Download The Radiographic Appearance of Pulmonary Tuberculosis

David A. Walton
Gillian Lieberman, M. D.
The Radiographic Appearance of
Pulmonary Tuberculosis
David Walton, Harvard Medical School, Year IV
Gillian Lieberman, M.D.
David A. Walton
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Gillian Lieberman, M. D.
Patients History
A clinic in rural Haiti
• 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
David A. Walton
Gillian Lieberman, M. D.
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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.
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DDx of upper lobe
infiltrates and cavitation:
Tuberculosis
Atypical mycobacteria
Sarcoidosis
Silicosis
Wegner’s granulomatosis
Collagen vascular disease
Adenosquamous cancer
Lymphoma (esp. Hodgskins)
Actinomycosis
Histoplasmosis
Source: Clinic Bon Sauveur, Cange, Haiti
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David A. Walton
Gillian Lieberman, M. D.
Sputum microscopy revealed
numerous acid-fast bacilli
Pt started on a four drug anti-tuberculous
regimen (INH, RIF, PZA, ETH)
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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
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Diagnosis
• Smear microscopy
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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
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Gillian Lieberman, M. D.
Histopathology
Small PM, Fujiwara PI. NEJM 2001; 189-200, p. 191.
Ziehl Neelsen smear of acid fast
Mycobacterium tuberculosis
Source: http://www.mssm.edu/medicine/infectious-disease/consultative/case_11.html
Culture of Mycobacterium
tuberculosis on LowensteinJensen medium
Note: Mycobacterium tuberculosis is an aerobic, acid-fast Gram positive rod
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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
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Global Incidence of Tuberculosis, 1997
World Health Organization. WHO report on the tuberculosis epidemic, 2000
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Gillian Lieberman, M. D.
Reported TB Cases
United States, 1953 - 1998
100,000
Cases
(Log Scale)
70,000
*
50,000
*
30,000
20,000
10,000
53
60
70
80
90
Year
*Change in case definition
Source: http://www.cdc.gov/nchstp/tb/pubs/slidesets/core/html/trans3_slides.htm
98
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Gillian Lieberman, M. D.
Transmission and Pathogenesis
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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.
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Gillian Lieberman, M. D.
Transmission and Pathogenesis
in the lungs
Inhalation and deposition of the
tubercle bacillus leads to one of
three possible outcomes:
• Immediate clearance of the
organism
Source: http://telpath2.med.utah.edu/
• Primary disease
• Active disease many years after
initial infection (post-primary
disease)
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Transmission of Tuberculosis and Progression of Latent Infection
Small PM, Fujiwara PI. NEJM 2001; 189-200, p. 192.
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Gillian Lieberman, M. D.
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
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Gillian Lieberman, M. D.
The natural history of primary tuberculosis
in adults
Event
Time
Alveolar deposition
of tubercle bacilli
0
Bacilli proliferate and disseminate
3-8 weeks
Some patients develop pleurisy;
A minority develop miliary disease
8-26 weeks
High-risk period for pulmonary and
Extrapulmonary disesase
26-156 weeks
Iseman MD. A clinical guide to tuberculosis, 1999, p. 130
Comments
Bacilli engulfed by
alveolar macrophage
Tuberculin skin test
becomes reactive;
chest x-ray may
become abnormal
10% infected will
develop TB
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Gillian Lieberman, M. D.
Primary Tuberculosis
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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
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Gillian Lieberman, M. D.
Radiographic Residuals of Primary Infection
Source: Iseman MD. A clinical guide to tuberculosis, 1999, p. 137.
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Gillian Lieberman, M. D.
Primary Tuberculosis
Ranke’s Complex
Simon Foci
Source:Cotran et al. Robbins Pathologic Basis of Disease, 1999, p. 723.
Source: Clinic Bon Sauveur, Cange, Haiti
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Gillian Lieberman, M. D.
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
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Gillian Lieberman, M. D.
Post-Primary Tuberculosis
The radiographic appearance of post-primary
disease can include::
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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
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Gillian Lieberman, M. D.
Post-Primary Tuberculosis
Source: Cotran, et al. Robbins Pathologic Basis of Disease, 1999, p. 724.
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Gillian Lieberman, M. D.
