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Block 9 Week 3 > Barsky > Pulmonary Neoplasm > Flashcards

Barsky > Pulmonary Neoplasm Flashcards

1
Q

what is the most common cancer found in the lung?

A

METASTASIS to the lung

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2
Q

which cancers commonly metastasize to the lung?

A 
CARCINOMAS: 
breast
colorectal
endometrial 
AND
soft tissue & bone sarcoma
skin melanoma
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3
Q

if a cancer spreads via transcoelomic spread, cancer of WHAT can occur?

A

PLEURA

esp from breast & ovarian cancer

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4
Q

why is distinguishing primary lung cancer from metastasis important?

A

staging
prognosis
therapy

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5
Q

what is the staging difference btwn metastatic & primary lung cancer?

A

metastatic is stage 4

primary can be stages 1-3

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6
Q

what 5 tools can you use to distinguish primary from metastatic lung cancer?

A
  1. microscopy
  2. multiple vs solitary lesion
  3. precursor lesions
  4. organ specific immunocytochem
  5. molecular profiling
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7
Q

what cancer is the leading cause of cancer death for men?

A

lung

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8
Q

what cancer is the leading cause of cancer death for women?

A

lung

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9
Q

which cancer has the highest # of estimated NEW cases per year for men?

A

prostate

lung is 2nd

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10
Q

which cancer has the highest # of estimated NEW cases per year for women?

A

breast

lung is 2nd

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11
Q

what are the 7 possible causes of human cancer?

A
  1. environmental
  2. UV radiation
  3. ionizing radiation
  4. viruses
  5. lifestyle, diet, immune status
  6. hereditary/genetic
  7. unk
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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

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13
Q

what regulates chemical carcinogens in the body?

A

phase I & phase II enzymes

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14
Q

how does UV radiation & other ionizing radiation cause cancer?

A

similar to chemical > DNA adducts

but cause single & double stranded DNA breaks

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15
Q

what is the leading cause of lung cancer?

A

SMOKING

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16
Q

what is the 2nd leading cause of lung cancer?

A

RADON

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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

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18
Q

what are the 5 basic categories of oncogenes?

A
  1. growth factors
  2. growth factor receptors
  3. signal transducing proteins
  4. nuclear transcription factors
  5. cyclins & CDKs
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19
Q

what are antioncogenes?

A

cancer suppressor genes

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20
Q

how can antioncogenes cause cancer?

A

inactivation of antioncogenes (genes whose pdts suppress cell proliferation)

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21
Q

what are the 4 types of antioncogenes?

A
  1. growth inhib factors
  2. cell adhesion regulators
  3. signal transduction regulators
  4. nuclear transcription & cell cycle regulators
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22
Q

what does EGFR signaling promote?

A

proliferation & cell survival

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23
Q

how does the EGF receptor work?

A

dimerization

tyrosine kinase receptor w/ transphosphorylation

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24
Q

how can EGFR be involved in cancer?

A

overexpression can lead to increased signaling > cell survival & proliferation

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25
Q

which HER receptor does EGF interact w/?

A

HER1

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26
Q

what are the 6 possible consequences of HER dysregulation?

A
  1. inc angiogenesis
  2. inc proliferation
  3. inc invasion
  4. inc metastasis
  5. inc survival
  6. DEC apoptosis
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27
Q

what is “the guardian of the genome”?

A

TP53

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28
Q

what is one of the most commonly mutated genes seen in virtually ALL types of human cancers?

A

TP53

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29
Q

what is TP53 involved w/ in the cell?

A

antiproliferation

apoptosis

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30
Q

how does TP53 work?

A

senses DNA damage
arrests cell in G1
induces DNA repair

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31
Q

how does TP53 induce DNA repair?

A

inc CDK1 p21 > prevents phosphorylation of RB

induces GADD45 > DNA repair

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32
Q

what happens if TP53 can’t repair DNA?

A

apoptosis genes are induced (BAX)

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33
Q

what are the 4 anatomical divisions of lung cancer?

