Key words
EBUS-TBNA - computed tomography - mediastinum - lymph node - anthracosis - sarcoidosis
- lymphadenopathy - occupational/environmental hazards
Introduction
Anthracosis is a form of pneumoconiosis, which is not only caused by coal dust, but
also other environmental factors such as air pollution, biomass fuels used extensively
for cooking (“hut lung”), and cigarette smoking [1]
[2]
[3]
[4]
[5]. Thus, it is not a disease per se and may occur in many different conditions and
diseases. Since anthracosis not only causes alterations of the lung parenchyma, but
also of the lymph nodes [6], radiologists should be aware of pathological findings in mediastinal lymph nodes
also in this condition.
The aim of this comparative study of EBUS-TBNA and chest computed tomography (CT)
was to demonstrate the findings in enlarged mediastinal lymph nodes with signs of
anthracosis.
Material and methods
We performed a retrospective study on all patients of our institutions showing enlarged
hilar or mediastinal lymph nodes on CT in which EBUS-TBNA confirmed the diagnosis
of lymph node anthracosis. The period of patient recruitment was April 2009 to April
2012.
Multidetector CT examinations (MSCT) were carried out using a Siemens Somatom 64 (Siemens
Medical Solutions, Forchheim, Germany) or a Toshiba Aquilion 64 (Toshiba Medical Systems,
Tokyo, Japan) CT system. Images were obtained at full inspiration using a 64 × 0.75 mm
slice collimation with a tube voltage of 120 kV. The tube current (mA) was adjusted
in relation to patient attenuation by means of the Care Dose® modus (Siemens Medical Solutions) or the Sure Exposure® modus (Toshiba Medical Systems). The reconstruction slice thickness was 3 – 5 mm.
During MDCT 100 – 120 ml of 300 mg or 400mgI/l contrast medium were generally administered
intravenously at a rate of 2 – 3 ml/s with a power injector followed by a normal saline
“chaser”.
Retrospective evaluation of computed tomographic examinations was performed consensually
by two board certified radiologists (JK, RK). Mediastinal and hilar lymph node evaluation
comprised measurement of size (short axis and long axis). In this setting, lymph node
enlargement was defined as showing a size of more than 7 – 11 mm on the short axis
depending on the regional nodal station following Glazer et al. [7]. Enlarged lymph nodes were assessed for density (prevalence of calcification or
central low density as a sign of fatty involution), shape (oval, round) and contour
(sharp, ill-defined). The presence of lymph node necrosis and noticeable contrast
enhancement was documented. Nodal necrosis was considered present when an enlarged
lymph node showed ill-defined low-attenuation areas [8]. Noticeable lymph node enhancement was determined as nodal density > 60HU in CT.
The site of the enlarged lymph nodes was documented on a standardized protocol according
to the regional lymph node classification of the American Thoracic Society [9]. The evaluation comprised a correlation of CT findings and EBUS reports. In this
context, a determination which lymph nodes in CT had been aspirated by TBNA had been
performed.
EBUS-TBNA
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was performed
with the patient under sedation or under general anesthesia as previously described
[10]. A linear array 7.5 MHz ultrasonic bronchoscope (CP EBUS, Olympus Medical Systems,
Tokyo, Japan) with a 90° angle of view was introduced orally or through an intubation
tube. After ultrasound identification of a suspicious lymph node, transbronchial needle
aspiration was performed using a 22G needle (model NA 201 SX 402, Olympus Medical
Systems, Tokyo, Japan) under real-time ultrasound guidance. The aspirated material
was prepared on glass slides, air-dried and stained.
We retrospectively evaluated the patients’ medical reports and computed tomographic
examinations with special regard to the underlying illnesses (diagnosis at admission
and discharge), the presence of COPD and emphysema, the smoking status or occupational
dust exposure as well as definitive pathologic findings. The nicotine dependence degree
was estimated by the consumption of cigarettes throughout life (number of pack-years).
Patients were classified as non-smokers, having moderate (< 20 pack-years) or severe
dependence (> 20 pack-years).
