Barsky > Pulmonary Neoplasm Flashcards
(137 cards)
1
Q
what is the most common cancer found in the lung?
A
METASTASIS to the lung
2
Q
which cancers commonly metastasize to the lung?
A
CARCINOMAS: breast colorectal endometrial AND soft tissue & bone sarcoma skin melanoma
3
Q
if a cancer spreads via transcoelomic spread, cancer of WHAT can occur?
A
PLEURA
esp from breast & ovarian cancer
4
Q
why is distinguishing primary lung cancer from metastasis important?
A
staging
prognosis
therapy
5
Q
what is the staging difference btwn metastatic & primary lung cancer?
A
metastatic is stage 4
primary can be stages 1-3
6
Q
what 5 tools can you use to distinguish primary from metastatic lung cancer?
A
- microscopy
- multiple vs solitary lesion
- precursor lesions
- organ specific immunocytochem
- molecular profiling
7
Q
what cancer is the leading cause of cancer death for men?
A
lung
8
Q
what cancer is the leading cause of cancer death for women?
A
lung
9
Q
which cancer has the highest # of estimated NEW cases per year for men?
A
prostate
lung is 2nd
10
Q
which cancer has the highest # of estimated NEW cases per year for women?
A
breast
lung is 2nd
11
Q
what are the 7 possible causes of human cancer?
A
- environmental
- UV radiation
- ionizing radiation
- viruses
- lifestyle, diet, immune status
- hereditary/genetic
- unk
12
Q
how do chemical carcinogens work?
A
form DNA adducts > mutations in hot spots > cancer
mutation in a non-coding zone can be harmless
13
Q
what regulates chemical carcinogens in the body?
A
phase I & phase II enzymes
14
Q
how does UV radiation & other ionizing radiation cause cancer?
A
similar to chemical > DNA adducts
but cause single & double stranded DNA breaks
15
Q
what is the leading cause of lung cancer?
A
SMOKING
16
Q
what is the 2nd leading cause of lung cancer?
A
RADON
17
Q
where are radon levels measured in the environment?
A
in homes prior to sale
if levels are above threshold, you have to air ventilate the house to reduce
18
Q
what are the 5 basic categories of oncogenes?
A
- growth factors
- growth factor receptors
- signal transducing proteins
- nuclear transcription factors
- cyclins & CDKs
19
Q
what are antioncogenes?
A
cancer suppressor genes
20
Q
how can antioncogenes cause cancer?
A
inactivation of antioncogenes (genes whose pdts suppress cell proliferation)
21
Q
what are the 4 types of antioncogenes?
A
- growth inhib factors
- cell adhesion regulators
- signal transduction regulators
- nuclear transcription & cell cycle regulators
22
Q
what does EGFR signaling promote?
A
proliferation & cell survival
23
Q
how does the EGF receptor work?
A
dimerization
tyrosine kinase receptor w/ transphosphorylation
24
Q
how can EGFR be involved in cancer?
A
overexpression can lead to increased signaling > cell survival & proliferation
25
which HER receptor does EGF interact w/?
HER1
26
what are the 6 possible consequences of HER dysregulation?
1. inc angiogenesis
2. inc proliferation
3. inc invasion
4. inc metastasis
5. inc survival
6. DEC apoptosis
27
what is "the guardian of the genome"?
TP53
28
what is one of the most commonly mutated genes seen in virtually ALL types of human cancers?
TP53
29
what is TP53 involved w/ in the cell?
antiproliferation
| apoptosis
30
how does TP53 work?
senses DNA damage
arrests cell in G1
induces DNA repair
31
how does TP53 induce DNA repair?
inc CDK1 p21 > prevents phosphorylation of RB
| induces GADD45 > DNA repair
32
what happens if TP53 can't repair DNA?
apoptosis genes are induced (BAX)
33
what are the 4 anatomical divisions of lung cancer?
central
peripheral
mid-zonal
pancoast
34
where is central lung cancer located in the lung?
near the hilum
35
where is peripheral lung cancer located in the lung?
near the periphery, like near the pleura/chest wall but still in lung tissue
36
where is mid-zonal lung cancer located in the lung?
in the middle?
37
where is pancoast tumor located in the lung?
apices
38
what are the sx of CENTRAL lung cancer?
cough
chest pain
hemoptysis
sputum
39
what are the sx of MID-ZONAL lung cancer?
chest pain
40
what are the sx of PERIPHERAL lung cancer?
silent!
| picked up INCIDENTALLY on chest x-ray or CT
41
what are the sx of PANCOAST lung cancer?
Horner's syndrome (ptosis, enophthalmos, miosis, anhidrosis) d/t invasion of sympathetic ganglion & chain
42
how many types of primary lung cancer are there?
