The Laryngoscope

C 2015 The American Laryngological,

V
Rhinological and Otological Society, Inc.

The Efficacy of the Interferon-c Release Assay for Diagnosing

Cervical Tuberculous Lymphadenitis: A Prospective Controlled Study

Kyung Hee Kim, MSN; Rock Bum Kim, MD; Seung Hoon Woo, MD

Objectives/Hypothesis: The whole-blood interferon (IFN)-c release assay (IGRA) has been studied mainly for diagnos-
ing latent tuberculosis (TB). We prospectively evaluated its diagnostic usefulness in patients with suspected cervical TB
lymphadenitis.
Study Design: Prospective cohort study.
Methods: An IGRA was performed in subjects with suspected TB lymphadenitis. To evaluate the diagnostic performance
of the IGRA, we calculated the sensitivity and specificity of culture, radiologic imaging, polymerase chain reaction testing, fine
needle aspiration, and excisional biopsy.
Result: Of the 271 adult patients with suspected TB lymphadenitis, 42 were diagnosed with the disease. The overall
sensitivity and specificity of the IGRA were 78.8% and 95.5%, respectively. When the cutoff value of IFN-c was set to 0.26
IU/mL, it met the inclusion criteria for suspicious TB lymphadenitis, with sensitivity and specificity of 83.3% and 95.1%,
respectively.
Conclusions: The IGRA is useful in diagnosing TB lymphadenitis, with high sensitivity and specificity.
Key Words: Tuberculosis, interferon-c release assay, lymphadenitis, culture, diagnosis.
Level of Evidence: 4.
Laryngoscope, 126:378–384, 2016

INTRODUCTION tent physical and laboratory findings.3–5 Invasive proce-

Cervical TB lymphadenitis is the most common
manifestation of mycobacterial infections encountered in
the head and neck region, accounting for 30% to 40% of
cases in a reported series.1 The incidence of TB lymph-
adenitis has increased in parallel with the increase in
the incidence of mycobacterial infections worldwide. TB
lymphadenitis, also referred to as cervical neck mass (or
scrofula), could be a manifestation of systemic TB dis-
ease or a unique clinical entity localized to the neck. It
can result from direct extension or hematogenous spread
of the infection.2
Diagnosis of TB lymphadenitis is usually more diffi-
cult and problematic than that of pulmonary TB because
it mimics other pathologic processes and yields inconsis-
From the Department of Otolaryngology (K.H.K., S.H.W.), Institute
of Health Sciences (S.H.W.), College of Nursing (K.H.K.), Gyeongsang
National University, Jinju, Korea; and the Regional Cardiocerebrovascu-
lar Center (R.B.K.), Dong-A University Hospital, Busan, Korea.
Editor’s Note: This Manuscript was accepted for publication July
6, 2015.
K.H.K. and R.B.K. contributed equally.
This research was supported by the Basic Science Research Program
through the National Research Foundation of Korea (NRF) funded by the
Ministry of Science, ICT, and Future Planning (2013R1A1A1012542). This
research was also supported by the Leading Foreign Research Institute
Recruitment Program through the National Research Foundation of Korea
(NRF) funded by the Ministry of Education, Science, and Technology
(MEST) (2012K1A4A3053142).
The authors have no other funding, financial relationships, or con-
flicts of interest to disclose.
Send correspondence to Seung Hoon Woo, MD, Department of
Otorhinolaryngology–Head and Neck Surgery, Gyeongsang National
University Hospital, 90 Chilam-dong, Jinju, South Korea, 660-702.
E-mail: lesaby@hanmail.net
DOI: 10.1002/lary.25540
dures for microbiologic and pathologic diagnosis are
usually required, and these are the diagnostic proce-
dures of choice for TB lymphadenitis.3,6 However, myco-
bacterial culture can take several weeks and is a very
insensitive method due to the paucibacillary nature of
the specimens.7 The radiographic or histopathologic find-
ings are frequently inconclusive.5 Although the tubercu-
lin skin test (TST) and polymerase chain reaction (PCR)
have proven to be useful in the clinical diagnosis of TB,
they have considerable variability and several limita-
tions in accuracy and reliability.8–12 To assess the risk of
TB in countries such as Korea, in which the majority of
the population has a history of bacillus Calmette-Guerin
(BCG) vaccination, a new method of screening such as
immunologic testing, rather than the TST, is necessary.
The whole-blood interferon (IFN)-c release assay
(IGRA) has generated promising results in the diagnosis
of TB.11 However, the assay has been studied mainly for
the diagnosis of latent TB infection or whole or extrapul-
monary TB infection.13–19 It is diagnostic performance
for the detection of TB lymphadenitis that has not been
well defined. Here, we prospectively evaluated the diag-
nostic usefulness of the IGRA in individuals with sus-
pected TB lymphadenitis.
MATERIALS AND METHODS
Study Population
All adult patients with suspected TB lymphadenitis were
prospectively enrolled from February 2009 to March 2012 at
Gyeongsang National University Hospital. The inclusion crite-
ria were defined as palpable lymphadenopathy on physical