The thickening of bronchial walls as a sign of chronic bronchitis was classified as
moderate or severe compared with the representative HRCT images of airway wall thickness
as published by Awadh et al. [11]. Vascular attenuation (thinning of pulmonary vessels and reduction in their number)
and distortion (increased branching angle or straightening) were considered as signs
of emphysema. The severity of emphysema was classified semi-quantitatively as mild,
moderate or severe.
Descriptive data were presented as means with ranges, if appropriate; categorical
data were given as counts and percentages. We correlated the different CT findings
as lymph node size, shape, contour, etc. with the clinical conditions performing rank
correlation by means of a specialized computer algorithm (MedCalc© Software, Mariakerke, Belgium). The local significance level is set to 0.05. An adjustment
to multiplicity is not performed. Therefore, an overall significance level is not
determined and cannot be calculated. The presented findings may be used to generate
new hypotheses.
The study was approved by the ethics committee of our university and was compliant
with the “Health Insurance Portability and Accountability Act of 1996” (HIPAA). Patient
informed consent was not deemed necessary by the ethics committee.
Results
In 39 retrospectively enrolled patients, cytologically confirmed anthracosis ([Fig. 1]) was diagnosed in 53 lymph nodes. These patients showed a mean age of 65.1 years
(range 19 – 88 years) with a predominance of the male gender (28/39, 71.8 %).
Fig. 1 EBUS-TBNA in lymph node anthracosis: Cytologic specimen of a lymph node fragment
with deposition of anthracotic pigment in macrophages and in the extracellular space.
At the periphery of the microphotograph, erythrocytes, some inflammatory cells and
some normal epithelial cells are present. Papanicolaou staining, 2.5 × 2.
Abb. 1 EBUS-TBNA bei Lymphknotenanthrakose: Zytologisches Präparat von Lymphknotenfragmenten
mit deutlich erkennbarer Ansammlung anthrakotischen Pigments sowohl im Extrazellularraum
als auch in einzelnen Makrophagen. Am Rande des Gesichtsfeldes sind neben Erythrozyten
und vereinzelten Entzündungszellen auch Epithelien zu erkennen. Färbung nach Papanicolaou.
2,5 × 2.
Clinical conditions
The retrospective analysis of the electronic health records of these patients yielded
that 7 patients had accompanying malignancy (5 cases of bronchial cancer, 2 cases
of NHL). Slightly more than half of our patients were smokers (22/39, 56.4 %). Moderate
nicotine abuse was documented in 15 (38.5 %) patients and severe nicotine abuse in
7 (17.9 %) patients. Only one patient had occupational exposure to dust.
The vast majority of our patients (32/39, 82.1 %) showed thickening of the bronchial
walls as a sign of chronic bronchitis. This finding was classified as moderate in
18 cases (46.2 %) and severe in 14 cases (35.9 %). Mild emphysema was seen in 16 patients
(41.0 %), moderate emphysema in 5 (12.8 %) and severe emphysema in 2 patients (5.1 %).
Distribution of the examined lymph nodes ([Τable 1])
Comparing the distribution of EBUS-confirmed enlarged lymph nodes in the ATS regions,
we found that the most common site of anthracotic lymph nodes was ATS region 7 (in
total 22 nodes, i. e. 41.5 %). On closer inspection of the other regions, an accumulation
of anthracotic lymph nodes was seen on the right side (2 R, 4 R, 10 R, 11 R). In these
regions 26/53 (49.1 %) of all enlarged nodes with signs of anthracosis were found.
Table. 1
Distribution of the EBUS-confirmed anthracotic lymph nodes with respect to the ATS
regions. The most common site was ATS region 7.
