**5. Clinical evaluation**

Thyroid nodules can present as anterior neck swelling. Most nodules grow very slowly over years. Patients may also present with history of rapid increase in size, which can be suggestive of a malignancy, or a haemorrhage into a nodule, especially if associated with pain. Significant sized nodules can result in compressive symptoms based on the anatomical structure being compromised. Larger nodules can result in compression of underlying structures leading to symptoms like dyspnoea, dysphagia, and hoarseness of voice with compression of trachea, oesophagus and recurrent laryngeal nerves respectively. Patient can also present with thyroid dysfunction. Younger patients with adenoma and thyrotoxicosis (Toxic adenoma) tend to present with the classical symptoms of thyrotoxicosis like nervousness, weight loss despite increased appetite, tremors, palpitations, heat intolerance and sweating. On the other hand, thyrotoxicosis in elderly can present with non-specific symptoms like anorexia, atrial fibrillation, congestive heart failure, and is difficult to diagnose due to lack of classical symptoms. A hypothyroid presentation with fatigue, constipation, cold intolerance is more indicative of a diagnosis of autoimmune thyroiditis in patients with nodular goitre.


#### **Table 2.**

*Risk factors for malignancy.*

Findings suggestive of hyperthyroidism or hypothyroidism should be actively elicited during examination. Size of the gland and qualitative and quantitative description of palpable nodules and lymph nodes should be noted, including size, tenderness, consistency and fixity to surrounding anatomical structures. Smaller thyroid nodules <1 cm, and posteriorly or substernally located nodules can be difficult to palpate, and would be better characterised by imaging techniques.

Increasingly nodules are being detected during neck imaging for other indications. The clinical importance of diagnosis of thyroid nodules lies in excluding malignancy in these patients. 4–6.5% of thyroid nodules can harbour malignancy [1]. History of rapid growth of the nodule, hoarseness of voice due to paralysis of vocal cords suggests a malignant aetiology. Examination features in such cases could include a hard consistency of the nodule, fixation to surrounding structures, presence of regional lymphadenopathy or distant metastases. The risk of a nodule being malignant increases with extremes of age and with male sex. The frequency of malignancy in patients with solitary nodules is not different from nodules seen in multinodular thyroid disease [21].

Other risk factors which impart increased risk of malignancy should be enquired in all patients. History of prior exposure to radiation for various indications like haematopoietic malignancies and stem cell transplantation, head and neck, mediastinal and CNS tumours should be sought, as this increases the likelihood of malignancy in thyroid nodules. Familial forms of thyroid cancers should be considered in differential diagnosis in the presence of supportive history. Most common form of familial thyroid cancers is seen in medullary thyroid carcinomas (MTC). Familial MTC can occur either as an isolated problem inherited in an autosomal dominant fashion, or as a component of MEN 2A (MTC, primary hyperparathyroidism, pheochromocytoma) MEN 2B (MTC, pheochromocytoma, ganglioneuromas, Marfanoid habitus, thickened corneal nerves). Familial papillary thyroid carcinoma (PTC) can occur as an autosomally dominantly inherited isolated form, or can be a component of Pendred syndrome or intestinal polyposis syndromes like Familial adenomatous polyposis (FAP), Gardner syndrome and Peutz Jeghers syndrome. Follicular thyroid carcinoma (FTC) can be associated with Cowden disease and Bannayan Riley Ruvalcaba syndrome. Carney complex type I can be associated with either PTC or FTC, whereas Werner's syndrome can be associated with PTC, FTC or anaplastic thyroid carcinoma (ATC) [22]. Factors suggestive of an increased likelihood of malignancy have been summarised in **Table 2**.

#### **6. Laboratory evaluation**

#### **6.1 Serum TSH**

The initial evaluation in all patients presenting with a thyroid nodule should include a measurement of serum TSH. If TSH levels are low, possibility of

**85**

*Thyroid Nodule: Approach and Management DOI: http://dx.doi.org/10.5772/intechopen.91627*

**6.2 Serum thyroid antibodies**

differentiated thyroid cancer [23, 24].

with differentiated thyroid cancers.

