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Original Article

Fine Needle Aspiration Cytology in Childhood TB


Lymphadenitis
J. Balaji, S. Shanmuga Sundaram, S. Nataraja Rathinam, P. Amutha Rajeswari and
M.L. Vasantha Kumari

Institute of Child Health and Research Centre, Government Rajaji Hospital and Madurai Medical College,
Madurai, Tamil Nadu, India

ABSTRACT
Objective. To evaluate the efficacy of Fine Needle Aspiration Cytology (FNAC) to diagnose Tuberculous (TB) lymphadenitis
with compare to excision biopsy and to correlate TB lymphadenitis with clinical, cytological, radiological and mantoux test
features.

Methods. This was a prospective correlational study. FNAC was done by a pediatrician for 135 children with persisting
lymphadenitis after two weeks of antibiotic therapy in the period of January 2005 to June 2006 and compared with excision
biopsy in a tertiary care hospital.

Results. Forty Six cases (34.07%) were TB lymphadenitis diagnosed by FNAC. Excision biopsy and cytological correlation
was done in 100 cases. Sensitivity, specificity and diagnostic accuracy for TB lymphadenitis were found to be 98%, 100%
and 99% respectively. Positive and negative predictive values were 100 and 98 respectively. Large (>2cm) (86.9%), multiple
(52.1%), matted (47.8%), posterior cervical and submandibular group nodes with history of contact (P=0.0016), positive
mantoux test (P=0.0001) and Grade III and IV Protein Energy Malnutrition (PEM) (P=0.0041) were significantly seen in TB
lymphadenitis. Ziehl Neelson staining for Acid Fast Bacilli (AFB) was positive in 32.5% cases of TB Lymphadenitis.

Conclusion. Pediatrician himself can do FNAC which is an excellent first line method to diagnose TB lymphadenitis and it
has equal accuracy to excision biopsy. [Indian J Pediatr 2009; 76 (12) : 1241-1246] E-mail: jbalaji_1993@yahoo.com

Key words : Excision biopsy; FNAC; Lymphadenitis; Malignant; Mantoux test; Tuberculosis

Lymphadenopathy is a common clinical problem in extrapulmonary lesion. With the advent of fine needle
paediatric age group. It may be a sign of inflammation, aspiration cytology (FNAC) the scenario has changed.
tuberculosis, malignant lymphoma or metastasis. FNAC is a simple, cost effective, non invasive technique
Tuberculosis (TB) is a major cause of morbidity and readily performed in the out patient (O.P) setting and
mortality in India. Tuberculous lymphadenopathy is a has proved to be useful in the diagnosis of TB from
prominent cause of peripheral adenopathy amongst practically any site in the body.3 In this era of HIV, TB
children in the developing world; amongst Indian lymphadenitis should be considered, diagnosed and
children it is, not only the commonest cause of such treated properly.
adenopathy 1 , but is also the commonest form of
The objectives of our study were (1) to evaluate the
extrapulmonary tuberculosis.2
efficacy of FNAC as a diagnostic tool in cases of
Demonstration of acid fast bacilli (AFB) in smears clinically suspected TB lymphadenitis with compare to
and culture of sputum are widely employed for excision biopsy, (2) to correlate TB lymphadenitis with
diagnosis of pulmonary tuberculosis, while biopsy clinical, cytological, radiological and mantoux test
with histopathologic examination and demonstration of features and (3) to find out the prevalence and pattern
AFB is the gold standard for diagnosis of of TB lymphadenitis in children.

Correspondence and Reprint requests : Dr J Balaji, M.D. MATERIAL AND METHODS


(Paediatrics), S/o Mr T Jayaraman, (Rtd.,) ADE / TNEB, Mullai
Nagar, Periyampatty Post, Dharmapuri Dt Tamil Nadu. 635 A prospective correlational study was done in the
205, India. department of pediatrics of a tertiary care hospital at
[DOI-10.1007/s12098-009-0271-2 Madurai during January 2005 to June 2006. All the
[Received November 26, 2008; Accepted May 28, 2009] children attended pediatric out patients with significant

