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Flashcards in Thirty Two Deck (19):

Explain smoking as a risk factor for lung cancer.

Exposure to tobacco smoke is by far the most substantial
risk factor for development of lung cancer, and is at least
partially avoidable. Approximately 80%-90% of all patients
diagnosed with lung cancer are either current or former smokers.
The association between tobacco smoke and lung cancer was
postulated a century ago and clearly demonstrated by epidemiologic
studies in the 1950s (Fig. 32.3). In the United States,
the lifetime risk of lung cancer for a nonsmoker is <1% and
increases to 15%-30% with long-term tobacco use. The risk of
lung cancer increases with the amount and duration of tobacco
exposure, and conversely the risk declines with abstinence.
A decrease in risk can be demonstrated within 5 years of quitting
smoking, and by 15 years there is an 80%-90% reduction in
the risk of developing lung cancer, although that risk remains
higher than for a never-smoker. Cigarettes seem to confer a
higher risk of lung cancer than the use of pipes and cigars.
Passive or “second-hand” exposure to tobacco smoke also
increases the risk of lung cancer, but to a much lesser degree
than active smoking. Never-smoking women married to husbands
who smoke have up to a two-fold increase in the risk
of lung cancer compared to never-smoking women with nonsmoking


What is the second leading risk factor for lung cancer? What are various other risk factors? What is a protective factor?

Exposure to radon, a radioactive gas released by the decay
of naturally occurring 238uranium, is the second leading cause of lung cancer in the United States and accounts for up to 10%
of all lung cancer cases. Radon gas collects in poorly ventilated
portions of some homes and buildings. Air pollution
may account for 2% of lung cancer cases in the United States,
but is a more signifi cant factor worldwide, notably where
biomass fuels are used for residential heating and cooking.
Asbestos exposure alone modestly increases the risk of lung
cancer, but when combined with tobacco use the risk increases
dramatically by 50- to 60-fold (Fig. 32.4). Other risk factors
for lung cancer include COPD, interstitial lung disease, and
a family history of lung cancer. Finally, the risk of lung cancer
is inversely proportional to intake of fruits and vegetables,
although prospective trials involving such dietary supplementation
have not shown a clear benefi t.


WHat is the general pathogenesis of lung cancer? What are some common genetic and molecular abnormalities? What clinical implications does this pathogenesis have? What is a possible pathogenesis?

The pathogenesis of lung cancer involves a multistep process
that is not completely understood. In most cases, lung cancer
is initiated by adverse interactions between carcinogens
and the respiratory epithelium that lead to genetic alterations.
These alterations can be found in histologically normal tissue
from smoker’s lungs. New DNA sequencing technologies
have uncovered multiple and varied genetic abnormalities that
reveal the heterogeneous nature of lung cancer even within a
single cell type. Common genetic and molecular alterations
include p53 tumor suppressor gene mutations, K-ras protooncogene
mutations, and epidermal growth factor (EGF)
and EGF receptor abnormalities. Genetic evidence of human
papilloma virus (HPV) infection also suggests a role for
viruses in lung cancer pathogenesis. The genetic and molecular characteristics of a cancer affect its promotion, progression,
invasion, and metastasis. Although the heterogeneity of lung
cancer might frustrate hopes of a single effective treatment,
knowledge of the varied abnormalities allows for an individualized
approach to treatment and prognostication. In some
cases, certain genetic mutations suggest a likelihood of a dramatic
response to very specifi c chemotherapeutic agents.


Where are adenocarcinomas found? How might they appear/progress there? Why does bronchioalveolar CA require special attention? How common are they? Among who especially ?

Adenocarcinoma is the most common histologic type of
lung cancer accounting for up to 35% of all lung cancers, and
this proportion seems to be increasing as compared to other
cell types. It is more common in women and is the lung cancer
type found in nearly all nonsmokers.

