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Shirish Chandanwale et al, Int J Pharm Biomed Sci 2012, 3(3), 97-102

2012 PharmaInterScience Publishers. All rights reserved. www.pharmainterscience.com

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specificity in the preoperative evaluation of thyroid lesions

[9-11]. It is considered as the gold standard investigation in

diagnosis of thyroid nodules. However, even FNAC has

limitations because of low yield of cells, loss of histological

architecture and inability to distinguish follicular adenoma

and well differentiated follicular carcinoma [11-13].This

study was be done in Padmashree. Dr. D. Y. Patil medical

college from March 2009 to March 2011. Aim of this study

was to evaluate accuracy of FNAC in diagnosis of nodular

lesions of thyroid in comparison with other diagnostic

modalities and to make early and accurate differentiation of

benign and malignant thyroid nodules with special focus on

incidence of malignancy in thyroid nodules.

2. MATERIALS AND METHODS

Study included 150 patients. An inclusion criterion was

patients with thyroid enlargement coming to the cytology

department for FNAC irrespective of age, sex. An exclusioncriterion was patients without any apparent thyroid disease.

All patients underwent FNAC after prior consent. FNAC was

done with aseptic precautions by using 10cc syringe and 23

gauze needle. Material obtained was smeared on glass slides.

2 slides were air dried and stained with Leishmanns stain.

Remaining slides were wet fixed by using ethanol and were

stained with Papanicolau method. Detailed clinical history,

radiological findings and status of thyroid function test (TFT)

were noted. In case of multiple nodules, more than one

aspirate was done from prominent nodules. In cystic nodules,

the cyst contents were aspirated, centrifuged and the slides

were made from the sediment for microscopic examination.

Aspirates were taken as adequate when cytology smears

contain five to six groups of well preserved follicular cells,

with each group containing 10 or more cells [14]. However,

adequacy also depends upon the lesion being aspirated. For

example in case of colloid goiter FNAC many times yields

only colloid with scanty cells, but it is adequate if the lesion

is taken into consideration. No serious complication occurred

in our study. Only pain for few minutes after aspirations was

noted in few cases. Surgical specimens of thyroid were

received in 10% formalin either in the form of lobectomy,

isthemectomy, subtotal thyroidectomy, or totalthyroidectomy. A small specimen up to 5 cm in diameter,

entire circumference of the specimen was sectioned. In larger

specimen additional sections were taken for each additional

centimeter in diameter. Most of the sections included tumor

capsule and adjacent thyroid tissue. Tissues were formalin

fixed and paraffin processed. 3 to 5 sections were cut and

stained with Haematoxylin and Eosin. H&E).

A standard reporting format as suggested by the

Papanicolaou Society of Cytology was used to study cytology

smears in order to communicate results clearly to the

clinicians [14]. This is particularly important in relation tothyroid nodules since clinical management is to large extent

decided by the cytology report. Smears which were reported

as Non-diagnostic / unsatisfactory, diagnosis was not made

because of inadequate cellular material. Benign nodules

included multinodular goiter, hyperplastic goiter, colloid

goiter, Graves disease, autoimmune thyroiditis,

granulomatous thyroiditis and thyroid cysts. Indeterminate or

Suggestive / suspicious of neoplasms included follicular

neoplasm and Hurthle cell neoplasms. Malignant nodules

included papillary carcinoma, medullary carcinoma, poorly

differentiated carcinoma, anaplastic carcinoma, and

lymphoma. Pre-operative FNAC results were then compared

with the definitive histological diagnosis. The sensitivity,

specificity, diagnostic accuracy, positive predictive valve

(PPV) and negative predictive value (NPV) of FNAC in

diagnosing thyroid malignancy was calculated.

3. RESULTS AND DISCUSSION

Thyroid enlargement, whether diffuse or nodular leads to

a battery of investigations, mainly to rule out the possibility

of a neoplastic or non-neoplastic lesions. Timely interventionin nodular lesions of thyroid can significantly reduce

morbidity and mortality. FNAC is found to be the most

useful first line of investigation than other investigations like

USG, TFT, thyroid scan and serologic studies. FNAC leads

to early diagnosis and aids in the treatment of thyroid lesions.

FNAC has good amount of accuracy up-to 97% in the

preoperative diagnosis of various thyroid lesions. This has

been claimed by various authors [11,15-20], while others

believe, correct preoperative diagnosis can be made only in

25%, hence there is marked discrepancy regarding this

subject [21]. Total 150 patients were included in the study.

