Monica Bhargava

Gillian Lieberman, MD

July 2001

Manifestations of Pulmonary Aspergillosis

Monica Bhargava, Harvard Medical School Year IV
Gillian Lieberman, MD

Monica Bhargava
Gillian Lieberman, MD

Case Presentation: Patient P.R.

CC: P.R. is a 69-year-old Caucasian female with a hx of COPD and
heavy smoking who presents with hemoptysis.

HPI: The pt. was sitting at the hairdressers one day when she

suddenly began to cough up several tablespoons of blood. She denies

fevers/chills/sweats or syncope. She has lost 18 lbs. in the past 18
months. She denies recent foreign travel.

PMH: COPD (oxygen-dependent)

Interstitial Lung Disease
Anemia

Social Hx: 25 pack-year smoking history

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Monica Bhargava
Gillian Lieberman, MD

Case Presentation, continued: P.R.

Physical Exam:
Gen: Cachectic, bedridden, on oxygen
CV: RRR
Lung: Bibasilar crackles, R>L
Abdomen: non-tender, non-distended
Neuro: non-focal
Labs: WBC 22

HCT 37

What is this patients baseline?

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Monica Bhargava
Gillian Lieberman, MD

P.R.: Baseline CXR (one year prior)

PA View

BIDMC

Lateral View

BIDMC

Radiographic features: Lungs are hyperinflated with diaphragmatic

flattening.
flattening Increased interstitial markings throughout. Volume loss in the
right lung, with shift of hilum.
hilum Pleural thickening bilaterally (R>L).

Monica Bhargava
Gillian Lieberman, MD

P.R.: CXR on presentation

PA View

BIDMC

Lateral View

BIDMC

Radiographic features: CXR initially read as no significant change from

baseline. But CT performed later that day revealed a right apical mass.
mass
Can you see it on CXR?
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Monica Bhargava
Gillian Lieberman, MD

Differential Diagnosis:
Solitary Nodule (<4 cm)

Common:

Bronchial adenoma
Bronchogenic carcinoma
Granuloma (TB, histo, coccidiomycosis)
Hamartoma
Metastasis

Monica Bhargava
Gillian Lieberman, MD

Differential Diagnosis with Clinical Hx

Clinical history includes weight loss,
hemoptysis
Bronchogenic carcinoma (smoking-linked:
squamous, small cell ca.)
Tuberculosis (reactivation in apices?)

Monica Bhargava
Gillian Lieberman, MD

P.R.: CT on presentation
Radiographic features:
R. apical cavity filled with
dependent, sponge-like
debris.
Volume loss in the right
lung.
Note: Irregularly shaped,
sponge-like mass in a cavity is
highly suspicious for
mycetoma,
mycetoma or fungus ball.
8

Monica Bhargava
Gillian Lieberman, MD

Differential Diagnosis:
Mass Within a Cavity

Most common cause: Fungus Ball

(most common species is Aspergillus fumigatus or Aspergillus flavus,
so it is also termed aspergilloma)

Other causes:

Blood clot in tuberculous cavity

Abscess with inspissated pus
Cavitated tumor with debris

Monica Bhargava
Gillian Lieberman, MD

Aspergillus and Human Health

http://uhsweb.edu/tdemark/00t1/htm

Grants Atlas of Anatomy

Aspergillus is a ubiquitous dimorphic fungus found especially on

decaying vegetation. It can cause pulmonary disease under unique

circumstances: (1) pre-existing cavitary lung disease and (2)
immunocompromised states. Histologically, it consists of branching,
septate hyphae. Its most common portal of entry is the respiratory tract.
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Monica Bhargava
Gillian Lieberman, MD

The Varied Forms of Aspergillus Infection

Mycetoma a fungal mass growing inside a preexisting lung cavity.

Semi Invasive and Invasive Pulmonary

Aspergillosis organism erodes through tissue and
into blood vessels.

Allergic Aspergillosis fungus acts as an antigen

and initiates hypersensitivity reaction in the
respiratory tree (usually in asthmatics).

