II. Definitions
- Lung Nodule
- Spherical opacity on xray <3 cm in diameter
- Completely surrounded by aerated lung
- Solitary Lung Nodule
- Isolated, single Lung Nodule
- Lung Mass
- Lung Lesion >3 cm diameter
- Considered to be Lung Cancer until proven otherwise
- Multiple Lung Nodules
- More than 10 diffuse Lung Nodule
III. Epidemiology
- More than 1.5 Million Lung Nodules are identified on lung imaging each year in U.S. (5% are malignant)
- Lung Nodule Incidence
- Chest XRay: 0.2% of all Chest XRays identify a Lung Nodule
- CT Chest: 13-15% of all scans identify a Lung Nodule
IV. Background
- Obtain CT Chest to further evaluate Lung Mass identified on Chest XRay
- Evaluation below is based on the CT Chest
- Compare findings to prior imaging (critical!)
V. Precautions
- Screening for Lung Nodules even in high risk groups (Tobacco users) has low yield of malignancy
VI. Differential Diagnosis: Lung Mass or Nodule
- Benign
- Benign Tumors (10%)
- Infectious Granuloma (80%)
- Cryptococcosis
- Histoplasmosis
- Tuberculosis (esp. apical, cavitary Lung Lesion)
- Atypical Mycobacteria
- Aspergillosis
- Coccidioidomycosis
- Lung Abscess
- Congenital Causes
- Arteriovenous Malformation
- Bronchogenic Cyst
- Rheumatologic
- Other causes
- Amyloidosis
- Intrapulmonary Lymph Node
- Malignant
- Lung Adenocarcinoma (60%)
- Lung Squamous Cell Carcinoma (20%)
- Metastasis to Breast, colon or Kidney (10%)
- Lung small cell carcinoma (4%)
- Other causes (uncommon to rare)
- Carcinoid Tumor
- Extranodal Lymphoma
VII. Differential Diagnosis: Anterior Mediastinal Mass (5 T's)
- Background: Seen on lateral Chest XRay obscuring heart-chest wall interface
- Thymoma (consider Myasthenia Gravis)
- Thyroid mass (retrosternal mass)
- Teratoma
- T-Cell Lymphoma
- "Terrible": Bronchogenic Carcinoma (most common cause)
VIII. Imaging: Modalities
-
Chest XRay (PA and lateral)
- Nodules at 5 mm may be visualized
- Poor Test Sensitivity (high False Negative Rate)
- Nodules often noted as incidental XRay finding
- CT Chest (thin slice)
- Greater Test Sensitivity and Test Specificity than Chest XRay
- CT is a first-line test in evaluation of Solitary Lung Nodules found on Chest XRay
- FDG-PET
- High Test Specificity and Test Sensitivity for Solitary Lung Nodules >8-10 mm
- Indicated when indeterminate findings persist on CT or findings discordant with estimated cancer risk
- False Positive uptake by some inflammatory or infectious Nodules
- MRI Chest
- Not recommended in evaluation of Solitary Lung Nodule
IX. Imaging: Re-assuring imaging findings suggestive of BENIGN Lesions
- Benign calcification patterns (central, concentric, popcorn-pattern, diffuse or complete)
- Smooth, solid lesions
- Dominant Nodule
- Location at the perifissure or subpleural
- Small lesions <6 mm
- Lesion doubling time <30 days (more consistent with infection)
- Lesion doubling time >400 days (slower growth)
X. Imaging: Red flag findings on CT Chest (suggestive of malignancy)
-
Nodule size >8 mm
- Contrast with benign lesions which are typically <5 mm in size
- Irregular border
- Contrast with benign lesions which have a smooth border
- Spiculated border
- Odds Ratio 2.8 for >4 mm Nodule
- Doubling time between 1 month and 1 year
- Contrast with benign lesions that double in weeks or over years
- Infection is more likely with fast growth <1 month
- Aggressive lung malignancies may double in size up to every 3-4 months
- Upper lobe location
- Contrast enhancement
- Non-enhancing lesion has 97% Negative Predictive Value for cancer
- Swenson (2000) Radiology 214: 73-80 [PubMed]
- Non-calcified lesion (or eccentric calcification)