Ages of the patients ranged from 18-65 years. Commonest

age group (49%) was 21-40 years with preponderance of

benign lesions. This was supported by Kapur and coauthors

who found 54% of the patients in 20-40 yrs of age group.[22]

While other workers found 30-50 years as the common age

group.[6,7]Ages of the 6 malignant lesions in our study

ranged from 5070 yrs, with mean age of 41 years. Females

(66.6%) were more commonly affected than males (33.3%).

Similar findings were stated by Tabaqchali et al.[20] and

Ergete W et al.[23] The male to female ratio in our study

was 1:9 The higher prevalence of nodular diseases of

thyroid in female sex is further substantiated by manyauthors in their study [20,23-25]. Out of 150 patients,

100(66.6%) had clinically palpable solitary thyroid nodules

and 50(33.4%) patients had more than one nodule. Right lobe

(61%) was more commonly involved than left lobe (39%).

Similar findings were noted by many authors [19,23,26,27].

The duration of symptoms gave no clue regarding the nature

of thyroid swelling. There was no significance of mode of

presentation in our study since majority of patients in our

study presented as swelling, 66.6% had solitary nodule and

33.4% complained of more than l nodule in thyroid. Similar

observations were made by other authors [18,22,28].However mode of presentation is quintessential in Graves

disease because the diagnosis of Graves disease mainly

depends on clinical findings which was seen in 2 cases in

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our study. Commonest associated symptom was hoarseness

of voice (25%) followed by dysphasia (24.6%), symptoms of

Hyperthyroidism (4.6%) and Hypothyroidism (4%). 41.8%

patients had no associated symptoms. Thyroid function tests

(T3, T4, TSH) were done in all cases. 117(78%) patients

were euthyroid, 18(12%) patients had hyperthyroidism and

15(10%) patients had hypothyroidism. Out of 18

hyperthyroid cases, 15 cases were of colloid goiter, one case

was of Graves disease, one case was Follicular neoplasia and

one case was Hashimotos thyroiditis on FNAC. Out of 15

hypothyroid cases 14 cases were diagnosed as colloid goiter

and one was thyroid cyst on FNAC. Thyroglobulin is a

protein made by the thyroid gland. Measuring the

thyroglobulin level in the blood cannot be used to diagnose

thyroid cancer, but it can be helpful after treatment. It

provides a clue about residual neoplasm or recurrence of

malignancy [29]. These findings suggests that TFT is just a

preliminary tool in evaluation of nodular lesions of thyroid.

They lack sensitivity and specificity in the diagnosis ofthyroid nodules, however they can be very useful in diagnosis

of Graves disease.

USG of neck was done in 108(72%) cases out of which

16 cases were reported as descriptive and in 8 cases findings

were within normal limits. Out of remaining 84 cases,

positive correlation with FNAC was seen in 62(73.8%) cases.

Thirteen cases which were diagnosed as colloid goiter on

USG, 3 cases were neoplastic, 9 cases were thyroiditis and 1

case was Graves disease on FNAC. Six cases which were

diagnosed as thyroid cyst on USG, 5 were found to be colloid

goiter with cystic change and 1 case as papillary thyroidcarcinoma (PTC) in thyroglossal duct cyst (TDC) on FNAC.

Three cases which were diagnosed as adenomatoid goiter on

USG, 2 were colloid goiter and one was follicular neoplasm

on FNAC. Though certain features are predictive of

malignancy such as hypoechogenicity, irregular margins,

presence of calcifications and absence of a hypoechoic rim

[25].These findings suggest that USG can not conclusivelydifferentiate between benign and malignant thyroid nodules.

However it lowers the rates of non-diagnostic aspirations

by allowing sampling of the cellular portions of

predominantly cystic nodules. These findings are further

substantiated by Yassa et al[24] in 2007.

In our study there was one cystic nodule which was

diagnosed as papillary carcinoma on FNAC which is known

to occur, whereas remaining 5 cystic nodules were non

malignant. Sohail Raza et al.[18] found no malignancy in

cystic nodules and 9% incidence of malignancy in solid

nodules whereas Ergete W et al.[24] found incidence of

carcinoma in cystic lesion

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Table 2

Clinical and FNAC correlation

Clinical diagnosis FNAC diagnosis

Colloid goitre Thyroiditis FN & HCN Cyst Graves Malignancy Unsatisfactory

Colloid goitre(86) 75 2 1 6 2

Thyroiditis(20) 2 16 2

Solitary nodule(29) 17 10 1 1

Graves(3) 2 1

Malignancy(12) 4 1 2 3 2Total(150) 98 19 13 9 2 6 3

FN- Follicular neoplasm, HCN- Hurthle Cell Neoplasm

Table 3

FNAC and histology correlationFNAC diagnosis Histology diagnosis

Colloid goitre Thyroiditis FN HCA Papillary Ca Medullary Ca

Colloid goitre(23) 21 1 1(FNUMP)

