Thyroid Nodule (Incidental)

thyroidnodule

Thyroid Nodule (Incidental)

• Thyroid nodules are defined as discrete lesions within the thyroid gland that are radiologically distinct from the surrounding thyroid parenchyma. They represent a common diagnostic challenge. Palpable nodules have been reported to occur in 5.3% of women and 0.8% of men 1 and in 20% to 76% of ultrasound examinations performed in the adult population. 2,3,4 In many cases they are discovered incidentally on carotid Doppler ultrasound. Incidental thyroid nodules (ITNs) are also found in about 16% of CT and MRI scans which include the thyroid region 3
• Although thyroid nodules are common, only around 4-7% of all nodules are malignant, 5 rising to about 15% in nodules larger than 10mm that are subjected to FNA. 6 This may be an overestimate given that obviously benign nodules, such as pure cysts are not usually subject to FNA. The other causes of thyroid nodules include colloid nodules, thyroid cysts, thyroiditis and benign follicular neoplasms
• Thyroid cancers may be of four types: papillary (85%), follicular (11%), medullary (3%) and anaplastic (1%) 7
• The numbers of thyroid cancers diagnosed have increased as a result of being found incidentally on imaging, some might say to epidemic proportions. Thyroid cancer rates have increased 2.4-fold between 1973 and 2002 8 and doubled between 2000 and 2009 9
• The vast majority of these are papillary type; these lesions, if they are less than 2 cm in size have an excellent prognosis – 99% of patients are alive at 20 years. Patients with small lesions, no personal history of radiation exposure and no family history of thyroid cancer, who have favourable signs at thyroid ultrasound, have a low risk of progression. 7 Although the incidence of papillary thyroid cancer has increased, the mortality rate has remained stable. In addition, autopsy series have shown a high prevalence of subclinical papillary thyroid cancers. 7 This suggests that there is a problem of over-diagnosis and that many individuals will die with their thyroid cancer rather than of it. This has led to suggestions for a change in nomenclature; to rename low risk papillary lesions as “micropapillary lesions of indolent course” (microPLICs). MicroPLICs are defined as low-risk lesions (smaller than 20 mm in patients with no family history or radiation exposure and no ultrasound evidence of extraglandular invasion). 7 However it should be noted that this term is not yet endorsed by any expert group. Patients with these lesions may be offered surveillance rather than active treatment 7,10
• Papillary thyroid microcarcinomas have an excellent prognosis. Hay et al followed up 900 patients with papillary thyroid microcarcinomas (WHO nomenclature) for a mean of 17 years and reported a mortality of 0.3% 11,28
• There are several international evidence and expert-consensus based guidelines for the management of thyroid nodules which provide sources for the present guideline 3,13,15,28,
• All patients with ITNs should undergo clinical assessment and serum thyroid stimulating hormone (TSH) measurement
• Patients with increased risk of thyroid cancer should proceed to US guided FNA
• Patients at average personal risk of thyroid cancer with low TSH levels should undergo thyroid scintigraphy
• Patients at average personal risk of thyroid cancer with normal or high TSH levels should undergo US of the thyroid

nomore

Consider No Further Evaluation

• In patients without systemic symptoms or signs and without local symptoms of thyroid disease, no risk factors for thyroid cancer and particularly older patients with co-morbidities, strong consideration should be given to no further investigation. Patients with lesions appearing invasive or with local nodal enlargement should be further evaluated
• Even in those patients who have non-benign nodules, the vast majority of these are papillary type lesions which, if they are less than 2 cm in size have an excellent prognosis; 99% of patients are alive at 20 years. Patients with small lesions, no personal history of radiation exposure and no family history of thyroid cancer, who have favourable signs at thyroid ultrasound, have a low risk of progression. 7 Although the incidence of papillary thyroid cancer has increased, the mortality rate has remained stable. In addition, autopsy series have shown a high prevalence of subclinical papillary thyroid cancers. 7 This suggests that there is a problem of over-diagnosis and that many individuals will die with their thyroid cancer rather than of it. This has led to suggestions for a change in nomenclature - to rename low risk papillary lesions (< 2 cm, no historical risk factors and no US signs of extra-glandular invasion) as "micropapillary lesions of indolent course" (microPLICs) 7

increasedrisk

Patients At Increased Risk Of Thyroid Cancer

• Prior radiation
• Rapid growth of a thyroid nodule
• Symptoms of hoarseness, vocal cord paralysis or dysphagia
• Family history of thyroid cancer or multiple endocrine neoplasia (MEN) syndromes
• Personal history of MEN syndrome
• Past history of partial thyroidectomy
• Palpable cervical lymph nodes
• Young patient < 35 (particularly male)