- Non-calcified, ground-glass or eccentrically calcified lesions are a risk for malignant Nodules
- Other Calcification patterns (central, concentric, popcorn-pattern, diffuse or complete) suggest a benign lesion
- Semi-solid or subsolid Nodules (includes ground-glass appearance)
- Malignant in up to 63% of cases
- Contrast with 18% malignancy with ground-glass lesions
- Contrast with 7% malignancy with solid lesions
- Henschke (2002) AJR 178: 1053-7 [PubMed]
- Size (most important factor)
- Size 2-5 mm: Less than 1% malignancy risk
- Size 5-10 mm: 6-28% malignancy risk
- Size 11-20 mm: 33-60% malignancy risk
- Size 20-30 mm: 64-82% malignancy risk
- Wahidi (2007) Chest 132: 94-107 [PubMed]
- References
XI. Risk Factors: Lung Cancer (used below to distinguish low risk from high risk)
- See Lung Cancer
- Current or past Tobacco use
- History of >20 pack years of Tobacco Smoking
- Odds Ratio 7.9 for >7 mm Nodule (OR 2.2 for >4 mm Nodule)
- Age over 40 years
- Asbestos Exposure
- Family History of Lung Cancer
- Radiation Exposure (esp. Radon Gas)
- Immunocompromised (esp. HIV Infection)
- History of prior malignancy
- New Lung Nodule is an ominous finding in a patient with prior Lung Cancer history
- New Lung Nodule has a 25% risk of malignancy in a patient with extrathoracic cancer history
- Odds Ratio: 3.8 (for >4 mm Nodule)
XII. Grading: Lung-RADS
- Category 0: Incomplete (1% of cases)
- Requested prior CT Chest for comparison OR
- Could not evaluate part of lungs (additional CT imaging needed) OR
- Infectious or inflammatory process suspected (repeat low dose CT in 1 to 3 months)
- Category 1: Negative (39% of cases)
- No Lung Nodules found OR
- Lung Nodules with benign features (e.g. fat containing or calcification pattern complete, central, popcorn or concentric)
- Category 2: Benign (45% of cases)
- Juxtapleural node <10 mm mean diameter at baseline or NEW and solid, smooth margins and shape oval, lentiform, triangular OR
- Solid Nodule <6 mm at baseline or NEW <4 mm OR
- Part solid Nodule <6 mm total mean diameter at baseline OR
- Nonsolid Nodule (ground glass Nodule) <30 mm at baseline new or growing, or >30 mm stable or slow growing OR
- Airway Nodule, subsegmental at baseline, new or stable OR
- Category 3 Nodule that is stable or decreased in size at 6 month follow-up CT OR
- Category 3 or 4A Nodules that resolve on follow-up OR
- Category 4B findings that are proven benign with workup
- Category 3: Probably Benign (9% of cases, repeat low dose CT in 6 months)
- Solid Nodule >=6 to <8 mm baseline or NEW 4 to <6 mm OR
- Part solid Nodule >=6 mm Total mean diameter
- Baseline: Solid component <6 mm
- New: Solid component<6 mm in total diameter
- Nonsolid Nodule (ground glass Nodule) >=30 mm at baseline or new OR
- Atypical pulmonary cyst
- Growing cystic component (mean diameter) of a thick walled cyst OR
- Category 4A Nodule that is stable or decreased in size at 3 month follow-up CT (excluding airway Nodules)
- Category 4A: Suspicious (4% of cases, repeat low dose CT In 3 months, or obtain PET/CT if >8 mm solid Nodule or solid component)
- Solid Nodule >=8 to <15 mm at baseline or GROWING <8 mm or NEW 6 to <8 mm OR
- Part Solid Nodule >= 6 mm
- Solid component >=6 to <8 mm at baseline OR
- NEW or GROWING <4 mm solid component OR
- Airway Nodule, segmental or more proximal at baseline or new OR
- Atypical pulmonary cyst
- Thin walled cyst OR
- Multilocular cyst at baseline OR
- Multilocular cyst that had been thin or thick walled
- Category 4B: Very Suspicious (2% of cases, refer for further evaluation, multiple imaging and tissue sampling options)
- Airway Nodule, segmental or more proximal and stable or new OR
