LIST OF ABBREVATIONS USED

AFB – Acid Fast Bacilli

ALL – Acute Lympholastic Leukemia

ASL – Acute Suppurative Lymphadenitis

AIDS – Acquired Immuno Deficiency Syndrome

CLL – Chronic Lymphocytic leukemia

CNSL – Chronic Non Specific Lymphadenitis

DLBL – Diffuse Large B-cell Lymphoma

EBV – Epstein-Barr Virus

EMA – Epithelial Memrane Antigen

ESR – Erythrocyte Sedimentation Rate

FISH – Flourescent Insitu Hybridization

FL – Follicular Lymphoma

FNAC/FNA – Fine Needle Aspiration Cytology

H&E – Hematoxylin & Eosin

HIV – Human Immunodeficiency Virus

HTLV1 – Human T cell Leukemia Virus

1
HL – Hodgkin Lymphoma

LEU – Leukemia

LN – Lymphnode

MET – Metastasis

MALT – Mucosa Associated Lymphoid Tissue

NHL – Non-Hodgkin lymphoma

NTGL – Non Tuberculous Granulomatous

Lymphadenitis

NK – Natural Killer

REAL – Revised European American

RS cell – Reed-Sternberg cells

RL – Reactive Lymphadenitis

SLL – Small Lymphocytic Lymphoma

TB – Tuberculosis

TBLN – Tuberculous Lymphadenitis

USG – Ultra Sound Guided

ZN – Ziehl – Neelsen stain

2
 ABSTRACT

Background:

Lymphadenopathy is an abnormal increase in size and/ or altered consistency of

lymph nodes. It is a very common clinical manifestation of regional or systemic disease

caused by the invasion or propagation of either inflammatory cells or neoplastic cells into

the node and serves as an excellent clue to the underlying disease.

Objectives :
The study was undertaken to evaluate the diagnostic efficacy of the fine needle

aspiration cytology of lymphadenopathy as compared to open biopsy for histopathologi-

cal examination, to study the frequency of various neoplastic versus non-neoplastic le-

sions, their distribution in different age groups and to study the different cytomorpholog-

ical patterns associated with various lymphadenopathies.

Methods :
A prospective study was conducted from August 2009 to July 2011 for a period

of 2 years in 400 patients with lymphadenopathy referred to the Departmet of pathol-

ogy,S.V.S Medical college & Hospital ,Mahabubnagar.The patients were subjected to

FNAC and the material obtained was stained with H & E, and Z.N Stain.. FNA diagno-

sis was subsequently correlated and compared with the biopsy diagnosis in the available

cases.

3
Results :
Out of 400 patients of FNAC for lymphadenopathy excisional biopsy was avail-

able in only 85 cases . Non neoplastic & neoplastic lesions were seen in 308 cases & 64

cases respectively . 28 smears were non diagnostic .

Tuberculous lymphadenitis was the most common lesion in 45.75% of the cases.

Male to female ratio was 1:1.13 with most cases between 11-40 years age group.

The overall diagnostic accuracy of FNAC in the present study was 89.41.% with

accuracy of 87.19 % for tuberculous lymphadenitis and 1000.00% for metastatic carci-

noma. Cervical group of lymphnodes were the most commonly affected group of lymph

nodes 59.75%.

Epithelioid granulomas with necrosis was the predominant microscopic pattern

seen in 55.19% cases Overall AFB positivity was seen in 31.14% cases & predomi-

nantly seen in necrosis alone pattern(79%), In our study sensitivity , specificity ,Positive

and negative predictive values of FNAC in lymphadenopathy were 100 % , 96.97% ,

90.48% and 100 % respectively.

Conclusion:
FNAC is a simple,rapid,cost effective diagnostic tool for patients having signifi-

cant lymphadenopathy. The metastatic carcinomas, and tuberculous lymphadenopathy

can be diagnosed by FNAC with a high degree of accuracy. If FNAC is positive surgeon

can proceed to treat the patient without excisional biopsy of the enlarged lymph nodes &

most of the diseases are medically curable with limited role for surgery in non-neoplas-

4
tic lesions. Lack of tissue architecture on FNAC can be overcome by subjecting samples

to flow cytometry, T-cell, B-cell markers and immunocytochemistry analysis.

Key words :

Lymphadenopathy; diagnostic efficacy; fine needle aspiration cytology andhistopatholog-

ical examination

5
 TABLE OF CONTENTS

LIST OF TABLES

SL.NO. PARTICULARS PAGE NO.

1. INTRODUCITON

2. AIMS AND OBJECTIVES

3. REVIEW OF LITERATURE

4. MATERIAL AND METHODS

5. RESULTS

7. DISCUSSION

8. CONCLUSION

9. SUMMARY

10. BIBLIOGRAPHY

ANNEXURE I – PHOTOGRAPHS
11.

12. ANNEXURE II - PROFORMA

13. ANNEXURE III - MASTER CHART

14. ANNEXURE IV – KEY TO MASTER CHART

6
7
TABLE. PAGE
DESCRIPTION
NO. NO.

1. Principal lesions of lymph nodes

Conditions assosciated with reactive lymphoid

2.
hyperplasia:predominant histologic pattern by etiology

3. Cytodiagnositc criteria for tuberculous lymphadenitis

World health organization classification of the neoplastic

4.
diseases of the lymphoid tissues

Differential diagnosis of small cell lymphomas

5.

Primary sites of neoplasms and common sites of lymph

node
6.
metastases

7. Showing comparison of FNAC and biopsy

Showing the number and percentage of non-neoplastic and

8.
neoplastic lesions

9. showing non neoplastic lesions

showing neoplastic lesions

10.

Showing age distribution of lymphnodal lesions

11.

showing sex distribution in various lesions

12.

showing various sites involved in lymphnode lesions :

13.

8
14. showing size of lymphnode lesions
 LIST OF FIGURES

9
 LIST OF GRAPHS

S.No. Graph Page.No.

Showing the distribution of Non-neoplastic and Neoplastic

1
lesions

2 Showing the distribution of Non neoplastic lesions

3 Showing the distribution of Non neoplastic lesions

4 Showing sex distribution in various lesions

5 showing various sites involved in lymphnode lesions

6 showing various sites involved in lymphnode lesions

7 Cytological features of tuberculosis

8 Microscopic patterns of tuberculosis assosciated with

AFB positivity

9 Showing cytological diagnosis of Metastatic lesions

10
11
 INTRODUCTION

INTRODUCTION

Lymphadenopathy is an abnormal increase in size and/ or altered consistency of

lymph nodes. It is a clinical manifestation of regional or systemic disease and serves as

an excellent clue to the underlying disease. (1)

12
 The use of fine needle aspiration cytology (FNAC) in the investigation of lym-

phadenopathy has become an acceptable and widely practiced minimally invasive tech-

nique, which is safe, simple, rapid and relatively pain-free.

FNAC is highly cost effective and accurate as a first line investigative technique

with differential diagnosis including reactive hyperplasia/inflammatory conditions, gran-

ulomatous disorders and malignancy, stratifying cases requiring further investigations,

surgical intervention or clinical follow-up(1).

In the past the assessment of the lymphadenopathy was made indirectly from the

clinicopathological parameters or biopsy, but with the resurgence of the FNA as

diagnostic tool in the evaluation of lymphadenopathy,procedure of biopsy is avoided in

most of the cases as FNA is fairly accurate in the diagnoses of Lymphadenopathy(3). The

value of FNAC, besides making a diagnosis, also lies in early direction of appropriate in-

vestigations.

Aspirates from lymph nodes are usually very cellular and their interpretation

varies from clear diagnosis to a firm request for histopathology. However,limitations and

pitfalls of the procedure should be recognized. The knowledge of the pattern of lym-

phadenopathy in a given geographical region is essential for making a confident diagno-

sis or suspecting a disease.(2)

Tuberculosis is the commonest cause of lymphadenopathy in developing coun-

tries like India and should be considered in every case of granulomatous lymphadenopa-

thy unless proved otherwise(2).

The cytomorphological features obtained in needle aspiration, frequently corre-

late very well with histologic appearance of the same lesion and in some situations has

13
qualities of a micro-biopsy. In conjunction with radiologic studies, it provides ease in

following patients with known malignancy and ready identification of metastasis or re-

currence (3).

The diagnostic accuracy can be further increased if cytological findings are corre-

lated with clinical findings and other simple investigations such as X- Rays, peripheral

smear, ESR and Mantoux test. The appropriate use of FNA may obviate the need for an

open biopsy.

Use of aspiration cytology is accepted as a primary method of diagnosis in reac-

tive(4),infective and metastatic lymphadenapathy and in combination with immunologi-

cal evaluation has distinctly improved diagnostic accuracy in cases of

lymphoma(5,6) .But, predominantly, cytomorphology alone decides the nature of lym-

phadenopathy.

FNA cytology remains the first line investigation in cases of lymphadenopathy.

Besides initial diagnoses of lymphoma, it helps in detection of residual disease, recur-

rence and progression of low grade to high grade lymphoma and helps in the staging of

disease. Various special ancillary techniques are now being performed on lymph node as-

pirates to diagnose lymphoma versus other malignancies and to decide the functional

character of lymphoma and their clonal nature(7).

FNAC has become the primary investigative procedure for mass lesions in HIV-

positive patients, particularly in the assessment of lymphadenopathy. Lymphadenopathy

is one of the earliest manifestations of HIV. This may be due to the presence and effects

of HIV.8 Lymphadenopathy may also be a manifestation of opportunistic infections, lym-

phoid malignancy developing in an immunodeficient individual.

14
 The procedure is rapid, easily performed and in many cases obviates excision

while guiding subsequent therapy or observation(9).

FNA is a useful tool to determine whether the enlarging lymph nodes are related

to viral or opportunistic infections, Kaposi sarcoma, high-grade lymphoma, or metastatic

carcinoma . Needle aspiration biopsy and flow cytometry of lymph nodes has been pro-

posed as potentially useful in assessing the clinical status of HIV-infected patients .

The use of Fine Needle Aspiration Cytology (FNAC) for the diagnosis of

metastatic malignancies in the lymph nodes is a well-established method (10). Lym-

phadenopathy may be the first sign of malignancy in a patient. FNAC not only confirms

the presence of metastatic disease, but also gives clues regarding the nature and origin of

the primary tumour.

In patients with enlarged lymph nodes and previously documented malignancy,

FNAC can obviate further surgery performed merely to confirm the presence of metasta-

sis(11). The false- positive rate of lymph node FNAC for the detection of metastasis is

quite low (in the range of 0.9-1.7%). 2 Avoiding false-positive diagnosis is of obvious im-

portance since therapeutic and surgical decisions are often based exclusively on cytology

results (10).

It is safe alternative to excision biopsy and recommended as a first line investiga-

tion as compared to excisionbiopsy because it diagnosed 80% of T.B by FNA(12).Its sen-

sitivity and specificity have been documented by several studies in the past(13). FNA of

15
lymph nodes has high sensitivity and specificity in the distinction between a benign and

malignant lesion.

Accuracy estimates for lymph node FNA vary because of local variations in tech-

nique and referral patterns, but most investigators report over 90% accuracy in the diag-

nosis of metastatic tumor to lymph nodes, and a positive predictive value of almost 100%

(10,16). Similarly, the accuracy of a diagnosis of Hodgkin lymphoma is high,(17,18)

with a positive predictive value over 90%.(19)

The present study is undertaken to evaluate the usefulness of FNAC as a diagnos-

tic tool in cases of lymphadenopathy and study the different cytomorphological patterns

associated with various lympadenopathies in H & E and performing acid fast staining in

suspected tuberculous cases.

16
 AIMS
AND
OBJECTIVES

2.OBJECTIVES OF THE STUDY

This study is carried out in S.V.S Medical college and Hospital, Mahabubnagar.

The aim of this study was:

17
 1) To evaluate the diagnostic efficacy of the fine needle aspiration cytology of lym-

phadenopathy as compared to open biopsy for histopathological examination

2) To find out the frequency of lymphadenopathy in different age groups

3) To study the frequency of various neoplastic versus non-neoplastic lesions of

the lymph node

4) To study the different cytomorphological patterns associated with various

lymphadenopathies.

18
 LITERATURE RE-
VIEW

3.REVIEW OF LITERATURE:

HISTORICAL ASPECTS:

19
 Herophilus first noted lymph node enlargement and he named them as “Glandu-

lae”. Most of the early writers have called them “Glands’, although there are no features

to suggest as glands, because they have no glandular functions. Later Nermine anatomical

adapted the term ‘Node’ for the lymph glands in 1955.

Charaka, the ancient Hindu Physician had stated in his famous “Charaka

Samhitha”,Adhyaya 12, and Sloka Sankhya 79 – “If there is single swelling by the side of

the neck it is called Galaganda. If these are many, called Galamala. They are regarded as

curable, but are incurable if accompanied by coryza, pleurodynia, cough, fever…”

“Scrofula or the King’s Evil” are the historical names of tuberculous

lymphadenopathy, involvement of superficial lymphatics especially those of the neck

has plagued the mankind throughout the recorded history.The term scrofula, meaning

glandular swelling (Latin) and full necked sow(French).(20)

Robert Koch in 1882, discovered tubercle bacillus, the causative organism of

tubercular lymphadenitis (21).

Needle aspiration of lymph nodes is one of the oldest applications of the tech-

nique in the diagnosis of human disease. Kun first used the technique of aspiration cytol-

ogy in 1847. In 1904, two British military surgeons, Greig and Gray, working in Uganda,

published a paper describing the diagnosis of sleeping sickness by recognizing mobile

trypanosomes in lymph node aspirates.

In 1921, Guthrie of Johns Hopkins described the application of needle aspiration

to the diagnosis of tumors. He successfully diagnosed cases of Syphilis, Tuberculosis,

Malignant lymphoma, Leukemia, Metastatic carcinoma by needle aspirations.

20
 In 1930, Martin and Ellis of Memorial Hospital for Cancer (now the Memorial

Sloan-Kettering Cancer Center) introduced the technique of needle aspiration biopsy, in-

cluded tumors that had metastasized to the lymph nodes among the targets of aspiration

biopsy.As a result of the pioneering work of Franzén et al (1960) and the widespread cur-

rent acceptance of the technique, aspiration of lymph nodes has become a standard labo-

ratory procedure(22)

Stewart in 1933 published the first of several reports on aspiration cytology from

the Memorial hospital, New York. Cardozo while analyzing cytodiagnosis in 1526 cases

of various inflammatory and neoplastic lesions of lymphnodes encountered diagnostic ac-

curacy in 80% of cases.Comparative study of lymphnode cytology by puncture and

histology was studied byBloch (1967) and malignancy was correctly diagnosed in 87% of

cases.

The term “lymphoma” was first introduced by Virchow in 1862-63 to denote a

malignant tumor of lymphoreticular tissue. In year 1666 Malpighi published the first

recorded description of Hodgkin’s disease in his paper “De viscerum structuru

exercitatio anatomica”.

In 1832 Thomas Hodgkin published his paper on lymphatic disease “On some

morbid appearances of the absorbent glands and spleen” in Medico-Chirurgical

Transactions, the journal of the medical and chirurgical society in London.

Greenfield was the first to observe the presence of large multinucleated cells in the

lymph nodes of patients with Hodgkin’s disease. However the investigators whose

names have become associated with these pathognomonic multinucleate giant cells

are Dorothy Reed and Sternberg.

21
 An important contribution to the recognition,classification and diagnosis of

Hodgkin’s disease was provided by Jackson and Parker in the early 1940s. 20 years later

come the major contribution of Lukes and Butler tothe understanding and classification

of Hodgkin’s disease; the Rye’s modification of the dukes and Butler classification is still

used today (23).

Dennis Burkitt, an Irish surgeon working in Uganda, gave the first definitive

description of Burkitt’s tumor. The first descriptions of follicular lymphoma are

usually attributed to Brill, Baehr and Rosenthal and to Douglas Symmers; the

condition came to be known as Brill-Symmer’s disease. A lymphoepitheloid

lymphoma, now commonly called Lennert’s Lymphoma, was first described in 1952

as a special variant – epitheloid cell lymphogranulomatosis of Hodgkin’s disease (23).

Many classifications for NHLs have been proposed over the years.The Rappaport

classification was the standard classification in the 1960s and 1970s.Many competing

classifications have appeared since 1970s, Such as the Kiel, Lukes and Collins, WHO,

Dorfman and British National Lymphoma Investigation classification.

The Chaos in terminology echo to the development of the working formulation,

which was intended as a means for translation of terminology among the different lym-

phoma classifications but which eventually became a widely used lymphoma classifica-

tion in the 1980s and 1990s. During the same period, the updated Kiel classification was

also used, especially in Europe.

The international Lymphoma study group proposed the Revised European –

American Lymphoma (REAL) classification in 1994. The REAL classification has been

22
widely used throughout the world since its publication, and many studies have demon-

strated its clinical relevance.

The new world health organization (WHO) classification, published in 2000,

incorporates the REAL classification with minor modifications based on new data

occurred since 1994(24, 25).

Over the last two decades studies from various institutes like Ramzy et al, 1985;

Carter et al, 1988; Frable and Kardos, 1988; Cardillo, 1989; Cafferty et al, 1990; Sneige

et al, 1990; Gupta et al, 1991; Suhrland and Wieczorek, 1991; Moriarty et al, 1993; Steel

et al, 1994; Prasad et al, 1996; Dunphy and Ramos, 1997; Jeffers et al, 1998; Wakely et

al, 1998; Young et al, 1998; Das, 1999; Meda et al, 2000; Nasuti et al, 2000; Nicol et al,

2000 document the value of FNA in the diagnosis and subclassification of non-Hodgkin

lymphomas in conjunction with ancillary studies, to document residual or recurrent lym-

phoma or to assess the stage of the disease.(22)

ETIOPATHOGENESIS:

The body has approximately 600 lymph nodes, but only those in the submandibu-

lar, axillary or inguinal regions may normally be palpable in healthy people.

23
 Lymphadenopathy refers to nodes that are abnormal in size, consistency or num-

ber.There are various classifications of lymphadenopathy, but a simple and clinically use-

ful system is to classify lymphadenopathy as “generalized” if lymph nodes are enlarged

in two or more non contiguous areas or “localized” if only one area is involved. In pri-

mary care patients with unexplained lymphadenopathy, approximately three fourth of pa-

tients will present with localized lymphadenopathy and one fourth with generalized lym-

phadenopathy (30).

The three commonest causes of lymph node enlargement in the neck in India are

tuberculous lymphadenitis, malignant lymphoma and metastasis in the neck nodes. It

should not be taken for granted that nodes are due to particular cause alone, history sug-

gestive of lymphoma and secondary neck nodes should be elicited, even if all signs and

symptoms point in direction of tuberculosis.

Fine Needle Aspiration Biopsy

Fine needle aspiration biopsy is being increasingly used for the evaluation

of lymphadenopathy.8 It can be used to determine whether a suspected enlarged

lymph node is indeed lymphoid tissue, to obtain material for special studies

(including culture, immunophenotyping studies, and molecular studies), to

diagnose metastatic tumors, to diagnose reactive hyperplasia or infectious

lymphadenitis, to diagnose and stage Hodgkin’s disease and non-Hodgkin’s

lymphomas, to identify residual recurrent lymphoma, and to diagnose

transformation of lymphoma..

24
 Table.No.1

PRINCIPAL LESIONS OF LYMPH NODES(22)

Metastatic
Benign lymphadenopathies Lymphomas
tumors

*Acute or subacute lymphadenitis *Hodgkin lymphoma *Metastases from

* Hyperplastic lymphnodes *Non-Hodgkin lym- various primary

o Chronic lymphadenitis phomas sites

(Reactive Hyperplasia)

o Paracortical hyperplasia

o Granulomatous lym-

phadenitis

o Sinusoidal expansion

Acute(suppurative) Lymphadenitis(22):

Clinically, acute lymphadenitis usually appears as a red, hot, tender area. Superfi-

cial lymph nodes that drain a dental abscess, an inflamed appendix, a tubo-ovarian ab-

25
scess, or an infected wound are typically affected. The most common causes of acute

lymphadenitis are bacteria or their toxic products.

In the Early aspirates contain an admixture of neutrophils and lymphocytes.

Later, the aspirates contain a purulent material composed of neutrophils and cellular de-

bris . As the acute inflammatory process subsides, neutrophils are admixed with plasma

cells and large macrophages containing fragments of phagocytized material, known as

tingible body macrophages.

