Lung Nodule

Aka: Lung Nodule, Pulmonary Nodule, Lung Mass, Lung Lesion, Coin Lesion of Lung, Solitary Lung Nodule, Solitary Pulmonary Nodule, Lung Incidentaloma, Lung Neoplasm, Lung Cancer Screening CT Chest, Mediastinal Mass

1. See Also
   1. Incidentaloma
2. Definition
   1. Lung Nodule
      1. Spherical opacity on xray <3 cm in diameter
      2. Completely surrounded by aerated lung
   2. Solitary Lung Nodule
      1. Isolated, single Lung Nodule
   3. Lung Mass
      1. Lung Lesion >3 cm diameter
      2. Considered to be Lung Cancer until proven otherwise
   4. Multiple Lung Nodules
      1. More than 10 diffuse Lung Nodule
3. Epidemiology
   1. Lung Nodule Incidence
      1. Chest XRay: 0.2% of all Chest XRays identify a Lung Nodule
      2. CT Chest: 13-15% of all scans identify a Lung Nodule
4. Background
   1. Obtain CT Chest to further evaluate Lung Mass identified on Chest XRay
   2. Evaluation below is based on the CT Chest
   3. Compare findings to prior imaging (critical!)
5. Precautions
   1. Screening for Lung Nodules even in high risk groups (Tobacco users) has low yield of malignancy
      1. McWilliams (2013) N Engl J Med 369(10): 910-9 [PubMed]
6. Differential Diagnosis: Lung Mass
   1. Benign
      1. Lung Hamartoma (10%)
      2. Infectious Granuloma (80%)
         1. Cryptococcosis
         2. Histoplasmosis
         3. Tuberculosis (esp. apical, cavitary Lung Lesion)
         4. Atypical Mycobacteria
         5. Aspergillosis
         6. Coccidioidomycosis
      3. Other causes (uncommon to rare)
         1. Arteriovenous Malformation
         2. Intrapulmonary Lymph Node
         3. Sarcoidosis
   2. Malignant
      1. Lung Adenocarcinoma (60%)
      2. Lung Squamous Cell Carcinoma (20%)
      3. Metastasis to Breast, colon or Kidney (10%)
      4. Lung small cell carcinoma (4%)
      5. Other causes (uncommon to rare)
         1. Carcinoid Tumor
         2. Extranodal Lymphoma
7. Differential Diagnosis: Anterior Mediastinal Mass (5 T's)
   1. Background: Seen on lateral Chest XRay obscuring heart-chest wall interface
   2. Thymoma (consider Myasthenia Gravis)
   3. Thyroid mass (retrosternal mass)
   4. Teratoma
   5. T-Cell Lymphoma
   6. "Terrible": Bronchogenic Carcinoma (most common cause)
8. Imaging: Modalities
   1. Chest XRay (PA and lateral)
      1. Nodules at 5 mm may be visualized
      2. Poor Test Sensitivity (high False Negative Rate)
      3. Nodules often noted as incidental XRay finding
   2. CT Chest (thin slice)
      1. Greater Test Sensitivity and Test Specificity than Chest XRay
      2. CT is a first-line test in evaluation of Solitary Lung Nodules found on Chest XRay
   3. FDG-PET
      1. High Test Specificity and Test Sensitivity for Solitary Lung Nodules >8-10 mm
      2. Indicated when indeterminate findings persist on CT or findings discordant with estimated cancer risk
   4. MRI Chest
      1. Not recommended in evaluation of Solitary Lung Nodule
9. Imaging: Red flag findings on CT Chest (suggestive of malignancy)
   1. Non-calcified or eccentric calcification
   2. Nodule size >8 mm
      1. Contrast with benign lesions which are typically <5 mm in size
   3. Irregular or spiculated border
      1. Contrast with benign lesions which have a smooth border
   4. Non-solid, ground-glass appearance
      1. Contrast with benign lesions that are dense and solid
   5. Doubling time between 1 month and 1 year
      1. Contrast with benign lesions that double in weeks or over years
10. Risk Factors: Lung Cancer (used below to distinguish low risk from high risk)
    1. Current or past Tobacco use
       1. Odds Ratio 7.9 for >7 mm Nodule (OR 2.2 for >4 mm Nodule)
    2. Age over 40 years
    3. Asbestos Exposure
    4. Family History of Lung Cancer
    5. History of prior malignancy
       1. New Lung Nodule is an ominous finding in a patient with prior Lung Cancer history
       2. New Lung Nodule has a 25% risk of malignancy in a patient with extrathoracic cancer history
          1. Odds Ratio: 3.8 (for >4 mm Nodule)
    6. Worrisome findings on imaging (general)
       1. Nodule >8 mm
       2. Irregular borders
       3. Eccentric calcification or non-calcified
       4. Spiculation
          1. Odds Ratio 2.8 for >4 mm Nodule
       5. Non-solid or subsolid Nodule (ground glass or part solid)
       6. Size doubling time 1 month to 1 year (infection more likely with faster growth <1 month)
    7. Upper lobe location
       1. Swenson (1997) Arch Intern Med 157: 849-55 [PubMed]
    8. Contrast enhancement
       1. Non-enhancing lesion has 97% Negative Predictive Value for cancer
       2. Swenson (2000) Radiology 214: 73-80 [PubMed]
    9. Non-calcified lesion
