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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
98
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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99
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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101
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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