DOI:10.2214/AJR.04.1599
AJR 2005; 185:1531-1539
© American Roentgen Ray Society
Idiopathic Pulmonary Fibrosis: Spectrum of High-Resolution CT Findings
Carolina Althoff Souza1,
Nestor L. Müller1,
Julia Flint2,
Joanne L. Wright2 and
Andrew Churg2
1 Department of Radiology, Vancouver General Hospital, University of British
Columbia, 899 W. 12th Ave., Vancouver, BC V5Z 1M9, Canada.
2 Department of Pathology, Vancouver General Hospital, University of British
Columbia, Vancouver, BC V5Z 1M9, Canada.
Received October 12, 2004;
accepted after revision December 8, 2004.
Address correspondence to N. L. Müller.
Abstract
OBJECTIVE. Characteristic high-resolution CT (HRCT) findings of
idiopathic pulmonary fibrosis (IPF) include reticulation, architectural
distortion, and honeycombing involving mainly the lung periphery and the lower
lobes. In 50% of IPF patients, HRCT is nonspecific. This article illustrates
the HRCT findings of IPF correlating with the pathology.
CONCLUSION. The spectrum of HRCT manifestations varies from typical
findings that allow confident diagnosis to atypical patterns mimicking other
diseases, including predominance of ground-glass opacity, consolidation,
nodules, and atypical distribution of lesions.
Introduction
Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of
chronic fibrosing interstitial pneumonia of unknown cause, limited to the
lungs and associated with a histologic pattern of usual interstitial pneumonia
(UIP) [1,
2]. It is slightly more common
in men and occurs mainly in patients over 50 years old. Clinically, IPF is
characterized by the insidious onset of a nonproductive cough and dyspnea and
the presence of fine end-inspiratory crackles. The prognosis is poor; the
median survival from the time of diagnosis is 2.5-3.5 years
[1].
The characteristic high-resolution CT (HRCT) manifestations of IPF consist
of symmetric bilateral reticulation, architectural distortion, and
honeycombing involving mainly the subpleural lung regions and lower lobes
[1]. In approximately 50% of
cases, HRCT scans are sufficient to allow a confident diagnosis of IPF,
obviating lung biopsy [2]. It
is important to realize, however, that in the remaining 50% of patients the
HRCT findings are relatively nonspecific and may mimic those of other
interstitial lung diseases.
The aim of this pictorial essay is to illustrate the spectrum of HRCT
findings that may be seen in patients with IPF and to compare the HRCT
findings with the pathologic findings.
Characteristic HRCT and Pathologic Findings of IPF
On HRCT, a confident diagnosis of IPF is based on the presence of
bilateral, predominantly subpleural, and basal reticular opacities with
associated traction bronchiectasis and honeycombing in the absence of small
nodules or extensive ground-glass opacity
[1-3]
(Figs. 1A and
1B).
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Fig. 1A —Classic idiopathic pulmonary fibrosis in 70-year-old man.
High-resolution CT shows bilateral subpleural reticulation, traction
bronchiectasis (curved arrow), and honeycombing (straight
arrows).
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Histologically, IPF is characterized by the presence of variable
proportions of interstitial inflammation, fibroblastic foci, and established
fibrosis and honeycombing coexisting with areas of normal lung parenchyma
[1-3]
(Figs. 2,
3A, and
3B).
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Fig. 2 —Photomicrograph of histopathologic specimen of 57-year-old
man with mild usual interstitial pneumonia shows paucicellular dense fibrosis
concentrated in periphery of lobule (arrows). (H and E,
x50)
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Fig. 3A —54-year-old man with severe idiopathic pulmonary fibrosis who
underwent lung transplantation. Extremely low-power view of pathologic
specimen from transplanted lung shows extensive honeycomb changes (curved
arrows) and less severely affected areas (straight arrow). (H
and E, x10)
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Fig. 3B —54-year-old man with severe idiopathic pulmonary fibrosis who
underwent lung transplantation. Photomicrograph of histopathologic specimen
(higher-power view) of less severely affected areas shows patchy interstitial
fibrosis and occasional fibroblast foci (arrows). (H and E,
x50)
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Spectrum of Manifestations of IPF
Ground-Glass Predominance
Extensive bilateral ground-glass opacity in patients with interstitial
fibrosis favors the diagnosis of nonspecific interstitial pneumonia (NSIP),
chronic hypersensitivity pneumonitis, or desquamative interstitial pneumonia
(DIP) over IPF [1]. MacDonald
et al. [4] showed that an
increased proportion of ground-glass opacity in NSIP is the most important
distinguishing feature from IPF (odds ratio, 1.04 for each 1% increase in the
proportion of ground-glass opacity). However, in that study, approximately 33%
of patients with IPF had equivalent extents of reticulation and ground-glass
opacity, and 12% had predominant ground-glass opacity. The authors therefore
concluded that there is considerable overlap between the HRCT patterns of NSIP
and IPF [4]. It should be noted
that the study was biased toward patients with atypical HRCT patterns of IPF
because patients with typical HRCT features seldom undergo lung biopsy.