Chronic Lymphadenitis (Reactive Hyperplasia) :

Chronic lymphadenitis, more often referred to as reactive hyperplasia of lymph

nodes, is the most common cause of lymphadenopathy and the most common diagnosis

made on lymph node aspirates.

Lymph node enlargement in chronic conditions may be caused by an enlargement

of the lymphoid follicles, the pulp of the lymph nodes, the peripheral sinuses, or a combi -

nation of all three. In reactive hyperplasia, one component of the lymph node usually pre-

dominates and, therefore, the disorder is usually classified by pattern . However, the ar-

chitectural pattern cannot be assessed by FNA and, therefore, it is difficult to determine

specific causes of benign hyperplasia in a cell sample.

Follicular and Paracortical Hyperplasia:

26
 Follicular hyperplasia can occur at any age, but it is more common in children.

The cervical, axillary, and inguinal lymph nodes are frequently involved . Reactive nodes

are usually less than 3 cm in diameter, although they may be larger in children.(22)

Cytology :

In general, the aspirates are quite cellular and are composed of dispersed, isolated,

single cells with marked variability in size and configuration. Small lymphocytes are usu-

ally the dominant cell type . Follicle center cells, which are a mixture of small and large

lymphocytes with cleaved nuclei, large cells with vesicular nuclei, and immunoblasts, are

present in varying proportions. Plasma cells and tingible body macrophages are usually

present.Dense, basophilic fragments of apoptotic nuclei and occasional mitotic figures

may be seen.

Table No.2

Conditions assosciated with reactive lymphoid hyperplasia:predominant

histologic pattern by etiology

27
Type of hyperplasia

Follicular and : Lesion assosciated

paracortical hyperplasia Rheumatoid arthritis

Castleman disease

Syphilis

Bacterial infection (early)

Dermatopathic lymphadenopathy

Kimura disease

Viral infection

Post vaccinal lymphadenopathy

Drug-induced hypersensitivity

Kikuchi lymphadenitis

Systemic lupus erythematosus

Lymph nodes draining carcinoma (rare)

Whipple disease (some cases)

Granulomatous lymphadenitis : Mycobacterial infections

Fungal infections

Toxoplasmosis

Whipple disease (some cases)

Berylliosis
28
 Bacterial infections, including

cat-scratch disease, lymphogranuloma

venereum, tularemia, and yersinial lym-

phadenitis

Lymphoma (some cases)

Lymph nodes draining carcinoma (few

cases)

Sinusoidal expansion Sinus histiocytosis with massive

lymphdenpathy

Lymphangiogram effect

Whipple disease (some cases)

FOLLICULAR AND PARACORTICAL HYPERPLASIA :

Rheumatoid arthritis is an autoimmune disease that is associated with lym-

phadenopathy. In rheumatoid arthritis, aspirates show florid, reactive hyperplasia and nu-

merous plasma cells with eosinophilic, cytoplasmic inclusions, known as Russell bodies.

Systemic lupus erythematosus (SLE) is also associated with lymphadenopathy.

Aspirates taken from patients with SLE show numerous small lymphocytes, transformed
29
lymphocytes, and tingible body macrophages in a background of necrosis. In addition,

LE cells in various stages of formation may be observed. The LE cells contain amor-

phous basophilic bodies, composed of aggregates of DNA, polysac-charides, and im-

munoglobulins, and ranging from 5 to 12 microns in diameter .(31)

Castleman disease :

Castleman disease is also known as giant lymph node or angiofollicular hyperpla-

sia. There are two morphologic subtypes: the more common hyaline-vascular and the less

common plasma cell variant. The hyaline-vascular type can affect patients of any age, but

most are asymptomatic young adults. The mediastinum is most commonly involved, fol-

lowed by the cervical lymph nodes. Aspirates taken from patients with the hyaline-vascu-

lar form of Castleman disease show primarily small, mature lymphocytes and occasion-

ally larger, atypical cells consistent with follicular dendritic cells. Capillaries are often in-

termixed with the lymphocytes and reticular cells .

The plasma cell variant of Castleman disease may be localized or multicentric.

The localized form tends to affect the mediastinum and the intraabdominal lymph nodes.

The multicentric form is more common in patients who are middle-aged or older

and who have peripheral lymphadenopathy; they tend to have more severe systemic

symptoms than patients with the localized form. Aspirates show a polymorphous lym-

phoid population with occasional immunoblasts and higher than normal numbers of

plasma cells, some of which contain Russell bodies.(32,33)

30
Kikuchi lymphadenitis :

It is a self-limited disease of unknown cause . Most patients are young women

who have painful unilateral cervical lymphadenopathy. Infrequently, the lymphadenopa-

thy is generalized. Histologically, there are localized areas of necrosis in cortical or para-

cortical areas with prominent karyorrhexis but no polymorphonuclear infiltrate. Atypical

mononuclear cells and immunoblasts are on the periphery. Some patients have hemato-

logic abnormalities.

Smears taken from such patients show a heterogeneous population of small and

large transformed lymphocytes and tingible body macrophages. Scattered in the back-

ground are necrotic debris and karyorrhectic (apoptotic) cells.(34,35)

Kimura disease:

It is a chronic inflammatory disorder of unknown origin that may be an aberrant

immune reaction to an unknown stimulus. This disease is more prevalent in men than in

women among Asian populations. Patients often have painless lymphadenopathy of the

head and neck region with cutaneous or subcutaneous nodular lymphoid infiltrates. Aspi-

31
rates are consistent with florid reactive lymphoid hyperplasia with Warthin-Finkeldey-

type multinucleated giant cells .(36)

Dermatopathic Lymphadenopathy :

In the presence of chronic skin disorders, lymph node enlargement is common.

Histologically, there is follicular and paracortical hyperplasia and accumulation of phago-

cytized granules of melanin. Pigment from tattoos may mimic melanin accumulation The

principal cells involved are the interdigitating reticulum cells .(37)

VIRAL INFECTIONS:

Virus infections such as with the Epstein-Barr virus (EBV) and the human im-

munodeficiency virus (HIV), are usually associated with lymphadenopathy. Occasion-

ally, cytomegalovirus, the measles- and varicella-zoster viruses, and herpesvirus can also

affect the lymph nodes.

Infectious mononucleosis:

Infectious mononucleosis is associated with EBV. It is a self-limited infectious

disease that affects young patients and can result in fever, pharyngitis, rash, and cervical

adenopathy. The axillary and inguinal lymph nodes can also be affected. Atypical lym-

32
phocytes are present in the peripheral blood. Most of these cases are diagnosed clinically

and confirmed with a heterophil antibody (Monospot) test.,.

Aspirates of infectious mononucleosis can be quite variable, but they usually

show a polymorphous population of small and large transformed lymphocytes, im-

munoblasts with binucleation, tingible body macrophages, plasma cells, eosinophils, and

mast cells. The immunoblastic proliferation may be so florid that it may be mistaken for

lymphoma, but the spectrum of immunoblastic maturation in cells with plasmacytoid fea-

tures is not seen in lymphomas. Binucleated immunoblasts, resembling the Reed-Stern-

berg cells observed in Hodgkin lymphoma, have been described in infectious mononucle-

osis and postvaccinal lymphadenitis; however, these cells usually do not meet the strict

criteria for Reed-Sternberg cells .(38,39)

Infection with Human Immunodeficiency Virus:

Individuals infected with HIV commonly have lymphadenopathy. HIV lym-

phadenitis may be associated with a spectrum of changes, ranging from florid lymphoid

hyperplasia to marked lymphoid depletion. As in other types of viral lymphadenitis, aspi-

rates from florid lymphoid hyperplasia typically show a heterogeneous population of

small, intermediate, and large lymphocytes; plasma cells; and tingible body

macrophages(40) . Multinucleated giant cells or polykaryocytes with multiple small nu-

clei that resemble osteoclasts (Warthin-Finkeldey cells, also seen in measles) and epithe-

lioid histiocytes have also been observed.

33
 In the depletion phase, aspirates often have sparse follicular center cells, im-

munoblasts, and tingible body macrophages but high numbers of plasma cells.

Macrophages may also be seen. In such cases, infections caused by mycobacteria and

fungi should be ruled out.

GRANULOMATOUS LYMPHADENITIS(22)

In histologic sections, the presence of granulomas, composed of epithelioid and

giant cells with or without central necrosis, is the hallmark of granulomatous lym-

phadenitis. Granulomas are approximately spherical structures of various sizes, com-

posed of elongated epithelioid cells with pale, eosinophilic cytoplasm and giant cells,

usually of Langhans type, with a garland of peripheral, small nuclei. Granulomatous lym-

phadenitis can be seen, not only in infectious processes such as tuberculosis, atypical my-

cobacteriosis, brucellosis, or infections caused by fungi or Pneumocystis carinii, but also

in sarcoidosis, foreign-body reactions, non-Hodgkin lymphoma, Hodgkin lymphoma,

and, rarely, lymph node-draining carcinoma.

Cytology :

In aspirates, granulomatous lymphadenitis is characterized by epithelioid histio-

cytes in a background of lymphocytes and plasma cells. Epithelioid histiocytes are elon-

gated polygonal cells with pale cytoplasm, indistinct cell borders, and elliptical, some-

34
times comma- or boomerang-shaped pale nuclei with finely granular chromatin, and fre-

quently slight lateral indentations . These cells may form loose aggregates or cohesive

clusters that are reminiscent of granulomas when seen in tissue sections. Multinucleated

giant cells of foreign-body-type with dispersed nuclei or Langhans type giant cells are of-

ten present. Granulomatous lymphadenitis may or may not show associated necrosis,

which appears as acellular granular material on smears.

Conditions Associated with Granulomatous Lymphadenitis:

Mycobacterial infections, including those caused by Mycobacterium tuberculosis

and atypical mycobacteria, are associated with granulomatous lymphadenitis. World-

wide, tuberculosis is the leading infectious cause of morbidity and mortality. The num-

ber of new cases of tuberculosis has increased over the last decade, primarily in areas

where HIV infection is prevalent. Individuals at high risk for tuberculosis include infants

and young children, elderly adults, and immunocompromised patients such as those in-

fected with HIV.

Very rarely, smears from the lymph nodes of patients with tuberculous lym-

phadenitis may show only necrotic material and neutrophils . The demonstration of AFB

is done by the Ziehl-Neelsen stain which is available in many laboratories .

Negative images of bacilli are seen in Romanowsky stained smears as the bacilli

have a lipid coat which resists the Romanowsky stain.(41) The bacilli are seen as opti-

cally clear rods or striations. These may be extra or intracellular and are not visible with

Papanicolaou stain.

35
Cytomorphological features of tuberculous lymphadenitis shows three major

patterns :

1) Epithelioid granulomas with caseous necrosis

2) Epithelioid granulomas without caseous necrosis

3) Necrosis alone without epthelioid granulomas.(57,58)

Table No.3

Cytodiagnositc criteria for tuberculous lymphadenitis 37

Cytological feature ZN stain Diagnostic label

A.Epithelioid cells + multi nucle- a) AFB positive a)Tuberculous lymphadenitis

ated giant cells + necrosis b) AFB negative b)Granulomatous lymphadenitis

B.Necrotic material without ep- a) AFB positive. a)Tuberculous lymphadenitis

ithelioid cells b) AFB negative b) Repeat FNAC advised for

cytodiagnosis, ZN staining and /

or for culture of AFB.

Mycobacterium avium-intracellulare infection shows aggregates of large histio-

cytes filled with negatively stained linear cytoplasmic inclusions, particularly in patients

36
who are immunosuppressed(42) . In lepromatous leprosy, the characteristic cell is a syn-

cytial histiocyte (Virchow or globus cell), which is frequently multinucleated and has a

vacuolated cytoplasm that contains numerous lepra bacilli (43).

Fungal infections like Histoplasma capsulatum, Coccidioides immitis, and Cryp-

tococcus neoformans, may involve lymph nodes.

Histoplasmosis involving the mediastinal lymph nodes may be associated with

inflammation and proliferation of fibrous tissue resulting in sclerosing mediastinitis. As-

pirates of lymph nodes from patients with coccidioidomycosis often show extensive

necrosis; careful examination may reveal thick-walled cysts containing endospores .

Cryptococcus may affect both immunocompetent and immunosuppressed pa-

tients. Aspirates of lymph nodes from infected patients show epithelioid histiocytes,

yeast-filled giant cells, and lymphocytes . The narrow-based budding yeasts usually have

a thick mucopolysaccharide capsule that stains positive with mucicarmine stain..(44)

Lymphadenitis in toxoplasmosis usually affects the posterior cervical lymph

nodes, although other lymph nodes may be involved. Infection most commonly results

from exposure to contaminated cat feces or ingestion of undercooked meat. Aspirates

show a polymorphous lymphoid population admixed with loosely aggregated epithelioid

histiocytes and tingible body macrophages. The crescent-shaped organisms are rarely ob-

served in aspirates (45). Pneumocystis carinii can also cause granulomatous lymphadeni-

tis in AIDS.

37
 Sarcoidosis is a granulomatous disease usually diagnosed in the third and fourth

decades of life. It can affect any organ, including cervical and hilar lymph nodes . Similar

granulomas may occur in lymph nodes draining metastatic cancer.

Cat-scratch disease is caused by a pleomorphic Gramnegative bacillus, Bartonella

henselae. The disease should be suspected if the aspirate from an axillary or neck lymph

node reveals granulomatous inflammation accompanied by neutrophils, necrosis, and oc-

casional multinucleated giant cells (suppurative granulomatous inflammation) in a young

patient who has had close contact with a cat.(22)

Lymphogranuloma venereum, caused by Chlamydia trachomatis, should be con-

sidered when the aspirate of an inguinal lymph node exhibits suppurative granulomatous

inflammation .

SINUSOIDAL EXPANSION OF LYMPH NODES :

Sinus histiocytosis is a common type of lymph node hyperplasia that affects

mainly the axillary and inguinal areas. This type of hyperplasia may also be observed in

lymph nodes that drain cancers. In histologic sections of lymph nodes, the markedly di-

lated sinuses are filled with macrophages that have abundant, foamy cytoplasm. In aspi-

rates, a few macrophages with phagocytic material and occasional neutrophils are seen.

(46,47))

38
Conditions Associated with Sinusoidal Expansion:

Sinus histiocytosis with massive lymphadenopathy, also known as Rosai-Dorf-

man disease, is a benign, generally self-limited condition. It usually affects children and

adolescents , is characterized by bilateral cervical lymphadenopathy. Aspirates usually

contain numerous histiocytes, some containing whole lymphocytes within their cyto-

plasm (a phenomenon known as emperipolesis) , plasma cells, and few neutrophils .

Langerhans cell histiocytosis is a rare disorder, usually occurring in children and

young adults. It most commonly presents as a single lytic bone lesion (eosinophilic gran-

uloma), composed of mature, lipid-laden histiocytes, Langerhans' cells with pale

eosinophilic cytoplasm, and a finely textured characteristically indented or grooved nu-

clei (48)and varying numbers of eosinophils, plasma cells, and neutrophils with a few

multinucleated giant cells. (49)

Leaking or rupture of silicone implants used in breast augmentations or joint pros-

theses may result in silicone reaching the regional lymph nodes, which are generally en-

larged. Aspirates from the lymph nodes of such patients may show silicone lym-

phadenopathy, which is characterized by the presence of numerous vacuolated

macrophages and multinucleated giant cells. The vacuoles contain silicon, a refractile ho-

mogeneous material that is not birefringent. Asteroid bodies, which are crystalloid struc-

tures resembling stars, may be seen in the cytoplasm of the macrophages(50) .

39
POSTTRANSPLANTATION LYMPHOPROLIFERATIVE DISORDERS:

Posttransplantation lymphoproliferative disorders occur in approximately 2% of

organ-transplant recipients who were given immunosuppressive therapy. Epstein-Barr

virus (EBV) is commonly associated with these disorders..

Aspirates from patients who have posttransplantation lymphoproliferative disor-

der may have either a polymorphous or monomorphous cell population. In the former, as-

pirates show a heterogeneous population of mature and immature lymphocytes, with scat-

tered plasma cells and histiocytes in the background, whereas aspirates from the latter

contain predominantly large cells resembling lymphoma.(51,52).

Knowles et al (1995) classified posttransplantation lymphoproliferative disorders

into three categories according to distinct morphologic and molecular findings:

 Plasmacytic hyperplasia

 Polymorphic B-cell hyperplasia and polymorphic B-cell lymphoma

 Immunoblastic lymphoma or multiple myeloma(22)

MALIGNANT LYMPHOMAS :

In the past, the principal role of FNA of lymph nodes was to determine the pres-

ence of metastatic carcinoma or sarcoma. The idea that one could diagnose and subclas-

40
sify lymphoid neoplasms by FNA was met with skepticism by pathologists and clinicians

(Hajdu and Melamed, 1984). Although the presence of an atypical lymphoid population

was recognized on FNA specimens in most instances of lymphoma, a definitive diagnosis

of lymphoma was usually rendered only on excised lymph nodes. The use of FNA to ren -

der a primary diagnosis of lymphoma remains controversial .

Many of the limitations of FNA in the diagnosis of lymphoproliferative disorders

have been addressed by Katz and Caraway (1995). One of the major drawbacks to the use

of FNA is the lack of lymph node architecture that is important in the subclassification of

some lymphomas. However, because many lymphomas have distinctive cytomorpho-

logic, immunophenotypic, and proliferative profiles, the absence of architecture can be

overcome in these instances by immunophenotyping. A subsequent lymph node excision

is performed if the material is inadequate, if the results are ambiguous, or if the clinical

and radiographic findings are not in accord with the cytologic interpretation.

CLASSIFICATION OF LYMPHOMAS :

Revised European-American Classification of Lymphoid Neoplasms (REAL) was

proposed by the International Lymphoma Study Group (55). The REAL system catego-

rizes entities on the basis of the neoplasm's cell of origin. Because this system places

greater emphasis than previous systems on cytomorphologic features, immunophenotype,

and results of molecular studies, it can be applied easily, using a multiparameter approach

to FNA specimens. The new (1998) World Health Organization (WHO) classification for

41
lymphomas is similar to the REAL system; minor modifications have been made as addi-

tional data have become available (56).

Table.No.4

WORLD HEALTH ORGANIZATION CLASSIFICATION OF THE NEOPLAS-

TIC DISEASES OF THE LYMPHOID TISSUES(22)

B-Cell Neoplasms

Precursor B-cell lymphoblastic leukemia/lymphoma

Mature B-cell neoplasms

 Chronic lymphocytic leukemia/small lymphocytic lymphoma

 Prolymphocytic leukemia

 Lymphoplasmacytic lymphoma (lymphoplasmacytoid lymphoma)

 Mantle cell lymphoma

 Follicular lymphoma (follicle center lymphoma)

 Marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT)

 Nodal marginal zone lymphoma with or without monocytoid B-cells

 Splenic marginal zone B-cell lymphoma

 Hairy cell leukemia

 Diffuse large B-cell lymphoma

o Subtypes: mediastinal (thymic),

o Intravascular,

42
 o Primary effusion lymphoma

 Burkitt lymphoma

 Plasmacytoma

 Plasma cell myeloma

T-Cell and NK-cell Neoplasms

Precursor T-cell lymphoblastic leukemia/lymphoma

Mature T-cell and NK-cell neoplasms

 T-cell prolymphocytic leukemia

 T-cell large granular lymphocytic leukemia

 NK-cell leukemia

 Extranodal NK/T-cell lymphoma, nasal-type (angiocentric lymphoma)

 Mycosis fungoides

 Sézary syndrome

 Angioimmunoblastic T-cell lymphoma

 Peripheral T-cell lymphoma (unspecified)

 Adult T-cell leukemia/lymphoma (HTLV1+)

 Systemic anaplastic large cell lymphoma (T- and null-cell types)

 Primary cutaneous anaplastic large cell lymphoma

 Subcutaneous panniculitis-like T-cell lymphoma

 Enteropathy-type intestinal T-cell lymphoma

 Hepatosplenic γ/Δ T-cell lymphoma

43
 Nodular lymphocyte predominance Hodgkin's lymphoma

Classic Hodgkin lymphoma

 Hodgkin lymphoma, nodular sclerosis type (grades I and II) H

 Classic Hodgkin lymphoma, lymphocyte-rich ph

 Hodgkin lymphoma, mixed cellularity

 Hodgkin lymphoma, lymphocytic depletion (includes “Hodgkin-like

anaplastic large cell lymphoma”)

Principles of Cytologic Diagnosis of Malignant Lymphomas:

The population of cells in non-Hodgkin's lymphomas is usually monotonous, that

is, the cells are of approximately equal sizes. In assessing smears, the lymphoid cells are

classified as “small” if they are equal in size or slightly larger than normal resting

lymphocytes; “intermediate” if they are one and one-half times larger than the size of a

normal lymphocyte but not larger than the nucleus of a macrophage; or “large” if they

are two or more times the size of a normal lymphocyte.

