke)
lung, larynx, mouth, throat, esophagus, pancreas, bladder, kidney
72
chemical carcinogens-aflatoxin (moldy grain and peanuts)
hepatocellular carcinoma
| COMPLETE CARCINOGEN
73
chemical carcinogens-asbestos
lung cancer, mesothelioma
74
chemical carcinogens-estrogen
endometrial carcinoma, post-menopausal breast cancer (maybe, current thinking increases probability)
75
what if you are asked "does substance X cause cancer?"?
you have to do the research
| approach same way as "does a drug work?"
76
radiation carcinogenesis
induces breaks in DNA
| -direct or free radical formation
77
what types of radiation cause radiation carcinogenesis?
ultraviolet and ionizing
78
carcinogenesis-ultraviolet radiation
most skin cancers
79
carcinogenesis-ionizing radiation
remember leukemias
80
occupations more susceptible to radiation carcinogenesis
radiologists
| uranium miners
81
what patient population is at risk for radiation carcinogenesis?
patients receiving therapeutic radiation
82
viral carcinogenesis
important in a few human cancers
83
viral carcinogenesis-HPV (certain strains)
benign warts, cancer of cervix, vulva, penis
| -viral proteins inactivate tumor-suppressor proteins
84
viral carcinogens-epstein-barr
Burkitt's lymphoma
85
viral carcinogenesis-hep b and c
promotors for hepatocellular carcinoma
86
are common human cancers caused by viral carcinogenesis contagious?
no
87
what can predispose to squamous cell carcinoma?
bad or repetitive skin trauma
| Marjolin's ulcer
88
proto-oncogenes (mitogenes)
- essential genes that govern normal tissue growth, differentiation and apoptosis
- hormone or vitamin receptors or their signal transduction pathways
- general cell "turn-ons"
- roughly 200 known
89
oncogenes
mutated ("activated") proto-oncogenes that help transform a benign cell into a cancer cell
90
oncogenes-mechanisms of activation
point mutation
translocation
amplification
receptor tyrosine kinases
91
oncogenes MOA point mutation
gene product is stuck on the "on" position ("gain of function")
92
oncogenes MOA translocation
```
gene product is under control of the wrong promoter
fusion gene (half-one gene, half-another) produces a fusion gene product that promotes cell division
```
93
oncogenes MOA amplification
too many copies of the gene
94
oncogenes-receptor tyrosine kinases
epidermal growth factor receptor family
- erbB-squamous cell cancers
- HER2-adenocarcinomas (especially breast)
- RET-endocrine tumors (remember MEN IIa and IIb), mucosal neuromas
95
what was the first inherited oncogene discovered?
RET-endocrine tumors (MEN IIa and IIb), mucosal neuromas
96
oncogenes-cytoplasmic tyrosine kinases
c-abl-translocated from 9 to 22 (Philadelphia chromosome) in CML and other leukemias
97
what is MEN?
multiple endocrine neoplasias
98
oncogenes-g proteins
ras family-involved in initiation of mitosis
characteristic point mutations at codons for AA
loss of GTPase activity-stuck in "on" position-keep dividing
mutations found in large proportion of human cancers (pancreatic, others)
99
ras family
involved in initiation of mitosis
100
oncogenes-DNA binding proteins
myc family-involved in DNA synthesis
amplification and/or translocation
c-myc translocated from 8 to 14 in Burkitt's lymphoma (next to an immunoglobulin gene)
amplified in oat cell lung carcinomas
101
myc family
involved in DNA synthesis
102
what are tumor suppressor genes also known as?
anti-oncogenes
103
what do tumor-suppressor genes do?
prevent cells from overgrowing, even with activated oncogenes
104
what must happen for tumor suppressor genes to lose effect?
both alleles must be altered
105
knudson's "two-hit" law
one hit: cell with an increased propensity to turn neoplastic
two hits: tumor cell
106
tumor-suppressor gene deletion syndrome
```
"tumor-susceptibility syndrome"
mutant allele is inherited
autosomal dominant
all somatic cells carry mutation
greatly increased risk for particular cancer
```
107
tumor-suppressor genes malignant phenotype
2nd allele mutated in cell of origin
autosomal recessive (now 2 bad copies)
OR
both mutations can also occur spontaneously
108
tumor-suppressor genes
| retioblastoma
RB1-13q14
- gene product central to regulating cell cycle
- binds to nuclear proteins
- DNA tumor viruses bind and inactivate gene product (HPV)
109
what is p53 (TP53)?
