Standards of the Polish Ultrasound Society – update. Ultrasound examination of thyroid gland and ultrasound-guided thyroid biopsy

Abstract

Ultrasonography is a primary imaging technique in patients with suspected thyroid disease. It allows to assess the location, size and echostructures of the thyroid gland as well as detect focal lesions, along with indication of their size, echogenicity, echostructure and vascularity. Based on these features, ultrasound examination allows to predict abnormal focal lesions for biopsy and monitor the biopsy needle track. This paper presents the standards of thyroid ultrasound examination regarding ultrasound apparatus technical requirements, scanning techniques, readings, measurements, and the description of the examination. It discusses the ultrasound features of increased malignancy risk in focal lesions (nodules) found in the thyroid gland. It presents indications for fine needle aspiration biopsy of the thyroid gland for the visibility of single nodules (focal lesions) and numerous lesions as well as discusses contraindications for thyroid biopsy. It describes the biopsy technique, possible complications and rules for post-biopsy monitoring of benign lesions. The paper is an update of the Standards of the Polish Ultrasound Society issued in 2011. It has been prepared on the basis of current literature, taking into account the information contained in the following publications: Thyroid ultrasound examination and Recommendations of the Polish Ultrasound Society for the performance of the FNAB of the thyroid.

This paper is an update of Standards of the Polish Ultrasound Society issued in 2011. It has been prepared on the basis of current literature and information contained in the following publications: Thyroid ultrasound examination ⁽¹⁾ and Recommendations of the Polish Ultrasound Society for the performance of the FNAB of the thyroid ⁽²⁾.

Introduction

Ultrasonography (USG) examination is a primary imaging examination in patients with suspected thyroid disease. It allows to assess the location, size and echostructure of the thyroid gland as well as check the parenchyma for inflammatory and focal lesions, including accurate measurements of their size, determining their nature and monitoring the biopsy needle track. An integral element of thyroid ultrasound is the assessment of lymph nodes located in the vicinity. Thanks to advanced technologies of radiological and ultrasound imaging, the number of accidentally detected thyroid focal lesions has increased. According to the Polish National Cancer Registry, nodular lesions of the thyroid gland occur frequently, in approximately half of the population. The majority of them are benign. Malignant nodules represent 1–2% of all the abnormalities diagnosed in the thyroid gland⁽³⁾. According to the American Thyroid Association, thyroid nodules are detected by ultrasound in 19–67% of the examined patients and 5–15% of them are carcinomas⁽⁴⁾.

Over the past two decades the number of new cases of thyroid cancer in Poland has significantly increased – 2192 cases (384 men and 1808 women) were recorded in 2010. Five-year survival rate among thyroid cancer patients has improved and amounted to 76.8% in men and 90.7% in women (data from 2009). The peak incidence of thyroid cancer is between 40 and 50 years of age⁽³⁾.

Indications for thyroid ultrasound

• Enlarged thyroid without palpable nodules.

• A palpable nodule or nodular goiter.

• Accidental detection of a focal lesion in the thyroid during ultrasound examination, computed tomography, magnetic resonance imaging or positron emission tomography, all performed due to other indications.

• Suspicion of thyroid disease based on abnormal laboratory test results, including hyperthyroidism, hypothyroidism, thyroiditis.

• Differentiation of causes of hyperthyroidism and hypothyroidism, clinical suspicion of thyroiditis.

• Cervical lymphadenopathy (excluding cases of infectious etiology).

• Screening in the group of increased risk of thyroid cancer (family history of thyroid cancer, carrying RET mutation, previous exposure of the neck to ionizing radiation, especially in childhood).

• Selection of a focal lesion with the highest malignancy risk for fine needle aspiration biopsy.

• Monitoring the size of benign thyroid nodules/focal lesions.

• Monitoring parenchymatous goiter treatment effects.