The nuclei are round, cleaved,or lobulated, or show irregularities of the membrane

with small protrusions. The coarse or fine patterns of chromatin distribution and the

presence or absence of nucleoli must be noted.

Lymphoglandular bodies (Søderstrøm bodies) are helpful in recognizing the

lymphocytic origin of a neoplasm if the cell population is difficult to classify, as is

sometimes the case in large-cell lymphomas.

44
B-CELL LYMPHOMA:
Marginal Zone and MALT Lymphoma :

Marginal zone lymphoma is a rare low-grade, B-cell neoplasm that can have

several clinical manifestations, including the involvement of extranodal sites, lymph

nodes, the spleen, and the gastrointestinal tract. Each of these is considered a distinct en-

tity in the updated WHO classification system(56) .

Extranodal marginal zone lymphoma is also known as mucosa-associated lym-

phoid tissue lymphoma (MALT), and most patients have localized disease. Nodal mar-

ginal zone lymphoma is also known as monocytoid B-cell lymphoma . (59)

Cytology :

Lymph node aspirates from patients with marginal zone lymphoma can be

quite variable but usually have a heterogeneous population of monocytoid cells, small

cleaved cells, large noncleaved cells, and plasma cells .

The monocytoid cells are of intermediate size with moderate to abundant amounts

of pale cytoplasm; they may have a plasmacytoid appearance.

The nuclei can be somewhat variable with oval or reniform nuclei, vesicular or

coarse chromatin, and inconspicuous nucleoli. Tingible body macrophages have also

been observed in some cases .

45
 .

Follicular Lymphomas:

Follicular lymphomas (FLs) are B-cell neoplasms composed of a mixture of

cleaved follicle center cells (centrocytes) and large noncleaved follicle center cells (cen-

troblasts).

In the REAL classification, the FLs are subdivided into three cytologic grades: I,

predominantly small cells; II, mixed small and large cells; and III, predominantly large

cells.(60 & 55 SAME)

Cytology :

Smears of follicular lymphomas are composed of a mixture of small, irregular

lymphocytes and larger cells. The lymphocytes, only slightly larger than normal lympho-

cytes, have nuclei showing irregular contours and inconspicuous nucleoli.

The larger cells are centroblasts characterized by sharply demarcated basophilic

cytoplasm and round, non-cleaved nuclei with finely granular chromatin and 2 to 3 pe-

ripheral nucleoli .

Centroblasts must be differentiated from centrocytes with cleaved nuclei and fol-

licular dendritic cells, characterized by wispy cytoplasm, indented reniform nuclei, and

small nucleoli. An increase in the proportion of centroblasts indicates a higher grade of

follicular lymphoma.

46
 Table.No.5

DIFFERENTIAL DIAGNOSIS OF SMALL CELL LYMPHOMAS

Lymphoma CD5 CD23 CD10 CD20 Cytogenetics

CLL/SLL + + - + Trisomy 2

Lymphoplsmacytic No specific ab-

- + - + normality

Mantle cell + - + t(11;14)

Marginal zone - +/- - + Trisomy 3;

t(11;18)

Follicular - +/- + t(14,18)

Large B-Cell Lymphoma:

Large B-cell lymphomas comprise 30% to 40% of adult non-Hodgkin lym-

phomas. They usually occur in the sixth decade of life, but the age range is broad and in -

cludes children and young adults. Patients typically present with a rapidly enlarging neck

or retroperitoneal mass.

47
Cytology:

Large B-cell lymphoma is a heterogeneous group of neoplasms consisting primar-

ily of large cleaved and noncleaved cells. In large noncleaved cell lymphoma, the cells

have round to ovoid nuclei that contain one or more distinct nucleoli . Large cleaved cell

lymphoma, on the other hand, features irregular nuclear profiles, often with nuclear pro-

trusions (“nipples”). Nuclei may be vesicular with inconspicuous nucleoli. Lymphoglan-

dular bodies are usually numerous.(60)

Ancillary Studies :

Immunophenotyping shows positive staining for B-cell-associated antigens

(CD19 and CD20). Expression of CD45 and CD10 is variable. DNA ploidy analysis usu-

ally demonstrates a diploid population with high proliferative activity . Approximately

30% of cases show bcl-2 gene rearrangement .

Burkitt Lymphoma :

Burkitt lymphoma occurs predominantly in children. Cases reported in adults are

often associated with immunodeficiency. In endemic areas in Africa, the jaws and facial

bones are the most commonly involved sites, whereas in nonendemic areas, the disease

involves distal ileum, cecum, ovaries, retroperitoneum, kidneys, or breasts. Epstein-Barr

virus (EBV) is commonly present in the endemic form of this lymphoma but rarely in the

48
nonendemic cases. Burkitt lymphoma may sometimes mimic an acute leukemia. This tu-

mor is highly aggressive but potentially curable.

In histologic sections, Burkitt lymphoma has the typical “starry-sky” pattern

caused by the large number of macrophages intermingled with lymphoma cells.

Cytology

Aspirates are composed of malignant lymphocytic cells. The nuclei are spherical,

with a fine to coarse chromatin pattern, and they contain two to five distinct nucleoli . On

air-dried Diff-Quik smears, the cells have deeply basophilic cytoplasm and prominent cy-

toplasmic vacuoles .

A “starry-sky” pattern may be present as the result of an admixture of tingible

body macrophages. Necrotic debris and mitotic figures are frequently seen .(61)

Ancillary Studies

Immunophenotyping shows positivity for B-cell-associated antigens (CD19 and

CD20) and CD10, and negativity for CD5 and CD23.

Plasmacytoma/Plasma Cell Myeloma :

Plasmacytoma occurs in adults, usually as a disseminated bone marrow disease

(plasma cell myeloma), but sometimes as a solitary bone or extramedullary tumor.(56)

Involvement of the lymph nodes is rare.

49
Cytology

The tumor cells resemble mature or immature plasma cells with abundant cyto-

plasm with an eccentrically located nucleus . The nuclei are usually round with coarsely

clumped chromatin (cartwheel arrangement of chromatin), but they may also be cleaved

or resemble immunoblasts .(62)

T-CELL LYMPHOMAS :

Lymphomas of T-cell lineage comprise only a small proportion of nodal lym-

phomas. They are more difficult to identify on FNA than B-cell lymphomas by routine

analysis because of difficulties in detecting the clonal population of abnormal T-cells by

immunophenotyping.

Peripheral T-Cell Lymphoma

Smears exhibit a spectrum of atypical cells with nuclei varying in shape and rang-

ing from small to large . The small nuclei are often convoluted with condensed chromatin

, whereas the larger nuclei are round or irregular, with either vesicular or condensed chro-

matin. The background contains a variable admixture of neutrophils, eosinophils, plasma

cells, and epithelioid and nonepithelioid histiocytes. (63)

50
Mycosis Fungoides and Sézary Syndrome :(22)

Mycosis fungoides and Sézary syndrome are two different manifestations of the

same or similar disorder, having in common the presence of abnormal T-helper cells with

characteristic cerebriform configuration of nuclei.

Cytology

In fixed smears stained with Papanicolaou, the abnormal lymphocytes have irreg-

ularly shaped nuclei showing peripheral indentations and large nucleoli. The peculiar

small lymphocytes with longitudinally grooved, cerebriform configuration of chromatin

are much better seen in air-dried smears, stained with one of the hematologic stains .

Lymphoblastic Lymphoma :

Lymphoblastic lymphoma occurs predominantly in adolescents and young adult

men but it can occur in all age groups. The first manifestation of disease is usually a me-

diastinal mass. The disease progresses rapidly to involve the peripheral blood, bone mar-

row, central nervous system, and gonads.

Cytology

Aspirates taken from patients with lymphoblastic lymphoma show a monomor-

phous population of lymphoid cells of intermediate size with nuclei that may be lobu-

lated, convoluted, or, less often, round or oval. The chromatin is finely granular or

opaque, and the nucleoli are inconspicuous . (64)

51
Anaplastic Large-Cell Lymphoma :

Most commonly, aspirates contain large cells with pleomorphic, hyperchromatic

nuclei and abundant cytoplasm, often mimicking epithelial cancer cells. Small cell and

lymphohistiocytic variants have also been described. In the pleomorphic type, the nuclei

can be multilobulated, horseshoe-shaped, bagel-shaped, or multiple and contain one or

more prominent nucleoli . The multinucleated forms may resemble Reed-Sternberg cells.

(22)

HODGKIN LYMPHOMA :

Hodgkin lymphoma accounts for approximately 20% of newly diagnosed lym-

phomas. The updated WHO classification lists two distinct types of Hodgkin's lymphoma

—classic and nodular lymphocyte-predominant.(56)

FNA has an important but limited role in the initial diagnosis of Hodgkin lym-

phoma (63). If the cytomorphologic features and immunophenotypic findings are sugges-

tive of a diagnosis of Hodgkin lymphoma, then a tissue biopsy is recommended for con-

firmation and subclassification. However, FNA is very useful in diagnosing recurrent dis-

ease. (66,67) The diagnosis of Hodgkin’s lymphoma can be made with more confidence

than a diagnosis of NHL on cytology according to Iyengar et al.30

Cytology

The cytologic diagnosis of Hodgkin lymphoma mainly is made on the basis of the

presence of classic Reed-Sternberg cells in a background of lymphocytes, plasma cells,

eosinophils, and histiocytes. Classic Reed-Sternberg cells are large binucleated or multin-

ucleated cells with pale abundant cytoplasm that contain nuclei with reticulated chro-

52
matin and prominent macronucleoli . The nucleus often appears surrounded by a clear,

empty cytoplasmic halo.

Instead of classic Reed-Sternberg cells some aspirates contain Hodgkin cells,

which are large mononuclear cells with reticulated chromatin and one or two prominent

nucleoli Aspirates from lymph nodes of patients with nodular, sclerosing Hodgkin lym-

phoma, the most common subtype, usually contain classic Reed-Sternberg cells, lacunar

cells, eosinophils, lymphocytes, and histiocytes.

Lacunar cells are large cells with abundant clear or pale cytoplasm that contain in-

dented or overlapping segmented nuclei; these cells are not specific for Hodgkin lym-

phoma. The mixed cellularity subtype of Hodgkin lymphoma has cells very similar to

those of the nodular sclerosis subtype, except for the absence of lacunar cells.(22)

In the lymphocytic depletion subtype of Hodgkin lymphoma, aspirates are often

sparsely cellular consisting of Reed-Sternberg and Hodgkin cells in a background of lym-

phocytes or fibroblasts.

The nodular lymphocyte-predominant subtype of Hodgkin lymphoma may be

suggested by cytologic preparations that have epithelioid histiocytes and the polyploid

variant of Reed-Sternberg or the so called L and H cells in a background of mature lym-

phocytes.

Ancillary Studies:

Most Reed-Sternberg cells and their variants are positive for CD15 and CD30

53
except for those in nodular lymphocyte-predominant Hodgkin lymphoma, and are nega-

tive for CD45 and EMA . They are usually negative for B-cell and T-cell markers. The

lymphocytes in Hodgkin lymphoma are nonneoplastic and have a T-cell origin.(22)

Cells that mimick Reed-sternberg cells :

 Immunoblasts

 Megakaryocytes

 Plasmablasts

 Anaplastic Lymphoma Cells

 Large Cell Lymphoma Cells

 Melanoma

 Large cell carcinoma

METASTATIC TUMORS IN LYMPH NODES

Metastatic cancer is a far more common cause of enlarged peripheral lymph nodes

than malignant lymphoma, especially in patients older than 50 years. FNA is a reliable

method of diagnosing metastatic cancer, a task that is much easier than diagnosing lym-

phomas. Aspirates serve to not only establish the diagnosis of a metastatic tumor, but to

also usually permit a definition of the histologic type and sometimes the organ of origin

of the metastasis. (48)

54
 Carcinomas, melanomas, germ cell tumors, and sarcomas can all metastasize to

lymph nodes; carcinomas are the most frequent.

Squamous Cell Carcinoma:

The cytologic appearance of squamous carcinoma depends on the degree of dif-

ferentiation by the tumor. Keratinizing cancers are readily identified when cells with

abundant, sharply demarcated, dense, eosinophilic cytoplasm and pyknotic nuclei are

present in smears.

Nonkeratinizing squamous carcinomas or epidermoid carcinomas are represented

by round, oval, or polygonal cells with sharply demarcated pale cytoplasm and coarsely

granular nuclear chromatin.(22)

Nasopharyngeal carcinoma :

Nasopharyngeal carcinoma is subtyped as keratinizing squamous carcinoma (type

1), nonkeratinizing carcinoma (type 2), and undifferentiated carcinoma, also known as

lymph-oepithelioma or Schimke tumor .

It is a common tumor in Asians, affects men more commonly than women, and

has a bimodal age distribution with peaks in the second and sixth decades.

Cervical lymphadenopathy may be the first manifestation of this disease, although

nasal discharge or epistaxis, and middle ear symptoms may be noted. (22)

Cytomorphology of nasopharyngeal Carcinoma(69)

• clusters of undifferentiated large cells

• large nuclei with pale chromatin

• with or without prominent nucleolus

55
 • moderate amount of cytoplasm

• lymphocytes, often commingled with epithelial cells

• lymphoglandular bodies

Table.No.6

PRIMARY SITES OF NEOPLASMS AND COMMON SITES OF LYMPH NODE

METASTASES (22)

Cervical Lymph Nodes

 Oral Cavity
 Larynx
 Nasopharynx
 Thyroid
 Skin of Face

Mediastinal Lymph Nodes

 Lung
 Axillary Lymph Nodes
 Breast
 Skin (Melanoma)

Abdominal (retroperitoneal) Lymph Nodes

 Gastrointestinal Tract
 Pancreatabiliary Tract
 Kidney
 Uterine corpus
 Gonads

Pelvic Lymph Nodes

 Ceviix
 uterine body
 prostate

Inguinal Lymph Nodes

 Skin (melanoma)
 Cervix
56  Vulva&perineum
Adenocarcinoma:

Aspirates from the lymph nodes of patients with metastatic adenocarcinomas, re-

gardless of the site of origin, usually contain tumor cells that are arranged singly or in co-

hesive groups consisting of ball-like clusters, papillary fragments, loose clusters, or acini

with central lumina. The tumor cells may be round, cuboidal, or columnar. The appear-

ance of the cytoplasm may vary from homogeneous to markedly vacuolated. Left supra-

clavicular lymph node (Virchow node) may be the site of metastases of gastrointestinal

tumors.

Large signet-ring cells with intracytoplasmic mucin are commonly associated

with gastric carcinomas Columnar cancer cells with elongated, palisading nuclei in a

background of necrotic debris suggest a colonic primary tumor

In general, the presence of intracytoplasmic mucin excludes hepatocellular, renal,

adrenal, or thyroid carcinomas. (22)

Renal cell carcinoma :

The cells of this tumor are usually arranged in monolayered sheets of various

sizes, have abundant clear cytoplasm, often with well-defined cytoplasmic borders, and

round nuclei with prominent nucleoli.

In men, glandular cells, arranged in a cribriform pattern with round nuclei and

prominent nucleoli or occurring in small clusters, are suggestive of a prostatic primary

tumor.(48)

57
Thyroid papillary carcinoma :

Thyroid papillary carcinomas often metastasize to the lymph nodes of the neck.

Smears from aspirates may show papillary fragments, monolayered sheets, syncytial

groups, and/or single cells. The nuclei are often oval-shaped and have fine, powdery

chromatin, intranuclear cytoplasmic inclusions, intranuclear grooves, and small nucleoli .

The cytoplasm is usually dense and well defined. Psammoma bodies alone, even

if not accompanied by cells observed in an aspirate from a neck lymph node, are sugges-

tive of metastatic thyroid carcinoma. The presence of colloid is a helpful distinguishing

characteristic. These tumors show positive immunostaining with thyroglobulin and thy-

roid transcription factor-1 (TTF-1) (70)

Metastatic breast carcinoma should be one of the diagnoses considered when

evaluating axillary lymph node aspirates from women, especially those older than 50

years. Aspirates from the nodes of patients with metastatic ductal carcinoma show cancer

cells singly, in cohesive groups, or both.

Small-Cell Carcinoma :

Small-cell carcinoma most often arises in the lung, but it also can be observed in

other primary sites such as the prostate, urinary bladder, larynx, paranasal sinuses, cervix,

and skin (e.g, Merkel cell carcinoma). Aspirates from the lymph nodes of patients with

metastatic small-cell carcinoma usually contain small cancer cells occurring singly and in

loosely cohesive groups.

The tumor cells are two to three times larger than mature lymphocytes and have

only a small rim of cytoplasm. The nuclear chromatin is finely granular but the nuclei can

be hyperchromatic and, at times, pyknotic . Nucleoli are inconspicuous or absent.

58
 The presence of aggregates of tumor cells with nuclear molding and extensive

necrosis is characteristic of small-cell carcinoma(71) . The necrotic material derived from

crushed nuclei may appear in the form of “blue streaks” of DNA in the background of the

smear.

Malignant Melanoma :

Malignant melanoma is aptly named the great masquerader.Lymph nodes are

among the most commonly aspirated metastatic sites.(72)

Cytomorphology of melanoma:

• dispersed single cells and loose clusters

• epithelioid, spindle, or pleomorphic shapes

• nuclei eccentrically placed, commonly binucleated

• nuclear inclusions

• single small to large nucleoli

• cytoplasm: melanin pigment variable, vacuoles variable

• no lymphoglandular bodies

Melanin pigment is seen in less than 50% of aspirate smears. (72)The differential

diagnosis of amelanotic malignant melanoma includes DLBL,Seminoma or Germinoma

Testicular and mediastinal seminomas or germinomas commonly metastasize to deep

lymph nodes of the abdomen and chest, respectively.

59
Sarcomas :

Most sarcomas tend not to metastasize to lymph nodes: less than 3% of patients

with sarcoma develop lymphnode metastases. A subset of sarcomas breaks rank with the

“anti-lymph node” imperative, however.

Sarcomas that more commonly involve lymphnodes include:

• synovial sarcoma

• epithelioid sarcoma

• angiosarcoma

• rhabdomyosarcoma

• Kaposi sarcoma

• follicular dendritic cell sarcoma

Synovial sarcoma :

synovial sarcoma has monomorphic,bland-appearing ovoid nuclei with finely

granular chromatin,smooth nuclear outlines, and scant amounts of tapering cytoplasm.

Kaposis sarcoma :

Smears are variably cellular with abundant red cells, and the cytomorphology is

similar to that of any spindle cell sarcoma.(75) Hyaline globules, a typical histologic fea-

ture, are usually difficult to find in smears. Definitive diagnosis nearly always requires

immunocytochemistry. The spindle cells are positive for CD31 and CD34.

60
Follicular dendritic cell sarcoma:

It is a rare tumor of young to middle-aged adults that arises in lymph nodes and

in extranodal sites. It is a slow-growing tumor with metastatic potential. Smears show

loose, flat aggregates and single cells with oval and spindle shapes.(76)Intermediate-sized

nuclei have smooth borders andsmall, inapparent nucleoli.

Germ Cell Tumors :

Germ cells tumors occur more frequently in men than in women and have a peak

incidence in the second and third decade. Although these tumors usually arise from the

testes and ovaries, they occasionally develop in extragonadal sites, usually located along

the midline, such as the mediastinum, retroperitoneum, sacrococcygeal area, and pineal

body. These tumors may metastasize to regional lymph nodes, most commonly those in

the retroperitoneum.

Aspirates of the lymph nodes from patients with seminoma show a predominantly

dispersed population of large cancer cells admixed with small mature lymphocytes,

plasma cells, and sometimes epithelioid histiocytes and multinucleated giant cells.

