AJR 2005; 184:639-642
© American Roentgen Ray Society
Pulmonary Tuberculosis: Another Disease Showing Clusters of Small Nodules
Jeong-Nam Heo1,
Yo Won Choi,
Seok Chol Jeon and
Choong Ki Park
1 All authors: Department of Diagnostic Radiology, Hanyang University Hospital,
17 Haengdang-Dong, Sungdong-Gu, Seoul 133–792, South Korea.
Received September 24, 2003;
accepted after revision May 18, 2004.
Address correspondence to Y. W. Choi
(ywchoi{at}hanyang.ac.kr).
Supported by the research fund of Hanyang University (HY-2003-I).
Abstract
OBJECTIVE. Pulmonary sarcoidosis was recently reported to show the
"sarcoid galaxy" sign, indicating large pulmonary nodules composed
of coalescent small nodules. The purpose of this study was to review cases of
pulmonary tuberculosis showing CT features indistinguishable from the sarcoid
galaxy sign.
CONCLUSION. Large nodules arising from the coalescence of small
nodules may be seen in active tuberculosis and in sarcoidosis. The CT finding
was termed "clusters of small nodules" instead of the
"sarcoid galaxy sign" in this article. A single cluster of small
nodules, clusters of small nodules in the superior segment of the lower lobe,
or clusters of small nodules not associated with lymphadenopathy or associated
with tree-in-bud lesions would favor the diagnosis of active pulmonary
tuberculosis rather than pulmonary sarcoidosis.
Introduction
Sarcoidosis may show large parenchymal nodules with the characteristic
appearance of coalescent small nodules on CT, according to a recent report
[1]. The CT finding simulated
the appearance of a galaxy and was termed "sarcoid galaxy" sign
[1]. To our knowledge, no other
disease has been reported to show such pulmonary nodules with the galaxy
sign.
Recently we encountered patients with pulmonary tuberculosis who showed
pulmonary nodules with the galaxy sign indistinguishable from those seen in
pulmonary sarcoidosis [1]. In
this article, we use "clusters of small nodules" instead of
"sarcoid galaxy sign" because of our concern that the use of terms
without precise descriptions of the pathologic morphology may not be
understood exactly the same way by everyone. We retrospectively performed this
study to evaluate the clusters of small nodules reminiscent of a galaxy in
pulmonary tuberculosis.
Materials and Methods
Among 86 cases registered as pulmonary tuberculosis in our radiologic
teaching files, eight cases showing clusters of small nodules were identified.
As in the study of Nakatsu et al.
[1], a "cluster of small
nodules" was defined as a large parenchymal nodule (1 cm in diameter)
consisting of numerous small nodules.
The patients were four men and four women whose ages ranged from 28 to 66
years (mean, 50 years). Sputum examination did not reveal acid-fast bacilli in
any patients. The diagnosis of active tuberculosis was based on histologic
visualization of caseating granulomas typical of tuberculosis (n = 8)
in lung specimens obtained by means of percutaneous needle aspiration or
biopsy (n = 7) or transbronchial biopsy (n = 1); the
presence of acid-fast bacilli (n = 8) identified by means of a smear
of the biopsy specimen (n = 7) or culture of sputum (n = 2);
and radiographic improvement after the institution of antituberculous
medication (n = 8). No one had diabetes mellitus, acquired
immunodeficiency syndrome (AIDS), or a history of steroid medication,
alcoholism, or antituberculous medication. All patients had taken
antituberculous medication for 6–24 months (mean, 10 months).
The eight patients underwent chest radiography for 7–30 months (mean,
15 months) after the initial detection of lung lesions. Radiographic follow-up
was usually performed at least once a week during the first month and at 1- to
3-month intervals thereafter. The chest radiographs were reviewed to assess
any abnormality in the lung, mediastinum, pleura, or chest wall at the time of
diagnosis.
CT scans obtained before the administration of antituberculous medication
were available in all eight patients. Follow-up CT was not performed in any of
the eight patients. CT was performed at full inspiration on a CT 9800 scanner
(GE Healthcare) in two patients and a Somatom Plus 4 scanner (Siemens Medical
Solutions) in six patients. In all patients, CT examinations were performed
both before and after the administration of contrast media. Unenhanced CT
scans were obtained with 1-mm collimation at 20-mm intersection intervals, and
a high-spatial-frequency algorithm was used. Contiguous 8-mm sections through
the chest were also obtained after a bolus injection of 100 mL of iopromide
(Ultravist 300, Schering). All images were printed at both mediastinal (window
width, 350–450 H; window level, 20–35 H) and lung (window width,
1,500 H; window level, –700 H) window settings.