**6.3 Serum thyroglobulin**

**6.4 Serum calcitonin**

**7. Imaging**

**7.1 Radionuclide scan**

subclinical or overt hyperthyroidism should be considered. Approximately 10% of solitary nodules can be associated with a subnormal TSH. Multinodular goitres, on the other hand, are frequently associated with suppressed TSH due to development of autonomy in the nodules. Serum free T4 levels and T3 levels should be obtained for documentation of hyperthyroidism; the latter may especially be obtained in areas with iodine deficiency due to preferential secretion of T3 over T4 in these circumstances. Patients with a thyroid nodule and subnormal TSH can be taken for

In patients with elevated TSH, anti-thyroid peroxidase (anti-TPO) antibodies may be measured which point to a diagnosis of Hashimotos thyroiditis. However, positive anti-TPO does not obviate the need for a cytopathological evaluation, as a coexisting malignancy needs to be ruled out. A raised or even a normal TSH is associated with an increased risk of malignancy, as well as a more advanced stage of

Thyroglobulin (Tg) is a storage form of thyroid hormones, synthesised by thyroid follicular cells. Serum Tg levels are elevated in many benign and malignant thyroid disorders. An elevated level of serum Tg cannot differentiate malignancy in a thyroid nodule with certainty. Measurement of serum thyroglobulin has a role in postoperative monitoring for residual, recurrent or metastatic disease in patients

Calcitonin is produced by the parafollicular C cells of the thyroid gland and is a marker for medullary thyroid cancer (MTC). Basal and pentagastrin stimulated serum calcitonin has a role in early diagnosis as well as post-operative monitoring of patients with MTC. Serum calcitonin is measured in patients with family history of MTC or MEN-2 syndrome. Unstimulated serum calcitonin levels >50–100 pg/ml are commonly associated with MTC. There are no recommendations for the routine use

of calcitonin in evaluation of thyroid nodules in current recommendations.

radioiodine scanning, up to 30% of which can be malignant [25].

Hyper-functioning thyroid nodules comprise up to 10% of thyroid nodules. Currently ATA recommends performing a thyroid radionuclide scan in patients with thyroid nodule associated with subnormal TSH. Two radionuclides are primarily used for functional evaluation of thyroid nodules: I123 and Tc 99 m pertechnetate. Both the radioisotopes are taken up by thyroid follicular cells, but only radioiodine is organified and stored within the gland. A thyroid nodule can be classified as "hot/hyperfunctioning", "warm/isofunctioning" and "cold/hypofunctioning" on scintigraphy. A functioning nodule is nearly always benign. 5% of nodules that appear hot or warm on pertechnetate scanning can appear cold on

On the contrary, the risk of malignancy in non-functioning nodules is 4–6.5% [26–29]. Since malignancy is rarely encountered in hyperfunctioning nodules,

a Nuclear Thyroid Scan to document the functional status of the nodule.

*Thyroid Nodule: Approach and Management DOI: http://dx.doi.org/10.5772/intechopen.91627*

*Goiter - Causes and Treatment*

Age < 20 years or > 70 years

Increasing size/rapid growth

Childhood H/O exposure to radiation

Male sex

syndromes

*Risk factors for malignancy.*

**Table 2.**

multinodular thyroid disease [21].

**6. Laboratory evaluation**

**6.1 Serum TSH**

Findings suggestive of hyperthyroidism or hypothyroidism should be actively elicited during examination. Size of the gland and qualitative and quantitative description of palpable nodules and lymph nodes should be noted, including size, tenderness, consistency and fixity to surrounding anatomical structures. Smaller thyroid nodules <1 cm, and posteriorly or substernally located nodules can be difficult to palpate, and would be better characterised by imaging techniques.

Nodules >4 cm in size Hard consistency Fixed nodule Vocal cord palsy

Regional lymphadenopathy Distant metastases

**History Findings**

Compressive symptoms: dyspnoea, dysphagia, hoarseness of voice

Family H/O thyroid malignancies, MEN2, intestinal polyposis

Increasingly nodules are being detected during neck imaging for other indications. The clinical importance of diagnosis of thyroid nodules lies in excluding malignancy in these patients. 4–6.5% of thyroid nodules can harbour malignancy [1]. History of rapid growth of the nodule, hoarseness of voice due to paralysis of vocal cords suggests a malignant aetiology. Examination features in such cases could include a hard consistency of the nodule, fixation to surrounding structures, presence of regional lymphadenopathy or distant metastases. The risk of a nodule being malignant increases with extremes of age and with male sex. The frequency of malignancy in patients with solitary nodules is not different from nodules seen in

