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The Radiographic Appearance of
Pulmonary Tuberculosis
David Walton, Harvard Medical School, Year IV
Gillian Lieberman, M.D.
David A. Walton
Gillian Lieberman, M. D.
David A. Walton
Gillian Lieberman, M. D.1
• CM, a 34-year-old male Haitian peasant farmer p/w 2 months of fever, night sweats, fatigue, weight loss, and 2 episodes of hemoptysis
• CXR was obtained
Patients History A clinic in rural Haiti
David A. Walton
Gillian Lieberman, M. D.2
CXR
CXR revealed a RUL infiltrate with three right perihilar cavitary lesions
Source: Clinic Bon Sauveur, Cange, Haiti
David A. Walton
Gillian Lieberman, M. D.3DDx of upper lobe
infiltrates and cavitation:
Source: Clinic Bon Sauveur, Cange, Haiti
• Tuberculosis• Atypical mycobacteria• Sarcoidosis• Silicosis• Wegner’s granulomatosis• Collagen vascular disease• Adenosquamous cancer• Lymphoma (esp. Hodgskins)• Actinomycosis• Histoplasmosis
David A. Walton
Gillian Lieberman, M. D.4
Sputum microscopy revealed numerous acid-fast bacilli
Pt started on a four drug anti-tuberculous regimen (INH, RIF, PZA, ETH)
David A. Walton
Gillian Lieberman, M. D.5
Symptoms of Pulmonary TB
Respiratory Constitutional
Cough (initially dry, later productive) Malaise
Chest pain Lassitude
Hemoptysis (sparse early, heavy Fever
w/ cavitation) Sweats
Shortness of breath Anorexia
David A. Walton
Gillian Lieberman, M. D.6
Diagnosis• Smear microscopy
• Ziehl-Neelsen• Kinyoun• Rhodamine auramine
• Culture– Can take up to six weeks to identify positive cultures (TB doubling time
is 15-24 hours)• Chest radiography
– Suggestive, not diagnostic• Bronchoscopy• Tuberculin skin testing
– Does not differentiate latent infection or BCG vaccination from active disease
David A. Walton
Gillian Lieberman, M. D.7
Histopathology
Small PM, Fujiwara PI. NEJM 2001; 189-200, p. 191. Source: http://www.mssm.edu/medicine/infectious-disease/consultative/case_11.html
Ziehl Neelsen smear of acid fast Mycobacterium tuberculosis
Culture of Mycobacterium tuberculosis on Lowenstein- Jensen medium
Note: Mycobacterium tuberculosis is an aerobic, acid-fast Gram positive rod
David A. Walton
Gillian Lieberman, M. D.8
Epidemiology
• One third of the world’s population—two billion people—is infected with the tubercle bacillus
• Eight million people per year develop active disease• Two million deaths per year are attributable to M.
tuberculosis• Tuberculosis remains the world’s leading infectious
cause of adult mortality• Estimates for the next 20 years include one billion new
infections, 200 million with active disease, and 35 million deaths
David A. Walton
Gillian Lieberman, M. D.9
World Health Organization. WHO report on the tuberculosis epidemic, 2000
Global Incidence of Tuberculosis, 1997
David A. Walton
Gillian Lieberman, M. D.10
Reported TB CasesUnited States, 1953 - 1998
Year
10,000
20,000
*
*
30,000
50,000
70,000
100,000
Cas
es(L
og S
cale
)
*Change in case definition
53 60 70 80 90 98
Source: http://www.cdc.gov/nchstp/tb/pubs/slidesets/core/html/trans3_slides.htm
David A. Walton
Gillian Lieberman, M. D.11
Transmission and Pathogenesis• Tuberculosis is an
airborne infection spread by droplet nuclei (5-10µm)
• When inhaled, droplet nuclei are deposited in terminal airspaces of the lung
• Macrophages ingest the bacilli and transport them to regional lymph nodes
• Further dissemination occurs via lymphohematogenous routes to other parts of the lungs and extrapulmonary sites
Source: Centers for Disease Control and Prevention. Core Curriculum on Tuberculosis, 4th ed. 2000.
