Shinshu M ed J, 60⑸ :249 〜255, 2012Endobronchial Ultrasound‑guided Transbronchial Needle Aspiration
for the Diagnosis of Intrathoracic Lesions:
Experience of a Single Academic Medical Center
Masanori YASUO , Takashi KOBAYASHI , Yayoi TOKORO , Toshimichi HORIUCHI
Michiko ITO , Kazushi KOJIMA , Kayoko IKEGAWA , Atsuhito USHIKI
Hiroshi YAMAMOTO , M asayuki HANAOKA , Tomonobu KOIZUMI
Akihiko YOSHIZAWA , Takayuki HONDA and Keishi KUBO
1) Endoscopic Examination Center, Shinshu University School of Medicine, Shinshu University Hospital2) First Department of Internal Medicine, Shinshu University School of Medicine
3) Comprehensive Cancer Center, Division of Clinical Oncology, Shinshu University School of Medicine,
Shinshu University Hospital4) Undergraduate, School of Medicine, Shinshu University School of Medicine
5) Department of Laboratory Medicine, Shinshu University School of Medicine

Endobronchial ultrasound‑guided transbronchial needle aspiration (EBUS‑TBNA)has been recognized asa minimally‑invasive and eﬀective method for the diagnosis and nodal staging of lung cancer.
We describe our initial experience with this method,including diagnostic sensitivity,safety,importance ofobtaining histological samples,and diagnostic pitfalls.We retrospectivelystudied 100 patients (108 consecutive
procedures)with radiologically suspicious intrathoracic lesions who were investigated by EBUS‑TBNA.
The procedures were performed between January 2005 and December 2011 at our institute. Adequate
sampling value was 91.7%.Total diagnostic yield was 68.5% (74/108).In diagnosed subjects,malignancy andbenign disease were identiﬁed in 68 and 6 cases, respectively. Diagnostic yield was relatively high in malignancy (88.3%), and poor in benign (19.4%). In the subgroup of malignant subjects, the diagnostic yield washigher in lung cancer (96.2%)than in other malignancies (72.0%)but,the diﬀerence disappeared if malignant
lymphoma was excluded. No major complications were associated with the procedure.
EBUS‑TBNA is useful in accessing the circumference of the central airway tumor for diagnosis.
Compared with previous studies,the diagnostic yield of mediastinal lymphoma and benign lesions is worse in
our laboratory.Adequate tissue sampling and preparation are needed for the deﬁnitive diagnosis of malignant
lymphoma and benign lesions. Shinshu Med J 60 : 249 ―255, 2012
(Received for publication M ay 11, 2012;accepted in revised form June 28, 2012)
Key words:EBUS‑TBNA, bronchoscopy, diagnosis, mediastinal lymph node

Introduction

under real‑time ultrasonographic guidance . The
procedure is usually performed for the nodal stag-

Endobronchial ultrasound‑guided transbronchialing of lung cancer and for the diagnosis of circum-

needle aspiration(EBUS‑TBNA)is a novel,minimallyferential central airway lesions. There are many

invasive method for peribronchial mass sampling

reports and reviews which have described its usefulness in the diagnosis of malignancy or nodal staging

Corresponding author:Masanori Yasuo
Endoscopic Examination Center, First Department ofof lung cancer.EBUS‑TBNA is now consideredInternal Medicine,Shinshu UniversitySchool of M edicine,

one of the most important diagnostic modalities for

3‑1‑1 Asahi, M atsumoto, Nagano 390‑8621 Japanlymphnode staging in lung cancer before sur-No. 5, 2012249

Yasuo.Kobayashi.Tokoro et al.

. Previous comparative studies have shown

EBUS‑TBNA at the time of their ﬁrst bronchos-its superiority to positron emission tomography

copy,it was the second procedure in a few patients(PET) and/or chest computed tomography .

after a prior negative result from conventional

Furthermore,EBUS‑TBNA mayreplace the role ofbronchoscopy with transbronchial biopsy or TBNA

mediastinoscopy for the lymphnode staging of lungfor peripheral or peribronchial lesions. A contrast

cancer before surgery .

enhanced chest computed tomography (CT) was

gery

There are some reports describing the application

routinely performed in all patients except whenof EBUS‑TBNA in benign disease such as sarcoid-

contraindicated. Positron emission tomography

osis(PET)/CT was performed in most subjects, espe-

and tuberculosis .Recently,theeﬀectivenessof the diagnosis in malignant lymphoma was also
reported. However, few reports describe thetotal diagnostic value of EBUS‑TBNA in serial
subjects with undeﬁned intrathoracic lesions.

cially when malignancy was suspected.
EBUS‑TBNA technique
Local anesthesia and conscious sedation withintramuscular injection of pethidine hydrochloride

The minimal invasiveness, lower cost and re-or intravenous injection of midazolam were ad-peatability of EBUS‑TBNA have been reported

ministered before the procedure as for conventional

many times;however, it is well recognized that

bronchoscopy. Topical anesthesia was achieved

performing EBUS‑TBNA requires training.Not all

by endobronchial instillation of 2% lidocaine. The

institutions can achieve a diagnostic accuracy

pulse oximetry saturation,resting pulse and electro-

equivalent to that of mediastinoscopy, especiallycardiograms were monitored during the procedure.

when a well‑trained expert is absent

Bronchoscopy was performed in all cases with a.