Indian Journal of Pediatrics, Volume 76—December, 2009 1241


J. Balaji et al

lymphadenitis were investigated routinely along with cells 3. In Ziehl-Neelson staining, AFB are seen as red
Mantoux test and chest X-ray. They were treated with beaded rod-like structures against a blue background
antibiotics for a period of 2 weeks. 4 If nodes remain under the oil immersion lens 3. The results of FNAC
persistently enlarged even after 2 weeks of antibiotics, further correlated with the histological diagnosis by
FNAC of lymphnode was done by the pediatrician (the biopsy. No adverse reactions occurred. Data was
author – who undertook the study) and sent for entered in excel spread sheet and statistical analysis
histopathological and microbiological evaluation. 4 was done by using epidemiological information
Excision biopsy was also done by the pediatric package. KRUSKAL – WALLI’S chi square test was
surgeon. used. P value <0.05 was taken to represent significant
difference.
Inclusion criteria : (1) cervical, axillary and inguinal
adenitis persisting even after 2 weeks of antimicrobial
therapy in children among the age group of 0-12 years, RESULTS
(2) lymphnode size > 1.5cm in the inguinal region and
> 1 cm in the cervical and axillary region. Exclusion Nine hundred and sixty cases of significant
criteria : (1) isolated left axillary adenitis in an infant lymphadenitis were treated with antibiotics and out of
(BCG adenitis), (2) Drug induced lymphnode which 135 were subjected to FNAC. 100 cases turned
enlargement out for excision biopsy. 88 specimen were sent for AFB
FNAC was done after informed consent from parents smear (ZN) and AFB culture was done for 38 cases. The
and institutional ethical clearance, using 22 or 23 G patients were evaluated in to 3 broad categories as
needle and syringe. After the enlarged lymphnode was reactive adenitis, TB lymphadenitis and malignancy.
fixed by fingers, needle inserted into the lymphnode. In FNAC, TB lymphadenitis constitute 34.07% (46
With maintaining the negative pressure, aspiration cases). 9 cases (6.6%) were reported as having malig-
was done by inserting the needle into various nant disease, of which 6 (4.4 %) were primary
directions of the lymphnode. After fixing the malignancies, all were Hodgkin’s lymphoma and
lymphnode material, slides were sent for remaining 3 (2.2%) cases were acute lymphoblastic
pathologicacl and microbiological examination. In all leukemia with lymph node metastasis. 80 cases (59.25
the cases, isopropyl alcohol fixed smears were made %) were reactive adenitis. Biopsy revealed 48 (48%) of
and stained with papanicolaou, eosin and reactive adenitis, 42 (42%) of TB adenitis and 10 (10%)
hematoxylin stain. Another two slides containing cases of malignancy. 7 cases were primary malignancy.
aspirated material were heat fixed and sent for Ziehl Out of 7cases, 6 were Hodgkin’s lymphoma and 1 case
Neelson staining for AFB. Some of the material were was non Hodgkin’s lymphoma. The remaining 3 cases
collected at sterile container for acid fast bacilli culture were leukemia.
and sent to microbiology department. A correlation was done in 100 cases which were
For TB lymphadenitis, the essential component is diagnosed by FNAC and histopathology (Table 1). Of
the presence of epithelioid cell granulomas and the 100 cases, 98 cases of FNAC results correlate with
caseous necrosis with or without Langhan’s giant histopathology. Overall sensitivity, specificity and

TABLE 1. Correlation of Cytology (FNAC) and Histopathology (Biopsy)


Negative predictive value

Biopsy Results
Positive predictive Value
Diagnostic Accuracy (%)

FNACResults
Reactive Adenitis

False Negative -
False Positive +
True Negative -
True Positive +

Sensitivity (%)

Specificity (%)
No. of cases

Lymphoma

Metastasis
TB

Reactive Adenitis 5 0 48 1 1 - 48 50 2 - 100 96 98 96 100


TB 41 - 41 - - 41 58 - 1 98 100 99 100 98
Lymphoma 6 - - 6 - 6 93 - 1 86 100 99 100 99
Metastasis 3 - - - 3 3 97 - - 100 100 100 100 100
Overall 100 48 42 7 3 50 48 - 2 96 100 98 100 96

