The Radiology of Pulmonary The Radiology of Pulmonary SarcoidosisSarcoidosis

Wally Bethune, Harvard Medical School Year IIIWally Bethune, Harvard Medical School Year IIIGillian Lieberman, MDGillian Lieberman, MD

November 2003Wally Bethune, HMS IIIGillian Lieberman, MD

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OutlineOutline

IntroductionIntroductionAnatomyAnatomyPlain FilmPlain FilmCT ScanCT ScanGallium ScanGallium ScanPatient PresentationPatient PresentationSummarySummary

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IntroductionIntroduction

What is What is sarcoidosissarcoidosis??SarcoidosisSarcoidosis is a chronic is a chronic noncaseatingnoncaseating granulomatousgranulomatous disease of disease of unknown etiology that affects many organs and tissues. unknown etiology that affects many organs and tissues.

The organs most affected are as follows: The organs most affected are as follows: Lungs 90%Lungs 90%LymphaticsLymphatics 75% 75% Skin/Eyes/Joint 25% Skin/Eyes/Joint 25% Bone marrow/Spleen 30Bone marrow/Spleen 30--40%40%Liver 60Liver 60--90% 90% CNS/MSK/Heart 5% CNS/MSK/Heart 5%

PrevalencePrevalenceEstimated at 10Estimated at 10--40 per 100,000 with slight female preponderance40 per 100,000 with slight female preponderanceHigher among U.S. blacks than whites by at least 10:1Higher among U.S. blacks than whites by at least 10:1Individuals aged 20Individuals aged 20--40 years are at highest risk.40 years are at highest risk.

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Introduction cont’dIntroduction cont’dDisease PresentationDisease Presentation

50% of cases are discovered incidentally on CXR in asymptomatic 50% of cases are discovered incidentally on CXR in asymptomatic individuals.individuals.Most common presenting Most common presenting sxsx are cough, are cough, dyspneadyspnea and chest pain.and chest pain.Clinicians beware: MANY other presentations are possible.Clinicians beware: MANY other presentations are possible.40% acute onset & constitutional vs. 60% chronic & pulmonary40% acute onset & constitutional vs. 60% chronic & pulmonary

Diagnosis (* indicates Diagnosis (* indicates required criteria)required criteria)*Characteristic clinical and radiologic findings*Characteristic clinical and radiologic findings*Tissue biopsy evidence of *Tissue biopsy evidence of noncaseatingnoncaseating granuloma(sgranuloma(s))*Negative bacterial and fungal cultures (R/O infection, especial*Negative bacterial and fungal cultures (R/O infection, especially TB)ly TB)Pulmonary Function Tests: low FVC, Pulmonary Function Tests: low FVC, nlnl FEV1/FVC, low DLCOFEV1/FVC, low DLCOElevated serum ACEElevated serum ACE

Treatment of symptomatic individuals is with steroids & Treatment of symptomatic individuals is with steroids & immunosuppressivesimmunosuppressives lung transplant for severe disease. lung transplant for severe disease. Prognosis: Two thirds of cases resolve spontaneously, one third Prognosis: Two thirds of cases resolve spontaneously, one third are are longlong--term, and 5% result in fatality. term, and 5% result in fatality.

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AnatomyAnatomy

http://www.vh.org/adult/provider/radiology/LungAnatomy/ www.uptodate.com

Aortopulmonary windowNormal hilar markings

Normal interstitial markings

Right paratracheal area

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Plain Film Chest RadiographyPlain Film Chest Radiography

CXR (PA & lateral) is the initial diagnostic study of choice. CXR (PA & lateral) is the initial diagnostic study of choice. CXR is also useful in monitoring disease progression. CXR is also useful in monitoring disease progression. AdvantagesAdvantages

FastFastCheapCheapWidely availableWidely availableRelative ease of interpretationRelative ease of interpretation

LimitationsLimitationsCXR is a useful CXR is a useful anatomicalanatomical guide to lung involvement but it guide to lung involvement but it cannot stage the biological cannot stage the biological activityactivity of the disease process and of the disease process and cannot assess functional defects.cannot assess functional defects.CXR is not as sensitive for CXR is not as sensitive for sarcoidosissarcoidosis as CT.as CT.

