The Solitary Pulmonary Nodule

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The Solitary Pulmonary Nodule

• Suneel S. Kumar MD

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The Solitary Pulmonary Nodule

• Coin lesion
• Defined as lt 3 cm
• Completely surrounded by lung parenchyma
• Lesions gt 3 cm called masses and often malignant

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The Solitary Pulmonary Nodule

• Incidence of cancer from 10 70
• Found on 0.09 to 0.20 of all CXRs
  (approximately 1 in 500)
• 90 incidental findings
• 150,000 SPNs found annually
• Increased with incidental findings on CT

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The Solitary Pulmonary Nodule

• Patients with best prognosis are stage IA
  (T1N0M0)
• 61 75 5-year survival following surgical
  resection
• Approximately half of all lung cancers have
  extrapulmonary spread by time of diagnosis
• 5-year survival 10 15

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The Solitary Pulmonary Nodule

• Most SPNs are benign
• Primary malignancy found in about 35
• Solitary metastases may account for 23

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Differential Diagnosis

• Neoplasm
• Infection
• Inflammation
• Vascular lesion
• Post-traumatic
• Congenital
• Lung cyst
• Pulmonary infarct
• Amyloidosis

• Rheumatoid nodules
• Intrapulmonary lymph nodes
• Plasma cell granulomas
• Sarcoidosis
• Mucoid impaction
• Hematoma
• Nipple shadow

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The Solitary Pulmonary Nodule

• Since the SPN by definition is a radiographic
  finding, radiological imaging is intrinsic to the
  diagnostic workup

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Radiology

• Failure to recognize lung cancer on CXR is one of
  most frequent causes of missed diagnosis in
  radiology
• Rate of failure to diagnose ranges from 25 90
  in different studies with different designs
• Error rate of 20 50 for radiological detection
  of lung cancer is generally accepted

Guiss, Cancer 19601391-5
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Radiology

• Study looked back at CXRs in 259 patients with
  proven NSCLC
• Found 19 incidence of missed diagnosis
• Those missed had significantly smaller nodules
  (median diameter 16 mm), more superimposing
  structures, and more indistinct borders

Quekel, Chest 1999115720-32
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Radiology

• Time of delay in diagnosis was significant at 472
  vs 29 days
• Resulted in 43 of lesions being upstaged from T1
  to T2 during the delay period

Quekel, Chest 1999115720-32
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Patterns of Margins

• Corona radiata sign
• Fine linear strands extending 4-5 mm outward
• Spiculated on CXRs
• 84 90 are malignant

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Patterns of Margins
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Patterns of Margins
Spiculated lipoid pneumonia
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Patterns of Margins

• Scalloped border
• Intermediate probability of cancer
• Smooth border suggestive of benign diagnosis

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Other Characteristics

• Air bronchograms and pseudocavitation more
  commonly malignant
• Cavitation with thick (gt15 mm vs lt 5 mm) more
  often maligant

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Air Bronchograms
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Calcification

• Suggests benign diagnosis
• With CT the reference standard, CXR has
  sensitivity 50, specificity 87, and PPV 93 for
  identifying calcification

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Calcification

• Laminated or central pattern typical of granuloma

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Histoplasmoma
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Popcorn Calcification

• Classic popcorn pattern often seen in
  hamartomas
• HRCT can show fat and cartilage in half of cases

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Hamartoma
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Calcification

• Stippled or eccentric patterns
• Have been associated with cancer

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Calcification
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Rounded Atelectasis
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Rounded Atelectasis
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Growth Rate

• Volume-doubling time for malignant bronchogenic
  tumors rarely lt 1 month or gt 1 year
• If considered spherical, 30 increase in diameter
  represents a doubling of volume

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Growth Rate

• Traditionally, stability of SPN on CXR for 2
  years suggested benign disease
• Bronchoalveolar cell carcinoma and typical
  carcinoids occasionally appear stable for more
  than 2 years
• Hamartomas often grow over time
• Initial studies were retrospective and reviewed
  only cases which were resected

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Growth Rate

• One study examined 156 solitary lesions 1 14 cm
  in size
• Previous CXR in 74
• Previously documented no growth in 26
• 9 of these were malignant
• Absence of growth over 2 years on CXR has
  predictive value of 65 for benign lesions

Yankelevitz, Am J Roentgenol 1997168325-8
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Growth Rate

• Use of stability predicated on accurate
  measurement of growth
• Thus, it is dependent on resolution of imaging
  technique
• Thin-section high-resolution CT has better
  estimation of nodule size and growth
  characteristics

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Growth Rate

• Limit of detectable changes on CXR estimated to
  be 3 5 mm
• CT has resolution of 0.3 mm
• Reasonable to use two-year stability on CT as a
  practical guideline

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Follow-Up

• Optimal time not known
• Traditionally follow every three months for first
  year, then six months the second year
• Provided CT is used

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Nonsurgical Approaches

• CT Densitometry
• Contrast-enhanced CT
• Bronchoscopy
• Transthoracic fine needle aspiration biopsy
• Positron emission tomography

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CT Densitometry

• Involves measurement of attenuation values
• Expressed in Hounsfield units, as compared to
  reference phantom
• Usually higher for benign nodules
• Allows for identification of 35 55 of
  subsequently identified benign lesions