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Fine Needle Aspiration Cytology in Childhood TB Lymphadenitis

diagnostic accuracy were 96%, 100% and 98% Posterior cervical (50%) followed by submandibular
respectively. Of the 50 cases of reactive adenitis, 2 cases group (47.8%) commonly involved in TB. Posterior
of FNAC diagnosis did not correlate with cervical (100%) followed by axillary (55.5%) and
histopathological diagnosis. One was diagnosed as anterior cervical (44.4%) commonly involved in
tuberculosis and other one as lymphoma on malignancy (Table 2). Multiple nodes were commonly
histopathology. The sensitivity, specificity and present in TB lymphadenitis (52.1%) whereas
diagnostic accuracy for this group were 100%, 96% and generalized lymphadenopathy was more frequent in
98% respectively. In cases of tuberculosis, Hodgkin’s malignancy (66.6%). 95% of reactive and 88.8% of
lymphoma and metastasis diagnosed by FNAC, all malignant nodes were discrete. 47.8% cases of TB were
cases showed exact correlation in histopathology. matted (P=0.0001). Though H/o contact with open TB
Sensitivity, specificity and diagnostic accuracy for TB was present in 32.6 % cases of TB lymphadenitis, 15 out
lymphadenitis were found to be 98%, 100% and 99% of 22 cases (68.1 %) who had history of contact
respectively. Sensitivity, specificity and diagnostic developed TB lymphadenitis (P=0.0016). Out of 41
accuracy for lymphoma were found to be 86%, 100% and children without BCG scar, 19 (46.3%) had TB adenitis
99% respectively. Sensitivity, specificity and diagnostic (P=0.163). Out of 40 mantoux positive children, 29
accuracy for metastasis were found to be 100%. (72.5%) had TB adenitis whereas in 86 mantoux
negative children, only 17 children (19.8%) had TB
TB lymphadenitis were commonly seen (65.2%) adenitis (P=0.163). Positive Mantoux test was
among 7 to 12 years age group (P=0.0235 significant). significantly (P=0.0001) associated with TB
Whereas malignancy commonly (66.7%) affects 4 to 6 lymphadenitis. But negative mantoux test does not rule
years age group (Table 2). There was no significant out TB always.
difference in the prevalence of all the three groups of
lymphadenitis among both sexes (P=0.6943). In the present Though Grade III and IV Protein Energy
study, lymph node size was more than 2 cm in 86.9% and Malnutrition (PEM) were present only in 28.3% of TB
100% cases of TB and malignant lymphadenopathy lymphadenitis, out of 19 PEM cases, 13 (68.4%) had TB
respectively (P=0.0001 Significant). (Table 2). lymphadenitis. It was statistically significant (P=0.0041)

TABLE 2. Prevalence and Pattern of Various Lymphadenitis in FNAC


TB Lymph adenitis Reactive Adenitis Malignancy
N = 46 N =80 N=9
1. Age group
0 – 3 years 3 (6.5%) 1 3 (16.3%) 1 (11.1%)
4 -6 years 1 3 (28.3%) 3 3 (41.2%) 6 (66.7%)
7 – 12 years 3 0 (65.2%) 3 4 (42.5%) 2 (22.2%)
Youngest Age 3 years 10 months 2 years
Eldest Age 12 years 12 years 11 years
2) Male : Female 24 : 22 46 : 34 5:4
1.09 : 1 1.35 : 1 1.25 : 1
3) Size of Node (> 2cm) 4 0 (86.9%) 1 9 (23%) 9 (100%)
4) Site of Node Posterior cervical (50%) Posterior cervical (61%) Posterior cervical (100%),
submandibular (47.8%) submandibular (33.75%) axillary (55.5%) and
axillary (15.2%) axillary (15%) anterior cervical (44.4%)
5) Single node 1 6 (34.7%) 4 6 (57.5%) 1 (11.1%)
Multiple nodes 2 4 (52.1%) 2 9 (36.2%) 2 (22.2%)
Generalised Lymphadenopathy 6 (13%) 5 (6.2%) 6 (66.6%)
6) Matted Nodes 2 2 (47.8%) 4 (5%) 1 (11.1%)
Discrete Nodes 2 4 (52.1%) 7 6 (95%) 8 (88.8%)
7) H/o Contact with Open TB 1 5 (32.6%) 7 (8.75%) -
8) BCG scar not present 1 9 (41.3%) 2 2 (27.5%) -
9) Grade III PEM 1 2 (26.1%) 6 (7.5%) 2 (22.2%)
Grade IV PEM 1 (2.2%) 0 -
10) Mantoux + ve 2 9 (63.04%) 1 1 (13.75%) -
11) (i) Positive findings in 8 (17.39%) 8 (10%) 1 (11.1%)
chest X-ray
(ii) CT Thorax 4/4 -
12) Significantly elevated ESR 6 (13.04%) 3 (3.8%) 4 (44.4%)