Laryngoscope 126: February 2016 Kim et al.: Diagnosis of Cervical TB Lymphadenitis

378
examination persisting for more than 1 month. All patients
underwent thorough history taking and physical examination.
Single and multiple lymphadenopathies of various sizes were
included. Patients with the following conditions were excluded
from the study: a previous history of TB, recent exposure to TB,
and a chest x-ray (CXR) suggestive of TB; signs and symptoms
of acute upper respiratory infection or acute febrile illness;
apparent benign mass; overt primary focus of head and neck
malignancy; or known lymphoma.
The total number of patients was 318; however, 47
patients were excluded, so the initial number of enrolled
patients was 271. Of the 271 patients with suspected cervical
TB lymphadenitis, 37 patients were subsequently excluded
(they refused the excisional biopsy); therefore, the final number
of patients enrolled in the study was 244. These 244 patients
all received neck computed tomography (CT) imaging, fine-
Fig. 1. Flow diagram of enrollment and analysis. CT 5computed
needle aspiration biopsy (FNAB), TB-PCR, culture, excisional tomography; FNA 5 fine-needle aspiration; IGRA 5 interferon-c
biopsy, and the IGRA test (Fig. 1). release assay; PCR 5 polymerase chain reaction; TB 5 tuberculosis.
The demographic data collected included age, sex, and
immunocompromised status (diabetes, liver cirrhosis, chronic
Sterile distilled water was used as a negative control. Analysis
renal failure, solid tumor, hematologic malignancy, human
of the PCR products was performed by electrophoresis in ethi-
immunodeficiency virus infection, or receipt of immunosuppres-
dium bromide (0.5 lg/mL)-stained 1.7% agarose gels.
sive treatment within 3 months). In addition, we recorded any
history of TB, treatment with anti-TB medication, or recent (2
years) close exposure to patients with TB. To determine the
Mycobacterial Culture
BCG vaccination status, we documented BCG scars.
Mycobacteria were cultured on Middlebrook 7H9 Agar
(Difco Laboratories Inc., Detroit, MI) supplemented with 10%
Ethics Middlebrook OADC Enrichment medium (BBL, Sparks, MD) at
The purpose of the study was explained to all the patients 378C for 2 to 4 weeks. The presence of 10 to 100 bacilli per cubic
and their written consent was obtained. The institutional millimeter of the specimen is sufficient for a positive culture
review board of our hospital had previously approved the entire result.
study (GNUHIRB-2009-37).
Excisional Biopsy—Histopathology
Radiology For histology, the acquired specimens were fixed in 10%
On CT imaging of the neck, the presence of conglomerated buffered formalin, and 8-mm sections were processed in an
nodal masses with central necrosis, a thick irregular rim of con- automated tissue processor for 12 hours, embedded in paraffin,
trast enhancement and inner nodularity, a varying degree of and stained with H&E and Ziehl-Neelsen stain. Histopathologic
homogeneous enhancement in smaller nodes, and engorgement examination is one of the most important methods for diagnos-
of the lymphatics and thickening of the adjacent muscles may ing TB lymphadenitis. Langhans giant cells, caseating necrosis,