The tumor cells have moderate amounts of cytoplasm that occasionally contain

multiple small vacuoles. Nuclei are round to slightly irregular, have fine, granular chro-

matin, and often have one large prominent nucleolus . The cytoplasm is fragile and may

be stripped during smearing, resulting in peculiar streaks of basophilic material, known as

a tigroid background, best seen on Diff-Quik preparations .

The tigroid background is a helpful feature, but it is observed in only 39% of

cases (73). Both embryonal carcinomas (Fig. 31-56) and endodermal sinus tumors (or

61
yolk-sac tumors) show cohesive groups of large cells with pleomorphic nuclei. Aspirated

cells from endodermal sinus tumors have markedly vacuolated cytoplasm that may con-

tain homogeneous hyaline inclusions containing alpha fetoprotein(74)

INDICATIONS AND ADVANTAGES OF FNAC :

Enlarged lymph nodes are a prime target for fine-needle aspiration (FNA). In an

adult, lymphadenopathy is an immediate source of concern, and unless the cause is evi-

dent, the enlarged node is usually aspirated. In children,lymphadenopathy is common and

usually the result of reactive hyperplasia; for this reason, it is often watched and not aspi -

rated. Nevertheless, FNA is readily applicable to children also, particularly if lym-

phadenopathy persists.

Indications for lymph node fine-needle aspiration:

 Confirm a clinical impression of reactive hyperplasia

 Diagnose a suspected infection

 Diagnose a suspected malignancy

 Hodgkin lymphoma

 Non-Hodgkin lymphoma

 Metastatic tumor of unknown primary

 Document a metastasis in a patient with a known malignancy

62
  Confirm transformation of a known lymphoma to one of higher grade.

Advantages of lymph node fine-needle aspiration over biopsy:

 Rapid turn around time

 Low cost

 Easily provides cells for immunophenotyping and

 Provides material for molecular diagnostic tests

 Less morbidity

 Sensitivity and specificity are high.

 It eliminates or modifies lengthy periods of “watchful waiting.”

 It is safe and almost painless.

 It usually is an office procedure, necessitating neither patient preparation nor spe-

cialized anesthesia.

FNA avoids uncommon but serious morbidity associated with lymph node exci-

sion, like accessory spinal nerve injury.(77 )FNA is ideal particularly for those with

rapidly progressive disease,an oncologic emergency (e.g., spinal cord compression,air-

way compromise, superior vena cava syndrome),deep or surgically inaccessible nodes,

advanced age, or comorbid clinical conditions that preclude surgical biopsy or excision.

(78)

Limitations of lymph node fine-needle aspiration:

63
  Sampling error

Small or deep-seated lymph node

Nodal fibrosis

Excessive necrosis or inflammation

 Partial involvement of lymph node by the lesion

 Important architectural or vascular patterns are lost in some entities:

 Progressively transformed germinal centers

 Human immunodeficiency virus (HIV) Lymphadenopathy

 Vascular transformation of lymph node sinuses

 Toxoplasma lymphadenitis

 Castleman disease

 Nodular lymphocyte predominant Hodgkin

 Lymphoma

 Diffuse large B-cell lymphoma arising in follicular lymphoma.

Contraindications to FNAC are few:.

 1. Hemorrhagic diathesis

 2. Known suspected aneurysm, vascular malformations.

DIAGNOSTIC ACCURACY:

The frequency of nondiagnostic (unsatisfactory) results ranges from 5% to 15% of

64
cases FNA of lymph nodes has high sensitivity and specificity in the distinction between

a benign and malignant lesion.

Accuracy estimates for lymph node FNA vary because of local variations in tech-

nique and referral patterns, but most investigators report over 90% accuracy in the diag-

nosis of metastatic tumor to lymph nodes, and a positive predictive value of almost

100%. Similarly, the accuracy of a diagnosis of Hodgkin lymphoma is high, with a posi-

tive predictive value over 90%.

Most studies published in the last decade show a sensitivity for recognizing NHL

that is higher than 80%, with specificity greater than 90%. Accuracy is even higher when

FNA is performed for recurrent, as opposed to newly diagnosed, NHL.

Table .No.7:

SHOWING COMPARISON OF FNAC AND BIOPSY:

Biopsy FNAC

1. Length of procedure > 5 minutes < 5 minutes

2.. Anaesthesia Required Not Required

Not required

3.Report 1-2 days 1-2 hours

4.False positive None Rare

5.False negatives Very few Some

6.cost High Low

65
 7.Done In operation the- As an outpatient

atre

8.Trauma More Little if any

Ancillary Studies :

When evaluating a lymph node FNA for a possible lymphoproliferative disorder,

a variety of specializedstudies like flow cytomtry,immunocytochemistry,polymerase

chain reaction,FISH,gene expression profiling are indispensable. These require additional

effort and increase the turnaround time of the case, but the extra effort and time are often

rewarded by precise diagnosis and classification of the neoplastic process.

Ancillary studies help to:

 Distinguish lymphoid from nonlymphoid lesions

 Distinguish NHL from reactive lesions by confirming clonality

 Subclassify a lymphoma

Review of clinical trials and research of FNAC for lymphadenopathies

The study done by EngZell , Schour and chu (1973) reported the accuracy of cyto -

logic diagnosis as 90% and 97% in carcinoma metastatic to the lymph nodes..

66
 The study done by Shaha A. (1986) concluded that, FNAC is safe,accurate and

valuable tool for evaluation cervical lymphadenopathy. He has reported 100% accuracy

in making diagnosis of metastatic epidermoid carcinoma.

The study done by S.K. Lau. et al (1990 )said that though the granulomatous

lymphadenitis can be due to various causes, the mycobacterial infection as a cause for it

has to be considered first in the developing countries where mycobacterial tuberculosis

infection is common. Therefore the mere presence of granulomas in FNAC smears is

highly suggestive of tuberculosis. The sensitivity of FNAC in detecting tuberculous lym-

phadenopathy was 77%..

The study conducted by Maria Rosaria et al (1989).There were only two cyto-

logic false-negative results. In spite of the drawbacks of inadequate and false-negative

smears, fine-needle aspiration cytology is valuable in preliminary diagnosis of diseased

lymph nodes and subsequent management.

The study done by Sarda A. K. (1990) concludes that FNAC is painless,cheap, ex-

peditious, readily repeatable with low incidence of complications. He reported overall ac-

curacy of 96.00% in cytological diagnosis for cervical lymphadenopathies.

The Study done by Das DK et al(1990) analysed Cytomorphologic features of tu-

berculous lymphadenitis & revealed that necrosis was the only independent contributing

factor towards AFB positivity.

67
 The study conducted by Chih Hsu et al(1990) Sensitivity and specificity of cytol-

ogy reached 95% and 96.5%, respectively.. The most common metastatic carcinomas in

various groups of LNs were nasopharyngeal carcinoma in the cervical LN. breast carci-

noma in the axillary LN, and cervical carcinoma in both the groin and pelvic LNs.:

FNAC showed a sensitivity of 76.9% in the detection of TB lymphadenopathy.

According to Das D.K et al(1991) The success rate of FNAC ranges from 80% -

90% in diagnosis of NHL and from 67.5% - 86% in its subtype.

The study done by Shapiro A. L. (1991) concluded that appropriate use of needle

aspiration obviate the need for excisional biopsy and facilitate the diagnosis of cervical

lymph node and is recommended for all AIDS patients with unilateral cervical lymph

node and bilateral lymph node with a larger node more than 2 cms.41

The study done by Gupta AK (1991) concluded that FNAC is simple, safe, reli-

able and cost effective diagnostic tool for lymphadenopathies. But the limitations of the

procedure should be kept in mind and excision biopsy used whenever required. He re-

ported highest accuracy of 84.60% for metastatic carcinoma and similar accuracy i.e.

76.78%, 76.90% and 75.00% for tuberculosis lymphadenitis, reactive hyperplasia and

lymphoma respectively with non hodgkin’s lymphoma proved difficult to diagnose.

The study done by Arun Kumar Gupta and Mohini Nayar(1992) categorized tu-

berculous lymphadenitis into four groups.

68
- Epitheloid clusters with or without Langhan’s giant cells without necrosis.

- Epitheloid clusters with or without Langhan’s giant cells with necrosis.

- Occasional epitheloid cells without characteristic necrosis or giant cells.

- Necrosis without epitheloid clusters or Langhan’s giant cells.

The diagnosis of tuberculous lymphadenitis was offered with confidence in the first two

groups constituting about 82.49% cases and in the third and fourth group the smears were

subjected to Ziehl-Neelsen staining for Acid Fast bacilli which was positive in 12.5% and

75.6% of cases respectively. The AFB positive rate was particularly high when only pus

or necrotic material was aspirated.

The study conducted by Alan et al(1992) the sensitivity was 81%, specificity

89%, positive predictive value 91% and negative predictive value 78% . It was noted that

diagnostic accuracy improved with experience and good communication between the

cyto-pathologist and the clinician.. The study confirms the useful application of fine nee-

dle aspiration cytology in managing head and neck disease appropriately.

The study done by Prasad R (1993) concluded that FNAC is reliable, safe,rapid

and economical procedure and that negative result on FNAC does not rule out diagnosis

of tuberculosis or lymphoma and if clinical suspicion is strong FNAC should be followed

by lymphnode open biopsy for histopathological examination. He reported accuracy of

69
 90% for tuberculosis lymphadenitis, 75% for lymphoma and 100% accuracy for

metastatic carcinoma.

The study done by Silvan pilotti et al (1993) showed that there is a high rate of

conclusive cytologic diagnosis in the assessment of metastatic malignancies with an ac-

curacy rate of 99.1% & typing accuracy rate of 96.5%.

The Study done by Ajith Avinash pandit etal (1993)showed that in tuberculous

lymphadenitis, FNAC smears showing only caseous necrosis & AFB negativity ,presence

of multiple pink, homogenous structures with irregular shape and well-defined margins:

eosinophilic structures (ES) are degenerated granuloma and thus form an extended diag-

nostic criterion

The study conducted by Gamba et al (1995)showed that the sensitivity was

100% and the specificity was 96% & confirms that FNAC is a fast, cheap, simple, and

accurate diagnostic method and should be used for screening in all children with doubtful

superficial masses.

The study conducted by Steel BL et al (1995) showed that FNA cytology of

nodes provides a high level of diagnostic accuracy, as shown by the 3.4% false-negative

and 0.9% false-positive rates. Lymphoid marker studies of cytologic material greatly en-

hance our ability to diagnose and properly classify lymphomas and reduce the false-nega-

tive rate.

70
 The study done by C.V. Raghuveer et al (1996) compared the diagnosis of tuber-

culosis by FNAC with histopathology and it showed a specificity of 100% and sensitivity

of 71.4%. Study also showed that FNAC has a definite place in the diagnosis of primary

lymphoma. It may be diagnostic and but more often it may confirm the need for immedi-

ate excision biopsy.

The study conducted by Mostafa MG et al (1996) concluded that the the accu-

racy for necrotizing granulomatous lymphadenitis, suppurative lymphadenitis and reac-

tive changes were 69 per cent, 75 per cent and 95 per cent, respectively. The accuracy for

metastatic disease was 97 per cent. The specificity and sensitivity of FNAC were 99 per

cent and 94 per cent, respectively.

The study done by T W Shek etal (1996) repoted two patients who were young

adult males & found to have metastatic undifferentiated carcinoma on fine needle aspi-

ration of the enlarged cervical lymph nodes showing positivity for PLAP and negative for

EMA. The conclusion of the study was that Clinicians and pathologists should be aware

of the possibility of germ cell tumour when encountering a young adult male with

metastatic poorly differentiated carcinoma..

71
 The study conduted by Geoffrey et al(1997) showed that the sensitiviy & speci-

ficity for diagnosing malignant melanomas was found o be 100% & concluded that the

FNA biopsy of enlarged palpable nodules in patients with melanoma is accurate, rapid,

and cost-efficient.

The study done by Dong W. L. (1998) concludes that FNAC is useful in initial di-

agnosis of lymphadenopathy as well as in follow-up of patients with the known malig-

nancy while the results on malignant lymphomas were less accurate than other malignant

lesions.

The Study coducted by C J Stewart et al (1998)showed that FNA cytology accu-

rately distinguished reactive lymphoid hyperplasia from malignant lymphoma in 97% of

cases& ancillary studies can be applied to cytological samples and contribute to the diag-

nosis in most cases.

The study done by Reeves C. V. 1998 concludes that FNAC is viable and simple

procedure in metastasis of unknown origin investigations.43

In the study conducted by kim hs et al (1999), The overall diagnostic accuracy

was 96.8%. false negativity 6.0%, and false positivity 0.0%. Sensitivity of metastatic

carcinoma, malignant lymphoma ,tuberculosis was 98.0%,87.9%,53.9% respectively.

The study concluded that lymph node FNAC is an excellent non-invasive diagnostic

tool for the diagnosis of metastatic carcinoma..

72
 The study conducted by Lioe, T. F. et al (1999) The diagnostic accuracy was

94.4%, sensitivity 85.4% and specificity 100%. The false-negative rate was 12.5% but

decreased to 3.5% when lymphoma cases were excluded

The Study conducted by Nasuti, J. F et al (2000), reported only one false-posi-

tive diagnosis of a metastatic squamous carcinoma . no false positives in lymphomas;.

Unsatisfactory cases accounted for 12% & concluded that lymphnode FNAC can be an

accurate, economical and rapid diagnostic procedure.

The study done by Haque M. A. 2003 concludes that before resorting to surgical

intervention FNAC is a helpful procedure in the diagnosis of both the neoplastic and non

neoplastic lesion of the lymph nodes. He reported sensitivity and specificity of 82.76%

and 97.92% respectively for malignancy of lymphnode.

The study done by Chhieng et al (2001) reviewed the performance of cytology

supplemented by immunophenotyping in 56 cases of small-cell lymphomas of various

types and organs. The correct diagnosis could be established in 46 or 82% of these cases,

most of which were lymph node aspirates.

The study conducted by Shabnam Jaffer et al(2002) showed that the sensitivity

and specificity of FNAC of Axillary lymphodes were 94.7% and 97.1% and the ade-

quacy rate was 85.7%. The sensitivity, specificity, and adequacy rates of USG FNAC

73
were 100%& concluded that FNAC of Axillary lymphodes is an excellent method for

diagnosing reactive conditions as well as neoplasms.

The study conducted by M. Pradeep Reddy et al (2002)showed that FNAC’s sen-

sitivity and specificity as compared to ’gold standard of excision lymph node biopsy was

94% and 100% respectively. FNAC as a diagnostic modality is almost as sensitive and as

specific as excision lymph node biopsy when an adequate aspirate is examined by expert

eyes.

The Study done by Ajmal Farooq et al(2003) showed that the excision Biopsy

was more sensitive than FNAC (94% vs 80%) in diagnosing tuberculous cervical lym-

phadenopathy but FNAC is a safe alternative to Excision Biopsy and it should be recom-

mended as first line and Excision Biopsy as second line investigation only if results of

FNAC are negative

In the study conducted by I. N. Bagwan et al (2003) Cytology results were unsat-

isfactory in 9%specimens , negative or reactive in 25% and suspicious or positive for

malignancy in 1299 specimens (65.67%). The most common metastasis to the neck

nodes was of squamous carcinoma arising in the oral cavity.: FNA of head and neck

masses proved to be a useful tool in diagnosing metastasis with good certainty.

The study conducted by chau et al (2003) showed that in ultrasound and fine-

needle aspiration cytology of palpable lymph nodes an accuracy of 97 and 84% was

74
found, respectively. In conclusion, a multidisciplinary lymph node diagnostic clinic en-

ables a rapid, concerted approach to a common medical problem and patients with malig-

nant diseases were diagnosed in a timely fashion.

The study done by Kristian T. Schafernak (2003) showed that Patients with a his-

tory of malignancy are more than twice as likely to show malignancy on lymph node

FNA compared to those without such a history (87% vs. 41%). The study concluded that-

Knowing whether a patient has a history of malignancy provides the appropriate level of

suspicion for ordering ancillary investigations or even recommending excisional biopsy

for further evaluation

The study conducted by v koo et al(2006) showed that a definitive diagnosis on

FNAC with ancillary investigations was achieved in 82% (18 out of 22) of the cases &

concluded that a significant number of cases of FNAC diagnosed as granulomatous lym-

phadenitis have an identifiable underlying cause. Patients with reactive cytological

changes, who clinically appear benign, can avoid unnecessary surgery.

The study done by Vittorio Altomare et al(2006) showed that Echo-guided

FNAC of the axillary lymph nodes should thus be included among the regular diagnostic

procedures of presurgical staging as it was possible to avoid a sentinel lymph node biopsy

in 30% of the cases; the sensitivity was 68%, specificity 100%, PPV 100%, and NPV

65%.

The study done by Ruchi kajuria et al(2006) showed that the incidence of Tuber-

culous lymphadenitis, reactivehyperplasia, metastatic carcinoma, pyogenic lymphadenitis

75
and lymphomas were in 52.3%, 37.2%, 3.8%, 1% and 2% respectively.. Cervical lymph

nodes were involved most often in all types of lymphadenopathy(bibliography 2)

In the study conducted by D. Agarwal, P.et al Meerut (2006- 2009) patients of

lymphadenopathy who underwent FNAC were divided into 3 groups: Group I( 0-15

years), GroupII( 16-45 years) and Group III (>45 years) & found that the Commonest

cause of lymphadenopathy are ,in Group I- reactive hyperplasia 353(70.88%), Group II-

Tubercular lymphadenitis 261(40.78%) and Group III- Metastatic carcinoma

115(54.25%).the study concluded that different etiological factors play role in causation

of lymphadenopathy in different age groups and that aspiration cytology provided a reli-

able, safe, rapid and economical method of screening these patients with accuracy.

The study done by Abdul bari et al (2007) concluded that FNAC is a reliable

easy and economic technique of diagnosis & particularly be adopted in children as fairly

accurate cytodiagnosis is possible especially when majority of the cases of lym-

phadenopathy are inflammatory in nature.

The study conducted by vanisri et al(2008) showed that tuberculosis (58.3%)

was the predominant lesion in HIV patients followed by reactive lymphadenitis

(36.1%),) & the study concluded that FNAC is an important diagnostic tool in the evalua-

tion of lymphadenopathy in HIV-positive patients.

A retrospective study conducted by konar k et al (2008) showed that the speci-

ficity and sensitivity of FNAC in the detection of positive cases of metastatic squamous

cell carcinoma were 96.05and 96.5% respectively.

76
 The study conducted by J.-L. Roh et al(2008) showed that the Diagnostic accu-

racy of FNA was not significantly improved by repeat core needle biopsy and im-

munophenotyping. Delay from FNA to tissue diagnosis was significant in the benign

FNA-diagnostic group .

77
 MATERIAL
AND
METHODS

METHODOLOGY

Materials :

The study was conducted in S.V.S Medical college & hospital ,Mahabubnagar. patients

with significant lymphadenopathy referred to the department of pathology during the

time period of 1st August 2009 to 31st July 2011 were included in the study.

Sample Size:

400 patients

Inclusion Criteria

 Age 1 to 80 years
78
  Enlarged non-tender lymph nodes ≥ 0.5 cm in diameter

 patients presenting with superficial or deep lymphnode enargement

Exclusion Criteria

 Patients less than 1 year of age.

 Patients where FNAC of the node could not be carried out

were excluded.

A proforma drafted for the study of all patients presenting with

lymph node swellings was used. A detailed history was taken and a note

was made regarding age, sex, duration of symptoms, constitutional symp-

toms and history of contact with tuberculosis patient. A complete physical

examination was carried out.

Thorough general physical examination was carried out. Palpable peripheral

lymphnodes were examined noting their size, location, consistency, number, mobility,

presence of matting and presence of any local changes like redness, discharge or sinus

formation.

79
 The area drained by enlarged lymphnodes was examined for presence of features

of infection or inflammation. An attempt was made to find out the primary tumour in

cases of lymph nodes suspicious as secondaries in neck.

Fine Needle aspiration cytology (FNAC) was done for all the patients in study group after

selecting the most prominent node & The results of FNAC were further correlated with paraf-

fin embedded sections of tissue blocks for the available cases.In the present sudy out of 400

cases of FNAC only 90 cases were followed by biopsy.

Equipment required:

⎯ Standard needle used is 22 or 23 G between 30-50 mm length.

⎯ Standard 10-20 ml plastic syringe and syringe holder.

⎯ Slides, cover slips, mounting media.

