Defines the disease, presentation, diagnosis and treatmeny.

1. LUNG CANCER
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2. o Rare below age 40, incidence increases until age 80
o Smoking is the primary cause of lung cancer; for every 15 cigarettes
smoked, one genetic mutation occurs
o Smokers have a 10 to 20-fold risk and second-hand smokers have a 30%
risk for developing lung cancer
o Smoking increases the risk for all major lung cancer cell types
o Other risk factors: occupational exposure, low fruit and vegetable intake
during adulthood, ionizing radiation, genetics

3. Lung cancers arise from the respiratory epithelium (bronchi, bronchioles and
alveoli); there are four types:
o Small-cell lung cancers (SCLC) – consist of small cells with scant cytoplasm, ill-
defined cell borders, finely granular nuclear chromatin, absent or
inconspicuous nucleoli, and a high mitotic count
Non-small cell lung cancers (NSCLC)
o Adenocarcinoma – most common histologic type; from glandular
differentiation; with mucin productions
o Squamous cell carcinoma – composed of sheets of cells showing keratinization
o Large cell carcinoma – least common; lacks the features of the first three types

4. o Adenocarcinoma in situ
• Small solitary adenocarcinomas (≤3 cm)
• Pure lepidic growth (single layer of atypical cuboidal cells coating the alveolar
walls)
o Minimally invasive adenocarcinoma
• predominant lepidic growth with ≤5 mm invasion
o Both have a near 100% 5-year disease-free survival with complete
resection

5. IMMUNOHISTOCHEMISTRY
o Used to differentiate primary from metastatic adenocarcinomas:
• Thyroid transcription factor-1 (TTF-1) – positive in 70% lung adenocarcinomas
• Napsin-A (Nap-A) – positive in 90% of lung adenocarcinomas
• Other sources of adenocarcinomas should still be ruled out
• A negative TTF-1does not exclude a lung primary
o Also used to differentiate equivocal histology:
• Primary lung adenocarcinoma (Nap-A positive, TTF-1 positive)
• Primary lung squamous cell CA (Nap-A negative, TTF-1 negative)
• Primary small cell lung CA (Nap-A negative, TTF-1 positive)

6. PATHOGENESIS
o Loss-of-function mutations in tumor-suppressor genes
• TP53, RB1, RASSF1A, CDKN2A/B, LKB1 (STK11) and FHIT
• Nearly 90% of SCLCs harbor mutations in TP53 and RB1
o Gain-of-function mutations in oncogenes
• Driver mutations in genes encoding for signal proteins, leading to: increased
cell proliferation, angiogenesis, metastasis; and decreased apoptosis
• Adenocarcinoma mutations are the most studied model

9. SCREENING
o Model: National Lung Screening Trial (NLST)
o High risk: age 55 to 74, at least 30-pack year smoker
o Screening tool: low-dose, non-contrast, thin-slice spiral chest computed
tomography (LDCT)
o Duration: once a year for 3 years
o Positive screening: ≥4 mm, non-calcified nodule or mass
o Disadvantage: expensive, false positive of 96.4%, unneeded further
evaluation, emotional stress
o Advantage: 40% of true positives had early-stage IA cancers, 20%
reduction in mortality from lung cancer

10. SIGNS AND SYMPTOMS
o More than 50% of cases are metastatic at diagnosis
o Typical patient: 60+ years old, current or former smoker
o Probable case:
• 40+ years old with chronic cough  hemoptysis in a current or former smoker
with COPD
• A persistent pneumonia  constitutional symptoms and
unresponsive to repeated courses of antibiotics
o Constitutional symptoms include anorexia, weight loss, weakness,
fever, and night sweats

12. o Central or endobronchial growth:
• cough, hemoptysis, wheeze, stridor, dyspnea, postobstructive pneumonitis
o Peripheral growth:
• Pain from pleural or chest wall involvement, dyspnea on a
restrictive basis, and symptoms of a lung abscess resulting from tumor
cavitation
o Regional spread of tumor in the thorax :
• Tracheal obstruction, esophageal compression with dysphagia, recurrent
laryngeal paralysis with hoarseness, phrenic nerve palsy with elevation of the
hemidiaphragm and dyspnea, and sympathetic nerve paralysis with Horner’s
syndrome (enophthalmos, ptosis, miosis, and anhydrosis)
o Malignant pleural effusions can cause pain, dyspnea, or cough

13. o Pancoast (or superior sulcus tumor) syndrome
• Local extension of a tumor located in the lung apex
• Compress C8, T1 and T2 nerves to present with shoulder pain that radiates to
the ulnar distribution of the arm
o Other manifestations resulting from regional spread:
• Superior vena cava syndrome from vascular obstruction
• Cardiac extension with tamponade, arrhythmia, or cardiac failure
• Lymphatic obstruction with resultant pleural effusion
• Transbronchial spread into alveoli with impaired gas exchange, respiratory
insufficiency, dyspnea, hypoxemia, and sputum production

15. o Extrathoracic metastases
• Any organ, most commonly: brain, bone, liver
• 30% of metastases produce location-dependent symptoms
• 50% of squamous cell lung carcinomas
• 80% of adenocarcinomas and large cell lung carcinomas
• 95% of small cell lung carcinomas

