This document provides information on lung cancer, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). It discusses risk factors like smoking, symptoms, diagnosis, staging, pathology, and treatment approaches. The main types of lung cancer - NSCLC subtypes like adenocarcinoma and squamous cell carcinoma, as well as SCLC - are described in terms of characteristics, histology, and prognosis. Diagnostic tests include imaging, biopsy procedures, and staging evaluations. Treatment depends on cancer type and extent of disease, and may involve surgery, radiation, chemotherapy, or a combination.

1. LUNG CANCER
(Bronchogenic Carcinoma)
INTRODUCTION
̵ The term lung cancer, or bronchogenic carcinoma, refers to malignancies that
originate in the airways or pulmonary parenchyma
̵ Approximately 95 % of all lung cancers are classified as either small cell lung cancer
(SCLC) or non-small cell lung cancer (NSCLC).
This distinction is essential for staging, treatment, and prognosis.
̵ Other cell types comprise approximately 5 % of malignancies arising in the lung.
Epidemiology
Bronchogenic carcinoma is the leading cause of death because of malignancy in men
and women. The overall 5-year survival rate for small cell cancer is 5% and non-small cell
cancer is 8%.
Risk Factors
1) Smoking
The >85% of cases are directly related to cigarette smoking;
Adenocarcinoma has the lowest association with smoking of all lung cancers.
All lung cancers are associated with smoking.
• Active smokers have 10× greater risk compared with nonsmokers
• There is a linear relationship between pack-years of smoking and risk of lung
cancer.
• The risk of developing lung cancer for a current smoker of one pack per day for 40
years is approximately 20 times that of someone who has never smoked
2) Other factors — may affect the risk of developing lung cancer:
▪ Radiation therapy (RT) in patients who have been treated for other malignancies.
▪ Environmental toxins:
 Second-Hand Smoke = Environmental Tobacco Smoke
It’s a mixture of 2 forms of smoke that come from burning tobacco:
* Mainstream smoke: The smoke exhaled by a smoker.

2. * Sidestream smoke: Smoke from the lighted end of a cigarette, pipe, or
cigar, or tobacco burning in a hookah. This type of smoke has higher
concentrations of carcinogens and is more toxic than mainstream smoke.
It also has smaller particles than mainstream smoke. These smaller particles
make their way into the lungs and the body’s cells more easily.
 Asbestos
- Common in shipbuilding and construction industry, car mechanics, painting
- Smoking and asbestos in combination synergistically increase the risk of
lung Cancer
 Radon: high levels found in basements
▪ Pulmonary fibrosis
▪ HIV infection
▪ Genetic factors
▪ Alcohol
Pathology
a) Small cell lung cancer (SCLC)—25% of lung cancers
b) Non–small cell lung cancer (NSCLC)—75% of lung cancers; includes
squamous cell carcinoma, adenocarcinoma (including bronchoalveolar type), large
cell carcinoma

3. The most common lung cancers are adenocarcinoma (~40% in some studies) and
squamous cell carcinoma.
1) Adenocarcinoma
̵ Adenocarcinoma is a peripherally located lesion.
̵ This lesion metastasizes widely to essentially the same sites as small-cell carcinoma.
̵ Bronchioalveolar carcinoma is a subtype of adenocarcinoma; it is a low-grade
carcinoma that can occur in single or multiple nodules.
̵ Asbestos exposure can be an underlying causative agent, usually after a latent period of
30 years.
̵ Adenocarcinoma is usually associated with pleural effusions that have high
hyaluronidase levels.
̵ Diagnosis often requires thoracotomy with pleural biopsy.
2) Squamous Cell Carcinoma.
̵ Squamous cell carcinoma is a centrally located lesion. It is associated with cavitary
lesions.
̵ Squamous cell carcinoma usually metastasizes by direct extension into the hilar node
and mediastinum.
̵ These lesions are associated with hypercalcemia from the secretion of a parathyroid
hormone–like substance.

