diagnostic value of blood clot core during endobronchial ultrasound-guided transbronchial needle...
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INTERVENTIONAL BRONCHOSCOPY
Diagnostic Value of Blood Clot Core During EndobronchialUltrasound-Guided Transbronchial Needle Aspirate
Emily N. Amin • Christopher D. Russell •
Konstantin Shilo • Shaheen Islam • Karen L. Wood
Received: 7 January 2013 / Accepted: 10 March 2013 / Published online: 31 March 2013
� Springer Science+Business Media New York 2013
Abstract
Background Endobronchial ultrasound-guided transbron-
chial needle aspiration (EBUS-TBNA) is being increasingly
used in the sampling of pulmonary masses and mediastinal
lymphadenopathy. The blood clot core (BCC) often obtained
during EBUS-TBNA may not be a true core and therefore
may not be submitted for histological analysis. The fre-
quency in which the blood clot core is positive in patients
with negative cytology undergoing EBUS-TBNA is not
known. The purpose of this study was to evaluate the diag-
nostic role of the blood clot core obtained during EBUS-
TBNA.
Methods An Institutional Review Board-approved retro-
spective chart review was performed from January through
September 2011 for all patients who underwent EBUS-
TBNA at The Ohio State University. The data collection
included cytology and histology results for each procedure.
Blood clot cores obtained from the EBUS-TBNA needle
were sent in formalin for histological examination.
Results Seventy patients underwent EBUS-TBNA and 51
(72.8 %) patients had procedures that yielded a BCC for
histology and aspirate for cytology. Forty-nine percent of
patients with a BCC were diagnosed with malignancy. Of
those with a BCC obtained, five (9.8 %) patients diagnosed
with malignancy were done so based only on the results of
blood clot core alone with negative cytology.
Conclusions Blood clot cores obtained at EBUS-TBNA
contain diagnostic material and should be subjected histo-
pathological examination. When blood clot cores are sent
for analysis, there is the potential to spare up to 10 % of
patients more invasive diagnostic biopsy procedures.
Keywords Endobronchial ultrasound � Transbronchial
needle aspiration � Mediastinal lymph node �Mediastinal staging � Core biopsy
Introduction
Transbronchial needle aspiration (TBNA) is a widely avail-
able diagnostic option to obtain cytologic material from
mediastinal lymph nodes and lung masses. Recently, endo-
bronchial ultrasound-guided TBNA (EBUS-TBNA) has been
increasingly used compared with conventional TBNA for a
variety of indications, including mediastinal staging of lung
cancers [1]. EBUS-TBNA has been shown to have a higher
sensitivity and specificity than conventional TBNA without
ultrasound guidance with only modest increase in duration of
the procedure [2]. The 21- or 22-gauge EBUS-TBNA needles
result in aspiration samples for cytologic examination and
often a blood clot core (BCC) is obtained from the needle
during the procedure when suction is applied. Unlike the core
that can be obtained with the 19-gauge needle used in con-
ventional TBNA, this BCC obtained during EBUS-TBNA
may not represent a true core biopsy specimen. Therefore, it
may not be sent for pathologic examination. In our practice,
we routinely send the BCC when available for pathological
examination in addition to the needle aspiration specimen,
which is examined by a pathologist. The present study was
done to evaluate the diagnostic role of BCC when combined
with cytologic analysis.
E. N. Amin (&) � C. D. Russell � S. Islam � K. L. Wood
Division of Allergy, Pulmonary, Critical Care and Sleep
Medicine, The Ohio State University Medical Center, 201
DHLRI, 473 West 12th Avenue, Columbus, OH 43210, USA
e-mail: [email protected]
K. Shilo
Department of Pathology, The Ohio State University,
Columbus, OH, USA
123
Lung (2013) 191:305–309
DOI 10.1007/s00408-013-9457-5
Materials and Methods
An Institutional Review Board-approved retrospective chart
review of patients who underwent EBUS-TBNA at our
institution from January through September 2011 was per-
formed. Data, including demographics, cytology, and histo-
pathology results, as well as diagnosis, were recorded for each
patient. All EBUS-TBNA procedures were performed pri-
marily by a pulmonary fellow under the supervision of a
skilled pulmonologist under deep sedation in the bronchos-
copy suite using the same EBUS bronchoscope (BF-UC160F-
0L8, Olympus America, Inc.). The number of passes per sta-
tion was not standardized. The specimen from the EBUS
needle was expelled onto a slide by first replacing the guide-
wire to push any solid material out. Then, a 10-cc syringe was
used to expel the remaining material from the needle onto the
slide and was collected in Roswell Park Memorial Institute
medium (RPMI). Any BCC that was expelled on the slide was
then transferred to 10 % formalin using a blunt needle. Rapid
on-site cytology examination (ROSE) analysis was routinely
performed by a cytotechnician. Cytology smears were stained
with hematoxylin-eosin and Papanicolaou. Cell blocks were
stained with hematoxylin-eosin and when indicated with
immunohistochemical stains.
