Common misconceptions and mistakes
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Believing that IV contrast is required to screen for pathologic mediastinal adenopathy
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Being reassured about a lesion that has demonstrated growth over time because it is “cold on PET scan”
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Designing a therapeutic plan for advanced lung cancer without a multidisciplinary chest tumor board
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Comparing imaging reports rather than actual imaging
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Failing to ensure radiographic resolution of pneumonia
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Attributing enlarged mediastinal lymph nodes to acute bacterial pneumonia
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Performing a biopsy of a lung abscess
Lung cancer epidemiology
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Lung cancer always grows, producing symptoms by occupying space and compressing/eroding into normal structures, ultimately killing the patient via a complication associated with the above process, or a systemic complication like venous thromboembolic disease or other paraneoplastic syndrome
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> 95% of lung cancers are carcinomas (ie, epithelial cell origin)
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> 85% of lung cancers are caused by cigarette smoking
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Risk increases with the total number of cigarettes smoked
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Precise quantification via “pack-years” = (average number of packs per day) × (number of years); useful in research, not clinically
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Clinically, ~ 10 cigarettes a day for ≥ ~ 10 years equals a significant exposure, thereby increasing the risk of lung cancer (and chronic obstructive pulmonary disease [COPD])
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Tobacco smoke contains tobacco-specific nitrosamines and polycyclic hydrocarbons, which are known carcinogens
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Cigar and pipe smoking (less smoke inhalation) poses a significantly lower (but real) risk of lung cancer
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Other significant risk factors for lung cancer include:
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Asbestos exposure, which dramatically increases the risk for lung carcinoma and is associated with the rare mesothelioma (pleural-based malignancy of mesothelial cell origin)
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Risk of lung cancer is very high among smokers with asbestos exposure (synergy)
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Asbestos alone confers a 2- to 5-fold increased risk
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Cigarette smoking alone confers a 10-fold increased risk
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Cigarette smoking and asbestos confer a 40-fold increased risk
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Pulmonary fibrosis and other focal parenchymal scaring (eg, as seen after tuburculosis [TB])
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Radon exposure (typically residential) which confers a definite risk of unclear magnitude
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Radon (gas) decay product of radium-226 occurs naturally and is a known lung carcinogen
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Exposure potentially occurs in homes (with basements built on soil/rock high in radium)
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Occupational exposures/risk factors other than asbestos
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Heavy metals
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Ionizing radiation in uranium miners
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Halo ethers in chemical industry workers
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Polycyclic aromatic hydrocarbons in petroleum and foundry workers
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Inherited genetic vulnerabilities
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Individual genetic factors place some at higher risk after exposure to carcinogens than others
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First-degree relatives of lung cancer patients have higher rates of lung cancer
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Candidate genetic factors include:
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Enzymes of the cytochrome P-450 system responsible for metabolizing cigarette smoke products to carcinogens
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Role of the immune system in tumor surveillance and suppression
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Diets low in β-carotene and vitamin E
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However, vitamin supplementation is not only ineffective, but it appears to cause more lung cancers
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Chronic exposure to wood smoke, via poorly ventilated indoor cooking, causes a significant amount of lung cancers (and COPD) worldwide, particularly among women
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Concern for lung cancer
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Concern for lung cancer usually arises because of abnormal thoracic imaging (most commonly a chest x-ray [CXR]) showing a focal, dominant opacity:
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“Dominant,” as opposed to “solitary” acknowledges that multiple unrelated small abnormalities are often present on thoracic imaging (eg, linear scaring)
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The most common cause of a focal CXR opacity is pneumonia
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Pneumonia tends to:
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Be accompanied by symptoms of cough and fever
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Appear quickly (ie, clear CXR 2 months prior) ( Fig. 9.1 )
Fig. 9.1
Encapsulated case showing the reassuring nature of very rapid growth with regard to lung cancer. Despite the opacities very concerning round, mass-like appearance, a doubling time of 4–9 days rules out lung cancer. Doubling time is estimated by assuming that a 0.1 cm to 1 cm opacity could have been missed on the initial film. Because of its concerning appearance, short-interval imaging follow-up is indicated (4–6 weeks) to ensure antibiotic response.
