Abstract

OBJECTIVE. The purpose of this study was to evaluate the large parenchymal nodules in pulmonary sarcoidosis and to describe a new CT sign termed the “sarcoid galaxy.”
CONCLUSION. The CT appearance of pulmonary sarcoidosis suggests that the large nodules arise from a coalescence of small nodules. The large nodules are surrounded by many tiny satellite nodules. These findings were considered to simulate the appearance of a galaxy. This observation was supported by radiologic—pathologic correlation. The sarcoid galaxy sign may be a useful adjunct in the diagnosis of pulmonary sarcoidosis.

Introduction

Sarcoidosis is a systemic disorder of unknown cause characterized by the presence of noncaseating granulomas [1, 2]. The prevalence of sarcoidosis in Japan involves two to three per 100,000 individuals, which is less frequent than in the United States where 40-60 per 100,000 individuals are affected. Although small parenchymal nodules along the bronchoarterial bundles, interlobular septa, and major fissures and in the subpleural regions are frequently observed in pulmonary sarcoidosis on CT [3,4,5,6,7,8,9,10], large nodules (≥1 cm in diameter) are less common [3]. To our knowledge, a detailed description of large nodules in pulmonary sarcoidosis has not been reported in previous research. The purpose of this study was to evaluate the large parenchymal nodules in pulmonary sarcoidosis on CT and to describe a new CT sign the “sarcoid galaxy” sign.

Materials and Methods

Patients

Fifty-nine patients (37 men and 22 women) ranging in age from 21 to 73 years (mean age, 42.7 years) with histologically confirmed pulmonary sarcoidosis were included in this retrospective study. All CT scans showed parenchymal abnormalities. Histologic proof was obtained by means of bronchial biopsy (n = 28), mediastinal or peripheral nodal biopsy (n = 12), transbronchial lung biopsy (n = 11), open lung biopsy (n = 5), and biopsy of other organs (n = 3).

CT Examination

CT studies were performed with a helical scanner (X-Vigor; Toshiba Medical, Tokyo, Japan). After routine helical CT scans were obtained with a 10-mm collimation, CT scans with a 3-mm collimation at 10-mm intersection spacing (120 kVp, 200 mA, and 1.0-sec scanning time) were acquired. A high-spatial-frequency algorithm (bone-detail algorithm) with a field of view of 20 cm and a matrix of 512 × 512 was used. All scans were obtained from the lung apices to the bases during suspended end-inspiration, and all patients were in the supine position when examined. All images were observed and photographed at window settings appropriate for pulmonary parenchyma (level, -700 H; width, 900 H) and mediastinum (level, 30-50 H; width, 350-500 H).

Data Analysis

Large nodules in pulmonary sarcoidosis were defined as round areas of soft-tissue attenuation greater than or equal to 1 cm in diameter [3, 4]. The presence of large nodules was assessed by three radiologists who were experienced in chest radiography and CT and who were informed that all patients had pulmonary sarcoidosis; however, the radiologists were unaware of other clinical information. A conclusion was reached by consensus if there was disagreement. The number, character, size, and extension of the large nodules and their relation to other findings, including mediastinal and hilar lymphadenopathy and ground-glass areas of attenuation, were examined. The large nodules were classified according to diameter (1-2 cm, 2-3 cm, and >3 cm). The spatial distribution was also assessed independently for the upper, middle or lingual, and lower lobes of each lung. CT—pathologic correlation was performed in five patients who underwent open lung biopsy.

