Errors and mistakes in ultrasound diagnostics of the thyroid gland

Abstract

Ultrasound examination of the thyroid gland permits to evaluate its size, echogenicity, margins, and stroma. An abnormal ultrasound image of the thyroid, accompanied by other diagnostic investigations, facilitates therapeutic decision-making. The ultrasound image of a normal thyroid gland does not change substantially with patient's age. Nevertheless, erroneous impressions in thyroid imaging reports are sometimes encountered. These are due to diagnostic pitfalls which cannot be prevented by either the continuing development of the imaging equipment, or the growing experience and skill of the practitioners. Our article discusses the most common mistakes encountered in US diagnostics of the thyroid, the elimination of which should improve the quality of both the ultrasound examination itself and its interpretation. We have outlined errors resulting from a faulty examination technique, the similarity of the neighboring anatomical structures, and anomalies present in the proximity of the thyroid gland. We have also pointed out the reasons for inaccurate assessment of a thyroid lesion image, such as having no access to clinical data or not taking them into account, as well as faulty qualification for a fine needle aspiration biopsy. We have presented guidelines aimed at limiting the number of misdiagnoses in thyroid diseases, and provided sonograms exemplifying diagnostic mistakes.

Introduction

The thyroid is an endocrine gland, situated in an anterior and lateral position to the larynx and the esophagus, located superficially under the skin, the subcutaneous tissue (the isthmus) and a layer of cervical muscles (the lobes). It is surrounded by a fibrous sheath. Septa composed of connective tissue extend from the capsule into the gland. It is covered anteriorly by the pretracheal fascia. The thyroid consists of two lateral lobes joined medially by the isthmus. From 10% to 30% of cases display also the pyramidal lobe, situated in the proximity of the isthmus⁽¹⁾.

The superficial location of the gland makes it easily accessible for an ultrasound scan which is usually taken when clinically palpable thyroid nodules or laboratory abnormalities suggestive of diseases of the thyroid gland are found^{(2, 3)}.

The ultrasound image of a normal thyroid does not alter substantially with patient's age, therefore the interpretation of abnormalities such as focal lesions, or generalized or focal alterations of echogenicity is relatively easy. Nevertheless, erroneous impressions in thyroid ultrasound reports still happen due to the existing diagnostic pitfalls irrespective of the continuous technical development (equipment) and the increasing experience of the practitioners. This article deals with the most common mistakes made in thyroid ultrasound imaging, the elimination of which should improve the quality of the rendered examinations and interpretation thereof.

The major diagnostic errors in the sonographic evaluation of the thyroid may be technique-related, be caused by a similarity of the neighboring anatomical structures to abnormal changes in the gland, be due to a wrong or inaccurate assessment of anomalies in the neighboring organs, or be the result of not taking into consideration the clinical data available. The most frequently encountered mistakes result from a wrong evaluation of focal lesions, not adherent to the standards of Polish Ultrasound Society (Polskie Towarzystwo Ultrasonograficzne, PTU)⁽⁴⁾.

Mistakes related to a faulty examination technique

Transducer frequency

Ultrasound examinations of the thyroid should be conducted with a linear, electronic transducer of a minimal frequency of 7.5 MHz. Application of a lower frequency transducer or a convex one may not permit to visualize small focal lesions, of a diameter <5 mm, or to allow an accurate interpretation of the visible lesions. The lesion showed in fig. 1 may serve as an example. It is a thyroid cancer of 6 mm in diameter which was not visible in a scan conducted with a 3.5 MHz transducer. Ultrasound conducted with a linear 7.5 MHz transducer revealed a hypoechoic lesion, with no vascularity features in a color Doppler examination, morphologically similar to a cystic degeneration.

Fig. 1.

Sonogram shows a solitary, hypoechoic focal lesion 6 mm in diameter, found in the right thyroid lobe (arrow). Histopathology: follicular thyroid carcinoma

Thyroid size measurements

Numerous diagnostic mistakes result from an inaccurate assessment of thyroid size. The lobular volume is calculated using a simplified spheroid formula (V = 0.5 × lobular depth × width × length). Most mistakes occur when taking length measurement of lobes exceeding the length of the transducer's head. A difference in the lobular length of approx. 1 cm (e.g. 4.5 cm, instead of 5.5 cm) results in a 20% difference in the calculated thyroid volume. Where only a transducer with a 40 mm head is available, the measurements should be taken after putting together the longitudinal section image of the entire lobe from partial images. Measurement of the lobular length of a large goiter may be conducted with a convex transducer. In the case of an endothoracic (retrosternal) goiter (the presence of the lower poles of the thyroid in the anterior mediastinum), it is recommended to give two measurements of each lobe in a transverse section and the available length, measured to the point of the jugular notch. When evaluating the size of focal lesions (nodules), it is necessary to take measurements in three dimensions taking into account their hypoechoic rim. The vascularity of focal lesions (nodules) should be assessed with power Doppler or color Doppler modality, and the machine should be calibrated to allow depiction of the slowest flowing vessels.