• Monitoring after the removal of the thyroid gland due to nodular goiter in order to assess treatment efficacy and analyze its effects (first examination after 6 months, subsequent scans every 12 months).

• Monitoring after thyroidectomy performed due to thyroid cancer in order to assess the radicalness of surgery and analyze the effects of treatment.

It is not recommended to perform ultrasound screening for the presence of clinically silent focal lesions in patients with no increased risk of cancer. Such examinations can be considered in obese individuals (BMI >30)^{(5, 6)}.

Apparatus

According to the standards of the Polish Ultrasound Society, thyroid ultrasound apparatus should meet the following technological requirements⁽¹⁾:

• electronic broadband linear transducer in the frequency range of 7–12 MHz (14 MHz); in case of nodular goiter and in obese patients transducers with a frequency of 4–8 MHz may prove useful;

• transducer head not shorter than 40 mm;

• at least 128 transceiver channels;

• second harmonic frequency;

• color Doppler and power Doppler modes;

• support programs for the calculation of length, surface area and volume.

It is also recommended to use transducers with 60–80 mm long heads, panoramic imaging mode or expanded field of view mode, which all facilitate the execution of the test in patients with enlarged thyroid. Ultrasonic beam focus should be set at half the thickness of thyroid lobe (lobes), with a possibility to adjust in order to optimize the image at selected depths. Pre-programmed setting parameters for thyroid scanning should be used.

Scanning technique and measurements

Thyroid ultrasound should be preceded by a subjective and objective examination in the field of thyroid disease.

As each ultrasound, also thyroid ultrasound requires the development of a certain pattern of conduct that will ensure a complete evaluation of the gland. The scanning usually starts with placing the transducer transversely to the midline of the body in order to evaluate the position of the thyroid gland in relation to the midline (thyroid located properly or displaced to the right/left). This is followed by obtaining an image of each thyroid lobe in the longitudinal and transverse axes. Subsequently, one should: measure the size of lobes and the isthmus, evaluate echogenicity of the parenchyma, assess the echostructure for the presence of focal lesions, assess the vascularity of parenchyma and focal lesions, and finally inspect the lymph nodes along the carotid vessels. Thyroid echogenicity is assessed in comparison to the echogenicity of the sternoclavicular and sternohyoid muscles located forward from the thyroid gland – under normal conditions it is higher than for the mentioned muscles. A healthy thyroid gland is characterized by a homogeneous echostructure. Heterogeneous echostructure may result from the presence of inflammatory or focal lesions. Echogenicity of focal changes within the thyroid gland must be assessed in relation to the echogenicity of the surrounding parenchyma.

In order to determine the size of the thyroid, measurement cursors should be positioned on the outer contours of each lobe corresponding to the sack. Three dimensions of each lobe (thickness, width and length) and the thickness of the isthmus must be measured. The thickness of the lobes and the isthmus, and the width of the lobes are measured at the maximum cross-section, and the length of the lobes – at the maximum longitudinal section of each lobe. Thyroid volume is calculated on their basis with a simplified formula for the volume of a spheroid: V = 0.5 × W × H × L, where V – volume of the lobe, 0.5 – simplified coefficient, W – width, H – height, L – length. The volume of the thyroid gland is the sum of the volumes of the right and left lobe. The volume of the isthmus is ignored when calculating the volume of the thyroid.

Enlarged thyroid is diagnosed on the basis of increased volume of the whole gland and not the values of individual dimensions. The correct volume of the thyroid should not exceed 20 ml in women and 25 ml in men^{(1, 7)}.

