AJR 2002; 178:1395-1399
© American Roentgen Ray Society
Pulmonary Aspergillosis in Immunocompetent Hosts Without Underlying Lesions of the Lung: Radiologic and Pathologic Findings
Eun-Young Kang1,
Dae Hyun Kim1,
Ok Hee Woo1,
Jung-Ah Choi1,
Yu-Whan Oh1 and
Chul Hwan Kim2
1 Department of Diagnostic Radiology, College of Medicine, Korea University Guro
Hospital, 80 Guro-dong, Guro-ku, 152-050 Seoul, Korea.
2 Department of Pathology, College of Medicine, Korea University Guro Hospital,
Guro-ku, 152-050 Seoul, Korea.
Received August 6, 2001;
accepted after revision December 10, 2001.
Address correspondence to E.-Y. Kang.
Abstract
OBJECTIVE. The purpose of this study was to determine the radiologic
and pathologic findings associated with pulmonary aspergillosis in
immunocompetent hosts without underlying lesions of the lung.
CONCLUSION. In immunocompetent hosts without preexisting lesions of
the lung, pulmonary aspergillosis may manifest on CT primarily as a single
nodule or mass with or without an air crescent or as a localized
consolidation.
Introduction
Pulmonary aspergillosis shows variable unique patterns of lung disease that
mainly depend on the patient's immune status and underlying lung status.
Aspergilloma in immunocompetent patients, semiinvasive aspergillosis in
patients who are in a mildly immune-suppressed state, invasive pulmonary
aspergillosis in immunocompromised patients, and allergic bronchopulmonary
aspergillosis in patients who are in a hypersensitive state are well-known
manifestations of pulmonary aspergillosis
[1,2,3,4,5,6].
In immunocompetent patients, an aspergilloma is the most common pattern of
pulmonary aspergillosis and usually develops in a preexisting cavity, bulla,
or cyst [1,
3,4,5,6,7].
A stable solitary nodule or mass and acute pneumonia that resulted in a fatal
outcome have been reported as unusual manifestations of pulmonary
aspergillosis in immunocompetent hosts
[2,
8].
We observed unusual cases of pulmonary aspergillosis that did not fall into
any known pattern of pulmonary aspergillosis. These cases of pulmonary
aspergillosis developed in patients with normal immune status who did not have
any preexisting lung diseases. The aim of this study was to assess the
radiologic and pathologic findings of pulmonary aspergillosis in
immunocompetent patients without recognized underlying lesions of the
lung.
Materials and Methods
This study included 11 consecutive patients with histologically confirmed
aspergillosis. All had abnormalities observed on chest radiographs without
underlying lung lesions. None of the patients were neutropenic or
immunocompromised. The mean age of the 11 patients was 48.2 years (range,
31-72 years); five were men, and six were women. In eight of the 11 patients,
the clinical symptoms at presentation were hemoptysis (n = 3),
blood-tinged sputum (n = 2), cough (n = 1), fever and sputum
(n = 1), or dyspnea (n = 1). The remaining three patients
did not have any chest symptoms. In these patients, abnormal findings were
incidentally discovered on chest radiographs during a preoperative workup.
Chest radiographs were obtained using the standard posteroanterior and
lateral projections with a high-kilovoltage technique. CT (Somatom Plus 40,
Siemens, Erlangen, Germany; or Sytec 3000, General Electric Medical Systems,
Milwaukee, WI) was performed with a 10-mm collimation and a 10-mm
reconstruction interval in 10 patients, and additional high-resolution CT
scans were obtained at the level of the lesion in six patients. In one
patient, only high-resolution CT scans were obtained. Images obtained with
mediastinal (width, 450 H; level, 35 H) and lung (width, 1500 H; level, -700
H) window settings were printed. IV contrast material was used in 10
patients.
Two radiologists retrospectively reviewed chest radiographs and CT scans
together and then made a consensus interpretation. Radiographic findings were
reviewed for the pattern of the lesion, the location of the lesion, and the
associated findings. On CT scans, an intrapulmonary nodule or mass was
characterized by its shape, size, and location and whether it had an internal
low-attenuation area. The size of the lesion was measured as the longest
diameter of the lesion on CT scans obtained using lung window settings. The
location of the lesion was subdivided according to anatomic lobes and was
described as central or peripheral, depending on whether the lesion involved
sites proximal or distal to a segmental bronchus. Enlarged lymph nodes were
defined as nodes with a short axis of greater than 1 cm.