David A. Walton
Gillian Lieberman, M. D.12
Transmission and Pathogenesis in the lungs
Source: http://telpath2.med.utah.edu/
Inhalation and deposition of the tubercle bacillus leads to one of three possible outcomes:
• Immediate clearance of the organism
• Primary disease
• Active disease many years after initial infection (post-primary disease)
David A. Walton
Gillian Lieberman, M. D.13
Transmission of Tuberculosis and Progression of Latent Infection
Small PM, Fujiwara PI. NEJM 2001; 189-200, p. 192.
David A. Walton
Gillian Lieberman, M. D.14
Primary Tuberculosis
• Most often a childhood infection in endemic settings• Few clinical symptoms in immunocompetent hosts• Lymphangitic spread to hilar and paratracheal nodes
result in enlargement of these structures• Often the only residua of primary infection is a positive
skin test and the Ranke complex• Primary progressive tuberculosis occurs in a minority
of cases
David A. Walton
Gillian Lieberman, M. D.15
The natural history of primary tuberculosis in adults
Event Time CommentsAlveolar deposition 0 Bacilli engulfed byof tubercle bacilli alveolar macrophage
Bacilli proliferate and disseminate 3-8 weeks Tuberculin skin test becomes reactive; chest x-ray may become abnormal
Some patients develop pleurisy;A minority develop miliary disease 8-26 weeks
High-risk period for pulmonary and 26-156 weeks 10% infected will Extrapulmonary disesase develop TB
Iseman MD. A clinical guide to tuberculosis, 1999, p. 130
David A. Walton
Gillian Lieberman, M. D.16
Primary Tuberculosis• Lymphadenopathy is the hallmark of
primary disease in childhood, seen in up to 90% of cases
• Usually affects the hilum and right paratracheal regions
• Bilateral adenopathy occurs in one third of cases
• Adenopathy usually seen in association with parenchymal consolidation or atelectasis
• Lymphadenopathy can be the only manifestation of TB in young children
• Adenopathy resolves slowly, and nodal calcification may occur six months after the initial infection
• Pleural effusion may occur in a minority of cases Source: Dr. Seymor Shalek, BIDMC
David A. Walton
Gillian Lieberman, M. D.17
Radiographic Residuals of Primary Infection
Source: Iseman MD. A clinical guide to tuberculosis, 1999, p. 137.
David A. Walton
Gillian Lieberman, M. D.18
Primary TuberculosisRanke’s Complex Simon Foci
Source:Cotran et al. Robbins Pathologic Basis of Disease, 1999, p. 723.
Source: Clinic Bon Sauveur, Cange, Haiti
David A. Walton
Gillian Lieberman, M. D.19
Post-Primary Tuberculosis
• Post-primary TB represents 90 percent of adult cases in the non-HIV-infected population
• Results from reactivation of a previously dormant focus seeded at the time of primary infection
• Apical-posterior segments of the upper lobes (80 to 90 percent of patients), followed in frequency by the superior segment of the lower lobes and the anterior segment of the upper lobes
• The original site of spread is occasionally associated with Simon foci—residual uni- or bilateral apical fibronodular shadows from primary infection
• Post-primary disease also known as reactivation TB, recrudescent TB, chronic TB, endogenous reinfection, and adult type progressive TB
David A. Walton
Gillian Lieberman, M. D.20
Post-Primary Tuberculosis
• Upper lobe infiltrates• Cavitary lesions• Tuberculomas• Absence of lymphadenopathy• Complete lobar or lung opacification and lobar
collapse in severe cases• Complications, including effusion, empyema,
bronchiectasis, mililary pattern, and spontaneous pneumothorax
The radiographic appearance of post-primary disease can include::
David A. Walton
Gillian Lieberman, M. D.21
Post-Primary Tuberculosis
Source: Cotran, et al. Robbins Pathologic Basis of Disease, 1999, p. 724.