Errors resulting from the similarity of the abnormal changes in the thyroid to the neighboring structures

In physiological conditions, diagnostic mistakes may occur due to the anatomical structures neighboring with the thyroid and the ones within the gland itself.

The cervical portion of the esophagus

The cervical portion of the esophagus in transverse section may mimic a focal thyroid lesion, especially where the echogenicity of the thyroid parenchyma is altered. Usually, the esophagus is located to the left from the midline, in a posterior position from the larynx and the trachea, and is adjacent to the medial-posterior surface of the left thyroid lobe⁽³⁾. Examination carried out in the long axis of the lobes allows to visualize the layer structure of the esophageal walls, the presence of gas bubbles in its lumen, and its peristalsis (fig. 2).

Fig. 2A, B.

Sonogram shows the esophagus visible in a transverse section (arrow), mimicking a focal lesion located in the inferior pole. In the longitudinal section visible: layer structure of the esophagus, fluid and gas bubbles in the lumen

Blood vessels

The ramifications of the superior thyroid vein, inferior thyroid vein and thyroid ima vein as well as the superior, inferior and ima artery present in the thyroid parenchyma can mimic small hypoechoic focal lesions. For a conclusive picture it is necessary to obtain scans in several sections, including the longitudinal ones which show the course of the vessels as well as with the help of color Doppler or power Doppler modality (fig. 3).

Fig. 3A, B.

Gray scale sonogram shows a hypoechoic focal lesion occupying the left thyroid lobe (arrow, A). Color Doppler sonogram shows the inferior thyroid vein and the inferior thyroid artery (arrow, B)

Mistakes resulting from the presence of anomalies in the proximity of the thyroid gland

Zenker's diverticulum

Zenker's diverticulum (pharyngoesophageal diverticulum) is an outpouching of the esophageal wall which occurs spontaneously or due to an outward pull. It may be palpable on the left side of the larynx, and clinically mimic a thyroid nodule. The incidence of esophageal diverticula is much lower than the one of focal lesions or thyroid nodules. There have been reports of pathological structures mimicking Zenker's diverticulum⁽⁵⁾. In an ultrasound scan the outpouching, just like a focal thyroid lesion, may present as an oval or circular structure. The food remnants or gas bubbles present in the diverticulum may mimic microcalcifications similar to the ones present in papillary thyroid carcinoma. The presence of peristalsis within the diverticulum, and association with the esophageal wall help to differentiate the anomaly. In dubious cases, an X-ray examination of the esophagus with a barium swallow is conclusive.

Parathyroid adenomas

Due to their proximity to the thyroid gland, parathyroid adenomas may cause false diagnoses of focal thyroid lesions. There are usually four parathyroid glands, dorsally located to the superior and inferior poles of the thyroid. Their location may, however, vary, including the mediastinum, the vicinity of the bifurcation of the common carotid arteries, or they may even be found within the thyroid gland. Normal parathyroid glands are not visible in an ultrasound examination. Typical adenomas of the parathyroid glands are oval, homogeneous, hypoechoic lesions, surrounded by a hyperechoic capsule, with a typical vascular pattern (a large vessel entering the adenoma, with a pointed end several millimeters from the capsule's margin). Intrathyroid parathyroid adenomas may simulate focal lesions (nodules) of the thyroid gland, whereas hypoechoic extrathyroid nodules may wrongly indicate parathyroid adenomas⁽⁶⁾. In such situations the conclusive signs and procedures include the clinical picture, scintigraphy using technetium-sestamibi as well as an elevated parathyroid hormone (PTH) level (figs. 4, 5).

Fig. 4.

Sonogram shows parathyroid hypertrophy (white arrow) visible as a hypoechoic, well-defined lesion, situated below the inferior pole of the right thyroid lobe in a patient with chronic renal insufficiency. Additionally, the patient presented with esophagus located on the right side of the neck (red arrow)

Fig. 5.