Other risk factors which impart increased risk of malignancy should be enquired in all patients. History of prior exposure to radiation for various indications like haematopoietic malignancies and stem cell transplantation, head and neck, mediastinal and CNS tumours should be sought, as this increases the likelihood of malignancy in thyroid nodules. Familial forms of thyroid cancers should be considered in differential diagnosis in the presence of supportive history. Most common form of familial thyroid cancers is seen in medullary thyroid carcinomas (MTC). Familial MTC can occur either as an isolated problem inherited in an autosomal dominant fashion, or as a component of MEN 2A (MTC, primary hyperparathyroidism, pheochromocytoma) MEN 2B (MTC, pheochromocytoma, ganglioneuromas, Marfanoid habitus, thickened corneal nerves). Familial papillary thyroid carcinoma (PTC) can occur as an autosomally dominantly inherited isolated form, or can be a component of Pendred syndrome or intestinal polyposis syndromes like Familial adenomatous polyposis (FAP), Gardner syndrome and Peutz Jeghers syndrome. Follicular thyroid carcinoma (FTC) can be associated with Cowden disease and Bannayan Riley Ruvalcaba syndrome. Carney complex type I can be associated with either PTC or FTC, whereas Werner's syndrome can be associated with PTC, FTC or anaplastic thyroid carcinoma (ATC) [22]. Factors suggestive of an increased likelihood of malignancy have been summarised in **Table 2**.

The initial evaluation in all patients presenting with a thyroid nodule should

include a measurement of serum TSH. If TSH levels are low, possibility of

**84**

subclinical or overt hyperthyroidism should be considered. Approximately 10% of solitary nodules can be associated with a subnormal TSH. Multinodular goitres, on the other hand, are frequently associated with suppressed TSH due to development of autonomy in the nodules. Serum free T4 levels and T3 levels should be obtained for documentation of hyperthyroidism; the latter may especially be obtained in areas with iodine deficiency due to preferential secretion of T3 over T4 in these circumstances. Patients with a thyroid nodule and subnormal TSH can be taken for a Nuclear Thyroid Scan to document the functional status of the nodule.

#### **6.2 Serum thyroid antibodies**

In patients with elevated TSH, anti-thyroid peroxidase (anti-TPO) antibodies may be measured which point to a diagnosis of Hashimotos thyroiditis. However, positive anti-TPO does not obviate the need for a cytopathological evaluation, as a coexisting malignancy needs to be ruled out. A raised or even a normal TSH is associated with an increased risk of malignancy, as well as a more advanced stage of differentiated thyroid cancer [23, 24].

#### **6.3 Serum thyroglobulin**

Thyroglobulin (Tg) is a storage form of thyroid hormones, synthesised by thyroid follicular cells. Serum Tg levels are elevated in many benign and malignant thyroid disorders. An elevated level of serum Tg cannot differentiate malignancy in a thyroid nodule with certainty. Measurement of serum thyroglobulin has a role in postoperative monitoring for residual, recurrent or metastatic disease in patients with differentiated thyroid cancers.

#### **6.4 Serum calcitonin**

Calcitonin is produced by the parafollicular C cells of the thyroid gland and is a marker for medullary thyroid cancer (MTC). Basal and pentagastrin stimulated serum calcitonin has a role in early diagnosis as well as post-operative monitoring of patients with MTC. Serum calcitonin is measured in patients with family history of MTC or MEN-2 syndrome. Unstimulated serum calcitonin levels >50–100 pg/ml are commonly associated with MTC. There are no recommendations for the routine use of calcitonin in evaluation of thyroid nodules in current recommendations.

## **7. Imaging**

#### **7.1 Radionuclide scan**

Hyper-functioning thyroid nodules comprise up to 10% of thyroid nodules. Currently ATA recommends performing a thyroid radionuclide scan in patients with thyroid nodule associated with subnormal TSH. Two radionuclides are primarily used for functional evaluation of thyroid nodules: I123 and Tc 99 m pertechnetate. Both the radioisotopes are taken up by thyroid follicular cells, but only radioiodine is organified and stored within the gland. A thyroid nodule can be classified as "hot/hyperfunctioning", "warm/isofunctioning" and "cold/hypofunctioning" on scintigraphy. A functioning nodule is nearly always benign. 5% of nodules that appear hot or warm on pertechnetate scanning can appear cold on radioiodine scanning, up to 30% of which can be malignant [25].