Results

Of the 59 patients, 16 (27%; 14 men and two women; age range, 21-70 years; mean age, 31.4 years) were found to have large nodules on CT. Multiple large nodules were seen in 15 patients, whereas a solitary nodule was noted in only one patient. The large parenchymal nodules consisted of numerous small nodules and showed irregular margins (Figs. 1A,1B,1C,2A,2B,2C,3A,3B). In the periphery of the large nodules, each constituent small nodule had a relatively distinct margin. Small low-attenuation spots were seen in the large nodules (Figs. 1B and 1C). This characteristic appearance of large parenchymal nodules resembled a galaxy that is a vast collection of millions and occasionally billions of stars (Fig. 4). This sign was recognized in all 16 patients.
Fig. 1A. 23-year-old man with mild cough. Posteroanterior chest radiograph shows mediastinal and hilar lymphadenopathy. Large parenchymal nodules are also seen in both lung fields.
Fig. 1B. 23-year-old man with mild cough. CT scan of right upper lobe shows “sarcoid galaxies” that are composed of numerous small granulomas. Fine nodular opacities are seen around large nodules. Small low-attenuation spots are noted in periphery of large nodules (arrows).
Fig. 1C. 23-year-old man with mild cough. CT scan of left lung shows another sarcoid galaxy. Small low-attenuation spot is seen in periphery of large nodule (arrow). Distortion of left major fissure is also seen (arrowhead).
Fig. 2A. Asymptomatic 22-year-old man who was found to have radiologic abnormalities by routine examination. Posteroanterior chest radiograph shows mediastinal and hilar lymphadenopathy and large parenchymal nodules in both upper lung fields (arrows).
Fig. 2B. Asymptomatic 22-year-old man who was found to have radiologic abnormalities by routine examination. CT scan of right upper lobe shows large nodule with partially smooth margin (arrows); however, “sarcoid galaxy” appearance is also evident in remaining margin (arrowhead).
Fig. 2C. Asymptomatic 22-year-old man who was found to have radiologic abnormalities by routine examination. CT scan of left upper lobe shows sarcoid galaxies located in periphery.
Fig. 3A. Asymptomatic 23-year-old woman who was found to have radiologic abnormalities by routine examination. Posteroanterior chest radiograph shows mediastinal and hilar lymphadenopathy and large parenchymal nodules in both lung fields. Cavitary nodule is observed in right upper zone.
Fig. 3B. Asymptomatic 23-year-old woman who was found to have radiologic abnormalities by routine examination. CT scan of right upper lobe shows cavitary wall is round and smoothly marginated. “Sarcoid galaxy” sign is also noted.
Fig. 4. Photograph shows globular cluster M92 (NGC 6341), class IV, in Hercules cluster of galaxies. Globular clusters are distributed in spherical halo around galactic center. Stars are more concentrated toward galactic center than in periphery. (Courtesy of Takahashi H, Tokyo, Japan)
Smooth boundaries in three of the large nodules caused investigators to disagree about their classification as the sarcoid galaxy sign. However, galaxy appearances were also evident in portions of these questionably large nodules (Fig. 2B). After reaching a consensus, we categorized these large nodules with partially smooth boundaries as sarcoid galaxies. Fine nodular opacities and large nodules were observed predominantly along the bronchoarterial bundles and, to a lesser extent, in the subpleural lymphatics and along the interlobular septal lymphatics.
A sarcoid galaxy sign with cavitation was noted in two patients (Fig. 3B). Both cavities were located in the center of the nodules, and the cavitary walls were round and smoothly demarcated. The diameters of the cavities were 1.5 and 1.8 cm, respectively. No fungus balls were observed. Ground-glass attenuations were observed in nine (56.3%) of the 16 patients.
The sarcoid galaxy of the large nodule represents innumerable coalescent granulomatous lesions. This finding was clearly revealed by the CT—pathologic correlation (Fig. 5A,5B). Toward the center of the sarcoid galaxy, granulomas were much more concentrated than in its periphery. When granulomas were not so densely assembled, it was possible to identify individual macroscopic granulomas. Peripheral low-attenuation spots corresponded to the spaces between partially coalescent small nodules (Fig. 5A,5B).
Fig. 5A. Pathologic specimens of pulmonary sarcoidosis. Photograph of open lung biopsy specimen shows 11-mm-diameter lesion (arrow). (Distance between marks on ruler indicates 1 mm.)
Fig. 5B. Pathologic specimens of pulmonary sarcoidosis. Photomicrograph of histopathologic specimen shows large sarcoid nodule produced by numerous small granulomas. Peripheral low-attenuation spots on CT correspond to spaces between partially coalescent small nodules (arrow). (H and E, ×5)
The number of sarcoid galaxies is shown in Figure 6. The upper and middle lobes revealed almost the same frequency of sarcoid galaxies, whereas the lower lobes had a small number of sarcoid galaxies in both lungs. Most (>50) sarcoid galaxies were 1-2 cm in diameter, seven were 2-3 cm, and one was greater than 3 cm. Fifteen (93.8%) of the 16 patients were associated with mediastinal and hilar lymphadenopathy that was also identified on helical CT with 10-mm collimation.
Fig. 6. Graph shows number of “sarcoid galaxies.” Multiple large nodules were seen in 15 patients, whereas solitary nodule was noted in only one patient.