A

central
peripheral
mid-zonal
pancoast

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34
Q

where is central lung cancer located in the lung?

A

near the hilum

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35
Q

where is peripheral lung cancer located in the lung?

A

near the periphery, like near the pleura/chest wall but still in lung tissue

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36
Q

where is mid-zonal lung cancer located in the lung?

A

in the middle?

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37
Q

where is pancoast tumor located in the lung?

A

apices

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38
Q

what are the sx of CENTRAL lung cancer?

A

cough
chest pain
hemoptysis
sputum

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39
Q

what are the sx of MID-ZONAL lung cancer?

A

chest pain

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40
Q

what are the sx of PERIPHERAL lung cancer?

A

silent!

picked up INCIDENTALLY on chest x-ray or CT

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41
Q

what are the sx of PANCOAST lung cancer?

A

Horner’s syndrome (ptosis, enophthalmos, miosis, anhidrosis) d/t invasion of sympathetic ganglion & chain

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42
Q

how many types of primary lung cancer are there?

A

70+!

but most are minor

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43
Q

what are the 2 MAJOR types of lung cancer?

A

small cell carcinoma
AND
non-small cell carcinoma

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44
Q

what are the 3 types of NON-small cell carcinoma?

A

squamous cell carcinoma
large cell undifferentiated carcinoma
adenocarcinoma

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45
Q

what are the 2 types of adenocarcinoma?

A

invasive

non-invasive (bronchioloalveolar)

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46
Q

what is the food description of small cell carcinoma?

A

oat cell

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47
Q

which has smaller cells: small cell carcinoma or NON-small cell?

A

NON! haha!

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48
Q

what term is often used for central & mid-zonal primary lung cancers?

A

bronchogenic

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49
Q

what are the possible cancer types of bronchogenic cancer?

A

small cell or NON (squamous, adeno, or non-differentiated)

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50
Q

what is the peak age of bronchogenic cancer?

A

55-65 yo

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51
Q

what is the leading cause of cancer death in men & women?

A

bronchogenic cancer

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52
Q

what is the survival rate of bronchogenic cancer?

A

14% at 5 years

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53
Q

what % of pts have mets at dx of bronchogenic cancer?

A

50%

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54
Q

what is bronchogenic cancer strongly linked w/?

A

SMOKING

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55
Q

what is the treatment for small cell carcinoma?

A 
chemo w/ or w/o radiation
NO SURGERY (not amenable)
56
Q

what is the treatment for NON-small cell carcinoma?

A

surgery!

poor response to chemo

57
Q

what % of lung cancers are small cell?

A

14-18%

58
Q

what is the behavior of small cell carcinoma?

A

occurs in central bronchi

infiltrates widely & metastasizes early

59
Q

what % of small cell carcinomas metastasize?

A

70%

60
Q

what are small cell carcinomas derived from?

A

neuroendocrine stem cells (NSE, neurosecretory granules, neurofilaments)

61
Q

what can cause paraneoplastic syndromes w/ small cell carcinoma?

A

polypeptide hormones

62
Q

what are paraneoplastic syndromes? (not explicitly in slides but worth knowing i think)

A

non-local cancer effects d/t ILLEGITIMATE TRANSCRIPTION of humoral factors

63
Q

what are examples of paraneoplastic syndromes assoc w/ small cell carcinoma?

A 
CUSHING'S
SIADH
NEUROMUSCULAR SYNDROMES
Hypercalcemia
Pulmonary osteoarthropathy
64
Q

what is the sx assoc w/ pulmonary osteoarthropathy?

A

finger clubbing

65
Q

who gets squamous cell carcinomas in their lungs?

A

more common in men

66
Q

what is the behavior of squamous cell lung carcinoma?

A
  1. central airway w/ obstruction
  2. tends to cavitate
  3. spreads to lymph nodes in thorax early (but later outside of thorax)
67
Q

what paraneoplastic syndromes are assoc w/ squamous cell carcinoma?