most common genetic injury in human cancer
110
what does p53 do?
gene product binds DNA and prevents mitosis during cell injury
111
what is p53 known as?
guardian of the genome
112
what can p53 induce?
apoptosis
113
what is p53 mutation linked to?
hepatocellular carcinoma
| aflatoxin induces p53 mutation
114
what do astrocytomas become with p53 mutation?
astrocytomas (low-grade) become glioblastomas (high-grade) with p53 mutation
115
what do benign tumors cause problems by?
-compressiong surrounding structures "malignant by location"
-over-secreting a substance (adenomas)-hormones
-existing in multiple places
transformation into malignant tumor
116
are benign tumors lethal?
rarely
117
benign tumor problems-malignant by location
- pituitary adenomas crushing the normal gland and optic nerves
- atrial myxoma blocking blood flow through the heart
- meningiomas compressing the brain
- pleomorphic adenoma of the parotid gland encasing the facial nerve
118
benign tumor problems-hormone production
pituitary and adrenal adenomas
| insulinomas and glucagonomas
119
benign tumor problems-multiple tumors
Von Recklinghausen's neurofibromatosis
| classical autosomal defect
120
benign tumor problems-large size
100-pound ovarian cystadenomas
121
benign tumor problems-torsion and infarction
ovarian tumors
122
malignant tumors-local effects (primary or metastasis)
- brain damage and herniation
- pulmonary edema
- bone fractures
- cytopenias
- hemorrhage
- bowel obstruction-
- pleural effusions and pericardial effusions
123
malignant tumors local effects brain damage and herniation
tumors growing inside the brain
124
malignant tumors local effects pulmonary edema
cancer blocking pulmonary lymphatics
125
malignant tumors local effects bone fractures
cancer metastasis to the bone
126
malignant tumors local effects cytopenias
bone marrow replacement by tumor
127
malignant tumors local effects hemorrhage
thrombocytopenia and/or vascular invasion
128
malignant tumors local effects bowel obstruction
large tumors
129
malignant tumors local effects pleural effusions and pericardial effeusions
both quite common
130
paraneoplastic syndromes
result from elaboration of substances by tumor
131
examples of paraneoplastic syndromes
- fever
- cushing's syndrome
- masculinization
- feminization
- hyponatremia
- hypokalemia
- hypercalcemia
- carcinoid syndrome
- erythrocytosis
- hyperviscosity syndrome
- autoimmune hemolytic anemia
- eaton-lambert syndrome
- venous thrombosis
132
paraneoplastic syndrome elaboration fever
mostly lymphomas, suspect in "fever of unknown origin"
133
paraneoplastic syndrome elaboration cushing's syndrome
excess cortisol, common adrenal cortical tumors and oat cell carcinoma of lung
134
paraneoplastic syndrome elaboration masculinization
common in certain ovarian and adrenal tumors
135
paraneoplastic syndrome elaboration feminization
breast development in a male, postmenopausal uterine bleeding; testicular or ovarian tumors
136
paraneoplastic syndrome elaboration hyponatremia
oat cell carcinoma, hypersecretion of ADH
137
paraneoplastic syndrome elaboration hypokalemia
villous adenoma of the colon, hypersecretion of potassium
138
paraneoplastic syndrome elaboration hypercalcemia
bone mets from any tumor or PTH-like substances produces by squamous cell carcinoma of lung
139
paraneoplastic syndrome elaboration carcinoid syndrome (paroxyms of flushing, wheezing and diarrhes)
production of serotonin and bradykinin by certain APUDomas
140
paraneoplastic syndrome elaboration erythrocytosis (excessive red cell mass)
excessive erythropoietin from renal cell carcinoma
141