Discussion

To our knowledge, this is the first report focusing on large sarcoid nodules. CT showed the characteristic pattern of large parenchymal nodules in pulmonary sarcoidosis resembling a galaxy, which corresponded to coalescent granulomas. This observation was proven by the CT—pathologic correlation. Some small nodules aggregated loosely and appeared to be in the process of composing a large nodule. In addition, we found some large nodules with partially smooth margins.
The sarcoid galaxy was found in 16 (27%) of 59 patients in our study. In previous publications on pulmonary sarcoidosis, large parenchymal nodules or spherical (alveolar) masslike areas of attenuation were observed in 25% (2/8), 15% (4/27), and 7.3% (3/41) of patients [3, 6, 7]. The incidence of large nodules in our study appears slightly high. First, patients with mediastinal and hilar lymphadenopathy without parenchymal abnormalities on CT were not included in our study. Second, patients with advanced pulmonary sarcoidosis were referred to our institution from outside hospitals. These factors may have resulted in the slightly higher incidence of large nodules.
Pathology studies show that sarcoid granulomas are present mostly along the lymphatics in the peribronchoarterial sheath and, to a lesser extent, in the subpleural and interlobular septal lymphatics [5]. On CT, irregularly thickened bronchoarterial bundles in the lung parenchyma correspond to granulomas formed in the connective tissue sheath around the pulmonary vessels and airways. Nodular densities represent noncaseating granulomas that are distributed along the lymphatics, a distribution that is considered to be the pathologic hallmark of sarcoidosis.
The appearance of a coalescence of numerous noncaseating granulomas is different from spiculation of adenocarcinoma of the lung. However, when too much contrast is shown, CT window settings could create spiculations that are actually not present by the fusion of peripheral micronodules, resulting in a more or less linear arrangement. Therefore, in some cases of large nodules of sarcoidosis, different diagnoses, including lung carcinoma, might be considered. Although the incidence of extensive mediastinal and hilar lymphadenopathy is relatively small in peripheral non—small cell lung carcinoma less than 3 cm in diameter [11], extensive mediastinal and hilar lymphadenopathy was observed in 15 (93.7%) of the 16 patients with pulmonary sarcoidosis in this study.
Although sarcoidosis can sometimes have an appearance resembling progressive massive fibrosis associated with coal worker's disease and silicosis [12], differentiation of large sarcoid nodules from other nodular lesions on CT is not difficult in typical cases that show the sarcoid galaxy sign; as a result, unnecessary intervention may be avoided. However, histologic confirmation is needed in some cases, especially for a solitary or growing large nodule. In such cases, CT may also be helpful in suggesting the best site to obtain a tissue sample for diagnosis.
Although high-resolution CT is usually performed with a slice thickness of 1-2 mm, a 3-mm collimation was used for the evaluation of large sarcoid nodules in this study. A 3-mm CT collimation may show more peripheral micronodules and more bronchioles and their branches as three-dimensional structures than will images obtained with a 1-mm collimation. However, future studies could evaluate the sarcoid galaxy sign on 1-mm CT collimation.
In conclusion, we described a new CT sign for large sarcoid nodules. Although the sensitivity, specificity, and accuracy of the sarcoid galaxy sign should be tested in a future prospective study, this sign may be a useful adjunct in the diagnosis of pulmonary sarcoidosis.

Acknowledgments

We thank Lorene M. Yoxtheimer and Justin Kung for their contributions to the preparation of this manuscript.

Footnote

Address correspondence to H. Hatabu.

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Information & Authors

Information

Published In

American Journal of Roentgenology
Pages: 1389 - 1393
PubMed: 12034602

History

Submitted: June 4, 2001
Accepted: December 6, 2001

Authors

Affiliations

Masashi Nakatsu
Department of Radiology and Nuclear Medicine, Kyoto University Hospital, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Present address: Department of Radiology, University of Pennsylvania Medical Center, 3400 Spruce St., Philadelphia, PA 19104.
Hiroto Hatabu
Department of Radiology and Nuclear Medicine, Kyoto University Hospital, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Present address: Department of Radiology, University of Pennsylvania Medical Center, 3400 Spruce St., Philadelphia, PA 19104.
Kenji Morikawa
Department of Radiology and Nuclear Medicine, Kyoto University Hospital, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Hidemasa Uematsu
Present address: Department of Radiology, University of Pennsylvania Medical Center, 3400 Spruce St., Philadelphia, PA 19104.
Yoshiharu Ohno
Present address: Department of Radiology, University of Pennsylvania Medical Center, 3400 Spruce St., Philadelphia, PA 19104.
Koichi Nishimura
Chest Disease Research Institute, Kyoto University Hospital, Sakyo-ku, Kyoto 606-8507, Japan.
Sonoko Nagai
Chest Disease Research Institute, Kyoto University Hospital, Sakyo-ku, Kyoto 606-8507, Japan.
Takateru Izumi
Chest Disease Research Institute, Kyoto University Hospital, Sakyo-ku, Kyoto 606-8507, Japan.
Junji Konishi
Department of Radiology and Nuclear Medicine, Kyoto University Hospital, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Harumi Itoh
Department of Radiology, Fukui Medical University, 23 Shimoaizuki, Matsuoka-cho, Yoshida-gun, Fukui 910-1193, Japan.

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