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Monica Bhargava
Gillian Lieberman, MD

What Is a Mycetoma?
Definition: A fungal mass growing inside a preexisting lung cavity that can be associated with
significant morbidity and mortality in certain patient
populations.
Risk fx: Chronic lung disease
Hx of cavitary lung disease
- TB, sarcoid, histoplasmosis, PCP (in HIV+)
- Lung abscess
- Cancer
- Bronchiectasis, emphysematous bullae
- Pulmonary infarcts

Epidemiology: approximately one in a million

Uncommon for mycetoma to progress to invasive
form.

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Monica Bhargava
Gillian Lieberman, MD

Mycetoma: Clinical Considerations

Clinical features

Patients often asymptomatic

If symptomatic, hemoptysis is the most common CC. Over
70% will experience hemoptysis during their course. > 25%
will have severe hemoptysis (> 150 ml/d).

In HIV+ patients: fever may be present.

Diagnosis

Radiologically: CXR, CT
Bronchoscopy (obtain specimen for culture)
Sputum culture

Menu of tests:

Follow with CXR, CT if symptoms worsen

or do not improve. Try lateral decubitus on CXR. Note: CT is
the more sensitive test.
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Monica Bhargava
Gillian Lieberman, MD

Mycetoma: Radiologic Features on CXR

Classic features:
rounded mass in
pre-existing cavity
air-crescent sign
pleural thickening
upper lobe
propensity
BIDMC

Patient P.R.: AP View

(2 weeks after presentation)

Note: Mycetoma has

worsened over 2 weeks.
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Monica Bhargava
Gillian Lieberman, MD

Mycetoma: Air-Crescent Sign on CXR

www.refindia.net

1997

The air-crescent or meniscus sign indicates the presence of a

mass within a pre-existing cavity. This is a patient with a fungus ball
in the right apical cavity.
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Monica Bhargava
Gillian Lieberman, MD

Mycetoma: Mass Within Old Cavities

www.sbu.ac.uk

Figure A.

Clinics in Chest Medicine. Vol. 18. No. 4. Dec. 1997

Figure B.

Fig. A. shows a fungus ball growing within an old tuberculous

cavity (CXR). Note the very thin air crescent.
crescent Fig. B. shows
cavitary pulmonary sarcoidosis with an aspergilloma,
aspergilloma gross cut
surface of the lung.

16

Student
Monica Name
Bhargava
Gillian
Gillian Lieberman,
Lieberman,MD
MD

Mycetoma: Radiologic Features on CT

BIDMC

P.R.: Axial CT, 2 weeks after presentation.

P.R.: Axial CT, on presentation.

BIDMC

Classic features: (1) Irregular, sponge-like mass in an apical

cavity. (2) Pleural thickening.
thickening (3) Air-crescent sign. Note further
consolidation adjacent to mass. Also note presence of bullae,
bullae
which are risk factors for mycetoma.

17

Monica Bhargava
Gillian Lieberman, MD

Mycetoma: Additional CT Images

Figure A.

Figure B.

Chest. Vol. III. No. 3. 1997

www.refindia.net

Fig. A. is an axial CT
of an HIV+ positive
patient with a left
lung aspergilloma.
Note mass and
walled cavity. This
patient went on to
develop invasive
aspergillosis.
Fig. B. is an axial CT
of a fungus ball in
the right lung. Note
attachment to chest
wall.
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Monica Bhargava
Gillian Lieberman, MD

Mycetoma: Treatment and Prognosis

Treatment:

- Asymptomatic:

nothing

- Symptomatic: 1. Surgical excision of affected lung

2. Arterial embolization of bleeding vessel

3. Intracavitary placement of antibiotics
4. IV amphotericin B x 2 weeks and lifelong
oral itraconazole (as in P.R.s case)

Prognosis:

Non-AIDS 8% mortality (massive hemoptysis)

AIDS (CD4 < 100) 50% disease progression
Immune status largely determines prognosis.
19