scintigraphy

Thyroid Scintigraphy

• With the widespread use of fine needle aspiration biopsy in the evaluation of thyroid nodules, the role of thyroid scintigraphy has diminished. However, it still has an important role in the patient with a palpable thyroid nodule and suppressed thyroid stimulation hormone (TSH) level 28
• Scintigraphy is most commonly done with technetium-99m pertechnetate, although radioiodine I-123 is sometimes used 22
• It is useful for classifying nodules as hyperfunctioning, hypofunctional or indeterminate according to the visible pattern of tracer uptake 23
• Hyperfunctioning nodules are rarely malignant and account for approximately 5-10% of thyroid nodules. Patients with hyperfunctioning nodules are usually managed with either surgery or radioiodine ablation
• Approximately 90-95% of palpable nodules will be hypofunctional or indeterminate on thyroid scintigraphy and these nodules should proceed to US 22
• Information for consumers on Thyroid Scintigraphy

ultrasound

Ultrasound

• All published evidence-based guidelines agree that ultrasound is the imaging modality of choice for the evaluation of the morphology of the thyroid gland. The need for imaging in asymptomatic individuals should be tempered by the known “benign” course of the majority of papillary cancers (which make up 90-95%) of thyroid cancers. Patients with unrelated co-morbidities and elderly patients may therefore not require further investigation of their ITN 7
• Clinically “solitary” nodules are in fact found to be part of a multinodular process in up to 70% of cases when US is performed. Patients with multiple thyroid nodules have the same risk of malignancy as those with solitary nodules. However, one large study found that a solitary nodule had a higher likelihood of malignancy than did a non-solitary nodule (p < 0.01), although the risk of malignancy per patient was the same and independent of the number of nodules 6
• Thyroid scintigraphy should also be considered in patients with multiple thyroid nodules, if the serum TSH is in the low or low-normal range, with fine needle aspiration (FNA) being performed on those nodules that are hypofunctioning 28
• Nodules should be assessed individually for suggestion of malignancy and those nodules which differ sonographically to surrounding nodules, or those with features of malignancy should undergo FNA
• All major guidelines suggest US-guided FNA on nodules with suspicious imaging features
• Features on ultrasound that suggest malignancy include 3,9,13,15,24,25,26,27,28
• Increased height to width ratio
• Irregular margins (infiltrative, spiculated or microlobulated)
• Microcalcifications
• Evidence of extrathyroidal extension (cervical lymph nodes, distant metastases)
• Solid hypoechoic nodule
• Increased blood flow centrally
• Absence of “halo”
• Low to moderate quality evidence suggests that individual ultrasound features are not accurate predictors of thyroid cancer. 24 However, the diagnostic accuracy of individual ultrasound features varies which must be considered when assessing the overall risk of malignancy. In a systematic review and meta-analysis of 31 studies looking at the accuracy of thyroid nodule ultrasound features in the prediction of thyroid cancer the high risk features which had the highest diagnostic odds ratio (DOR) and specificities include 24
• Taller than wider (DOR 11.14 95% CI 6.6-18.9, specificity 93%)
• Infiltrative margins (DOR 6.89 95% CI 3.35-14.1, specificity 79%)
• Internal calcifications (DOR 6.78 95% CI 4.48-10.24, specificity 81%)
• Features that are highly specific for benignity, and therefore will often militate against FNA include 26,27,28
• Spongiform configuration
• Cyst with colloid clot
• Giraffe pattern
• Diffuse hyperechogenicity
• Rather than rely on individual sonographic features, pattern recognition can be applied to identify benign nodules. In one series recognition of specific morphologic patterns was found to be an accurate method of identifying benign thyroid nodules that do not require cytologic evaluation and would have obviated more than 60% of thyroid biopsies 27
• Management of nodules < 10 mm in size should be considered based upon patient demographics, risk factors for malignancy and US findings. The accuracy of the features described that help distinguish benign and malignant nodules is dependent on size and reduced for nodules < 10 mm
• The incidence of cancer in nodules less than and greater than 10mm is not significantly different. However there is evidence that the micropapillary carcinomas that are the most frequently discovered cancers in the small lesions, rarely progress to clinically significant lesions. 7 FNA is not recommended routinely for nodules < 10 mm unless there are suspicious US features or the patient has clinical risk factors for thyroid cancer 28
• US-guided FNA of nodules should be performed on patients with increased personal risk of thyroid cancer 3
• Qualitative sonoelastography (ultrasound elastography) is an additional method of assessment which looks at tissue distortion when an external force is applied. 29 The most common method of reporting this modality is an elasticity score, usually between 1-4 or 1-5 with lower numbers representing greater elasticity and higher numbers representing greater firmness. The more firm the thyroid nodule, the increased likelihood of malignancy. 30 Quantitative approaches like strain ratio measurement and shear-wave elastography are new developments in sonoelastography 30
• Sonoelastography has a high sensitivity and specificity for the identification of thyroid nodules with the use of qualitative methods (elasticity score) of comparable sensitivity and specificity to quantitative methods (strain ratio). 31 The performance of sonoelastography distinguishing between benign and malignant thyroid nodules compared with FNA cytologic and histopathologic examination has revealed that sonoelastography is an excellent adjunctive screening tool for characterising thyroid nodules with a negative predictive value of an elasticity score of 1 at approximately 0.995. Given this the use of sonoelastography to determine which nodules are benign and not requiring FNA and therefore can be clinically followed up, is a promising area
• Whilst sonoelastrography is a promising area it is yet to achieve mainstream use in radiological practice. This is mainly due to factors including expertise, cost and logistical considerations. Additionally despite its potential as a screening tool, appropriate follow up for those assessed by elastrography to have benign nodules have not been delineated and require further consideration