70+!
| but most are minor
43
what are the 2 MAJOR types of lung cancer?
small cell carcinoma
AND
non-small cell carcinoma
44
what are the 3 types of NON-small cell carcinoma?
squamous cell carcinoma
large cell undifferentiated carcinoma
adenocarcinoma
45
what are the 2 types of adenocarcinoma?
invasive
| non-invasive (bronchioloalveolar)
46
what is the food description of small cell carcinoma?
oat cell
47
which has smaller cells: small cell carcinoma or NON-small cell?
NON! haha!
48
what term is often used for central & mid-zonal primary lung cancers?
bronchogenic
49
what are the possible cancer types of bronchogenic cancer?
small cell or NON (squamous, adeno, or non-differentiated)
50
what is the peak age of bronchogenic cancer?
55-65 yo
51
what is the leading cause of cancer death in men & women?
bronchogenic cancer
52
what is the survival rate of bronchogenic cancer?
14% at 5 years
53
what % of pts have mets at dx of bronchogenic cancer?
50%
54
what is bronchogenic cancer strongly linked w/?
SMOKING
55
what is the treatment for small cell carcinoma?
```
chemo w/ or w/o radiation
NO SURGERY (not amenable)
```
56
what is the treatment for NON-small cell carcinoma?
surgery!
| poor response to chemo
57
what % of lung cancers are small cell?
14-18%
58
what is the behavior of small cell carcinoma?
occurs in central bronchi
| infiltrates widely & metastasizes early
59
what % of small cell carcinomas metastasize?
70%
60
what are small cell carcinomas derived from?
neuroendocrine stem cells (NSE, neurosecretory granules, neurofilaments)
61
what can cause paraneoplastic syndromes w/ small cell carcinoma?
polypeptide hormones
62
what are paraneoplastic syndromes? (not explicitly in slides but worth knowing i think)
non-local cancer effects d/t ILLEGITIMATE TRANSCRIPTION of humoral factors
63
what are examples of paraneoplastic syndromes assoc w/ small cell carcinoma?
```
CUSHING'S
SIADH
NEUROMUSCULAR SYNDROMES
Hypercalcemia
Pulmonary osteoarthropathy
```
64
what is the sx assoc w/ pulmonary osteoarthropathy?
finger clubbing
65
who gets squamous cell carcinomas in their lungs?
more common in men
66
what is the behavior of squamous cell lung carcinoma?
1. central airway w/ obstruction
2. tends to cavitate
3. spreads to lymph nodes in thorax early (but later outside of thorax)
67
what paraneoplastic syndromes are assoc w/ squamous cell carcinoma?
hypercalcemia
| pulmonary osteoarthropathy
68
what is the mechanism for finger clubbing?
not known!
69
what is the angle at the nail bed that is suggestive of clubbing?
180+ degrees
70
what % of lung cancers are large cell carcinoma?
10-18%
71
what do large cell carcinomas look like in terms of cell differentiation?
undifferentiated under light microscopy
special studies may reveal some signs of differentiation
72
what is the behavior of large cell carcinoma?
poor prognosis
| early metastasis
73
what is the behavior of adenocarcinoma?
grow slowly
| metastasize early
74
what gene is assoc w/ adenocarcinoma?
K-RAS defect
| in 30%
75
what % of lung cancers are adenocarcinomas?
37-47%
76
who gets adenocarcinomas?
nonsmoking women in their 40s
77
what is the behavior of adenocarcinoma?
```
grow slowly
metastasize early
generally PERIPHERAL
assoc w/ scars
pneumonia-like
```
78
what is the behavior of bronchioloalveolar lung cancer (BAC)?
```
usu PERIPHERAL
multifocal
bilateral
diffuse
mimics pneumonia
assoc w/ pre-existing pulmonary scars
mucinous or non
```
79
what is BAC a form of?
adenocarcinoma in situ
80
what does adenocarcinoma imply?
invasion
81
what 2 cancers do you find together frequently?
BAC areas adjacent to adenocarcinoma areas
82
what does BAC look like on histo?
well differentiated
83
what airways are affected by BAC?
terminal (bc it's peripheral)
84
what is lepidic spread?
spread that mimics the pattern of scales on a butterfly wing (like down & out growth)
85
what are the 3 OTHER important lung cancers?
```
carcinoid (neuroendocrine)
benign hamartomas (chondromas)
MESOTHELIOMAS
```
86
what cells are assoc w/ carcinoid tumors?
Kulchitsky
87
what type of differentiation is involved w/ carcinoid tumors?
neuroendocrine
88
what is assoc w/ rare carcinoid syndrome & carcinoid tumor?
neurosecretory granules
89
where do carcinoid tumors occur?
mostly in mainstem bronchi
90
T/F: carcinoid tumors are easy to remove
yes, if they're in mainstem bronchi
91
what is the behavior of atypical or malignant carcinoid lesions?
metastasize to hilar lymph nodes or distant sites
more mitoses
more areas of necrosis
92
what % of carcinoid tumors are atypical or malignant?