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Have air bronchograms and vague borders (or complete lobar consolidation), suggestive of an alveolar filling process; much more common in pneumonia than cancer
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An opacity is concerning for lung cancer whenever the clinical radiographic presentation does not support pneumonia (in individuals over the age of 40 years)
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Lung cancer tends to:
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Appear slowly (ie, smaller opacity visible in the same location on prior imaging during the previous 1 to 2 years, often only in retrospect [ Fig. 9.2 ])
Fig. 9.2
Computed tomography (CT) scans (unfortunately) show the natural history of squamous cell carcinoma, highlighting the profound cavitation and the tendency to progress locally before metastasizing distantly.
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Appear as a solid, often rounded opacity
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Be asymptomatic, unless it is enormous and/or invading critical structures, causing pain and/or malfunction (eg, pathologic rib fracture or laryngeal nerve involvement)
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Concern for lung cancer increases with individual risk factors:
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Personal history of lung cancer (single biggest risk factor)
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Age > 55 years
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Total number of cigarettes smoked (cumulative)
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Concomitant COPD
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Family history of lung cancer
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Other significant or synergistic exposures (eg, asbestos)
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Reviewing prior imaging (if available) is the first step in establishing concern or reassurance with regard to lung cancer ( Fig. 9.3 )
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A rapidly appearing opacity (days to weeks) should be presumed infectious (eg, typical pneumonia or lung abscess), whereas a stable opacity (≥ 2 years) can be presumed to be benign (ie, scarring)
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Stability of a solid lesion for ≥ 2 years or a ground glass lesion for ≥ 5 years provides reassurance that a lesion is nonmalignant and most likely represents scarring or a benign process (eg, hamartoma)
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Pneumonia that fails to radiographically improve in 3 to 6 weeks, and/or resolve in months, is very worrisome for lung cancer
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Steady growth of a lesion over several months to years makes it a cancer until proven otherwise
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Growing from 1 cm to 2 cm in 3 months (doubling time of 30 days) is about as fast as lung cancer grows
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Fig. 9.3
Flow diagram outlining the evaluation of a dominant opacity seen on imaging that is concerning for lung cancer (because it is not associated with PNA symptoms). A noncontrast chest computed tomography (CT) scan and positron emission tomography (PET) scan provide most of the information required to decide whether a lesion should be reimaged, biopsied, or resected/definitively treated. Biopsy via endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is the preferred approach because it is low morbidity, high yield, and often provides diagnosis and stage in a single procedure. Additionally, if adenopathy is nondiagnostic, the primary lesion can often be approached by radial probe. Occasionally a lung abscess must be empirically treated before a diagnosis of lung cancer can be pursued. Biopsy of a lung abscess can lead to pleural seeding, empyema, and persistent bronchopleural (BP) fistula (see CH 11 ).
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When growth characteristics are concerning for malignancy, indeterminate, or not known (ie, no prior imaging), a noncontrast chest computed tomography (CT) scan should be obtained
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A noncontrast CT scan of the chest is the standard for evaluating any “unexplained” CXR opacity
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Unexplained means not easily attributable to acute and/or resolving pneumonia or known prior scarring (eg, stable from prior imaging)
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Prior scarring is most reliably assessed by undertaking a detailed comparison of new imaging to old imaging (not reports)
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Any suggestion of change over time should prompt consideration for CT scanning because adenocarcinoma of the lung is more likely to occur in areas of prior scarring (a.k.a. scar carcinoma)
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Noncontrast chest CT:
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Characterizes the lesion as likely benign (eg, fat attenuation suggesting hamartoma) vs likely malignant (eg, necrosis)
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Localizes the lesion
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Reveals other smaller abnormalities not appreciated on the CXR that may either reassure (eg, evidence of prior granulomatous disease) or further increase concern (eg, enlarged hilar, mediastinal lymph nodes, or a small effusion)
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In cases in which lung cancer is known (or near certain), chest CT provides 90% of the information required for staging
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Other common x-ray findings concerning for lung cancer:
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Nonresolving pneumonia
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Every pneumonia should be reimaged to complete resolution
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Pneumonia can be:
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Caused by lung cancer via airway obstruction
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Hidden by a pneumonia
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Or misdiagnosed as pneumonia (in an individual with bronchitis/COPD exacerbation)
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A pneumonia that fails to radiographically improve in 6 weeks or persists for 3 months should prompt a noncontrast chest CT looking for findings concerning for lung cancer
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Ominous Lobar collapse
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Lung collapse not associated with foreign body aspiration or significant mucus production always raises concern for a (possibly malignant) airway lesion
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Lobar collapse is particularly ominous (ie, worrisome for airway obstruction from lung cancer) when it occurs in the upper lobe (less likely to be aspirated foreign material or impacted secretion) in high-risk individuals
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Additionally, collapse without the anticipated volume loss or collapse with volume gain are also very concerning for malignant airway obstruction (as the mass makes up for the lost volume of lung) ( Fig. 9.4 )
Fig. 9.4
Chest x-ray comparing typical right upper lobe collapse to ominous right upper lobe collapse. Ominous lung collapse has the concerning feature of volume gain, implying mass and collapse rather than airway obstruction from foreign body or mucus, which produces collapse with volume loss.
