Barsky > Pulmonary Neoplasm Flashcards
what is the most common cancer found in the lung?
METASTASIS to the lung
which cancers commonly metastasize to the lung?
CARCINOMAS: breast colorectal endometrial AND soft tissue & bone sarcoma skin melanoma
if a cancer spreads via transcoelomic spread, cancer of WHAT can occur?
PLEURA
esp from breast & ovarian cancer
why is distinguishing primary lung cancer from metastasis important?
staging
prognosis
therapy
what is the staging difference btwn metastatic & primary lung cancer?
metastatic is stage 4
primary can be stages 1-3
what 5 tools can you use to distinguish primary from metastatic lung cancer?
- microscopy
- multiple vs solitary lesion
- precursor lesions
- organ specific immunocytochem
- molecular profiling
what cancer is the leading cause of cancer death for men?
lung
what cancer is the leading cause of cancer death for women?
lung
which cancer has the highest # of estimated NEW cases per year for men?
prostate
lung is 2nd
which cancer has the highest # of estimated NEW cases per year for women?
breast
lung is 2nd
what are the 7 possible causes of human cancer?
- environmental
- UV radiation
- ionizing radiation
- viruses
- lifestyle, diet, immune status
- hereditary/genetic
- unk
how do chemical carcinogens work?
form DNA adducts > mutations in hot spots > cancer
mutation in a non-coding zone can be harmless
what regulates chemical carcinogens in the body?
phase I & phase II enzymes
how does UV radiation & other ionizing radiation cause cancer?
similar to chemical > DNA adducts
but cause single & double stranded DNA breaks
what is the leading cause of lung cancer?
SMOKING
what is the 2nd leading cause of lung cancer?
RADON
where are radon levels measured in the environment?
in homes prior to sale
if levels are above threshold, you have to air ventilate the house to reduce
what are the 5 basic categories of oncogenes?
- growth factors
- growth factor receptors
- signal transducing proteins
- nuclear transcription factors
- cyclins & CDKs
what are antioncogenes?
cancer suppressor genes
how can antioncogenes cause cancer?
inactivation of antioncogenes (genes whose pdts suppress cell proliferation)
what are the 4 types of antioncogenes?
- growth inhib factors
- cell adhesion regulators
- signal transduction regulators
- nuclear transcription & cell cycle regulators
what does EGFR signaling promote?
proliferation & cell survival
how does the EGF receptor work?
dimerization
tyrosine kinase receptor w/ transphosphorylation
how can EGFR be involved in cancer?
overexpression can lead to increased signaling > cell survival & proliferation
which HER receptor does EGF interact w/?
HER1
what are the 6 possible consequences of HER dysregulation?
- inc angiogenesis
- inc proliferation
- inc invasion
- inc metastasis
- inc survival
- DEC apoptosis
what is “the guardian of the genome”?
TP53
what is one of the most commonly mutated genes seen in virtually ALL types of human cancers?
TP53
what is TP53 involved w/ in the cell?
antiproliferation
apoptosis
how does TP53 work?
senses DNA damage
arrests cell in G1
induces DNA repair
how does TP53 induce DNA repair?
inc CDK1 p21 > prevents phosphorylation of RB
induces GADD45 > DNA repair
what happens if TP53 can’t repair DNA?
apoptosis genes are induced (BAX)
what are the 4 anatomical divisions of lung cancer?
central
peripheral
mid-zonal
pancoast
where is central lung cancer located in the lung?
near the hilum
where is peripheral lung cancer located in the lung?
near the periphery, like near the pleura/chest wall but still in lung tissue
where is mid-zonal lung cancer located in the lung?
in the middle?
where is pancoast tumor located in the lung?
apices
what are the sx of CENTRAL lung cancer?
cough
chest pain
hemoptysis
sputum
what are the sx of MID-ZONAL lung cancer?
chest pain
what are the sx of PERIPHERAL lung cancer?
silent!
picked up INCIDENTALLY on chest x-ray or CT
what are the sx of PANCOAST lung cancer?