       1. Calcification either centrally or completely suggests a benign lesion
    10. Semi-solid Nodules or subsolid/non-solid (63% malignant)
        1. Contrast with 18% malignancy with ground-glass lesions
        2. Contrast with 7% malignancy with solid lesions
        3. Henschke (2002) AJR 178: 1053-7 [PubMed]
    11. Size (most important factor)
        1. Size 2-5 mm: Less than 1% malignancy risk
        2. Size 5-10 mm: 6-28% malignancy risk
        3. Size 11-20 mm: 33-60% malignancy risk
        4. Size 20-30 mm: 64-82% malignancy risk
        5. Wahidi (2007) Chest 132: 94-107 [PubMed]
    12. References
        1. Swensen (2003) Radiology 226(3): 756-61 [PubMed]
        2. Gould (2007) Chest 131(2): 383-8 [PubMed]
11. Evaluation: Nodule 8-30 mm
    1. General
       1. Discuss with pulmonology, thoracic surgery or radiology for work-up
       2. Some Lung Nodules may be distinguished as benign by appearance
          1. Benign calcified lesions (old ganuloma)
          2. Vascular pattern consistent with hamartoma or Arteriovenous Malformation
       3. Cancer probability (used below) is calculated from VA Model or Mayo Model
       4. Consider starting preoperative evaluation while awaiting biopsy
          1. Pulmonary Function Tests
          2. Electrocardiogram and other cardiac testing as needed
          3. Optimize comorbid conditions
    2. Low probability of cancer (<5% chance of cancer)
       1. Repeat Non-contrast CT chest in 3, 6, 9-12 and 18-24 months
    3. Intermediate probablity of cancer (5-65% chance of cancer)
       1. Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET)
          1. Preferred modality (with biopsy) as of 2013 ACCP Guidelines (esp. with pretest probability >5%)
          2. Interpretation
             1. Negative or mild update
                1. Follow low probability CT protocol as above
             2. Moderate or intense uptake
                1. Obtain biopsy via techniques below
       2. Biopsy techniques (for moderate or intense uptake on FDG-PET)
          1. CT chest with trans-thoracic fine needle aspirate (TTNA)
             1. Prior to FDG-PET, was first choice due to high Specificity (97%) and high sensitivity (90%)
             2. Schreiber (2003) Chest 123:1155 [PubMed]
          2. Bronchoscopy with biopsy
             1. Video assisted thoracoscopic surgery with frozen sections and resection
    4. High probability of cancer (>65% chance of cancer)
       1. Perform staging including evaluation for metastases
          1. Consider Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) for staging
       2. Video assisted thoracoscopic surgery with frozen sections and resection
          1. Indicated if no metastases
12. Evaluation: Nodule <8 mm (Fleischner Society 2017)
    1. Approach to surveillance imaging for small Nodules
       1. Unless otherwise specified, use low-dose, non-contrast CT Chest for surveillance (lower radiation)
       2. Malignant Nodules double in volume within 400 days
          1. A Lung Nodule without change over 2 years is considered benign
          2. Exception: Ground glass lesions have slower doubling time and require longer observation
       3. High risk patients have Lung Cancer risk factors
          1. Tobacco Abuse history
          2. Age >65 years old
          3. Malignancy history
    2. Nodule <6 mm
       1. Low risk patient
          1. Require no further follow-up for either single or multiple Nodules <6 mm
       2. High risk patient
          1. Optional follow-up Chest CT in 12 months for either single or multiple Nodules
    3. Single Nodule 6 to 8 mm
       1. Repeat noncontrast CT chest in 6-12 months AND
       2. Repeat noncontrast CT chest again in 18-24 months
    4. Multiple Nodules with largest 6 to 8 mm
       1. Repeat noncontrast CT chest in 3 to 6 months AND
       2. Repeat noncontrast CT chest again in 18-24 months
13. Evaluation: Subsolid Lung Nodules (semi-solid, non-solid, Fleischner Society 2017)
    1. Solitary pure-ground glass Nodule
       1. Lung Nodules <6 mm
          1. No further CT follow-up
       2. Lung Nodules >=6 mm
          1. Repeat noncontrast chest CT at 6 to 12 months AND
          2. If persistent, repeat noncontrast CT chest every 2 years for a total of 5 years
    2. Solitary part-solid Nodule
       1. Repeat noncontrast chest CT at 3 months to confirm persistence
       2. Persistent Nodules <6 mm
          1. No follow-up needed for Nodules <6 mm
          2. However Nodules are not distinguished as solid until 6 mm
       3. Persistent Nodules >=6 mm
          1. Solid component >6 mm
             1. Refer for Nodule biopsy or Nodule resection
             2. Part solid Nodules are considered suspicious lesions