A

hypercalcemia

pulmonary osteoarthropathy

68
Q

what is the mechanism for finger clubbing?

A

not known!

69
Q

what is the angle at the nail bed that is suggestive of clubbing?

A

180+ degrees

70
Q

what % of lung cancers are large cell carcinoma?

A

10-18%

71
Q

what do large cell carcinomas look like in terms of cell differentiation?

A

undifferentiated under light microscopy

special studies may reveal some signs of differentiation

72
Q

what is the behavior of large cell carcinoma?

A

poor prognosis

early metastasis

73
Q

what is the behavior of adenocarcinoma?

A

grow slowly

metastasize early

74
Q

what gene is assoc w/ adenocarcinoma?

A

K-RAS defect

in 30%

75
Q

what % of lung cancers are adenocarcinomas?

A

37-47%

76
Q

who gets adenocarcinomas?

A

nonsmoking women in their 40s

77
Q

what is the behavior of adenocarcinoma?

A 
grow slowly 
metastasize early
generally PERIPHERAL
assoc w/ scars
pneumonia-like
78
Q

what is the behavior of bronchioloalveolar lung cancer (BAC)?

A 
usu PERIPHERAL
multifocal
bilateral
diffuse
mimics pneumonia
assoc w/ pre-existing pulmonary scars
mucinous or non
79
Q

what is BAC a form of?

A

adenocarcinoma in situ

80
Q

what does adenocarcinoma imply?

A

invasion

81
Q

what 2 cancers do you find together frequently?

A

BAC areas adjacent to adenocarcinoma areas

82
Q

what does BAC look like on histo?

A

well differentiated

83
Q

what airways are affected by BAC?

A

terminal (bc it’s peripheral)

84
Q

what is lepidic spread?

A

spread that mimics the pattern of scales on a butterfly wing (like down & out growth)

85
Q

what are the 3 OTHER important lung cancers?

A 
carcinoid (neuroendocrine)
benign hamartomas (chondromas)
MESOTHELIOMAS
86
Q

what cells are assoc w/ carcinoid tumors?

A

Kulchitsky

87
Q

what type of differentiation is involved w/ carcinoid tumors?

A

neuroendocrine

88
Q

what is assoc w/ rare carcinoid syndrome & carcinoid tumor?

A

neurosecretory granules

89
Q

where do carcinoid tumors occur?

A

mostly in mainstem bronchi

90
Q

T/F: carcinoid tumors are easy to remove

A

yes, if they’re in mainstem bronchi

91
Q

what is the behavior of atypical or malignant carcinoid lesions?

A

metastasize to hilar lymph nodes or distant sites
more mitoses
more areas of necrosis

92
Q

what % of carcinoid tumors are atypical or malignant?

A

30%

93
Q

what do bronchial chondromas look like on imaging?

A

coin lesion

94
Q

what is the issue w/ spiral CT scans & bronchial chondromas?

A

spiral CTs detect lots of “false posi” cancers that turn out to be bronchial chondromas (so then they’re not false posi???)

95
Q

what are the 2 types of neoplastic pleural disease?

A
  1. secondary (metastatic)

2. primary (malignant mesothelioma)

96
Q

what is malignant mesothelioma assoc w/?

A

asbestos exposure (NOT SMOKING)

97
Q

how does malignant mesothelioma manifest?

A

direct pushing & invasion of thoracic structures
encased lung
plaques d/t asbestos

98
Q

T/F: mesothelioma usually metastasizes

A

FALSE

mets are rare

99
Q

what patterns are assoc w/ mesothelioma?

A

sarcomatoid
epithelial
biphasic (both)

100
Q

T/F: mesothelioma has a long latency period

A

TRUE

101
Q

what is the CAUSE of malignant mesothelioma?

A

asbestosis d/t asbestos exposure (asbestos bodies on micro)

102
Q

T/F: most lung cancers have precursor lesions

A

TRUE

103
Q

what precursor lesions appear in the CENTRAL BRONCHUS?