In all 11 patients, aspergillosis was confirmed either by surgery
(n = 5) or by percutaneous trans-thoracic needle aspiration of the
lesions (n = 6). The interval between chest CT and histopathologic
diagnosis ranged from 3 to 55 days.
One pathologist retrospectively reviewed the histopathologic findings
again. All the slides from the percutaneous needle aspirations and the
surgical specimens were available for review. From one to 22 H and
E—stained slides were available for each case. Special stains including
Gomori's methenamine silver stain and Ziehl-Neelsen stain, which is an
acid-fast stain, were used in seven cases. The polymerase chain reaction test
for tuberculosis was performed in one case.
Results
Radiologic Findings
All 11 patients had a single lesion. On chest radiographs, nine lesions
appeared as a single nodule or mass, and two appeared as a localized
consolidation.
Of the nine lesions with a nodule or mass, three were located in the left
upper lobe, three in the left lower lobe, and three in the right lower lobe;
all nine were found in peripheral lung zones. The diameter of the nodules and
masses ranged from 1.5 to 4 cm. Within three of the nodules and masses, an air
crescent was visible on CT (Fig.
1A,1B,1C,1D),
whereas the remaining six nodules and masses did not show an air crescent
(Fig.
2A,2B,2C).
A focal low-attenuation area within the nodule or mass was noted in two (Fig.
2A,2B,2C).
Additionally, adjacent focal bronchial dilatation was seen in one, nodular
pleural thickening was seen in three (Fig.
2A,2B,2C),
and mediastinal lymph node enlargement was seen in one. Four lesions were
resected surgically. Among the five lesions with a mass or nodule that were
confirmed by percutaneous needle aspiration, one lesion showed improvement on
the follow-up radiographs (Fig.
2A,2B,2C)
and finally resolved completely, two lesions were unchanged at the 2- and
4-year follow-ups, and two lesions were lost to follow-up.
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Fig. 1A. —31-year-old woman with blood-tinged sputum. Chest radiograph
shows 1.5-cm nodule (arrow) in left upper lobe. Solitary pulmonary
nodule was only abnormality detected on chest radiography.
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Fig. 1D. —31-year-old woman with blood-tinged sputum. Photomicrograph
shows dense collection of fungal hyphae (arrow) within cavity covered
by chronic inflammatory granulation tissue. Note surrounding lymphoplasmacytic
infiltrate around cavity. (H and E, x40)
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Fig. 2B. —53-year-old man with sputum and fever. Enhanced CT scan
(soft-tissue window settings, 10-mm collimation) shows 3.5-cm mass located
mainly in right lower lobe with internal low-attenuation area. Nodular pleural
thickening (arrows) can be seen in right posterior hemithorax.
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Two lesions appeared as an area of consolidation. One was located in the
left upper lobe, and the other was located in the left lower lobe. The areas
of consolidation were triangular and showed a segmental distribution. Both
lesions had focal internal low-density areas (Figs.
3A,3B,3C
and
4A,4B).
One lesion was resected surgically (Fig.
3A,3B,3C).
The other lesion decreased in size with antifungal treatment (Fig.
4A,4B)
and continued to appear as a bandlike opacity on follow-up examinations.
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Fig. 3A. —42-year-old man with hemoptysis. CT scan (soft-tissue window
setting, 10-mm collimation) obtained at level of tracheal bifurcation shows
triangular-shaped consolidation in left upper lobe. Lesion contains internal
low-attenuation area.
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Fig. 3B. —42-year-old man with hemoptysis. Photograph of surgical
specimen shows relatively well-defined, soft brown-gray mass containing gritty
brown material. Surrounding tissue appears fibrotic, vaguely nodular. Several
dilated bronchi and bronchioles can be seen.