suggest mycobacterial cervical lymphadenitis. granulomatous inflammation, and calcification can be seen in
TB lymphadenitis. The presence of microabscesses, ill-defined
granulomas, noncaseating granulomas, and a small number of
FNAB—Smear and Stain giant cells are more prominent in nontuberculosis lymphadeni-
The FNAB was performed on the palpable lymph nodes of tis when compared with TB lymphadenitis.
the suspected cases by an experienced pathologist. Drops of the
aspirate material were immediately expressed and spread on
glass slides, fixed, and stained with Papanicolaou stain, hema- IGRA—QuantiFERON-TB Gold In-Tube
toxylin and eosin (H&E), and Ziehl-Neelsen stain. The material The IGRA was performed with collected heparinized
remaining in the syringe or another aspirated sample was used venous blood, and whole blood was mixed with mycobacterial
directly for a Mycobacterium tuberculosis culture or PCR reac- antigens before incubation at 378C. After more than 18 hours of
tion (TB-PCR). incubation at 378C, IFN-c responses were measured by enzyme-
linked immunosorbent assay. After correcting for negative con-
trol responses, IFN-c  0.35 IU/mL was considered positive.
TB-PCR—Molecular Testing
We used the PCR assay targeting the IS6110 or MPB64
intergenic region of the M tuberculosis genome. The amplifica- Evaluation of Diagnostic Performances
tion reaction mixture consisted of 10 mM Tris-HCl, 50 mM KCl, Final diagnosis were classified into three clinical catego-
1.5 mM MgCl2, 200 lM of each primer, 1.5 units of Taq DNA ries: “confirmed” (positive culture result or positive M tuberculo-
polymerase (Bioneer Corp., Daejeon, Korea), and 20 ng of sis PCR result with a specimen from the infection site),
genomic DNA was used as the template. PCR amplification was “suggestive” (histologic finding from biopsy tissue showing typi-
performed in an automated thermal cycler (PTC-100 Program- cal caseating necrosis in the absence of acid-fast bacilli or posi-
mable Thermal Controller; MJ Research, Inc., Waltham, MA). tive TB if acid-fast bacilli were detected by Ziehl-Neelsen stain),
The cycling parameters were 948C for 5 minutes, followed by 35 and “not” TB (no evidence of TB). Patients with confirmed and
cycles of denaturation at 948C for 30 seconds, annealing at 688C suggestive TB were diagnosed as the reference standards for
for 30 seconds, and a final extension at 728C for 7 minutes. positive TB lymphadenitis, and those with not TB were

Laryngoscope 126: February 2016 Kim et al.: Diagnosis of Cervical TB Lymphadenitis

379
 1.05 (0.73-1.52)
0.44 (0.29-0.67)

0.05 (0.01-0.19)
0.18 (0.08-0.37)

CI 5 confidence interval; FNA 5 fine needle aspiration; IGRA 5 interferon-c release assay; LR1 5 positive likelihood ratio; LR2 5 negative likelihood ratio; NPV 5 negative predictive value; PCR 5 polymerase
0.72 (0.550.95)
TABLE I.

LR2 (95% CI)

0.22 (0.1-0.4)
Clinicopathological Characteristics of TB Lymphadenitis and Non-
TB Lymphadenitis.
TB Lymphadenitis Non-TB Lymphadenitis
Variable (N 5 42) (N 5 202)

Age, yr 33.7 6 12.6 35.5 6 13.0

Gender 12:30 89:113
(male: female)

32.06 (14.54–70.73)
Diagnosis Confirmed Lymphadenitis: 150

4.44 (3.26-6.04)
0.96 (0.71-1.30)
3.33 (2.32-4.78)
2.06 (1.33-3.20)
LR1 (95% CI)