Results
During the study period, a total of 70 patients underwent
EBUS-TBNA at our institution. Age, sex, and diagnoses are
listed in Table 1. Fifty-one (72.8 %) patients had procedures
that yielded a BCC for histopathologic examination in addi-
tion to cytology. BCC samples (Fig. 1) commonly included
abundant blood components (Fig. 2) admixed with solid
fragments of diagnostic tissue (Fig. 3). Of these 51 patients,
25 (49 %) were diagnosed with malignancy, 8 (15.7 %) had
granulomatous disease, 15 (29.4 %) had benign lymphocytes
on cytology and histology, and 3 (5.9 %) had inadequate
specimens. Of the eight patients with granulomatous disease,
three (37.5 %) were diagnosed with sarcoid, three (37.5 %)
had histoplasmosis, and two (25 %) had granulomas without a
specific diagnosis.
Of the 25 patients diagnosed with malignancy, 15
patients had malignant cells present in both the BCC and
cytology material. These included six with adenocarci-
noma, eight with small cell carcinoma, and one with B-cell
lymphoma. In five patients, only the cytology was positive
for malignancy and the BCC was nondiagnostic. These
included three squamous cell carcinomas and two adeno-
carcinomas. Mutations were obtained from the BCC in six
of the eight patients diagnosed with adenocarcinoma.
The remaining five patients diagnosed with malignancy
had positive BCC with negative or nondiagnostic cytology
results. These included two with squamous cell carcinoma,
one with melanoma, one with B-cell lymphoma, and one
with undifferentiated non-small cell carcinoma (Table 2).
These five patients account for 9.8 % of patients with a
BCC sent for examination. Overall, a diagnosis in 5 of 70
(7.1 %) patients would not have been made if the BCC was
not sent for histology.
The overall diagnostic yield, including a malignancy
diagnosis or granulomas, was obtained in 14 of 19 (73.6 %)
patients if a BCC was not sent and 33 of 51 (64.7 %)
patients if a BCC was evaluated.
Table 1 Characteristics of study population
Patients with BCC
obtained (n = 51)
Patients with BCC not
obtained (n = 19)
Age (year) 15–84 (median 61) 28–87 (median 60)
Sex 51 % male 74 % male
Malignant diagnosis
Adenocarcinoma 8 (16 %) 4 (21 %)
Squamous cell
carcinoma
5 (10 %) 2 (11 %)
Small cell
carcinoma
8 (16 %) 4 (21 %)
NSCLC NOS 1 (2 %) 1 (5 %)
Lymphoma 2 (4 %) 1 (5 %)
Melanoma 1 (2 %) 0 (0 %)
Nonmalignant diagnosis
Sarcoid 3 (6 %) 2 (11 %)
Histoplasmosis 3 (6 %) 0 (0 %)
Granulomas, no
specific
diagnosis
2 (4 %) 0 (0 %)
Benign
lymphocytes
15 (29 %) 4 (21 %)
Inadequate
specimen
3 (6 %) 1 (5 %)
Fig. 1 Gross picture of a BCC obtained during EBUS-TBNA
306 Lung (2013) 191:305–309
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Discussion
EBUS-TBNA has become an important diagnostic proce-
dure in both the interventional pulmonology and thoracic
surgery fields. It has been shown to be a valuable diagnostic
tool for the evaluation of mediastinal lymphadenopathy and
masses. It has been studied most extensively in the role of
mediastinal staging in lung cancer patients. American Col-
lege of Chest Physician (ACCP) guidelines found a com-
bined sensitivity from eight studies of 90 % for EBUS-
TBNA when utilized for staging [1]. These guidelines rec-
ognize EBUS-TBNA as a reasonable modality to stage the
mediastinum in patients with suspected or known non-small
cell lung cancer (NSCLC) with discrete mediastinal lymph
node enlargement or those with central tumors or N1 lymph
nodes. Two studies since the guidelines were published
directly compared EBUS-TBNA and mediastinoscopy and
showed no significant difference between the two procedures
in their ability to stage the mediastinum in patients with
NSCLC [3, 4]. EBUS-TBNA also has been shown to have
good diagnostic yield for benign diseases, including sarcoid
and tuberculosis, especially when combined with other
standard bronchoscopic modalities [5–7].
