Idiopathic Pulmonary Fibrosis: Spectrum of High-Resolution ... idiopathic pulmonary fibrosis (IPF) shows

  • View

  • Download

Embed Size (px)

Text of Idiopathic Pulmonary Fibrosis: Spectrum of High-Resolution ... idiopathic pulmonary fibrosis (IPF)...

  • AJR:185, December 2005 1531

    AJR 2005; 185:1531–1539


    © 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


    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 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 predomi- nance of ground-glass opacity, consolidation, nodules, and atypical distribution of lesions.

    diopathic 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 his- tologic 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-in- spiratory 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, architec- tural distortion, and honeycombing involv- ing 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, how- ever, 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, predomi-

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

    Histologically, IPF is characterized by the presence of variable proportions of interstitial inflammation, fibroblastic foci, and estab- lished fibrosis and honeycombing coexisting with areas of normal lung parenchyma [1–3] (Figs. 2 and 3).

    Spectrum of Manifestations of IPF Ground-Glass Predominance

    Extensive bilateral ground-glass opacity in patients 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 of ground-glass opacity in NSIP is the most im- portant distinguishing feature from IPF (odds ratio, 1.04 for each 1% increase in the propor- tion of ground-glass opacity). However, in that study, approximately 33% of patients with IPF had equivalent extents of reticula- tion and ground-glass opacity, and 12% had predominant ground-glass opacity. The au- thors therefore concluded that there is consid- erable overlap between the HRCT patterns of NSIP and IPF [4]. It should be noted that the study was biased toward patients with atypi- cal HRCT patterns of IPF because patients with typical HRCT features seldom undergo lung biopsy.


  • Souza et al.

    1532 AJR:185, December 2005

    Although the presence of predominant ground-glass opacity in patients with IPF can mimic the findings seen in NSIP and hyper- sensitivity pneumonitis (Figs. 4, 5, and 6), 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 pre- dicting response to therapy.

    Although ground-glass opacity may re- flect the presence of potentially reversible active inflammation, it may also result from interstitial fibrosis and microscopic honey- combing 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 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

    AJR:185, December 2005 1533

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

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

    years, with progression of parenchymal abnor- malities on serial HRCT scans (Fig. 8). A small percentage 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) of more 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)

  • Souza et al.

    1534 AJR:185, December 2005

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

    Consolidation and Nodules Consolidation 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 32 patients with proven IPF reported by Mac- Donald et al. [4], nodules and consolidation were not found. Risk of lung cancer is in-

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

    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 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 sever