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J. Balaji et al

when compared to reactive adenitis. As chest X-ray There are 5 cytomorphological spectrum of TB
findings were not statistically significant (P=0.4059), lymphadenitis diagnosed by FNAC. 3,5 They were
Chest X-ray alone not enough to start anti tuberculous necrosis with granuloma, epithelioid cell granuloma,
treatment. Elevated ESR was not significant (P=0.0503) caseation necrosis, focal granuloma with inflammatory
to diagnose TB whereas it may help in cases of exudates and inflammatory exudates only with
malignancy as 44.4% cases of malignant lympha- occasional langhan’s giant cell in the present study.
denitis had elevated ESR. Caseous necrosis with epithelioid cell granuloma (50%)
was the most common cytomorphological spectrum
which is more characteristic feature of TB
TABLE 3. Comparative Statement of FNAC Accuracy Rates lymphadenitis. Ziehl Neelson staining was positive in
(Sensitivity) in Respect of TB Lymphadenitis 32.5% cases. AFB was mostly found in inflammatory
Authors Year No. of No. of cases % exudates with occasional langhan’s giant cells
cases* correctly cytological spectrum (66.7%) followed by the necrosis
diagnosed group (60%).
by FNAC
1. Bloch, M 11 1967 10 8 80
DISCUSSION
2. Nagpal, B.L. 11 1982 22 21 95.45
3. Patra, A.K 11 1983 39 34 87.18 FNAC findings constitute 46 (34.07%) cases of TB
4. Dandapat, M.C 11
1987 36 30 83.33 lymphadenopathy in the present study. There are
similar finding as well as variations in the prevalence of
5. Lau, S.K 9 1990 90 69 77
TB are seen in various studies.6,7,8 These variations may
10
6. Narang, R.K 1990 31 27 87 be due to local geographical prevalence of TB, age and
7. Jain, NK8 1992 64 52 81.2 immunological status of the patients selected.
8. Ahmad, S.S et al6 2005 35 33 97
Correlation study was done between cytological and
histopathological diagnosis in 100 cases. The finding of
9. Our study 2006 42 41 98
the present study compared with other authors are
* As confirmed by histopathological studies of the biopsy
shown in tables 3 and 4.1, 6, 8-11 The present study showed
specimen.
that sensitivity, specificity and diagnostic accuracy for
TB lymphadenitis were 98%, 100% and 99%
respectively which correlates well with Ahmad et al.6
TABLE 4. Sensitivity, Specificity and Accuracy of FNAC with Positive and negative predictive values were 100 and 98
Histopathology for Various Lymphadenitis respectively. Most of the study population of other
Cytological Authors Sensiti- Specifi- Diagnostic studies included both adults and children. As AFB
Diagnosis vity % city % Accuracy % stain was also included and more number of children
1. Reactive R.K. Narang et al10 33.3 - -
were correlated in the present study, accuracy rate is
also good. Sensitivity, specificity and diagnostic
Adenitis S.S. Ahmad et al 6 91.6 99 97.3
accuracy of reactive adenitis, lymphoma and metastasis
Our study 100 96 98
of the present study also very well correlates with
Ahmad et al study.6
2. TB R.K. Narang et al10 87 - -
S.S. Ahmad et al 6 97 97.5 97.4 As in this study, Ahmad et al6 and Bedi et al7 reported
Our study 98 100 99 TB and malignant nodes were > 1 cm in their studies.
Most of the studies mention the site generally cervical
3. Lymphoma R.K. Narang et al10 88.8 - - group instead of whether posterior or anterior cervical.
S.S. Ahmad et al 6 89.6 97.6 95.6 Bezabih et al 12 and Ahmad et al 6 reported in their
Our study 86 100 99 studies that cervical nodes followed by axillary nodes
were commonly involved in TB. Consensus statement
4. Metastasis R.K. Narang et al10 100 - - of IAP working group mentioned that posterior cervical
S.S. Ahmad et al6 100 100 100 lymphadenopathy was rare in TB4. But in the present
Our study 100 100 100
study, posterior cervical (50%) followed by
submandibular nodes (47.8%) were commonly involved
5. Overall R.K. Narang et al10 85 - - in TB, whereas posterior cervical (100%) followed by
Reddy M.P. et al1 94 100 -
axillary (55.5%) and anterior (44.4%) cervical nodes
6
were commonly involved in malignancy. Khan RA et
S.S. Ahmad et al 94.6 98.5 97.6
al13, the pediatric surgery text book by Jay L. Grosfeld et
Our study 96 100 98
al14 and B.D.Chaurasia15 supports our findings.