4. 3) Small-Cell Carcinoma.
̵ Small-cell carcinomas are centrally located lesions.
̵ These tumors are rapidly growing with early distant metastasis to extrathoracic sites
such as liver, adrenal glands, brain, and bone.
̵ Prognosis does not improve with early diagnosis.
̵ Small-cell carcinoma is associated with Eaton-Lambert syndrome, syndrome of
inappropriate antidiuretic hormone (SIADH), and other paraneoplastic syndromes.
̵ Small-cell carcinoma is also the most common cause of venocaval obstruction
syndrome.
 Squamous and Small cell carcinomas are Sentral (central) and often caused by Smoking.
4) Large-Cell Carcinoma.
̵ Large-cell carcinoma is a peripherally located lesion.
̵ This carcinoma can metastasize to distant locations late in the course of disease.
̵ Large-cell carcinoma in early stages is associated with cavitation.
TYPE LOCATION CHARACTERISTICS HISTOLOGY
Small cell
Small cell (oat
cell) carcinoma
Central • Undifferentiated  very
aggressive.
• May produce ACTH
(Cushing syndrome),
ADH (SIADH), or
Antibodies against
presynaptic Ca2+
channels (Lambert-
Eaton myasthenic
syndrome) or neurons
(paraneoplastic myelitis,
encephalitis, subacute
cerebellar degeneration).
Amplification of myc
oncogenes common.
• Managed with
chemotherapy +/–
radiation.
• Neoplasm of
neuroendocrine
Kulchitsky cells 
small dark blue cells
• Chromogranin A
⊕, neuron-specific
enolase ⊕,
synaptophysin ⊕.
Non-small cell

5. Adenocarcinoma Peripheral • Most common 1° lung
cancer.
• More common in
women than men, most
likely to arise in
nonsmokers.
• Activating mutations
include KRAS, EGFR,
and ALK.
• Associated with
hypertrophic
osteoarthropathy
(clubbing).
• Bronchioloalveolar
subtype
(adenocarcinoma in
situ):
CXR often shows hazy
infiltrates similar to
pneumonia; better
prognosis.
• Glandular pattern
on histology, often
stains mucin ⊕
• Bronchioloalveolar
subtype:
grows along alveolar
septa  apparent
“thickening” of
alveolar walls. Tall,
columnar cells
containing mucus.
Squamous cell
carcinoma
Central Hilar mass arising from
bronchus; Cavitation;
Cigarettes; hyperCalcemia
(produces PTHrP).
Keratin pearls and
intercellular bridges
Large cell
carcinoma
Peripheral • Highly anaplastic
undifferentiated tumor;
poor prognosis.
• Less responsive to
chemotherapy; removed
surgically.
• Strong association with
smoking.
Pleomorphic giant
cells
Bronchial
carcinoid
tumor
Central or
peripheral
• Excellent prognosis;
metastasis rare.
• Symptoms due to mass
effect or carcinoid
syndrome (flushing,
diarrhea, wheezing).
• Nests of
neuroendocrine
cells; chromogranin
A ⊕

6. Symptoms
̵ Unfortunately, signs and symptoms are generally nonspecific for lung cancer, and
by the time they are present, disease is usually widespread.
1. Local manifestations (most commonly with squamous cell carcinoma)
a. Airway involvement  cough, hemoptysis, obstruction, wheezing, dyspnea
b. Recurrent pneumonia (post-obstructive pneumonia)
2. Constitutional symptoms
a. Anorexia, weight loss, weakness
b. Usually indicative of advanced disease
3. Local invasion (SPHERE of complications)
a. Superior vena cava (SVC) syndrome—occurs in 5% of patients
• Caused by obstruction of SVC by a mediastinal tumor
• More commonly occurs with SCLC
• Findings: facial fullness; facial and arm edema; dilated veins over anterior
chest, arms, and face; jugular venous distention (JVD)
b. Phrenic nerve palsy—occurs in 1% of patients
• Destruction of phrenic nerve by tumor; phrenic nerve courses through the
mediastinum to innervate the diaphragm
• Results in hemi-diaphragmatic paralysis
c. Recurrent laryngeal nerve palsy (3% of patients)—causes hoarseness
d. Horner syndrome
• due to invasion of cervical sympathetic chain by an apical tumor.
• Symptoms: unilateral facial anhidrosis (no sweating), ptosis, and miosis
e. Pancoast tumor
• Superior sulcus tumor—an apical tumor involving C8 and T1–T2 nerve roots,
causing shoulder pain radiating down the arm
• Usually squamous cell cancers
• Symptoms: pain; upper extremity weakness due to brachial plexus invasion;
• associated with Horner syndrome 60% of the time
f. Malignant pleural effusion—occurs in 10% to 15% of patients
Prognosis is very poor—equivalent to distant metastases
4. Metastatic disease
most common sites are brain, bone, adrenal glands, and liver
5. Paraneoplastic syndromes