Monica Bhargava
Gillian Lieberman, MD

What is Invasive Pulmonary

Aspergillosis? (IPA)

Definition: A fungal infection of the lung in which the

organism erodes through lung tissue and invades blood

vessels, resulting in hemorrhagic infarction of lung tissue.
Broadly disseminated infection may also occur. This
infection is associated with a high mortality rate.
Risk factors: Immunosuppression (neutropenia)
-BMT
-Hematologic malignancy
-Solid organ transplant recipients
-AIDS (CD4 < 50) (esp. hx of pulmonary CMV, PCP)
-High-dose steroid use + Diabetes may result in semiinvasive Aspergillosis
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Monica Bhargava
Gillian Lieberman, MD

IPA: Clinical Considerations

Clinical Features: fever, cough, dyspnea, pleuritic
chest pain, new pulmonary infiltrate unresponsive to
antibiotics.

Diagnosis:

1. Tissue biopsy with isolation of fungus on culture or

histopathology. (open lung or bronchoscopy with transtracheal
biopsy)
2. Brochoalveolar lavage (BAL) positive for Aspergillus, in the
appropriate clinical context.
3. CT: nodule with halo sign, plus BAL positive for Aspergillus
Note: Sputum, blood cultures rarely positive.

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Monica Bhargava
Gillian Lieberman, MD

IPA: Menu of Tests

Radiologic tests: CXR, CT.
According to one study
CXR: > 70% of pts. with IPA had
abnormalities suggestive of IPA. 10% were
normal. But is it specific?
CT: > 85% of pts. with IPA had
abnormalities suggestive of IPA.
Follow patients clinically. If suspect that infection is

worsening: CXR, CT again. CT more sensitive.

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Monica Bhargava
Gillian Lieberman, MD

IPA: Radiologic Features on CXR

Diverse features:

Seminars in Roentgenology. April 2000. Vol. XXXV. No. 2.

CXR: AP View, lateral decubitus. This is a 4-year-old immunocompromised

child with IPA.

Patchy or diffuse infiltrates

(> 70%)
Multiple nodules (often
abutting pleural surface)
(14%)
Cavitary disease (central
cavitation within pulmonary
opacities) (> 30%)
Air-crescent sign this
time referring to lung
infarction and retraction,
leaving a rim of air around
the opacity. A good
prognostic sign: 67%
survival with sign.
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Monica Bhargava
Gillian Lieberman, MD

IPA: Infiltrative vs. Cavitary Disease

(CXR)

Seminars in Roentgenology. April 2000. Vol. XXX. No. 2.

Figure A: Infiltrative disease.

Radiologic Clinics of North America. September 1997. Vol. 35. No. 5.

Figure B: Cavitary Disease.

Fig. A. illustrates patchy infiltrates in a diabetic patient with IPA. This infection can
mimic other bilateral pneumonias on CXR. Fig. B. illustrates multiple bilateral nodular
densities as well as two large, irregular, thick-walled cavities in the right lung.
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Monica Bhargava
Gillian Lieberman, MD

IPA: Radiologic Features on HRCT

Radiologic Clincs of North America. July 1994. Vol. 32. No. 4.

Axial HRCT of a 50-year-old patient with leukemia who developed IPA.

Classic feature: Pulmonary mass(es)

or nodules surrounded by a zone of
mass
lower attenuation: the halo sign. This represents an inner mass of
coagulative necrosis with a rim of hemorrhagic infarction. This patient has
25
a soft-tissue nodule in the RUL.

Monica Bhargava
Gillian Lieberman, MD

IPA: More Radiologic Features on HRCT

Radiologic Clincs of North America. July 1994. Vol. 32. No. 4.

Axial HRCT of a 29-year-old patient with leukemia who developed IPA.

Extensive destruction: This picture shows bilateral, mostly

peripheral (abutting pleural surface), areas of consolidation
representing hemorrhagic infarction of lung tissue.
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Monica Bhargava
Gillian Lieberman, MD

IPA: Treatment and Prognosis

Treatment:
IV amphotericin B x 2 weeks plus lifelong
oral itraconazole. Surgical intervention may
be necessary. Therapy often ineffective.
Prognosis:
Depends on severity of immunosuppression.