Although the presence of predominant ground-glass opacity in patients with
IPF can mimic the findings seen in NSIP and hypersensitivity pneumonitis
(Figs. 4A,
4B,
5,
6A, and
6B), ground-glass opacity
tends to be associated with an improved prognosis. In a prospective study of
38 cases of biopsy-proven IPF, Gay et al.
[5] showed that the extent of
ground-glass opacity on HRCT correlated with greater likelihood of response to
treatment and that HRCT was superior to pulmonary function tests and open lung
biopsy in predicting response to therapy.
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Fig. 4B —42-year-old woman with biopsy-proven idiopathic pulmonary
fibrosis. Photomicrograph of histopathologic specimen (low-power view) shows
typical patchy interstitial fibrosis and areas of microscopic honeycombing
(arrows). (H and E, x30)
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Fig. 5 —High-resolution CT (HRCT) in 56-year-old woman with
biopsy-proven idiopathic pulmonary fibrosis (IPF) shows subtle areas of
ground-glass opacity involving both lungs and minimal subpleural reticulation.
HRCT findings are more suggestive of hypersensitivity pneumonitis or
nonspecific interstitial pneumonia than IPF.
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Fig. 6A —68-year-old man with biopsy-proven idiopathic pulmonary
fibrosis (IPF). High-resolution CT shows patchy ground-glass opacities and
fibrosis with reticulation and traction bronchiectasis (straight
arrow). Some lobules appear relatively radiolucent, reflecting mosaic
perfusion and air-trapping (curved arrows). Findings are more
suggestive of hypersensitivity pneumonitis than IPF.
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Fig. 6B —68-year-old man with biopsy-proven idiopathic pulmonary
fibrosis (IPF). Low-power view of autopsy specimen shows severe fibrosis and
honeycombing consistent with idiopathic pulmonary fibrosis. Microscopic
findings were characteristic of usual interstitial pneumonia; there was no
microscopic evidence of hypersensitivity pneumonitis. (H and E, x10)
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Although ground-glass opacity may reflect the presence of potentially
reversible active inflammation, it may also result from interstitial fibrosis
and microscopic honeycombing below the resolution of HRCT. Ground-glass
opacity should be considered as consistent with active inflammation only when
there are no superimposed findings of fibrosis such as reticulation,
architectural distortion, or traction bronchiectasis
[6]. Other potential causes of
ground-glass opacity in patients who have IPF include honeycomb cysts filled
with secretions (Figs. 7A and
7B), superimposed diffuse
alveolar damage, or a superimposed complication such as an infection or drug
reaction.
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Fig. 7B —61-year-old woman with biopsy-proven idiopathic pulmonary
fibrosis. Photomicrograph of histopathologic specimen obtained from region of
ground-glass opacity on CT shows microscopic honeycombing with airspaces
filled by mucus and inflammatory cells (arrows). (H and E,
x150)
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The clinical course of IPF is characterized by gradual deterioration over
several months or years, with progression of parenchymal abnormalities on
serial HRCT scans (Figs. 8A,
8B,
8C, and
8D). A small percentage of
patients develop acute exacerbation of IPF, a condition characterized by
marked exacerbation of dyspnea and a decrease in arterial oxygen tension
(PaO2) of more than 10 mm Hg within 1 month in the absence of
infection or heart failure. Histologically, these patients have diffuse
alveolar damage superimposed on the interstitial fibrosis. Acute exacerbation
is characterized on HRCT by the rapid development of multifocal bilateral
areas of ground-glass opacity, consolidation, or both superimposed on a
background of interstitial fibrosis (Figs.
9A,
9B,
9C, and
9D). In this setting, the
presence of extensive areas of ground-glass opacity correlates with a poor
prognosis [1].
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Fig. 8A —57-year-old man with biopsy-proven idiopathic pulmonary
fibrosis. High-resolution CT (HRCT) shows patchy bilateral areas of
ground-glass opacity. Fine reticulation is observed in subpleural regions.
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Fig. 8B —57-year-old man with biopsy-proven idiopathic pulmonary
fibrosis. HRCT at same approximate level as A, 2 years later, shows
ground-glass opacities more prominent in subpleural regions, reticulation, and
mild honeycombing.
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Fig. 8C —57-year-old man with biopsy-proven idiopathic pulmonary
fibrosis. HRCT at same approximate level as A, 3 years later, shows
extensive reticular opacities, traction bronchiectasis, and honeycombing in
areas previously involved by ground-glass opacities.
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Fig. 8D —57-year-old man with biopsy-proven idiopathic pulmonary
fibrosis. Gross pathologic specimen from autopsy shows predominantly lower
lobe, peripheral, and subpleural fibrotic lesions that alternate with areas of
normal lung (asterisks). Honeycombing cysts are seen in subpleural
regions (arrow).
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Fig. 9B —Accelerated idiopathic pulmonary fibrosis (IPF) in
62-year-old man. HRCT obtained 10 days later shows extensive areas of
ground-glass opacity and patchy consolidation involving both lungs.