Sonogram shows an adenoma of the right parathyroid presenting as a solid, oval, hypoechoic lesion situated below the inferior pole of the right thyroid lobe (photo courtesy of professor RZ Słapa M.D. PhD)

Lymph nodes

The assessment of the cervical lymph nodes is an integral part of a sonographic thyroid evaluation. Suspicion of a neoplastic process or metastases to the lymph nodes is established based on the analysis of their echostructure, echogenicity, shape, capsule contours, the presence/absence of calcifications, hilum, anechoic areas, and the vascular pattern. The size of the lymph nodes is not a key parameter in terms of their character⁽⁷⁾. As there are numerous underlying reasons for lymphadenopathy, differentiation of abnormal lymph nodes visible on the neck may prove tricky. Where there are coexisting focal thyroid lesions and suspicious cervical lymph nodes, fine needle aspiration (FNA) biopsy of both changes is expedient (figs. 6, 7).

Fig. 6.

Sonogram shows hypoechoic, rounded cranial lymph nodes (arrows), with ill-defined capsule margins, and no visible hila, with metastatic involvement in a patient with papillary thyroid carcinoma

Fig. 7A.

Sonogram shows metastatic lymph nodes (arrows) in a patient with papillary thyroid carcinoma. Noticeable hyperechoic sinuses with microcalcifications

Fig. 7B.

Color Doppler sonogram shows papillary thyroid carcinoma, visible numerous tortuous vessels entering the lesion

Interpretation of thyroid image without considering the clinical background

Wrong interpretation of thyroid parenchyma echogenicity alterations is among the most frequent mistakes encountered in thyroid ultrasound reports. The echogenicity of the gland's normal parenchyma is higher than the echogenicity of the layer of muscles situated anteriorly to the thyroid (sternothyroid and sternohyoid muscle). A decrease in the echogenicity accompanied by the presence of antithyroid antibodies is consistent with autoimmune thyroiditis. It also allows to monitor the course of therapy, as the level of decrease in the echogenicity corresponds to the level of the antithyroid antibodies⁽⁸⁾.

A decrease in thyroid echogenicity is, however, unspecific on its own. It may also be featured in Hashimoto's thyroiditis (due to diffuse lymphocyte infiltrates), in Graves’ disease (due to a decreased colloid amount, diminished size of the thyroid follicles, and increased blood flow through the gland's parenchyma), in an advanced stage of sub-acute thyroiditis as well as in a majority of other thyroiditis types (such as radiation-induced thyroiditis or drug- induced thyroiditis). Therefore, ultrasound reports should not contain a definitive diagnosis of Hashimoto's thyroiditis where background clinical data is not known or available. Suspicion of autoimmune thyroiditis is the advisable descriptive term in such cases.

Increased vascularity found in a qualitative Doppler examination is the hallmark of hyperthyroidism in Graves’ disease and in the hyperactive stage of Hashimoto's thyroiditis. Moderately increased flows are also revealed in some of the cases of hypothyroidism related to acute thyroiditis in Hashimoto's thyroiditis (fig. 8). Increased parenchymal flow is not found in the advanced stages of the disease⁽⁹⁾.

Fig. 8.

Sonogram shows an increased blood flow in the thyroid parenchyma in the course of hyperthyroidism

Doppler ultrasound examination allows to estimate the advancement of the inflammatory changes, which, compared against the clinical picture and laboratory findings, facilitates the diagnosis and monitoring of the course of the disease. The application of color and power Doppler modalities is useful for evaluating the vascularity of the thyroid focal lesions when selecting nodules for FNA biopsy, particularly in a multinodular goiter. Increased intranodular vascular distribution (type 3, i.e. a marked flow signal within the lesion) is the qualifying criterion in selecting nodules for the biopsy^{(9, 10)}. Quantitative Doppler examination has no application in thyroid diagnostics.

Figs. 9–11 display samples of sonograms of hyper- (fig. 9) and hypoactive (fig. 10) thyroid, and of autoimmune thyroiditis (fig. 11), where a good correlation between the level of thyroid hormones and antithyroid antibodies was established.

Fig. 9.

Sonogram shows hyperthyroidism in the course of Graves’ disease: moderate enlargement of the thyroid gland, heterogeneous echogenicity, visible dilated blood vessels in the thyroid parenchyma (arrows). The image was erroneously interpreted as parenchymatous goiter

Fig. 11.