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CXR: CXR: SarcoidSarcoid Stage IStage I

Enlarged Enlarged bilateral bilateral hilarhilar, , right right paratrachealparatracheal (arrow),(arrow),and and aortopulmonaryaortopulmonarywindow (arrowhead) window (arrowhead) nodesnodesNormal parenchymaNormal parenchymaDdxDdx

SarcoidosisSarcoidosisLymphoma/LeukemiaLymphoma/LeukemiaTuberculosisTuberculosisCA MetsCA MetsFungal InfectionFungal Infection

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CXR: CXR: SarcoidSarcoid Stage IIStage II

Bilateral Bilateral hilarhilaradenopathyadenopathyFine linear and Fine linear and reticular opacities in reticular opacities in perihilarperihilar lung lung parenchymaparenchyma

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CXR: CXR: SarcoidSarcoid Stage IIIStage III

Interstitial disease, now Interstitial disease, now withoutwithout hilarhilar LANLANDdxDdx: :

CHF CHF lymphangiticlymphangitic spread of CA spread of CA infection (viral, infection (viral, mycoplasmamycoplasma) ) pneumoconiosis pneumoconiosis collagen vascular diseasecollagen vascular diseaseSarcoidosisSarcoidosis

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CXR: CXR: SarcoidSarcoid Stage IVStage IV

Interstitial opacities with upper Interstitial opacities with upper zone predominance, volume zone predominance, volume loss, and advanced fibrosis.loss, and advanced fibrosis.DdxDdx

Collagen vascular disease (RA, Collagen vascular disease (RA, scleroderma) scleroderma) SarcoidSarcoid stage IV stage IV Silicosis Silicosis Asbestosis Asbestosis Hypersensitivity Hypersensitivity pneumonitispneumonitisIdiopathic fibrosis Idiopathic fibrosis Drug/radiation toxicityDrug/radiation toxicity

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High Resolution CT ScanHigh Resolution CT Scan

HRCT uses very thin slices HRCT uses very thin slices (1mm) to achieve better spatial (1mm) to achieve better spatial resolution & precision.resolution & precision.HRCT is indicated after normal HRCT is indicated after normal CXR in a symptomatic patient CXR in a symptomatic patient --the setting of high clinical the setting of high clinical suspicion of disease.suspicion of disease.AdvantagesAdvantages

High sensitivity for High sensitivity for adenopathyadenopathy, , infiltrates, and architectural infiltrates, and architectural distortion.distortion.HRCT can identify areas of HRCT can identify areas of reversible vs. irreversible lung reversible vs. irreversible lung damage.damage.

DisadvantageDisadvantageExpensiveExpensive

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CT: CT: SarcoidSarcoid Stage IStage I

Bilateral Bilateral hilarhilaradenopathyadenopathyDdxDdx

SarcoidosisSarcoidosisTuberculosisTuberculosisCA MetsCA MetsFungal InfectionFungal InfectionLymphoma/LeukemiaLymphoma/Leukemia

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CT: CT: SarcoidSarcoid Stage IIStage II

Bilateral Bilateral hilarhilar lymph lymph node enlargementnode enlargementMultiple Multiple miliarymiliaryperibronchiolarperibronchiolarnodules scattered nodules scattered diffusely throughout diffusely throughout both lungs.both lungs.

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CT: CT: SarcoidSarcoid Stage IIIStage III

Beaded or irregular thickening Beaded or irregular thickening of of bronchovascularbronchovascular bundles bundles with nodules along bronchi, with nodules along bronchi, vessels, and vessels, and subpleuralsubpleuralregions.regions.Normal Normal hilarhilar lymph nodeslymph nodesDdxDdx: :

CHF CHF lymphangiticlymphangitic spread of CAspread of CAinfection (viral, infection (viral, mycoplasmamycoplasma) )

pneumoconiosis pneumoconiosis collagen vascular diseasecollagen vascular diseaseSarcoidosisSarcoidosis

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CT: CT: SarcoidSarcoid Stage IVStage IV

Broad bands of fibrosis in Broad bands of fibrosis in the upper lobes.the upper lobes.DdxDdx

Collagen vascular disease Collagen vascular disease (RA, scleroderma) (RA, scleroderma) SarcoidSarcoid stage IV stage IV Silicosis Silicosis Asbestosis Asbestosis Hypersensitivity Hypersensitivity pneumonitispneumonitisIdiopathic fibrosis Idiopathic fibrosis Drug/radiation toxicityDrug/radiation toxicity

