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Reversed Halo Sign on High-Resolution CT of Cryptogenic Organizing Pneumonia: Diagnostic Implications

¹ Department of Diagnostic Radiology, Yonsei University College of Medicine, YongDong Severance Hospital, Seoul 135-270, Korea.
² Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Ilwon-Dong, Kangnam-Ku, Seoul 135-710, Korea.
³ Research Institute of Radiologic Science, Yonsei University, Seoul 120-752, Korea.
⁴ Department of Diagnostic Radiology, Yonsei University Wonju College of Medicine, Wonju 220-701, Korea.

Received September 10, 2002; accepted after revision October 25, 2002.

 
Address correspondence to K. S. Lee.

Abstract

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OBJECTIVE. The aim of our study was to evaluate the usefulness of the reversed halo sign on high-resolution CT in the diagnosis of cryptogenic organizing pneumonia.

MATERIALS AND METHODS. Between 1996 and 2001, we saw 31 patients with biopsy-proven cryptogenic organizing pneumonia. During the same period, we also saw 30 patients with non-cryptogenic organizing pneumonia diseases, from which cryptogenic organizing pneumonia should be differentiated: Wegener's granulomatosis (n = 14), diffuse bronchioloalveolar carcinoma (n = 10), chronic eosinophilic pneumonia (n = 5), and Churg-Strauss syndrome (n = 1). Two independent observers analyzed CT findings and recorded how frequently the so-called reversed halo sign (central ground-glass opacity and surrounding air-space consolidation of crescentic and ring shape) was seen on high-resolution CT.

RESULTS. The most common patterns of parenchymal abnormalities of cryptogenic organizing pneumonia were ground-glass opacity (28/31 patients, 90%) and consolidation (27/31, 87%). The ground-glass opacity pattern showed random distribution, and the consolidation pattern showed subpleural or peribronchovascular (20/27 patients, 74%) distribution with predominance in the middle or lower lung zone. The reversed CT halo sign was seen in six (19%) of 31 patients with cryptogenic organizing pneumonia and in none of the patients with the diseases that needed to be differentiated from cryptogenic organizing pneumonia on CT.

CONCLUSION. The reversed halo sign, although seen only in one fifth of patients with the disease, appears relatively specific to make a diagnosis of cryptogenic organizing pneumonia on CT.

Introduction

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Cryptogenic organizing pneumonia is now considered the preferred term even in the United States for idiopathic bronchiolitis obliterans organizing pneumonia. The disease is characterized histopathologically by the presence of polypoid granulation tissue in the lumina of bronchioles and alveolar ducts associated with a variable amount of interstitial and air-space infiltration of mononuclear cells and foamy macrophages [1, 2]. The most common CT finding of cryptogenic organizing pneumonia has been reported to be bilateral patchy areas of air-space consolidation that show predominantly subpleural or peribronchovascular distribution [3]. This pneumonia may also appear on CT as multiple nodules or masses containing the open bronchus sign [4].

Voloudaki et al. [5] reported two cases of cryptogenic organizing pneumonia that appeared on high-resolution CT as central ground-glass opacity surrounded by more dense air-space consolidation of crescentic and ring shapes. In their study, the central ground-glass opacity corresponded histopathologically to the area of alveolar septal inflammation and cellular debris, and the ring-shaped or crescentic peripheral air-space consolidation, to the area of organizing pneumonia within the alveolar ducts. Halo sign on high-resolution CT in pulmonary disease refers to the condition in which a less dense or ground-glass area of lung attenuation (compared with the central nodule or mass) extends around the entire circumference of the central nodule or mass [6]. Because central ground-glass opacity was surrounded by more dense air-space consolidation of crescentic and ring shape in the cryptogenic organizing pneumonia cases of Voloudaki et al. [5], we call this appearance the "reversed halo sign."

Although the reversed halo sign on thin-section chest CT was characteristic enough to suggest the diagnosis of cryptogenic organizing pneumonia in the patients of Voloudaki et al. [5], we do not know how frequently the sign is seen in patients with cryptogenic organizing pneumonia or how specific the sign is. The aim of this study was to evaluate the usefulness of the so-called reversed halo sign in the diagnosis of cryptogenic organizing pneumonia.

