Idiopathic Pulmonary Fibrosis: Spectrum of High-Resolution ... · idiopathic pulmonary fibrosis (IPF) shows subtle areas of ground-glass opacity involving both lungs and minimal subpleural

AJR:185, December 2005 1531

AJR 2005; 185:1531–1539

0361–803X/05/1856–1531

© American Roentgen Ray Society

Souza et al.Idiopathic Pulmonary Fibrosis on CT

C h e s t I m ag i n g • P i c t o r i a l E s s ay

Idiopathic Pulmonary Fibrosis: Spectrum of High-Resolution CT Findings

Carolina Althoff Souza1

Nestor L. Müller1

Julia Flint2

Joanne L. Wright2

Andrew Churg2

Souza CA, Müller NL, Flint J, Wright JL, Churg A

DOI:10.2214/AJR.04.1599

Received October 12, 2004; accepted after revision December 8, 2004.

1Department of Radiology, Vancouver General Hospital, University of British Columbia, 899 W. 12th Ave., Vancouver, BC V5Z 1M9, Canada. Address correspondence to N. L. Müller.

2Department of Pathology, Vancouver General Hospital, University of British Columbia, Vancouver, BC V5Z 1M9, Canada.

OBJECTIVE. Characteristic high-resolution CT (HRCT) findings of idiopathic pulmo-nary fibrosis (IPF) include reticulation, architectural distortion, and honeycombing involvingmainly 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 thatallow confident diagnosis to atypical patterns mimicking other diseases, including predomi-nance of ground-glass opacity, consolidation, nodules, and atypical distribution of lesions.

diopathic pulmonary fibrosis(IPF) is defined as a specific formof chronic fibrosing interstitialpneumonia of unknown cause,

limited to the lungs and associated with a his-tologic pattern of usual interstitial pneumonia(UIP) [1, 2]. It is slightly more common inmen and occurs mainly in patients over 50years old. Clinically, IPF is characterized bythe insidious onset of a nonproductive coughand dyspnea and the presence of fine end-in-spiratory crackles. The prognosis is poor; themedian survival from the time of diagnosis is2.5–3.5 years [1].

The characteristic high-resolution CT(HRCT) manifestations of IPF consist ofsymmetric bilateral reticulation, architec-tural distortion, and honeycombing involv-ing mainly the subpleural lung regions andlower lobes [1]. In approximately 50% ofcases, HRCT scans are sufficient to allow aconfident diagnosis of IPF, obviating lungbiopsy [2]. It is important to realize, how-ever, that in the remaining 50% of patientsthe HRCT findings are relatively nonspecificand may mimic those of other interstitiallung diseases.

The aim of this pictorial essay is to illustratethe spectrum of HRCT findings that may beseen in patients with IPF and to compare theHRCT findings with the pathologic findings.

Characteristic HRCT and Pathologic Findings of IPF

On HRCT, a confident diagnosis of IPF isbased on the presence of bilateral, predomi-

nantly subpleural, and basal reticular opaci-ties with associated traction bronchiectasisand honeycombing in the absence of smallnodules or extensive ground-glass opacity[1–3] (Fig. 1).

Histologically, IPF is characterized by thepresence of variable proportions of interstitialinflammation, fibroblastic foci, and estab-lished fibrosis and honeycombing coexistingwith areas of normal lung parenchyma [1–3](Figs. 2 and 3).

Spectrum of Manifestations of IPFGround-Glass Predominance

Extensive bilateral ground-glass opacity inpatients with interstitial fibrosis favors the di-agnosis of nonspecific interstitial pneumonia(NSIP), chronic hypersensitivity pneumoni-tis, or desquamative interstitial pneumonia(DIP) over IPF [1]. MacDonald et al. [4]showed that an increased proportion ofground-glass opacity in NSIP is the most im-portant distinguishing feature from IPF (oddsratio, 1.04 for each 1% increase in the propor-tion of ground-glass opacity). However, inthat study, approximately 33% of patientswith IPF had equivalent extents of reticula-tion and ground-glass opacity, and 12% hadpredominant ground-glass opacity. The au-thors therefore concluded that there is consid-erable overlap between the HRCT patterns ofNSIP and IPF [4]. It should be noted that thestudy was biased toward patients with atypi-cal HRCT patterns of IPF because patientswith typical HRCT features seldom undergolung biopsy.

