AJR 2000; 174:51-56
© American Roentgen Ray Society
Semiinvasive Pulmonary Aspergillosis in Chronic Obstructive Pulmonary Disease
Radiologic and Pathologic Findings in Nine Patients
Tomás Franquet1,
Nestor L. Müller2,
Ana Giménez1,
Pere Domingo3,
Vicente Plaza3 and
Ramón Bordes4
1
Department of Radiology, Hospital de Sant Pau, Universidad
Autónoma de Barcelona, San Antonio M. Claret
167, 08025 Barcelona, Spain.
2
Department of Radiology, University of British Columbia and Vancouver Hospital
and Health Sciences Centre, 855 W. 12th Ave., Vancouver, British Columbia, V5Z
1M9 Canada.
3
Department of Internal Medicine, Hospital de Sant Pau, Universidad
Autónoma de Barcelona, 08025, Barcelona,
Spain.
4
Department of Pathology, Hospital de Sant Pau, Universidad
Autónoma de Barcelona, 08025, Barcelona,
Spain.
Received April 7, 1999;
accepted after revision June 21, 1999.
Address correspondence to T. Franquet.
Abstract
OBJECTIVE. The purpose of this study is to assess the radiographic,
thin-section CT, and histologic findings of semiinvasive aspergillosis in
patients with chronic obstructive pulmonary disease (COPD).
MATERIALS AND METHODS. The study included nine patients with COPD
seen at the Hospital de Sant Pau during a 3-year period who had
histopathologically proven aspergillosis with tissue invasion. Chest
radiography and thin-section (2-mm collimation) CT of the chest were available
in all cases.
RESULTS. Nine patients had semiinvasive aspergillosis proven at
autopsy (n = 7) or by thoracoscopically guided lung biopsy
(n = 2). The radiologic findings consisted of parenchymal
consolidation (n = 6) and nodules larger than 1 cm in diameter
(n = 3). Parenchymal consolidation involved the upper lobes in five
patients and was bilateral in four. Cavitation was present in two of the
patients with consolidation and in two of the patients with nodular opacities.
Adjacent pleural thickening was revealed by CT in four patients.
Histologically, the areas of consolidation represented active inflammation and
intraalveolar hemorrhage containing Aspergillus organisms. In the
three patients with multiple cavitated nodules, a variable degree of central
necrosis was observed. The inflammatory infiltrate extended into the
surrounding lung parenchyma, and adjacent areas of hemorrhage were also seen.
Aspergillus colonies were identified within the lung tissue.
CONCLUSION. Upper lobe consolidation or multiple nodules in patients
with COPD should raise the possibility of semiinvasive aspergillosis.
Introduction
Most pulmonary diseases caused by Aspergillus have been
categorized as invasive, saprophytic, or allergic
[1,
2]. However, semiinvasive
aspergillosis, also called chronic necrotizing aspergillosis, has recently
been recognized as a different type of infection that does not fit into the
three traditional categories
[3,
4]. Although invasive forms of
aspergillosis involve previously healthy areas of lung as a complication of an
immunosuppressed state [5,
6], semiinvasive aspergillosis
is more indolent and tends to occur in patients who have mildly impaired
immunity due to chronic debilitating illness, advanced age, or prolonged
corticosteroid administration, or in patients with underlying bronchiectasis
or chronic obstructive pulmonary disease (COPD)
[3,
4,
7,
8,
9]. Some studies suggest that
semiinvasive aspergillosis is increasing in frequency and may be severe or
fatal if untreated [8,
9].
The radiographic appearance of semiinvasive pulmonary aspergillosis has
been described as consisting mainly of upper lobe consolidation and pleural
thickening, and may be indistinguishable from pulmonary tuberculosis
[3,
4].
Limited information is available about the CT findings and the histologic
basis for the radiologic abnormalities. Respiratory infection is an important
cause of morbidity and mortality in patients with COPD. Accurate diagnostic
evaluation and familiarity with the radiologic manifestations of semiinvasive
aspergillosis is necessary to guide proper therapy and improve patient
survival [10].