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Gallium 67 Gallium 67 ScintigraphyScintigraphy

A nuclear medicine test used largely to support diagnosisA nuclear medicine test used largely to support diagnosisRadioactive gallium is injected intravenously and imaged Radioactive gallium is injected intravenously and imaged 11--2 days later.2 days later.AdvantagesAdvantages

NonNon--invasiveinvasiveSerial exams monitor disease progressionSerial exams monitor disease progressionGallium distinguishes areas of fibrosis from areas of inflammatiGallium distinguishes areas of fibrosis from areas of inflammationonFullFull--body scan detects extrabody scan detects extra--pulmonary spread of diseasepulmonary spread of disease

LimitationsLimitationslow specificity low specificity difficult interpretation.difficult interpretation.

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Whole Body Gallium ScanWhole Body Gallium ScanWally Bethune, HMS IIIGillian Lieberman, MD

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Patient PresentationPatient Presentation

1/26/01 1/26/01 –– EM is a 40 EM is a 40 yoyo previously healthy previously healthy F F p/wp/w fever, cervical and posterior fever, cervical and posterior auricular auricular adenopathyadenopathy, intermittent HA and , intermittent HA and neck pain/stiffness, intermittent right neck pain/stiffness, intermittent right upper extremity weakness. upper extremity weakness. ESR was elevated. She was ESR was elevated. She was seropositiveseropositive((IgMIgM) to both EBV & CMV. ) to both EBV & CMV. Radiologic studies were done…Radiologic studies were done…

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Patient Presentation: MRPatient Presentation: MRRtRt paraspinalparaspinal soft tissue masssoft tissue mass

Infiltrates epidural space at Infiltrates epidural space at T1/T2T1/T2Bony erosion of posterior Bony erosion of posterior vertebral elementsvertebral elementsNo cord compression or disc No cord compression or disc herniationherniation apparentapparent

DdxDdx::Infection (CMV, EBV, other)Infection (CMV, EBV, other)Neoplasm (lymphoma)Neoplasm (lymphoma)

The mass is found to be a The mass is found to be a cryptococcalcryptococcal abscess. abscess. EM’sEM’s sxsxresolve with medication.resolve with medication.

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Patient Presentation: CXRPatient Presentation: CXR3/26/02 3/26/02 –– EM returns now EM returns now c/o c/o adenopathyadenopathy and and discomfort spreading down discomfort spreading down to chest and back. She to chest and back. She describes “heaviness in her describes “heaviness in her lungs” without frank lungs” without frank dyspneadyspnea or cough. She or cough. She also has a new skin lesion also has a new skin lesion on the right forearm.on the right forearm.Initial CXR is Initial CXR is unremarkable.unremarkable.Further radiologic Further radiologic evaluation is performed…evaluation is performed…

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Patient Presentation: CTPatient Presentation: CT

Bilateral upper lobe Bilateral upper lobe infiltrates with infiltrates with nodular nodular septalseptalthickeningthickeningAxillaryAxillary adenopathyadenopathy

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Patient Presentation: Patient Presentation: CTCT

Normal Normal hilahilaNormal basesNormal basesDdxDdx

CHF CHF lymphangiticlymphangitic spread of CAspread of CAinfection (infection (cryptococcuscryptococcus) ) pneumoconiosis pneumoconiosis collagen vascular diseasecollagen vascular diseaseSarcoidosisSarcoidosis, Stage III, Stage III

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Patient Presentation: Patient Presentation: DxDx & Mgmt& Mgmt

5/13/02 5/13/02 -- EM is diagnosed with EM is diagnosed with sarcoidosissarcoidosis::Radiographic evidence as discussedRadiographic evidence as discussedCultures are negative.Cultures are negative.Skin lesion Skin lesion bxbx reveals nonreveals non--caseatingcaseating granulomasgranulomas..Serum ACE is elevated.Serum ACE is elevated.

Because she is largely asymptomatic, she decides Because she is largely asymptomatic, she decides ––in concert with her physician in concert with her physician –– to conservatively to conservatively monitor her disease and forego treatment for now.monitor her disease and forego treatment for now.1/26/03 1/26/03 –– repeat chest CT is unchanged. EM repeat chest CT is unchanged. EM continues to be asymptomatic and clinically stable.continues to be asymptomatic and clinically stable.