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Fig. 9D —Accelerated idiopathic pulmonary fibrosis (IPF) in
62-year-old man. Another area of same lung shows hyaline membranes of diffuse
alveolar damage (arrows). Changes of diffuse alveolar damage are
typical microscopic finding in accelerated IPF. (H and E, x150)
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Consolidation and Nodules
Consolidation and nodules are uncommon radiologic manifestations of IPF in
the absence of complications such as acute exacerbation, superimposed
infection, or pulmonary carcinoma
[7]. In the series of 32
patients with proven IPF reported by MacDonald et al.
[4], nodules and consolidation
were not found. Risk of lung cancer is increased in patients who have IPF,
thus the presence of a nodule or focal area of consolidation within areas of
fibrosis should be carefully evaluated
(Fig. 10).
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Fig. 10 —High-resolution CT of 71-year-old man with idiopathic
pulmonary fibrosis shows extensive reticulation, subpleural honeycombing, and
architectural distortion. Subpleural irregular nodule (curved arrow)
is seen within area of severe fibrosis in right lung. Diagnosis of pulmonary
carcinoma was proven by biopsy.
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Patients with IPF are also at increased risk for tuberculosis, which may
also present as a solitary nodule
[8]. Another cause of nodules
in IPF is pulmonary ossification, a rare condition in which mature bone, often
containing marrow, is formed in the lung parenchyma. HRCT shows sharply
defined small calcified nodular opacities typically confined to areas of
fibrosis [9] (Figs.
11A and
11B).
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Fig. 11B —74 year-old-man with idiopathic pulmonary fibrosis and
pulmonary ossification. HRCT image photographed using soft-tissue windows at
same level as A shows bilateral small calcified nodules (curved
arrows) within areas of fibrosis.
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Distribution of Abnormalities
The characteristic basal and peripheral predominance of the abnormalities
on HRCT scans is an important clue to the diagnosis of IPF
[1]. It is important to
realize, however, that the fibrosis tends to involve all lobes. In a recent
study by Hunninghake et al.
[3], 85% of patients (45/53)
with IPF had reticulation in the upper lobes, whereas only 31% (11/36) with
other interstitial pneumonias presented with this finding.
The results of this study showed that, although more extensive and severe
in the lower zones, the presence of fibrosis in the upper lobes is an
important predictor of IPF and increases the specificity of HRCT in the
diagnosis.
Familial IPF
Some authors have suggested that familial IPF, a rare condition defined as
the presence of IPF in at least two family members, should be considered
separately from nonfamilial IPF
[1]. Although the clinical
presentation of familial IPF is similar to sporadic IPF, the long-term
prognosis is better. The findings on HRCT are similar to those described in
the nonfamilial condition except for a lower prevalence of predominant basal
distribution and honeycombing
[10].
Diseases Mimicking IPF
There is considerable overlap between the HRCT findings of IPF and those of
NSIP [11,
12]. MacDonald et al.
[4], in a comparative study
between 21 patients with histologic diagnosis of IPF and 32 with NSIP, found
that HRCT had an accuracy of 66% for discrimination between NSIP and IPF. The
sensitivity of CT for the diagnosis of IPF was 63% and the specificity was 70%
for IPF with a corresponding sensitivity of 70% and specificity of 63% for
NSIP. Predominance of ground-glass opacity was seen more commonly in patients
with NSIP and predominance of reticulation was seen more commonly in patients
with IPF [4].
The other forms of idiopathic interstitial pneumonias seldom mimic the HRCT
findings of IPF [1]. DIP is
characterized by extensive bilateral ground-glass opacities and minimal or no
fibrosis [1]. The majority of
patients improve or the condition resolves with treatment. However, severe
fibrosis mimicking IPF may be seen in patients with long-standing disease
(Figs. 12A,
12B, and
12C).
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Fig. 12B —63-year-old man with biopsy-proven desquamative interstitial
pneumonia (DIP). Photomicrograph of histopathologic specimen obtained by
surgical biopsy shows mild thickening of alveolar septa and extensive airspace
filling by macrophages (arrows). (H and E, x100) Inset:
Higher-power view shows airspace macrophages and chronic interstitial
inflammatory infiltrate (arrow). (H and E, x250) Findings are
characteristic of DIP.
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Fig. 12C —63-year-old man with biopsy-proven desquamative interstitial
pneumonia (DIP). HRCT scan at same approximate level as A 13 years
later shows extensive fibrotic changes with irregular reticular opacities,
traction bronchiectasis, and subpleural honeycombing (arrows).
Findings are those of end-stage fibrosis and mimic those of idiopathic
pulmonary fibrosis.
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HRCT manifestations of IPF may be identical to those seen in UIP associated
with collagen-vascular diseases, particularly rheumatoid arthritis and
asbestosis [1]. Presence of
pleural plaques and parenchymal bands and visualization of ferruginous
asbestos bodies on biopsy allow a correct diagnosis of asbestosis
[1,
13]. Chronic hypersensitivity
pneumonitis, sarcoidosis, and certain drug-induced lung reactions can also
occasionally result in a pattern of fibrosis indistinguishable from IPF. In
such cases, correct diagnosis requires clinical, serologic, and histologic
correlation [1].
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Abstract
Introduction