CT scans were reviewed to evaluate the number, marginal character, size,
and distribution of the clusters of small nodules and additional pulmonary
abnormalities, including bronchial wall change and tree-in-bud lesions
suggestive of active pulmonary tuberculosis
[2]. Calcification, air
bronchogram, or cavitation within the cluster was also recorded. Clusters were
classified according to size of diameter (1–2, 2–3, and >3 cm).
In addition, the presence of pleural, hilar, mediastinal, or chest wall
lesions was assessed. Two chest radiologists reviewed all chest radiographs
and CT scans simultaneously, and findings were recorded by consensus.
Results
On initial chest radiographs, a total of 11 clusters of small nodules 1 cm
or larger in diameter were identified in the eight patients. All the clusters
were in the upper lobe and the superior segment of the lower lobe and were ill
defined in margin, but internal cavitation or calcification was not evident on
conventional radiography in any patient. Peribronchial haziness, focal
consolidation, and multiple small nodules in the upper lung zone were also
seen in four, three, and three patients, respectively. No abnormality was
evident in the hilum, mediastinum, pleura, or chest wall.
On CT scans, a total of 19 clusters of small nodules were identified in the
eight patients (Figs. 1A,
1B,
1C,
1D and
2A,
2B). The number of clusters was
single in four patients and multiple in the other four (six, four, three, and
two nodules, respectively). Most of the clusters (15/19 clusters, 75%) were
1–2 cm in diameter, one was 2–3 cm, and three were greater than 3
cm. The clusters were irregular in margin, but constituent small nodules in
the periphery of the clusters showed relatively smooth margins. Most of the
clusters (18/19 clusters) were in the upper lobe (nine clusters) or the
superior segment of the lower lobe (nine clusters). The remaining one cluster
was in the basal segment of the lower lobe. Two clusters of small nodules
contained a cavity with a smooth internal surface that was less than 5 mm in
diameter. Calcification and air bronchogram within the clusters were noted in
one and three patients, respectively.
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Fig. 1A. —Asymptomatic 66-year-old man with tuberculosis in whom lung
lesions were incidentally detected at chest radiography. Posteroanterior chest
radiograph shows two ill-defined lung nodules (arrows) in both upper
lung zones.
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Fig. 1B. —Asymptomatic 66-year-old man with tuberculosis in whom lung
lesions were incidentally detected at chest radiography. Thin-section CT scans
at mediastinal (B) and lung (C) window settings obtained at
level of aortic arch show irregular nodule in left upper lobe that is composed
of numerous small nodules. Note internal calcification (arrow,
B) and air bronchograms (arrowheads, C).
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Fig. 1C. —Asymptomatic 66-year-old man with tuberculosis in whom lung
lesions were incidentally detected at chest radiography. Thin-section CT scans
at mediastinal (B) and lung (C) window settings obtained at
level of aortic arch show irregular nodule in left upper lobe that is composed
of numerous small nodules. Note internal calcification (arrow,
B) and air bronchograms (arrowheads, C).
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Fig. 1D. —Asymptomatic 66-year-old man with tuberculosis in whom lung
lesions were incidentally detected at chest radiography. Thin-section CT scan
a little lower than B and C shows another cluster of small
nodules in right upper lobe. Periphery of cluster seen in B and
C is also noted in left upper lobe. No lymphadenopathy or tree-in-bud
lesion was seen in this patient.
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Fig. 2B. —Asymptomatic 35-year-old woman with tuberculosis.
Thin-section CT scan just above aortic arch shows cluster of small nodules and
adjacent bronchial wall thickening (arrow) in left upper lobe. No
lymphadenopathy or tree-in-bud lesion was seen in this patient.
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CT showed abnormalities associated with clusters of small nodules in four
of the eight patients. Adjacent tree-in-bud lesions and bronchial wall
thickening (Fig. 2A,
2B) were noted in two patients
each. One of the two patients with bronchial wall thickening also showed hilar
lymphadenopathy. The other four patients did not show any abnormality other
than clusters of small nodules. Abnormality in the pleura, mediastinum, or
chest wall was not seen in any patient.
Discussion
Nakatsu et al. [1] recently
reported a new CT sign termed the "sarcoid galaxy" sign, which
refers to large pulmonary nodules composed of multiple small nodules and
surrounded by many tiny satellite nodules in pulmonary sarcoidosis, simulating
the appearance of a galaxy. They suggested the sign might be useful in the
diagnosis of pulmonary sarcoidosis. To our knowledge, the finding has been
reported only in pulmonary sarcoidosis
[1].
In our study, eight of 86 patients with active pulmonary tuberculosis
showed single or multiple large nodules composed of coalescent small nodules.
The large nodules were irregular in margin, but each constituent small nodule
in the periphery of the large nodules had a relatively distinct margin. These
features appeared indistinguishable from the sarcoid galaxy sign
[1], and thus the galaxy sign
is not unique to sarcoidosis.