30%
93
what do bronchial chondromas look like on imaging?
coin lesion
94
what is the issue w/ spiral CT scans & bronchial chondromas?
spiral CTs detect lots of "false posi" cancers that turn out to be bronchial chondromas (so then they're not false posi???)
95
what are the 2 types of neoplastic pleural disease?
1. secondary (metastatic)
| 2. primary (malignant mesothelioma)
96
what is malignant mesothelioma assoc w/?
asbestos exposure (NOT SMOKING)
97
how does malignant mesothelioma manifest?
direct pushing & invasion of thoracic structures
encased lung
plaques d/t asbestos
98
T/F: mesothelioma usually metastasizes
FALSE
| mets are rare
99
what patterns are assoc w/ mesothelioma?
sarcomatoid
epithelial
biphasic (both)
100
T/F: mesothelioma has a long latency period
TRUE
101
what is the CAUSE of malignant mesothelioma?
asbestosis d/t asbestos exposure (asbestos bodies on micro)
102
T/F: most lung cancers have precursor lesions
TRUE
103
what precursor lesions appear in the CENTRAL BRONCHUS?
squamous cell dysplasia
| carcinoma in situ
104
what precursor lesions appear in the PERIPHERY?
adenomatous hyperplasia
| atypical adenomatous hyperplasia
105
what precursor lesions are assoc w/ mesothelioma?
pleural fibrous plaques
106
what precursor lesions are assoc w/ carcinoid & small cell carcinoma?
kulchitsky cell hyperplasia
107
what % of lung cancers are squamous cell carcinomas?
25-32%
108
what can precede squamous cell carcinoma?
years of metaplasia-dysplasia-CIS (whatever that is)
109
where does squamous cell carcinoma show up in the lung?
central airway (w/ obstruction)
110
T/F: squamous cell carcinoma is always poorly differentiated
FALSE
| well-diff to poorly-diff
111
what are the precursor lesions for peripheral adenocarcinoma &/or BAC?
scar
| AH & AAH
112
what cell type gets transformed in BAC?
type II pneumocytes
113
what are the 3 staging categories for cancer?
tumor (size)
nodes
metastases (# of sites)
114
what are the specific staging notes for lung cancers?
```
T = tumor size
N = mediastinal & hilar lymph node status
M = distal mets
```
115
historically, how were ALL non-small carcinomas of the lung treated?
the same!
| didn't matter what caused it or what type of cancer it was
116
what is the basis for therapeutic molecular classification of lung cancers?
EGFR tyrosine kinase signaling
&
ALK (anaplastic lymphoma kinase) & ROS gene rearrangement tyrosine kinase signaling
117
what % of NON-small cell cancers in non-smokers have EGFR tyr kinase molecular alterations?
10%
118
what % of NON-small cell cancers in non-smokers have ALK rearrangements?
5%
119
what % of non-small cell cancers in non-smokers have ROS rearrangements?
3-5%
120
can you distinguish the different types of molecular classifications of cancers pathologically?
NOPE (you can't tell what fucking receptor it has or what gene mutation it has just by looking at it)
121
how does trastuzumab work?
inhibits HER dimerization
122
how does cetuximab work?
anti-EGFR ab
| stops EGF from binding to receptor
123
how do erlotinib, geftinib, & lapatinib work?
tyrosine kinase inhibitors
124
how do TP-38, DAB 389 EGF, & scFv-14e1-ETA fusion toxin work?
ligand-toxin conjugates (inhibit tyrosine kinase and kill the cell after they get internalized)
125
what exons are affected in EGFR activating mutations?
19 or 21
126
what do the affected exons in EGFR activating mutations DO?
tyrosine kinase activity of EGFR
127
what type of mutation causes the EGFR activation?
exon deletion
| point mutation
128
what do the EGFR activating mutations CAUSE?
self activation
OR
downstream signaling
129
what happens to exon 19?
deleted
130
what happens to exon 21?
L858R mutation > AA substitution at position 858 in EGFR from Leucine to Arginine
131
how can you detect the exon changes?
PCR test then sequencing on paraffin embedded tumoral material
132
how can you treat the exon deletion or mutation?
tyrosine kinase inhibitors:
| Tarceva or Iressa
133
what can EGFR activating mutation &/or deletion result in?
oncogene addiction
134
what mutation happens on chromosome 2 that can cause cancer?
ALK-EML4 rearrangement (fusion protein)
135
how can you tell there's been an ALK rearrangement?
split ALK signal on fluoroscopy
136
what is the principle of ROS gene arrangement?
same as ALK
137
what drug can you use for tumors w/ an ALK or ROS gene rearrangement?
crizotinib