On the contrary, the risk of malignancy in non-functioning nodules is 4–6.5% [26–29]. Since malignancy is rarely encountered in hyperfunctioning nodules,

further cytological evaluation is not necessary if a corresponding hot nodule is identified on scintigraphy.

#### **7.2 Ultrasonography**

Ultrasonography has become an indispensable tool for the evaluation of thyroid nodules. Ultrasound is easily available, non-invasive and invaluable for dileniation and prognostication in these patients. Ultrasound in the hands of an experienced sonologist enables accurate identification of size, number of nodules, composition, echogenicity, margins, presence and type of calcifications, shape if taller than wide, vascularity and status of cervical lymph nodes. The pattern of sonographic characteristics of a nodule confers a risk for malignancy. Categories of high suspicion nodules are then subjected to invasive modalities like Fine Needle Aspiration (FNA) and cytological evaluation is done. Features with the highest specificities (median > 90%) are microcalcifications, irregular margins and tall shape, even though the sensitivities are significantly low for any single feature.

Ultrasound is also invaluable in assessing the risk of malignancy in lymph nodes. Location of the lymph nodes adds to the diagnosis. Malignant nodes are more likely to occur in levels III, IV and VI than in level II. PTC tumours arising in upper pole of the thyroid may be an exception as they have a propensity to demonstrate skip metastases to levels III and II. Size of >1 cm, ratio of long axis to short axis (also called as Solbiati index of <2), punctate calcification, presence of hyperechogenicity/mixed echogenicity/cystic changes, loss of hilum and peripheral hypervascularity are some of the features predictive of malignancy. While peripheral vascularity has the highest sensitivity of 86%, punctate calcifications are 100% specific for malignant involvement [30, 31]. However, no single sonographic feature is adequately sensitive for determining malignant involvement. Sonographically suspicious lymph nodes ≥8–10 mm in the smallest diameter should therefore undergo FNA to look for evidence of malignant involvement.

Ultrasound Elastography is a novel modality performed with an ultrasound machine using an elastography computational module. It provides a measure of tissue stiffness, and is being used for malignancy risk assessment. In a study by Azizi et al., thyroid nodule stiffness by elastography was an independent predictor of thyroid carcinoma, with a PPV of 36%, comparable to that of microcalcifications. On the contrary, in another study by Moon et al., elastography alone or in combination with grey scale ultrasound showed an inferior performance compared to grey scale ultrasonographic assessment for differentiation of benign and malignant thyroid nodules [32]. Guidelines currently do not recommend universal use or widespread adoption of ultrasound elastography for malignancy risk assessment.

#### **7.3 CT and MRI neck**

Since ultrasound is operator dependent and cannot adequately image deep anatomic structures and those acoustically shadowed by bone or air, preoperative cross sectional imaging like CT/MRI can be used as an adjunct in patients with clinical suspicion of advanced disease, like patients with an invasive primary tumour, or clinically apparent multiple or bulky nodal involvement. These modalities permit imaging beyond the routine cervical regions imaged by the ultrasound, like infraclavicular, retropharyngeal, parapharyngeal regions and the mediastinum. These also aid in preoperative planning to accurately delineate the inferior border, extent of laryngeal tracheal, oesophageal or vascular involvement.

Combined ultrasound and CT may have a higher sensitivity for macroscopic nodal metastasis detection preoperatively, compared to ultrasound alone [33, 34].

**87**

**Figure 1.**

*nodules and differentiated thyroid cancer [1]).*

*Thyroid Nodule: Approach and Management DOI: http://dx.doi.org/10.5772/intechopen.91627*

outcome in metastatic thyroid cancer [31].

**7.4 FDG PET**

variability.

