International J.

of Healthcare and Biomedical Research, Volume: 03, Issue: 01, October 2014, Pages 127-137

Original article:
Diagnosis of lymphadenopathies by FNAC: a prospective study
Dr. Kandukuri Mahesh Kumar, Dr. Chinthakindi Sravan, Dr. Swarupa Ravuri, Dr. Divyagna

Department of Pathology, Malla Reddy Institute of Medical Sciences, Suraram , Hyderabad, India
Corresponding author : Dr. Kandukuri Mahesh Kumar

Abstract:
Objective: To determine the incidence of various pathological lesions involving lymph nodes by using simple and easy
diagnostic tool (FNAC) and prove the diagnostic importance of FNAC.
Materials and methods: Our study included 1926 cases of lymphadenopathy, between January 2012 and December 2013.
Patients with palpable lymph nodes anywhere in the body with a valid requisition were included in the study. All the
demographic details, history and clinical findings of the swelling are taken by the attending pathologist.
Results: Our study included 1926 cases of lymphadenopathy , we reported 1136 cases (59 %) as granulomatous lymphadenitis ,
500 cases ( 26 %) of Non-specific lymphadenitis , 232 cases (12%) of Lympho-proliferative disorders (Hodgkin’s and Non-
Hodgkin’s disease) 58 cases (03%) metastases from primary site. Our study also showed the incidence of lympho-proliferative
diseases in association with Human Immuno-deficiency Virus (HIV) infection (144 cases). Majority of the granulomatous
lymphadenitis cases were associated with HIV cases constituting about 66.5 % (756 cases).
Conclusion: Fine Needle Aspiration Cytology is a simple, safe, rapid, cost effective and reasonably accurate method of
establishing the diagnosis of lymphadenopathy. Overall accuracy of FNAC in comparison with the histopathological study is
very high and may obviate the need of excision biopsy when the findings are compatible with the clinical diagnosis. The high
accuracy rate of aspiration cytology of lymph nodes calls for its wide application in daily practice.
Keywords: Lymphadenopathy, Lympho-proliferative disorder, FNAC.

Introduction: Lymphadenopathy is one of the
commonest clinical presentations of
attending the outdoor clinics in most hospitals. The
aetiology varies from an inflammatory process to a
(1)
malignant condition. The use of fine needle
aspiration cytology (FNAC) in the investigation of
lymphadenopathy has become an acceptable and
widely practiced , safe, simple, rapid, painless and
minimally invasive technique. FNAC is highly cost
effective out-patient procedure and
accuracy. FNAC was initially conceived as a means
to confirm a clinical suspicion of local recurrence or
metastasis of known malignancy without subjecting
the patient to further surgical intervention. Many
clinicians feel that this remains the most important
patients, contribution of the technique from practical point of
view, but the clinical value of FNAC is not limited to
neoplastic conditions. FNAC is also valuable in the
diagnosis of inflammatory, infectious, reactive,
degenerative conditions. Samples which were
aspirated from the swelling can be used for
microbiological and biochemical analysis in addition
to cytological preparations. Now –a-days FNAC is
has high used as a first line investigative technique in any
palpable and visible swellings of the body. Few of
the differential diagnoses of the lymphadenopathy
include reactive hyperplasia/ inflammatory
conditions, granulomatous disorders and malignancy.