paraneoplastic syndrome elaboration hyperviscosity syndrome
erythrocytosis or cancers that elaborate IgM, thick blood sludges in the brain
142
paraneoplastic syndrome elaboration autoimmune hemolytic anemia
lymphomas
143
paraneoplastic syndrome elaboration eaton-lambert syndrome (NMJ problem like myasthenia gravis)
oat cell lung cancer, autoantibody against calcium channels blocks release of acetylcholine
144
paraneoplastic syndrome elaboration venous thrombosis
pancreatic cancer ("Trosseau's other sign") and many others
145
cancer death examples
```
pneumonia
sepsis
hemorrhage
pulmonary embolism
paraneoplastic syndromes
iatrogenic
suicide and active euthanasia
```
146
cancer death-pneumonia
most common, multifactorial
- neutropenia (bone marrow replacement)
- airway obstruction
- atelectasis (alveolar collapse)-bedridden, pleural effusions
- aspiration
- narcotics
147
cancer death-sepsis (gram-negatives)
pneumonia, UTI
| remember stercoraceous ulcer from constipation
148
cause of sepsis-stercoraceous ulcer
frequently missed-stercoraceous ulcer-pain treated by narcotics, cause constipation, erodes rectal wall, rectal ulcer provides path to bloodstream, frequently avoidable cause of sepsis
149
cancer death-hemorrhage
thrombocytopenia
150
cancer death-iatrogenic
surgery, radiation, chemotherapy
151
cancer death-pulmonary embolism
DVTs lead to pulmonary embolus
152
tumor markers
substances produced by tumors, useful in diagnosis or detection of recurrence
153
tumor markers Ig light chains
plasma cell (multiple) myeloma
154
tumor markers carcinoembryonic antigen (CEA)
various adenocarcinomas; used to detect recurrence of colon cancer
IMPORTANT ONE
155
tumor markers alpha-fetoprotein (AFP)
hepatocellular carcinoma
156
tumor markers calcitonin
medullary thyroid carcinoma
157
tumor markers prostate-specific antigen (PSA)
prostate cancer, only marker used for screening
158
what is the only tumor marker used fo screening?
PSA
159
tumor markers CA-125
ovarian cancer
160
tumor markers-CA-19-9
stomach, colon, especially pancreatic cancer
161
what type of genetic disorders are genetic cancer syndromes?
autosomal dominant
162
genetic cancer syndromes-familial polyposis coli (familial adenomatous polyposis, FAP)
```
APC gene (tumor suppressor), 5q22
hundreds of colon polyps, premalignant
colonoscopy early and often
colon cancer before 40
prophylactic colectomy by age 25
```
163
genetic cancer syndromes-multiple endocrine neoplasia (MEN) syndromes MENI
MEN I
"PPP", "Wermer's syndrome"
-chromosome 11, gene MENI, protein menin, tumor suppressor
parathyroid
-hyperplasia/adenoma(s) (95%)
-pituitary adenoma (15-90%)
-pancreatic endocrine tumors (usually gastrinoma) (30-80%)
164
genetic cancer syndromes-multiple endocrine neoplasia (MEN) syndromes MEN IIa
MEN IIa
"PPM", "Sipple's syndrome"
-chromosome 10, gene RET, protein tyrosine kinase, proto-oncogene
-parathyroid adenoma(s) (50%)
-pheochromocytoma (33-50%)
-medullary thyroid cancer (100%)
these people get prophylactic thyroidectomy
165
genetic cancer syndromes-multiple endocrine neoplasia (MEN) syndromes MEN IIb
MEN IIb
"PMM", "Wagenmann-Froboese syndrome"
-chromosome 10, gene RET, protein tyrosine kinase, proto-oncogene
-pheochromocytoma (50%)
-medullary thyroid cancer (85%)
-mucosal neuromas (100%), also Marfanoid body habitus
these people get prophylactic thyroidectomy as well
166
genetic cancer syndromes-breast and ovary cancer
BRCA1
- 17q2
- tumor suppressor
- 60% get breast or ovarian cancer by age 50
- breast lifetime risk 60-70%, ovarian 40-50%
- common in male breast cancers
- prophylactic mastectomy/oophorectomy
