Lung Cancer

Lung cancer is the malignant transformation of lung tissue and the leading cause of cancer-related deaths. The majority of cases are associated with long-term smoking. The disease is generally classified histologically as either small cell lung cancer or non-small cell lung cancer. Molecular profiling of the cancer provides further distinction of the tumor’s biological behavior, prognosis, and treatment options. Symptoms include cough, dyspnea, weight loss, and chest discomfort. Regional and metastatic spread cause additional symptoms and complications depending on the location and organ(s) affected. Related paraneoplastic syndromes include hypercalcemia, hyponatremia, Lambert-Eaton syndrome, Cushing’s syndrome, polydermatomyositis, and dermatomyositis. Definitive diagnosis and staging are made by biopsy, genetic mutation with biomarker testing, and imaging. Management is guided by the cancer stage and associated molecular profile. Lung cancer carries an overall poor prognosis.

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  • Lung cancer is the leading cause of cancer-related death in the United States:
    • 90% of cases are fatal.
    • 5-year survival in approximately 18% of cases (even with advances in treatment)
    • Annual deaths:
      • 160,000 in the United States
      • 1.6 million worldwide
  • 230,000 new cases are reported annually in the United States (accounts for 13% of all cancer cases).
  • Incidence increases with age:
    • Rare under 50 years old
    • Incidence peaks at 75–79 years old.
  • 85%–90% of lung cancer cases are attributed to smoking.

Risk factors

  • Smoking (most common):
    • Increased risk related to the number of cigarettes smoked per pack-year (pack-year = number of packs of cigarettes smoked per day multiplied by the years the person has smoked, assuming 20 cigarettes in 1 pack)
    • Lung cancer is more likely to develop by smoking at a lower intensity for a long time than smoking at a higher intensity for a short time.
    • The association with electronic cigarettes is not yet clear.
  • Environmental exposures:
    • Secondhand smoke
    • Air pollution
    • Asbestos
    • Radon
    • Chromium
    • Nickel
    • Arsenic
    • Polycyclic aromatic hydrocarbons
  • Radiation treatment
  • Lung disease:
    • Idiopathic pulmonary fibrosis
    • Alpha-1 antitrypsin deficiency
    • Chronic obstructive pulmonary disease (COPD)
  • HIV infection
  • Family history
  • Alcohol consumption

Pathophysiology and Classification


  • Incompletely understood
  • Cigarette smoking exposes patients to carcinogens:
    • Polycyclic aromatic hydrocarbons produce mutations in p53 → tumor suppression is compromised
    • Believed to be a factor in the accumulation of acquired driver mutations (alterations initiating malignancy development in a noncancerous cell)
  • Nonsmokers:
    • Approximately 25% of lung cancers (more often women)
    • Most are adenocarcinomas; associated targetable mutations are found (likely epidermal growth factor (EGF) receptor mutations).
  • Precursor lesions:
    • Atypical adenomatous hyperplasia
    • Adenocarcinoma in situ
    • Squamous dysplasia and carcinoma in situ
    • Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia

Classification scheme

  • Major histologic types of lung cancer:
    • Non-small cell lung carcinoma (NSCLC) makes up 85% of all lung cancers and generally subcategorized into:
      • Adenocarcinoma
      • SCC
      • Large cell carcinoma
    • Small cell lung carcinoma (SCLC) makes up 15% of all lung cancers.
  • World Health Organization 2015 classification:
    • Recognizes heterogeneous histological and molecular profiles of lung cancers
    • Classification utilizes immunohistochemistry and histologic findings to characterize tumors.
    • Guides treatment approach to personalize treatment strategies (molecular-targeted therapies)

