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Updated: Jun 10 2024

Lung Cancer
  • A 65-year-old man with a 40 pack-year smoking history presents to his primary care physician for fatigue and cough. He reports that his symptoms began approximately 1 year ago and has progressively worsened. He has noticed a streak of blood when coughing into a napkin. He says that about 2-3 times a week, he wakes up from sleep drenched in sweat. Compared to his last visit 4 months ago, he has lost 12 pounds, which he states is unintentional. Physical examination is notable for finger clubbing. Radiography of the chest demonstrates the finding seen in the image. No prior imaging is available. A CT scan of the chest demonstrates an 11 mm pulmonary eccentric nodule located peripherally.
  • Overview
    • lung cancer is a malignancy that affects the lung parenchyma or airways
      • most lung cancers can be divided into
        • small cell lung cancer 
        • non-small cell lung cancer
  • Epidemiology
    • incidence
      • second most common cancer
      • leading cause of cancer-related death
    • risk factors
      • cigarette smoking
        • most important risk factor
        • second-hand smoke exposure is also a risk factor
      • asbestos
      • radon
      • family history of lung cancer
  • Prognosis
    • depends on cancer type and severity
  • Screening
    • performed with a low-dose computerized tomography (CT) scan of the chest  
      • indicated in patients 50-80 years of age who have a 20 pack-year smoking history and either of the following
        • currently smoke
        • has quit smoking within the past 15 years 
Small Cell Lung Cancer (SCLC)
Associated Findings Histology
Small cell (oat cell) lung cancer
  • Central
  • MYC gene amplication
  • May produce
    • adrenocorticotropic hormone (ACTH)
      • leads to Cushing syndrome 
    • excessive anti-diuretic hormone (ADH)
      • leads to syndrome of inappropriate ADH (SIADH)
    • presynaptic calcium channel antibodies
      • leads to Lambert Eaton syndrome 
  • Small size of tumor cells with lack of nucleoli and high nuclear:cytoplasm ratio
  • Positive for
    • neuron-specific enolase
    • chromogranin A
Non-Small Cell Lung Cancer (NSCLC)
Associated Findings Histology
  • Peripheral
  • Most common  
    • cause of lung cancer in non-smokers
    • cause of lung cancer (excluding metastasis)
  • Adenocarcinoma in situ
    • tumor growth along alveolar structures
      • lepidic growth pattern
  • Patients may have hypertrophic osteoarthropathy
  • Common gene mutations include
    • KRAS
    • EGFR
    • ALK
  • Typically mucin positive and has a glandular appearance
Large cell carcinoma
  • Peripheral
  • Associated with a poor prognosis
  • Highly associated with smoking
  • Pleomorphic giant cells
Squamous cell carcinoma of the lung 
  • Central
  • Can arise from the bronchus
  • Hypercalcemia
    • Tumor secretion of PTHrP, a PTH receptor agonist  
  • Keratin pearls
  • Intracellular bridges 
Bronchial carcinoid tumor
  • Central or peripheral
  • Carcinoid syndrome
  • Better prognosis
  • Neuroendocrine cells
  • Chromogranin A positive
  • Symptoms
    • cough
    • wheezing
    • unintentional weight loss
    • hemoptysis
    • chest pain
    • dyspnea
    • hoarseness
      • suggests involvement of the recurrent laryngeal nerve
  • Physical exam
    • finger clubbing
  • Radiography
    • indication
      • initial imaging modality when evaluating a patient with symptoms concerning for lung cancer
        • very important to review previous chest imaging to assess for lesion properties and changes 
  • Computerized tomography (CT) scan
    • indication
      • perform with low-doses to screen for lung cancer (review "screening" in the introduction)
      • further evaluate pulmonary nodule found on radiography
        • chest CT should be obtained for all patients with an unclearly characterized solitary pulmonary nodule seen on radiography 
  • Laboratory testing
    • complete blood count
    • liver function tests (e.g., alanine aminotransferase, aspartate aminotransferase, and total bilirubin)
      • abnormalities may suggest liver metastasis
    • alkaline phosphatase
      • abnormalities may suggest liver or bone metastasis
        • a gamma-glutamyl transpeptidase (GGT) should be obtained to differentiate between liver or bone involvement
    • calcium
      • abnormalities may suggest bone metastasis or paraneoplastic syndromes
  • Pulmonary function tests
  • Evaluation of an incidental solitary pulmonary nodule
    • introduction
      • benign features
        • diffuse
        • central
        • popcorn
        • concentric
      • malignant features
        • ground-glass
        • eccentric
    • initial step is to compare to prior chest X-ray to evaluate for interval change 
    • solitary pulmonary nodule < 8mm
      • if there are or aren't risk factors, one typically does surveillance with a chest CT in a few months depending on the size of the lesion
    • solitary pulmonary nodule > 8mm
      • very low probability of malignancy
        • CT surveillance 
      • low/moderate probability of malignancy
        • positron emission tomography (PET) scan  
          • if absent or mild uptake
            • CT surveillance
          • if moderate or intense uptake
            • biopsy or video-assisted thoracoscopic surgery
      • high probability of malignancy
        • staging evaluation with or without PET scan
  • Flexible bronchoscopy
    • indication
      • to evaluate for an endobronchial mass in patients with recurrent pneumonia and extensive smoking history    
  • Tuberculosis
    • differentiating factors
      • abnormal quantiferon or purified protein derivative (PPD) test
      • history of ? risk of exposure (e.g., household contact with someone with diagnosed tuberculosis or travel to tuberculosis-endemic area)
  • Small cell lung cancer
    • most cases are non-resectable and thus require chemotherapy (e.g., carboplatin and etoposide)
  • Non-small cell lung cancer
    • treatment includes surgical removal, lymph node sampling or dissection, radiation, and chemotherapy
      • depends on the staging
  • Superior vena cava syndrome  
  • Pancoast tumor   
    • may cause Horner syndrome  
  • Metastasis 
  • Pericardial effusion
  • Pleural effusion
  • Paraneoplastic syndromes
    • Lambert-Eaton syndrome
    • SIADH
    • Cushing syndrome

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