During thyroid ultrasound the following should be assessed:

• location of the thyroid;

• dimensions of the lobes, thickness of the isthmus and volume of the thyroid;

• borders (even, uneven, with signs of traction, visible in segments, invisible);

• parenchymal echogenicity (normal, reduced, increased);

• echostructure (normal, heterogeneous in its entirety, without the presence of/with the presence of focal lesions);

• presence of abnormal focal lesions, their echogenicity (normoechoic, hypoechoic, hyperechoic, with mixed echogenicity) and echostructure (solid, fluid-filled, solid and fluid-filled);

• presence of calcifications in the parenchyma and focal lesions in the thyroid (macrocalcifications of diameter >2.0 mm, microcalcifications of diameter <2.0 mm);

• presence of hyperechoic echoes from the stromal connective tissue of the thyroid;

• vascularity of the thyroid parenchyma and abnormal focal lesions using color Doppler and power Doppler (qualitative);

• number, size, shape and echostructure of cervical lymph nodes.

If the thyroid is significantly enlarged and the lower poles of the thyroid lobes are located in the frontal mediastinum, the description of the examination should include retrosternal location of the lower poles and, if possible, it should be measured how deep the lower poles descend below the zygomatic notch of the sternum^{(1, 8)}.

Description of the examination

Each description of thyroid ultrasound examination should include the following information:

• patient details (name and surname, date of birth/patient identification number);

• name of ultrasound apparatus, transducer type and frequency;

• name of the unit which carried out the examination;

• details of the examining physician;

• description of the examination which should include:

  • dimensions of the lobes and the volume of the thyroid,
  • assessment of the echogenicity of parenchyma and the borders,
  • assessment of the echostructure,
  • description of morphological abnormalities in the thyroid parenchyma of scattered (fluid degenerations, calcifications, parenchymal heterogeneity) or focal nature (solid, solid and cystic, cystic lesions),
  • in case of focal lesions: their location, echogenicity and echostructure, dimensions (three), presence of calcifications and fluid degenerations; qualitative assessment of the vascularity of thyroid parenchyma and focal lesions; description of enlarged cervical lymph nodes located in the thyroid gland area, including their morphology and features which may indicate lymph node metastases. If the thyroid ultrasound scan reveals abnormalities in carotid arteries, their branches supplying the brain and in the surrounding soft tissues, relevant information should be included in the description of the examination with indication of the need for further diagnosis. The description of the examination shall also include general information on the history of surgery or radioiodine treatment, with reference to the data obtained from the patient (“according to the data obtained from the patient”) or detailed information indicating the date of the treatment provided there is access to medical records.

The description of the examination should also distinguish between clinical lesions (palpable) which must be described as thyroid nodules, and non-clinical lesions (non-palpable) which must be described as an abnormal focal lesions.

Terminology of pathological diagnoses (such as adenoma or carcinoma) or clinical conditions (such as Graves’ disease, Hashimoto's thyroiditis, etc.) should not be used in the description of the examination. If parenchyma of the thyroid lobes contains numerous focal lesions (more than five in each lobe), three dimensions of the largest and smallest lesions should be stated; if the lesions form a conglomerate, three dimensions of the conglomerate should be stated along with a detailed description of features that increase malignancy risk. If there are less than five abnormal focal lesions in each thyroid lobe, the description should include the size and location of each such lesion.

The same evaluation standards apply to surgically treated thyroid. Description of the thyroid ultrasound should be completed by a diagnostic conclusion, such as “thyroid normal,” “parenchymal goiter,” “nodular goiter,” “suspected inflammation of the thyroid gland.” If there are deviations from the normal condition, the conclusion should provide information about the need for scheduling a follow-up thyroid ultrasound examination or other diagnostic tests such as chest X-ray, scintigraphy, fine needle biopsy, or computed tomography. The description of the examination must be accompanied by photographic documentation demonstrating the abnormalities⁽¹⁾.

Recommendation by the Polish Ultrasound Society on the performance of ultrasound-guided fine needle aspiration biopsy of the thyroid

The presence of nodular lesions in the thyroid gland is associated with increased risk of cancer. Ultrasound examination in presentation B still does not allow, despite the use of color Doppler, power Doppler, 3D/4D imaging, elastography and ultrasound contrast agents, for unambiguous differentiation between benign and malignant thyroid lesions. The primary test used to diagnose thyroid cancer is ultrasound-guided fine needle aspiration biopsy (FNAB), performed under the control of ultrasound image. It does not require special preparation, results in minor pain and enables a rapid cytological diagnosis⁽⁷⁾.