Post-Primary Tuberculosis
Bilateral upper lobe involvement
seen in this patient with postprimary disease
Source: Dr. Seymor Shalek, BIDMC
Advanced post-primary tuberculosis
in an immunocompetent host
Source: Clinic Bon Sauveur, Cange, Haiti
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Gillian Lieberman, M. D.
Cavitary Disease
• 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
Source: Clinic Bon Sauveur, Cange, Haiti
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Gillian Lieberman, M. D.
Cavitary Disease
Source: Socios en Salud, Lima, Peru
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Gillian Lieberman, M. D.
Pathology
• 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
Source: http://pathhsw5m54.ucsf.edu/case32/image327.html
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Gillian Lieberman, M. D.
Cavitary Disease
Source: Dr. Seymor Shalek, BIDMC
Source: Socios en Salud, Lima, Peru
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Gillian Lieberman, M. D.
Tuberculoma
• Single or multiple rounded, wellcircumscribed, focal lesions
• Manifestation of primary or postprimary 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
Source: Juhl JH, et al. Paul and Juhl's Essentials of Radiologic Imaging, 7th ed., 1998, p. 872.
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Gillian Lieberman, M. D.
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.
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
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Gillian Lieberman, M. D.
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.
Complications of Post-Primary Tuberculosis
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Tuberculous effusion
Tuberculous empyema
Bronchostenosis
Broncholithiasis
Spontaneous pneumothorax
Dissemination to other organs
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Gillian Lieberman, M. D.
Tuberculous effusion
Pre-thoracentesis
Source: Clinic Bon Sauveur, Cange, Haitit
Post-thoracentesis
Source: Clninc Bon Sauveur, Cange, Haiti
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Spontaneous pneumothorax
End-inspiration
End-expiration
Source: Dr. Seymor Shalek, BIDMC
Source: Dr. Seymor Shalek, BIDMC
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Gillian Lieberman, M. D.
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
Source: Brigham and Women’s Hospital, Boston, Massachusetts
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Gillian Lieberman, M. D.
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
Source: Dr. Seymor Shalek, BIDMC
David A. Walton
Gillian Lieberman, M. D.
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Differential of a miliary pattern on chest
radiograph or CT:
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
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Miliary Tuberculosis
Source: http://www.UpToDate.com
Millet seeds, after which the disease was
named. The size of the seeds correspond to
the size of the lesions seen on chest
radiograph
Source: http://www-medlib.med.utah.edu/WebPath/LUNGHTML/LUNG039.html
Gross specimen of lung
demonstrating the diffuse nature of
miliary disease
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Gillian Lieberman, M. D.
Challenge Patient
61-year-old female Haitian
peasant with cough, SOB,
and significant weight loss
over 4 months
What is the cause for the miliary
pattern?
Source: Clinic Bon Sauveur, Cange, Haiti
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Gillian Lieberman, M. D.
There is a differential:
DDX:
Miliary TB
Sarcoidosis
Metastatic Disease
Diffuse fungal infection
Source: Clinic Bon Sauveur, Cange, Haiti
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Gillian Lieberman, M. D.
Miliary Metastases
**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
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Gillian Lieberman, M. D.
Other causes of Miliary patterns:
Source: Brigham and Women’s Hospital, Boston, MAssachusetts
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
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Gillian Lieberman, M. D.
Radiographic findings for patients with
pulmonary TB, according to HIV status
Finding
HIV-positive
(n=72)
HIV-negative
(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 mediastinal
lymphadenopathy
28 (39%)
6 (12%)
Normal
8 (11%)
3 (6%)
Alpert, et al. Clinical Infectious Diseases 1997; 24:661-8.
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Gillian Lieberman, M. D.
Radiological features of pulmonary TB in 963 HIV-infected
adults compared to 1000 HIV-negative adults with TB
HIV-positive
(n=963)
HIV-negative
(n=1000)
Cavitation
319 (33%)
784 (78%)
Lymphadenopathy
253 (26%)
131 (13%)
Pleural effusions
159 (16%)
68
(7%)
Miliary pattern
94
52
(5%)
Atelectasis
112 (12%)
237 (24%)
Consolidation
94
(10%)
32
(3%)
Interstitial changes
120 (12%)
68
(7%)
Radiological feature
Tshibwabwa-Tumba, et al. Clinical Radiology 1997; 52:837-841.
(9.8%)
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Summary
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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
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References
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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.
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References
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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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Acknowledgements
I 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