Materials and Methods

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During 6 years (January 1996 to December 2001), we saw 31 patients from two tertiary hospitals (one with 700 beds and one with 1200 beds) who had biopsy-proven cryptogenic organizing pneumonia. We did not include patients with associated collagen vascular diseases, known causes of organizing pneumonia, or secondary organizing pneumonia in our study. The patients included 13 men and 18 women from 20 to 79 years old, with a mean age of 53 years. In all patients, CT was performed with a 9800 or a HiSpeed Advantage scanner (General Electric Medical Systems, Milwaukee, WI). Thin-section (1- to 1.5-mm thickness) scanning was performed in all patients through the thorax at 10-mm intervals, and imaging data were reconstructed with bone algorithm (high-resolution CT). The scans were obtained using lung (window width, 1500-2000 H; window level, -700 to -800 H) and mediastinal (window width, 400 H; window level, 30 H) window settings.

Cryptogenic organizing pneumonia, in which characteristic CT findings are bilateral patchy areas of air-space consolidation showing predominantly subpleural or peribronchovascular distribution, must be differentiated from diseases of similar pattern and distribution [2, 3, 4]. For comparison, we collected the records of patients with biopsy-proven chronic eosinophilic pneumonia, Churg-Strauss syndrome, the diffuse form of bronchioloalveolar carcinoma, and Wegener's granulomatosis. During the same period in which the 31 patients with cryptogenic organizing pneumonia were seen, we encountered 14 patients with Wegener's granulomatosis (seven men and seven women; age range, 16-78 years; mean age, 50 years), 10 patients with the diffuse form of bronchioloalveolar carcinoma (four men and six women; age range, 36-78 years; mean age, 57 years), five patients with chronic eosinophilic pneumonia (one man and four women; age range, 26-71 years; mean age, 52 years), and one patient with Churg-Strauss syndrome (a 21-year-old man). In these patients, CT images were obtained with the same machines as in those patients with cryptogenic organizing pneumonia, and imaging data were reconstructed using the same protocol. High-resolution (1- to 2-mm collimation) CT scans were obtained in all patients at 10- to 20-mm intervals.

For this study, all CT scans of patients with cryptogenic organizing pneumonia and with non-cryptogenic organizing pneumonia diseases were mixed and analyzed in random order. Two independent chest radiologists who were unaware of the pathologic results of the CT scans analyzed the CT findings. Patterns of parenchymal abnormalities were subdivided into nodules ( 3 cm in diameter), masses (> 3 cm in diameter), consolidation (increased opacity with obscuration of underlying vessels), ground-glass opacities (without obscuration of underlying vessels), or irregular linear opacities (any linear opacity of irregular thickness of 1-3 mm, distinct from interlobular septa, bronchovascular bundles, and nodular opacities) [7]. The presence of the reversed halo sign was also evaluated.

The reversed halo sign was defined as central ground-glass opacity surrounded by denser consolidation of crescentic (forming more than three fourths of a circle) or ring (forming a complete circle) shape [5] of at least 2 mm in thickness (Figs. 1A, 1B). The distribution of parenchymal abnormalities was classified as predominantly in the upper, middle, or lower lung zone. The abnormalities were classified as central, subpleural, or random; diffuse or patchy; and peribronchovascular or random. Presence of bronchial dilatation, mediastinal lymph node enlargement, and pleural or pericardial effusion was also evaluated. Bronchial dilatation was regarded as present when the airways distal to lobar bronchi had diameters greater than those of accompanying arteries or did not show tapering with distal branching. Mediastinal nodes were regarded as enlarged when short-axis diameter was more than 10 mm in diameter. Other findings, if any, were also recorded.

View larger version (100K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1A. —48-year-old man with cryptogenic organizing pneumonia. Thin-section (1.5-mm collimation) CT scans obtained at levels of aortic arch (A) and bronchus intermedius (B) show patchy ground-glass opacity, consolidation, and nodule (small arrow, B) mainly with peribronchovascular distribution. Some abnormalities appear with reversed halo signs (central ground-glass opacity and surrounding air-space consolidation of crescentic and ring shapes) (large arrows).