Cytology examination has some significant limitations. It does not allow for the differentiation between cancer and follicular adenoma as well as some cases of papillary carcinoma and autoimmune thyroiditis. FNAB is subject to a relatively high risk of false negative results in case of thyroid cancer: 1.3–13.6%. This entails the need to repeat or conduct a follow-up test relatively soon in case of lesions revealing a high probability of malignancy in ultrasound⁽⁹⁾. The percentage of false positive cytology results (fine needle biopsy) is significantly lower and amounts to 0.25–3%%⁽⁷⁾.

Core needle biopsy (CNB) of the thyroid (19–20 Ga) is an additional method used when FNAB gives inconclusive results. It is rarely used, usually for suspected lymphoma or differential diagnosis of hypocellular fibrous lesions, e.g. Riedel's thyroiditis⁽¹⁰⁾.

Indications for FNAB based on clinical examination and thyroid ultrasound

Clinical factors of increased malignancy risk of thyroid focal lesions (nodules)^{(4, 6, 11, 12)}:

• nodule rapidly growing, hard, non-displaceable during a clinical examination;

• enlarged lymph nodes;

• positive family history of thyroid cancer;

• history of exposure to ionizing radiation;

• nodule appearing before 20 or after 60 years of age;

• nodule size >4 cm.

Ultrasound features of increased malignancy risk of thyroid focal lesions (nodules)^{(1, 4, 6, 13, 14)}:

• abnormal lymph nodes;

• invasion of surrounding organs and tissues;

• microcalcifications;

• low echogenicity of lesions;

• predominance of the anterior-posterior dimension over the lateral dimension of lesions (height greater than width);

• solidity;

• irregular, lobular edges;

• power Doppler examination reveals vessels inside lesion with increased flow and chaotic course.

The above features occurring individually within focal lesions in the thyroid do not have enough predictive power to indicate cancerous nature (except metastases to cervical lymph nodes). Diagnosing two or more features greatly increases the risk of cancer and is an indication for scheduling FNAB. Selection (typing) of thyroid nodules for FNAB is carried out on the basis of the morphological characteristics and nodule size. If there are numerous lesions of similar morphology, a lesion dominant in terms of size should be biopsied.

Features of an ultrasound image with a higher predictive power of malignancy risk include: the presence of lymph node metastases, invasion of adjacent structures and microcalcifications within focal lesions. Ultrasound image features such as very low echogenicity of nodules, solid echostructure, predominance of anterior-posterior dimension over lateral dimension (height greater than width), irregular borders and presence of blood in the nodules of an irregular course have less predictive power of malignancy risk.

Indications for FNAB in case of a single nodule (focal lesion)

• Nodule palpable in physical examination and confirmed by ultrasound, larger than 5 mm in all dimensions – unless autonomous in terms of scintigraphy.

• Nodule non-palpable in physical examination, detected in ultrasound test, larger than 10 mm in all dimensions, particularly if solid and hypoechoic – unless there are no other foci demonstrating higher malignancy risk.

• Nodule palpable in physical examination, detected in ultrasound test, measuring 5–10 mm – if at least one clinical or ultrasound feature of high predictive power of malignancy risk present or if two ultrasound features of smaller predictive power of malignancy risk coexist.

• Nodule size >4 cm, regardless of the presence of factors indicating benignity of the nodule.

• Nodule of any size, if diagnosis revealed lymph nodes metastases, distant and high concentration of calcitonin or RET mutation predisposing to medullary carcinoma.

• Nodule revealed in FDG-PET or scintigraphy (99Tc-MIBI) as a hot nodule^{(1, 4, 6)}.