17.63 (9.1–34.0)
TB: 32
Suggestive Kikuchi disease: 36
TB: 10
Sarcoidosis: 3
Toxoplasmosis: 1
Lymphoma: 3
Acute inflammation: 6
Cat scratch disease: 1

98.9% (96.4–99.7)
82.1% (73.7–88.2)
86.9% (81.3–91.1)
96.4% (92.5–98.4)
91.6% (86.6–94.8)

96.0% (92.3–98.0)
NPV % (95% CI)
Cancer: 2 (thyroid)

TB 5 tuberculosis.

considered the standards for negative TB lymphadenitis.

The Results of TB Lymphadenitis Diagnostic Testing.

Patients with indeterminate IGRA results were considered as
negative.

86.9% (74.3–93.9)
16.6% (11.4–23.8)
30.0% (19.9–42.5)
48.0% (37.1–59.1)
40.9% (29.9–53.0)

79.1% (64.8–88.6)
Statistical Analyses

PPV % (95% CI)

To evaluate the diagnostic performances of the IGRA, we
calculated the sensitivity, specificity, positive predictive value,
negative predictive value (NPV), likelihood ratio for positive
TABLE II.

test, and likelihood ratio for negative test. Confidence intervals

for sensitivity and specificity were produced with the Wilson
score method.20 Confidence intervals for positive and negative
likelihood ratios were calculated using the method described by
Simel and colleagues.21 The optimal cutoff was determined
using the Euclidean method (minimum value of square root [(1-
Specificity % (95% CI)

97.0% (93.7–98.6)
43.1% (36.4–50.0)
79.2% (73.1–84.2)
80.7% (74.7–85.5)
80.7% (74.7–85.5)

95.5% (91.7–97.9)
sensitivity)^2 1 (1-specificity^2)]) deriving values for sensitivity
and specificity.

RESULTS
Clinical Characteristics
The final number of patients enrolled in the study
chain reaction; PPV 5 positive predictive value; TB 5 tuberculosis.

was 244. Among the patients, 42 (17.2%) were given a

diagnosis of TB lymphadenitis, and 202 patients (82.8%)
Sensitivity (%) (95% CI)

were given a diagnosis of non-TB lymphadenitis. There

78.8% (63.2 – 89.7)
95.2% (84.2–98.7)
54.8% (40.0–68.8)
42.9% (29.1–57.8)
85.7% (72.2–93.3)
64.3% (49.2–77.0)

were more females than males (172/244, 70.5%), and the

mean age was 33 years (mean 5 33.2 6 18.1 years). Of
the patients with a diagnosis of TB lymphadenitis, 32
patients were classified as confirmed TB lymphadenitis
and 10 patients as suggestive TB lymphadenitis. Among
the 202 patients with a diagnosis of non-TB lymphadeni-
tis, 150 patients were diagnosed with lymphadenitis, 36
patients with Kikuchi disease, three patients with sar-
coidosis, and the rest with various other conditions
FNA (stain and smear)

(Table I).
Excisional biopsy

IGRA shows a consistently higher ratio of diagnosis

TB Lymphadenitis:

Radiologic test

than other TB tests. A comparison of several tests

related to TB lymphadenitis revealed that among all the
42 Patients

TB-PCR

TB lymphadenitis tests, sensitivity was the highest in

Culture

IGRA

the excisional biopsy (95.2%), followed by culture

(85.7%), and IGRA (78.8%); however, specificity was

Laryngoscope 126: February 2016 Kim et al.: Diagnosis of Cervical TB Lymphadenitis