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Fig. 3C. —42-year-old man with hemoptysis. Photomicrograph shows
tangled fungal hyphae (arrows) within cavity and fibrosis and
lymphocytic infiltration in surrounding tissue. Inset shows nonnecrotizing
granuloma (arrows). (H and E, x40; inset: H and E,
x100)
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Fig. 4B. —41-year-old man with hemoptysis. CT scan (soft-tissue window
settings, 10-mm collimation) shows triangular-shaped consolidation with
internal low-attenuation areas in left lower lobe.
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Pathologic Findings
In four of the nine patients with a pulmonary nodule or mass, the nodule or
mass was resected. One of the two patients with an area of consolidation also
underwent surgical resection. Percutaneous needle aspiration was performed in
five patients with a nodule or mass and in one patient with an area of
consolidation.
Specimens obtained from percutaneous transthoracic needle aspiration
(n = 6) appeared on microscopy as tangled fungal hyphae admixed with
either neutrophils or respiratory epithelial cells. The use of H and E or
Gomori's methenamine silver stains revealed that the fungal hyphae had septate
filaments that branched at acute angles; these findings are consistent with
the morphology of Aspergillus. No parenchymal invasion by the fungus
was seen.
Five patents underwent thoracotomy, including two wedge resections and
three lobectomies. Macroscopically, the fungal ball appeared as a gray to
red-brown mass. The surrounding parenchyma showed some congestion and had a
fibrotic appearance (Figs.
1A,1B,1C,1D
and
3A,3B,3C).
Microscopically, the main changes involved the bronchi or bronchioles, and all
cases showed a fungal ball characterized by a dense collection of fungal
hyphae within a cavity. The branching septate hyphae suggested
Aspergillus. The lining of the cavity revealed respiratory-type
epithelium or chronic inflammatory granulation tissue
(Fig. 1D). The fungus was in
the lumen of a cavity without invading the tissues. In a 42-year-old man,
multiple granulomas were found in the surrounding lung parenchyma. Foci of
interstitial fibrosis and myxoid granulation tissues in alveoli suggested
organizing pneumonia (Fig.
3C). However, the findings for an organism in the granulomatous
lesion were negative, and results of the polymerase chain reaction for
tuberculosis were negative in pathologic specimens. In all cases, no
histologic evidence of invasive aspergillosis—such as intraalveolar
fibrinous exudate, thrombosis of the capillaries, or necrosis of the
tissue—was detected.
Discussion
Aspergilloma, or secondary noninvasive aspergillosis, is the most common
pattern of pulmonary aspergillosis in a healthy host. An aspergilloma is a
mass of Aspergillus mycelia that accumulates in a preexisting cavity,
bulla, or cyst. Preexisting diseases that are associated with aspergilloma
include tuberculosis, bronchiectasis, pneumoconiosis, sarcoidosis, and
pneumonia; in addition, preexisting bronchial cyst, bulla, or lung abscess and
sites of prior surgery are associated with aspergilloma
[1,2,3,4].
The organism causes little or no reaction in the host, and tissue invasion
does not occur. The fungus grows as a parasite and is freely movable within
the cavity. Most researchers believe that the fungus enters a preexisting
cavity and grows as a saprophyte, eventually coalescing to form a dense ball
of fungal filaments within a matrix of fibrin, mucin, and inflammatory cells
[9]. As the organism grows, it
creates extensive granulation tissue that lines the cavity and may cause
hemoptysis [4,
7]. Chest radiographs and CT
scans show the aircrescent sign, a thin-walled cavity containing a mobile
fungus ball that changes position within the cavity with the changing position
of the patient [5,
9]. The lesion is usually
single but may be multiple. Aspergillomas occur predominantly in the upper
lobes, probably reflecting the predilection for cavity formation at this site
and the relative imbalance in perfusion and ventilation in the lung apices,
which provide an oxygen-rich environment for invading organisms
[7].