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CT scan and bronchoscopy (with endobronchial ultrasound [EBUS] capability) is the preferred approach
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Unilateral pleural effusion concerning for malignancy
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Evaluation of a unilateral effusion begins with the fair presumption that it represents an exudative process
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If the patient is obviously sick with pneumonia (eg, fever, cough, increased white blood cell count), a parapneumonic effusion is likely
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If the patient has risk factors for lung cancer and does not have signs or symptoms of pneumonia, a malignant effusion should be high on the differential
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Malignant pleural effusion (Seen in lung cancer > metastatic cancer > lymphoma > mesothelioma)
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Common presentation of stage IV lung cancer (often discovered by CXR imaging obtained to investigate gradual DOE)
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Malignant effusions may occur from either:
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Tumor-associated lymphatic obstruction, or
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Tumor metastasis to the parietal pleural surface
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Malignant effusions are typically moderate to large at presentation
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Thoracentesis often reveals a macroscopically bloody pleural fluid appearance
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Pleural pressures should be measured during thoracentesis, because the likelihood of lung entrapment is high with malignant pleural disease (see CH 17 )
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Diagnostic yield is maximized at 100 mL per thoracentesis
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Overall diagnostic yield goes up with a second 100-mL sample during repeat thoracentesis and slightly again with a third 100-mL sample
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Management:
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If the effusion is large enough to tap safely, a diagnosis should be attempted via thoracentesis
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In general, a CT scan should be obtained after thoracentesis to maximize the ability to see underlying pathology
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If CXR and ultrasound investigation reveal a complex pleural space (eg, adhesions or loculations), CT scan may be obtained before drainage (to help plan the procedure)
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The initial thoracentesis should attempt complete drainage (possible when the total volume of fluid in the effusion is estimated to be ≤ ~ 2000 mL)
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If the effusion is massive (ie, clearly > 2–3 L) a small bore chest tube (placed via seldinger technique) should be considered (with overnight admission) to facilitate rapid, complete drainage
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1-2 L may be intermittently drained (q 4–6 hours) as tolerated by reexpansion symptoms
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This aggressive approach aimed at timely, complete drainage is appropriate because it is indicated in the initial management of:
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Parapneumonic effusion/empyema
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Malignant effusion
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Idiopathic exudative effusion
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Complete drainage may prevent recurrence up to 10% of the time in addition to maximizing the ability to visualize the lung and pleural surface on the subsequent postdrainage CT scan
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If the postdrainage CT scan shows a dominant parenchymal focus and pleural fluid is negative, consider repeat diagnostic thoracentesis (ie, 100 mL for cytology)
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If the repeat thoracentesis is nondiagnostic (or not technically feasible), attention should shift to any abnormal adenopathy or the parenchymal lesion itself
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If the CT scan reveals abnormal pleura without adenopathy or a dominant parenchymal focus, video-assisted thoracoscopic surgery (VATS) biopsy may be required to make the diagnosis
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VATS is a particularly attractive option if the fluid recurs and causes symptoms, because it may provide both diagnosis and definitive therapy (via pleurodesis)
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A persistent, unexplained, lymphocytic predominant exudate in a patient with advanced lung cancer (behaves statistically like, so) can be assumed to be malignant in origin, despite negative pleural cytology
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Evaluation and Management of the Worrisome Parenchymal Lesion(s) During a Chest CT Scan (Number, Size, Appearance, and Growth)
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Evaluation and management of multiple pulmonary nodules :
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Likelihood of lung cancer based on number of lesions:
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The greater the number of nodules, the lower the likelihood of lung cancer