The purpose of this study was to determine theﬂexible videobronchoscope equipped with a 7.5‑

diagnostic sensitivity of EBUS‑TBNA in undeﬁned

M Hz linear ultrasound probe (Olympus model BF‑

intrathoracic lymphadenopathy. This report will

UC260F‑OL8; Olympus Ltd, Tokyo, Japan). All

also discuss the usefulness and pending improve-

procedures were performed by at least three bron-ments for the deﬁnitive diagnosis of undiagnosed

choscopists experienced in EBUS‑TBNA withintrathoracic lesions.

exclusive nursing staﬀ.As previously reported,thisM aterial and M ethods

EBUS distal probe can produce linear parallel scansof the mediastinal and peribronchial tissues and aThis was a retrospective analysis of 108 consecu-

working channel suited to the performance oftive EBUS‑TBNA procedures performed at Shin-

TBNA under direct ultrasound guidance .Biopsies

shu University Hospital (Endoscopic examination

were performed using a 21 or 22‑gauge needle(NA‑center) between January 2005, and December 2011.

201SX‑4012/4022, Olympus Optical Co Ltd.) spe-

Written informed consent was obtained from all

cially designed for use with the ultrasound bron-patients prior to the procedure.Because the EBUS‑

choscope. The needle was guided through the chan-

TBNA procedure has alreadybeen listed as a healthnel to the airway lumen and then pushed forward

insurance examination and because it was not afrom the sheath and inserted into the central airway

prospective controlled study, this study did not gowall under ultrasound guidance.A schematic of thethrough our Institutional Review Board.We perfor-procedure is shown in Fig. 1. Once the needle was

med the procedure in compliance with the Declara-

inside the target,negative pressure was maintainedtion of Helsinki. All patients enrolled this study

with a syringe at the proximal end of the catheter

were referred for EBUS‑TBNA for deﬁnitive

while the needle was pushed back and forth.

diagnosis of their mediastinal and/or hilar

Sample preparation

lymphadenopathy or mediastinal or lung mass.

The aspirated material in the needle was prepar-

Although most of the patients were examined by

ed for histological analysis by pushing it out of the250

Shinshu Med J Vol.60

EBUS‑TBNA for diagnosis

ʻinadequateʼand diagnosed as “
not diagnostic”asdescribed previously .
Diagnosis
A histological sample is important for thedeﬁnitive diagnosis. However, for example, if acytologist deﬁned it was “Class V adenocarcinoma”
and the origin of the lesion was easily presumed
clinically (e.g. lymphnode metastasis of lung cancer), we considered the diagnosis to be deﬁnitive.
Statistical analysis
Statistical analysis was performed using SPSS
14.0 software (SPSS Inc, Chicago, IL, USA) for
Windows (Microsoft Inc, Redmond, WA, USA).
Diﬀerence of diagnostic yields between malignancy
and benign, and between lung cancer and otherFig. 1 Schematic sampling image of EBUS‑TBNA
Peribronchial tissue is directly sampled. (with thepermission of Olympus Ltd)

malignancies were analyzed by the χ test. Diﬀerences between target diameters were analyzed
by Welchʼs test.The target diameters are expressed
as means ± standard deviation.

needle using a wire stylet included with the needle

Results

kit. In addition, we made cell‑block preparations
from the beginning of 2011.In our institute,if visible

A total of 108 procedures were performed in 100

aspirated material was pushing out into the normal

subjects (77 males and 23 females). EBUS‑TBNA

saline, the sample was picked up and prepared for

was administered to one patient three times and tohistological analysis (i.e. paraﬃn embedded speci-

6 other patients two times.The average age of thesemen), then the residual pieces of tissue and cells

100 patients was 66.1 ± 12.6 years. The EBUS‑

were centrifuged and made into a cell‑block sam-

TBNA diagnosis and patient outcomes are indicat-

ple. The residual specimens in the needle wereed in Fig.2.The locations of the EBUS‑TBNA sites

sprayed by a syringe onto slides for cytologicalare indicated in Table 1. The average number ofanalysis and ﬁxed with 95% ethanol.