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Thus FNAC gives a clear picture of the case/cases
requiring further investigations, medical
management, surgical intervention or just clinical
follow-up. FNAC is a valuable diagnostic technique
with least number or nil contraindications. Shakya et
al. also mentioned that the cytology is more readily
accepted for the evaluation of deeply seated lymph
nodes (i.e. surgically inaccessible) with primary
lymphoma or for medically unfit patients for surgery.
We planned study to determine the incidence of
various pathological lesions involving lymph nodes
by using simple and easy diagnostic tool (FNAC) and
prove the diagnostic importance and accuracy of
FNAC.
MATERIALS AND METHODS
Our study included 1926 cases of lymphadenopathy,
between January 2012 and December 2013. Patients
with palpable nodes were referred to department of
pathology after clinical examination by the clinician
and surgeon .Routine FNAC was performed by the
attending pathologist on receiving the requisition
duly filled by the consultant surgeon. All the
demographic details of the patient, history and
clinical findings of the swelling are taken by the
attending pathologist and entered in a cytology
register. Under aseptic precautions, aspiration of
enlarged lymph nodes was performed free hand using
a 23 G needle with 5 cc or 10 cc syringe. The cellular
aspirate is spread on a dust-free glass slide and
immediately transferred to coplin jars filled with
alcohol for fixation. After fixation, slides are stained
with Hematoxylin and Eosin (H & E). Diagnosis was
given on the same of FNAC procedure.
Granulomatous inflammation is recognized
cytologically by observing aggregates of histiocytes
with or without associated multinucleated giant cells.
A dirty necrotic background would suggest caseation
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and possibly tuberculosis. In cases where an infective
aetiology was suspected, needle washings were sent
for bacteriological culture and sensitivity. When TB
was suspected, an additional sample was sent for
culture and slides were also stained with Ziehl-
Neelsen methods to detect acid fast bacilli (AFB)
directly. The eventual diagnosis of granulomatous
inflammation by FNAC was confirmed either by
other supportive laboratory investigations or by
surgery in difficult or in doubtful cases where the
definitive opinion is not possible. In non-specific or
reactive lymphadenopathy cases, a repeat FNAC was
done after a period of 7 to 10 days after a course of
antibiotic therapy. In Lympho-proliferative disorders,
malignancies or metastases, FNAC diagnosis was re-
confirmed by histopathological examination.
RESULTS
In our study, we reported 1926 cases presented with
lymphadenopathy at various locations of the body,
most common being cervical lymphadenopathy.
1) In a total study of 1926 cases of
lymphadenopathy , we reported 1136 cases
(59 %) as granulomatous lymphadenitis ,
500 cases ( 26 %) of Non-specific
lymphadenitis , 232 cases (12%) of
Lympho-proliferative disorders (Hodgkin’s
and Non- Hodgkin’s disease ,58 cases (03%)
metastases from primary site.
2) Our study also showed the relative incidence
of lympho-proliferative diseases in
adults(218 cases) and pediatric population
(14 cases ) and also incidence of lympho-
proliferative diseases in association with
Human Immuno-deficiency Virus (HIV)
infection (144 cases).( FIGURE 1 & 2)
3) Among the total incidence of granulomatous
lymphadenitis reported, 71 % (806 cases)of
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the cases were reported in adults and 29 % lymphadenitis cases were associated with
(330) of cases were reported in the pediatric HIV cases constituting about 66.5 % (756
population. Majority of the granulomatous cases).(FIGURE 3 & 4)

250 218
200
150
14
100
50
0

FIGURE 1 – Incidence of Lymph proliferative diseases in adults (218 cases) and paediatric age group (14
cases)

88 Cases in Non- HIV

HIV
144 Cases Associated
with HIV Non- HIV

FIGURE 2- Incidence of Lympho-proliferative diseases associated with HIV (88 cases )

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1000 806 330

500
0

FIGURE 3- Incidence of granulomatous lymphadenitis in adult (806 cases) and pediatric population (330
cases)
INCIDENCE OF GRANULOMATOUS LYMPHADENITIS IN HIV PATIENTS

380 non-HIV cases HIV

showing
Granulomatous
lymphadenitis
756 HIV cases showing
Granulomatous lymphadenitis

FIGURE 4- Incidence of Granulomatous Lymphadenitis in HIV patients ( 756 cases).

DISCUSSION immunohistochemical, radiological, biochemical and

The well-defined role of FNAC in the investigation special staining techniques) is useful for obtaining a
(2,3)
of lymphadenopathy has previously been studied. definitive diagnosis. The algorithm shows a useful
In the context of granulomatous disorders, the classification of the aetiology of granulomatous
possible aetiology is wide and the use of FNAC with lymphadenopathy. (FIGURE 5)
other ancillary tests (microbiological,

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Aetiologies of Lymphadenopathies :

FNAC OF LYMPHADENOPATHY

Non- Granulomatous Inflammations Granulomatous Inflammations

Infective Neoplastic
Tuberculosis
Atypical Mycobacterium
Sarcoidosis
Toxoplasmosis
Lymphoma Carcinoma
Hodgkin’s Lymphoma Metastatic
Non-Hodgkin’s Lymphoma

Tuberculosis cervical lymphadenopathy usually predominant , the upper deep jugular nodes in
present with multiple lymph node enlargements, less posterior triangle were most commonly involved.
constitutional symptoms, tuberculosis is an important Tuberculosis lymphadenopathy constituted the
(4)
public health problem and it is commonest cause commonest lesion followed reactive lymphadenitis,
of infectious diseases affecting the lymphatic tissues lymphoproliferative disorders and metastatic
(5)
of the body . The diagnosis is based on high index malignancies, which is correlating with most of the
(6-10)
of doubt with hematological and pathological studies of Indian authors . Maximum AFB
investigations this diseases can be diagnose with positivity is seen in cases showing caseous necrosis
FNAC (FIGURE 7). In our study family history was with occasional epithelioid cells. Sometimes in
not present in most of the patients while commonest absence of AFB positivity the diagnosis of highly
age group affected was 18 to 35 years, and male were suspicious of tuberculosis was given in these lesions
with strong clinical suspicion, high ESR and chest X-