2015 classification

  • Lists the most common NSCLCs, and groups SCLCs with other tumors exhibiting neuroendocrine differentiation
  • Epithelial tumors:
    • Adenocarcinoma
    • SCC
    • Large cell carcinoma
    • Neuroendocrine carcinoma: 
      • Small cell carcinoma 
      • Large cell neuroendocrine carcinoma
      • Carcinoid (typical or atypical)
    • Other rare epithelial tumors:
      • Adenosquamous carcinoma 
      • Pleomorphic carcinoma
      • Spindle cell carcinoma
      • Giant cell carcinoma
      • Carcinosarcoma
      • Pulmonary blastoma
      • Other and unclassified carcinomas
      • Salivary gland–type carcinomas
  • Mesenchymal tumors
  • Lymphohistiocytic tumors
  • Tumors of ectopic origin
  • Metastatic tumors



  • Most common (about 40%–50% of lung cancers)
  • Location: peripheral
  • Associated mutations:
    • EGF receptor
    • Anaplastic lymphoma kinase (ALK)
    • KRAS
    • BRAF
    • RET
    • ROS1
    • MET
  • Pathology:
    • Neoplastic gland formation
    • Intracytoplasmic mucin
    • Pneumocyte/immunohistochemical markers: 
      • Thyroid transcription factor 1 (TTF-1)
      • Napsin A


  • Preinvasive: 
    • Atypical adenomatous hyperplasia (≤ 5 mm growth)
    • Adenocarcinoma in situ (≤ 3 cm, lepidic growth or noninvasive growth along alveolar structures)
  • Invasive (based on predominant pattern):
    • Minimally invasive: ≤ 3 cm lepidic growth, ≤ 5 mm invasion
    • Lepidic: Growth pattern is lepidic with > 5 mm invasion.
    • Papillary: Tumor cells coat papillae (with central fibrovascular core).
    • Micropapillary: Tumor cells coat papillae (no central fibrovascular core).
    • Acinar: Tumor cells form gland-like spaces.
    • Solid: lacking glandular features
    • Invasive mucinous: former mucinous bronchioloalveolar carcinoma
    • Colloid: abundant extracellular mucin
    • Fetal: similar to endometrioid adenocarcinoma
    • Enteric: resembles adenocarcinoma arising from colorectum

Squamous cell carcinoma

  • Approximately 20% of lung cancers 
  • Location: 
    • Central 
    • Arise mostly in the proximal tracheobronchial tree
  • Associated mutations/chromosome deletions in:
    • 3p
    • 9p (site of CDKN2A gene)
    • 17p (site of TP53 gene)
  • Pathology:
    • Intercellular bridges/desmosomes
    • Keratinization: squamous pearls or cells with eosinophilic cytoplasm
    • Infiltrating nest of tumor cells shows central necrosis, which results in cavitation.
    • Immunohistochemical markers: 
      • p40
      • Cytokeratin 5/6
      • p63
  • Associated with parathyroid hormone-related peptide secretion


  • Keratinizing
  • Nonkeratinizing
  • Basaloid

Large cell carcinoma

  • 2% of lung cancers
  • Location: peripheral
  • Pathology:
    • Undifferentiated
    • Large tumor cells (large nuclei, prominent nucleoli, moderate cytoplasm); possibly arranged in sheets
    • Does not express any immunohistochemical markers of adenocarcinoma or SCC
  • Can secrete beta-human chorionic gonadotropin and cause gynecomastia

Small cell lung carcinoma

  • About 15% of all lung cancers
  • Highly aggressive: rapid presentation and > 60% with metastatic disease at diagnosis
  • Almost always seen in smokers
  • Location: central
  • Associated gene mutations:
    • TP53
    • MYC
    • RB1
    • BLC2
    • Deletion in 3p
  • Pathology:
    • Sheets of small blue cells, rosette formation, necrosis
    • High mitotic rate (> 11 mitoses/2 mm²)
    • Neuroendocrine Kulchitsky cells: 
      • Small cells with scant cytoplasm
      • Hyperchromatic nuclei with finely granular chromatin (salt-and-pepper pattern)
    • Neuroendocrine markers:
      • CD56 (detected in 90%–100% of cases)
      • Chromogranin A
      • Synaptophysin
      • Neurospecific enolase
    • Can be positive for TTF-1
  • May produce peptide hormones:
    • Adrenocorticotropic hormone (ACTH)
    • Arginine vasopressin or antidiuretic hormone (ADH)
    • Atrial natriuretic peptide (ANP) 
    • Gastrin-releasing peptide