passes in our series was 2.90 ± 1.03 per target

Deﬁnition of adequate sampling

lesion. According to the above criteria , weIf lymphocytes or malignant cells were identiﬁed
in lymphnode sampling, or if bronchial epithelium

achieved 99 adequate samplings in a total of 108
procedures (91.7%).

or pigmented alveolar macrophages were identiﬁed

We obtained 74 positive results, thus the overall

in lung sampling in cytological samples,the sample

diagnostic yield was 68.5% (74/108). 68 of thesewas considered ʻadequateʼ. If lymphocytes were

results were malignant and 6 were benign lesions.

found in LN sampling or bronchial epithelium or

The diagnostic yield of overall and malignant (lungpigmented macrophages were found in lung sam-cancer or other malignancies)lesions are shown inpling without the existence of malignant cells, theTable 2. The diagnostic yield of lung cancer was

specimen was considered ʻadequateʼand diagnosed

signiﬁcantly higher than that of other malignancies

as “
reactive lymphnode” or “benign/no‑metas-(P＜0.005). However, the diﬀerence between lungtasis”. If there was only blood and no lymphocytes

cancer and other malignancies disappeared when

and/or bronchial epithelial cells and cartilaginous

malignant lymphoma was excluded (3 diagnosed

tissues were identiﬁed,the case was interpreted as aand 3 undiagnosed (Fig. 2)). The diagnostic yield

No. 5, 2012251

Yasuo.Kobayashi.Tokoro et al.

Fig. 2 Outcomes of patients undergoing EBUS‑TBNA
Ad :adenocarcinoma,SCC :squamous cell carcinoma,NSCLC :non‑small cell lung cancer,
LCNEC :large cell neuroendocrine cell carcinoma, SCLC :small cell lung cancer,
LN :lymphnode, M AC :mycobacterium avium complex
Table 1 The locations of the EBUS‑TBNA sites

according to the lesion size is indicated in Table 3.
#2R
#2L
#4R
#4L
#5
#7

2
1

It clearly shows the diagnostic yield worsened with26
6

In benign lesions, the diagnostic yield was poor

smaller lesion size.
(6/31, 19.4%)in our laboratory. Benign lesions are

3
36
2
1

#10R
#10L
#11R
#11L

seldom diagnosed deﬁnitively only by cytology.We
consider the fact that the deﬁnitive diagnosis of abenign lesion requires not only cytological samples

14
1

Mediastinal tumor
LN with tumor
Lung tumor

but also histological samples as the major reason

7
5
8

for the low diagnostic yield in benign lesions.Until
the end of 2010,we did not request the pathologist to
make cell‑blocks. From 2011 on, we started to#:number of the mediastinal lymph node stations
Table 2 Diagnostic yields in several disease categories

Diagnostic
Not diagnostic
Total
Diagnostic yield (%)

Overall

M alignancy

LungcancerOther
malignancy

74
34
108
68.5

68
9
77
88.3

50
2
52
96.2

18
7
25
72.0

a :P＝0.007 vs. Other malignancy
252

Shinshu Med J Vol.60

EBUS‑TBNA for diagnosis

make cell‑blocks to obtain improved histologicalferential central airway lesions. The procedure

information from the EBUS‑TBNA samples. For

provided a high diagnostic yield in malignancy

example, we could not obtain a good diagnostic(88.3%), especially in lung cancer (96.2%). No

yield of sarcoidosis prior to making cell‑blocks (1major complications were associated with this pro-diagnosed in 7 procedures). Afterwards, however,cedure except for a small amount of bleeding at thewe established a deﬁnitive diagnosis in all sar-sites penetrated by the TBNA needle.

coidosis patients, although the data is still limited

Similar diagnostic yields have been reported in(three patients).The change in the diagnostic yields

several studies . We experienced a variety of

before and after making cell‑blocks is shown inbenign lesions, primary malignancy and metastatic

Table 4. The diagnostic yields after making cell‑

cancer, and infectious disease in this study. Some

blocks tend to be higher than before in benign

patients were suspected of either malignant or

lesions, due to the 100% diagnostic yield of sar-benign lesions, others were referred to our hospital

coidosis. There seemed to be no change in the

because of a mediastinal tumor or lymphadenopathy

diagnostic yield of malignant lymphoma betweenof unknown cause. In comparison to the system-

before and after making cell‑blocks (Table 4).