          2. Solid component <6 mm
             1. Follow-up CT at 3 to 6 months to confirm persistent AND
             2. if persistent and solid component <6 mm, repeat annual CT for 5 years
    3. Multiple Nodules
       1. Follow-up Chest CT at 3 to 6 months
       2. Consider repeat Chest CT at 2 and 4 years in high risk patients
       3. Management is based on most suspicious Nodule
       4. Discuss with pulmonology, thoracic surgery or radiology for CT surveillance versus Nodule biopsy
       5. Evaluate for malignancy probability
14. Evaluation: Lung Cancer Screening low-dose, noncontrast CT Chest
    1. Annual Screening low dose noncontrast CT Chest Indications (USPTF 2021 and medicare recommendations)
       1. Adults 50 to 80 years old with >20 pack year history of smoking AND
       2. Currently smoking or quit within last 15 years
    2. Advantages
       1. Number Needed to Screen in 5 years to prevent one death: 312
       2. All cause mortality Relative Risk Reduction: 6.7%
    3. Disadvantages
       1. Cummulative radiation and cost ($12 billion/year) with annual screening will be substantial
       2. High False Positive Rate with screening (96%) will require significant resources to evaluate
    4. Indications to stop screening
       1. Patients who have quit smoking for >15 years
       2. Limited Life Expectancy <10 years
       3. Patient unwilling to undergo curative lung surgery
    5. Guidelines updated 2021 (USPTF)
       1. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/lung-cancer-screening
       2. Aberle (2011) N Engl J Med 365(5): 395-409 [PubMed]
       3. de Koning (2020) N Engl J Med 382(6): 503-13 [PubMed]
       4. Jonas (2021) JAMA 325(10): 971-87 [PubMed]
       5. Gates (2014) Am Fam Physician 90(9): 625-31 [PubMed]
       6. Kovalchik (2013) N Engl J Med 369(3): 245-54 [PubMed]
       7. Krist (2021) JAMA 325(10): 962-70 [PubMed]
    6. Negative noncontrast CT Chest
       1. Criteria
          1. No Lung Nodules OR
          2. Lung Nodules with specific calcification pattern (complete, central or popcorn calcification)
       2. Approach
          1. Consider repeat low-dose, noncontrast CT Chest in 12 months
    7. Benign noncontrast CT Chest
       1. Criteria
          1. Solid Lung Nodules (<6 mm or new Nodules <4 mm) OR
          2. Part-solid Lung Nodules <6 mm total diameter at baseline OR
          3. Ground-glass Lung Nodules <20 mm OR unchanged/slowly growing and >20 mm
       2. Approach
          1. Consider repeat low-dose, noncontrast CT Chest in 12 months
    8. Probably benign noncontrast CT Chest
       1. Criteria
          1. Solid Lung Nodules (6-8 mm or new Nodules 4-6 mm) OR
          2. Part-solid Lung Nodules >=6 mm total diameter AND solid component <6 mm OR
          3. Ground-glass Lung Nodules >=20 mm (baseline CT or new)
       2. Approach
          1. Repeat low-dose, noncontrast CT Chest in 6 months
    9. Suspicious noncontrast CT Chest
       1. Criteria
          1. Solid Lung Nodules (8-15 mm or growing at <8 mm or new 6-8 mm) OR
          2. Part-solid Lung Nodules >=6 mm total diameter AND solid component 6-8 mm OR
          3. Endobronchial Nodule
       2. Approach
          1. Repeat low-dose, noncontrast CT Chest in 3 months
          2. Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) when >=8 mm solid component
    10. Very suspicious noncontrast CT Chest
        1. Criteria
           1. Solid Lung Nodules (>=15 mm or growing at >8 mm)
        2. Approach
           1. Chest CT with and without contrast
           2. Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) when >=8 mm solid component
    11. References
        1. ACR Guidelines (accessed 12/14/2015)
           1. https://www.acr.org/~/media/ACR/Documents/PDF/QualitySafety/Resources/LungRADS/AssessmentCategories.pdf
15. Resources
    1. Online calculator of Lung Cancer risk
       1. http://www.yourdiseaserisk.wustl.edu/
       2. http://reference.medscape.com/calculator/solitary-pulmonary-nodule-risk
       3. Establishes pretest probability of cancer and helps drive evaluation based on patient risk
16. References
    1. Midthun (2011) Internal Medicine, Mayo Conference, Kauai
    2. Swadron (2019) Pulmonary 2, CCME Emergency Medicine Board Review, accessed 6/16/2019
    3. Albert (2009) Am Fam Physician 80(8): 827-31 [PubMed]
    4. Gould (2013) Chest 143(5 suppl):e935-1205 +PMID:23649456 [PubMed]
    5. Gould (2007) Chest 132(suppl 3):108S-130S [PubMed]
    6. Hitzeman (2014) Am Fam Physician 90(11): 784-9 [PubMed]
    7. Kikano (2015) Am Fam Physician 92(12): 1084-91 [PubMed]
    8. MacMahon (2005) Radiology 237(2):395-400 [PubMed]
    9. MacMahon (2017) Radiology 284(1): 228-243 +PMID:28240562 [PubMed]