Horner’s syndrome (ptosis, enophthalmos, miosis, anhidrosis) d/t invasion of sympathetic ganglion & chain
how many types of primary lung cancer are there?
70+!
but most are minor
what are the 2 MAJOR types of lung cancer?
small cell carcinoma
AND
non-small cell carcinoma
what are the 3 types of NON-small cell carcinoma?
squamous cell carcinoma
large cell undifferentiated carcinoma
adenocarcinoma
what are the 2 types of adenocarcinoma?
invasive
non-invasive (bronchioloalveolar)
what is the food description of small cell carcinoma?
oat cell
which has smaller cells: small cell carcinoma or NON-small cell?
NON! haha!
what term is often used for central & mid-zonal primary lung cancers?
bronchogenic
what are the possible cancer types of bronchogenic cancer?
small cell or NON (squamous, adeno, or non-differentiated)
what is the peak age of bronchogenic cancer?
55-65 yo
what is the leading cause of cancer death in men & women?
bronchogenic cancer
what is the survival rate of bronchogenic cancer?
14% at 5 years
what % of pts have mets at dx of bronchogenic cancer?
50%
what is bronchogenic cancer strongly linked w/?
SMOKING
what is the treatment for small cell carcinoma?
chemo w/ or w/o radiation NO SURGERY (not amenable)
what is the treatment for NON-small cell carcinoma?
surgery!
poor response to chemo
what % of lung cancers are small cell?
14-18%
what is the behavior of small cell carcinoma?
occurs in central bronchi
infiltrates widely & metastasizes early
what % of small cell carcinomas metastasize?
70%
what are small cell carcinomas derived from?
neuroendocrine stem cells (NSE, neurosecretory granules, neurofilaments)
what can cause paraneoplastic syndromes w/ small cell carcinoma?
polypeptide hormones
what are paraneoplastic syndromes? (not explicitly in slides but worth knowing i think)
non-local cancer effects d/t ILLEGITIMATE TRANSCRIPTION of humoral factors
what are examples of paraneoplastic syndromes assoc w/ small cell carcinoma?
CUSHING'S SIADH NEUROMUSCULAR SYNDROMES Hypercalcemia Pulmonary osteoarthropathy
what is the sx assoc w/ pulmonary osteoarthropathy?
finger clubbing
who gets squamous cell carcinomas in their lungs?
more common in men
what is the behavior of squamous cell lung carcinoma?
- central airway w/ obstruction
- tends to cavitate
- spreads to lymph nodes in thorax early (but later outside of thorax)
what paraneoplastic syndromes are assoc w/ squamous cell carcinoma?
hypercalcemia
pulmonary osteoarthropathy
what is the mechanism for finger clubbing?
not known!
what is the angle at the nail bed that is suggestive of clubbing?
180+ degrees
what % of lung cancers are large cell carcinoma?
10-18%
what do large cell carcinomas look like in terms of cell differentiation?
undifferentiated under light microscopy
special studies may reveal some signs of differentiation
what is the behavior of large cell carcinoma?
poor prognosis
early metastasis
what is the behavior of adenocarcinoma?
grow slowly
metastasize early
what gene is assoc w/ adenocarcinoma?
K-RAS defect
in 30%
what % of lung cancers are adenocarcinomas?
37-47%
who gets adenocarcinomas?
nonsmoking women in their 40s
what is the behavior of adenocarcinoma?
grow slowly metastasize early generally PERIPHERAL assoc w/ scars pneumonia-like
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
what is BAC a form of?
adenocarcinoma in situ
what does adenocarcinoma imply?
invasion
what 2 cancers do you find together frequently?
BAC areas adjacent to adenocarcinoma areas
what does BAC look like on histo?
well differentiated
what airways are affected by BAC?
terminal (bc it’s peripheral)
what is lepidic spread?
spread that mimics the pattern of scales on a butterfly wing (like down & out growth)
what are the 3 OTHER important lung cancers?
carcinoid (neuroendocrine) benign hamartomas (chondromas) MESOTHELIOMAS
what cells are assoc w/ carcinoid tumors?
