the radiographic appearance of pulmonary tuberculosis

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


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:


• Tuberculosis• Atypical mycobacteria• Sarcoidosis• Silicosis• Wegner’s granulomatosis• Collagen vascular disease• Adenosquamous cancer• Lymphoma (esp. Hodgskins)• Actinomycosis• Histoplasmosis

David A. Walton


Sputum microscopy revealed numerous acid-fast bacilli

Pt started on a four drug anti-tuberculous regimen (INH, RIF, PZA, ETH)

David A. Walton


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


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


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


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


World Health Organization. WHO report on the tuberculosis epidemic, 2000

Global Incidence of Tuberculosis, 1997

David A. Walton


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


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


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


Transmission of Tuberculosis and Progression of Latent Infection

Small PM, Fujiwara PI. NEJM 2001; 189-200, p. 192.

David A. Walton


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


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


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


Radiographic Residuals of Primary Infection

Source: Iseman MD. A clinical guide to tuberculosis, 1999, p. 137.

David A. Walton


Primary TuberculosisRanke’s Complex Simon Foci

Source:Cotran et al. Robbins Pathologic Basis of Disease, 1999, p. 723.


David A. Walton


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



• 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



Source: Cotran, et al. Robbins Pathologic Basis of Disease, 1999, p. 724.

David A. Walton




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


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

David A. Walton


Cavitary Disease

Source: Socios en Salud, Lima, Peru

David A. Walton


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


Cavitary Disease

Source: Socios en Salud, Lima, PeruSource: Dr. Seymor Shalek, BIDMC

David A. Walton


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



Interval improvement of 4 x 2 cm cavitary mass abutting right hilum after 4 months of effective therapy

Source: BiDMC

David A. Walton


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


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


Complications of Post-Primary Tuberculosis

• Tuberculous effusion• Tuberculous empyema• Bronchostenosis• Broncholithiasis• Spontaneous pneumothorax• Dissemination to other organs

David A. Walton


Tuberculous effusionPost-thoracentesisPre-thoracentesis

Source: Clinic Bon Sauveur, Cange, Haitit Source: Clninc Bon Sauveur, Cange, Haiti

David A. Walton


Spontaneous pneumothoraxEnd-expirationEnd-inspiration

Source: Dr. Seymor Shalek, BIDMC Source: Dr. Seymor Shalek, BIDMC

David A. Walton


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




• 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


• 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



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


61-year-old female Haitian peasant with cough, SOB, and significant weight loss over 4 months


Challenge Patient

What is the cause for the miliary pattern?

David A. Walton


DDX:Miliary TB

Sarcoidosis

Metastatic Disease

Diffuse fungal infection


There is a differential:

David A. Walton


**S/p left mastectomy for breast CA**

DDX:Miliary TB

Sarcoidosis

Metastatic Disease

Diffuse fungal infection

Absent left breast shadow


Miliary Metastases

David A. Walton


Source: Brigham and Women’s Hospital, Boston, MAssachusetts

Other causes of Miliary patterns:


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


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


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


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


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


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.

http://www.mssm.edu/medicine/infectious-disease/consultative/case_11.html

http://telpath2.med.utah.edu/

http://www.uptodate.com/

David A. Walton


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

the radiographic appearance of pulmonary tuberculosis

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