atic review ,our data shows a high diagnostic yield

As indicated in Fig. 2, no diagnosis was obtainedin malignancy (especially lung cancer). Conversely,in 34 patients.These patients were ﬁnallydiagnosed

we had a low diagnostic yield (19.4%) for the

byother modalities:surgery(5 patients),endoscopic

diagnosis of benign lesions.We expect that we will

ultrasound ‑guided ﬁne needle aspiration (2obtain better results after making cell‑blocks aspatients), re‑try EBUS‑TBNA (2 patients), periph-

described above.The results for the diagnostic yielderal lung nodule sampling byconventional bronchos-of malignant lymphoma were also poor. In our

copy (one patient), muscle biopsy (one sarcoidosis

study, the sensitivity of a deﬁnitive diagnosis waspatient) and clinical follow‑up of more than 6

50% (3 diagnosed in 6 procedures in the totalmonths (21 patients). No signiﬁcant complications

period, 1 diagnosed in 3 procedures after the intro-

occurred during the procedures.

duction of cell‑blocks, Fig. 2). The poor diagnostic
yield in this disease caused a signiﬁcant diﬀerence in

Discussion

diagnostic yield between lung cancer and other

This study describes the usefulness and safety ofmalignancies. Although the usefulness for the

EBUS‑TBNA for the deﬁnitive diagnosis of circum-

deﬁnitive diagnosis of malignant lymphoma by
EBUS‑TBNA has not been deﬁned , it has beenreported by several institutes

Table 3 Diagnostic yield according to the lesion size
Size

Diagnostic yield (%)

10 mm
10.1‑20 mm
20.1‑30 mm

40.0＞30 mm. In these reports,

the diagnostic yield of malignant lymphoma varied
between 57 to 90.9 %. Like benign lesions,

suﬃcient tissue is also required for the deﬁnitive
diagnosis of malignant lymphoma including exami-

51.0
72.4
87.5

nations such as cytology,histology,molecular anal-

Table 4 Transition of the diagnostic yields before and after making cell‑blocks

All benign lesions
Sarcoidosis
M alignant lymphoma
No. 5, 2012

Total period(2005〜2011)

before (〜2010)

after (2011〜)

19.4% (6/31)
40.0% (4/10)
50.0% (3/6)

13.0% (3/23)
14.3% (1/7)
50.0% (2/4)

37.5% (3/8)
100% (3/3)
50.5% (1/2)
253

Yasuo.Kobayashi.Tokoro et al.

mediastinal/lung abscess,or empyemaysis, and immunophenotyping.

.M edias-

In addition to making cell‑block samples,we may

tinal abscess is perhaps a very rare complication.

need more passes per lesion to obtain more samples.

Clinically signiﬁcant bacteremia following EBUS‑

The average passes per lesion in our study was

TBNA was also rare .

2.89 ± 1.03. The average passes per lesion in our

Conclusion

positive result of lymphoma (3 cases) was 4.33. In
contrast, the average passes in our negative result

We reviewed our instituteʼs results and comparedof lymphoma (3 cases) was 2.67. A review article

the data with previous reports.EBUS‑TBNA was arecommends that EBUS‑TBNA needs three to

useful and safe procedure for the deﬁnitive diagno-

four aspirations per one site for the diagnosis.

sis of undiagnosed lesions around the central air-

Lymphoma may need more passes to reach aways. However, the deﬁnitive diagnosis of benign

deﬁnitive diagnosis.

lesions and malignant lymphoma seems moreWe thus need to perform histological analysis

diﬃcult.Preparing cell‑blocks for histological anal-

more than ever;however,it may be insuﬃcient forysis may improve the diagnostic yield. Increasing

the deﬁnitive diagnosis of malignant lymphoma

the number of passes per lesion should also bebecause EBUS‑TBNA usually obtains smallerconsidered to obtain more tissue samples.

amounts of samples. It is also insuﬃcient for the

Acknowledgement

deﬁnitive diagnosis of benign lesions if we cannot
obtain suﬃcient histological samples.Furthermore,

The authors thank Yukihiro Kobayashi, Ph. D.

a deﬁnitive diagnosis of reactive lymphnode or no‑from the Department of Laboratory M edicine,Shin-metastasis may not be made only by the result of

shu University School of Medicine for his analysis

EBUS‑TBNA. For the deﬁnitive diagnosis of suchof our cytological samples. The authors would likebenign lesions, we need to wait for the surgicalto thank Harm J. Bogaard, M . D., Ph. D. from theresult or the long‑term follow up result.

VU University M edical Center for his valuable

The safety of EBUS‑TBNA has been alreadyshown

advice and for kindlychecking the English language. No major complications were seen inusage in our manuscript. The authors also thankour series except for acceptable amounts of bleed-Thomas Taylor for kindly checking the English

ing. We have not observed some of the other previ-

grammatical usage in our manuscript.

ously reported complications,including bacteremia,
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