|
ATS region
|
total
|
(%)
|
|
2 R
|
3
|
5.7
|
|
2 L
|
1
|
1.9
|
|
4 R
|
4
|
7.5
|
|
4 L
|
4
|
7.5
|
|
7
|
22
|
41.5
|
|
10 R
|
9
|
17
|
|
10 L
|
1
|
1.9
|
|
11 R
|
9
|
17
|
|
11 L
|
0
|
0
|
|
total
|
53
|
100
|
CT findings of enlarged lymph nodes ([Τable 2])
The short axis of the histologically proven enlarged anthracotic lymph nodes ranged
from 8mm–23 mm with a mean diameter of 13.7 mm. The long axis ranged from 12mm–31 mm
with a mean diameter of 19.3 mm. The majority of these lymph nodes (45/53, i. e. 84.9 %)
showed an oval shape ([Fig. 2]). Only five nodes were round-shaped (15.1 %), and three nodes (5.7 %) showed a polycyclic
shape ([Fig. 3]). Confluence of two or more enlarged lymph nodes ([Fig. 4]) was seen in 17/53 (32.1 %). Calcification-like hyperdensities were documented in
13 of the examined lymph nodes (24.5 %). These calcifications were sometimes subtle
and spotted, but also diffuse and homogenous ([Fig. 5]). Contrast enhancement was documented in 2/53 (3.8 %). Central hypodensity due to
fatty involution was seen in two of the anthracotic lymph nodes (3.8 %). Lymph node
necrosis was not seen.
Table 2
CT findings in enlarged lymph nodes with signs of anthracosis: anthracotic lymph nodes
often show an oval shape, well defined margins and demonstrate hyperdensities like
small calcifications.
|
size
|
short axis
|
13.7 mm
|
|
long axis
|
19.3 mm
|
|
|
%
|
n
|
|
shape
|
oval
|
84.9
|
45
|
|
round
|
15.1
|
5
|
|
polycyclic
|
5.7
|
3
|
|
margin
|
ill defined
|
1.9
|
1
|
|
well defined
|
66.0
|
35
|
|
confluence
|
32.1
|
17
|
|
contrast enhancement
|
3.8
|
2
|
|
calcification
|
24.5
|
13
|
|
fat
|
3.8
|
2
|
|
colliquation
|
0
|
0
|
|
total
|
|
53
|
Fig. 2 Chest CT (MSCT 64 × 0.75 mm slice collimation, tube voltage 120 kV, axial reconstruction)
shows a moderately enlarged (10x20 mm) well-defined oval lymph node without hyperdensities
in ATS region 2R; EBUS-TBNA revealed deposition of anthracotic pigment.
Abb. 2 EBUS-TBNA gesicherte mediastinale Lymphknotenanthrakose; die computertomografische
Untersuchung (MSCT 64 × 0,75 mm Kollimation, Röhrenspannung 120 kV, axiale Rekonstruktion)
zeigt einen mäßig vergrößerten, scharf abgrenzbaren, ovalären Lymphknoten der ATS-Region
2 R.
Fig. 3 Distinctly enlarged, well-defined lymph node with EBUS-TBNA-confirmed anthracosis
in ATS region 10 L demonstrating incipient polycyclic shape.
Abb. 3 Deutlich vergrößerter, scharf abgrenzbarer, angedeutet polyzyklisch konfigurierter
Lymphknoten der ATS-Region 10 L (zytologisch Lymphknotenanthrakose).
Fig. 4 Confluence of enlarged anthracotic lymph nodes in ATS region 4 R and 4L; nodes in
region 4 L show subtle calcifications.
Abb. 4 Deutlich vergrößerte konfluierende Lymphknoten der ATS-Regionen 4 R und 4 L bei mediastinaler
Lymphknotenanthrakose. Die konfluierenden LK in der Region 4 L zeigen feine Verkalkungen.
Fig. 5 Total and homogeneous hyperdensity of an enlarged mediastinal lymph node (ATS 2 R)
demonstrating lymph node anthracosis in EBUS-TBNA.
Abb. 5 Diffuse Verdichtung eines vergrößerten mediastinalen Lymphknoten in der ATS-Region
2 R auf dem Boden einer zytologisch nachgewiesenen Lymphknotenantrakose.
Correlation between CT findings and clinical conditions ([Table 3])
We compared clinical characteristics and the most frequent CT findings in enlarged
anthracotic lymph nodes. Neither the male gender nor smoking history nor emphysema
was correlated with any CT finding of enlarged anthracotic lymph nodes. If at all,
only two findings showed correlations with clinical conditions: Calcifications of
enlarged anthracotic lymph nodes seemed to be more often present in older patients.
