Thyroid
diseases are common problem in surgical practice and even now been manage at
primary care level. However, the problem comes in managing thyroid nodules. In
the era of technology, the treatment of thyroid problem especially in a group
of well differentiated tumour give a good prognosis and overall survival. In
view of this, the early detection of thyroid nodule is imperative for early
evaluation and treatment. The initial evaluation should always include complete
history and physical examination focusing in features suggestive of malignancy.
Tissue biopsy and imaging modalities should thoroughly be done to improve the
pre-operative diagnosis and provide good treatment options for patients with
thyroid nodules. 

In Malaysia,
only a few studies focused on thyroid nodule and risk associated with thyroid
malignancies. Sothi et al reported only 31 cases of thyroid malignancy reported
between 1985-1989 with highest incidence in 5th and 6th
decade (Sothy et al., 1991). The demographic data in this study is
slightly different with mean age of 44.36 years (SD14.69). In present study,
the age of patient ranged from 16-85 years old comparable to other previous
study. The peak incidence is at 4th -6th decade of life.
Another study done by Htwe et al describe in Kelantan between 1994–2004, 28.1%
of 1,480 thyroid lesions were neoplastic, the incidence of cancer was 3.5 per
100,000 admission and thyroid cancer made up 4.9% of all cancers seen in
hospital admission (Htwe, 2012).

Many literatures
have stated thyroid incidence are more common in female. Epidemiological
studies indicated approximately 5% of women and 1% of men resident in iodine
sufficient area have palpable thyroid nodule. This is a bit different with our
study whereby women with thyroid nodule are 10 times higher compare to man
(Table 1). From final histopathology report, majority are benign (68.4%) and
malignant case is 31.6% (Figure 3). 52.5% were solitary nodule followed by
33.2% multinodular and diffuse goitre is 14.3%. the proportion of disease is
similar with other study.(Sinna and
Ezzat, 2012).

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Gharib et al suggested that the most sensitive test
available to detect thyroid lesions is High-resolution ultrasound.(Gharib et al.,
2010).
Some author even suggested ultrasound is an independent predictor for
malignancy in indeterminate thyroid nodule (Cheung et al.).
USG features suggestive of malignant growth including presence of solid
component, hypoechogenicity, microcalcifications, increase vascularity,
lobulated or irregular margins, infiltrative margins, taller-than-wide shape on
transverse view.(Haugen et al.,
2016)  Laura et al
concluded the presence of suspicious US features did not discriminate malignant
from benign nodules. The risk of thyroid cancer of nodule more than 4 cm with
no suspicious US features was 20 %. The false negative rate of benign cytology
was 10.4 %, and the absence of suspicious US features did not reliably exclude
malignancy. At minimum, thyroid lobectomy should be strongly considered for all
nodules > 4 cm (Wharry et al., 2014) In our study, 55% of initial assessment from USG is
benign/low risk, followed by suspicious/intermediate risk (15%) and the
category high risk/high suspicion ultrasound finding is 13.3%. The rest was not
done pre-operatively. Among reasons are patient was undergoing CT scan of neck
rather than USG, presence of ulcer, and patient refusal. From benign USG
finding, 25 of 160 (15%) of the final histology were malignant. It was slightly
higher as compare to ATA which reported in low suspicious thyroid ultrasound
the expected risk of malignancy was 5-10%. (Haugen et al., 2016). Expected risk for intermediate/ suspicious
group is 10-20%. In this study, it is 19/45(42.2%) and for high suspicious
group, we found that 32/40(80%) were malignant and within the expected risk
between 70-90% in other literature.(Haugen et al., 2016) the difference of result is due to different
grading/ grouping system used by radiologist to stratify risk of malignancy.
Some author has suggested a standardize reporting method as demonstrate by AACE/AME/ETA:

In 2007, the
National Cancer Institute (NCI) hosted the NCI ‘Thyroid Fine-Needle Aspiration
State of the Science Conference’ in Bethesda, and subsequently published ‘The
Bethesda System for Reporting Thyroid Cytopathology’ in 2008.(Edmund S.
Cibas and Syed Z. Ali, 2009) Its aim was to establish comprehensive
guidelines regarding terminology and morphological criteria in reporting
thyroid FNAC. It delineates the reporting of ‘suspicious for malignancy’ as an
aspirate containing some features of malignancy, but lacking definitive
diagnostic changes. Many studies have proved that FNAC is a diagnostic tool for
thyroid nodule due to its sensitivity and specificity. However, we want to
examine the agreement between cytology and histology with regards to local
data. The complete sensitivity in our study was moderate (63%) as the positive
predictive value of malignancy is 61%, a specificity of 81% and negative
predictive value of 82%. Although its lower than other study, it still within
accepted range (table 10). The wide difference may due to number of cases,
classification of cytology, and diagnostic category (Popoveniuc
and Jonklaas, 2012)

Positive
predictive value (PPV) is a correctly malignant histopathology from pre-
operative malignant cytology express as a percentage of all cytological diagnosed
malignancies. The higher percentage is a good indicator to demonstrate the
reliability of the test itself. In our study, PPV is 61% which lower as compare
to other study but still within accepted range. A study in Egypt reported PPV
of 94.6%(Sinna and
Ezzat, 2012) whereby other study is 98.6% (Sangalli et al., 2006). One of the reason the low PPV value in this
study is due to large number of inadequate sample from histology which turn out
to be malignant post-operatively.
Inadequate samples may be because of large
areas of cystic degeneration or necrosis and sclerotic or calcified lesions. To increase the PPV value, other measure
should be implied such as to repeat FNAC or use an adjunct such as USG guided
FNAC to minimised inadequate sample in pre-operative cytology.