Sonogram shows a typical image of lymphocytic thyroiditis: numerous hypoechoic infiltrates in the thyroid parenchyma

Fig. 10.

Sonogram shows hypothyroidism: the thyroid small, decreased echogenicity, thyroid margins ill-defined, visible echoes from the stroma (arrows)

Ultrasound examinations following thyroidectomy due to a multinodular goiter are conducted to evaluate the presence of nodular lesions in the stumps of thyroid lobes. The lesions found most commonly tend to be benign hyperplastic nodules, yet they qualify for FNA biopsy, in adherence to the generally accepted rules. The most frequent errors include inaccurate size evaluation of the stumps of the thyroid lobes, descriptions referring to bilateral stumps in patients who have undergone a unilateral surgery, and focal lesion diagnoses where irregular structure of the stumps is found due to the presence of postsurgical scarring. The remaining thyroid parenchyma is susceptible to echogenicity disturbances in the form of calcifications and fibrosis (fig. 12).

Fig. 12.

Sonogram shows stumps of the thyroid lobes following thyroidectomy. Heterogeneous echogenicity of the stump parenchyma, numerous minor calcifications in the parenchyma (arrows)

Patients having undergone malignant thyroid tumor resection are evaluated in terms of potential recurrence in the tumor bed and metastases to the lymph nodes. Among possible mistakes one that is definitely worth mentioning is a displaced sternothyroid and sternohyoid muscle being mistaken for as thyroid tissue remnant. Differentiating a local tumor recurrence from a postoperative area of fibrous tissue is also challenging.

Errors resulting from misinterpretation of focal lesions in the thyroid parenchyma and referring them for further diagnostics, including FNA biopsy procedure

Despite the high incidence of thyroid focal lesions and nodules, thyroid carcinoma is a rare condition only found in 1–2% of lesions. Even though nodules (focal lesions) are referred for FNA biopsy based on the risk factors described in the subject literature and Polish Ultrasound Society standards⁽⁴⁾, the procedure confirms the presence of a malignant tumor in no more than 13% of cases.

On the one hand, wrong evaluation of focal lesions and thyroid nodules in terms of warranting biopsy usually concerns small lesions which do not meet the qualifying criteria, yet can be foci of the neoplastic disease. On the other, there are also cases where despite the presence of sonographic features of increased malignancy risk, no cancer is detected in the microscopic examination.

Cystic thyroid nodules (CTN)

A cystic thyroid nodule or lesion in the thyroid parenchyma may be either:

• a simple cyst displaying sonographic cyst features – smooth margins, echo-free in the lumen, enhancement behind the posterior wall (fig. 13);

• a degenerative cyst, most frequently associated with degenerative processes, presenting as a small hypoechoic focus, usually of a diameter of 2–6 mm (fig. 14).

Fig. 13.

Sonogram shows a typical image of a thyroid cyst

Fig. 14.

Sonogram shows small cystic nodules (CTN) in the thyroid parenchyma

CTNs, especially solitary ones, may be erroneously interpreted as solid hypoechoic lesions with indications for FNA biopsy. Differentiation is facilitated by the evaluation of their vascular pattern. However, grim consequences may arise from forgoing the biopsy of cystic nodules with a solid component. There are literature reports of papillary carcinomas of a solid-cystic structure, accounting for 25–30% of cases of all papillary cancers. Oncocytic tumors (thyroid oncocytoma) are another example of solid-cystic lesions (fig. 15). Spongiform (microcystic) degeneration within a lesion is a benign feature allowing to forgo the biopsy.

Fig. 15.

Sonogram shows a solid-cystic focal lesion with well-defined margins, with solitary peripheral vessels. Cytology: oncocytic tumor

Multinodular goiter

Selecting a focal lesion for FNA biopsy in a multinodular goiter tends to be the trickiest stage of thyroid imaging diagnostics. The risk of cancer incidence in patients with a multinodular goiter is similar to that in patients with a solitary nodule (focal lesion). In cases of a multinodular goiter, selection of a nodule (focal lesion) for a biopsy should depend on the clinical and sonographic features of the increased malignancy risk. The clinical malignancy features include: rapid nodule (focal lesion) growth, a hard nodule palpably appearing to be bound to its environment, lymphadenopathy, family history of thyroid cancer, family history of MEN2 syndromes, having sustained exposure to ionizing radiation, the lesion's occurrence under 20 years of age or over 60 years of age as well as a nodule >4 cm. The ultrasound characteristics include: microcalcifications (the only feature of an out-weighing predictive value), decreased echogenicity, solidity, irregular margins, increased internal vascularity, taller than wide in transverse view.