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Although the presence of predominantground-glass opacity in patients with IPF canmimic the findings seen in NSIP and hyper-sensitivity pneumonitis (Figs. 4, 5, and 6),ground-glass opacity tends to be associatedwith an improved prognosis. In a prospectivestudy of 38 cases of biopsy-proven IPF, Gayet al. [5] showed that the extent of ground-glass opacity on HRCT correlated with

greater likelihood of response to treatmentand that HRCT was superior to pulmonaryfunction tests and open lung biopsy in pre-dicting response to therapy.

Although ground-glass opacity may re-flect the presence of potentially reversibleactive inflammation, it may also result frominterstitial fibrosis and microscopic honey-combing below the resolution of HRCT.

Ground-glass opacity should be consideredas consistent with active inflammation onlywhen there are no superimposed findings offibrosis such as reticulation, architecturaldistortion, or traction bronchiectasis [6].Other potential causes of ground-glass opac-ity in patients who have IPF include honey-comb cysts filled with secretions (Fig. 7), su-perimposed diffuse alveolar damage, or a

A B

Fig. 1—Classic idiopathic pulmonary fibrosis in 70-year-old man.A, High-resolution CT shows bilateral subpleural reticulation, traction bronchiectasis (curved arrow), and honeycombing (straight arrows).B, Coronal reformatted image shows characteristic predominance of abnormalities in subpleural and basal regions.

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, ×50)

Idiopathic Pulmonary Fibrosis on CT


superimposed complication such as an infec-tion or drug reaction.

The clinical course of IPF is characterizedby gradual deterioration over several months or

years, with progression of parenchymal abnor-malities on serial HRCT scans (Fig. 8). A smallpercentage of patients develop acute exacerba-tion of IPF, a condition characterized by

marked exacerbation of dyspnea and a de-crease in arterial oxygen tension (PaO2) ofmore than 10 mm Hg within 1 month in the ab-sence of infection or heart failure. Histologi-

Fig. 3—54-year-old man with severe idiopathic pulmonary fibrosis who underwent lung transplantation.A, 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, ×10)B, Photomicrograph of histopathologic specimen (higher-power view) of less severely affected areas shows patchy interstitial fibrosis and occasional fibroblast foci (arrows). (H and E, ×50)

A B

A B

Fig. 4—42-year-old woman with biopsy-proven idiopathic pulmonary fibrosis.A, High-resolution CT shows patchy bilateral ground-glass opacities and mild predominantly subpleural reticulation.B, Photomicrograph of histopathologic specimen (low-power view) shows typical patchy interstitial fibrosis and areas of microscopic honeycombing (arrows). (H and E, ×30)

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cally, these patients have diffuse alveolar dam-age superimposed on the interstitial fibrosis.Acute exacerbation is characterized on HRCTby the rapid development of multifocal bilat-eral areas of ground-glass opacity, consolida-tion, or both superimposed on a background ofinterstitial fibrosis (Fig. 9). In this setting, thepresence of extensive areas of ground-glassopacity correlates with a poor prognosis [1].

Consolidation and NodulesConsolidation and nodules are uncommon

radiologic manifestations of IPF in the ab-sence of complications such as acute exacer-bation, superimposed infection, or pulmo-nary carcinoma [7]. In the series of 32patients with proven IPF reported by Mac-Donald et al. [4], nodules and consolidationwere not found. Risk of lung cancer is in-

creased in patients who have IPF, thus thepresence of a nodule or focal area of consol-idation within areas of fibrosis should becarefully evaluated (Fig. 10).

Patients with IPF are also at increased riskfor tuberculosis, which may also present as asolitary nodule [8]. Another cause of nodulesin IPF is pulmonary ossification, a rare condi-tion in which mature bone, often containing

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.

A B

Fig. 6—68-year-old man with biopsy-proven idiopathic pulmonary fibrosis (IPF).A, 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.B, 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, ×10)



marrow, is formed in the lung parenchyma.HRCT shows sharply defined small calcifiednodular opacities typically confined to areasof fibrosis [9] (Fig. 11).

Distribution of AbnormalitiesThe characteristic basal and peripheral

predominance of the abnormalities onHRCT scans is an important clue to the di-

agnosis of IPF [1]. It is important to realize,however, that the fibrosis tends to involveall lobes. In a recent study by Hunninghakeet al. [3], 85% of patients (45/53) with IPF

A B

Fig. 7—61-year-old woman with biopsy-proven idiopathic pulmonary fibrosis.A, High-resolution CT shows subpleural ground-glass opacity (arrow) and mild reticulation.B, 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, ×150)

A B

Fig. 8—57-year-old man with biopsy-proven idiopathic pulmonary fibrosis.A, High-resolution CT (HRCT) shows patchy bilateral areas of ground-glass opacity. Fine reticulation is observed in subpleural regions.B, HRCT at same approximate level as A, 2 years later, shows ground-glass opacities more prominent in subpleural regions, reticulation, and mild honeycombing.(Fig. 8 continues on next page)

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had reticulation in the upper lobes, whereasonly 31% (11/36) with other interstitialpneumonias presented with this finding.