7. Paraneoplastic effects of tumor are remote effects that are not related to the direct
invasion, obstruction, or metastasis.
a. Syndrome of inappropriate ADH:
• usually associated with small cell carcinoma (10% of SCLC patients)
b. Cushing syndrome:
• due to ectopic ACTH secretion,
• typically associated with small cell carcinoma
c. Hypercalcemia:
• commonly due to PTH-like hormone secretion,
• most commonly squamous cell carcinoma
d. Hypertrophic pulmonary osteoarthropathy:
• associated with both adenocarcinoma and squamous cell carcinoma;
• severe long-bone pain may be present, and leads to digital clubbing.
e. Eaton–Lambert syndrome:
• most common in SCLC;
• clinical picture is similar to that of myasthenia gravis, with proximal muscle
weakness/fatigability, diminished deep tendon reflexes, paresthesias (more
common in lower extremities)

8. A. Paraneoplastic
phenomena
 Endocrine
▪ Hypercalcemia
̵ May arise from a bony metastasis or less commonly tumor
secretion of a parathyroid hormone-related protein (PTHrP),
calcitriol or other cytokines, including osteoclast activating
factors.
▪ SIADH secretion
Frequently caused by SCLC & results in hyponatremia
▪ Cushing's syndrome:
̵ Ectopic production of adrenal corticotropin (ACTH).
̵ relatively common in patients with SCLC and with carcinoid
tumors of the lung, as well as extrathoracic malignancies.
̵ Typically present with muscle weakness, weight loss,
hypertension, hirsutism, and osteoporosis.
̵ Hypokalemic alkalosis and hyperglycemia are usually present
 Neurologic
̵ Lung cancer is the most common cancer associated with
paraneoplastic neurologic syndromes; typically these are
associated with SCLC.
̵ Paraneoplastic neurologic syndromes are thought to be
immune-mediated
̵ The most common manifestations is Lambert-Eaton
myasthenic syndrome (LEMS) which may be seen in
approximately 3 % of patients with SCLC
 Hematologic
▪ Anemia: frequent and can contribute to fatigue and dyspnea
▪ Leukocytosis: found in 15 % of patients. Nearly all had
NSCLC. associated with a poor prognosis
▪ Thrombocytosis is common (14 % of patients) & has been
identified as an independent predictor of shortened survival
▪ Eosinophilia is rare, but reported with large cell carcinoma
▪ Hypercoagulable disorders:
o Trousseau syndrome (migratory superficial
thrombophlebitis)
o Deep venous thrombosis and thromboembolism
o Disseminated intravascular coagulopathy
o Thrombotic microangiopathy
o Nonthrombotic microangiopathy
 Musculoskeletalandcutaneous

9. ▪ Hypertrophic pulmonary osteoarthropathy (HPO) is
defined by the presence of clubbing and periosteal
proliferation of the tubular bones
▪ Dermatomyositis and polymyositis
two distinct forms of inflammatory myopathy, manifested
clinically by muscle weakness
SPHERE of complications:
• Superior vena cava/thoracic outlet syndromes
• Pancoast tumor
• Horner syndrome
• Endocrine (paraneoplastic)
• Recurrent laryngeal nerve compression (hoarseness)
• Effusions (pleural or pericardial)

10. Diagnosis
̵ It is crucial to differentiate between small cell (25%) and non–small cell (75%) types
because the treatment approach is completely different. A tissue diagnosis is
necessary to make this differentiation.
1. CXR
• Most important radiologic study for diagnosis, but not used as a screening test
• Demonstrates abnormal findings in nearly all patients with lung cancer
• Stability of an abnormality over a 2-year period is almost always associated with a
benign lesion
2. CT scan of the chest with IV contrast
• Very useful for staging
• Can demonstrate extent of local and distant metastasis
• Very accurate in revealing lymphadenopathy in mediastinum
• Consider CT of abdomen to screen for metastases to adrenal glands and liver
3. Cytologic examination of sputum
• Diagnoses central tumors (in 80%) but not peripheral lesions
• Provides highly variable results with low yield; if negative and clinical suspicion is
high, further tests are indicated
4. Fiberoptic bronchoscopy with endobronchial ultrasound
• Can only be inserted as far as secondary branches of bronchial tree; first choice for
diagnosing central visualized tumors but not peripheral lesions
• The larger and more central the lesion, the higher the diagnostic yield; for visible
lesions, bronchoscopy is diagnostic in >90% of cases
If CXR show pleural effusion:
• Next step in such a patient is to do thoracocentesis and cytologic evaluation of
the pleural fluid.
• 90% of tumors with malignant effusions are unresectable.
• These tumors are usually adenocarcinomas.
• Atelectasis on chest x-ray suggests central airway obstruction.