Contrast enhanced CT helps in the accurate delineation of the primary tumour and the metastatic disease with the surrounding areas. There exists a small risk of precipitating hyperthyroidism due to iodine content in the contrast agents. Iodine from the IV contrast agents is generally cleared within 4–8 weeks of the scan, as assessed by the urinary iodine levels returning to baseline. Hence a waiting period of atleast a month is advisable to allow urinary iodine levels to return to normal before moving forward to the use of diagnostic or therapeutic radioiodine post-operatively. There is no evidence to suggest this could translate into adverse outcome for thyroid cancer patients currently [31, 35]. MRI is prone to respiration artefacts and can be

Functional imaging with 18 F – FDG PET is currently not recommended routinely prior to initial surgery. However, it has been widely accepted as a modality for detecting recurrence of differentiated thyroid cancer, particularly in non-iodine avid disease. PET avidity has also been shown to be a strong predictor of poor

**7.5 Guidelines for evaluation, reporting and management of thyroid nodules**

Sonographic Scoring systems are used to stratify nodules according to risk of malignancy to allow centres for uniform reporting and reduce interobserver

The **American Thyroid Association (ATA**) risk stratifies nodules into high suspicion, intermediate suspicion, low suspicion, very low suspicion and benign categories based on imaging characteristics. The sonographic features have been shown in **Figure 1** and the FNA cut-offs have been summarised in **Table 3**.

Similar to Breast reporting, the **American College of Radiology** has developed

a reporting system for thyroid nodules known as **Thyroid Imaging Reporting and Data System (TIRADS)** for risk stratification based on points assigned for

*Sonographic characteristics of thyroid nodules (Adapted from ATA guidelines for adult patients with thyroid* 

more difficult to interpret by surgeons in the operating room.

*Thyroid Nodule: Approach and Management DOI: http://dx.doi.org/10.5772/intechopen.91627*

Contrast enhanced CT helps in the accurate delineation of the primary tumour and the metastatic disease with the surrounding areas. There exists a small risk of precipitating hyperthyroidism due to iodine content in the contrast agents. Iodine from the IV contrast agents is generally cleared within 4–8 weeks of the scan, as assessed by the urinary iodine levels returning to baseline. Hence a waiting period of atleast a month is advisable to allow urinary iodine levels to return to normal before moving forward to the use of diagnostic or therapeutic radioiodine post-operatively. There is no evidence to suggest this could translate into adverse outcome for thyroid cancer patients currently [31, 35]. MRI is prone to respiration artefacts and can be more difficult to interpret by surgeons in the operating room.

## **7.4 FDG PET**

*Goiter - Causes and Treatment*

identified on scintigraphy.

**7.2 Ultrasonography**

further cytological evaluation is not necessary if a corresponding hot nodule is

though the sensitivities are significantly low for any single feature.

undergo FNA to look for evidence of malignant involvement.

adoption of ultrasound elastography for malignancy risk assessment.

of laryngeal tracheal, oesophageal or vascular involvement.

Ultrasound is also invaluable in assessing the risk of malignancy in lymph nodes. Location of the lymph nodes adds to the diagnosis. Malignant nodes are more likely to occur in levels III, IV and VI than in level II. PTC tumours arising in upper pole of the thyroid may be an exception as they have a propensity to demonstrate skip metastases to levels III and II. Size of >1 cm, ratio of long axis to short axis (also called as Solbiati index of <2), punctate calcification, presence of hyperechogenicity/mixed echogenicity/cystic changes, loss of hilum and peripheral hypervascularity are some of the features predictive of malignancy. While peripheral vascularity has the highest sensitivity of 86%, punctate calcifications are 100% specific for malignant involvement [30, 31]. However, no single sonographic feature is adequately sensitive for determining malignant involvement. Sonographically suspicious lymph nodes ≥8–10 mm in the smallest diameter should therefore

Ultrasound Elastography is a novel modality performed with an ultrasound machine using an elastography computational module. It provides a measure of tissue stiffness, and is being used for malignancy risk assessment. In a study by Azizi et al., thyroid nodule stiffness by elastography was an independent predictor of thyroid carcinoma, with a PPV of 36%, comparable to that of microcalcifications. On the contrary, in another study by Moon et al., elastography alone or in combination with grey scale ultrasound showed an inferior performance compared to grey scale ultrasonographic assessment for differentiation of benign and malignant thyroid nodules [32]. Guidelines currently do not recommend universal use or widespread

Since ultrasound is operator dependent and cannot adequately image deep anatomic structures and those acoustically shadowed by bone or air, preoperative cross sectional imaging like CT/MRI can be used as an adjunct in patients with clinical suspicion of advanced disease, like patients with an invasive primary tumour, or clinically apparent multiple or bulky nodal involvement. These modalities permit imaging beyond the routine cervical regions imaged by the ultrasound, like infraclavicular, retropharyngeal, parapharyngeal regions and the mediastinum. These also aid in preoperative planning to accurately delineate the inferior border, extent

Combined ultrasound and CT may have a higher sensitivity for macroscopic nodal metastasis detection preoperatively, compared to ultrasound alone [33, 34].