The risk of neoplastic process in a multinodular goiter is sufficiently ruled out when 3–4 lesions have been negatively verified in the biopsy. On the other hand, where there are numerous, morphologically consistent focal lesions with no malignancy features, it is recommended to verify the largest lesion, or to perform the procedure in two stages (within a period of no more than 6 months). It should be remembered that the number of complications increases with too many punctures and so do the costs.

In spite of the strict FNA indications and qualifying criteria, it is the multinodular goiter where preoperatively undiagnosed thyroid cancers are found. Multinodular goiter is also the main reason for reoperation due to cancer being found in the postoperative material in the course of histopathological examination. Poor diagnostics results can occur due to nodules being located retrosternally as well as due to the multifocal nature (amounting to 40% of cases) of the most common thyroid cancer type, namely the papillary carcinoma.

“Halo” sign

Wrong interpretation of the “halo” sign (fig. 16) which is commonly encountered in ultrasound images of solid focal lesions in the thyroid parenchyma is another diagnostic mistake. Contrary to popular beliefs, the symptom is not pathognomonic of nodules which have a capsule (such as follicular nodules or Hürthle cell lesions) where no vascular flow is detected⁽¹¹⁾. It is also present in hyperplastic nodules which lack a capsule. It occurs due to the pressure and hyperemia on the border with the surrounding thyroid parenchyma, caused by the slowly growing nodule. The information about the presence of the “halo” sign should always be included in the ultrasound report, yet diagnostic conclusions concerning the character of the focal lesion cannot be based on it (nodule).

Fig. 16.

Sonogram shows a typical ultrasound image of the halo sign in a solitary thyroid nodule (A), and hyperplastic nodules in a multinodular goiter (B) (arrows)

Micro- and macrocalcifications

Calcifications in the thyroid parenchyma, in focal lesions, and in the peripheral areas of nodules are clearly visible in an ultrasound, and are found in over 30% of focal thyroid lesions (fig. 17A, B).

Fig. 17A.

Sonogram shows a hypoechoic focal lesion with micro- and macrocalcifications (arrow), warranted FNA biopsy, with a visible needle end in the lesion

Fig. 17B.

Sonogram shows a solid hypoechoic lesion with well-defined margins, with micro- and macrocalcifications. Cytology: a hyperplastic nodule

Differentiating the nature of the focal lesions based on the calcification pattern (type) present within focal thyroid lesions is subject to numerous limitations. Microcalcifications, defined as echoic foci with or without posterior acoustic shadowing (<2 mm in diameter), in a microscopic examination correspond to calcium deposits in necrotic cells, termed psammoma bodies. They constitute a sensitive predictor of an increased malignancy risk in the focal thyroid lesions. Where microcalcifications are found (typically, but not limited to, in papillary carcinomas), neoplastic nature of a focal lesion is predicted with 95% sensitivity. Five percent of benign lesions also present with microcalcifications⁽¹²⁾.

The absence of acoustic shadowing may impede differentiation between microcalcifications and echoic foci with comet tail artifact. In the case of cystic lesions, the latter is indicative of the presence of colloid crystals within (fig. 18). These changes are typical for benign nodules and allow to forgo FNA biopsy. However, where they accompany calcifications within focal lesions, they may be suggestive of papillary carcinoma.

Fig. 18.

Sonogram shows a comet tail artifact (arrow) in a colloidal degeneration of a thyroid nodule

Macrocalcifications, defined as calcifications exceeding 2 mm in diameter with the presence of acoustic shadowing, are found within benign lesions (more commonly), and in malignant tumors. The so-called egg-shell or rim calcifications tend to indicate a benign nodule.

Conclusion

Ultrasound examination of the thyroid gland is the leading imaging modality thereof. Frequently, the evaluation of the thyroid parenchyma and its focal lesions poses challenges, as is the case with other organs too^(13–17). In the case of thyroid ultrasound, the resulting mistakes may be due to a faulty examination technique, or the similarity of the neighboring anatomical structures to the abnormal changes within the gland. Most commonly, they consist in a misinterpretation of the visible focal lesions and misguided qualification for a biopsy procedure. The updated thyroid examination standards by the Polish Ultrasound Society provide a useful background, helpful in limiting the number of diagnostic mistakes⁽⁴⁾.

Conflict of interest

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