Large cell neuroendocrine carcinoma

  • Rare but aggressive lung cancer 
  • Associated with smoking
  • Location: peripheral
  • Pathology:
    • Cellular arrangement: nests, rosette formation, necrosis 
    • Cells are large with abundant eosinophilic cytoplasm.
    • High mitotic rate (> 10 mitoses/2 mm²)
    • Neuroendocrine markers:
      • Chromogranin
      • Synaptophysin
      • CD56


  • 1%–2% of all lung cancers
  • Well-differentiated neuroendocrine tumors (generally slow growth)
  • Younger, nonsmoking patients
  • Location: central > peripheral
  • Pathology:
    • Typical carcinoid: absent or mild nuclear atypia with < 2 mitoses/2 mm²
    • Atypical carcinoid: moderate nuclear atypia with 2–10 mitoses/2 mm²

Clinical Presentation

General symptoms

  • Asymptomatic in approximately 25% of patients
  • Cough (most common):
    • New-onset cough in a smoker or ex-smoker
    • Frequent symptom in squamous and small cell cancers due to central location
    • May have hemoptysis
  • Dyspnea due to malignancy-related:
    • Airway obstruction
    • Atelectasis
    • Pleural effusion
    • Pneumothorax
    • Anemia
  • Chest pain:
    • Vague
    • Localized
    • Pleuritic
  • Fatigue
  • Cancer cachexia: 
    • Loss of muscle mass and fat, weight loss, anorexia
    • Inflammatory mediators play a role (lead to skeletal muscle degradation)

Regional spread

  • Recurrent laryngeal nerve encroachment: hoarseness
  • Phrenic nerve encroachment:
    • Diaphragmatic paralysis (elevated diaphragm)
    • Dyspnea
    • Hypoxia
  • Superior vena cava (SVC) syndrome:
    • SCLC > NSCLC
    • Compression or invasion of the SVC resulting in:
      • Headache
      • Head fullness
      • Facial swelling
      • Upper extremity swelling
      • Orthopnea
      • Dilated neck, face, and trunk veins
      • Facial plethora (flushing)
  • Pancoast syndrome:
    • Mostly due to NSCLC 
    • Apical tumors invade the brachial plexus, pleura, or ribs resulting in: 
      • Shoulder and upper extremity pain
      • Upper extremity weakness
      • Atrophy of the ipsilateral hand
      • Horner’s syndrome: ptosis, miosis, anhidrosis
  • Pericardial spread:
    • Pericarditis → chest pain 
    • Pericardial effusion (can lead to cardiac tamponade) → dyspnea
  • Esophageal compression: dysphagia 


  • Liver:
    • Abdominal pain
    • Nausea
    • Early satiety
  • Brain:
    • Behavioral changes and confusion
    • Aphasia
    • Focal neurologic deficits
    • Nausea and vomiting
    • Seizures
  • Bone:
    • Pain (back, chest, extremities)
    • Pathologic fractures
  • Adrenal glands:
    • Usually asymptomatic
    • Adrenal insufficiency (if both glands are affected by metastatic cancer):
      • Weakness
      • Nausea
      • Anorexia
      • Electrolyte imbalances