David A. Walton
Gillian Lieberman, M. D.22
Post-Primary Tuberculosis
Source: Clinic Bon Sauveur, Cange, Haiti
Advanced post-primary tuberculosis in an immunocompetent host
Bilateral upper lobe involvement seen in this patient with post- primary disease
Source: Dr. Seymor Shalek, BIDMC
David A. Walton
Gillian Lieberman, M. D.23
Cavitary Disease
Source: Clinic Bon Sauveur, Cange, Haiti
• A characteristic finding of post-primary disease
• Cavitation implies a high bacillary burden and high infectivity
• Cavity size ranges from a few mm to several cm
• Variable wall thickness• Air fluid levels rare, and
may be an indication of bacterial or fungal superinfection
David A. Walton
Gillian Lieberman, M. D.24
Cavitary Disease
Source: Socios en Salud, Lima, Peru
David A. Walton
Gillian Lieberman, M. D.25
Pathology
Source: http://pathhsw5m54.ucsf.edu/case32/image327.html
• Gross specimen of upper lobe cavitary disease and endobronchial spread to both upper and lower lobes
• Infected bronchi appear as small, pale nodules with a hyperemic border
David A. Walton
Gillian Lieberman, M. D.26
Cavitary Disease
Source: Socios en Salud, Lima, PeruSource: Dr. Seymor Shalek, BIDMC
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Gillian Lieberman, M. D.27
Tuberculoma
Source: Juhl JH, et al. Paul and Juhl's Essentials of Radiologic Imaging, 7th ed., 1998, p. 872.
• Single or multiple rounded, well- circumscribed, focal lesions
• Manifestation of primary or post- primary disease
• Easily mistaken for coin lesions or metastatic disease on chest radiograph
• Vary in size from a few millimeters to 5 or 6 cm in diameter but usually range from 1 to 3 cm.
• They may or may not contain calcium
David A. Walton
Gillian Lieberman, M. D.28
Post-Primary Tuberculosis
Interval improvement of 4 x 2 cm cavitary mass abutting right hilum after 4 months of effective therapy
Source: BiDMC
David A. Walton
Gillian Lieberman, M. D.29
Role of CT in Pulmonary Tuberculosis
• Chest radiography remains the first choice of initial evaluation of patients with tuberculosis
• CT may be helpful in the patients who initially present with a normal chest radiograph and high suspicion of active disease
• Various patterns of primary and post-primary disease may necessitate CT as a diagnostic tool in pulmonary tuberculosis
• CT facilitates differentiation of pulmonary tuberculosis from lung cancer or other granulomatous lung disease
David A. Walton
Gillian Lieberman, M. D.30
Role of CT in Pulmonary Tuberculosis
CT reveals 4 x 3 cm right hilar cavitary mass poorly seen on chest X-ray
Source: BIDMC
Source: BIDMC
David A. Walton
Gillian Lieberman, M. D.31
Complications of Post-Primary Tuberculosis
• Tuberculous effusion• Tuberculous empyema• Bronchostenosis• Broncholithiasis• Spontaneous pneumothorax• Dissemination to other organs
David A. Walton
Gillian Lieberman, M. D.32
Tuberculous effusionPost-thoracentesisPre-thoracentesis
Source: Clinic Bon Sauveur, Cange, Haitit Source: Clninc Bon Sauveur, Cange, Haiti
David A. Walton
Gillian Lieberman, M. D.33
Spontaneous pneumothoraxEnd-expirationEnd-inspiration
Source: Dr. Seymor Shalek, BIDMC Source: Dr. Seymor Shalek, BIDMC
David A. Walton
Gillian Lieberman, M. D.34
Source: Brigham and Women’s Hospital, Boston, Massachusetts
Miliary Tuberculosis
• Results from hematogenous dissemination of tubercle bacilli
• Seen in both primary and post-primary disease
• Occurs more frequently in young children and immunocompromised patients
David A. Walton
Gillian Lieberman, M. D.35
Source: Dr. Seymor Shalek, BIDMC
Miliary Tuberculosis
• Characteristic radiographic appearance is a faint reticulonodular pattern consisting of widespread nodular opacities measuring 2-3 mm in diameter scattered diffusely throughout both lungs
• Associated lymphadenopathy seen in 95% of children, 12% of adults
David A. Walton
Gillian Lieberman, M. D.36