View larger version (99K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1B. —48-year-old man with cryptogenic organizing pneumonia. Thin-section (1.5-mm collimation) CT scans obtained at levels of aortic arch (A) and bronchus intermedius (B) show patchy ground-glass opacity, consolidation, and nodule (small arrow, B) mainly with peribronchovascular distribution. Some abnormalities appear with reversed halo signs (central ground-glass opacity and surrounding air-space consolidation of crescentic and ring shapes) (large arrows).

After the analysis, the high-resolution CT findings of cryptogenic organizing pneumonia were recorded. The interobserver agreement for the presence of consolidation, ground-glass opacity, a nodule or mass, irregular linear opacity, and the reversed halo sign in patients with cryptogenic organizing pneumonia was assessed using kappa statistics [8]. The frequency of each pattern of abnormality seen on CT in each disease is the sum of the determinations of the two observers. The generalized linear model for categoric data (GENMOD procedure) was used to compare the frequency of findings of the reversed halo sign on scans of patients with cryptogenic organizing pneumonia and scans of those with non-cryptogenic organizing pneumonia diseases.

Results

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The CT pattern in cryptogenic organizing pneumonia most frequently found in our study was ground-glass opacity, seen in 90% (28/31, = 0.893) of patients (Figs. 1A, 1B, 2A, and 2B). Ground-glass opacity was bilateral in all patients, with no zonal predominance in the longitudinal planes and patchy and random distribution in the transaxial planes (Table 1).

View larger version (95K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2A. —73-year-old man with cryptogenic organizing pneumonia. Thin-section (1.5-mm collimation) CT scans obtained at level of azygos arch (A) and bronchus intermedius (B) show patchy consolidation and ground-glass opacity in both lungs. Note parenchymal abnormalities with reversed halo signs (arrows).

View larger version (92K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2B. —73-year-old man with cryptogenic organizing pneumonia. Thin-section (1.5-mm collimation) CT scans obtained at level of azygos arch (A) and bronchus intermedius (B) show patchy consolidation and ground-glass opacity in both lungs. Note parenchymal abnormalities with reversed halo signs (arrows).

The second most frequent pattern was multifocal consolidation, seen in 27 (87%) of 31 patients ( = 0.751) (Figs. 1A, 1B). Consolidation was bilateral in 26 (96%) of 27 patients and showed slightly middle and lower zonal predominance in the longitudinal planes. The consolidation was predominantly patchy (23/27, 85%), subpleural (14/27, 52%), and peribronchovascular (14/27, 52%). It was both subpleural and peribronchovascular in eight (30%) of 27 patients. Therefore, consolidation showed subpleural or peribronchovascular distribution in 20 (74%) of 27 patients (Table 1).

Nodules or masses were seen in 13 (42%) of 31 patients ( = 0.576) (Figs. 2A, 2B). Nodules were bilateral in all patients and showed no zonal predominance in the longitudinal planes. In the transaxial planes, nodules showed patchy (13/13, 100%) and random distribution. Irregular linear opacities were seen in nine (29%) of 31 patients ( = 0.889). These opacities were bilateral in eight (89%) of nine patients and showed slightly middle and lower zonal predominance in the longitudinal planes. In the transaxial planes, the opacities showed patchy (9/9, 100%) and subpleural (7/9, 78%) distribution (Table 1).

Bronchial dilatations were seen in 11 (35%) of 31 patients ( = 0.642) with cryptogenic organizing pneumonia. These dilatations were found within consolidation or ground-glass opacity. Mediastinal lymph nodes were enlarged in six (19%) of 31 patients. Right lower paratracheal (4R) nodes were enlarged in five patients, subcarinal (7) nodes were enlarged in five patients, and right high paratracheal (2R) nodes were enlarged in one patient. Pleural effusion was seen in three (10%) of 31 patients. The effusion was bilateral and small in amount in all patients.