The results of this study showed that, al-though more extensive and severe in thelower zones, the presence of fibrosis in the

upper lobes is an important predictor of IPFand increases the specificity of HRCT in thediagnosis.

Fig. 8 (continued)—57-year-old man with biopsy-proven idiopathic pulmonary fibrosis.C, 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.D, 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).

DC

A B

Fig. 9—Accelerated idiopathic pulmonary fibrosis (IPF) in 62-year-old man.A, High-resolution CT (HRCT) shows patchy bilateral ground-glass opacities and subpleural reticulation.B, HRCT obtained 10 days later shows extensive areas of ground-glass opacity and patchy consolidation involving both lungs.(Fig. 9 continues on next page)



Familial IPFSome authors have suggested that famil-

ial IPF, a rare condition defined as thepresence of IPF in at least two familymembers, should be considered separatelyfrom nonfamilial IPF [1]. Although theclinical presentation of familial IPF is sim-ilar to sporadic IPF, the long-term progno-sis is better. The findings on HRCT aresimilar to those described in the nonfamil-

ial condition except for a lower prevalenceof predominant basal distribution and hon-eycombing [10].

Diseases Mimicking IPFThere is considerable overlap between the

HRCT findings of IPF and those of NSIP[11, 12]. MacDonald et al. [4], in a compar-ative study between 21 patients with histo-logic 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 ofIPF was 63% and the specificity was 70% forIPF with a corresponding sensitivity of 70%and specificity of 63% for NSIP. Predomi-nance of ground-glass opacity was seenmore commonly in patients with NSIP andpredominance of reticulation was seen morecommonly in patients with IPF [4].

C D

Fig. 9 (continued)—Accelerated idiopathic pulmonary fibrosis (IPF) in 62-year-old man.C, Low-power view of lung at autopsy shows extensive fibrosis and honeycombing (arrow). (H and E, ×30)D, 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, ×150)

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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A BFig. 11—74 year-old-man with idiopathic pulmonary fibrosis and pulmonary ossification.A, High-resolution CT (HRCT) shows subpleural reticulation and mild ground-glass opacity.B, HRCT image photographed using soft-tissue windows at same level as A shows bilateral small calcified nodules (curved arrows) within areas of fibrosis.

A

Fig. 12—63-year-old man with biopsy-proven desquamative interstitial pneumonia (DIP).A, High-resolution CT (HRCT) shows patchy bilateral areas of ground-glass opacity and mild reticulation.B, Photomicrograph of histopathologic specimen obtained by surgical biopsy shows mild thickening of alveolar septa and extensive airspace filling by macrophages (arrows). (H and E, ×100) Inset: Higher-power view shows airspace macrophages and chronic interstitial inflammatory infiltrate (arrow). (H and E, ×250) Findings are characteristic of DIP.C, 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.

B C



The other forms of idiopathic interstitialpneumonias seldom mimic the HRCT findingsof IPF [1]. DIP is characterized by extensive bi-lateral ground-glass opacities and minimal or nofibrosis [1]. The majority of patients improve orthe condition resolves with treatment. However,severe fibrosis mimicking IPF may be seen inpatients with long-standing disease (Fig. 12).

HRCT manifestations of IPF may be identi-cal to those seen in UIP associated with col-lagen-vascular diseases, particularly rheuma-toid arthritis and asbestosis [1]. Presence ofpleural plaques and parenchymal bands andvisualization of ferruginous asbestos bodies onbiopsy allow a correct diagnosis of asbestosis[1, 13]. Chronic hypersensitivity pneumonitis,sarcoidosis, and certain drug-induced lung re-actions can also occasionally result in a patternof fibrosis indistinguishable from IPF. In suchcases, correct diagnosis requires clinical, sero-logic, and histologic correlation [1].

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Idiopathic Pulmonary Fibrosis: Spectrum of High-Resolution ... · idiopathic pulmonary fibrosis (IPF) shows subtle areas of ground-glass opacity involving both lungs and minimal subpleural