Kulchitsky
what type of differentiation is involved w/ carcinoid tumors?
neuroendocrine
what is assoc w/ rare carcinoid syndrome & carcinoid tumor?
neurosecretory granules
where do carcinoid tumors occur?
mostly in mainstem bronchi
T/F: carcinoid tumors are easy to remove
yes, if they’re in mainstem bronchi
what is the behavior of atypical or malignant carcinoid lesions?
metastasize to hilar lymph nodes or distant sites
more mitoses
more areas of necrosis
what % of carcinoid tumors are atypical or malignant?
30%
what do bronchial chondromas look like on imaging?
coin lesion
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???)
what are the 2 types of neoplastic pleural disease?
- secondary (metastatic)
2. primary (malignant mesothelioma)
what is malignant mesothelioma assoc w/?
asbestos exposure (NOT SMOKING)
how does malignant mesothelioma manifest?
direct pushing & invasion of thoracic structures
encased lung
plaques d/t asbestos
T/F: mesothelioma usually metastasizes
FALSE
mets are rare
what patterns are assoc w/ mesothelioma?
sarcomatoid
epithelial
biphasic (both)
T/F: mesothelioma has a long latency period
TRUE
what is the CAUSE of malignant mesothelioma?
asbestosis d/t asbestos exposure (asbestos bodies on micro)
T/F: most lung cancers have precursor lesions
TRUE
what precursor lesions appear in the CENTRAL BRONCHUS?
squamous cell dysplasia
carcinoma in situ
what precursor lesions appear in the PERIPHERY?
adenomatous hyperplasia
atypical adenomatous hyperplasia
what precursor lesions are assoc w/ mesothelioma?
pleural fibrous plaques
what precursor lesions are assoc w/ carcinoid & small cell carcinoma?
kulchitsky cell hyperplasia
what % of lung cancers are squamous cell carcinomas?
25-32%
what can precede squamous cell carcinoma?
years of metaplasia-dysplasia-CIS (whatever that is)
where does squamous cell carcinoma show up in the lung?
central airway (w/ obstruction)
T/F: squamous cell carcinoma is always poorly differentiated
FALSE
well-diff to poorly-diff
what are the precursor lesions for peripheral adenocarcinoma &/or BAC?
scar
AH & AAH
what cell type gets transformed in BAC?
type II pneumocytes
what are the 3 staging categories for cancer?
tumor (size)
nodes
metastases (# of sites)
what are the specific staging notes for lung cancers?
T = tumor size N = mediastinal & hilar lymph node status M = distal mets
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
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
what % of NON-small cell cancers in non-smokers have EGFR tyr kinase molecular alterations?
10%
what % of NON-small cell cancers in non-smokers have ALK rearrangements?
5%
what % of non-small cell cancers in non-smokers have ROS rearrangements?
3-5%
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)
how does trastuzumab work?
inhibits HER dimerization
how does cetuximab work?
anti-EGFR ab
stops EGF from binding to receptor
how do erlotinib, geftinib, & lapatinib work?
tyrosine kinase inhibitors
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)
what exons are affected in EGFR activating mutations?
19 or 21
what do the affected exons in EGFR activating mutations DO?
tyrosine kinase activity of EGFR
what type of mutation causes the EGFR activation?
exon deletion
point mutation
what do the EGFR activating mutations CAUSE?
self activation
OR
downstream signaling
what happens to exon 19?
deleted
what happens to exon 21?
L858R mutation > AA substitution at position 858 in EGFR from Leucine to Arginine
how can you detect the exon changes?
PCR test then sequencing on paraffin embedded tumoral material
how can you treat the exon deletion or mutation?
tyrosine kinase inhibitors:
Tarceva or Iressa
what can EGFR activating mutation &/or deletion result in?
oncogene addiction
what mutation happens on chromosome 2 that can cause cancer?
ALK-EML4 rearrangement (fusion protein)
how can you tell there’s been an ALK rearrangement?
split ALK signal on fluoroscopy
what is the principle of ROS gene arrangement?
same as ALK
what drug can you use for tumors w/ an ALK or ROS gene rearrangement?
crizotinib