Pneumonia can be caused by Aspergillus in immunocompetent hosts
without preexisting disease. This form of aspergillosis, primary invasive
aspergillosis, develops in a host with a massive inoculum of
Aspergillus. Primary invasive aspergillosis is rare in an
immunocompetent hosts but, when encountered, may prove fatal
[8,
9]. Secondary invasive
aspergillosis in an immunocompromised patient has a rapidly progressive course
and may result in death. The fungus enters the lung through the bronchi and
produces localized bronchitis. The fungus then infiltrates through the wall
into the adjacent pulmonary artery, producing thrombosis and infarction. As
the fungi then proliferate rapidly through the hemorrhagic and infarcted lung,
they produce a round expanding infarct
[6]. Primary invasive
aspergillosis manifests as bilateral diffuse infiltrates or localized
infiltrates that progress to diffuse infiltrates radiographically
[8]. In secondary invasive
aspergillosis, radiographic manifestations are variable and
nonspecific—varying from a normal appearance early in the disease to
focal or diffuse peripheral infiltrates that can progress to large areas of
consolidation
[1,2,3].
On CT scans, nodules with the halo sign are rather characteristic findings of
secondary invasive aspergillosis. As healing occurs, the central necrotic
tissue shrinks and retracts from the surrounding viable tissue, creating an
air crescent
[3,4,5].
The aspergillosis lesions described in this study do not fit into the
previously well-defined patterns of secondary noninvasive aspergillosis or
invasive aspergillosis for the following reasons. All the patients in our
study had a normal immune status and did not have a preexisting underlying
lung lesion or a history of massive exposure to Aspergillus.
Radiologic findings were not specific for well-known patterns of aspergilloma
or invasive aspergillosis. Neither tissue nor vascular invasion was detected
at histology of the surgically resected specimens. The overall prognosis for
these patients was good. A single nodule or mass was interpreted as a primary
lung malignancy or tuberculoma on the initial radiographs and CT scans.
Localized areas of consolidation were interpreted as tuberculosis, pneumonia,
or actinomycosis. Radiologic findings of aspergillosis in this study—a
single nodule or mass with or without an air crescent or as a localized
consolidation—were indistinguishable from those of malignant neoplasm,
granuloma, and other chronic infections.
Sider and Davis [2]
described unusual radiographic findings in three patients with pulmonary
aspergillosis: a stable, well-defined nodule or mass and no evidence of
underlying cavitary disease. Our four surgically proven cases of aspergilloma
consisted of a nodule or mass. On chest radiographs and CT scans of each of
these cases, a single lesion was located in the peripheral zone of the upper
or lower lobe and no underlying lung pathology was visible. These findings did
not fall into a well-known pattern of aspergilloma. Some of nodules or masses,
including these surgically confirmed cases, were similar to the cases
described by Sider and Davis rather than to a well-known pattern of
aspergilloma. Most authors believe that a fungal ball develops within a
preexisting cavity or cyst. However, other researchers believe that the fungus
is implanted in a normal bronchus, which gradually becomes dilated as a result
of the pressure created by the growing colony
[9]. Lesions in our study may
have been caused by previously unrecognized, focal, small bronchial
dilatations, which became colonized with fungus, or, more likely, by fungus
implanted in a normal bronchus, which gradually became dilated by the pressure
of the growing colony.
The massive inhalation of Aspergillus spores by healthy
individuals that led to acute, diffuse, self-limited pneumonitis with
spontaneous recovery taking several weeks has been described
[10]. In our study, nine
patients were available for follow-up. Five lesions were resected surgically,
two were treated with antifungal agents, and two were observed without
antifungal medication. Two lesions were stable during follow-up, and one mass
and one area of consolidation were improved (Figs.
2A,2B,2C
and
4A,4B).
Therefore, some of the aspergillosis lesions in this study—including
these two lesions—might follow the same clinical pattern as that
described in a previous report
[10].
In conclusion, pulmonary aspergillosis in immunocompetent hosts without a
preexisting underlying lung lesion may manifest primarily as a single nodule
or mass with or without an air crescent or as a localized consolidation on CT;
these appearances differ from the well-known pattern of aspergilloma within
preexisting structural lung disease and primary invasive aspergillosis in
immunocompetent hosts. Histopathologic findings of surgically resected lesions
revealed aspergilloma without tissue or vascular invasion. Therefore, these
patterns of aspergillosis may be called primary noninvasive pulmonary
aspergillosis.
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Abstract
Introduction