The purpose of the present study was to evaluate the radiographic and
thin-section CT findings of semiinvasive pulmonary aspergillosis infection in
patients with COPD and to compare the radiologic with the histologic
findings.
Materials and Methods
Patients
From January 1995 through July 1998, all patients with COPD and pathologic
evidence of semiinvasive pulmonary aspergillosis were identified by a review
of the pathology database records in the department of pathology at the
Hospital de Sant Pau. The records of nine smokers with COPD and a
pathologically proven diagnosis of semiinvasive aspergillosis were reviewed.
Semiinvasive aspergillosis was diagnosed at autopsy in seven patients and by
thoracoscopically guided biopsy in two patients. All patients had undergone
both conventional chest radiography and CT. The patients were all men with a
mean age of 68 years (range, 54-89 years).
Imaging Technique
All CT examinations were performed with a Toshiba 900 CT unit (Toshiba
Medical Systems, Tokyo, Japan). Thin-collimation (2-mm) sections were obtained
at 10-mm intervals extending from the lung apices to below the costophrenic
angles. A 35-cm field of view and a 512 x 512 reconstruction matrix were
used. Images were reconstructed with a high-spatial-frequency algorithm for
parenchymal analysis and with a standard algorithm for mediastinal evaluation.
CT scans were obtained at the suspended end-inspiratory volume with an imaging
time of 2 sec. All images were obtained at window levels appropriate for lung
parenchyma (window width, 1700 H; window level, -600 H) and mediastinum
(window width, 350 H; window level, 50 H).
Review of the Images
Chest radiographs and CT scans were independently evaluated by two chest
radiologists, and the interpretation was reached by consensus only when
discrepancies were identified. The conventional chest radiographs and the
corresponding CT images were reviewed. Conventional chest radiographs and CT
scans were analyzed for the presence of parenchymal consolidation, cavitation,
nodules, pleural thickening or fluid, bronchiectasis, and any other
significant finding. The distribution of lesions was recorded as predominantly
in the upper, middle, or lower lung zone, and as predominantly central,
peripheral, or random.
Histopathologic diagnosis was based on histologic findings of
Aspergillus colonies in the bronchial tree and lung parenchyma.
Results
Most patients (n = 7) had COPD of the chronic bronchitis type,
whereas two had centrilobular emphysema affecting predominantly the upper
lobes. Five patients had received low-dose corticosteroid treatment for COPD.
Six patients had received antibiotics for suspected pulmonary infection that
was not responsive to therapy. Three patients were alcoholics, one had
diabetes, and one had chronic renal insufficiency. Symptoms and signs at
presentation included cough (eight patients, 89%), sputum (seven patients,
78%), fever (six patients, 67%), shortness of breath (five patients, 56%), and
hemoptysis (two patients, 22%). Histologic and microbiologic proof of
semiinvasive aspergillosis was obtained from specimens taken at autopsy
(n = 7) or at thoracoscopically guided biopsy (n = 2).
Before death, all the patients had received a diagnosis of probable
semiinvasive aspergillosis based on clinical, microbiologic, and radiologic
criteria [3,
7].
On conventional chest radiographs, areas of consolidation were identified
in six patients; the areas were multiple and bilateral in four and focal in
two. The consolidation was located predominantly or exclusively in the upper
lobes in five patients. Areas of cavitation were present in two patients.
Multiple pulmonary nodules measuring greater than 1 cm in diameter without
associated halos of ground-glass attenuation were present in three patients;
multiple cavities were identified in two patients. Other findings included
pleural thickening in four patients and mycetomas seen on radiography in one
patient.
On CT, the areas of consolidation were shown to be segmental in all six
patients. Adjacent pleural thickening was identified on CT in four patients
(Fig. 1A,
Fig. 1B,
Fig. 1C). Cavities seen in two
patients with consolidation had irregular walls and ranged in size from 1 to 4
cm (Fig. 2A,
Fig. 2B,
Fig. 2C). The multiple nodular
opacities present on CT in three patients had ill-defined margins. Multiple
cavitations were seen in two patients with nodules. Mycetomas were identified
on CT in two patients (Fig. 3A,
Fig. 3B,
Fig. 3C).