The reversed halo sign (Figs. 1A, 1B, 2A, and 2B) was identified in the upper lung zone (n = 5), middle lung zone (n = 6), and lower lung zone (n = 6) in six (19%) of 31 patients ( = 1.000) with cryptogenic organizing pneumonia. The sign was not found on CT in any patients with Wegener's granulomatosis, diffuse bronchioloalveolar carcinoma, chronic eosinophilic pneumonia, or Churg-Strauss syndrome. The frequency of visualization of the reversed halo sign in cryptogenic organizing pneumonia was statistically significant compared with that of the other diseases (p = 0.0155).

Discussion

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Previous reports have suggested that the most common CT findings of cryptogenic organizing pneumonia consist of bilateral areas of consolidation involving mainly the subpleural and or peribronchovascular regions. However, the findings are seen in only approximately 60% of patients [2, 3]. In approximately 15% of patients with cryptogenic organizing pneumonia, the parenchymal lesions present with nodules or masses with poorly defined margins with which the open bronchus sign may be associated [4]. Because the CT patterns and distribution of consolidation and nodules or masses are still insufficient to make a correct diagnosis of cryptogenic organizing pneumonia in all patients, additional CT findings may be needed for a definitive diagnosis. We think the reversed halo sign that is specific enough may be another adjunct to make a diagnosis of cryptogenic organizing pneumonia on CT.

In our study, ground-glass opacity was seen as frequently as consolidation. However, because this opacity usually appeared with random distribution in the axial planes and showed no zonal distribution in the longitudinal planes, this finding was nonspecific and did not help in making a diagnosis of cryptogenic organizing pneumonia.

Histopathologic findings of cryptogenic organizing pneumonia include patchy distribution of intraluminal organizing fibrosis (plugs of granulation tissue) in distal air spaces including bronchioles, alveolar ducts, and alveoli. Mild and chronic mononuclear cell interstitial inflammation and mild intraalveolar cellular desquamation usually accompany these findings. On correlative studies using CT and histopathology, the areas of consolidation and nodule or mass on CT correspond histopathologically to the areas of intraluminal organizing fibrosis in distal air spaces including bronchioles, alveolar ducts, and alveoli. Ground-glass opacity corresponds histopathologically to the areas of alveolar septal inflammation and of alveolar cellular desquamation with a small amount of granulation tissue in the terminal air spaces [9, 10]. In the reversed halo sign on CT, the central ground-glass opacity corresponds histopathologically to the area of alveolar septal inflammation and cellular debris in the alveolar spaces, whereas the ring-shaped or crescentic peripheral air-space consolidation corresponds to the area of organizing pneumonia within the distal air spaces [5].

CT findings of bilateral patchy areas of air-space consolidation that show predominantly subpleural or peribronchovascular distribution [3] or findings of multiple nodules or masses containing the open bronchus sign [4] have been regarded as characteristic findings of cryptogenic organizing pneumonia. However, these findings can be seen in patients with chronic eosinophilic pneumonia, Churg-Strauss syndrome, the diffuse form of bronchioloalveolar carcinoma, and Wegener's granulomatosis [2, 5]. Of the diseases we studied, cryptogenic organizing pneumonia was the only one in which the reversed halo sign was seen. Therefore, after it was identified, the reversed halo sign was specific for making a diagnosis of cryptogenic organizing pneumonia.

Our study suffers from its retrospective nature. Because we included only the patients with biopsy-proven cases of cryptogenic organizing pneumonia, the observed frequency (19%) of the reversed halo sign on CT may not reflect the actual frequency with which it occurs. Although we could not see the sign in patients with those diseases necessitating differentiation from cryptogenic organizing pneumonia that were included in this study, we still do not know how specific the reversed halo sign is. Because cryptogenic organizing pneumonia and chronic eosinophilic pneumonia share many CT features and show overlapping characteristics [11], chronic eosinophilic pneumonia may be seen with the reversed halo sign on CT.

In conclusion, the most frequent patterns of CT findings of cryptogenic organizing pneumonia are consolidation and ground-glass opacity. The consolidation characteristically shows subpleural or peribronchovascular distribution, with middle and lower zonal predominance. The reversed halo sign, although seen in only one fifth of patients with the disease, appears to be relatively specific to make a diagnosis of cryptogenic organizing pneumonia on CT and may be another diagnostic adjunct.

References

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