380
 TABLE III.
Instances of False Positives and False Negatives in the IGRA.
False Positive: 9 Cases
Result of IGRA Finding
IGRA 2.56 IU/mL Chronic lymphadenitis
IGRA 1.24 IU/mL
IGRA 1.06 IU/mL
IGRA 0.49 IU/mL
IGRA 1.93 IU/mL B-cell lymphoma
IGRA 2.35 IU/mL
IGRA 1.25 IU/mL Toxoplasmosis
IGRA 1.77 IU/ml Sarcoidosis
IGRA 2.86 IU/mL
IGRA 5 interferon-c release assay; TB 5 tuberculosis.
highest in decreasing order in excisional biopsy (97%),
IGRA (95.5%), and culture (80.7%) (Table II).
There are instances of false positives and false neg-
atives in the IGRA. The IGRA had false-positive and
false-negative results (Table III). There were nine cases
of false positives (4.5%), usually among diseases that
form granulomas, which are difficult to distinguish from
TB lymphadenitis (sarcoidosis [two cases], toxoplasmasis
[one case]). Some of the false-positive cases were among
diseases such as malignant lymphoma, which are char-
acterized by an increase in cytokines. However, four
patients with chronic lymphadenitis also had false-
positive results.
There were eight cases of false negatives (19%).
After node biopsy, four cases were diagnosed as TB
lymphadenitis. Of these cases without specific causes
determined, only two patients showed IGRA test values
of 0.27 IU/mL and 0.24 IU/mL, respectively, not too far
from the cutoff value of 0.35 IU/mL. On the other hand,
other two patients with false-negative results had rela-
tively low test values of between 0.01 and 0.03 IU/mL.
This signifies a need for a change in the standard for
the diagnosis by adjusting the cutoff value.
The other four cases were not diagnosed as TB
lymphadenitis. Of these cases, three did not show any
abnormal findings in the chest radiologic test and his-
tory talking, but the patients suffered from the continu-
ously dry cough and were diagnosed with lung TB
because they showed abnormalities in the sputum stain
and culture, and one patient suffered from continuous
back pain and was diagnosed with spinal TB.
An adjustment of the cutoff value in the IGRA
can lead to a more accurate diagnosis of cervical TB
TABLE IV.
Adjustment of the Cutoff Value in the IGRA Leading to a More Accurate Diagnosis of TB Lymphadenitis.
IGRA Cutoff Value Sensitivity % (95% CI)
0.35 IU/mL 78.8 (63.2–89.7)
0.26 IU/mL 83.3 (68.6–93.0)
CI 5 confidence interval; IGRA 5 interferon-c release assay; LR1 5 positive likelihood ratio; LR2 5 negative likelihood ratio.
Laryngoscope 126: February 2016
False Negative: 8 Cases
Result of IGRA Finding
IGRA 0.13 IU/mL Lung TB
IGRA 0.03 IU/mL
IGRA 0.03 IU/mL
IGRA 0.09 IU/mL Spinal TB
IGRA 0.11 IU/mL TB lymphadenitis
IGRA 0.09 IU/mL
IGRA 0.27 IU/mL
IGRA 0.24 IU/mL
lymphadenitis. An analysis of the false-negative results
showed that some patients were not diagnosed as posi-
tive because their test values were not above the cutoff
value of 0.35 IU/mL, despite the fact that they were very
close. We can increase the sensitivity of such cases by
adjusting the cutoff value to 0.26 IU/mL using the
Euclidean method. This would lead to a slight increase
in sensitivity with similar specificity (Table IV, Fig. 2).
DISCUSSION
TB is a systemic disease, and cervical lymphadeni-
tis is the most commonly occurring form of extrapulmo-
nary TB. TB patients typically present with chronic,
nontender lymphadenitis6,22 and usually with fever,
night sweats, and weight loss.23,24 An optimal workup
for TB lymphadenitis is established and involves a thor-
ough history and physical examination, tuberculin test,
staining for acid-fast bacilli, radiologic examination, and
fine-needle aspiration (FNA). This will help to arrive at
an early diagnosis of TB lymphadenitis, which will allow
the early administration of treatment before a final diag-
nosis can be made by biopsy and culture.25–27
Although these basic tools provide important infor-
mation about the patient’s condition, it is not feasible or
practical to apply all of the diagnostic procedures in all
patients. This would be both time-consuming and expen-
sive. Testing should be individualized depending on the
location of the disease and the clinical evaluation. A
high index of suspicion is needed for a diagnosis of TB
lymphadenitis, which remains a diagnostic challenge for
many clinicians despite current advances in diagnostic
laboratory techniques.
Specificity % (95% CI) LR1 (95% CI) LR2 (95% CI)
95.5 (91.7–97.9) 17.6 (9.1–34.0) 0.22 (0.1–0.4)
95.1 (91.1–97.6) 16.8 (9.1–31.3) 0.18 (0.09–0.3)
Kim et al.: Diagnosis of Cervical TB Lymphadenitis
381