• Miliary tuberculosis• Atypical mycobateria• Disseminated fungal infection
(blastomycosis, histoplasmosis, etc.)• Metastatic neoplastic disease• Disseminated viral infection (varicella,
CMV, etc.)• Bacterial (nocardia, tuleremia, brucellosis,
staphylococcus, streptococcus, etc.)• Schistosomiasis• Pneumoconioses• Sarcoidosis• Hypersensitivity pneumonitis
Source: Brigham and Women’s Hospital, Boston, Massachusetts
Differential of a miliary pattern on chest radiograph or CT:
David A. Walton
Gillian Lieberman, M. D.37
Miliary Tuberculosis
Source: http://www.UpToDate.com
Source: http://www-medlib.med.utah.edu/WebPath/LUNGHTML/LUNG039.htmlMillet seeds, after which the disease was named. The size of the seeds correspond to the size of the lesions seen on chest radiograph
Gross specimen of lung demonstrating the diffuse nature of miliary disease
David A. Walton
Gillian Lieberman, M. D.38
61-year-old female Haitian peasant with cough, SOB, and significant weight loss over 4 months
Source: Clinic Bon Sauveur, Cange, Haiti
Challenge Patient
What is the cause for the miliary pattern?
David A. Walton
Gillian Lieberman, M. D.39
DDX:Miliary TB
Sarcoidosis
Metastatic Disease
Diffuse fungal infection
Source: Clinic Bon Sauveur, Cange, Haiti
There is a differential:
David A. Walton
Gillian Lieberman, M. D.40
**S/p left mastectomy for breast CA**
DDX:Miliary TB
Sarcoidosis
Metastatic Disease
Diffuse fungal infection
Absent left breast shadow
Source: Clinic Bon Sauveur, Cange, Haiti
Miliary Metastases
David A. Walton
Gillian Lieberman, M. D.41
Source: Brigham and Women’s Hospital, Boston, MAssachusetts
Other causes of Miliary patterns:
Source: Dr. Seymor Shalek, BIDMC
Varicella pneumonia is also part of the differential for a miliary pattern on chest radiograph
In immunocompromised patients, one must rule out Pneumocystis carinii pneumonia as a potential etiology of a miliary pattern on chest radiograph
David A. Walton
Gillian Lieberman, M. D.42
Radiographic findings for patients with pulmonary TB, according to HIV status
HIV-positive HIV-negativeFinding (n=72) (n=52)
Focal infiltrate 38 (53%) 46 (89%)
Upper-lobe infiltrate 19 (26%) 32 (62%)
One or more cavities 5 (7%) 23 (44%)
Hilar or mediastinallymphadenopathy 28 (39%) 6 (12%)
Normal 8 (11%) 3 (6%)
Alpert, et al. Clinical Infectious Diseases 1997; 24:661-8.
David A. Walton
Gillian Lieberman, M. D.43
Radiological features of pulmonary TB in 963 HIV-infected adults compared to 1000 HIV-negative adults with TB
HIV-positive HIV-negativeRadiological feature (n=963) (n=1000)
Tshibwabwa-Tumba, et al. Clinical Radiology 1997; 52:837-841.
Cavitation 319 (33%) 784 (78%) Lymphadenopathy 253 (26%) 131 (13%)Pleural effusions 159 (16%) 68 (7%)Miliary pattern 94 (9.8%) 52 (5%)Atelectasis 112 (12%) 237 (24%)Consolidation 94 (10%) 32 (3%)Interstitial changes 120 (12%) 68 (7%)
David A. Walton
Gillian Lieberman, M. D.44
Summary• Pulmonary tuberculosis is a disease with protean, non-specific symptoms, but
often associated with fever, weight loss, cough, night sweats, and hemoptysis• M. Tuberculosis is the world’s leading infectious cause of adult mortality, with
two billion infected worldwide• Tuberculosis is an airborne infection• After initial infection, one can develop primary TB, latent TB, or post-primary
TB• Primary TB characterized radiographically by lymphadenopathy• Post-primary TB characterized radiographically by upper lobe infiltrates,
cavitary lesions, and tuberculomas• Although chest radiograhy is indicated when TB is suspected, CT can aid in
the diagnosis• Miliary TB, which can be secondary to primary or post-primary disease, is
characterized by faint reticulonodular pattern consisting of widespread nodular opacities measuring 2-3 mm in diameter scattered diffusely throughout both lungs
David A. Walton
Gillian Lieberman, M. D.45
References• McAdams HP, Erasmus J, Winter JA. Radiologic manifestations of pulmonary tuberculosis.