A

squamous cell dysplasia

carcinoma in situ

104
Q

what precursor lesions appear in the PERIPHERY?

A

adenomatous hyperplasia

atypical adenomatous hyperplasia

105
Q

what precursor lesions are assoc w/ mesothelioma?

A

pleural fibrous plaques

106
Q

what precursor lesions are assoc w/ carcinoid & small cell carcinoma?

A

kulchitsky cell hyperplasia

107
Q

what % of lung cancers are squamous cell carcinomas?

A

25-32%

108
Q

what can precede squamous cell carcinoma?

A

years of metaplasia-dysplasia-CIS (whatever that is)

109
Q

where does squamous cell carcinoma show up in the lung?

A

central airway (w/ obstruction)

110
Q

T/F: squamous cell carcinoma is always poorly differentiated

A

FALSE

well-diff to poorly-diff

111
Q

what are the precursor lesions for peripheral adenocarcinoma &/or BAC?

A

scar

AH & AAH

112
Q

what cell type gets transformed in BAC?

A

type II pneumocytes

113
Q

what are the 3 staging categories for cancer?

A

tumor (size)
nodes
metastases (# of sites)

114
Q

what are the specific staging notes for lung cancers?

A 
T = tumor size
N = mediastinal & hilar lymph node status
M = distal mets
115
Q

historically, how were ALL non-small carcinomas of the lung treated?

A

the same!

didn’t matter what caused it or what type of cancer it was

116
Q

what is the basis for therapeutic molecular classification of lung cancers?

A

EGFR tyrosine kinase signaling
&
ALK (anaplastic lymphoma kinase) & ROS gene rearrangement tyrosine kinase signaling

117
Q

what % of NON-small cell cancers in non-smokers have EGFR tyr kinase molecular alterations?

A

10%

118
Q

what % of NON-small cell cancers in non-smokers have ALK rearrangements?

A

5%

119
Q

what % of non-small cell cancers in non-smokers have ROS rearrangements?

A

3-5%

120
Q

can you distinguish the different types of molecular classifications of cancers pathologically?

A

NOPE (you can’t tell what fucking receptor it has or what gene mutation it has just by looking at it)

121
Q

how does trastuzumab work?

A

inhibits HER dimerization

122
Q

how does cetuximab work?

A

anti-EGFR ab

stops EGF from binding to receptor

123
Q

how do erlotinib, geftinib, & lapatinib work?

A

tyrosine kinase inhibitors

124
Q

how do TP-38, DAB 389 EGF, & scFv-14e1-ETA fusion toxin work?

A

ligand-toxin conjugates (inhibit tyrosine kinase and kill the cell after they get internalized)

125
Q

what exons are affected in EGFR activating mutations?

A

19 or 21

126
Q

what do the affected exons in EGFR activating mutations DO?

A

tyrosine kinase activity of EGFR

127
Q

what type of mutation causes the EGFR activation?

A

exon deletion

point mutation

128
Q

what do the EGFR activating mutations CAUSE?

A

self activation
OR
downstream signaling

129
Q

what happens to exon 19?

A

deleted

130
Q

what happens to exon 21?

A

L858R mutation > AA substitution at position 858 in EGFR from Leucine to Arginine

131
Q

how can you detect the exon changes?

A

PCR test then sequencing on paraffin embedded tumoral material

132
Q

how can you treat the exon deletion or mutation?

A

tyrosine kinase inhibitors:

Tarceva or Iressa

133
Q

what can EGFR activating mutation &/or deletion result in?

A

oncogene addiction

134
Q

what mutation happens on chromosome 2 that can cause cancer?

A

ALK-EML4 rearrangement (fusion protein)

135
Q

how can you tell there’s been an ALK rearrangement?

A

split ALK signal on fluoroscopy

136
Q

what is the principle of ROS gene arrangement?

A

same as ALK

137
Q

what drug can you use for tumors w/ an ALK or ROS gene rearrangement?

A

crizotinib

Block 9 Week 3 (8 decks)

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