⎯Fixative 80% isopropranol

Technique of FNAC 54:

After explaining the procedure to the patient the largest lymph node is selected.

The selected lymph node is aspirated under strictaseptic precautions. Overlying skin is

stretched and the lymph node grasped between the index finger and thumb of left hand; a

80
sterile 22 or 23 gauge needle is fitted to a 5-10 ml syringe and pierced obliquely into the

lymph node.

Deep seated nodes were aspirated using USG or CT guidance under local anaes-

thesia..After entering the lymph node mass the plunger is withdrawn and the negative

pressure created in the syringe the needle is moved back and forth several times with a

constant suction. The negative pressure is released and the needle removed from the

mass.

The needle containing the aspirated material is then detached, and air is drawn

into the syringe. After reattachment of needle, content of the hneedle is ejected out on the

clean,dry and grease free glass slides. Smears are prepared using another glass slide ex-

erting light pressure.

The aspirate is examined for the amount and nature of the aspirated material, and

then several smears are prepared. Excess of blood if present, is removed using blotting

paper. In cases ,where fluid aspirated , slides were also made from the centrifuged de-

posit.Caution is exercised to minimize the cell damage and preserve cell distribution.

Smears are immediately fixed in 80% isopropyl alcohol and stained by Haema-

toxylin and eosin stain. Air-dried smears are also prepared and stained with Ziehl-

Neelsen stain for the cases where necrotic material is aspirated or tuberculosis

suspected,for the demonstration of acid-fast bacilli.

Smears are examined under microscope for the cytological picture.The smears

were examined in detail and inadequate aspirates were excluded.

81
H & E staining procedure :

 Smears Washed in distilled water 15 dips

 Dipped in Harris's hematoxylin for 2 minutes

 In Acid alcohol (1.5 ml of concentrated HCl in 650 ml of 70% ethyl alcohol)—

two to three dips or until specimen is red in color

 Washed in running tap water until excess stain is removed (approximately 1

minute)

 Washed in running tap water 30 seconds

 Ammonia water for 1 minute

 Washed in tap water 15 dips

 50% Ethyl alcohol 15 dips

 Eosin approximately 20 seconds

 95% Ethyl alcohol 15 dips

 95% Ethyl alcohol 15 dips

 Absolute ethyl alcohol 15 dips

 Absolute ethyl alcohol 1 minute

 Xylol 15 dips

 Xylol 15 dips

 Xylol 5 to 10 minutes

 Finally the smear is Mounted With DPX

82
 INTERPRETATION OF ASPIRATES:

After studying all the available clinical data, retrieved from the hospital the smears

were examined under the microscope. Based on the cellularity the smears were categorized

as of high, moderate or low celluarity. Those smears which were haemorrhagic or with

scanty cellularity to such an extent that diagnosis could not be offered were labelled as inad-

equate for opinion.

AFB staining procedure :

1. Air dried smear is used for AFB staining in smears suspicious of tuberculosis and

where pus is aspirated

2. smear is flooded with carbolfuchsin, the primary stain, for 3–5 minutes while heating

with steam or heating on hot plate.

3. The smear is Decolourised with 20% sulphuricacid for 1min.

4. Counterstain with methylene blue.

Interpretation of AFB smear:

AFB – Number - Numerous +

- Many 3 +

- Few 2+

- Occasional 1+

83
 - Absent 0

84
 RESULTS

RESULTS:

The present study includes 400 patients with lymphadenopathy referred to Depar-

ment of pathology, S.V.S medical college & Hospital between August 2009 and July

2011. These cases were taken for Fine Needle Aspiration Cytology (FNAC), but in 28

cases FNAC was inconclusive. Excisional biopsy was available in only 85 cases

(21.25%) , finally these cases were analysed in detail.

Maximum number of cases 255(63.75%) were between 11-40 years age group

85
and the female to male ratio was 1.13:1.

Out of these 400 cases, 183 cases(45.75%) were confirmed as tuberculous lym-

phadenitis, 91 cases (22.75%) as chronic non-specific lymphadenitis, 45 cases(11.25%)

as secondaries, 22 cases(5.5%) as non tuberculous granulomatous lymphadenitis, 17

cases (3.8%) as lymphomas,12 cases (3%) as acute suppurative

lymphadenitis,2cases(0.5%) as leukemic infiltration.

Thus among the lesion of lymph nodes tubercular etiology was the most com-

mon. The causes of lymphadenopathy were broadly classified as neoplastic and non-

neoplastic lesions.

Table No. 8
Showing the number and percentage of non-neoplastic and neoplas
tic lesions :

S.NO. TYPE OF LESION NO. %

1. NONNEOPLASTIC 308 77%

2. NEOPLASTIC 64 16%

86
3. INADEQUATE 28 07%
 In lymphnodes Nonneoplastic lesions were more common than neoplastic lesions

constituting77% of total cases.64 cases (16%) are of neoplastic in nature.Inadequate

smears constituting about 7% (28) of the total cases.

Table .No.9

Table showing non neoplastic lesions :

S.NO. TYPE OF LESION NO. %

1. Tuberculous granulomatous lymphadenitis 183 59.45%

2. chronic nonspecific lymphadenitis 91 29.5%

3. Non Tuberculous granulomatous lymphadenitis 22 7.15%

4. Acute suppurative lymphadenitis 12 3.90%

Total 308 100%

Granulomatous lymphadenitis of tuberculous etiology is the most

common Cause of lymphadenopathy seen in 183 cases(59.45%) followed by

chronic nonspecific lymphadenitis in 91 cases(29.5%).7.15% of the cases show

non tuberculous granulomatous lymphadenitis & acute suppurative lymphadenitis

in 12 cases (3.90%).

Table .No. 10

Table showing neoplastic lesions:

87
 S.NO TYPE OF LESION NO. %
45 70.4%
1. Metastasis
14 21.8%
2. Hodgkins lymphoma
3 4.6%
3. Nonhodgkins lymphoma
2 3.2%
4. Leukemic infiltration
64 100%
Total

Among the neoplastic lesions metastasis had maximum number of cases

45(70.4%) followed by Hodgkins lymphoma in 14 cases(21.8%) & Non hodgkins lym-

phoma in 2 cases(3.2%).leukemic infiltration is seen in only 2 cases(3.2%).

Table .No. 11

Table Showing age distribution of lymphnodal lesions :

Inadequate
Metastasis

Leukemia

Age
TBLN CNSL NTGL ASL HL NHL Total
range

1-10 21 20 01 02 00 03 00 01 03 51

11-20 45 22 05 02 01 05 02 00 05 87

21-30 61 23 04 04 04 01 00 00 08 105

31-40 32 11 06 02 05 01 00 00 06 63

88
 41-50 14 10 02 00 09 03 00 01 01 40

51-60 10 05 02 00 10 01 01 00 04 33

61-70 00 00 01 02 12 00 00 00 01 16

>70 00 00 01 00 04 00 00 00 00 05

TOTAL 183 91 27 12 45 14 03 02 28 400

The minimum age of the patient presenting with lymphadenopathy is 14 months

& the maximum age being 80 years. The maximum incidence was in the age group of 11

years to 40 years which was in 255 cases(63.75%). Maximum incidence of TB lym-

phadenitis was between the ages of 11 years to 40 years(138 cases,34.5%).In secondaries

maximum incidence was found between 40 years to 70 years(31 cases,7.75%).lympomas

reported were common between 11-30 years(8 cases2%).The age of the patients reported

as ALL & CLL were 10 years & 41 years respectively.

Table. No.12

showing sex distribution in various lesions:

s.no. Cytology diagnosis Males Females Total

Granulomatous
lymphadenitis

TB 79 104 183
1.

NTGL 12 10 22

89
 2. CNSL 45 46 91

3 METASTASIS 14 31 45

Lymphoma
HL 10 4 14
4.

NHL 1 2 3
s

5. ASL 02 10 12

6. LEUKEMIA 1 1 2

7. INADEQUATE 12 16 28

TOTAL 188 212 400

Male to female ratio was found to be 1.13 : 1,there is slight female preponderance

in most of the lesions .but in metastasis there is male predominance (2.9 : 1).

Table.No.13

Table showing various sites involved in lymphnode lesions :

leukemia
Metasta-

lymphoma
inade-
Total

CNS NTG
SITE TBLN ASL
L L
HL NHL

23
Cervical 118 58 12 09 25 02 02 00 16
9

90
 Sub-
22 17 07 02 04 07 01 00 09 69
mandibular

Axillary 14 08 00 00 10 01 00 00 02 35

Inguinal 02 03 01 00 04 01 00 00 00 11

00
Generalised 30 03 02 00 00 08 02 45
00

Others 00 02 00 02 02 01 00 00 01 08

40
Total 183 91 22 12 45 17 03 02 28
0

In all the type of lesions cervical group is the most common group involved in al-

most 239 cases(59.75%).tuberculous lymphadenopathy most commonly presented with

cervical lymphadenopathy in about 118 cases.(64.48%)Next common mode of presenta-

tion is generalized lymphadenopathy seen in 45 cases (%) which is seen mostly in tuber-

culous lymphadenitis(30 cases) & hodgkins lymphoma(8 cases),followed by sub-

mandibular group seen in 69 cases(%).Axillary group is involved in 35 cases(%) and

most of them are metastatic deposits from breast carcinoma.

Table .No.14

Table showing size of lymphnode lesions:

91
 S.NO Type of lesion <1Cm 1-2Cm >2Cm
1 TBLN 05 86 92
2 CNSL 10 50 31
3 NTGL 03 06 13
4 ASL 00 06 06
5 Metastasis 00 14 31
6 Lymphomas 00 01 16
7 Leukemias 00 01 01
8 Inadequate 17 07 04
9 Total 35 171 194

Majority of patients 194 cases (48.5%) presented with lymphnodes of more than 1

cm in size. Size ranging from 2×2 to 6×5 cm. 171 patients presented with lymphadenopa-

thy of 1-2Cm in size.

Only 35 patients (8.75%) had lymphnodes of less than 1 cm.

Table.No.15

Table Showing mode of presentation :

NO. %

FIRM 328 82%

HARD 47 11.7%
Consistency

RUBBERY 10 2.5%

92
 SOFT 15 3.75%

TOTAL 400 100%

PRESENT 80 20%
Matting
ABSENT 320 80%

TOTAL 400 100%

1-2 296 74%

3-4 66 16.5%
.lymphnodes

5-6 08 02%
No.of

MULTIPLE 30 7.5%

TOTAL 400 100%

Firm in consistency was the most commonest (82%) clinical finding. Matting was

present in 80 patients(20%) . The maximum number of nodes were between 1-2 in 296

patients(74%)

Table .No.16

Table showing Correlation of clinical & cytopathological diagnosis :

CYTOLOGY DIAGNOSIS
M

LYMPHOMA
L

93
 EUKEMIA
ETASTA-
CLINICAL TBLN CNSL NCGL ASL HL NHL

QUATE
NADE-
DIAGNOSIS

SIS
TBLN 81 06 07 02 10 14 00 01 07

CNSL 94 77 14 07 02 00 00 00 20

NTGL 01 00 00 00 00 00 00 00 00

ASL 00 02 00 02 00 00 00 00 00

METASTASIS 00 03 00 01 32 00 00 00 00

HL 04 00 01 00 01 00 00 00 01

NHL 00 00 00 00 00 00 02 00 00

LEUKEMIA 00 00 00 00 00 00 00 01 00

OTHERS 01 03 00 00 00 00 01 00 00

. The cytological diagnosis was correlating with clinical diagnosis in about 81

cases, in tuberculous lymphadenitis & in 77 cases in case of chronic nonspecific lym-

phadenitis .In Metastasis the clinical diagnosis was correlating with FNAC diagnosis in

32 cases.

Table.No.17

Table showing cytological features of tuberculosis:

Cytological feature N0. %

94
 Epitheloid cell granulomas with necrosis 101 55.19%

Epitheloid cell granulomas with out necrosis 42 22.95%

Necrosis 40 21.86%

Total 183 100%

In the present study epithelioid granulomas with necrosis was the predominant

microscopic pattern seen in 101cases (55.19%), followed by granulomas without necro-

sis in 42 cases(22.95%) and caseous necrosis without granuloma in remaining 40

cases(21.86%).

Table.No.18 showing Microscopic patterns & AFB positivity:

AFB POSITIVITY
CYTOLOGICAL FEATURE
NO. %
45 79%
Necrosis only
08 14%
Granulomas with necrosis
04 07%
Granulomas only
57 100%
Total

Out of 183 cases of tuberculous lymphadenitis AFB positivity is seen in 57

cases(31.14%).AFB positivity was seen predominantly (79%) in necrosis alone

pattern,followed by granulomas with necrosis pattern in (14%). AFB Positivity was seen

in only 04 cases(07%) in smears showing epitheloid cell granulomas alone.

95
 Table.No.19

Table showing cytological diagnosis of Metastatic lesions

s.no CYTOLOGICAL DIAGNOSIS NO. %

1 Squamous cell carcinoma 24 53.34%

2 Ductal cell carcinoma 08 17.78%

3 Papillary carcinoma 04 08.88%

4 Anaplastic carcinoma 03 06.68%

5 Adenocarcinoma 01 2.22%

6 Nasopharyngeal carcinoma 01 2.22%

7 Small cell carcinoma 01 2.22%

8 Testicular carcinoma 01 2.22%

Malignat melanoma 02 4.44%

9
TOTAL 45 100%

Among the seconadries to lymphnodes sqamous cell carcinoma deposits were

common seen in 24 cases(53.34 %).next common diagnosis being ductal cell carcinoma

in 8 cases(17.78%) followed by papillary carcinoma in (8.88%), anaplastic carcinoma

06.68%, adenocarcinoma ,nasopharyngeal carcinoma, small cell carcinoma ,testicular car

carcinoma & malignat melanoma in 2.22% cases.

CORRELATION BETWEEN CYTOLOGY & HISTOPATHOLOGY

DIAGNOSIS:

96
 Out of 400 cases of FNAC biopsy was available only in 85 cases & correlation

could be done in only these cases.

Table .No.20

Table Showing diagnostic co-relations of FNAC:

Histopathology diagnosis
Cytology LYM-
diagnosis TBLN CNSL NTGL METASTASIS PHOMA LEUKEMIA Total
HL NHL

TBLN 34 00 01 00 00 00 00 35

CNSL 04 18 00 00 00 00 00 22

NTGL 01 01 05 00 00 00 00 07

METASTASIS 00 02 00 07 00 00 00 09

HL 00 00 00 00 08 00 00 08

NHL 00 00 00 00 00 02 00 02

LEUKEMIA 00 00 00 00 00 00 02 02

Total 39 21 06 07 08 02 02 85

Out of 35 cases of FNAC diagnosis of tuberculous lymphadenitis 34 cases were

correlating with histopathology diagnosis.There was only one false positive case re-

ported which was later on reported as non tuberculous granulomatous lymphadenitis by

biopsy.

Table.No.21

Table Showing Results of Tuberculous lymphadenitis.

97
 Test HPR (+) HPR (-) Total
FNAC + 34 01 35

FNAC - 05 45 50

Total 39 46 85

The Sensitivity,Specificity,PPV & NPV of FNAC in diagnosing tuberculous lm-

phadenitis are 87.19%,97.8% , 97.14% & 90% respectively.

Table.No.22

Table showing Results of chronic nonspecific lymphadenitis

TEST HPR (+) HPR (-) TOTAL

FNAC + 18 04 22

FNAC - 03 60 63

TOTAL 21 64 85

Out of 22 cases of chronic nonspecific lymphadenitis on FNAC 18 cases were

confirmed by biopsy as chronic nonspecifc lymphadenitis & 4 false positive cases were

noted. Sensitivity,Specificity,PPV & NPV being 85.71 %,93.75 %,81.82 %,95.24 % respec-

tively.

Table.No.23

showing Results of non tuberculous granulomatous lymphadenitis

TEST HPR (+) HPR (-) TOTAL

FNAC + 05 02 07

FNAC - 01 77 78

98
 TOTAL 06 79 85

FNAC diagnosis of non tuberculous granulomatous lymphadenitis was confirmed

with biopsy in 5 cases & false positives seen in 2 cases. Sensitivity,Specificity,PPV &

NPV being 83.3 %,97.5%,71.4%,98.71% respectively.

Table.No.24

Showing Results of metastatic carcinoma

TEST HPR (+) HPR (-) TOTAL

FNAC + 07 02 09

FNAC - 00 76 76

TOTAL 07 78 85

9 cases of Metastatic deposits diagnosed on FNAC were followed by biopsy ,in

which 7 cases were correlating & 2 false positive cases were seen.

The Sensitivity,Specificity,PPV & NPV of FNAC in diagnosing metastatic de-

posits were 100%,97.4%,77.8% & 100 % respectively.

No false positives recorded in diagnosing lymphomas & leukemias by FNAC &

both the sensitivity & specificity were 100 %.

Table.No. 25
showing sensitivity & specificity of FNAC over biopsy in various le-
sions :
99
 False posi-
sensitivity

specificity

predictive

predictive

negatives
Negative
Positive

False
% of

% of
value

value
Type of le-

tives
sion

TBLN 87.2 % 97.8 % 97.14 % 90 % 12.82 % 2.17 %

CNSL 85.71 % 93.75 % 81.82 % 95.24 % 14.28 % 6.25 %

NTGL 83.3 % 97.5 % 71.4 % 98.71 % 16.67 % 2.53 %

Metastasis 100 % 97.4 % 77.78 % 100 % 00 % 2.56 %

HL 100 % 100 % 100 % 100 % 00% 00%

NHL 100 % 100 % 100 % 100 % 00 % 00 %

Leukemia 100 % 100 % 100 % 100 % 00 % 00 %

The sensitivity of FNAC for diagnosing tuberculosis , chronic non-specific lymphadeni-

tis , malignant secondaries , lymphomas was 87.2% , 85.71% , 100% & 100% respec-

tively.

OVERALL DIAGNOSTIC EFFICACY OF FNAC :

Table.No.26

Table Showing FNAC and Histopathologic results according to the

status of malignancy:

100
 HISTOPATHOLOGY
FNAC
BENIGN MALIGNANT TOTAL

BENIGN 64 00 64

MALIGNANT 02 19 21

Total 19 66 85

Comparing FNAC results with histopathologic diagnoses revealed that 64 cases

were diagnosed both by FNAC & Histopathology as benign .In 19 cases malignant le-

sions were diagnosed the same in histopathology also.In 02 cases benign lesions were

overdiagosed as malignant lesions representing false positives.there were no false nega-

tives in the present study.

Table.No.26

Showing overall diagnostic efficacy of FNAC :

TEST HPR (+) HPR (-) TOTAL

FNAC + 19 02 21

FNAC - 00 64 64
101
 TOTAL 19 66 85

FNAC had a sensitivity of 100 % and a specificity of 96.97% . Positive and

negative predictive values of this method were 90.48% and 100 % respectively.

Graph 1 :
Showing the distribution of Non-neoplastic and Neoplastic lesions

102
 0.07
0.16

0.77000000
0000003

NONNEOPLASTIC NEOPLASTIC INADEQUATE

Graph 2: Showing the distribution of Non neoplastic lesions

103
 200
180
160
140 183
120
No.Of.cases

100
80
91
60
40
20 22 12
0
TBLN CNSL NTGL ASL

Type of lesion

Graph 3 :Showing distribution of Neoplastic lesions

104
 45
40
35
30
25
No.of.cases

20
45
15
10
14
5
3 2
0
Metastasis HL NHL Leukemia
Type of lesion

Graph 4: Showing sex distribution in various lesions

105
 120
104
100
79 Males
80 Females

60
NO.of.cases

45 46

40 31

14 16
20 12 10 10 12
10 4 1 2 2 1 1
0
TB L IS HL L L IA
G
SL AS NH AS
NT T KE
M E
CN TA
S
U U AT
E L E
M EQ
AD
IN
Type of lesion

Graph 5 :showing various sites involved in lymphnode lesions

106
 250

200

150
No.of.cases

239

100

50
69
35 45
11 8
0
Cervical Submandibular Axillary Inguinal Generalised Others

Site involved

Graph 6 : Showing size of lymphnode lesions

107
 200
180
>2Cm 1-2Cm
160
140 92 <1Cm
120
No.of cases

100
80 31
60 86
40 50 31 4
20 13 6 16 1 7
5 10 6 3 6 14
1 1 17
0
TB SL GL AS
L IS AS IA
S
AT
E
CN NT TAS M M U
AS O E Q
ET PH UK DE
M M LE A
LY IN

Type of lesion

Graph 7:Cytological features of tuberculosis

108
 120

100 N0.

80
No.of cases of tuerculosis

60
101

40

42 40
20

cytological feature of tuberculosis:

Graph 8:

Microscopic patterns of tuberculosis assosciated with AFB positivity

109
 % OF AFB POSITIVITY

14% 7%

79%

Necrosis only Granulomas with necrosis Granulomas only

Graph 9 : Showing cytological diagnosis of Metastatic lesions

110
 Malignat melanoma 2

Testicular carcinoma 1

Small cell carcinoma 1

Nasopharyngeal carcinoma 1

1
Adenocarcinoma

Anaplastic carcinoma 3

Papillary carcinoma 4

Ductal cell carcinoma 8

Squamous cell carcinoma 24

0 5 10 15 20 25

111
 DISCUSSION

DISCUSSION :

112
 FNAC entails using a narrow gauge (22-23G) needle to collect the sample of a le-

sion for microscopic examination. It allows a minimally invasive, rapid diagnosis of tis-

sue but it does not preserve the histological architecture which limits its ability to make a

definitive diagnosis. However, rapid diagnosis by FNAC can shorten or avoid hospital

admission, speed a patient’s route to an appropriate specialist.