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SummarySummarySarcoidosisSarcoidosis is a chronic nonis a chronic non--caseatingcaseating granulomatousgranulomatousdisease, typically affecting the lungs with or without disease, typically affecting the lungs with or without extraextra--pulmonary involvement.pulmonary involvement.StageStage--specific findings are recognizable on CXR & CT specific findings are recognizable on CXR & CT allowing us to track progression of disease over time.allowing us to track progression of disease over time.

Stage I: bilateral Stage I: bilateral hilarhilar adenopathyadenopathyStage II: “ “ “ along with diffuse reticular and nodular interstStage II: “ “ “ along with diffuse reticular and nodular interstitial itial markings with upper zone predominancemarkings with upper zone predominanceStage III: interstitial disease, now Stage III: interstitial disease, now withoutwithout hilarhilar adenopathyadenopathyStage IV: fibrosisStage IV: fibrosis

DdxDdx includes infection (esp. TB), lymphoma & CA includes infection (esp. TB), lymphoma & CA metsmets: : these must be ruled out in order to make the diagnosis these must be ruled out in order to make the diagnosis of of sarcoidosissarcoidosis. Other diagnostic criteria are radiographic . Other diagnostic criteria are radiographic and pathologic evidence consistent with and pathologic evidence consistent with sarcoidosissarcoidosis..The prognosis is usually favorable.The prognosis is usually favorable.

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AcknowledgementsAcknowledgements

Phoebe Phoebe OlhavaOlhava, M.D., M.D.Gillian Lieberman, M.D.Gillian Lieberman, M.D.Pamela Pamela LepkowskiLepkowskiLarry BarbarasLarry BarbarasHMS/BIDMC Core Radiology studentsHMS/BIDMC Core Radiology students

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ReferencesReferencesBIDMC Patient Care Radiology Files. 2003. Beth Israel Deaconess Medical Center, Boston MA. GroskinGroskin, S. , S. The Lung:The Lung: Radiologic Correlations. 3Radiologic Correlations. 3rdrd Edition. Mosby. 1993.Edition. Mosby. 1993.HeitzmanHeitzman, ER. , ER. The The MediastinumMediastinum:: Radiologic Correlations with Anatomy and Radiologic Correlations with Anatomy and Pathology. 2Pathology. 2ndnd Edition. Springer Edition. Springer VerlagVerlag Publishing. New York. 1988.Publishing. New York. 1988.King, TE. “Overview of King, TE. “Overview of SarcoidosisSarcoidosis” on ” on UpToDateUpToDate 2003.2003.KovacicKovacic, K. , K. SarcoidosisSarcoidosis: Whole Body Gallium Imaging. : Whole Body Gallium Imaging. ActaActa clinclin CroatCroat 11--2001; 40:432001; 40:43--45. Web address: 45. Web address: www.acta-clinica.kbsm.hr/Acta5/KOVACIC.PDFLoyola University Medical Education Network 2003. Website addresLoyola University Medical Education Network 2003. Website address: s: www.meddean.luc.edu/lumen/MedEd/Radio/sarc/sarc.htmwww.meddean.luc.edu/lumen/MedEd/Radio/sarc/sarc.htmReeder, M. Reeder & Reeder, M. Reeder & Felson’sFelson’s GamutsGamuts in Radiology: Comprehensive Lists of in Radiology: Comprehensive Lists of Roentgen Differential Diagnosis. 3Roentgen Differential Diagnosis. 3rdrd Edition. Springer Edition. Springer VerlagVerlag Publishing. Publishing. New York. 1993.New York. 1993.University Hospitals of Cleveland Department of Radiology Body IUniversity Hospitals of Cleveland Department of Radiology Body Image mage Teaching Files. 2003. Website address: Teaching Files. 2003. Website address: www.uhrad.comwww.uhrad.com..University of Iowa Virtual Hospital 2003. Website address: University of Iowa Virtual Hospital 2003. Website address: www.vh.org/adult/provider/radiology/LungAnatomy/YakobiYakobi, R. “, R. “SarcoidosisSarcoidosis” on ” on eMedicine.comeMedicine.com 2003.2003.

Wally Bethune, HMS IIIGillian Lieberman, MD