Indications for FNAB in case of multiple nodules (focal lesions)

• Selection of a nodule for biopsy is carried out in accordance with the criteria specified for individual lesions, clinical and ultrasonographic characteristics of malignancy risk listed above being the main criterion.

• In case of multiple lesions of similar morphology, the largest nodule qualifies for biopsy as first.

• In case of multiple nodules that meet the eligibility criteria for biopsy, sufficient exclusion of malignancy risk is achieved only after diagnosing benignity of 3–4 nodules. It is permissible to perform FNAB of subsequent lesions in 3–6 month intervals. The order of performing the biopsies depends on the clinical and ultrasound criteria for malignancy of the nodules.

Indication for FNAB in case of thyroid cancer surgery patients

• Focal lesions visible in thyroid bed.

• Cervical lymphadenopathy (circular nodes without recesses, with a long axis of >1 cm and short axis >5 mm, heterogeneous, hypoechoic, displaying cystic degenerations and microcalcifications, vascularized on edges)⁽¹⁵⁾.

Indications and clinical interpretation of FNAB in children and pregnant women are the same as in other patients.

Criteria for withdrawal from the FNAB of thyroid nodules^{(1, 4)}

• A simple thyroid cyst (cancer risk <1%).

• A single autonomous nodule.

• An autonomous nodule in multinodular goiter.

• A normoechogenic nodule of spongy (small cyst) structure.

• A nodule with a diameter of <5 mm in all dimensions, except for a nodule of any size if diagnosis revealed lymph nodes metastases or distant, high concentrations of calcitonin or RET mutation predisposing to medullary carcinoma.

Patient's written, informed consent must be obtained prior to FNAB. In case of minors, consent must be given by the parent or legal guardian.

Contraindications to FNAB of the thyroid^{(1, 4)}

Mandatory:

• severe bleeding disorder;

• purulent foci in the skin of the neck;

• lack of cooperation from the patient.

Relative:

• treatment with anticoagulants.

Anticoagulant therapy may be associated with an increased risk of hematoma following thyroid biopsy. This risk depends on the type and dose of taken medicines. In any case, prior to FNAB one should determine the type of drugs, dosage and indications for their use. Proceedings before the scheduled biopsy is dependent on the risk of thromboembolic complications. In case of low risk (e.g. if the patient recovered from thromboembolism over a year ago, or suffers from atrial fibrillation with no history of internal diseases) it seems reasonable to interrupt the anticoagulation treatment. Moderate and high risk of thromboembolic complications justifies performing the biopsy during treatment or applying low molecular heparin bridging therapy. Biopsies in patients taking anticoagulants should be carried out using a needle with a diameter of 0.4 mm, with pressure applied on the puncture site for 5 minutes after the test.

Rules of procedure depending on the type of anticoagulants:

• antiplatelet drugs:

  • NSAIDs – biopsy permissible,
  • aspirin – biopsy permissible when daily dosage does not exceed 300 mg; at higher doses it is recommended to discontinue the medication for 7 days prior to the test (in patients with a low risk of thromboembolic complications),
  • clopidogrel – lack of research, probably comparable to aspirin; patients with a low risk of thromboembolic complications recommended to discontinue the drug 5 days prior to the test;
• oral anticoagulants:

  • acenocoumarol, warfarin – biopsy allowed at the rate of INR <2.5–3; it is necessary to check INR one day prior to the test,
• low molecular weight heparins:

  • prophylactic dose (lower risk of thromboembolic events) – biopsy allowed 8 hours after the administration of the last dose,
  • therapeutic dose (higher risk of thromboembolic events) – biopsy allowed 8 hours after the administration of the last dose;
• new oral anticoagulants:

  • dabigatran (Pradaxa) – recommended discontinuation of the drug one day prior to the biopsy,
  • rivaroxaban (Xarelto) – recommended discontinuation of the drug one day prior to the biopsy,
  • apixaban (Eliquis) – recommended discontinuation of the drug one day prior to the biopsy^{(6, 16, 17)}.