This study was undertaken to evaluate the diagnostic utilty of FNAC in clinically

significant lymphadenopathy. Symptoms and signs although indicative of the etiology of

lymphadenopathy cannot be substituted for a morphological diagnosis. Until recently, ex-

cision of diseased enlarged lymphnode for histopathological examination was the final

answer for the diagnosis.

With the advent of FNAC in recent years, it has provided the clinician with an ad -

ditional, safe, reliable, quick and inexpensive method for the diagnosis of lym-

phadenopathy.

In developing countries like India where tuberculosis is the major problem and fa-

cilities for the biopsy are not readily available at the primary health care level, FNAC

can be very useful in providing a diagnosis. It also reduces pressure on financial re-

sources necessary for surgical procedures like open biopsy for diagnosis confirmation.

In our study we attempted to evaluate the diagnostic efficacy and its limitation in

the clinical practice. All our patients as per inclusion criteria were subjected to FNAC &

113
some of those cases were followed by open biopsy of the same diseased enlarged lymph

node so as to remove any discrepancies in the cytological and histological diagnosis.

The present series in our study confirms the accuracy and clinical utility of FNAC

in the investigation of the patient with significant lymphadenopathy.

In our study out of 400 patients of lymphadenopathy 308 cases (77%) were of non

neoplastic(benign) in nature & 64 cases (16 %) were of neoplastic (malignant) in nature.

Non diagnostic smears constituting 7 % of the total cases.These findings correlate well with

the results reported by Ahmed et al who studied 50 cases out of which 37 cases(74%) were

benign ,11 cases (22%) were malignant & 4% 0f the cases were nondiagnostic smears.The

findings observed by Abdul et al,.,Rakshan et al are also comparable with the present study.

However, Steel et al reported 59% cases of malignant lesions and 29,8% cases of benign lesion-

s.This may be attributed to the fact that western countries,where these studies were carried out

show predominance of malignant conditions over benign conditions.

The total number of FNA samples with nondiagnostic smears was 7 % (28 cases)

in our study, which was in the lower limit of the acceptable range of less than 10- 15%

(16). These included cases in which the aspirated. material was either inadequate or un-

satisfactory due to poor preparation and/or staining.

Table No.28

Showing classification of lymphnodal Lesions in various studies

114
 Benign Malignant Inadqeuate
Study
Abdul et al (120 cases) 104 16
-
2007 (86.7 %) (38.1%)
Steel et al (1103 cses) 329 654 120
1992 (29.8%) (59.3%) (10.87%)
Ahmed et l (50 cases) 37 11 2
2005 (74%) (22%) (04%)
Rakshan et al (178cases) 101 50 27
2009 (56.7%) (28.1%) (17%)
308 64 28
Present study(400 cases)
(77%) (16%) (07%)

In our study bulk of diseases are of tubercular lesions and of reactive nature due to infec -

tions,which are uncommon in western countries. In the present series, tuberculosis accounted

for 45.75% of cases, 22.75% of cases were diagnosed as chronic non-specific lym-

phadenitis, 5.5% as non tuberculous granulomatous lymphadenitis, 3% as acute suppura-

tive lymphadenitis. Among the neoplastic lesions, malignant secondaries accounted for

11.25 % of cases and Hodgkin’s lymphomas in 3.5% of cases while non-Hodgkin’s lym-

phoma comprised 0.75% & leukemias in the remaining 0,05 % of the cases.Similar observa-

tions were made by Jha B.C. et al., 68

who studied 94 cases, of which tuberculosis

was confirmed in 63.8% cases, chronic non-specific lymphadenitis in 5.9% , reactive

lymphadenitis in 9.6% & malignant lesions consistig of metastatic deposits & lymphomas

in 20.79% of the cases.

115
 The findings observed by Jindal N. et al., 69 Arora B. et al. 71 are also comparable with

the present study. The lower incidence of tuberculosis in study by Kim L.H. et al. 72 is

probably because the patients were from non-prevalent areas.

Table No.29

showing distribution of different lesions in various studies

Studies TBLN CNSL RL Secondaries HL NHL

Shafiullah et al. 69% 3.8% 17.8% 2.9% 3.1% 3.4%

Jha B.C. et al. 63.8% 5.9% 9.6%

20.79%
(2001)

Jindal N. etal. 48.4% 22.5% 13.3% 15.8%

Arora B. et al . 62% 17% 6% 4%

11%
(1990)

KimL.H.et al. 13.9% 2.2% 33.1% 25.7%

8.08%
4.4%
(1999)

38% 11% 21% 15% 15%

Aruna Das.et al.

(1996)74

Present study NTG

TBLN CNSL ASL MET HL NHL LEU
L

45.75 22.75% 5.5% 3% 11.25 3.5% 0.75% 0.05%

116
 % %

In the present study out of 400 cases , 255 cases (63.75%) were recorded between

the age group of 11 years to 40 years which is comparable with the study done by

Shafiullah et al. where 72% of the cases were recorded in the age group of 11-30 years .

Of the 400 patients, 188 of them were males and 212 were females. The sex ratio in the

present study was 1: 1.13 (M:F), there is slight female preponderance.This is in comparision

with the studies done by Bedi R.S. et al, Ammari F.F. et al.76 ,Dworski I 77 ,Dandapat M.C. et al.78

Table No.30
showing comparative analysis of sex distribution

Bedi Ammari Dworski Dandapat Present

R.S. F.F. et I M.C. et study
et al. al. al.
M:F 1:1.7 1:2 1:1.38 1:1.2 1:1.13
ratio

Size of lymph nodes:

The study done by M..Pradeep Reddy et al showed that lymph nodes measuring

more than 1cms in the cervical and axillary region, more than 1.5cms in the inguinal re-

gion and at any other site more than 0.5cms are considered significant.5

In this study there were 35 cases of lymph nodes measuring <1cms in greatest di-

mension. Of this 33 were in the cervical region, 2 in the axillary region. Out of these 17

cases were inadequate for opinion due to scanty aspirate.

117
 In our study FNAC from the the lymph nodes measuring < 1cms were inadequate

in 48.57% of cases, but the other 51.43% cases yielded diagnostic material. Hence the

present study consider that the lymph node measuring < 1cms is significant.

118
.
Therefore an FNAC should be attempted even on cervical lymph nodes measuring

less than 1cms as a definitive diagnosis can be obtained.

Tuberculous lymphadenitis proved to be the most common diagnosis in our study

(45.75%). In India, tuberculous lymphadenitis is one of the most common type of lym-

phadenopathy encountered in clinical practice in India (3,4,7,8) ; whereas it is in sharp

contrast to very low frequency of 1.6% in western studies (9).

In our study maximum incidence of TB lymphadenitis was between the ages of 11

years to 40 years(138 cases,34.5%). with female preponderance,male to female ratio be-

ing 1:1.32. Lymph nodes of the neck (64.48%) followed by generalised lymphadenopathy

(7.5%) are the most common sites involved. The cervical group of lymph nodes was most

commonly involved as was the case in most other series. 5, 18,39,40, This is attributable to

the rich lymphatic supply in the neck region.2,41

Tuberculous lymphadenopathy was the most common diagnosis in our study ac-

counting for 45.75% of the total cases with an accuracy of 87.19 % on FNAC with

histopatholgical correlation which is comparable to similar studies.

The study done by Gupta K.A. (1990) has also reported accuracy of 76.78% for

tuberculous lymphadenopathy to an histological correlation.39A similar study done by

Bhargava P (2001) has reported accuracy of 98.50% for tuberculous lymphadenopathy to

histological correlation.45

The study done by Sarda A. K. (1990) reported accuracy of 96.00% for tubercu-

lous lymphnadenopathy.38

119
 In the present study out of 39 patients of tuberculous lymphdenopathy on biopsy

34 cases were reported on FNAC. In 04 cases the diagnosis of chronic non specific lym-

phadenitis & in 01case non tuberculous granulomatous lymphadenitis was offered in

FNAC.

The characteristic feature of tuberculous lymphadenitis on cytology examination

are the presence of epitheloid cell clusters, caseous necrosis and typical Langhan’s giant

cells. Epithelioid cell aggregate is the earliest cytological finding in tuberculous lymphadeni-

tis.38

In our study epithelioid granuloma with necrosis was the predominant cytological

pattern seen in 55.19% of cases which is in accordance with study conducted by Das D.K et

al, Handa U et al and Gupta A.K et al.37,35,45, The other common cytological pattern observed

was epithelioid granuloma without necrosis seen in 22.95% cases and caseous necrosis

alone seen in 21.86%. cases. However literature shows varying cytological results in epithe-

lioid granuloma without necrosis and necrosis alone group as shown in Table No

Table No.31

Comparative studies showing cytological findings in tuberculous

lymphadenopathy

Bharad- Das D. Bezabih Handa Gupta Presen

Microscopic
waj k M et U A.K t
features
K et al 19 et al 37 al38 et al 35 et al 45 Study

Epithelioid
granuloma 37.93% 39.08% 32.80% 46.86% 50.36% 69.09%
with
necrosis

120
 Epithelioid cell 44.83% 25.29% 15.80% 31.43% 35.00% 14.55%
granuloma
Necrosis 17.24% 35.63% 51.40% 21.71% 14.64% 16.36%
alone

In doubtful cases Ziehl –Neelsen staining is helpful in demonstrating the pres-

ence of acid fast bacilli. In the present study out of 183 cases of tuberculous lym-

phadenitis 57 cases(31.14%) were positive for acid fast bacilli on Ziehl–Neelsen staining

which helped in giving diagnosis of tuberculous lymphadenopathy.

Table .No.32

Comparative studies showing AFB % in Microscopic Patterns of tuber

culous lymphadenitis in Cytology

AFB% in Epithelioid AFB% in Epithelioid AFB% in

Granuloma with Necrosis Granuloma Necrosis
Study

Prasoon D et al7 20.68% 1.16% 78.16%

Present study 14% 07% 79%

AFB positivity was seen predominantly in necrosis alone pattern(79%),followed

by granulomas with necrosis pattern in 14% of total AFB positive cases. AFB Positivity

was seen in only 04 cases(07%) in smears showing epitheloid cell granulomas alone.

These findings correlated with Prasoon D et al7 studies as shown in Table No. .Thus a pre-

dominantly granulomatous reaction with little or no coexistent necrosis would be associated

with the presence of few or no AFB, while a predominantly necrotic reaction with few or no

coexistent granulomas would be expected to show more AFB.7

121
 It is believed that, there must be 10,000 to 1,00,000 organisms per millilitre of the

sample in order to detect AFB in a cytologic specimen.44 Increasing percentage of AFB is

being observed with increase in the observation of caseation necrosis. Conversely with more

epithelioid cell granulomas, the percentage of AFB positivity declined. 19

Das et al 37 also observed that foci of liquefaction necrosis was associated with

marked proliferation of tubercle bacilli and infiltration of polymorphs whereas lymphocytes,

epithelioid cells and multinucleated giant cells are likely to have some role in limiting the

proliferation of AFB.19,37

When multiplication of bacilli in a lymph node is not under control, the lymphnode

becomes necrotic and turns into an abscess. Therefore it is expected that the FNA from a tu-

berculous abscess contains more AFBs than early tuberculous lymphnodes.8

Problem arises in definite diagnosis in tuberculous lymphadenitis cases when

Langhan’s giant cell, and epitheloid cells are not seen in the smear or when smear con-

tains only caseous material or pus. Hence in our study we had 5 false negative reports on

FNAC for tuberculous lymphadenopathy being reported as nonspecific chronic lym-

phadenitis in 4 cases & non tuberculous granulomatous lymphadenitis in 1 case.

There was 1 false positive case reported in the present study this may because of

the presence of epitheloids & giant cells in hodgkins lymphomas well. In the present

study cervical group was the most common group affected with tuberculous lym-

phadenitis constituting 118 out of 183 cases (64.48%).

122
 In the present study, chronic non specific lymphadenitis is the next common cause

of lymphadenopathy accounting for 22.75 % of the total 400 cases.chronic non specific

lymphadenitis had high number of falsepositive cases (i.e. 4 cases) in the preset study as

patients with tuberculous lymphadenopathy, Hodgkin’s lymphoma may have similar

polymorphous picture on aspirates as chronic non specific lymphadenitis in absence of

Langhan’s cells / epitheloid clusters and Reed-Sternberg’s cells respectively. 18 cases

had histopathological confirmation as chronic non specific lymphadenitis.

The present study has accuracy of 85.71% for diagnosing chronic non specific

lymphadenitis on FNAC which is comparable with other studies.In the study done by

Gupta A. K. (1990) reported accuracy of 76.90% of cases on FNAC.39

In the present study, non tuberculous granulomatous lymphadenitis

is seen in 5.5 % of the total 400 cases. , non tuberculous granulomatous lymphadenitis

had 2 falsepositive cases in the preset study as non caseating granulomas can be present

in patients with tuberculous lymphadenopathy & Hodgkin’s lymphoma as well.07 cases

were available for histopathological correlation & 6 cases were confirmed by biopsy . In

the present study the diagnostic accuracy of FNAC for non tuberculous granulomatous

lymphadenitis in the present study was 83.33%.

In the present study, we had 17 cases of lymphomas out of which 14 were of

hodgkins type and 3 were Non-Hodgkin’s lymphoma. 08 cases of Hodgkin’s lymphoma

& 02 cases of Non-Hodgkin’s lymphoma were available for histopathogical examina-

tion. There were no false positive & false negative cases of lymphoma on FNAC.Out of

123
8 cases of hodgkins lymphoma 6 cases were of mixed cellularity type & 01 case of lym-

phocyte rich type & another case was of lymphocyte predomiat type.

In 03 cases of non hodgkins lymphoma one was reported as burkitts lymphoma

with starry sky pattern In the present study, number of cases of Non-Hodgkin’s lym-

phomas are too small hence accuracy of FNAC cannot be authentically arrived in our

study for non hodgkins lymphoma of lymphnodes. The other studies have reported diag-

nostic accuracy in the range of 80 –90%.44.

For Hodgkins lymphoma the diagnostic accuracy in the present study is 100

%.The study done by Das D.K. (1991), reported accuracy of 90.00%.46 .Another study

done by Kline T. S. (1978) had reported diagnostic accuracy of only 60.00% for lym-

phomas.47 T he increased accuracy of FNAC for lymphomasin the present study may be be-

cause of the typical clinical presentation and cytopathological features in all lymphoma patients.

In the present study, the overall diagnostic accuracy on cytopathological correla-

tion for metastatis to lymph nodes was 100.00%, as 7 out of 7 cases of metastatic de-

posits were diagnosed on FNAC.

There were 45 patients of metastatic carcinoma in the present study, of which 24

belonged to squamous cell carcinoma, 08 were of ductal cell carcinoma (breast carci-

noma), papillary carcinoma in 04 cases, anaplastic carcinoma in 03 cases, malignant

melanoma in 02 cases,adenocarcinoma, nasopharyngeal carcinoma ,small cell carci-

noma& testicular carcinoma in 01 case each.

Of the 45 cases of metastatic deposits on FNAC, 21(46.67%) cases had known

primary . In the study by Osama Gaber et al. , it was possible to establish primary in

86.7% whereas in the present study it was only 46.67%, this was because of limited re-

sources available in the hospital.

124
 The primary lesions in these 21 cases were as follows.In 10 cases of squamous

cell carcinoma deposits 4 patients had lung carcinoma, 2 patients had laryngeal carci-

noma and 02 patients had squamous cell carcinoma penis,1 had cervix carcioma & 1

patient had breast carcinoma. The key to diagnosis on FNAC is cohesive cell group and

common cell borders. The cells are of the large, keratinized and pleomorphic type.

In the present study 14 cases were diagnosed as metastatic squamous cell carci-

noma to the cervical lymph nodes on FNAC with unknown primary45. There were 02

false positive cases of squamous cell carcinoma reported as, chronic non specific lym-

phadenitis as the needle might have missed the particular area of malignant metastatic

cells in the lymph node.

`In the present study there were 6 cases of metastatic carcinoma to axillary nodes

from mammary origin & all were diagnosed on FNAC as infiltrating ductal carcinoma

giving an accuracy of 100 %.

In our study for the anaplastic carcinoma secondaries, primary was from esopha-

gus in one case & testes in another case.Toe was the primary site in malignant melanoma

secondary deposits.Thyroid was the primary site in papillary carcinoma metastasis to cer-

vical lymphnodes.For the small cell carcinoma metastasis lung was the primary site.

7 out of 7 cases of metastatic deposits were diagnosed on FNAC. There were no

false negative results but 02 false positive cases were seen. Thus the Sensitivity, Speci-

ficity,PPV & NPV of FNAC in diagnosing metastatic deposits were 100%, 97.4%,77.8%

& 100 % respectively.

125
 The study done by Prasad R. (1993) reported 100.00% accuracy in cases of

metastatic carcinoma to lymph nodes.40 The study done by Narang R. H. reported, 60-

89% accuracy for metastatic carcinoma.47The study done by Saha A. (1986) reported

100% accuracy for metastatic epidermoid carcinoma to cervical lymph nodes.36

Our findings also correlate with the above mentioned studies, reporting 100% ac-

curacy for metastatic carcinoma.The age in the present study for metastatic cell carci-

noma is between 35 – 65 years, disease more common in females than males by ratio of

2.21:1.The overall diagnostic accuracy in metastatic carcinoma in present study is

100.00% which is same as similar studies of Prasad R et al, Narang R. H et al ,Saha A et

al..

In the present study there were 2 cases of leukemias.In one case the diagnosis was

ALL & in another case the diagnosis was CLL.Both the leukemia patients had gener-

alised lymphadenopathy & the peripheral smear was showing ALL &CLL picture re-

spectively.ALL patient was 10 years old male & CLL patient was 41 years old .Both the

cases were confirmed by biopsy also.

In our study FNAC had a sensitivity of 100 % and a specificity of 96.97% .

Positive and negative predictive values of this method were 90.48% and 100 % respec-

tively.This is in comparision with other similar studies as shown in table.

126
 Table .No.33

Table showing Comparison of the results of the present study with other
similar studies
Sens. Spec. PPV NPV Accu.
Study n
(%) (%) (%) (%) (%)

Shamshad Ahmad et al 94.6 98.5 N/A N/A 97.6 115

Naeem Ahmad et al 95.8 100 N/A N/A 93 50

Rakshan et al 75.8 96.6 94 85.1 88 151

Our study 100 96.97 90.48 100 97.65 85

Sens: sensitivity; Spec: specificity; PPV: positive predictive value; NPV: negative predic-

tive value;Accu: accuracy; n: number of diagnostic aspirates; N/A: not available

Thus FNAC is safe, reliable, rapid and economic procedure. It is an excellent di-

agnostic tool. A negative result on FNAC does not rule out the diagnosis of tuberculous

lymphadenitis, malignancies and if clinical suspicion is strong, lymph node biopsy for

histopathological examination should be done.

127
 CONCLUSION

128
 CONCLUSION

Fine needle aspiration cytology was found to be reliable and cheapest method of

diagnosis without any significant morbidity and with good patient compliance. FNAC is

a reliable diagnostic tool in the patients having significant Lymphadenopathy.