Cystic lesion(9) 7 1(FA) 1

Thyroiditis(2) 2

FN(5) 5(3 Ca, 2 FA)HCA(1) 1

Papillary Ca(4) 4

Medullary Ca(2) 2

Inadequate(1) 1

Total(47) 29 3 7 1 5 2

FN- Follicular Neoplasm, HCA- Hurthle cell Adenoma, FNUMP- Follicular Neoplasm Unmalignant Potential, FA Follicular Adenoma, FC Follicular

Carcinoma, Ca- Carcinoma

arranged in poorly cohesive groups with moderate amount of

colloid suggesting the diagnosis of nodular goiter.

Cytological differentiation between follicular neoplasms andnodular colloid goiter is sometimes very difficult [3].

Aspiration in this case was probably done over colloid rich

areas of the neoplasm. Possible remedial measures includes

careful observation of cytological features like nuclear

overcrowding and overlapping, uniform cell patterns on

repeat aspirates, micro follicles and scanty or no colloid,

which may be helpful in distinguishing between the two

although none of them is conclusive. So cytohistological

concordance rate in colloid goiter was 95.45% (Table 3)

which was in line with other authours [11,34-36].

In our study 6% cases (n=9) were diagnosed as cystic

lesions on FNAC. Smears showed scanty cellularity withpresence of foamy macrophages, few follicular cells, and

colloid. In all 9 cases histology was available. Of the 9 cases,

7 cases were diagnosed as cystic changes in nodular goiter,

one case each was diagnosed as follicular adenoma and

primary papillary carcinoma arising in Thyroglossal Duct

Cyst (TDC). It is known that 20% of follicular neoplasms

and 25% of papillary carcinomas show cystic change [37].

Aspirate in these 2 cases yielded few follicular cells with

degenerative changes and macrophages and scanty colloid.

This can be explained on the basis of the sampling of cystic

areas rather than solid cellular areas. The possible remedy ismultiple aspirations from different parts of the swelling that

could demonstrate hypercellular areas or USG guided FNAC

which would aid in sampling the solid portions of cystic

nodules.

Out of 19 cases diagnosed as chronic thyroiditis onFNAC, 18 were diagnosed as Autoimmune thyroiditis

whereas 1 case was of Granulomatous thyroiditis. Only two

cases underwent subtotal thyroidectomy due to pressure

symptoms and histology confirmed the diagnosis of

autoimmune thyroiditis in one case. On FNAC other case

showed epithelioid cell granulomas along with multinucleate

giant cells against necrotic background. Acid Fast bacilli

were not seen on Zeihl Neilsen stain (ZN) and was diagnosed

as de Quervains thyroiditis. In our study M:F ratio was

1:18. The age of the patients ranged from 16 to 65 years and

mean age was 35 years. FNAC smears in autoimmune

thyroiditis showed Askanazy cells, variable numbers oflymphocytes and plasma cells destroying follicular epithelial

cells with scanty or no colloid. FNAC diagnosis of

thyroiditis in these cases led the patient to take medical line

of treatment, unnecessary surgeries and hospitalization was

avoided. So we feel that FNAC is very accurate in the

diagnosis of thyroiditis.

Two cases of Gravess disease presented with

characteristics clinical features of hyperthyroidism like

goiter, exophthalmoses, tremor and flushed skin, along with

raised levels of T3and T4 and were clinically also diagnosed

as Grave's disease. FNAC smears showed moderate amountof follicular epithelial cells arranged in follicular or ring

structure with abundant pale vacuolated cytoplasm. Mild

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nuclear enlargement and anisokaryosis on the background of

hemorrhage with little amount of thin colloid was seen. In

both cases "fire flares" were seen.

12 cases were diagnosed as follicular neoplasm and l case

as hurthle cell neoplasm. These were grouped under

INDETERMINATE category as recommended by Jogai S

[32], because the diagnosis of follicular and hurthle cell

carcinoma requires demonstration of capsular and/or vascular

invasion, which cannot be evaluated on cytology. FNAC

aspirates from the cases diagnosed as Follicular neoplasm

showed cellular smears containing syncytial, multilayered

cell clusters of variable sizes with nuclear crowding and

overlapping with many micro follicles. Repeat aspirate

showed repetitive uniform population of cells with scanty or

no colloid FNAC smears from the case diagnosed as Hurthle

cell neoplasm were cellular with many poorly cohesive

clusters of Hurthle cells which were large and polygonal with

abundant deep blue cytoplasm on MGG stain. Cytoplasm had

variable granularity with large vesicular nuclei with macronucleoli and focal pleomorphism, against a background of

scanty colloid. Out of 12 cases diagnosed as follicular

neoplasm on FNAC, 5 cases were subjected to histology. Of

these 5 cases, 2 cases were diagnosed as follicular adenoma

and three as poorly differentiated carcinoma on histology.