Clinically, adenocarcinomas tend to occur in the lung periphery
(Fig. 32.6) either synchronously with more than one primary
tumor at the same time, or metachronously with multiple primary tumors developing at different times. Bronchioloalveolar
carcinoma is a subtype of adenocarcinoma requiring special
attention as it can mimic pneumonia radiographically as a focal
opacity or as more diffuse opacities. Histologically, bronchioloalveolar
carcinoma is a well-differentiated tumor that grows along
intact alveolar septa in a so-called lepidic pattern (Fig. 32.7).


How common is squamous cell CA? In who especially? Where is it found? What are some presenting symptoms? What might imaging reveal?

Clinically, squamous cell carcinoma often
involves the large central airways, and initial symptoms may
include cough and hemoptysis. Imaging may reveal obstructive
collapse of a portion of the lung or a cavitary lesion (Fig. 32.8).


How common are small cell CA? In who especially? How do the tumors present? What is it the most likely tumor to do?

Small cell carcinoma accounts for up to 25% of all lung
cancers, and of all histologic types it is the most strongly associated
with smoking. Grossly, small cell tumors are typically
grey or tan and fl eshy in texture. Histologic fi ndings vary, but
the cells are generally small with hyperchromatic nuclei and
are fragile, crushing easily upon biopsy (Fig. 32.9). Clinically,
these tumors usually present as central masses with marked
lymphadenopathy on chest imaging (Fig. 32.9). Small cell carcinoma is the most likely cell type to present with metastatic
disease and paraneoplastic syndromes.


What are 3 categories of clinical manifestations?

Symptoms and signs of lung cancer are divided into those
caused by local tumor growth and invasion, by metastatic
spread, or by paraneoplastic syndromes. The symptoms and signs associated with growth and invasion vary with tumor location (Table 32.2).


What kind of tumors cause cough and hemoptysis? Wheezing? Chest pain? Dyspnea? Hoarseness? Horner Syndrome?

Tumors arising in a central location, that is, in and around
large airways, are the most likely to cause cough and hemoptysis.
Large airway involvement may also produce wheezing.
Peripheral tumors that involve the pleura or chest wall may
cause chest pain, as can central tumors that obstruct airways
and subsequently collapse of a portion of the lung or the entire
lung. Shortness of breath and dyspnea on exertion may result
from large airway obstruction or from compromise of the pulmonary
circulation by central tumors. Associated pleural or
pericardial effusions can also cause dyspnea. Hoarseness can
occur due to disruption of the recurrent laryngeal nerve, most
commonly on the left. Horner syndrome is a clinical triad
of ptosis, miosis, and anhidrosis that results from damage to
sympathetic neurons transversing the lung apex, and is associated
with superior sulcus tumors also known as Pancoast
tumors (Fig. 32.10).


What can superior sulcus tumors cause? What can cause paradoxical motion on inspiration of the hemidiaphragam? What is superior vena cava syndrome? What causes it?

Superior sulcus tumors also can affect the brachial plexus,
causing pain and weakness in the more distal upper extremity
as well as shoulder pain. An elevated hemidiaphragm with
paradoxical motion on inspiration suggests disruption of
the ipsilateral phrenic nerve by a central tumor (Fig. 32.11).
Finally, central tumors can compromise superior vena caval
blood fl ow. Patients with superior vena cava syndrome
report a sensation of fullness in the head and dyspnea. Physical
exam may reveal edema of the head and neck with plethora
and prominent superfi cial veins over the chest.


How common are metastases at the time of diagnosis of lung cancer? Where do they go primarily?

Nearly half of patients with lung cancer have metastatic
disease at the time of initial diagnosis, and many more develop
metastatic disease at a later time. Metastatic involvement of
other organs can give rise to a wide range of symptoms and
signs. The organs most commonly showing metastases are
liver, adrenal glands, bones, and brain.


What symptoms do metastases cause in the liver? Adrenal? Bone? brain?

Liver involvement is
typically asymptomatic and discovered only upon imaging
of the liver. More extensive involvement of the liver causes
abdominal pain, jaundice, and elevated serum [transaminases].