Ultrasonography has become an indispensable tool for the evaluation of thyroid nodules. Ultrasound is easily available, non-invasive and invaluable for dileniation and prognostication in these patients. Ultrasound in the hands of an experienced sonologist enables accurate identification of size, number of nodules, composition, echogenicity, margins, presence and type of calcifications, shape if taller than wide, vascularity and status of cervical lymph nodes. The pattern of sonographic characteristics of a nodule confers a risk for malignancy. Categories of high suspicion nodules are then subjected to invasive modalities like Fine Needle Aspiration (FNA) and cytological evaluation is done. Features with the highest specificities (median > 90%) are microcalcifications, irregular margins and tall shape, even

**86**

**7.3 CT and MRI neck**

Functional imaging with 18 F – FDG PET is currently not recommended routinely prior to initial surgery. However, it has been widely accepted as a modality for detecting recurrence of differentiated thyroid cancer, particularly in non-iodine avid disease. PET avidity has also been shown to be a strong predictor of poor outcome in metastatic thyroid cancer [31].

#### **7.5 Guidelines for evaluation, reporting and management of thyroid nodules**

Sonographic Scoring systems are used to stratify nodules according to risk of malignancy to allow centres for uniform reporting and reduce interobserver variability.

The **American Thyroid Association (ATA**) risk stratifies nodules into high suspicion, intermediate suspicion, low suspicion, very low suspicion and benign categories based on imaging characteristics. The sonographic features have been shown in **Figure 1** and the FNA cut-offs have been summarised in **Table 3**.

Similar to Breast reporting, the **American College of Radiology** has developed a reporting system for thyroid nodules known as **Thyroid Imaging Reporting and Data System (TIRADS)** for risk stratification based on points assigned for

#### **Figure 1.**

*Sonographic characteristics of thyroid nodules (Adapted from ATA guidelines for adult patients with thyroid nodules and differentiated thyroid cancer [1]).*


#### **Table 3.**

*Sonographic characteristics and FNA cutoffs of thyroid nodules Adapted from ATA guidelines for adult patients with thyroid nodules and differentiated thyroid cancer [1].*

#### **Figure 2.**

*The ACR-TIRADS scoring system of reporting for thyroid nodules (reproduced from www.acr.org).*

**89**

**Table 4.**

*Thyroid Nodule: Approach and Management DOI: http://dx.doi.org/10.5772/intechopen.91627*

**8. Fine needle aspiration (FNA)**

guideline one follows.

is preferred [29].

(AUS/FLUS)

composition, echogenicity, shape, margin and echogenic foci in the nodule. The total number of points is then used to classify a nodule into benign (TR1), not suspicious (TR2), mildly suspicious (TR3), moderately suspicious (TR4), and highly suspicious (TR5) categories. This system was proposed in a study by Horvath et al., and the probability of malignancy was 0, 3.4%, 14% and 87% in categories 2, 3, 4 and 5 respectively [36]. FNA is not indicated in TR1 and TR2 categories, whereas FNAC is advised if nodule size is ≥2.5, ≥1.5 and ≥ 1 cm, respectively, in TR3, TR4 and TR5 categories, respectively. The details of the scoring system are shown in **Figure 2**. Patients with multiple thyroid nodules ≥1 cm should be evaluated similarly as delineated above for patients with solitary nodule. Each nodule in a multinodular gland carries an independent risk of malignancy, and FNA should be done in sequentially based on imaging characteristics. In case of multiple sonologically similar low or very low risk pattern nodules, aspiration can be done in the largest

FNA is the single most valuable, cost effective and accurate method in the evaluation of a nodular goitre. It has demonstrated a sensitivity and specificity of 65–98 and 72–100%, respectively [22]. The use of FNA results in fewer surgeries, reduced cost of care, while improving the malignancy yield at thyroidectomy [37]. Selection of which nodule to subject to FNA is crucial for optimum yield of the procedure. This is based on the sonographic criteria and the size cut-offs depending on which