Given that EBUS-TBNA is a relatively new procedure,
ways to increase its diagnostic accuracy have been and will
continue to be investigated. Although ROSE has been shown
to decrease the number of aspirations needed for diagnosis, it
is not available uniformly [8]. Combination of EBUS-TBNA
with transesophageal ultrasound-guided fine needle aspirate
(EUS-FNA) also has been shown to increase the diagnostic
yield for patients undergoing mediastinal staging for known
or suspected lung cancer [9]. Three studies suggest that
obtaining a core biopsy during the EBUS-TBNA procedure
can increase diagnostic yield [10, 11]. In one study, patients
with metastatic malignancy of unknown primary or patients
with previous extrathoracic malignancy underwent EBUS-
TBNA to evaluate their mediastinal lymphadenopathy.
Tissue cores obtained with the 22-gauge needle were sent for
histology and it was noted that three patients had positive
histology despite negative cytology [10]. Another study
investigated the optimal number of aspirations from each
lymph node station during EBUS-TBNA without ROSE.
This study obtained tissue cores defined as the ‘‘solid sub-
stances in the aspiration needle’’ in the majority of their
aspiration attempts. When tissue cores were obtain in the first
or second aspiration of a lymph node, the sensitivity and
diagnostic accuracy was increased compared with those
without core tissue on the first two passes [11]. In another
study, evaluation of obtaining the ‘‘tissue clot coagulum’’ in
filter paper before placing in formalin for a cell block was
compared with a saline rinse of the coagulum. It was found
that sample adequacy and diagnostic yield was higher in the
‘‘tissue clot coagulum’’ cell block method samples [12].
Our review shows that solid material consisting of BCC
is frequently obtained during EBUS-TBNA procedures
when suction is applied. This is consistent with previous
findings [11]. We sent our BCC tissue in formalin, whereas
others have suggested putting blood clot core material
directly into RPMI for cell block. Our routine clinical
practice includes washing the needle in RPMI, and even
with this practice, the BCC secured the diagnosis in these
additional patients. It is unknown if there is a difference in
diagnostic yield between these two methods and prospec-
tive study is warranted. Although the BCC may not be a
true core biopsy, sending this sample from the EBUS-
TBNA needle for histopathologic evaluation is valuable.
This material can contain diagnostic tissue that in some
cases will be the only specimen that yields a diagnosis. In
Fig. 3 A solid component of the BCC in case 1 represents metastatic
poorly differentiated squamous cell carcinoma (hematoxylin and
eosin stain, 9400, original magnification)
Fig. 2 BCC obtained at EBUS-TBNA of right paratracheal lymph
node in case 1 reveals solid tumor fragments (hematoxylin and eosin
stain, 940, original magnification)
Lung (2013) 191:305–309 307
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our review, almost 10 % of patients (5/51) that had a BCC
sent received a diagnosis of malignancy based on the BCC
alone and were spared further invasive testing. Further-
more, mutations were able to be performed on the BCC in
six of eight patients diagnosed with adenocarcinoma. It is
unknown if these mutations would have been available on
cytology alone without the BCC. Prospective study to
determine if BCC increases the ability to perform muta-
tions would be beneficial. In addition, there are potential
cost savings by avoiding mediastinoscopy in favor of
EBUS-TBNA.
Interestingly, in this small sample we were able to
diagnose lymphoma in two cases. It is believed that his-
topathologic examination is necessary but aspirate when
combined with flow cytometry can yield a conclusive
diagnosis in some cases.
There are limitations to this review that should be noted.
First, it is a retrospective review, which may have limited our
conclusions, because the number of passes, experience of the
operator, and other potential factors were not standardized.
Second, the overall diagnostic yield was not improved by
sending the BCC compared with the group that did not have
the core sent. It may have been that the BCC was less likely to
be sent for formal pathologic examination if ROSE was
positive. This may have decreased the number of BCC
results that we had to review and affected the yield. There
also are occasions that a BCC may not be obtained depending
on the consistency of the lymph node or mass being aspi-
rated. Lastly, negative results were followed clinically in
most cases and were not confirmed with mediastinoscopy so
the sensitive and specificity were not able to be obtained for
this method. Prospective study is needed to eliminate some
of these biases and answer important questions that have
come from this study.
Conclusions
BCC evaluation may provide the only diagnostic tissue
during EBUS-TBNA when cytologic examination is neg-
ative. Given the clinical significance of saving potentially
7.1 % of patients from further invasive testing, the yield of
sending the BCC from each sample seems easily justified.
In addition, there is no increased risk to the patient or
change in procedure required. Therefore, our study adds to
data that suggest that any BCC obtained during EBUS-
TBNA should be sent for evaluation in conjunction with
cytologic examination.
Conflict of interest None.
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