Fig. 2. The cutoff value decision for IGRA as a positive marker for
result. AUC 5 area under the curve; IGRA 5 interferon-c release
assay.
The utility of FNA cytology in patients is highly
variable.6 Ziehl-Neelsen staining of the smears from
FNA may reveal mycobacteria only in fresh specimens,
and over 10,000 cells are needed for smear positivity.
Hence, a diagnosis by FNA would become difficult if not
enough cells are smeared or if the cells dry out during
the staining.
A culture of mycobacteria is a confirmatory diagnos-
tic method for mycobacterial cervical lymphadenitis.
However, a negative culture result should not exclude a
diagnosis of mycobacterial cervical lymphadenitis,
because cultures are positive in anywhere from 10% to
69% of cases.28,29 However, several weeks are needed to
obtain culture results, which may postpone the initiation
of treatment. Furthermore, the paucibacillary nature of
specimens results in low sensitivity of culture for TB
lymphadenitis, and it requires skillful technicians as
well.7
PCR is a confirmatory and sensitive technique for
the diagnosis of mycobacterial cervical lymphadenitis.
Its sensitivity ranges between 43% and 84%, and its
specificity between 75% and 100%.9,30 However, with
this assay, different PCR results can be obtained in dif-
ferent laboratories. Thus, more rapid and efficient meth-
ods of identification are needed.
On CT imaging, the presence of conglomerated
nodal masses with central necrosis, a thick irregular rim
of contrast enhancement, and inner nodularity may sug-
gest TB lymphadenitis.31,32 However, these findings may
also be seen in other diseases, such as lymphoma and
metastatic lymphadenopathy.31 Thus, the radiologic find-
ings are merely clues suggesting TB lymphadenitis.
Histopathologic examination with excisional biopsy
is one of the most important means for diagnosing myco-
bacterial cervical lymphadenitis.4,6,33,34 Langhans giant
cells, caseating necrosis, granulomatous inflammation,
Laryngoscope 126: February 2016
382
and calcification can be seen.35 However, an excisional
biopsy causes scarring and may lead to the formation of
a fistula. Thus, excisional biopsy is the last method for
diagnosing TB lymphadenitis.
In Western countries, most patients with TB lymph-
adenitis have a positive TST result.22,36 However, the
attitudes in Korea toward the usefulness of the TST are
still quite skeptical. In Korea, school-aged children were
vaccinated with the BCG vaccine until 1997, and 5% to
10% of individuals who receive the vaccine can show
positive results on a TST until 20 to 25 years later.37 In
these cases, the TST is not useful for the diagnosis of
tuberculosis.
This study began by asking the question of whether
the IGRA, an immunologic test, can be used as a method
to diagnose cervical TB lymphadenitis (one of the
extrapulmonary tuberculoses) overcome the above-
mentioned limitations of several diagnostic methods.
Extrapulmonary TB is fundamentally heterogeneous
and present at a variety of different sites; thus, it is dif-
ficult to diagnose these forms of the disease with a sin-
gle diagnostic method. This pattern is consistent with
that described by a recent report in South Korea.38 Fur-
thermore, as fragmentary as it is, the IGRA was the
only method that showed a significantly high sensitivity
and NPV for diagnosing TB lymphadenitis among all the
forms of extrapulmonary TB in the previously mentioned
study. In other words, the IGRA offers the clinical possi-
bility of diagnosing TB lymphadenitis among all the
extra-pulmonary tuberculoses. Thus, we conducted a
prospective study to diagnose TB lymphadenitis using
the IGRA.
In this study, the IGRA had high accuracy (78.8%
sensitivity and 95.5% specificity) for diagnosing TB
lymphadenitis. In the patients with a diagnosis of TB
lymphadenitis, eight patients (19%) had false-negative
results. Although there were no patients with dissemi-
nated disease, three of these patients had pulmonary