FNA is done as an outpatient procedure under local anaesthesia or no anaesthesia. 23–27 guage needles are used to obtain samples for cytopathology. For nodules with a high likelihood of non-diagnostic cytology (>25–50% cystic component) or sampling error (difficult to palpate or posteriorly located), ultrasound guided FNA

To address variability in reporting thyroid cytopathology, **Bethesda System for reporting thyroid cytopathology** was introduced in 2007. Cytologic adequacy for reporting was defined as presence of at least six groups of well visualised follicular cells, each group containing at least 10 well preserved epithelial cells, preferably on a single slide. The Bethesda system recognises six diagnostic categories and provides an estimation of cancer risk within each category, which has been summarised in **Table 4**.

Non diagnostic or unsatisfactory 1–4 20 (9–32) Benign 0–3 2.5 (1–10)

Suspicious for malignancy 60–75 70 (53–97) Malignant 97–99 99 (94–100)

*The Bethesda system for reporting cytopathology: diagnostic categories and risk of malignancy [38].*

**malignancy by Bethesda system, %**

**Actual risk of malignancy in surgically excised nodules, % median (range)**

5–15 14 (6–48)

15–30 25 (14–34)

nodule ≥2 cm, or surveillance can be continued without FNA.

**Diagnostic category Estimated risk of** 

Atypia of undetermined significance or follicular lesion of undetermined significance

Follicular neoplasm or suspicious for a follicular neoplasm (FN/SFN)

*Thyroid Nodule: Approach and Management DOI: http://dx.doi.org/10.5772/intechopen.91627*

*Goiter - Causes and Treatment*

**Ultrasound features Estimated** 

component of a partially cystic nodule with one

• Rim calcifications with small extrusive soft

• Evidence of extrathyroidal extension (ETE)

Hypoechoic solid nodule with smooth margins, without microcalcifications, ETE, or taller than

partially cystic nodule with eccentric solid areas, without microcalcification, irregular margin or

Spongiform or partially cystic nodules without any of the sonographic features described as low, intermediate or high suspicion patterns

*Sonographic characteristics and FNA cutoffs of thyroid nodules Adapted from ATA guidelines for adult* 

High suspicion Solid hypoechoic nodule or solid hypoechoic

or more of the following • Irregular margins

• Microcalcifications • Taller than wider shape

tissue component

Low suspicion Isoechoic or hyperechoic solid nodule, or

*patients with thyroid nodules and differentiated thyroid cancer [1].*

ETE or taller than wider shape

wider shape

(infiltrative, microlobulated)

**risk of malignancy**

>70–90% ≥1 cm

10–20% ≥1 cm

5–10% ≥1.5 cm

<3 ≥2 cm/

Observe

**FNA size cutoff (largest dimension)**

**Sonographic pattern**

Intermediate suspicion

Very low suspicion

**Table 3.**

**88**

**Figure 2.**

*The ACR-TIRADS scoring system of reporting for thyroid nodules (reproduced from www.acr.org).*

composition, echogenicity, shape, margin and echogenic foci in the nodule. The total number of points is then used to classify a nodule into benign (TR1), not suspicious (TR2), mildly suspicious (TR3), moderately suspicious (TR4), and highly suspicious (TR5) categories. This system was proposed in a study by Horvath et al., and the probability of malignancy was 0, 3.4%, 14% and 87% in categories 2, 3, 4 and 5 respectively [36]. FNA is not indicated in TR1 and TR2 categories, whereas FNAC is advised if nodule size is ≥2.5, ≥1.5 and ≥ 1 cm, respectively, in TR3, TR4 and TR5 categories, respectively. The details of the scoring system are shown in **Figure 2**.

Patients with multiple thyroid nodules ≥1 cm should be evaluated similarly as delineated above for patients with solitary nodule. Each nodule in a multinodular gland carries an independent risk of malignancy, and FNA should be done in sequentially based on imaging characteristics. In case of multiple sonologically similar low or very low risk pattern nodules, aspiration can be done in the largest nodule ≥2 cm, or surveillance can be continued without FNA.