Possible complications after FNAB of the thyroid^{(1, 3, 6)}

• Pain, swelling.

• Fainting.

• Hematoma (prevention – applying pressure, 30-minute observation in case of deeply located lesions).

• Hemorrhage or hematoma requiring surgical intervention.

• Paralysis of the recurrent laryngeal nerve (0.036%) – dysphasia and dysphonia usually develop after 48 hours after FNAB and take up to 4 months to subside.

• Infection – rare (at risk: patients with HIV, diabetes, tuberculosis or atopic dermatitis).

• Implementation of cancer cells along the needle track – does not occur when needles 23 Ga or smaller are used.

Performance technique of FNAB of the thyroid^{(1, 7)}

1. Selection and localization of a lesion in ultrasound test.

2. Disinfection of the skin of the neck with 70 percent alcohol or other disinfectant (approved for use by the manufacturer of ultrasound apparatus).

3. Puncturing the thyroid gland with a needle of the external diameter of 0.4–0.5 mm and the length of 2.5–4.0 cm. Needles with a diameter of 0.8 mm are used for emptying cysts with dense contents.

4. Puncturing the skin under the guidance of the ultrasound image, puncturing the needle into the lesion inside the thyroid and making quick sliding movements with it until the first level of liquid appears in the cone of the needle. Thyroid FNAB is performed “offhandedly,” without the use of a syringe and syringe holders used to create sub-pressure in its volume. The holder makes it difficult to maneuver the needle.

5. Registering the tip of the needle after insertion into the lesion in a digital image or via a videoprinter. The registration confirms the correctness of the puncture. It is recommended to attach the picture of the registered position of the needle inside the lesion to the description of the material obtained from the FNAB. Description of the examination would begin with the words: “The tip of the needle in the lesion, see attached photo documentation.”

6. Injecting the obtained aspirate onto a glass and performing thin smears, preserving them subsequently with 96 percent alcohol or cytofix. Coloring thus obtained preparations with hematoxylin and eosin.

7. Applying pressure on the puncture site for 5 minutes after the FNAB – minimizes the risk of hematoma.

Monitoring benign focal lesions/nodules after FNAB

• Clinical and ultrasound monitoring every 6–18 months.

• Enlargement of the nodule (increase in diameter by 20% or in volume by 50% with at least two dimensions increased by at least 2 mm) and emergence of high-risk malignancy features are an indication for re-biopsy to be scheduled after 6–12 months.

• Another FNAB should be considered after 3 months in case of correct or non-diagnostic biopsy result of a lesion displaying suspicious features in the ultrasound. If the assessment of the nodule indicates a high probability of malignancy, the period should be shorter than 3 months^{(1, 4, 18)}.

A new technique which allows to differentiate focal lesions of the thyroid on the basis of their different deformability is sonoelastography. Published test results are not sufficient to present clear criteria for differentiating benign lesions from malignant ones. However, this method allows to distinguish abnormalities suspected of malignancy which were not typed for FNAB in presentation B, and may be helpful in determining biopsy sites. Numerous sonoelastography restrictions, such as the pulsation of the common carotid artery, the size and complex structure of focal lesions and problems resulting from low reproductibility of the method (especially compression elastography), prevent this method from being considered as an alternative to FNAB^{(19, 20)}.

Conclusion

The presented article is an update on thyroid ultrasound examination standards by the Polish Ultrasound Society. For the past two years, the Society has been releasing updated standards for ultrasound examinations of different organs^(21–25) based on the most current guidelines, criteria and knowledge. Adherence to the standards is a prerequisite for a correct and accurate diagnosis, it also allows to reduce the number and the scope of diagnostic mistakes, including ones made in thyroid ultrasound evaluation⁽²⁶⁾.

Conflict of interest

Authors do not report any financial or personal links with other persons or organizations, which might affect negatively the content of this publication and/or claim authorship rights to this publication.