- Solid Nodule >=15 mm at baseline or NEW or GROWING >=8 mm OR
- Part solid Nodule
- Solid component >=8 mm at baseline OR
- NEW or GROWING >=4 mm solid component OR
- Atypical pulmonary cyst
- Thick walled cyst with growing wall thickness or nodularity OR
- Multilocular cyst growing mean diameter OR
- Multilocular cyst with increased loculation or new or increased nodularity, ground-glass, consolidation
- Slow growing solid or part solid Nodule with growth over multiple CT imaging studies
- Category 4X: Most Suspicious (<1% of cases, refer for further evaluation, multiple imaging and tissue sampling options)
- Category 3 or 4 Nodules with additional features that increase suspicion for Lung Cancer (e.g. spiculation, adenopathy)
- Modifiers
- Modifier S: Significant (10% of cases)
- May add "S" to any category to indicate significant findings unrelated to Lung Cancer
- Modifier S: Significant (10% of cases)
- References
XIII. Evaluation: Nodule 8-30 mm
-
General
- Lung Masses >30 mm are considered malignant until proven otherwise
- Discuss with pulmonology, thoracic surgery or radiology for work-up
- Some Lung Nodules may be distinguished as benign by appearance
- Benign calcified lesions (old ganuloma)
- Vascular pattern consistent with hamartoma or Arteriovenous Malformation
- Consider starting preoperative evaluation while awaiting biopsy
- Pulmonary Function Tests
- Electrocardiogram and other cardiac testing as needed
- Optimize comorbid conditions
- Cancer Probability Models (used below)
- Mayo Model
- PanCan (Brock University)
- BIMC Calculator
- U.S. VA Clinical Model
- Herder Model (uses PET/CT Findings)
- Low probability of cancer (<5% chance of cancer)
- Repeat Non-contrast CT chest in 3, 6, 9-12 and 18-24 months
- Intermediate probablity of cancer (5-65% chance of cancer)
- Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET)
- Preferred modality (with biopsy) as of 2013 ACCP Guidelines (esp. with pretest probability >5%)
- Interpretation
- Negative or mild update
- Follow low probability CT protocol as above
- Moderate or intense uptake
- Obtain biopsy via techniques below
- Negative or mild update
- Biopsy techniques (for moderate or intense uptake on FDG-PET)
- CT chest with trans-thoracic fine needle aspirate (TTNA)
- Prior to FDG-PET, was first choice due to high Specificity (97%) and high sensitivity (90%)
- Schreiber (2003) Chest 123:1155 [PubMed]
- Bronchoscopy with biopsy
- Video assisted thoracoscopic surgery with frozen sections and resection
- CT chest with trans-thoracic fine needle aspirate (TTNA)
- Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET)
- High probability of cancer (>65% chance of cancer)
- Perform staging including evaluation for metastases
- Consider Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) for staging
- Video assisted thoracoscopic surgery with frozen sections and resection
- Indicated if no metastases
- Perform staging including evaluation for metastases
XIV. Evaluation: Nodule <8 mm
- Two conflicting guidelines are listed
- Fleischner Society 2017
- American College of Chest Physicians 2013 (ACC)
- Approach to surveillance imaging for small Nodules
- Unless otherwise specified, use low-dose, non-contrast CT Chest for surveillance (lower radiation)
- Malignant Nodules double in volume within 400 days
- A Lung Nodule without change over 2 years is considered benign
- Exception: Ground glass lesions have slower doubling time and require longer observation
- High risk patients have Lung Cancer risk factors
- Tobacco Abuse history
- Age >65 years old
- Malignancy history
- Small Nodule <6 mm
- Low risk patient
- High risk patient
- Single Nodule 6 to 8 mm