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CT Densitometry

• One large, multicenter trial, only 1 of 66
  nodules identified as benign later found to be
  malignant
• Cutoff used was 264 Hounsfield units
• More conventional cutoff is 185, which yielded a
  higher false negative rate

Zerhouni, Radiology 1986160319-27
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Contrast-Enhanced CT

• Degree on enhancement on spiral CT after
  injection of contrast
• One study used an increase in attenuation of 20
  Hounsfield units as threshold for malignant
  lesions
• Sensitivity 95-100, specificity 70-93
• Awaits further validation
• Local expertise varies, and not widely used

Zhang, Radiology 1997205471-8
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Bronchoscopy

• Useful for lesions at least 2 cm
• Diagnostic yield varies in literature from 20
  80, depending on size of nodule and patient
  population
• Yield depends on nodule size and proximity to
  bronchial tree

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Bronchoscopy

• Yield 10 for lt 1.5 cm, and 40 60 for gt 2 3
  cm
• 70 yield when CT reveals a bronchus leading to
  lesion

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Bronchoscopy

• Relatively low risk
• Overall complication rate 5
• 3 risk of pneumothorax
• 1 risk of hemorrhage
• 0.24 risk of death

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Transthoracic FNA

• Diagnostic yield up to 95 in peripheral lesions
• Higher complication rate
• 30 pneumothorax
• About 5 of these require chest tube

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Positron Emission Tomography

• Uptake of 18-flurodeoxyglucose used to measure
  glucose metabolism
• Taken up by cells in glycolysis but is bound
  within cells and cannot enter normal glycolytic
  pathway
• Most tumors have greater uptake of FDG than
  normal tissue
• Due to increased metabolic activity

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Positron Emission Tomography

• Sensitivity for identifying a malignancy is 96.8
  and specificity 77.8
• False negatives can occur
• Notable in association with bronchoalveolar
  carcinoma, carcinoids, and tumors lt 1 cm in
  diameter

Gould, JAMA 2001285914-24
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Positron Emission Tomography

• For 450 nodules reviewed in a meta-analysis, mean
  sensitivity was 93.9 and specificity 85.8
• Median sensitivity 98 and specificity 83.3

Gould, JAMA 2001285914-24
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Gould, JAMA 2001285914-24
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Gould, JAMA 2001285914-24
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Gould, JAMA 2001285914-24
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Positron Emission Tomography

• For diagnosis of benign nodules, sensitivity 96
  and specificity 88 with 94 accuracy
• False positives usually in association with
  infectious or inflammatory processes

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Positron Emission Tomography

• Resolution is currently 7 8 mm
• Imaging of nodules lt 1 cm unreliable

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Positron Emission Tomography

• May provide staging information
• Up to 14 of patients otherwise eligible for
  surgery have occult extra thoracic disease on
  whole-body PET

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PET Images
Pieterman, NEJM 2000343254-61
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PET Images
Pieterman, NEJM 2000343254-61
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Integrated PET and CT
Lardinos, NEJM 20033482500-7
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Integrated PET and CT
Lardinos, NEJM 20033482500-7
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Positron Emission Tomography

• Decision-analysis model constructed to assess
  cost effectiveness showed strategy of CT combined
  with PET for staging was often superior to
  conventional approaches
• Reduced number of surgeries by 15
• Estimated cost savings per patient ranged from
  91 to 2,200 per patient

Gambhir, J Clin Oncol 1998162113-25
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Positron Emission Tomography

• More expensive than other imaging modalities
• Medicare reimbursement of 1,912 compared to
  chest CT (276) or transthoracic needle
  aspiration (560)

http//cms.hhs.gov, Dec 2002
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Positron Emission Tomography

• Question of using PET dependent on when clinical
  decision making will be changed by its findings
• Low-risk patients (pretest probability of
  malignancy 20) have posttest likelihood of
  malignancy with negative PET of 1
• Would support observation in this population with
  serial CT scans

Gould, JAMA 2001285914-24
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Positron Emission Tomography

• High-risk patients (pretest probability of
  malignancy 80) with negative PET still have 14
  posttest likelihood of malignancy
• Those with high risk of malignancy should have
  tissue diagnosis

Gould, JAMA 2001285914-24
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Positron Emission Tomography

• No indication for PET
• Negative lymph nodes on CT if operative
  intervention definitely planned or if it will
  otherwise not change management
• Known malignancy who has a questionable pulmonary
  metastasis vs primary lung cancer

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Positron Emission Tomography

• Some gamma cameras can now have PET capability
  added to them
• Question if these modified gamma cameras have
  same ability to detect malignant processes as
  specific PET equipment
• Requires further study

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Diagnostic Strategy

• Pretest probability of cancer determines most
  cost-effective strategy
• Low (lt 12) radiographic follow-up
• Intermediate (12 69) CT and PET
• High (gt 69 90) CT followed by biopsy or
  surgery
• Very high (gt 90) surgery

Gambhir, J Clin Oncol 1998162113-25
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Diagnostic Strategy
Ost, NEJM 20033482535-42
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Diagnostic Strategy

• Determining probability of cancer remains an
  inexact science
• Multivariate model incorporating age,
  cigarette-smoking status, history of cancer,
  diameter of nodule, presence of spiculation, and
  location of nodule proven similar to expert
  physician judgment in predicting cancer

Swenson, Arch Intern Med 1997157849-55
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Diagnostic Strategy
Ost, NEJM 20033482535-42
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