Likewise, adrenal metastases are often asymptomatic
and found upon imaging of the upper abdomen during the
staging process. A small percentage of patients with adrenal
metastases may develop adrenal insuffi ciency that is manifest
as weakness, nausea, orthostatic hypotension, hyponatremia,and hyperkalemia.

In contrast, bony metastases are usually
symptomatic and associated with osteolytic lesions evident
on radiographs; pathologic fractures may occur.

seizures, vomiting, cranial nerve defi cits, and visual fi eld loss
in a patient with lung cancer should raise suspicion for brain
metastasis. More subtle fi ndings include personality changes,
mood disturbance, cognitive diffi culty, and memory loss.


What are paraneoplastic syndromes? How common are they in lung cancer? Which CA is associated with most PNP syndromes? Which CA is associated with hypercalcemia? What does hypercalcemia result in?

Finally, symptoms and signs of lung cancer may be a
result of paraneoplastic phenomena, that is, disorders mediated
by secretory products of tumor cells or by anti-tumor
antibodies that cross-react with other tissues (Table 32.3).
Paraneoplastic syndromes occur in up to 20% of patients with
lung cancer, with hypercalcemia leading to constipation, dehydration,
lethargy, and confusion being common. Unlike most
paraneoplastic syndromes that are associated with small cell
lung cancers, hypercalcemia is most common among patients
with squamous cell lung cancer.


What is SIADH? What does it result in? What is Cushing Syndrome? How is it caused? What does it lead to? What are some PNS with skeletal manifestations? How are they characterized? Describe a neurologic PNS. What are some others? How are they treated?

The syndrome of inappropriate antidiuretic hormone
hypersecretion (SIADH) is another common paraneoplastic
entity. SIADH results in hyponatremia which may lead
to confusion, seizures, and coma.

Cushing syndrome due
to tumor cell production of ACTH can lead to hypertension,
hypokalemia, and hyperglycemia.

Clubbing and hypertrophic
pulmonary osteoarthropathy are paraneoplastic syndromes with
skeletal manifestations (Fig. 32.12). Hypertrophic osteoarthropathy is characterized by painful proliferative periostitis most commonly involving the wrists, elbows, ankles, or knees.

Neurologic paraneoplastic syndromes include Lambert-
Eaton myasthenic syndrome (LEMS) characterized by limb
weakness, autonomic dysfunction, and cranial nerve defi cits.
This syndrome displays a characteristic improvement in muscularresponse to repetitive nerve stimulation during neurophysiologic testing.

A hypercoagulable state, thrombocytosis,
cachexia, and malaise are all common paraneoplastic syndromes.

Treatment of the underlying lung cancer is paramount
in the treatment of the paraneoplastic syndromes, as many ofthese will improve if not completely resolved with effective treatment of the malignancy.


What is required for a diagnosis of lung cancer? Describe various ways in which it can be obtained?

Symptoms consistent with lung cancer with or without results
of imaging procedures may suggest lung cancer, but histologic
or cytologic analysis is required to make the diagnosis.
The least invasive means to obtain a specimen for analysis is sputum collection. Although not particularly sensitive, sputum
cytology may be helpful with larger central tumors with endobronchial
involvement (Chap. 19). Cytologic analysis of needle
aspirates of the primary tumor, the involved lymph nodes, or distant
metastases is an increasingly common means of establishing
the diagnosis. Very occasionally, needle aspirates can be obtained
from superfi cial structures without the use of imaging or endoscopy.
More commonly, CT or ultrasound imaging, bronchoscopy,
or a combination of these such as endobronchial ultrasound, can
be used to guide the aspiration needle to the correct location.
Bronchoscopy can also be used to obtain brushings and lavage
for cytologic analysis (Chap. 18). In addition, bronchoscopy can
provide direct tissue biopsy for histologic analysis if there is large
airway endobronchial involvement. Finally, more invasive surgical procedures such as mediastinoscopy, thoracoscopy, or thoracotomy
are occasionally required to obtain tissue for diagnosis.


How is staging performed?