fna

Ultrasound Guided Fine Needle Aspiration (FNA)

• Ultrasonography cannot accurately differentiate benign from malignant thyroid nodules and fine needle aspiration biopsy should be used selectively to avoid over-diagnosis and over-treatment. If the clinician follows current guidelines for the investigation of thyroid incidentalomas a proportion of malignant incidentalomas will inevitably be missed. Whether this is clinically important is controversial as it is generally agreed that the natural history of small incidental thyroid cancers is indolent. 7,34 Therefore, a one-size-fits-all approach is simply not practical. Instead, surveillance strategies should be individualised based on a nodule’s sonographic appearance. 35 Management of nodules < 10 mm in size should also be considered based upon patient demographics, risk factors for malignancy and US findings
• Fine needle aspiration (FNA) is the most accurate and cost-effective method for evaluating thyroid nodules 28 and is advised in patients with increased personal risk of thyroid cancer 9
• All major guidelines suggest US-guided FNA for nodules with suspicious imaging features. 3,15,25,28,36 Substantial growth can be defined as sonographic evidence of growth (20% increase in at least two nodule dimensions with a minimal increase of 2 mm or more than a 50% change in volume) or development of new suspicious sonographic features 28
• However, FNA is not indicated for purely cystic lesions and is likely to be unnecessary in a diffusely enlarged gland with multiple nodules of similar US appearance without intervening parenchyma 15
• In order to standardize the terminology used for reporting thyroid cytopathology from FNA, the National Cancer Institute Thyroid Fine-Needle Aspiration State of the Science Conference was held in Bethesda, Maryland in 2007
• The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) was created using the recommendations resulting from this conference 37
• TBSRTC recommends that each report begin with one of six general categories which each have an estimation of risk of malignancy (based on evidence and expert opinion) 28
• A meta-analysis of eight studies confirmed the validity of TBSRTC with a reported sensitivity of over 97%, a NPV for the benign category of 96.3% and a PPV for the malignant category of 98.6% 38
• The risk of malignancy for each category showed significant variability and it is recommended that risk of malignancy should be independently defined at each cytology centre or institution 28

• A benign result after US and FNA is reassuring, but a small risk of a false reassurance exists. This risk is much lower after a second benign FNA result. 39 Given this, international guidelines agree that some follow-up is sometimes appropriate depending on the ultrasound appearance on the nodule
• British guidelines recommend that patients with benign FNA results and benign ultrasound appearances do not require repeat FNA. On the other hand, they recommend that nodules with benign FNA results but suspicious ultrasound features should undergo repeat FNA. They are not specific about timing of follow-up 36
• American guidelines recommend that following an initial benign FNA result
• Nodules with highly suspicious US features should have repeat US and FNA within 1 year
• Nodules with low-to-intermediate suspicious US features should have repeat US at 12-24 months, with growth or increasingly suspicious features triggering either FNA or further US surveillance 28
• The American guidelines also state that
• There is insufficient evidence to guide firm follow-up recommendations for lesions with very low suspicion ultrasound findings and a single benign FNA result. It is not clear that further ultrasound is needed, but if it is performed, it should not routinely be done earlier than 2 years
• Nodules that have had benign cytology findings on two separate FNAs do not require further ultrasound surveillance 28
• An FNA is a relatively painless procedure that is sometimes done without local anaesthesia. A fine needle (23 gauge or thinner) is used and specimens are typically taken from several parts of the thyroid nodule. These tissue specimens are smeared immediately onto pathology slides for further staining and evaluation
• Information for consumers on Fine Needle Aspiration Biopsy