Moreover, we found an association between the CT finding of lymph node confluence
and a higher degree of chronic bronchitis.
Table 3
Correlation between CT findings in EBUS-TBNA-confirmed anthracotic lymph nodes and
clinical conditions.
|
CT finding
|
n
|
age (years)
|
male
|
smoking history (dependence degree)
|
chronic bronchitis (degree)
|
emphysema (degree)
|
|
size
|
short axis
|
53
|
p = 0.10
|
p = 0.054
|
p = 0.46
|
p = 0.88
|
p = 0.22
|
|
long axis
|
53
|
p = 0.13
|
p = 0.19
|
p = 0.60
|
p = 0.39
|
p = 0.15
|
|
oval shape
|
45
|
p = 0.56
|
p = 0.95
|
p = 0.73
|
p = 0.60
|
p = 0.07
|
|
confluence
|
17
|
p = 0.14
|
p = 0.90
|
p = 0.10
|
p = 0.04 r = 0.28
|
p = 0.28
|
|
calcification
|
13
|
p = 0.03 r = 0.29
|
p = 0.81
|
p = 0.60
|
p = 0.056
|
p = 0.62
|
Discussion
Although the CT finding of enlarged mediastinal lymph nodes in cases of lung cancer
is commonly interpreted as an indicator for metastatic disease, it is also seen in
many benign conditions like sarcoidosis, chronic heart failure, COPD and pneumoconiosis
[1]
[6]
[12]
[13]
[14]
[15]
[16]
[17]. While the occurrence of enlarged calcified mediastinal lymph nodes has been generally
accepted as a sign of pneumoconiosis in coal workers [16], to date – perhaps as a result of the decline of the coal mining and steel industries
in Western countries – less attention has been paid to the impact of dust on mediastinal
lymph node staging in cancer patients. Thus, occupational exposure to dust was documented
in only one patient in the present study. On the other hand the majority of patients
with EBUS-proven mediastinal lymph node anthracosis showed bronchial wall thickening
and emphysema in CT as signs of COPD or reported severe nicotine abuse. A distinct
association between degree of COPD, smoking history and CT findings of anthracotic
lymph nodes could not be demonstrated –at least not because of the methodological
limitations of the present study.
Nevertheless, the findings of the present study demonstrate that anthracosis may be
found in considerably enlarged mediastinal lymph nodes up to 23 mm in short axis diameter.
In these lymph nodes calcification was observed in approximately one third, which
is in accordance with the literature [18]
[19]
[20]. While some authors assessed nodal confluence as a reliable indicator of malignancy
[21], this finding was observed as well in nearly one third of the anthracotic lymph
nodes of our study. Therefore, we think that confluence of enlarged lymph nodes cannot
be interpreted as a sign of metastatic disease.
The findings of our study suggest that anthracotic lymph nodes may mimic mediastinal
lymph node metastases, due to the considerable sizes and nodal confluence. Although
FDG-PET has now become a standard diagnostic procedure, recent studies revealed that
the diagnostic accuracy of FDG-PET in patients suffering from pneumoconiosis [22]
[23]
[24] is rather low and similar to that of CT [25]
[26]
[27].
Limitations
There were remarkable limitations to our study. Firstly, the sample size was small,
preventing a generalization of our results. Secondly, the study design was retrospective
and therefore some critical clinical data are missing as the history of previous pneumonias
or other severe airway inflammation. Another methodic-based limitation seems to be
that not all enlarged nodes present on CT could have been evaluated.
In the present study no comparison has been presented with special regard to non-benign
causes of lymphadenopathy. Therefore, we can only infer that anthracosis could mimic
malignancy from the fact that some of the anthracotic lymph nodes were enlarged on
CT. Therefore, we consider our results preliminary.
Conclusion
Enlarged anthracotic mediastinal lymph nodes show most often an oval shape and are
well-defined. Nodal confluence and calcifications are frequent.
-
Radiologists should be aware of mediastinal lymph node enlargement due to anthracosis.
-
The majority of these lymph nodes show no calcifications.
-
Lymph node confluence may be observed in nearly one third of the anthracotic lymph
node.