TB; one patient had spinal TB. The differences in sensi-
tivity between the patients with cervical lymphadenitis
and those with lung involvement (including spinal TB)
can be explained in that a localized TB infection could
be the result of a more efficient immune response, which
allows for the detection of IFN-c production, whereas a
more active lung involvement could be consistent with
deficient IFN-c production, which leads to false-negative
results on the IGRA.14 In the current study, the lung TB
and spinal TB patients did not show positive results on
the IGRA and caused false-negative results. The diag-
nostic method of the IGRA seems to have some difficulty
in the presence of active TB. However, it is difficult to
draw conclusions because of the small number of
patients in our study with active pulmonary TB. Our
data suggest that the results of the IGRA should be
interpreted carefully in various clinical settings.
The IGRA also had false-positive (4.5%) results in
the current study, usually in patients with diseases in
which cytokine production is hardly distinguishable
from that of TB lymphadenitis. For example, there were
two cases of sarcoidosis, in which the antigen-presenting
cell and helper T-cell complex leads to the release of
Kim et al.: Diagnosis of Cervical TB Lymphadenitis
multiple cytokines. There was also one case of toxoplas-
mosis, which infects normal host cells, enabling them to
resist attempts by the host’s immune system to harm
them, as well as changing the host’s immune processes
and being implicated in the regulation of cytokines.
Finally, there were two cases of malignant B-cell lym-
phoma, a disease characterized by an increase in cyto-
kines, which produce IFN-c and confuse the IGRA test.
However, one should be cautious when interpreting
these results, because there were some simple chronic
lymphadenitis patients (four cases) who also had false-
positive results.
Currently, the cutoff value for the IGRA is set to
0.35 IU/mL. However, this value is only to identify
latent TB, not to diagnose TB lymphadenitis. Until now,
there had been no research that suggested an adjusted
cutoff value in accordance with certain situations. The
present study was able to confirm that adjusting the cut-
off value from 0.35 IU/mL to 0.26 IU/mL to successfully
diagnose TB lymphadenitis with the IGRA was effective
for screening out TB lymphadenitis by increasing sensi-
tivity, with a slight decrease in specificity. Hence, the
previous cutoff value of 0.35 IU/mL that was used to
diagnose latent TB should be adjusted to 0.26 IU/mL to
effectively diagnose TB lymphadenitis. Of course, more
data should be presented to support such a change.
In this study, biopsy had the highest sensitivity as
a testing method, with sensitivity of 95.2%, followed by
IGRA with 78.8%. The tests with the highest specificity
were biopsy and IGRA, with specificity of 97.0% and
95.5%, respectively. However, biopsy is not recommended
as a screening test because it is an invasive method.
Therefore, the IGRA, with consistently high sensitivity
and specificity, can be considered the most appropriate
approach as a method to diagnose TB lymphadenitis.
Furthermore, positive results on the IGRA are of clinical
significance in Korea, where most people receive the
BCG vaccine.
Our study does have some limitations. Most nota-
bly, because Korea has a high prevalence of TB, we
included suggestive TB in the diagnosis standard, which
in turn increased the overall sensitivity. Such results
could be useful only in regions with a high prevalence of
TB. Further studies that include more participants will
be required to address these issues.
CONCLUSION
The IGRA is useful in diagnosing TB lymphadenitis
with high sensitivity and specificity. We confirmed that
it can be more useful as a diagnostic test for TB lymph-
adenitis if the cutoff value is adjusted.
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