multiple

Multiple Nodules / Multinodular Goitre

• Clinically “solitary” nodules are in fact found to be part of a multinodular process in up to 70% of cases when US is performed. Patients with multiple thyroid nodules have the same risk of malignancy as those with solitary nodules. However, one large study found that a solitary nodule had a higher likelihood of malignancy than did a non-solitary nodule (p < 0.01), although the risk of malignancy per patient was the same and independent of the number of nodules 6
• Thyroid scintigraphy should be considered in patients with multiple thyroid nodules, if the serum TSH is in the low or low-normal range, with FNA being performed on those nodules that are hypofunctioning 1
• The management of patients with multinodular goitre and thyroid nodules has not yet been fully delineated in regards to which nodules should be biopsied
• Management strategies range from FNA of the dominant nodule to FNA of multiple nodules
• Where a dominant nodule is noted to be growing and / or changing in features, FNA should be undertaken 16
• Focusing on the most prominent nodule has been found to be the most predictive for malignancy in the few studies that have investigated the topic, though the diagnostic accuracy results of these studies was poor 17,18,19
• If a nodule has grown steadily, become distinctly dominant or has changed in nature then its risk for malignancy has been shown to be the same as that of a solitary nodule 20,21

suspicion

Degree of Suspicious Features on Ultrasound

• The American Institute of Ultrasound In Medicine 2013 Guidelines for Thyroid and Parathyroid Ultrasound Examination state that thyroid abnormalities should be imaged in a way that allows for reporting and documentation of the following 32
• The location, size, number and character of significant abnormalities, including measurements of nodules and focal abnormalities in three dimensions
• The localised or diffuse nature of any thyroid abnormality, including assessment of overall gland vascularity
• The sonographic features of any thyroid abnormality with respect to echogenicity, composition (degree of cystic change), margins (smooth or irregular), presence and type of calcification (if present) and other relevant sonographic patterns
• The presence and size of any abnormal lymph node in the lateral compartment of the neck
• Thyroid nodules can then be classified into five patterns according to the combination of ultrasound features present. 28 This method provides effective malignancy risk stratification for thyroid nodules, with a sensitivity of 95.3% and NPV 97.3% 33

High Suspicion (Malignancy Risk > 70-90%) 28

• Solid hypo-echoic nodule with one or more of
• Increased height to width ratio
• Irregular margins (infiltrative, spiculated or microlobulated)
• Microcalcifications
• Evidence of extrathyroidal extension (cervical lymph nodes, distant metastases)

Intermediate Suspicion (Malignancy Risk 10-20%)

• Solid hypoechoic nodule with
  • A smooth, regular margin and
  • No other suspicious features

Low Suspicion (Malignancy Risk 5-10%)

• Solid hyper-echoic or iso-echoic nodule with
• Regular margins
• No microcalcifications
• No extra-thyroid extension
• No other suspicious features

Very Low Suspicion (Malignancy Risk ≤ 3%)

• Spongiform configuration
• Partially cystic nodule
• No other suspicious features

Benign (Malignancy Risk ≤ 1%)

• Purely cystic nodule

followup

Follow-up

• A benign result after US and FNA is reassuring, but a small risk of a false reassurance exists. This risk is much lower after a second benign FNA result. 39 Given this, international guidelines agree that some follow-up is sometimes appropriate depending on the ultrasound appearance on the nodule
• British guidelines recommend that patients with benign FNA results and benign ultrasound appearances do not require repeat FNA. On the other hand, they recommend that nodules with benign FNA results but suspicious ultrasound features should undergo repeat FNA. They are not specific about timing of follow-up 36
• American guidelines recommend that following an initial benign FNA result
• Nodules with highly suspicious US features should have repeat US and FNA within one year
• Nodules with low-to-intermediate suspicious US features should have repeat US at 12-24 months, with growth or increasingly suspicious features triggering either FNA or further US surveillance 28
• The American guidelines also state that
• There is insufficient evidence to guide firm follow-up recommendations for lesions with very low suspicion ultrasound findings and a single benign FNA result. It is not clear that further ultrasound is needed, but if it is performed, it should not routinely be done earlier than two years
• Nodules that have had benign cytology findings on two separate FNAs do not require further ultrasound surveillance 28

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