Radiologic Clinics of North America 1995; 33(4):655-676.• Friedman LN, Selwyn PA. Pulmonary tuberculosis: presentation, diagnosis, and treatment. In:
Friedman LN (ed.). Tuberculosis: Current concepts and treatment. New York, CRC Press, 2001. • Farmer PE, Walton DA, Becerra MC. International tuberculosis control in the 21st century. In:
Friedman LN (ed.). Tuberculosis: current concepts and treatment. New York, CRC Press, 2001. • Iseman MD. A clinician’s guide to tuberculosis. Lippincott Williams and Wilkins, Philadelphia,
2000.• Cotran RS, Kumar V, Collins T. Robbins pathologic basis of disease. WB Saunders Company,
Philadelphia, 1999. • Juhl JH, Crummy AB, Kuhlman, JE. Paul and Juhl's essentials of radiologic imaging, 7th edition.
Lippincott, Williams and Wilkins, New York, 1998. • Small PM, Fujiwara PI. Management of tuberculosis in the United States. New England Journal of
Medicine 2001; 345(3): 189-200.• Rottenberg, GT, Shaw P. Radiology of pulmonary tuberculosis. British Journal of Hospital Medicine
1996; 56(5): 195-199.• Kwong JS, Carignan S, Kang EY, Muller NL, FitzGerald JM. Miliary tuberculosis: diagnostic
accuracy of chest radiography. Chest; 110(2): 339-42.
David A. Walton
Gillian Lieberman, M. D.46
References• www.mssm.edu/medicine/infectious-disease/consultative/case_11.html• www.cdc.gov/nchstp/tb/pubs/slidesets/core/html/trans3_slides.htm• World Health Organization. WHO report on the tuberculosis epidemic. Geneva: World Health
Organization; 2000.• Centers for Disease Control and Prevention. Core Curriculum on Tuberculosis, 4th ed. Centers for
Disease Control and Prevention, Atlanta, 2000.• http://telpath2.med.utah.edu/• http://pathhsw5m54.ucsf.edu/case32/image327.html• www.UpToDate.com• Alpert PL, Munsiff SS, Gourevitch MN, Greenberg B, Klein R. A prospective study of tuberculosis
and human immunodeficiency virus infection clinical manifestations and factors associated with survival. Clinical Infectious Diseases 1997; 24:661-668.
• Tshibwabwa-Tumba E, Mwinga A, Pobee J, Zumla A. Radiological features of pulmonary tuberculosis in 963 HIV-infected adults at three central African hospitals. Clinical Radiology 1997; 52: 837-841.
• Lee KS, Im JG. CT in adults with tuberculosis of the chest: characteristic findings and role in management. American Journal of Roentgenology 1995; 164: 1361-1367.
• Lee KS, Hwang JW, Chung MP, Kim H, Kwon OJ. Utility of CT in the evaluation of pulmonary tuberculosis in patients without AIDS. Chest 1996; 110(4): 977-984.
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AcknowledgementsI would like to thank:• Dr. Seymor Shalek for his dedication to teaching and sharing his
wonderful radiographic collection with me• Paul Farmer for his kindness, support, and mentorship• The staff of Zanmi Lasante• Dr. Fernet Leandre for helping me find cases in Haiti • The patients of Clinic Bon Sauveur• Dr. Phillip Boiselle for his assistance • Our webmasters, Larry Barbaras and Cara Lyn D’amour• Beverlee Turner and Pamela Lepkowski