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ray findings. The tuberculosis in HIV positive cases
showed caseous necrosis, while granulomas were less
and ill formed.
A suspicious clinical history of TB (pyrexia, night
sweats, recent travel to endemic areas, no previous
BCG vaccination) coupled with positive aspirate,
blood, sputum or urine tests for AFB and good
response to anti-tuberculous therapy supports the
diagnosis of TB. One disadvantage is the inherent
delay in culture result, but it is anticipated that as
polymerase chain reaction and other amplification
techniques become more common, detection time for
the organism will shorten, improving the value of
FNA in clinical practice. The presence of epithelioid
cells either with caseation or positive Ziehl-Neelsen
stain for acid-fast bacilli appears to be the best
criterion to diagnose tuberculous lymphadenitis by
fine needle aspiration. Bezabih et al found FNAC
reliable in helping to avert more invasive surgical
procedures undertaken in the diagnosis
(11)
tuberculous lymphadenitis . lymphocytes with a variable but much smaller
The typical FNAC features of toxoplasmosis include
the presence of follicular hyperplasia with secondary
germinal centre rich in macrophages, presence of
groups of epithelioid cells and presence
monocytoid histiocytes have been
(12,13)
described . A combination of FNA features with
positive serological testing and history of animal
contact gives the diagnosis of toxoplasmosis and thus
avoids unnecessary surgical excision. Sarcoidosis is a
disease of unknown aetiology that
characterized by the histological hallmark of
epithelioid non-caseating granulomas,
accompanied by multinucleated giant cells. Although
there is no single gold standard test, the important
role of FNAC in histological diagnosis and its under
utilization was highlighted by Tambouret et al (14).We
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agree with the authors that FNAC used in
conjunction with clinical findings, radiological and
laboratory investigations can be a cost effective
method in diagnosis toxoplasmosis.
The reactive pattern is variable depending on the
degree of stimulation, the number and size of the
germinal centres and on whether the sample derives
mainly from a germinal centre or from interfollicular
or paracortical tissue. Germinal centre material is
represented by poorly defined tissue fragments of
poorly cohesive cells. These fragments include
centroblasts, centrocytes, tingible body macrophages
and a number of lymphocytes which adhere to the
syncytial cytoplasm of dendritic reticulum cells.
Dendritic reticulum cells have oval or round nuclei
with a smooth nuclear membrane, a coarsely
granular, uniformly distributed chromatin and small
distinct nucleoli. The cytoplasm is dispersed in the
background. A smear, which derives mainly from
of interfollicular tissue, consists predominantly of
number of scattered immunoblasts, plasma cells, non-
specific histiocytes and endothelial cells. (FIGURE
8)
of The main features which distinguish a reactive
previously process from lymphoma are:
a) A mixed population of lymphoid cells
representing the whole range of lymphocyte
transformation from small lymphocytes to
immunoblasts and plasma cells.
can be b) A predominance if small , sometimes
slightly larger stimulated lymphocytes ,
usually which have small round nuclei and a
characteristic chromatin pattern of large ill-
defined condensations
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c) Centroblasts and centrocytes associated with rhabdomyosarcoma. This has been suggested to be
dendritic reticulum cells and tingible body either a response to necrotic material or an
macrophages derived from germinal centres. immunological T-cell mediated hypersensitivity
FNAC as a first line screening method has been reaction to cell surface antigens. However, the
(3&15)
recommended in suspected malignancy . precise mechanism is largely speculative as the exact
Granulomas may be encountered in both Hodgkin’s tumor or host factors that enable such a response
disease and non-Hodgkin’s lymphoma, particularly remain unknown. We agree with Lui et al (18) in their
T-cell lymphoma(16) Hodgkin’s lymphoma is pragmatic approach of diligent examination of FNAC
characterized by the classic Reed Sternberg cells in a slides combined with ancillary clinical, serological
background of sarcoid-like granuloma, reactive and imaging investigations in the drainage areas to
lymphoid cells and occasional eosinophils. identify any occult malignancy.
Occasionally, lymph nodes containing metastatic In the present study 232 cases of lymphomas have
carcinoma may also show features of granuloma. been reported 163 cases of Hodgkin's lymphoma
Previous reports have been described in metastatic which was diagnosed on FNAC due to preserved
nasopharyngeal carcinoma, seminoma and malignant Reed Sternberg (RS) cells (FIGURE 9 & 10). In
melanoma where granulomas were seen mimicking lymphoma group, with presence of RS cell, the
granulomatous lymphadenitis. Histologically, non- cytological diagnosis of Hodgkin's lymphoma is easy.
caseating granuloma composed of epithelioid FNAC is helpful in diagnosis of Hodgkin's
histiocytes with multinucleated giant cells are seen, lymphoma though biopsy is recommended for
but these can be indistinguishable from confirmation and classification.
granulomatous inflammation from other causes. A Cytological sub-typing of lymphoma in FNAC
(17)
series by Khurana et al highlighted the difficulties smears is difficult and requires extensive experience.
encountered in making a definitive diagnosis of It can be possible where the team of experience
malignant neoplasm that mimics, or occurs, in pathologists and oncologists are present. It is
association with granuloma. Granulomatous believed by many authors that in non-Hodgkin's
inflammation found in lymph nodes draining lymphoma biopsy are mandatory, and we also believe
carcinomas is a recognized phenomenon. Such in it.
phenomenon is reported in pulmonary small cell Below mentioned algorithm is useful in sub-typing
carcinoma, malignant melanoma, papillary thyroid the Lymphomas on FNAC. (FIGURE 6)
carcinoma, gastric carcinoma, and