Paraneoplastic syndrome

  • Hypertrophic pulmonary osteoarthropathy:
    • Noted in adenocarcinomas and large cell carcinomas
    • Clubbing
    • Periosteal proliferation of tubular bones:
      • Symmetrical, painful arthropathy
      • Involves ankles, knees, wrists, and elbows
  • Hypercalcemia:
    • Sources:
      • SCC produces parathyroid hormone-related protein.
      • Extensive bone metastases
    • Signs and symptoms:
      • Anorexia
      • Nausea
      • Constipation
      • Lethargy
      • Polyuria and polydipsia
      • Confusion
      • Coma
  • Syndrome of inappropriate antidiuretic hormone secretion (SIADH)/Schwartz-Bartter syndrome:
    • Associated with SCLC
    • Signs and symptoms:
      • Anorexia
      • Nausea, vomiting
      • Confusion, coma
      • Seizures
      • Hyponatremia
  • Lambert-Eaton syndrome:
    • Typically seen in SCLC
    • When associated with malignancy, a more rapid course is noted.
    • Progressive proximal muscle weakness or myasthenia in the pelvic girdle
  • Cushing’s syndrome:
    • SCLC can produce adrenocorticotropic hormone (ACTH).
    • Also seen in carcinoid tumors
    • Signs and symptoms:
      • Muscle weakness
      • Weight loss
      • Hypertension
      • Hirsutism
      • Osteoporosis
  • Hypercoagulability:
    • Migratory superficial thrombophlebitis (Trousseau syndrome)
    • Deep venous thrombosis and thromboembolism
    • Disseminated intravascular coagulopathy
  • Dermatomyositis and polymyositis:
    • Associated with lung cancer as well as malignancies of the ovaries, pancreas, bladder, and stomach
    • Signs and symptoms:
      • Proximal muscle weakness
      • Gottron papules
      • Heliotrope eruption
      • Shawl sign


Chest radiography

  • Not diagnostic, but often performed in patients with respiratory symptoms
  • Findings that should raise suspicion of malignancy:
    • New or enlarging focal lesion
    • Pleural effusion
    • Pleural nodularity
    • Enlarged hilar and paratracheal lymph nodes
    • Endobronchial lesion
    • Postobstructive pneumonia
    • Segmental or lobar atelectasis

Computed tomography

  • Used as a screening tool (low dose)
  • Low-dose CT produces high-resolution images with less radiation:
    • Concerning findings in a patient with a solitary pulmonary nodule:
      • Size > 15 mm
      • Irregular or spiculated borders
      • Location in an upper lobe
      • Cavitation
      • A solid component within a ground glass lesion
      • Growth is noted in follow-up imaging.
    • Multiple nodules should be concerning for pulmonary metastasis.
  • Abnormal findings should be followed up with diagnostic CT.
  • Performed in all patients with suspected lung cancer to assess the location of:
    • Tumor
    • Lymph node involvement
    • Metastases
  • Aids in biopsy planning

Follow-up imaging

In addition to CT, the following modalities are used to determine the extent of disease for staging purposes:

  • PET:
    • Evaluates for distant metastases
    • More accurate in evaluating mediastinal disease than CT
    • Assesses the metabolic activity of the primary tumor
  • MRI:
    • Preferred imaging for brain and spine metastases
    • Used to assess nerve involvement (e.g., brachial plexus)


  • Definitive pathology is required for diagnosis (tissue biopsy is preferred over cytologic specimen).
  • Tissue samples may be obtained by way of:
    • Bronchoscopy with endobronchial ultrasound (most common)
    • Mediastinoscopy
    • Transthoracic needle biopsy
    • Transesophageal endoscopic biopsy
    • Open lung biopsy
  • Cytologic specimen can be obtained from sputum, bronchial washings, and needle aspirates.
  • Histopathology: differentiates NSCLC from SCLC and classifies lung cancers 
  • Additional molecular testing (mutations and immune targets):
    • Techniques used for determining mutations (allows for targeted therapies in NSCLC):
      • DNA sequencing
      • FISH
      • Immunohistochemistry
    • Key driver mutations detected:
      • EGF receptor mutation
      • ALK rearrangements
      • ROS1 rearrangements
      • RET fusion
      • BRAF
      • MET mutation
    • Expression of programmed cell death ligand 1 (PD-L1) on immunohistochemistry helps determine use of checkpoint inhibitors in cancer therapies.
Bronchoscopy lung cancer

Lung cancer (arrows) in the left bronchus as seen with a bronchoscope

Image: “Lung cancer in L. Bronchus – bronchoscopic view” by JHeuser. License: CC BY 2.5

Laboratory evaluation

The following tests are possible findings for lung cancer:

  • CBC:
    • ↓ Hemoglobin
    • ↓ Platelets
  • Electrolytes:
    • ↓ Sodium → SIADH
    • ↑ Calcium → paraneoplastic manifestation, bone metastasis
  • ↑ Liver function test → liver metastasis:
    • ↑ Alkaline phosphatase may also be due to bone metastasis.