16. PARANEOPLASTIC SYNDROMES
o Occur in 12% of cases, most commonly in SCLC
o Hypercalcemia
• Ectopic PTH or more commonly PTHrP
• Most common life-threatening metabolic complication of malignancy
• Primarily occurs in squamous cell lung carcinoma
o Hyponatremia
• Dilutional, due to inappropriate secretion of ADH or ANP
• Sodium level should be maintained above 128 mEq/L

17. o Hypokalemia and Cushing’s syndrome
• Ectopic secretion of ACTH by SCLC
o Skeletal–connective tissue
• Clubbing, 30%, NSCLC
• Hypertrophic primary osteoarthropathy , 10%, adenocarcinomas
o Neurologic-myopathic
• Retinal blindness, SCLC
• Eaton-Lambert myasthenic syndrome – proximal muscle weakness, usually in
the lower extremities; SCLC

18. o Hematologic
• Trousseau’s syndrome – migratory venous thrombophlebitis
• Marantic (non-bacterial thrombotic) endocarditis
• Anemia, disseminated intravascular coagulation, granulocytosis
o Others
• Dematologic: acanthosis nigricans, dermatomyositis
• Renal: nephrotic syndrome, glomerulonephritis

19. MANAGEMENT
o Central (squamous cell, small-cell or endobronchial lesions like carcinoid
tumors) – bronchoscopy
o Peripheral (adenocarcinomas and large-cell carcinomas) – transthoracic
approach
o Suspected malignant pleural effusions testing negative for the first time
warrants a repeat thoracentesis

20. o Biopsy of the most distant metastatic site is preferred (skin, soft tissue,
lytic bone, bone marrow, pleural or liver lesion, or cell block from pleural
effusion)
o Sensitivity is highest for larger lesions and peripheral tumors
o Core biopsy superior to fine needle or routine cytology
o Sputum cytology – lower yield due to poor cell preservation
o Diagnostic yield depends on accessibility of the tumor, tumor size, tumor
type (SCLC > NSCLC), experience level of the bronchoscopist and
pathologist

21. SOLITARY PULMONARY NODULE
A CXR finding of a circumscribed density of any shape, usually 1 to 6 cm in
largest diameter, surrounded by normal, aerated lung tissue.
Possibility of malignancy
Age (years)
45 to 74 74%
74 and older 96%
Size (cm)
2 to less than 3 66%
3 or bigger 99%

22. o Ground glass opacities (GGOs)
• Atypical adenomatous hyperplasia (AAH)
• Adenocarcinoma in situ (AIS) – less than 5 mm, non-solid
• Minimally invasive adenocarcinoma – with a solid core 5 mm
o Predictors of malignancy
• Clinical: age, symptoms, smoking, previous diagnosis of cancer
• Radiologic: size, spiculation, upper lobe location
o Predictors of benignity
• Calcification
• Lack of growth for over 2 years

30. CT scan;
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32. o Lobectomy is superior to wedge resection
o VATS may be used in patients with co-morbidities or decreased
pulmonary reserve
o Pneumonectomy is reserved for central tumors and patients with
excellent pulmonary reserve
o In Stage I and II NSCLC, radiation has no role except in a patient who
refuses or is not a suitable candidate for surgery
o Pancoast tumors may benefit form combined chemoradiation therapy

33. o Monoclonal antibodies have NOT been proven to be effective in treating
NSCLC
o Maintenance chemotherapy for non-progressing metastases is NOT routinely
recommended
o TKIs (erlotinib, afatinib, gefitinib) may be used as second and third-line
agents in lung adenocarcinoma and advanced non-adenocarcinoma NSCLC
o Contraindications to potentially curative resection in NSCLC:
• extrathoracic metastases, superior vena cava syndrome, vocal cord and phrenic
nerve paralysis, malignant pleural effusion, cardiac tamponade, tumor within 2 cm
of the carina (potentially curable with combined chemoradiotherapy), metastasis
to the contralateral lung, metastases to supraclavicular lymph nodes, contralateral
mediastinal node metastases (potentially curable with combined
chemoradiotherapy) and involvement of the main pulmonary artery

35. STAGING FOR SQUAMOUS CELL LUNG CARCINOMA
o Limited-Stage Disease
• can be encompassed within a tolerable radiation port (cancer that is confined
to the ipsilateral hemithorax, contralateral supraclavicular nodes, recurrent
laryngeal nerve involvement, and superior vena caval obstruction)
o Extensive-Stage Disease
• cannot be encompassed within a tolerable radiation port (overt metastatic
disease, cardiac tamponade, malignant pleural effusion and bilateral
pulmonary parenchymal involvement)

38. o Mainstay of treatment: cisplatin or carboplatin plus etoposide or
irinotecan
o Surgery is not routinely recommended for limited-stage disease because
SCLCs dramatically responds to chemoradiotherapy
o Only 12% of LD-SCLC and 2% of ED-SCLC live beyond 5 years
o Radiotherapy is part of standard therapy in LD-SCLC but only palliative in
ED-SCLC and prophylactic for brain metastases

39. Thank you!