Indian J of Basic and Applied Medical Research

Is now with

IC Value 5.09

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ALGORITHM
CLASSIFICATION OF LYMPHOMA
FNAC LYMPHOID POPULATION OF CELLS

Monotonous population Heterogenous population Pleomorphic population

Predominant cell type Mainly small cells Large cells

Small Medium Large

Small Burkitt’s Diffuse a)Reactive hyperplasia a)Reactive Immunoblastic

Lymphocytic Lymphoma Large B cell b) Follicular Lymphoma(Gr 3)
Lymphoma Lymphomas b)Follicular Lymphoma
c) Peripheral T cell lymphoma
c) Marginal Zone lymphoma

a )Mantle cell Lymphoma d)Lymphoplasmacytic Lymphoma

b) Lymphocyte Predominant Hodgkin’s Lymphoma

c) Lymphocyte Rich Hodgkin’s Lymphoma

d)T-cell rich B cell Lymphoma

a) Anaplastic large cell lymphoma
b) Large cell Pleomorphic lymphomas (T-Cell & B-Cell type)
c) True histiocytic lymphoma (Histiocytic sarcoma)
d)Anaplastic plasmacytoma

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FIGURE 8
FIGURE 7

FIGURE 9 FIGURE 10

FIGURE 7- Smear shows clusters of epithelioid cells, lymphocytes , plasma cells , caseous necrosis.(TB
lymphadenitis)

FIGURE 8-Smear
FIGURE 9 shows small and large lymphocytes, tingible body10
FIGURE macrophages, centroblasts, centrocytes in
a hemorrhagic background.( Reactive Lymphadenitis)

FIGURE 9-Smear shows polymorphous population of cells comprising of lymphocytes , eosinophils ,

occasional plasma cells and large mono-nucleate and bi-nucleate pleomorphic Reed-Sternberg(RS) cells in a
hemorrhagic background (Hodgkin’s Lymphoma).

FIGURE 10- Smears shows bi-nucleate pleomorphic Reed- Sternberg (RS) cell.

CONCLUSION cases biopsy should be advised to support or confirm

Fine Needle Aspiration Cytology is a simple, safe,
rapid, cost effective and reasonably accurate method
of establishing the diagnosis of lymphadenopathy.
Non representative sampling usually in small
metastatic deposits may be an important cause of
false negative diagnosis and granulomatous reaction
to metastatic tumors may be misinterpreted as
granulomatous lymphadenitis on FNAC. In such
the FNAC diagnosis. Whenever necrosis is abundant
in cases of metastatic malignancy, cytomorphological
interpretation of smears should be done with caution.
Overall accuracy of FNAC in comparison with the
histopathological study is very high and may obviate
the need of excision biopsy when the findings are
compatible with the clinical diagnosis. The high
accuracy rate of aspiration cytology of lymph nodes

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calls for its wide application in daily practice. Thus in period of time and also makes the clinician decide
conclusion this simple procedure should be about the treatment so as to prevent the progress of
advocated by the clinicians so that early diagnosis of the disease.
cervical lymphadenopathy is possible in shortest

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