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Multiple nodules occur most commonly in granulomatous infections (eg, nontuburculous mycobacteria [NTM] infection, miliary TB) or inflammation (eg, sarcoidosis)
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Multiple small nodules (< 0.8 cm) should be evaluated with sputum specimens for acid-fast bacillus (AFB), immunologic screening for TB, endemic fungal infection, and Aspergillus with serial imaging (initially at 3 months)
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Steady growth of multiple nodules seen by serial imaging strongly suggests metastatic disease
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Steady growth of a single nodule in a chest with multiple nodules is concerning for concomitant early stage lung cancer occurring in the setting of prior granulomatous disease
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Three spiculated 1-cm lesions of the same size, in a patient with severe emphysema are more likely to represent atypical infection (eg, Aspergillus) rather then 3 synchronous primary lung cancers
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Multiple malignant nodules are seen in cancer that is metastatic to the lung, from a primary lung cancer or an extrathoracic malignancy (eg, colon)
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When multiple nodules represent metastatic lung cancer, a dominant lesion/mass is usually visible ( Fig. 9.5 )
Fig. 9.5
Chest x-ray and computed tomography (CT) scan showing metastatic lung adenocarcinoma in a “too numerous to count pattern.” The vessel associated and the random nature of nodules suggests that the majority of the metastasis was hematogenously spread.
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Renal cell, melanoma, colon, and breast cancer can cause oligometastatic disease (ie, a single or handful of pulmonary metastases, typically round, smooth-edged, lower-lobe lesions of similar size)
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≤ 5 metastases may be definitively treated (external beam radiation therapy [XRT] or subanatomic/wedge resection) to slow disease progression (if systemic options are lacking or failing)
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Multiple metastases (> 5) must be treated systemically
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Adenocarcinomas arising from the GI tract often metastasize widely to the lung
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Colon typically involves the liver and lung, but rectal, pancreatic, small bowel, and gastric adenocarcinomas may “skip” the liver on their way to the lung
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Bronchoscopy with blind transbronchial biopsies is a high-yield, low-morbidity approach to the diagnosis of metastatic adenocarcinoma to the lung when the pulmonary metastatic pattern is “too numerous to count (TNTC)” ( Fig. 9.6 )
Fig. 9.6
Chest x-ray and computed tomography (CT) scan showing metastatic lung adenocarcinoma in a “too numerous to count pattern.” The perilymphatic, pleural, and fissure-based nodules suggest that the majority of the metastasis were lymphatically spread.
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Otherwise, needle aspiration of the most accessible metastatic lesion (often extrathoracic) provides diagnosis and staging
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Evaluation of a dominant parenchymal lesion:
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A dominant lesion is much more concerning for primary lung cancer than multiple nodules of similar sizes
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Steady growth of a lesion over time (months to years) creates the highest possible pretest probability for lung cancer
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Growth trumps PET avidity (because PET avidity is a surrogate for growth)
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Lack of fluorodeoxyglucose (FDG) avidity on PET scan (ie, cold PET) does not provide reassurance with regard to a growing lesion
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It also is not a guarantee that the lesion is growing slowly, or will continue to grow slowly
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Increasing lesion size increases the likelihood of lung cancer (in at-risk individuals):
Lesion Size (cm)
Approximate prevalence of Lung Cancer
< 0.5
0.5%
< 0.8
5%
0.5–1.0
20%
1.1–2.0
50%
> 2.0
75%
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Likelihood of malignancy based on appearance:
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Solid lesions imply that no normal lung anatomy is visible, suggesting granuloma or tumor (ie, extra collection of tissue) based on size
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Principle differential diagnosis is granuloma vs hamartoma vs malignancy
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Granulomas are typically < 1 cm in size
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Hamartomas are typically < 3 in size
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This is why solid lesions > 3 cm are refereed to as a mass and presumed malignant until proven otherwise
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Semisolid lesions raise the possibility of an infectious or inflammatory process where the nonsolid portions actually represent airways (appearing as a tubular lucency) and/or inflammatory alveolar filling (appearing as ground glass), and the solid portions represent consolidated lung
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However, this constellation of findings may also be seen with invasive mucinous adenocarcinoma ( Fig. 9.7 )
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