The cluster of small nodules does not appear to coincide with any reported
pattern of pulmonary tuberculosis, such as tuberculoma or bronchogenically
spread nodules. Tuberculoma is a round or oval granuloma caused by acid-fast
bacilli that are encapsulated by connective tissue
[2] and usually regular and
smooth in outline on CT [3].
Although tuberculomas may have an irregular edge
[3], to our knowledge no
tuberculomas reported have showed such irregular surfaces resulting from a
conglomeration of small nodules as in our patients. Bronchogenic dissemination
is the most common means of spread in the postprimary or reinfection type of
tuberculosis [4,
5]. The most common finding of
bronchogenic spread of tuberculosis on thin-section CT is centrilobular
nodules and branching linear structures, giving a tree-in-bud appearance
[4,
5]. This finding is absolutely
different in appearance from tuberculous clusters of small nodules, although
both findings coexisted in 25% of our patients.
Pathologic findings of tuberculous clusters of small nodules cannot be
described here because an open lung biopsy specimen was not obtained in any of
our patients. However, the facts that both tuberculosis and sarcoidosis are
granulomatous diseases and both showed the same clusters of small nodules on
thin-section CT suggest that tuberculous and sarcoid clusters of small nodules
may have similar gross pathology. According to the CT–pathologic
correlation of sarcoid clusters, granulomas were much more concentrated toward
the center of the cluster than in its periphery, and individual macroscopic
granulomas could be identified when granulomas were not so densely assembled
[1]. We presume that the
histology of tuberculous clusters should be similar. Our hypothesis is
supported by the pathologic findings that showed granulomas in all of our
patients.
All tuberculous clusters of small nodules showed radiographic improvement
with the administration of antituberculous medication, which suggests the
clusters are findings of active tuberculosis. Although all of our patients had
active tuberculosis, half of them did not show centrilobular nodules,
tree-in-bud lesions, bronchial or bronchiolar wall thickening, or poorly
defined nodules that are known to be characteristic CT features of active
pulmonary tuberculosis [4]. In
addition, findings of acid-fast bacilli were negative at sputum examination in
all of the patients. Thus, clusters of small nodules in isolation may be
findings of active tuberculosis.
Whether the tuberculosis was primary or postprimary is speculative.
Documented conversion of the tuberculin skin test suggests primary
tuberculosis but, unfortunately, these data were not available because of the
retrospective nature of our study. From a radiologic point of view,
tuberculous clusters of small nodules seem to be postprimary because they were
mostly in the upper lobe and the superior segment of the lower lobe, common
locations of postprimary tuberculosis, and because most of them did not show
lymph node enlargement, a constituent of the Ranke complex.
Although tuberculous and sarcoid clusters of small nodules themselves
appear indistinguishable on CT, some features might be helpful for
differentiating between them. First, a single cluster of small nodules was far
more common in patients with tuberculosis (4/8 patients) than in those with
sarcoidosis (1/16 patients)
[1]. Second, sarcoid clusters
of small nodules were usually seen in the upper and middle lobes with almost
the same frequency and were rare in the lower lobes
[1], whereas most tuberculous
clusters (18/19 clusters) were in the upper lobe and the superior segment of
the lower lobe in the same frequency, reflecting the typical distribution of
postprimary pulmonary tuberculosis
[6]. Thus, clusters of small
nodules in the middle lobe favor the diagnosis of sarcoidosis, and those in
the lower lobe favor the diagnosis of tuberculosis. Finally, associated
findings may also help the differentiation. For example, lymphadenopathy is
common in patients with sarcoid clusters (15/16 patients)
[1] but is rare in patients
with tuberculous clusters (1/8 patients). Tree-in-bud lesions, one of the
characteristic features of tuberculosis
[4], should suggest the
diagnosis of tuberculosis.
Tuberculous clusters of small nodules associated with small scattered
tuberculomas may resemble progressive massive fibrosis associated with coal
worker's pneumoconiosis and silicosis. However, occupational histories and the
distribution patterns of associated small nodules (centrilobular distribution
of bronchogenically spread tuberculosis vs perilymphatic distribution of
pneumoconiosis) should easily help the differentiation
[7].
In conclusion, clusters of small nodules may be seen in pulmonary
tuberculosis and pulmonary sarcoidosis, and may be a CT finding of active
pulmonary tuberculosis. Findings of a single cluster of small nodules,
clusters of small nodules in the superior segment of the lower lobe, or
clusters of small nodules not associated with lymphadenopathy or associated
with tree-in-bud lesions should favor the diagnosis of pulmonary tuberculosis
rather than pulmonary sarcoidosis. Prospective studies are necessary in the
future; the retrospective nature and sampling bias of this study precluded
measurement of sensitivity, specificity, and accuracy of tuberculous clusters
of small nodules.
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Abstract
Introduction