A definite diagnosis by FNAC obviates the need for surgical excision as most of

the diseases diagnosed by FNAC itself without the need for biopsy like non-neoplas-

tic lesions are medically curable & with FNAC the lymph node lesions can be catego-

rized in to benign and malignant categories.

FNAC can be deemed as a frontline investigation with further investigations on

the basis of FNAC result. However, histopathological examination remains the most

dependable diagnostic tool.

Even if a lymph node measures <1cms it is still worthwhile to do an FNAC. In

our study even though FNAC from the 48.57% of the cervical lymph nodes measuring <

1cms were inadequate, the other 51.43% cases yielded diagnostic material.

The metastatic carcinomas, especially squamous cell carcinoma and tuberculous

lymphadenopathy can be diagnosed by FNAC with a high degree of accuracy. However

the differentiating features are not well demarcated in reactive hyperplasia .

In the present study, accuracy was of 87.19 % for tuberculous lymphadenitis

which had improved because of Zeihl-Neelsen staining for acid fast bacilli. Therefore it

must be stressed that when the fine needle aspirate appears purulent or when tuberculosis

is clinically suspected, specimen should be stained for acid fast bacilli. It improves diag-

129
nostic capability of fine needle aspiration cytology. In a granulomatous lymphadenopa-

thy a careful search for abnormal cells has to be done before wrongly diagnosing tubercu-

losis.

In the present study, overall diagnostic accuracy was 100.00% for metastatic car-

cinoma . In cases of metastasis of unknown origin to cervical and axillary lymphadenopa-

thy. FNAC is useful adjunct to diagnostic procedures and can point to primary depending

upon the cell type. In the present study FNAC could detect primary in 46.67% cases.

Open biopsy for histological confirmation is gold standard, but it has its limita-

tions because it distorts the surgical planes and may increase risk of induction of tumour

spread especially in metastatic upper and middle cervical lymph nodes which are poten-

tially curable with radiotherapy or node dissection. FNAC is preferable and if it is posi-

tive, surgeon can proceed to treat the neck without excisional biopsy of the enlarged

lymph nodes.

Early diagnosis of lymphoma by FNA especially Hodgkin’s disease, may contrib-

ute to cure of the disease . There is significant limitation in the assessment of low grade

Non-Hodgkin’s lymphoma in cases of substantial non malignant component but FNAC

can assess correctly high grade Non Hodgkin’s lymphoma.

The most difficult areas in diagnosis of lymph node disease by FNAC is differen-

tiating low grade lymphoma from reactive hyperplasia. Though limitations and pitfalls

exist in the diagnosis of lymphoma by FNA, but it still plays a major role in the primary

diagnosis & staging and in recurrence of the disease.

130
 Lack of tissue architecture can be overcome on FNAC samples by subjecting

them to dual parameter flow cytometry, T-cell, B-cell tumour markers and immunocyto-

chemistry analysis.

Finally we conclude that, FNAC is simple ,safe, self reliable, cost effective and

less time consuming out patient procedure which can be used as an initial diagnostic tool

for lymphadenopathies but the limitation of the procedure should be kept in mind. If

FNAC is negative it does not rule out the disease and should be followed by open biopsy

for histopathological confirmation.

131
 SUMMARY

132
 SUMMARY

. The clinical material of the present study includes details of 400 cases of lym-

phadenopathy who attended to the S.V.S hospital & college,Mahabubnagar over a pe-

riod of 2 years between August 2009 to July 2011 . A brief introduction and histori-

cal review of the lymphadenopathy has been presented.

A detailed review of relevant literature of anatomy,embryology,physiology,

pathology have been discussed. An attempt has been made to compare and discuss the

findings in the present series with previously reported literature regarding incidence

and accuracy of various lymphnodal lesions . In present study out of 400 cases of fine

needle aspiration cytology only 85 cases were available for biopsy. The diagnostic efficacy

of fine needle aspiration cytology was compared with that of histopathology.

In the present study following results were obtained :

 In present study out of 400 cases of fine needle aspiration cytology only 85 cases

were available for biopsy. 28 (7%) of the cases were non diagnostic.

 There were 308 non-neoplastic lesions and 64 neoplastic lesions.

 45.75% cases were confirmed as tuberculous lymphadenitis ,22.75% as chronic

non-specific lymphadenitis 5.5% as non tuberculous granulomatous lymphadeni-

tis, 3% as acute suppurative lymphadenitis,11.25% as malignant secondaries,3.8%

as lymphomas and as leukemias in the remaining 0.05 % of the cases.

 Majority of the patients (63.75%) were between 11-40 years age group & there

were 188 males and 212 females with a female predilection ,male to female ratio

133
 being 1:1.13 .

 Cervical lymph nodes were the most commonly affected group of lymph nodes

(59.75%). Among the cervical lymph nodes measuring < 1cms 48.57% cases

were inadequate, but the other 51.43% cases yielded diagnostic material .

 Tuberculous lymphadenopathy constituted 45.75% of the total cases being the

most common diagnosis & presenting with cervical Lymph nodes (64.48%) fol-

lowed by generalised lymphadenopathy (7.5%)

 Cytologically epithelioid granuloma with necrosis was seen in 55.19% of cases

followed by epithelioid cell granuloma in 22.95% of cases and necrosis in

21.86% cases..

 The accuracy was 87.19% on FNAC with histopatholgical correlation for tuber-

culous lymphadenitis which had improved because of ZN staining.

 Overall AFB positivity was seen in 31.14% of tuberculous cases, predominantly

seen in necrosis alone pattern(79%),followed by granulomas with necrosis pat-

tern in 14% of total AFB positive cases.

 Chronic non specific lymphadenitis had high number of false positive cases as the

patients with tuberculous lymphadenopathy and lymphomas may have same poly-

morphous picture on aspirates as reactive hyperplasia in absence of Langhan’s

cells / epitheloid clusters and Reed-sternberg cells. The diagnostic accuracy was

85.71% for chronic non specific lymphadenitis.

 The Sensitivity, Specificity,PPV & NPV of FNAC in diagnosing metastatic de-

posits were 100%, 97.4%,77.8% & 100 % respectively.

134
  In cases of metastasis of unknown origin to cervical and axillary lymphadenopa-

thy FNAC is useful adjunct to diagnostic procedures and can point to primary de-

pending upon the cell type. Of the 45 cases of metastatic deposits on FNAC,

21(46.67%) cases had known primary in the present study.

 There were 17 cases of lymphomas out of which 14 were of hodgkins type and 3

were Non-Hodgkin’s lymphoma with the diagnostic accuracy of 100 %.

 Mixed cellularity was the predominant subtype in hodgkins lymphoma. In 02

cases of non hodgkins lymphoma one was burkitts lymphoma & other case was

of low grade with diffuse pattern .

 There were 2 cases of leukemias one case was ALL & the other one was CLL.

 In the present study the sensitivity for various lesions are as below.

 Tuberculosis ⎯ 87.2%

 Chronic Non-Specific Lymphadenitis ⎯ 85.71%

 Malignant secondaries ⎯ 100%

 Lymphomas ⎯ 100%

 The overall diagnostic accuracy of FNAC was 89.41%.

 In our study FNAC had a sensitivity of 100 % and a specificity of 96.97% .

Positive and negative predictive values of this method were 90.48% and 100 %

respectively.

135
 REFERENCES

136
 BIBLIOGRAPHY:

(1)Role of Fine needle aspiration cytology in thediagnosis of Cervical lymphadenopathy

Md. Arif Hossain Bhuyan1, Md. Abu etal Bangladesh J of Otorhinolaryngology 2008;

14(2) : 63-65

(2) Pattern of Lymphadenopathy on Fine Needle Aspiration Cytology in Jammu Ruchi

Khajuria, K. C. Goswami, K. Singh, V. K. Dubey*JK SCIENCE Vol. 8 No. 3, July-Sep-

tember 2006

(3) Chu E.W., Hoye R.C. The clinician and the cytopathologist evaluate fine needle aspi-

ration cytology. Acta cytological.,1473; 21:413-17.

(4) Skoog L, Tani E. Lymphnodes. In: Gray W, Mckee GT, ed.Diagnostic Cytpathology

2nd ed. New York: Churchill Livingstone;2003.p.501-36.

(5) . Oertel J, Oertel B, Kastner M. The value of immunocytochemical staining of lymph

node aspirates in diagnostic cytology. Br JHaematol 1988;70:307-16.

(6). Ravinsky E, Morales C, Kutryk E, Chrobak A, Paraskevas T.Cytodiagnosis of lym-

phoid proliferations by fine needle aspiration on biopsy: Adjunctive value of flow cytom-

etry. Acta Cytol 1999;43(6):1070-78.

(7) Dilip K. Das - value and limitations of fine needle aspiration cytology in diagnosis

and classification lymphoma- Diagn. Cytopiathol.1992; 21:240-249)

137
(8)Vanisri HR, Nandini NM, Sunila R. Fine-needle aspiration cytology findings in human

immunodeficiency virus lymphadenopathy. Indian J Pathol Microbiol 2008;51:481-4

(9) Shobhana A, Guha SK, Mitra K, Dasgupta A, Negi DK, Hazra SC. People living with

HIV infection/AIDS: A study on lymphnode FNAC and CD4 count. Indian J Med Micro-

biol 2002;2:99-101

(10) ). Steel BL, Schwartz MR, Ramzy I. Fine needle aspiration biopsy in the diagnosis

of lymphadenopathy in 1103 patients. Role, limitations and analysis of diagnostic pitfalls.

Acta Cytol 1995;39:76-81. (s)

(11). Ustun M, Risberg B, Davidson B, Berner A. Cystic Change in metastatic lymph

Nodes: A common diagnostic pitfall in Fine-Needle Aspiration Cytology. Diagn Cy-

topathol 2002;27: 387-392. (s)

(12). Ajmal Farooq, Imran Ameen. Comparison of FNAC vs excision biopsy for sus-

pected tuberculous cervical lymphadenopathy. Annals King Edward med coll Sep

2003; 9(3):216-8).

(13). Shas A, Webber C, Marti J. Fine needle aspiration in the diagnosis of cervical lym-

phadenopathy. Am J Surg 1986;12(4):420-3.

(14)Malakar D, Jajoo ILN, Swaruup K, Gupta OP, JainAP, Poflee VW.A clinical evalua-

tion of fine needle aspiration cytology in thediagnosis of lymphadenopathy. Ind J Tub

1991;38:17.

(15).Hsu C, Leung BSY, Lau SK, Sham JST, Choy D, Engzell U. Efficacy of fine-needle

aspiration and sampling of lymph nodes in 1,484 chinese patients. Diagn Cytopathol.

2006;6(3):154-9.

138
(16) Lee RE, Kalaitis J, Kalis O, et al.: Lymph node examination by fine needle aspira-

tion in patients with known or suspected malignancy. Acta Cytol 1987;31:563-572.

(17) Dong HY, Harris NL, Preffer FI, Pitman MB: Fine-needle aspiration biopsy in the

diagnosis and classification of primary and recurrent lymphoma: a retrospective analysis

of the utility of cytomorphology and flow cytometry. Mod Pathol 2001;14:472-481.

(18) Kardos TF, Vinson JH, Behm FG, et al.: Hodgkin’s disease:diagnosis by fine needle

aspiration biopsy. Analysis of cytologic criteria from a selected series. Am J Clin Pathol

1986;86:286-291.

(19) Fulciniti F, Vetrani A, Zeppa P, et al.: Hodgkin’s disease:diagnostic accuracy of fine

needle aspiration; A report based on 62 consecutive cases. Cytopathology 1994;5:226-

233.

(20) 13. Iseman MD. Extrapulmonary tuberculosis in adults. In: A clinician’s guide to tu-

berculosis. Philadelphia: Lipincott Williams and Wilkins; 2000. p. 145-97.

(21). Mohan Harsh. Chapter 13. The lymphoid system, Text book of pathology. 4th

ed. New Delhi : Jaypee brothers medical publishers ; 2000. 407-30.

(22) Koss' Diagnostic Cytology and Its Histopathologic Bases, 5th Edition,chapter

31(1186 -1229)

(23). Henry K, Symmers W. St C. Volume 7 Thymus, lymph nodes, spleen and

lymphatics, Symmers W. St. C. Systemic pathology. 3rd ed. New York :

Churchill Living stone ; 1992. 141-543.

(24). Chan J. K. C. Chapter 21. Tumors of lymphoreticular system, Fletcher Christopher.

Diagnostic histopathology of tumors. 2nd ed. London : Churchill Livingstone ; 2000.

1099-317.

139
(25). Marchant Gerald, Hamlin Iris, Lennert K, Rilke F, Stansfeld AG, Van Unnik

J.A.M. Classification of Non Hodgkin’s lymphomas.The Lancet 1974 Aug;405-9.

(26)Pattent Bradly. Development of circulatory system. Chapter-19, in Human Embryol-

ogy, 2nd Edition, New York: McGraw Hill; 1953.608.

26..27 Williams, Peter L et al. The lymphatic system. Chapter 393, in: Grey’s Anatomy.

37th Edition, England; Churchill Livingstone; 1989. 821.

2728. Sahana SN. Lymphatic of head in neck. Chapter-1, in Sahana’s human anatomy

(Descriptive and Applied), Vol. II, 1st Edition. Calcutta:Ankur Publication: 1994. 179.

2829. Ramzy I. Lymph Nodes. In: Clinical cytopathology and aspiration biopsy.

fundamental principles and practice. USA: Appleton and Lange; 1990. p. 313-30.

2930. Heerde PV, Miliauskar J, Field A. Lymphnodes. In: Orell SR, Sterrette GF,

Whitaker D, editors. Fine needle aspiration cytology. 4thed. New Delhi:Churchill Living-

stone; 2005. p. 83-124.(CELLS)

2931. Schmid Geert, Schoenbein, John Ross Jr. Structure function relation in peripheral

circulation. Chapter-6 in: Best & Taylor’s 129 Physiological basis of medical practices.

12th Edition, West John B; New Delhi: 1996. 116.

3032. Ferrer Robert. Lymphadenopathy differential diagnosis and evaluation cover story.

American Family physician 1998 October ; 58 (6) : 1-10

3133. Ko YH, Lee JD. Fine needle aspiration cytology in lupus lymphadenopathy: A case

report. Acta Cytol 36:748-751, 1992.

32.34Meyer L, Gibbons D, Ashfaq R, et al. Fine-needle aspiration findings in Castle-

man's disease. Diagn Cytopathol 21:57-60, 1999.

140
3335.Hidvegi DF, Sorensen K, Lawrence JB, et al. Castleman's disease: Cytomorpho-

logic and cytochemical features of a case. Acta Cytol 26:243-246, 1982.

34.36 Kung ITM, Ng W-F, Yuen RWS, Chan JKC. Kikuchi's histiocytic necrotizing lym-

phadenitis. Diagnosis by fine needle aspiration. Acta Cytol 34:323-328, 1990.

3537.Tsang WYW, Chan JKC. Fine-needle aspiration cytologic diagnosis of Kikuchi's

lymphadenitis. Am J Clin Pathol 102:454-458, 1994.

36. 38Hui PK, Chan JKC, Ng CS, et al Lymphadenopathy of Kimura's disease. Am J

Surg Pathol 13:177-186, 1989.

3639. Asano S, Muramatsu T, Kanno H, Wakasa H. Dermatopathic lymphadenopathy.

Electron microscopic, enzyme-histochemical and immunohistochemical study. Acta

Pathol 37:887-900, 1987.

38.40Kardos TF, Kornstein MJ, Frable WJ. Cytology and immunocytology of infectious

mononucleosis in fine needle aspirations of lymph nodes. Acta Cytol 32:722-726, 1988.

39.41Stanley MW, Steeper TA, Horwitz CA, et al. Fine needle aspiration of lymph nodes

in patients with acute infectious mononucleosis. Diagn Cytopathol 6:323-329, 1990A.

4042.Oertel J, Oertel B, Lobeck H, Huhn D. Immunocytochemical analysis of lymph

node aspirates in patients with human immunodeficiency virus infection. J Clin Pathol

43:844-846, 1990.

141
41.43Stanley MW, Horwitz CA, Burton LG, Weisser JA. Negative images of bacilli and

mycobacterial infection: A study of fine-needle aspiration smears from lymph nodes in

patients with AIDS. Diagn Cytopathol 6:118-121, 1990B.

37.44 Das DK, Pant JN, Chachra KL, Murthy NS, Satyanarayan L,
Thankamma TC, et al. Tuberculous lymphadenitis: Correlation of cellular
components and necrosis in lymphnode aspirate with AFB positivity and
bacillary count. Indian J Pathol Microbiol 1990;33(1):1-10.

43.45Shabb N, Katz RL, Ordonez N, et al. Fine-needle aspiration evaluation of lympho-

proliferative lesions in human immunodeficiency virus-positive patients: A multiparame-

ter approach. Cancer 67:1008-1018, 1991.

42.46Gupta SK, Kumar B, Kaur S. Aspiration cytology in lymph nodes in leprosy. Int J

Lepr Other Mycobact Dis 49:9, 1981.

44.47Ro JY, Lee SS, Ayala AG. Advantage of Fontana-Masson stain in capsule-deficient

cryptococcal infection. Arch Pathol Lab Med 111:53-57, 1987.

45.48Argyle JC, Schumann GB, Kjeldsberg CR, Athens JW. Identification of a toxo-

plasma cyst by fine-needle aspiration. Am J Clin Pathol 80:256-258, 1983.

46.49Pettinato G, Manivel JC, d'Amore ES, Petrella G. Fine needle aspiration cytology

and immunocytochemical characterization of the histiocytes in sinus histiocytosis with

massive lymphadenopathy (Rosai-Dorfman syndrome). Acta Cytol 34:771-777, 1990.

4750. Deshpande AH, Nayak S, Munshi MM. Cytology of sinus histiocytosis with mas-

sive lymphadenopathy (Rosai-Dorfman disease). Diagn Cytopathol 22: 181-185, 2000.

48.51Koss LG, Woyke S, Olszewski W. Aspiration Biopsy. Cytologic Interpretation and

Histologic Bases, 2nd ed. New York, Igaku-Shoin Medical Publishers, Inc, 1992.

142
49.52Kakkar S, Kapila K, Verma K. Langerhans cell histiocytosis in lymph nodes: Cyto-

morphologic diagnosis and pitfalls. Acta Cytol 45:327-332, 2001.

5053.Dodd LG, Sneige N, Reece GP, Fornage B. Fine-needle aspiration cytology of sili-

cone granulomas in the augmented breast. Diagn Cytopathol 9:498-502, 1993.

51.54Gattuso P, Castelli MJ, Peng Y, Reddy VB. Posttransplant lymphoproliferative dis-

orders: A fine-needle aspiration biopsy study. Diagn Cytopathol 16: 392-395, 1997.

52. 55Dusenbery D, Nalesnik MA, Locker J, Swerdlow SH. Cytologic features of post

transplant lymphoproliferative disorder. Diagn Cytopathol 16:489-496, 1997.

53.56Frable WJ, Kardos TF. Fine needle aspiration biopsy: Applications in the diagnosis

of lymphoproliferative diseases. Am J Surg Pathol 12 (Suppl 1):62-72, 1988.

5418.Kardos TF, Vinson JH, Behm FG, et al. Hodgkin lymphoma: Diagnosis by fine-

needle aspiration biopsy. Analysis of cytologic criteria from a selected series. Am J Clin

Pathol 86:286-291,1986.

55.57 Harris NL, Jaffe ES, Stein H, et al. A revised European-American classification of

lymphoid neoplasms: A proposal from the International Lymphoma Study Group. Blood

84:1361-1392, 1994.

56.58 Jaffe ES, Harris NC, Diebold J, Muller-Hermelink H-K. World Health Organiza-

tion classification of neoplastic diseases of the hematopoietic and lymphoid tissues. A

progress report. Am J Clin Pathol 111(Suppl 1):S8-S12, 1999.

143
57.59 Handa U, Mohan H, Bal A. Role of fine needle aspiration cytology in evaluation of

paediatric lymphdenoapthy. Cytopathol 2003;14:66-9.

5860.Wojcik EM, Katz RL, Fanning TV, et al. Diagnosis of mantle cell lymphoma on tis-

sue acquired by fine needle aspiration in conjunction with immunocytochemistry and cy-

tokinetic studies. Possibilities and limitations. Acta Cytol 39:909-915, 1995.