The case of hurthle cell neoplasm was diagnosed as adenoma

on histology. M:F ratio was 1:2.25. The ages ranged from 40

years to 70 years. The incidence of indeterminate cases in our

study was 8.78%. Thus in our study the diagnosis of

follicular neoplasm was made when the hypercellular smear

showed many follicular epithelial cells distributed infollicular structures or sheets with a scanty quantity of

colloid. The diagnosis of hurthle cell neoplasm was made

when the oxyphilic cells were dominant component.

The incidence of malignancy was 6.75% in our study. The

false negative and false positive FNAC diagnosis for

malignancy in various series ranged from 5-10% [18-20, 38].

In our study 4% (n=6) cases were diagnosed as malignant on

FNAC out of which 2.7% were papillary carcinoma (n=4)

and 1.3% were medullary carcinoma (n=2). Histology was

available in all cases. Handa et al.[11] diagnosed 2.53% cases

as papillary carcinoma and 0.69% cases as medullar

carcinoma. Gupta et al.[19] found 12% Papillary carcinoma

and 0% Medullary carcinoma. Tabaqchali et al.[20] found

14% Papillary and 0.7% Medullary carcinoma.

In our study, out of 4 cases of papillary carcinoma 2 cases

had cystic changes and aspirations were repeated. The smears

of papillary carcinoma showed syncitial clusters of follicular

epithelial cells, at many places forming papillary architecture

with a central fibrovascular core with pale nuclei having

powdery chromatin, intranuclear cytoplasmic inclusions,

irregular nuclear outlines and nuclear grooves. Psammoma

bodies were seen in 1 case. The smears of medullary

carcinoma were cellular and showed many dispersed cells ofvaried morphology having plasmacytoid, small cell and

spindle cell appearance with abundant intact cytoplasm.

Nuclei were large showing moderate anisokaryosis and

uniform stippled chromatin. Few binucleate cells were seen.

Some cells had coarse granular chromatin. At places dense

amorphous magenta colored amyloid was seen. Malignancies

like malignant lymphoma or undifferentiated carcinoma can

be better treated with irradiation or chemotherapy rather than

a surgery. In our study no case malignant lymphoma or

undifferentiated carcinoma was found. Incidence of

malignancy was 4% on FNAC. In our study FNAC

represented an improvement in the clinical diagnosis of

malignancy and thyroid nodules, and little improvement in

the clinical diagnosis of goiter and thyroiditis, where it

supported the clinical diagnosis so unnecessary surgeries

were avoided.

The sensitivity of thyroid FNAC ranges from 80-98% and

its specificity from 58-100% [39-41]. Sensitivity and

specificity in our study was 90% and 100%, respectively with

PPV, NPV and diagnostic accuracy of 100%, 90% and

87.5%, respectively.Handa et al. [11] calculated the sensitivity of 97%,

specificity of 100%, diagnostic accuracy of 98.47% and

negative and positive predictive values were 100% and 96%,

respectively. Similar findings have been corroborated by

numerous authors like Tabaqchali et al. [20], Ergete W et al.

[23], Sohail raza et al. [18], Kessler et al. [32], Guhamallick

et al. [25], Gupta et al. [19]

4. CONCLUSIONS

FNAC of thyroid nodules provides the most accurate

preoperative diagnosis than any other diagnostic modalities.

Negative cytologic findings can support long term medical

management in clinically nonsuspicious benign lesions such

as colloid goiter and thyroiditis. By using specific diagnostic

terminology, FNAC of the thyroid bridges the gap between

clinical evaluation and final surgical pathologic diagnosis in

majority of cases. The positive influence of FNAC on the

management of thyroid lesions is perhaps best highlighted in

the low rate of surgical intervention, (26.66%) in this study.

Surgery was avoided mainly in colloid goiter and thyroiditis.

The assessment of patients with thyroid nodules include triple

modalities of clinical examination, FNAC and Radiologicinvestigations, however FNAC is an valuable and minimally

invasive procedure and hence considered as a gold standard

for preoperative assessment of patients with thyroid nodules.

It can significantly reduce morbidity as well as mortality of

patients by making early and accurate differentiation of

benign and malignant thyroid nodules.

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