The Solitary Pulmonary Nodule RevisitedNodule The Solitary Pulmonary Nodule RevisitedNodule Revisited

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    The Solitary Pulmonary The Solitary Pulmonary Nodule RevisitedNodule RevisitedNodule RevisitedNodule Revisited

    Eric Bensadoun MDEric Bensadoun MD Division of Pulmonary, Critical Care, and Sleep MedicineDivision of Pulmonary, Critical Care, and Sleep Medicine

    Multidisciplinary Lung Cancer ClinicMultidisciplinary Lung Cancer Clinicp y gp y g University of KentuckyUniversity of Kentucky

    DefinitionsDefinitions

    • Solitary Pulmonary Nodule (SPN) A discrete more or less rounded

    SPNSPN

    – A discrete, more or less rounded opacity < 3 cm in diameter, completely surrounded by lung parenchyma without associated adenopathy, atelectasis or pneumonia

    Lung MassLung Mass

    • Lung Mass – A discrete more or less rounded

    opacity > 3 cm in diameter

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    Common Causes of SPNsCommon Causes of SPNs

    MalignantMalignant BenignBenign

    Primary lung carcinoma Primary lung carcinoma Infectious Granulomas Infectious Granulomas

    Solitary metastasis Solitary metastasis HamartomaHamartoma

    Carcinoid tumorCarcinoid tumor Round pneumoniaRound pneumonia

    Primary lung lymphomaPrimary lung lymphoma AA--V malformationV malformation

    Rheumatoid noduleRheumatoid nodule

    Wegener’s granulomatosisWegener’s granulomatosis

    PseudonodulePseudonodule

    SPN: Prevalence of MalignancySPN: Prevalence of Malignancy

    StudyStudy Total # Total # of nodulesof nodules MalignantMalignant

    N d l (%)N d l (%) yy of nodulesof nodules Nodules (%)Nodules (%)

    Steele et al (1963)Steele et al (1963) 887 36

    VA Cooperative Study VA Cooperative Study (1975)(1975) 1134 32

    Toomes et al (1983)Toomes et al (1983) 955 49

    Rubins et al (1996)Rubins et al (1996) 370 79

    Early Lung Cancer Action Project (ELCAP) (1999)

    233 8.6

    Mayo Clinic Study (2002) 782 1.8

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    SPN Management: An Approach Based SPN Management: An Approach Based on the Probability of Malignancyon the Probability of Malignancy

    SPNSPN

    Probability assessmentProbability assessment based on clinical based on clinical and CT findingsand CT findings

    VATS orVATS or ThoracotomyThoracotomy

    Observation with Observation with serial imagingserial imaging

    “Watchful waiting”“Watchful waiting”

    More testing suchMore testing such as PET, FNA toas PET, FNA to

    further define riskfurther define risk

    Calculating Probability: Art or Science?Calculating Probability: Art or Science?

    • Informal estimate by clinician or radiologist based on risk factors test results and experienceon risk factors, test results and experience

    • Bayesian analysis – Uses likelihood ratios of various risk factors and imaging

    results to calculate the probability of cancer – Bayesian models assume variables are independent i.e., no

    interaction – Probability can be determined using Bayesian model at y g y

    this free website: www. chestx-ray.com • In general, assessments by prediction models are

    similar to those of experienced clinicians

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    SPN: Risk AssessmentSPN: Risk Assessment

    • Assess the risk of malignancy in each individual ti t b s d H P d si l i si t sts:patient based on H+P and simple non-invasive tests:

    – Clinical risk factors – Radiographic finding on CXR and/or CT

    • Use additional testing if necessary – Contrast enhanced CT and/or PET – Transthoracic needle biopsy or bronchoscopy

    • Based on the above risk assessment decide on the next step:

    – VATS or thoracotomy – Close observation with serial radiographic imaging

    Clinical Risk Factors for CaClinical Risk Factors for Ca

    • Age Risk of malignancy increases with age– Risk of malignancy increases with age

    – Malignancy very uncommon in patients < 35 yrs old

    • Smoking history – Risk increases with # pack-years – Ex-smokers still at risk

    • Prior history of malignancyy g y – 70-80% of SPNs are malignant (solitary metastasis or

    lung primary)

    • Symptoms – Most patients are asymptomatic

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    SPN: Imaging SPN: Imaging

    • CXR/CT characteristics – Size – Edge/margin characteristics – Presence of calcification and/or fat – Growth rate

    Prevalence of Malignancy Based on SizePrevalence of Malignancy Based on Size

    100

    94%94%

    Lung MassLung Mass

    20

    40

    60

    80

    Pe rc

    en t M

    al ig

    na nt

    31%31%

    48%48%

    82%82%

    0

    20

    3

    Nodule Diameter (cm)

    n=58 n=197 n=149 n=100

    Pooled data from Zerhouni et al, Radiology 1986; 160: 319Pooled data from Zerhouni et al, Radiology 1986; 160: 319--327 327 and Siegelman et al, Radiology 1986; 160: 307and Siegelman et al, Radiology 1986; 160: 307--312. (total n=886)312. (total n=886)

