Tumors of the Lung Flashcards
How do cancers progress?
The development of a malignant tumor is a multi-step process characterized by the progressive evolution and selection of a clone of transformed cells with malignant potential
Why are adenocarcinomas on the rise?
possibly because filters on cigarettes are causing deeper inhalation`
Describe the RAS signaling pathway
RTK cross-phosphorylation activates:
RAS, RAF, MEK, ERK which then enter the nucleus to promote cell growth
Describe the P13K signaling pathway
RTK cross-phosphorylation activates:
P13K, AKT1, and then mTOR which then enter the nucleus to promote cell growth
T or F. Most tumors arise from a single mutated cell
F. Most tumors are very heterozygous in the sense that different cell lines in the tumor will have evolved from different mutations so one therapy won’t kill the whole tumor
What are oncogenes?
genes (viral or cellular) which encode proteins that subvert normal growth control mechanisms and are typically caused by mutation of photo-oncogenes or can arise from environmental stimuli
T or F. Oncogenes can be introduced to humans via viruses
T.
What is the risk of lung cancer in smokers?
10% but there is a linear elation to pack-years (male lung cancer is declining and women are increasing)
2nd hand smoke produces a 2x risk of lung cancer
What environmental stimuli promote lung cancer?
- uranium
- asbestos
Lung cancer in non-smokers is usually _______
adenocarcinomas
What size lung nodule is likely cancerous?
3+cm (less than 0.8cm is usually not)
What nodule location favors malignancy likelihood?
upper lung
What nodule appearance favors malignancy?
spiculated (calcification usually favors benign)
What is a hamartoma?
abnormal mixing of the normal components of the organ
What is a choristoma?
a collection of normal organ components in the wrong organ
Describe the CXR appearance of hamartomas in the lung
usually rounded ‘coin lesions’ on CXR located in the periphery, well-circumscribed, solitary that are most likely neoplasms and not congenital
What are hamartomas typically composed of?
mature CT (often cartilage)
What clonal chromosomal translocations are common in pulmonary hamartomas?
6p21 or 12q14-15
Describe small cell carcinomas
-usually present at an advanced stage and more likely to be metastasized (aka surgery excluded from treatment)
T or F. NSCLC are more resistant to traditional chemo than SCLC
T.
What are the types of NSCLC?
- Adenocarcinoma
- Squamous Cell carcinoma
- Large cell carcinoma
What is superior ven cava (SVC) syndrome?
lung cancer causing facial swelling, headache, and blurry vision
What is superior sulcus syndrome?
accompanies a pancoast tumor that directly invades surrounding tissue (e.g. can have shoulder pain all the way down to the ulnar surface of the hand)
What is Horner’s syndrome?
results from an interruption of the sympathetic nerve supply to the eye and is characterized by the classic triad of miosis (ie, constricted pupil), partial ptosis, and loss of hemifacial sweating (ie, anhidrosis). Can happen in lung cancer
What is the 1-yr survival rate of lung carcinomas?
41%
Causes of lung carcinomas?
- tobacco smoke
- radon
What lymph nodes do lung carcinomas go to before metastasizing?
- bronchopulmonary
- hilar
- bronchial mediastinal
and then to other organs
What does a lung adenocarcinoma (been increasing over the last two decades due to cig filters) loom like on a CT scan?
like a comet (speculated peripheral mass) common in non-smokers and female smokers
What makes something an ‘adeno’ cancer?
glandular differentiation and mucin production
What is common in lung adenocarcinoma patients?
pneumonia-like consolidation (of the entire lobe) due to ‘lepidic’ growth along alveolar septa
What stain can be used to identify mucin from an adenocarcinoma?
mucicarmine stain (stains in pink)
What is lepidic growth?
cells ALONG the alveoli are larger, hyper chromatic (darker), N:C ratio is higher, and mitotic figures are present
What patient population commonly gets squamous cell carcinomas?
males over female and mostly occurs in smokers
Where are squamous cell carcinomas typically located?
centrally
Squamous cell carcinomas have the tendency to show what?
central necrosis or cavitation (can hemorrhage due to this)
Other signs of squamous cell carcinomas?
-keratinization (aka ‘keratin pearls’) and/or intercellular bridges
What might squamous cell carcinomas produce?
PTH related peptide (causes paraneoplastic syndrome)
What is a large cell lung carcinoma?
its an undifferentiated non-small cell carcinoma, and has large cells with prominent nucleoli and vesicular chromatin (no glandular or squamous differentiation is evident)
Where are large cell lung carcinomas typically found?
peripherally (poor diagnosis)
What is a small cell lung carcinoma?
high-grade neuroendocrine carcinoma with a strong relationship to smoking and aggressive growth and frequent metastasis
T or F. Small cell lung carcinomas are more chemo-radiosensitive than non-small cell carcinomas
T.