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Fig. 1. —Semiinvasive pulmonary aspergillosis in 72-year-old man with
centrilobular emphysema and 2-month history of cough and chest discomfort at
presentation.
A, Posteroanterior chest radiograph shows peripheral and right
apical air-space consolidation.
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Fig. 1. —Semiinvasive pulmonary aspergillosis in 72-year-old man with
centrilobular emphysema and 2-month history of cough and chest discomfort at
presentation.
B, CT scan obtained at same level as A shows segmental
air-space consolidation in posterior segment of right upper lobe that contains
multiple low-attenuation areas (arrowheads), small air bubbles, and
punctate calcifications.
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Fig. 1. —Semiinvasive pulmonary aspergillosis in 72-year-old man with
centrilobular emphysema and 2-month history of cough and chest discomfort at
presentation.
C, Photomicrograph of biopsy specimen obtained from right upper lobe
reveals widespread intraalveolar exudative eosinophil material mixed with
acute inflammatory cells, macrophages, and fungal hyphae (straight
arrows). Microabscess containing Aspergillus fumigatus colonies
(curved arrows) corresponds to low-attenuation areas seen on
B. (H and E, x400)
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Fig. 2. —Semiinvasive aspergillosis in 68-year-old man with chronic
bronchitis and recurrent episodes of mild hemoptysis.
A, Thin-section (2-mm collimation) CT scan obtained with lung
windows shows rounded area of consolidation with associated cavitation in left
upper lobe.
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Fig. 2. —Semiinvasive aspergillosis in 68-year-old man with chronic
bronchitis and recurrent episodes of mild hemoptysis.
B, Photograph of left upper lobe pathologic specimen from autopsy
shows irregular cavitary lesion with regular margins and dark-brown
appearance, consisting of necrotic material and Aspergillus
organisms.
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Fig. 2. —Semiinvasive aspergillosis in 68-year-old man with chronic
bronchitis and recurrent episodes of mild hemoptysis.
C, Photomicrograph of pathologic specimen shows cavitary lesion
containing fungal septate hyphae branching at an acute angle, which is
morphologically consistent with aspergillosis. Wall of abscess shows mild
inflammatory reaction. Surrounding pulmonary parenchyma is healthy. (H and E,
x400)
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Fig. 3. —Multiple bilateral nodules and cavitary aspergillosis in left upper
lobe in 54-year-old man with chronic bronchitis and recurrent episodes of
hemoptysis.
A, Posteroanterior chest radiograph shows multiple nodular opacities
in left lung (straight arrows); paramediastinal ill-defined density
is also visible (curved arrow).
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Fig. 3. —Multiple bilateral nodules and cavitary aspergillosis in left upper
lobe in 54-year-old man with chronic bronchitis and recurrent episodes of
hemoptysis.
B, Thin-section CT scan confirms presence of bilateral, multiple,
ill-defined nodules of various sizes. Cavitation with presence of air
crescent, not seen on conventional radiography, was easily shown by CT.
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Fig. 3. —Multiple bilateral nodules and cavitary aspergillosis in left upper
lobe in 54-year-old man with chronic bronchitis and recurrent episodes of
hemoptysis.
C, Patient died 4 months after CT examination shown in B. At
autopsy, aspergillosis abscesses and multiple small bronchial and bronchiolar
yellowish nodules corresponding to fungal bronchitis were found.
Photomicrograph shows massive Aspergillus hyphae invading bronchial
and bronchiolar epithelium (arrows). (H and E, x400)
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Histologic examination in the six patients with parenchymal consolidation
on radiography and CT showed Aspergillus organisms in alveolar
spaces, intraalveolar hemorrhage, active inflammation, and tissue necrosis
with microabscess formation (Fig.
4A, Fig. 4B,
Fig. 4C,
Fig. 4D). In the three
patients with multiple cavitated nodules, a variable degree of central
necrosis was observed. The inflammatory infiltrate extended into the
surrounding lung parenchyma, and adjacent areas of hemorrhage were also seen.
Aspergillus colonies were identified within the lung tissue. Culture
confirmation of Aspergillus fumigatus was obtained in all nine
patients. In one patient, Aspergillus hyphae were also found in the
liver and the gastrointestinal tract.