Tumor-nodes-metastases (TNM) staging

The following are the 8th-edition staging guidelines from the International Association for the Study of Lung Cancer:

Table: The primary tumor (T category)
Stage Description
Tx Primary tumor cannot be assessed.
T0 No evidence of a primary tumor
Tis Carcinoma in situ
T1 Tumor ≤ 3 cm, surrounded by lung or visceral pleura, without invasion of the main bronchus:
  • T1a: ≤ 1 cm
  • T1b: > 1 cm but ≤ 2 cm
  • T1c: > 2 cm but ≤ 3 cm
T2 Tumor > 3 cm but ≤ 5 cm, or:
  • Involves the main bronchus (without involvement of the carina)
  • Invades the visceral pleura
  • Associated with atelectasis or obstructive pneumonitis extending to the hilar region:
    • T2a: > 3 cm but ≤ 4 cm
    • T2b: > 4 cm but ≤ 5 cm
T3 Tumor > 5 cm but ≤ 7 cm, or associated tumor nodules in the same lobe as the primary tumor, or direct invasion of the chest wall, phrenic nerve, or parietal pericardium
T4 Tumor > 7 cm, or associated tumor nodules in a different ipsilateral lobe from the primary tumor, or invasion into the diaphragm, mediastinum, heart, great vessels, trachea, esophagus, recurrent laryngeal nerve, vertebral body, or carina
Table: The lymph nodes (N category)
Stage Description
Nx Unable to assess regional lymph nodes
N0 No regional lymph node metastasis
N1 Ipsilateral peribronchial and/or hilar lymph nodes and intrapulmonary node involvement
N2 Ipsilateral mediastinal and/or subcarinal lymph node involvement
N3 Contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node involvement
Table: Metastasis (M category)
Stage Description
M0 No distant metastasis
M1 Distant metastasis:
  • M1a: separate tumor nodules in the contralateral lobe, pleural or pericardial nodules, or malignant pleural or pericardial effusion
  • M1b: single extrathoracic metastasis
  • M1c: multiple extrathoracic metastases

Non-small cell lung cancer staging

Stage grouping TNM stage
  • TXN0M0
  • TisN0M0
  • IA1: T1aN0M0
  • IA2: T1bN0M0
  • IA3: T1cN0M0
  • IB: T2aN0M0
  • IIA: T2bN0M0
  • IIB: 
    • T1a‒cN1M0
    • T2a‒bN1M0
    • T3N0M0
  • IIIA:
    • T1a‒cN2M0
    • T2a‒bN2M0
    • T3N1M0
    • T4N0‒1M0
  • IIIB:
    • T1a‒cN3M0
    • T2a‒bN3M0
    • T3N2M0
    • T4N2M0
  • IIIC:
    • T3N3M0
    • T4N3M0
  • IVA: any T and N plus M1a or M1b
  • IVB: any T and N plus M1c

Small cell lung cancer staging

  • Staging is divided into limited and extensive disease (differs from NSCLC).
  • A simplified system is utilized as the majority of SCLCs present with locally advanced or metastatic (> 60%) disease.
Stage (SCLC) Description
Limited disease
  • Confined to the ipsilateral hemithorax
  • Involvement of regional lymph nodes
  • Corresponds to TNM stages I‒III
Extensive disease
  • Tumor beyond the ipsilateral hemithorax
  • Involvement of contralateral supraclavicular and hilar nodes
  • Distant metastases
  • Pericardial or pleural effusions
  • Corresponds to TNM stage IV
NSCLC: non-small cell lung cancer
SCLC: small cell lung cancer
TNM: tumor-nodes-metastases


Available treatment options


  • Assess performance status (comorbidities and pulmonary function) to determine if the patient is an appropriate surgical candidate.
  • Surgical lobectomy for those with excellent pulmonary reserve (preferred)
  • Sublobar resection or wedge resection for those who cannot tolerate a full lobectomy