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    Calcifications in SPNsCalcifications in SPNs

    • The presence of a benign pattern of calcification is i di ti f b i it (LR 0 01)indicative of benignity (LR=0.01)

    • Detection of calcifications on CXR (Berger et al. AJR 2001)(Berger et al. AJR 2001) • Sensitivity: 50% • Specificity: 81%

    • Thin-cut CT is gold standard for detection of and characterization of calcification within SPNsf f w

    • 6% of malignant nodules have Ca++ detected on CT – 85% of these tumors are >3 cm – Often punctate or eccentric pattern

    Patterns of Calcifications Patterns of Calcifications

    DIFFUSEDIFFUSE CENTRALCENTRAL POPCORNPOPCORNLAMINARLAMINAR

    ECCENTRICECCENTRIC STIPPLEDSTIPPLED

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    Nodule Margins in SPNsNodule Margins in SPNs

    SmoothSmooth LobulatedLobulated

    IrregularIrregular SpiculatedSpiculated

    DiagnosisDiagnosis SpiculatedSpiculated LobulatedLobulated SmoothSmooth

    Margin Characteristics of SPNsMargin Characteristics of SPNs

    DiagnosisDiagnosis SpiculatedSpiculated LobulatedLobulated SmoothSmooth

    Primary lung carcinoma 257 (84%) 112 (28%) 21 (11%)

    Solitary metastasis 13 (4%) 62 (16%) 34 (18%)

    Benign nodule 36 (12%) 222 (56%) 132 (71%)

    Pooled data from Zerhouni et al, Radiology 1986; 160: 319Pooled data from Zerhouni et al, Radiology 1986; 160: 319--327 327 and Siegelman et al, Radiology 1986; 160: 307and Siegelman et al, Radiology 1986; 160: 307--312312

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    SPN: Other Radiological SignsSPN: Other Radiological Signs

    • Intranodular fat on CT is a reliable indicator of a Intranodular fat on CT is a reliable indicator of a hamartoma – 20/20 nodules with fat or fat and Ca++ seen on CT scan

    were hamartomas (Siegelman et al, Radiology 1986)

    • Cavitation can be seen with both benign and malignant nodule (Woodring et al, AJR 1983)g – 95% of lesions with wall thickness < 5mm were benign – 84% of lesions with wall thickness > 15mm were malignant

    SPN: Growth RatesSPN: Growth Rates

    • The growth rate is expressed as the doubling time hi h f s t th d bli f lwhich refers to the doubling of volume

    – 4/3 r3 ie, 25% increase in the diameter equals a doubling of the volume

    • Most malignant tumors have doubling times between 30-450 days

    • No growth over a 2 year period (730 days) usually No growth over a 2 year period (730 days) usually indicates benignity (LR=0.01) – Can be established retrospectively (get old CXRs or CTs!) – Can be established prospectively in low risk patients

    (“watch and wait approach” with serial imaging)

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    “Watchful Waiting”“Watchful Waiting”

    • To establish nodule stability/benignity prospectively in low risk patients – Uses 2 year rule to confirm benignity – Serial CXR or CT (CT measurements more accurate) X 2 yrs

    • At 3, 6, 12 , 18, and 24 months – No growth over 2 year period = benign – Any growth during this period is an indication for VATS or

    bi psbiopsy

    NonNon--Invasive TestingInvasive Testing

    • Contrast enhanced CT • PET scan

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    Contrast Enhanced CTContrast Enhanced CT

    • Benign and malignant nodules differ in vascularity d b h diff tl ft t t and behave differently after contrast

    administration • Contrast-enhanced CT uses nodule enhancement to

    differentiate benign from malignant lesions • CT nodule enhancement protocol:

    – Contrast: 2 ml/sec, 300 mg iodine/ml, 420 mg/kg dose – Nodule is scanned pre-contrast and at 1, 2, 3, 4 min after

    contrast injection – Nodule enhancement (HU) = peak post-contrast

    measurement – pre-contrast measurement

    Swenson SJ et al. Radiology 2000; 214: 73Swenson SJ et al. Radiology 2000; 214: 73--8080

    Pre-contrast 1 min 2 min

    = Peak Post= Peak Post--contrast contrast –– PrePre--contrastcontrast Max Max =88=88--46= 42 46= 42

    4 min3 min

    Enhancement= 42 HUEnhancement= 42 HU

    Test Interpretation:Test Interpretation: ≤ 15 HU = Benign≤ 15 HU = Benign > 15 HU = Malignant> 15 HU = Malignant

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    Contrast Enhanced CTContrast Enhanced CT

    StudyStudy SensitivitySensitivity SpecificitySpecificity PPVPPV NPVNPV

    Swenson et al. 2000 * 98% 58% 68% 96%

    Meta-analysis Cronin et al. 2008

    93% 76% 80% 95%

    * C* C ff d 15 HU B i 15 HU M liff d 15 HU B i 15 HU M li