59.61 Isaacson PG. Lymphomas of mucosa-associated lymphoid tissue (MALT).

Histopathology 16:617-619, 1990.

60.62 Stastny JF, Almeida MM, Wakely PE Jr, et al. Fine-needle aspiration biopsy and

imprint cytology of small non-cleaved cell (Burkitt's) lymphoma. Diagn Cytopathol

12:201-207, 1995.

6163. Bangerter M, Hildbrand A, Waidmann O, Griesshammer M. Fine needle aspiration

cytology in extramedullary plasmacytoma. Acta Cytol 44:287-291, 2000.

62 64Young NA, Al-Saleem T. Diagnosis of lymphoma by fine-needle aspiration cytol-

ogy using the revised European-American classification of lymphoid neoplasms. Cancer

87:325-345, 1999.

63.65 Jacobs JC, Katz RL, Shabb N, et al. Fine-needle aspiration of lymphoblastic lym-

phoma: A multiparameter diagnostic approach. Acta Cytol 36:887-894, 1992.

6466.Das DK, Gupta SK. Fine needle aspiration cytodiagnosis of Hodgkin lymphoma

and its subtypes. II. Subtyping by differential cell counts. Acta Cytol 34: 337-341, 1990.

P.1226

144
6567.Das DK, Gupta SK, Datta BN, Sharma SC. Fine needle aspiration cytodiagnosis of

Hodgkin lymphoma and its subtypes. I. Scope and limitations. Acta Cytol 34:329-336,

1990.

66.68Edmund s.cibas & Barbara s.ducatman .Cytology: Diagnostic Principles and Clini-

cal

Correlates,3rd edition,2008,319-357.(352)

6769. Lau SK, Luthringer DJ, Eisen RN. Thyroid transcription factor-1: A review. Appl

Immunohistochem Mol Morphol 10:97-102, 2002.

6870.Shin HJC, Caraway NP. Fine needle aspiration biopsy of metastatic small cell carci-

noma from extra-pulmonary sites. Diagn Cytopathol 19: 177-181,1998.

6971. Perry MD, Gore M, Seigler HF, Johnston WW: Fine needle aspiration biopsy of

metastatic melanoma. A morphologic analysis of 174 cases. Acta Cytol 1986;30:385-396.

70.72Hales M, Bottles K, Miller T, et al.: Diagnosis of Kaposi’s sarcoma by fine-needle

aspiration biopsy. Am J Clin Pathol 1987;88:20-25.

71.73 Wright CA, Nayler SJ, Leiman G: Cytopathology of follicular dendritic cell tu-

mours. Diagn Cytopathol 1997;17:138-142.

72.74 Caraway NP, Fanning CV, Amato RJ, Sneige N. Fine-needle aspiration cytology of

seminoma: A review of 16 cases. Diagn Cytopathol 12:327-333, 1995.

7375.Akhtar M, Ali A, Sackey K, Jackson D, Bakry M. Fine-needle aspiration biopsy di-

agnosis of endodermal sinus tumor: Histologic and ultrastructural correlations. Diagn Cy-

topathol 6:184-192, 1990.

145
74. 76Nason RW, Abdulrauf BM, Stranc MF: The anatomy of the accessory nerve and

cervical lymph node biopsy. Am J Surg 2000;180(3):241-243.

75. 77Landgren O, Porwit MacDonald A, et al.: A prospective comparison of fine-needle

aspiration cytology and histopathology in the diagnosis and classification of lymphomas.

Hematol J 2004;5(1):69-76.

Chu EW, Hoye RC: The clinician and the cytopathologist evaluate FNAC. Acta Cytol

1973; 17: 413-417

Shaha A, Webber C, Marti J. Fine needle aspiration in the diagnosis of cervical lym-

phadenopathy. Am. J. Surg.1986; 152: 420-3.

Lau SK, Wei WI, Hsu C, Engzell UCG. Efficacy of fine needle aspiration cytology in

the diagnosis of tuberculous cervical lymphadenopathy. The Journal of Laryngology and

Otology. 1990; 104: 24-27.

Maria Rosaria Cardillo Fine-needle aspiration cytology of superficial lymph node,Diagn.

Cytopathol ; 1989. , 5(2): 166–173,

Sarda Ak, Bal S, Singh MK, Kapur MM. Fine needle aspiration cytology as a prelimi-

nary diagnostic procedure for asymptomatic cervical lymphadenopathy. J. Assoc. Physi-

cians India. 1990; 38(3): 203-5.

Das DK, Pant JN, Chachra KL, Murthy NS, Satyanarayan L, Thankamma TC, Kakkar

PK.Tuberculous lymphadenitis: correlation of cellular components and necrosis in

lymph-node aspirate with A.F.B. positivity and bacillary count. Indian J Pathol Micro-

biol. 1990 Jan;33(1):1-10

146
Chih Hsu., Betty S. Y. Leung., Sai-Kit Lau., Jonathan S. T. Sham.,., Damon Choy, Ulf

Engzell. Efficacy of fine-needle aspiration and sampling of lymph nodes in 1,484 chinese

patients; Diagn. Cytopathol ; 1990;6: 154–159.

Das DK, Gupta SK, Datta BN, Sharma SC. FNA cytodiagnosis of Non-Hodgkin’s lym-

phoma and its subtyping, under working formulation of 175 cases. Diagn. Cytopathol.

1991; 7: 489-98.

Shapiro AL, Pincus RL. Fine needle aspiration of diffuse cervical lymphadenopathy in

patients with acquired immunodeficiency syndrome.Otolaryngol Head Neck Surg. 1991;

105: 419-21.

Arun Kumar Gupta, Mohini Nayar. Reliability and limitations of Fine needle aspiration.

cytology of lymphadenopathies. An analysis of 1,201 cases. Acta Cytologica 1991; 35:

777-783

Gupta AK, Nayar M, Chandra M. Reliability and limitations of fine needle aspiration cy-

tology of lymphadenopathies: An analysis of 1,261 cases. Acta Cytologica. 1991; 35(6):

777-83.

Alan et. al. Cheng, Bren dorman; Fine needle aspiration cytology: the Auckland experi-

ence ANZ journal of surgery; 1992 ;62( 5): 368–372

Prasad R, Garg SK, Mukerji PK, Agarwal PK. Role of fine needle aspiration cytology in

the diagnosis of lymphadenopathy. Indian J. Chest.Dis. Allied Sci. 1993; 3591) 27-9.

147
Silvana Pilotti, Sivand Di Palma. Diagnositc assessment of enlarged superficial lymph

nodes by FNAC. Acta cytologica 1993; 37: 6: 853-865.

Ajita Avinash Pandit , Pushpa Hiranand Khilnani, Arunakumari S. Prayag. Tuberculous

lymphadenitis: Extended cytomorphologic features .Diagn Cytopathol 1995;12:23-27.

P. G. Gamba ,A. Messineo , L. M. Antoniello , P. Boccato , S. Blandamura , G. Cecchetto

, P. Dall'Igna , M. Guglielmi . A simple exam to screen superficial masses: Fine-needle

aspiration cytology; Medical and Pediatric Oncology ,Feb 1995 24( 2,): 97–99,

Steel BL, Schwartz MR, Ramzy I. Fine needle aspiration biopsy in the diagnosis of lym-

phadenopathy in 1,103 patients. Role, limitations and analysis of diagnostic pitfalls.Acta

Cytol. 1995 Jan-Feb;39(1):76-81.

C.V. Raghuveer, Muktha R. Pai. Role of FNAC in disorders of lymph node: Journal of

cytology 1996; 13: 45-49. Geoffrey C. Basler, Darrell J. Fader, Alan Yahanda, Ver-

non K. Sondak and Timothy M. Johnson .The utility of fine needle aspiration in the

diagnosis of melanoma metastatic to lymph nodes. .Journal of the American Academy of

Dermatology ,March 1997;36( 3): 403-408

Mostafa MG , Chiemchanya S, Srivannaboon S, Nitiyanant P Accuracy of fine needle

aspiration cytology in the evaluation of peripheral lymphadenopathy,J med asoc

thai ,1997 Sep;80 Suppl 1:S155-61.

T W Shek, S T Yuen, I S Luk, M P Wong ,Germ cell tumour as a diagnostic pitfall of

metastatic carcinoma. J Clin Pathol 1996;49:223-225

148
Geoffrey C. Basler, Darrell J. Fader, Alan Yahanda, Vernon K. Sondak and Tim-

othy M. Johnson .The utility of fine needle aspiration in the diagnosis of melanoma

metastatic to lymph nodes. .Journal of the American Academy of Dermatology ,March

1997;36( 3): 403-408

Lee DW, Jin SY, Kim DW. Diagnostic usefulness of fine needle aspiration cytology on

lymphadenopathy: An analysis of 1,216 cases.Acta. Cytol. 1998; 42: 523.

C J Stewart,J A Duncan, M Farquharson, J Richmond,Fine needle aspiration cytology di-

agnosis of malignant lymphoma and reactive lymphoid hyperplasia. J Clin Pathol

1998;51:197-203 doi:10.1136/jcp.51.3.197

Reyes CV, Thompson KS, Jensen JD, Choudhary AM. Mestastasis of unknown orogin:

The role of fine-needle aspiration cytology. Diagn.Cytopathol. 1998; 18(5): 319-22.

Kim hs, Kim ds, Oh yl, Ko yh, Ree h j. Diagnostic usefulness and limitation of fine

needle aspiration cytology of lymph node: Analysis of 176 cases confirmed by biop-

sy.korean j cytopathol 10(1):35-42 jun 1999

Lioe, T. F., Elliott, H., Allen, D. C. and Spence, R. A. J. (1999), The role of fine needle

aspiration cytology (FNAC) in the investigation of superficial lymphadenopathy; uses

and limitations of the technique. Cytopathology, 10: 291–297. doi: 10.1046/j.1365-

2303.1999.00183.x

Nasuti, J. F., Yu, G., Boudousquie, A. and Gupta, P. Diagnostic value of lymph node fine

needle aspiration cytology: an institutional experience of 387 cases observed over a 5-

year period. Cytopathology, 11: 18–31. doi: 10.1046/j.1365-2303.2000.00208.x

149
Haque MA, Talukder SI. Evaluation of fine needle aspiration cytology FNAC of lymph

node in mymensingh. Memensingh Med. J. 2003; 12(1) 33-5.

Chhieng DC, Cohen J-M, Cangiarella JF. Cytology and immunophenotyping of low- and

intermediate-grade B-cell non-Hodgkin's lymphomas with a predominant small-cell com-

ponent: A study of 56 cases. Diagn Cytopathol 24:90-97, 2001.

Shabnam Jaffer ., Maureen Zakowski Fine-needle aspiration biopsy of axillary lymph

nodes Diagn. Cytopathol. 2002;26:69–74; DOI 10.1002/dc.10051 © 2002 Wiley-Liss,

Inc

M. Pradeep Reddy, Nekhil Moorchung and Arun Chaudhary ,Clinico-pathological pro-

file of pediatric lymphadenopathy Indian. J. of Pediatrics,DEC 2002; 69(12): 1047-1051

Ajmal Farooq, Imran Ameen. Comparison of FNAC vs excision biopsy for suspected tu-

berculous cervical lymphadenopathy. Annals King Edward med coll Sep 2003; 9(3):216-

8).

N. Bagwan, S. V. Kane & R. F. Chinoy : Cytologic Evaluation of the Enlarged Neck

Node: FNAC Utility in Metastatic Neck Disease . The Internet Journal of Pathology.

2007 Volume 6 Number 2

Chau, M T Kelleher, D Cunningham, A R Norman, A Wotherspoon, P Trott, P Rhys-

Evans, G Querci Della Rovere, G Brown, M Allen, J S Waters, S Haque, T Murray and

L Bishop Rapid access multidisciplinary lymph node diagnostic clinic: analysis of 550

patients; British Journal of Cancer (2003) 88, 354–361.

150
Kristian T. Schafernak , Larry F. Kluskens., Reshma Ariga , Vijaya B. Reddy , Paolo

Gattuso Fine-needle aspiration of superficial and deeply seated lymph nodes on patients

with and without a history of malignancy: Review of 439 cases; Diagn. Cytopathol.

2003;29(6):315–319

Vittorio Altomare, Gabriella Guerriero, Rita Carino, Cleonice Battista, Angelo Primav-

era, Annamaria Altomare, Donata Vaccaro, Alessandro Esposito, Anna Maria Ferri and

Carla Rabitti, Axillary lymph node echo-guided fine-needle aspiration cytology enables

breast cancer patients to avoid a sentinel lymph node biopsy. preliminary experience and

a review of the literature Surgery Today ,Dec 2006 ; 37( 9), 735-739

V koo , TF Lioe ,RAJ Spence etal fine needle aspiration cytology in the diagnosis of

granulomatous lymphadenitis,Ulster Med J. 2006 January; 75(1): 59–64.

D. Agarwal, P. Bansal, B. Rani, S. Sharma, S. Chawla, V. Bharat & S. Sharma : Evalua-

tion of etiology of lymphadenopathy in different age groups using Fine Needle Aspiration

Cytology: A retrospective study. The Internet Journal of Pathology. 2010 Volume 10

Number 2

Abdul bari, Ahsal-ul-wadood, khawaja farooq qasim , jamil ahmed mirzkhawaja usman

masud, fine needle aspiration cytology:evaluation in the diagnosis of lymphadenopathy in

children ;professional med j june 2007;14(2):237-240

Vanisri HR, Nandini NM, Sunila R. Fine-needle aspiration cytology findings in human

immunodeficiency virus lymphadenopathy. Indian J Pathol Microbiol 2008;51:481-4

151
Konar K, Ghosh S, Ghosh T, Bhattacharya S, Sanyal S. Pitfalls in the cytodiagnosis of

metastatic squamous cell carcinoma in the head and neck: A retrospective study. J Cytol

2008;25:119-22

J.-L. Roh, Y.-W. Lee and J.-M. Kim Clinical utility of fine-needle aspiration for diagno-

sis of head and neck lymphoma European Journal of Surgical Oncology (EJSO), Volume

34, Issue 7, July 2008, Pages 817-821

DISCUSSION BIBLIOGRAPHY:

16Guidelines of the Papanicolaou Society of Cytopathology for fine-needle aspiration

procedure and reporting.The Papanicolaou Society of Cytopathology Task Force on Stan-

dards of Practice. Diagn Cytopathol 1997;17(4):239-47.

68. Jha B C, Dass A, Nagarkar NM, Gupta R, Sighal S. Cervical tuberculous lym-

phadenopathy: Changing clinical patterns and concepts in management. Post-graduate Med.

J 2001; March, 77(905):185-7.

69. Jindal N,Devi B, Aggarwal A. Mycobacterial cervical lymphadenopathy in child-

hood. Post-graduate Med. J 2002; 81:182-3.

70 .Nataraj G, Kurup S, Pandit A, Mehta P. Correlation of FNAC, smear and culture in

Tubercular lymphadenitis: a prospective study. Indian J Pathol.2001;82: 96-7.

71.Arora B, Arora DR. FNAC in diagnosis of tubercular lymphadentis. Indian J Medical

Research 1990 May; 91: 189-92.

72. Kim L H, Peh SC, Chen KS, Chai SP. P attern of lymph node pathology in a private

laboratory. Malays J Pathol 1999 Dec; 21(2):87-93.

73.Lau SK et la. Combined use of FNAC and tuberculin test in diagnosis of cervical TB

152
lymphadenitis. Arch Otolaryngol, Head and Neck Surgery 1991;117: 89-90.

74.Aruna D, Mohapatro S. Correlation of FNAC with histopathological study in pe-

ripheral lymph node lesions. Indian J Pathol Microbiol 1999;30(2):96-98.

75.Bedi RS et al. Clinicopathological study of superficial lymphadenopathy in

Northern India. Indian J of Tuberculosis 1987; 34: 189-91.

76.Ammari FF, Bani Hani AH, Gharibeh KI. Tuberculosis of lymph glands of neck: a

limited role for surgery. Otolaryngol Head Neck Surgery 2003 Apr;128(4):576-80.

77.Dworski I. Tuberculosis of cervical lymph nodes. Plucne Bolesti 1989 Jul-Dec;41(3-

4): 169-71.

78. Dandapat MC, Mishra BM, Dash SP, Kar PK. Peripheral lymph node tuberculosis: a

review of 80 cases. Br J Surg 1990 Aug; 77(8): 9 11-2

3. Prasad RR, Narasimhan R, Sankran V, Veliath AJ. Fine needle aspiration cytology in

the diagnosis of superficial lymphadenopathy: an analysis of 2418 cases. Diagno Cytol

1993 ; 15 : 382-86.

4. Paul PC, Goswami BK, Chakrabarty S, Giri A, Pramanik R.Fine needle aspiration cy-

tology of lymph nodes-An institutional study of 1448 cases over a five year period.J Cy-

tology 2004 ; 21 : 187-90.

7. Gupta AK, Nayar M, Chandra M. Critical appraisal of fine needle aspiration cytology

in tuberculosis. Acta Cytol 1992 ; 36 : 391-94.

8. Bhaskran CS, Kumar GH, Sreenivas M, Rajni K, Rao G,Aruna CA. Fine needle aspira-

tion cytology review of 1731 cases. Ind J Pathol Microbiol 1990 ; 33 : 387-97.

9. Kline TS, Khannan V, Line IK. Lymphadenopathy and aspiration biopsy cytology re-

view of 376 superficial lymph nodes. Cancer 1984 ; 54 : 1076-81.

153
39. Locham, Sanjiv Goyal. Lymphadenopathy in children – role of FNAC. Journal of Cy-

tology 2002; 19(4): 183-186.

40. Leon Van De schoot, Daniel C. Aronson. The role of FNAC in children with persis -

tent or suspicions lymphadenopathy. Journal of pediatric surgery. 2001; 36: 1: 7-11.

41. Hooper AA. Tuberculous peripheral lymphadenitis. Br J Surg 1972; 59: 353-59.

5. M. Pradeep Reddy, Nekhil Moor Chung. Clinico pathological profile of pediatric

lymphadenopathy. I J P 2002; 69: 1047-1051.

2. Karuna Rameshkumar. Tuberculous lymphadenitis in children. JAPI 1999; Vol 47,

No.10: 976-979

18. Oliver S. Soldes, John G. Younger. Predicators of malignancy in childhood peripheral

lymphadenoapthy. Journal of pediatric surgery; 1999; 34: 10: 1447-1452

44. Finger M, Perchick A, Burstein DE. FNA biopsy diagnosis of tuberculous lym-

phadenitis in patients with and without the AIDS. Acta Cytol 1991; 35: 325-32.

5.M. Pradeep Reddy, Nekhil Moor Chung. Clinico pathological profile of pediatric lym-

phadenopathy. I J P 2002; 69: 1047-1051.

Shamshad Ahmad, Shakeel Akhtar , Kafil Akhtar , Shano Naseem , Tariq Mansoor

.study of fine needle aspiration cytology in lymphadenopathy with special reference to

acid-fast staining in cases of tuberculosis. JK science 2005;7(1):1-4.

Comparision of fine needle aspiration cytology (FNAC) and excision biopsy in the diag-

nosis of cervical lymphadeopathy.Naeem ahmed,Saima israr,Muhammad sajjad

ashraf,pakisthan journal of surgery,vol.25,issue 2,2009.

13. Narang R, Pradhan S, Singh R, Chaturvedi S. Place of fine needle aspiration cytology

in the diagnosis of lymphadenopathy. Ind J Tub 1990;37(1):29-31.

154
11.AlAlwan N, AlHashimi A, Salman M, AlAttar E.Fine needle aspiration cytology ver-

sus histopathology in diagnosing lymph node lesions. Eastern Mediterranean health Jour-

nal 1996;2(2):320-5.

Osama G, Peter R, Charles E, Joseph J. Metastatic malignant disease of unknown ori-

gin. Am J Surg Pathol 145, 493-7.

Mohammad Rakhshan, Azadeh Rakhshan The Diagnostic Accuracy of Fine Needle Aspiration Cytology

in Neck Lymphoid Masses Iranian Journal of Pathology (2009)4 (4), 147- 150

Naeem ahmed,saima israr,Muhammad sajjad ashraf ;comparision of Fine Needle Aspiration Cytology and
excision biopsy in the diagnosis of cervical lymphadeopathy;pakisthan journal of surgery,volume 25 issue
2 2009.72-75.

155