  • Combination therapy: cisplatin-containing regimens (cisplatin plus vinorelbine, docetaxel, or paclitaxel)
  • Carboplatin: alternative to cisplatin

Radiation therapy:

  • Stereotactic body radiotherapy:
    • Radiation to a small, well-defined target
    • Preferred for tumors < 5 cm
  • Definitive radiotherapy with conventional fractionation for larger lesions

Targeted therapies:

  • Targets specific gene mutations (affects cell growth and replication)
  • Associated with improved survival
  • Can be used as 1st-line therapy
  • Available treatments:
    • EGF receptor inhibitors: osimertinib, erlotinib, gefitinib, and afatinib
    • ALK inhibitors: crizotinib, ceritinib, and alectinib
    • ROS1 inhibitors: crizotinib, entrectinib
    • RET inhibitors: selpercatinib, praseltinib
    • MET inhibitors: capmatinib
    • BRAF V600E mutations: dabrafenib plus trametinib


  • Utilized in tumors with PD-L1 expression (≥ 50%)
  • Programmed cell death receptor 1 (PD-1) and PD-L1 binding is targeted because:
    • PD-1:PD-L1 interaction inhibits tumor cell apoptosis.
    • Upregulation of PD-L1 allows cancer cells to evade the immune system (T cells are inactivated).
  • Used if there is tumor progression despite chemotherapy
  • Available medications:
    • Pembrolizumab
    • Atezolizumab
    • Nivolumab

Non-small cell lung cancer

Stage (NSCLC) Treatment approach
Stage I–II
  • Surgical lobectomy: treatment of choice if lesion is resectable
  • Radiation therapy:
    • Alternative for poor surgical candidates
    • Recommended after surgery if positive surgical resection margins
  • Adjuvant chemotherapy:
    • Not for stage IA
    • For stage II and some cases of stage IB
  • Chemoradiotherapy followed by surgical resection (for Pancoast tumor)
Stage III
  • Surgical resection, if feasible, followed by adjuvant chemotherapy
  • If resection is not feasible:
    • Chemotherapy with radiation therapy
    • Followed by immunotherapy (PD-L1 antibody) if no disease progression
Stage IV*
  • Therapy is guided by tumor mutations detected.
  • With targetable mutations, available therapy:
    • EGF receptor mutations: osimertinib, 1st line treatment (instead of chemotherapy)
    • ALK mutations: alectinib
    • ROS1 positive cancers: crizotinib
    • Other mutations: Available inhibitors are integrated into treatments.
  • Without targetable mutations:
    • Positive PD-L1 expression options:
      • Pembrolizumab
      • Atezolizumab
    • Low PD-L1 expression (adenocarcinoma):
      • Chemotherapy: carboplatin plus pemetrexed
      • Add immunotherapy: pembrolizumab (it still improves survival)
      • If immunotherapy is contraindicated: bevacizumab
    • Low PD-L1 expression (small cell cancer):
      • Chemotherapy: carboplatin plus paclitaxel
      • Add immunotherapy: pembrolizumab
  • For isolated metastasis (e.g., brain): radiation therapy
*Stage IV: palliative care with focus on alleviating symptoms and prolonging survival
NSCLC: non-small cell lung cancer
PD-L1: programmed cell death ligand 1
EGF: epidermal growth factor
ALK: anaplastic lymphoma kinase

Small cell lung cancer

Stage (SCLC) Description
Limited disease
  • Chemotherapy plus radiation therapy:
    • Combination is better than chemotherapy alone (in mediastinal or hilar lymph node involvement).
    • Chemotherapeutic agents: cisplatin or carboplatin plus etoposide
    • Radiation limits the risk of recurrence.
    • Chemotherapy is the preferred choice in SVC syndrome.
  • Surgical lobectomy:
    • For those with a small, focal tumor (no lymph nodes, no metastasis)
    • If lymph node involvement is identified in surgery, proceed to chemotherapy plus radiation.
  • Prophylactic radiation of the entire brain:
    • For those who respond to initial treatment
    • Reduces brain metastasis
    • Increases survival
Extensive disease*
  • Combination of:
    • Immunotherapy (humanized monoclonal anti-programmed death ligand 1 antibodies)
    • Chemotherapy
  • Radiation therapy for those with response to systemic treatment and with residual disease
  • Prophylactic or therapeutic whole brain radiation
*Extensive disease: palliative care with a focus on alleviating symptoms and prolonging survival
SCLC: small cell lung cancer
SVC: superior vena cava