Accompanying such diagnosis is the process of clinical
staging that takes into account characteristics of the primary
tumor and of nodal or distant metastasis to allow for accurate
survival predictions and worthwhile treatment options.
The preferred staging at present uses the International
Association of Lung Cancer (IASLC) TNM System (7th ed.)
(Table 32.4). This staging process for a patient with known or
suspected lung cancer starts with a thorough but focused history
and physical exam, followed by a CT scan of the chest
that includes the liver and adrenal glands. In most cases, the
patient will undergo whole body PET scanning or integrated
PET-CT scanning as an evaluation for metastatic disease In general, imaging alone should not be used to determine stage.
The suspected site that would provide for the highest stage,
such as a distant metastasis if present, should be biopsied to
confi rm the suspected stage..


Describe the TNM system and how it works. What is added for small cell CA?

The T descriptor in the TNM system is based on characteristics
of the primary tumor, and ranges from T1 for small
peripheral tumors that do not involve vital structures to T4
for tumors that involve vital, unresectable structures. The T
descriptor also increases with size of the primary tumor; a
‘T0’ indicates that no primary tumor has been found. The
N descriptor increases from N1 to N3 as progressively more
distant hilar and mediastinal lymph nodes are involved; ‘N0’
indicates no lymph nodes are involved with the cancer. Finally,
the M descriptor indicates the absence or presence of distant
metastases; an ‘M0’ indicates that no distant metastasis have
been found, while M1 indicates the presence of distant metastasis
or a malignant pleural effusion.
Although TNM staging can be used for both small cell
and non-small cell lung cancers, clinicians frequently distinguish
among small cell lung cancer patients with limited versus
extensive disease. Patients with limited disease include
those with no evidence of disease outside of one hemithorax.
All others would have extensive disease.


When is surgical resection appropriate? How is it done? What is a must in order to avoid post operative morbidity? What is a wedge resection and when is it appropriate? What is radiation surgery and when is it appropriate? When is chemotherapy appropriate?

Treatment of lung cancer depends on the cell type and stage of
disease. For stage I, stage II, and selected stage III non-small
cell lung cancers (Fig. 32.13), surgical resection is favored as
this approach offers a chance of cure and better survival. Left
untreated, stage I non-small cell lung cancer has a median survival
of ~13 months, whereas >50% of treated patients are alive
at 5 years. Lobectomy is the treatment of choice with more
extensive pneumonectomy reserved for patients with disease in locations not amenable to lobectomy. More limited wedge
resections are an option for patients with poor lung function,
advanced age, or very small tumors. Preoperative pulmonary
function testing is essential to predict how much lung can be
removed without undue postoperative morbidity (Chap. 16).
Radiation therapy, including precisely targeted high dose radiation
called radiosurgery, is an option for patients with early
stage non-small cell lung cancer who are unable or unwilling to
undergo surgery. Patients with stage II and stage III disease who
undergo surgery should receive postoperative or adjuvant chemotherapy
if they can tolerate the chemotherapeutic agents.


What is not an option in pts. with stage 4 or some stage 3 cancers? What can be done in these pts. if they don't have distant metastases? What if they do? What specificallly is used?

Surgical resection is not an option for patients with more
advanced stage IV non-small cell lung cancer, or for many patients
with stage III non-small cell lung cancer. For patients without distant
metastasis, concurrent radiation therapy with chemotherapy
offers the best survival. For patients with metastatic disease,
chemotherapy offers a survival advantage over supportive care
alone. Chemotherapy for non-small cell lung cancer usually consists
of a platinum-based agent plus one other drug.


What treatment is used for limited small cell CA? Extensive? What regimen is used/

Small cell lung cancer is usually considered a disseminated
disease at presentation, and thus surgical resection with curative
intent is usually not an option. For patients with limited disease,
concurrent chemoradiation therapy offers the best overall
survival and a chance for long-term survival. For patients with
extensive disease, chemotherapy alone is used. Like chemotherapy
for non-small cell lung cancer, a platinum-based agent plus
a second drug is the usual regimen for small cell lung cancer.