- Multiple Nodules with largest 6 to 8 mm
- Fleischner: Repeat noncontrast CT chest in 3 to 6 months AND again in 18-24 months
XV. Evaluation: Subsolid Lung Nodules (semi-solid, non-solid, Fleischner Society 2017)
- Solitary pure-ground glass Nodule
- Lung Nodules <6 mm
- No further CT follow-up
- Lung Nodules >=6 mm
- Repeat noncontrast chest CT at 6 to 12 months AND
- If persistent, repeat noncontrast CT chest every 2 years for a total of 5 years
- Lung Nodules <6 mm
- Solitary part-solid Nodule
- Multiple Nodules
XVI. Evaluation: Lung Cancer Screening Low-Dose, Noncontrast CT Chest
- Screening Indications: Annual Screening Low Dose Noncontrast CT Chest Indications (per USPTF 2021 and medicare)
- Adults 50 to 80 years old with >20 pack year history of smoking AND
- Currently smoking or quit within last 15 years
- Indications to stop screening
- Patients who have quit smoking for >15 years
- Limited Life Expectancy <10 years
- Patient unwilling to undergo curative lung surgery
- Advantages
- Number Needed to Screen in 5 years to prevent one death: 312
- All cause mortality Relative Risk Reduction: 6.7%
- Disadvantages
- Cummulative radiation and cost ($12 billion/year) with annual screening will be substantial
- High False Positive Rate with screening (96%) will require significant resources to evaluate
- Up to 27% of screening imaging identifies a Lung Nodule (1.1% are malignant)
- Negative noncontrast CT Chest
- Criteria
- No Lung Nodules OR
- Lung Nodules with specific calcification pattern (complete, central or popcorn calcification)
- Approach
- Consider repeat low-dose, noncontrast CT Chest in 12 months
- Criteria
- Benign noncontrast CT Chest
- Probably benign noncontrast CT Chest
- Suspicious noncontrast CT Chest
- Criteria
- Solid Lung Nodules (8-15 mm or growing at <8 mm or new 6-8 mm) OR
- Part-solid Lung Nodules >=6 mm total diameter AND solid component 6-8 mm OR
- Endobronchial Nodule
- Approach
- Repeat low-dose, noncontrast CT Chest in 3 months
- Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) when >=8 mm solid component
- Criteria
- Very suspicious noncontrast CT Chest
- Criteria
- Solid Lung Nodules (>=15 mm or growing at >8 mm)
- Approach
- Chest CT with and without contrast
- Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) when >=8 mm solid component
- Criteria
- Resources
- ACR Guidelines (accessed 12/14/2015)
- USPTF Guidelines (updated 2021)
- References
- Aberle (2011) N Engl J Med 365(5): 395-409 [PubMed]
- Church (2013) N Engl J Med 368(21): 1980-91 [PubMed]
- de Koning (2020) N Engl J Med 382(6): 503-13 [PubMed]
- Jonas (2021) JAMA 325(10): 971-87 [PubMed]
- Gates (2014) Am Fam Physician 90(9): 625-31 [PubMed]
- Kovalchik (2013) N Engl J Med 369(3): 245-54 [PubMed]
- Krist (2021) JAMA 325(10): 962-70 [PubMed]
XVII. Resources
- Online calculator of Lung Cancer risk
- https://siteman.wustl.edu/prevention/ydr/
- Establishes pretest probability of cancer and helps drive evaluation based on patient risk
XVIII. References
- Midthun (2011) Internal Medicine, Mayo Conference, Kauai
- Swadron (2019) Pulmonary 2, CCME Emergency Medicine Board Review, accessed 6/16/2019
- Albert (2009) Am Fam Physician 80(8): 827-31 [PubMed]
- Gould (2013) Chest 143(5 suppl):e935-1205 +PMID:23649456 [PubMed]
- Gould (2007) Chest 132(suppl 3):108S-130S [PubMed]
- Hitzeman (2014) Am Fam Physician 90(11): 784-9 [PubMed]
- Kikano (2015) Am Fam Physician 92(12): 1084-91 [PubMed]
- Langan (2023) Am Fam Physician 107(3): 282-91 [PubMed]
- Loverdos (2019) Ann Thoracic Med 14(4): 226-38 [PubMed]
- MacMahon (2005) Radiology 237(2):395-400 [PubMed]
- MacMahon (2017) Radiology 284(1): 228-243 +PMID:28240562 [PubMed]