Describe small cell lung carcinomas histologically?
small cells with scant cytoplasm and granular chromatin, nuclear molding, abundant mitoses, and crush artifacts
rapidly fatal
T or F. Small cell lung carcinomas have the highest association with paraneoplastic syndromes
T. Can also cause Lambert-Eaton syndrome
What can small cell lung carcinomas produce?
ADH or ACTH
What is a Azzopardi phenomenon?
DNA that has settled around a vessel and stains purple in small cell lung carcinoma
What immunohistostains can be used for small cell lung carcinomas?
chromogranin and synaptophysin
positive in neuroendocrine tumors
Describe carcinoid tumors
low-grade neuroendocrine carcinomas (1-5% of all lung tumors) that affect people in their 50s and have a good 5yr survival rate
Where are carcinoid tumors typically located?
centrally (aka endobronchial or collar-button) but can be in the periphery
How do carcinoid tumors typically present?
hemoptysis and dyspnea or can be discovered incidentally
How do carcinoid tumors look microscopically?
nests of bland cells with grandular (aka salt and pepper) chromatin
How does carcinoid syndrome present?
Clinically the syndrome consists of diarrhea, flushing and cyanosis.
What causes carcinoid syndrome?
It is typically serotonin or a serotonin like chemical that creates carcinoid syndrome. (Neuroendocrine cells contain serotonin as well as neuron-specific enolase, bombesin, calcitonin, or other peptides.)
These are typically, but not always, very advanced tumors because the liver will usually render these chemicals inactive.
Only about 10% of bronchial carcinoids give rise to this syndrome.
What is the TNM classification of lung cancer severity?
T-tumor size, visceral pleura or mainstream bronchus involvement
N- lymph node metastasis
M- distant metastases
Where do lung cancers like to metastasize?
adrenal, liver, brain, and bone
How long does EGFR TKI therapy response last?
only a few months before a sub clone pops up
What is the most common mutation in adenocarcinomas?
Kras (25%)
and the EGFR (10%)
What patient pop gets KRAS mutations most often?
smokers and older pts.
What patient pop gets EGFR mutations most often?
non-smokers, females, and Asians
What are the possible consequences of tumor obstruction of an airway?
pneumonia, abscess, lung collapse
What are the possible consequences of tumor impingement on the laryngeal nerve?
Hoarseness
What are the possible consequences of tumor invasion of sympathetic ganglion?
Horner Syndrome
What lung cancer can result in hypercalcemia?
Squamous cell carcinomas via PTH-related hormone induced paraneoplastic syndrome
What lung cancer can result in hyponatremia?
Small cell carcinoma via SIADH
What lung cancer can result in Cushing’s syndrome?
small cell carcinoma via ACTH
How do small cell carcinomas cause Lambert-Eaton Syndrome?
Antibodies to voltage-gated Ca2+ channels
Multiple well-circumscribed nodules suggests _____
metastasis
What are some common sites of origin that like to go to the lungs?
via blood or lymphatics
breast, colon, melanoma, and sarcomas
Describe the composition of the visceral pleura
there is an inner elastic layer that contains collagen, lymphatics, and blood vessels and then an outer elastic layer (that can be stained) and contains flat mesothelial cells
Most common tumors of the pleura?
metastatic far more common most commonly from the lung or breast
What is a common primary pleura tumor?
malignant mesothelioma (can arise from parietal or visceral pleura)
What causes most malignant mesotheliomas?
90% asbestos-related (lifetime risk 7-10% with heavy exposure). Ling (20+ yr) latency period
Does smoking increase the risk of malignant mesothelioma?
NO
What mutations are common in malignant mesothelioma?
deletions of 1p, 3p, 6q, 9p, or 22q
What virus is commonly associated with malignant mesothelioma?
simian virus 40 (SV40)
Prognosis of malignant mesothelioma?
50% die in less than 1 yr
What are the histologic types of malignant mesothelioma?
- epithelioid (resembles metastatic adenocarcinoma)
- sarcomatoid (resembles sarcoma)
- biphasic
What histochemical stain is used to ID mesothelioma?
hyaluronic acid
What immunohistochemical stain is used to ID mesothelioma?
catretinin
What immunohistochemical stain is used to ID metastatic adenocarcinoma?
Carcinoembryonic antigen (CEA)
What electron microscopy appearance suggests mesothelioma?
long slander microvilli
What electron microscopy appearance suggests adenocarcinoma?
stubby microvillous rootlets