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Fig. 4. —Semiinvasive pulmonary aspergillosis in 56-year-old man with chronic
bronchitis and history of tuberculosis.
A, Posteroanterior chest radiograph obtained 6 months before
presentation shows chronic bilateral upper lobe infiltrates with associated
calcified granulomas consistent with previous tuberculosis (arrows).
Perihilar irregular linear opacities are also seen.
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Fig. 4. —Semiinvasive pulmonary aspergillosis in 56-year-old man with chronic
bronchitis and history of tuberculosis.
B, Posteroanterior chest radiograph obtained at time of presentation
shows significant progression of upper lobe infiltrates.
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Fig. 4. —Semiinvasive pulmonary aspergillosis in 56-year-old man with chronic
bronchitis and history of tuberculosis.
C, Thin-section CT scan at level of upper lobes shows bilateral
parenchymal consolidation in both upper lobes.
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Fig. 4. —Semiinvasive pulmonary aspergillosis in 56-year-old man with chronic
bronchitis and history of tuberculosis.
D, Postmortem microscopic examination confirmed fungal infection
caused by Aspergillus fumigatus. Photomicrograph from small area of
consolidation shows tissue necrosis. Aspergillus hyphae
(arrows) could be identified in necrotic tissue. (H and E,
x400)
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Discussion
Aspergillus organisms are ubiquitous and are part of the normal
environmental flora that abound in the soil around us. Although all human
beings are commonly exposed to these organisms, disseminated and invasive
forms of aspergillosis can occur in immunologically compromised hosts
[1
2,
3,
4,
5,
11,
12,
13,
14].
In severely immunocompromised patients, invasive pulmonary aspergillosis
can develop [5,
6]. Predisposing factors for
the semiinvasive form of pulmonary aspergillosis include mildly impaired host
immunity and underlying lung disease. Semiinvasive aspergillosis, or chronic
necrotizing aspergillosis, has radiologic manifestations distinct from those
of classic invasive aspergillosis
[3,
7]. Conditions associated with
the development of semiinvasive pulmonary aspergillosis include chronic
debilitating illness, diabetes mellitus, malnutrition, alcoholism, advanced
age, prolonged corticosteroid administration, and chronic obstructive lung
disease [3,
7,
8,
9]. Clinical symptoms are often
insidious and include chronic cough, sputum production, fever, and
constitutional symptoms (weight loss and weakness). Hemoptysis is seen in only
15% of patients.
The diagnosis is often difficult to make because Aspergillus
organisms may be present in the sputum or bronchoalveolar lavage fluid in
patients who have colonization of the airways without tissue invasion
[15,
16]. In clinical practice, the
diagnosis of semiinvasive aspergillosis is usually based on the presence of
multiple cultures positive for Aspergillus organisms, chest
radiographs with abnormal findings, and bronchoscopy biopsy specimens
consistent with tissue invasion.
In patients with COPD, semiinvasive aspergillosis may present with a
variety of nonspecific clinical symptoms such as cough, sputum production, and
fever for more than 6 months. The slow progression of clinical and
radiographic findings (several months to years) may contribute to a delay in
diagnosis [3,
4,
7].
Despite the relatively nonspecific appearance on imaging, unilateral or
bilateral parenchymal opacities in the upper lung zones are the most common
radiographic findings in patients with COPD and semiinvasive aspergillosis.
This upper lobe predominance may be related to the fact that underlying
diseased areas of lung promotes this form of infection. The findings are
similar to those seen with tuberculosis. In COPD patients with semiinvasive
aspergillosis, a high prevalence of cavitation, occurring in 53% of lesions,
was observed. CT scans provide accurate information about the extent and
distribution of these cavities and about the associated pleural thickening.
The treatment of this form of aspergillosis remains controversial; however,
good results have been obtained in symptomatic patients using IV amphotericin
B, oral itraconazole, or both.
In conclusion, unilateral or bilateral segmental areas of consolidation and
multiple nodular opacities are the most frequent CT findings of semiinvasive
pulmonary aspergillosis. These findings are nonspecific, most commonly
mimicking those of reactivation tuberculosis.
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Abstract
Introduction