11. 5. Whole-body positron emission tomography (PET)
• provides additional information that primary tumor is malignant,
• detects lymph node and intrathoracic and distant metastases
6. Transthoracic needle biopsy (under fluoroscopic or CT guidance)
• Needle biopsy of suspicious pulmonary masses is highly accurate, and is useful for
diagnosing peripheral lesions as well
• Needle biopsy is invasive and must be used only in selected patients. This is a better
biopsy method for peripheral lesions, whereas central, peribronchial lesions should
be biopsied using bronchoscopy
7. Mediastinoscopy
• Allows direct visualization of the superior mediastinum
• Identifies patients with advanced disease who would not benefit from surgical
resection
Staging
a. NSCLC is staged via the primary TNM system.
b. SCLC is staged differently (though some recommend TNM staging still be used):
• Limited—confined to chest plus supraclavicular nodes, but not cervical or axillary
nodes
• Extensive—outside of chest and supraclavicular nodes
Regardless of the findings on CXR or CT scan, pathologic confirmation is required
for definitive diagnosis of lung cancer
Always perform a biopsy for intrathoracic lymphadenopathy (specificity for metastasis
is 60%).

12. Treatment
̵ Symptoms that suggest an unresectable lesion include
▪ weight loss >10%,
▪ bone pain or other extrathoracic metastases,
▪ CNS symptoms (treated by radiation or chemotherapy),
▪ superior vena cava syndrome, hoarseness,
▪ mediastinal adenopathy on the contralateral side,
▪ split-lung test tidal volume <800 ml,
▪ tumor classification of M1 within 3 months, and
▪ tumor involving the trachea, esophagus, pericardium, or chest wall.
̵ Effusions can be sclerosed with tetracycline.
̵ Complications are treated with radiation therapy, which in most cases is palliative.
1. NSCLC
a. Surgery is the best option for limited disease.
̵ A definitive pathologic diagnosis must be made prior to surgery.
̵ Patients with metastatic disease outside the chest are not candidates for surgery.
̵ Recurrence may occur even after complete resection.
b. Radiation therapy is an important adjunct to surgery.
c. Chemotherapy is of uncertain benefit !
Some studies show a modest increase in survival especially with novel
immunotherapy agents. More trials are underway.
CAP (cyclophosphamide, adriamycin, and platinum).
2. SCLC
a. For limited disease, combination of chemotherapy and radiation therapy is
used initially.
b. For extensive disease, chemotherapy is used alone as initial treatment.
If patient responds to initial chemotherapy treatment, prophylactic whole-
brain irradiation decreases incidence of brain metastases and prolongs
survival.
VP16 (etoposide and platinum) is the treatment of choice
c. Surgery has a limited role because these tumors are usually nonresectable.

13. Prognosis
̵ Overall, 5-year survival for lung cancer patients is 14%;
85% of patients with SCLC have extensive disease at the time of presentation, and
of these almost all die within 2 years.
̵ Prognosis is best after surgical resection of squamous-cell carcinoma (30–35%).
̵ Large-cell carcinoma and adenocarcinoma have a prognosis of 25%.
̵ Prognosis is poorest for small-cell carcinoma.
• For limited disease, 5-year survival is 10% to 13% (median survival ranges from
15 to 20 months).
• For extensive disease, 5-year survival rate is 1% to 2% (median survival is 8 to 13
months).
Screening
Recommendations for lung cancer screening are as follows:
• In cases where adults age 55–80 who have a 30-pack-year smoking history and
currently smoke or have quit within past 15 years, should receive annual screening
with low dose CT (non-contrast).
• In cases where patients age >80, quit >15 years, has other medical problems such as
severe COPD which significantly limits life expectancy or ability to undergo surgery,
no screening is recommended.