Benign cytology
in whom malignant lesions are later confirmed on histopathology is known as false
negative rate (FNR). Several studies have shown conflicting data regarding
large thyroid nodules with the accuracy of benign cytology. Meko et al. found a
false-negative rate of 17 % (5/30) in nodules >3 cm.(Meko and
Norton, 1995). Another published article examined 223
patients with nodules >4 cm and identified a false-negative rate of 13 %
(9/71) as well as higher incidence of cancer in larger nodules.(McCoy et al., 2007) Both studies recommended that large thyroid
nodules should be considered for surgery, regardless of FNA results. In
contrast, other author reviewed data from 743 ultrasound-guided FNA specimens
with benign cytology. Twenty percent (145/743) underwent thyroidectomy and only
one false-negative result (0.7 %) was identified on final pathology.(Porterfield et al., 2008) They concluded that with appropriate
aspiration and expert cytopathologic interpretation, the false-negative rate of
FNAC is extremely low and that diagnostic resection is unnecessary. However, it
is important to note that a most of patients with benign FNAC cytology did not
undergo surgery, thereby potentially decreasing the false-negative rate by a
significant margin. Unfortunately, in our study did not mention the size of nodule.
However, our entire patient went for thyroidectomy in nodule >1 cm as
suggested by many literatures

 

Comparison of
results of present study with various previous studies is shown in Table 10,
demonstrating that thyroid FNAC is a reliable screening test and a valuable
method of distinguishing neoplastic from non-neoplastic nodules preoperatively.
However, owing to some limitations of FNAC, it is recommended that surgical
indications must not depend solely on cytology. Indeed, the results of medical
history, physical examination, laboratory tests, and ultrasonography should
also be evaluated simultaneously. Due to high value of false negative and false
positive sample, the accuracy of this study is slightly lower (75%) as compared
to other study, Al- Sayer et al have accuracy of 92%, Afroze et al (94.5%), but
higher compare to Cusick et al 69%. It can be postulated that accuracy is
reducing with increasing number of patient. Chung et al suggested it can be
reduced by doing it at different site, repeat FNAC if inadequate sample, USG
guided FNAC and more than one cytopathologist involved in reviewing the slide.(Chung-Che
Charles Wang et al., 2011)

Suspicious
cytology findings account for 3.7–11 % all aspirates.(Baynes et al., 2014; Gharib et al., 1993; Raj et al., 2010) Our incidence of suspicious cytology was 8.6
%, therefore within range of this reported incidence. Suspicious cytology
carries a risk of malignancy of between 29 and 75 %(Bongiovanni et al., 2012; Cibas and Ali, 2009; Gharib et al., 1993) Of our suspicious FNAC results, 16 of 26
(69.2 %) were malignant on subsequent histology. This is the expected 60–75 %
reported in the Bethesda guidelines. Of these, the diagnosis of papillary
thyroid cancer was the most common in 13 cases (81.0 %), followed by follicular
(3,18%), anaplastic and micropapillary (1,6%). One study concluded surgical
removal of the nodules should be considered strongly as the incidence of
malignancy in suspicious lesions was high. Mundasad et al also concluded
in their study that suspicious and intermediate results prove to be an area of
uncertainty, often resolved by diagnostic surgical resection. (Mundasad et al., 2003)

It has been
thought that patients with hyperthyroidism are less likely to have cancer.(Sokal, 1954). The incidence of incidental thyroid cancer
in patients with toxic nodular goiter (TNG) has been estimated to be
approximately 3%.(Kang et al., 2002) In fact, the current recommendation from the
ATA is that a thyroid scan should be obtained as the initial test in a patient
with a thyroid nodule and a low serum thyroid stimulating hormone (TSH) level.(Cooper et al., 2009) If the nodule is found to be
hyperfunctioning, FNAC is not recommended as its rarely related to cancer. Over
the last 30 years, there has been a dramatic increase in the overall incidence
of thyroid cancer, from 3.6 per 100,000 in 1973 to 8.7 per 100,000 in 2002.(Davies and
Welch, 2006) However, it is unclear if this significant
increase in the incidence of thyroid cancer has also occurred in patients with
TNG. Two recent studies have reported higher rates of thyroid cancer, 15.6% and
18.3% in patients with TNG, suggesting that the rate of malignancy for TNG is
underestimated.(Smith et al., 2013a; Smith et al., 2013b) This has resulted in the hypothesis that factors
leading to the increased incidence of the thyroid cancer in the general
population may also be affecting patients with TNG. However thyroid toxicity
did not have significant risk for malignancy in our study as shown by Simple Logistic Regression model the crude ratio
is 1.

We able to
demonstrate that thyroid malignancy was marginally significant with increasing
age (in years) with Crude OR 5.22 (p =
0.046). Many literatures has described the incidence of thyroid cancer is
increasing in elderly (Raffaelli et al., 2010)  between 2.5% and 12% of differentiated
thyroid cancer occur in individuals older than 65 years.(Amato
et al., 2013) A retrospective study conducted by Lin et al analyzed 204 thyroid
cancer patients aged 60 years and older; 142 (70%) thyroid cancers were well
differentiated and Fifty-nine (29%) of the thyroid cancers were poorly
differentiated.(Lin
et al., 2005) In a more recent retrospective analysis of 1022 patients undergoing
thyroidectomy, the rate of malignancy was 68.7% in a group of 45 year old and
older.  well-differentiated thyroid
cancer and lymph node metastasis occurred more often in patients younger than
50 years while micropapillary carcinoma occurred more often in patients 50
years or older(Do
et al., 2014)

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