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Fine Needle Aspiration Cytology in Childhood TB Lymphadenitis

Acid fast staining in cases of TB showed a positivity Uma. Professor of Microbiology and Dr. Thirumalaikolundu
rate of 32.5%. These findings very well correlate with subramaniam, Former Professor and Head of the Department of
Medicine for their valuable suggestions and guidance throughout
Lau SK et al 9 (37 %) and Kumar et al 16 (33.5 %). But
the study. We also thank Mr. Aasaithambi for his help in the
Radhika et al17 (23.58 %) and Tarun Dua et al18 (27.11%) statistical analysis and all the children and their parents who
reported lower AFB smear positivity and Bezabih M et participated in the study.
al12 reported more positivity (59.4%). This variation may
Contributions: J.Balaji. Did the FNAC, collected the specimen,
be due to that AFB positivity and open TB are less concept and study design, analysis of data and drafting the
common in children and AFB positivity depends upon article; S.Shanmugasundaram, Involved in concept and study
the exposure and immunological status of the patient. design, analysis of data and critical revision of the draft;
Also needle aspiration may not be positive if it is done S.Nataraja rathinam, Involved in concept and study design,
at the normal portion of lymphnode where AFB or analysis of data and review of literature; P.Amutha Rajeswari,
Involved in executing the work, data analysis and drafting final
caseating necrosis is absent. AFB staining is must3,5,12,16 script; M.L.Vasathakumari, Involved in data analysis and
as it is mostly positive in cases where cytology showed interpretation of data and gave final approval for the paper.
inflammatory exudates only with occasional giant cells
Conflict of Interest: None.
which may suggest TB but will not be strongly reported
as TB lymphadenitis in cytology. But AFB load is high Role of Funding Source: RNTCP, Tamil Nadu, Division
in these smears.
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Acknowledgement
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We express our sincere thanks to the Department of Pediatric Cytopathology 2002; 13: 284-290.
surgery, Pathology and Microbiology for their valuable 13. Khan RA, Wahab S et al. Children with significant cervical
suggestions and kind cooperation throughout the study. We also lymphadenopathy: clinicopathological analysis and role of
extend our thanks to Dr.Ravikumar, Asst. Professor of Paediatric fine-needle aspiration in Indian setup. J Pediatr (Rio J) 2008;
Surgery, Dr. Sivagami, Assistant Professor of Pathology, Dr. A. 84: 449-454.

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ERRATUM

The article entitled "Impact of Attention-Deficit/Hyperactivity Disorder on Health-Related Quality-of-Life of Specific Learning
Disability in Children" authored by Sunil Karande and Kiran Kumar Bhosrekar, Published in November 2009 issue, Page No.
1119-1124. The title should read as "Impact of Attention-Deficit/Hyperactivity Disorder on Health-Related Quality-of-Life of
Specific Learning Disability Children" In Discussion part line 10 (page 1123) should read as "our data clearly shows that SpLD/
ADHD children more........."
The error is regretted.

Editor

1246 Indian Journal of Pediatrics, Volume 76—December, 2009