Palliative measures

  • Recurrent malignant pleural effusions:
    • Repeat thoracentesis
    • Pleurodesis
    • Indwelling pleural catheter
  • Bone metastasis:
    • Bisphosphonates
    • Denosumab (bone-modifying agent)
  • Tumors of the trachea or mainstem bronchi:
    • Bronchoscopic fulguration
    • Stent placement
  • End-of-life care:
    • Supplemental oxygen
    • Bronchodilators
    • Opiates
    • Antiemetics
    • Hospice program


Risk-factor modification is more effective than screening in reducing lung cancer death.

  • Smoking cessation:
    • Most important factor
    • The greatest benefit is seen in those who quit by 30-years-old.
    • With a median history of 21 pack-years, risk is lowered by 39% after quitting for 5 years.
  • Radon:
    • Testing and remediation can be done in private residences.
    • The effect on lung cancer incidence is unknown.

Differential Diagnosis

  • Pulmonary embolism: obstruction of the pulmonary arteries most often due to thrombus migration from the deep venous system. Signs and symptoms include pleuritic chest pain, dyspnea, tachypnea, and tachycardia. Severe cases can result in hemodynamic instability or cardiopulmonary arrest. A chest CT with angiography is the primary method of diagnosis. Management includes oxygenation, anticoagulation, and thrombolytic therapy for unstable patients.
  • Tuberculosis: Mycobacterium tuberculosis, a bacteria, attacks the lungs and other body parts. Symptoms include fever, productive cough, night sweats, and weight loss. Diagnosis is made with the identification of acid-fast bacilli on sputum culture. Multiple antimicrobial medications are required for management (isoniazid, rifampin, pyrazinamide, and ethambutol).
  • Pneumonia: infection of the lung parenchyma most commonly caused by a bacteria or virus. Presentation often includes fever, productive cough, and dyspnea, and chest X-ray shows consolidation. Empiric antibiotic treatment is generally initiated and may be tailored if culture data is available. 
  • Histoplasmosis: a pulmonary disease caused by Histoplasma capsulatum. Patients may have fever, cough, myalgias, dyspnea, and chest pain. Imaging may show diffuse, nodular infiltrates or a cavitary lesion. Diagnosis is confirmed with antigen testing or the presence of Histoplasma in the sputum. Management is based on presentation and includes itraconazole, fluconazole, or amphotericin B.
  • Sarcoidosis: an inflammatory condition causing noncaseating granulomas in organs, including the lungs. Presentation includes cough, dyspnea, fever, and weight loss. Imaging may show hilar and mediastinal lymphadenopathy and parenchymal abnormalities. Diagnosis is confirmed via biopsy and management includes corticosteroid and immunosuppressive medications.
  • Chronic obstructive pulmonary disease (COPD): a spectrum of conditions characterized by irreversible airflow limitation. Chronic obstructive pulmonary disease results from obstructive inflammation of the small airways and changes in the lung parenchyma. Most cases are caused by smoking. Patients have progressive symptoms with exacerbations of dyspnea and chronic cough. Diagnosis is based on history and pulmonary function tests. Management includes smoking cessation, pulmonary rehabilitation, and pharmacotherapy.
  • Mesothelioma: the malignant growth of mesothelial cells commonly affecting the pleura. The majority of cases are associated with occupational exposure to asbestos. Symptoms include dyspnea, chest pain, coughing, fatigue, and weight loss. Chest CT shows multifocal pleural thickening and pleural effusion. Pleural biopsy is required for confirmation and to rule out metastasis from lung or breast cancer. Management is rarely effective and the average survival is < 1 year.


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