Overall: 26-65% mortality

AIDS patients: > 80% mortality

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Monica Bhargava
Gillian Lieberman, MD

In Summary
Aspergillus is a ubiquitous fungus that occasionally takes up

residence in the human respiratory tract under the following

conditions: (1) pre-existing cavitary lung disease or (2) states of
severe immunosuppression.
Worrisome manifestations of this infection include
(1) minimally-invasive mycetomas and (2) invasive pulmonary
aspergillosis.
Radiology CXR, CT contributes a great deal to detection and
diagnosis.
Mycetomas are virtually pathognomonic on CT but are sometimes
obscured on CXR. They are a common cause of the air-crescent
sign. IPA often mimics other pneumonias on CXR, but it is often
associated with a halo sign on CT, representing angioinvasion.
Immunosuppression is crucial to the development of IPA, but not to
the development of mycetomas. In both circumstances, however,
immune status largely determines outcome.
outcome
28

Student
Monica Name
Bhargava
Gillian
Gillian Lieberman,
Lieberman,MD
MD

References

Addrizzo-Harris, Doreen J., Harkin, Timothy J., McGuiness, Georgeann, Naidich, David P., Rom, William N. Pulmonary aspergilloma and

AIDS. Chest. March 1997. Vol. III. No. 3.

Erasmus, Jeremy J., McAdams, H. Page, Rossi, Santiago, and Kelley, Michael J. Percutaneous management of intrapulmonary
air and fluid collections. Radiologic Clinics of North America. March 2000. Vol. 38. No. 2.
http://brighamrad.harvard.edu
http://refindia.net
http://www.edcenter.med.cornell.edu
http://www.Indianradiologist.com
http://www.mywebmd.com
http://www.sbu.ac.uk
http://www.thriveonline.oxygen.com
http://www.uhsweb.edu/tdemark.00T1/htm
Kumar, Nitin, and Miller, Wallace T. Mild immunodeficiency and its consequences. Seminars in Roentgenology. April 2000.
Vol. XXXV. No. 2.
Markowitz, Richard I., and Kramer, Sandra S. The spectrum of pulmonary infections in the immunocompromised child.
Seminars in Roentgenology. April 2000. Vol. XXXV. No. 2.
McGuiness, Georgeann. Changing trends in the pulmonary manifestations of AIDS. Radiologic Clincs of North America.
September 1997. Vol. 35. No. 5.
Mylonakis, Eleftherios, Barlam, Tamar F., Flanigan, Timothy, and Rich, Josiah D. Pulmonary aspergillosis and invasive disease
in AIDS. Chest. July 1998. Vol. 114. Number 1.
Patterson, Thomas F., Kirkpatrick, William R., White, Mary, Hiemenz, John W., Wingard, John R., Dupont, Bertrand, Rinaldi,
Michael G., Stevens, David A., Graybill, John R. Invasive aspergillosis. Medicine. July 2000. Vol. 79. No. 4.
Primack, Steven L., and Muller, Nestor L. High-resolution Computed Tomography in acute diffuse lung disease in the
immunocompromised patient. Radiologic Clinics of North America. July 1994. Vol. 32. No. 4.
Sheffield, Edward A. Pathogenesis of sarcoidosis. Clinics in Chest Medicine. December 1997. Vol. 18. No. 4.

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Student
Monica Name
Bhargava
Gillian
Gillian Lieberman,
Lieberman,MD
MD

Acknowledgements
Many thanks to Daniel Saurborn and Scott Lin of the BIDMC
Dr. Gillian Lieberman
Dr. Phillip Boiselle
Pamela Lepkowski and Beverlee Turner
Andrew Kuklewicz for his computer expertise and unflagging
patience
Arthur Liu for tips on PowerPoint
Lynda Vrooman and Vesna Ivancic
Special thanks to Larry Barbaras and Cara Lyn Damour,
our Webmasters

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