T h e Ro l e of So n o g r a p h y i n T h y ro i d Ca n c e r Stephanie F. Coquia, MD*, Linda C. Chu, MD, Ulrike M. Hamper, MD, MBA KEYWORDS Thyroid nodules Thyroid cancer Fine-needle aspiration biopsy Cervical lymph node metastases Lateral neck compartment Central neck compartment
KEY POINTS
INTRODUCTION According to the National Cancer Institute, an estimated 63,000 cases of thyroid cancer will be diagnosed in 2014.1 When pathologically well differentiated and diagnosed early, the disease is highly treatable and can be curable. The 5-year relative survival rate of most types of stage I thyroid cancer approaches 100%.2 US is used routinely in the diagnosis and management of thyroid cancer, from initial detection and diagnosis to preoperative planning to postoperative surveillance. This review discusses the various roles of sonography in managing patients with thyroid cancer and reviews the sonographic appearance of thyroid cancer and nodal metastases.
NORMAL ANATOMY AND IMAGING TECHNIQUE The thyroid gland is a bilobed gland that sits atop the trachea within the anterior-inferior neck
(Fig. 1). The isthmus connects the right and left thyroid lobes. Each lobe measures approximately 4 to 6 cm in length and less than 2 cm in width and in the anterior-posterior dimension.3 The normal isthmus measures less than 6 mm in the anterior-posterior dimension. The normal gland is homogeneous in echotexture and hyperechoic compared with the adjacent strap muscles (see Fig. 1). After documentation of any thyroid lesion that has suspicious features for primary thyroid cancer, the cervical lymph nodes are imaged. A normal lymph node has an elongated shape (a 2:1 ratio between length and short-axis dimensions) and demonstrates an echogenic fatty hilum. Vascular flow is seen entering into the lymph node via the fatty hilum (Fig. 2) and the cortex is symmetrically hypoechoic. The neck can be divided into nodal levels or stations by anatomic landmarks. The numeric classification system of the neck nodal stations is outlined in Table 1 and depicted in Fig. 3.4 Using this classification, the neck can be divided into
Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 601 North Caroline Street, Baltimore, MD 21287, USA * Corresponding author. 601 North Caroline Street, JHOC 3142, Baltimore, MD 21287. E-mail address: [email protected] Radiol Clin N Am - (2014) -–http://dx.doi.org/10.1016/j.rcl.2014.07.007 0033-8389/14/$ – see front matter Ó 2014 Elsevier Inc. All rights reserved.
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Thyroid nodules are commonly detected on ultrasound (US). Specific sonographic features are found in many malignant nodules and lymph nodes. Identification of cervical nodal metastasis is important for accurate staging and surgical management of de novo thyroid cancer. Pathologic diagnosis of a thyroid nodule requires fine-needle aspiration (FNA). US accurately provides imaging guidance for FNA of indeterminate or suspicious thyroid nodules and cervical lymph nodes. US is routinely used in the postoperative surveillance of the neck for tumor recurrence in the thyroid bed or nodal stations.
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Cervical Lymph Nodes
Fig. 1. Normal sonographic appearance of the thyroid. The thyroid (arrows) sits atop the trachea (T) and is a bilobed structure echogenic to the adjacent musculature (M).
central and lateral neck compartments. Stations I, VI, and VII are considered central neck compartments and stations II to V are considered lateral neck compartments. The medial edge of the common carotid artery serves as a landmark to divide the central from the lateral compartment. The distinction between the central and lateral neck compartments is important for the surgical management of thyroid cancer if nodal metastases are present (discussed later).
IMAGING PROTOCOLS Thyroid The thyroid gland is imaged with a linear highfrequency transducer (7–15 MHz). Occasionally, if the thyroid gland is enlarged, a curved, lowerfrequency transducer may be used to fully image the thyroid. The right and left thyroid lobes are imaged in the transverse and sagittal planes. Anterior-posterior dimension, width, and length are measured at the mid thyroid gland. The isthmus is measured in the anterior-posterior dimension. Nodules, if present, are measured in the transverse and
The neck nodes are imaged with the same transducers as the thyroid: a high-frequency linear transducer for most of the nodal stations and occasionally a curved transducer for the lower and, therefore, deeper level IV and VI lymph nodes. Each nodal station within the neck is evaluated to assess for the presence of normal or abnormal lymph nodes. Normal-appearing lymph nodes can be documented for each level, with the fatty hilum included in the image. Measurement of sonographically normal-appearing lymph nodes is not necessary. Abnormal lymph nodes (discussed later) should be imaged and measured in the transverse and sagittal planes. The nodes also should be interrogated with color Doppler US to assess for abnormal and disorganized blood flow. General imaging protocols for the thyroid gland and cervical lymph nodes are summarized in Table 2.
IMAGING FINDINGS AND PATHOLOGY Types of Thyroid Cancer There are several types of primary thyroid cancer. Papillary thyroid carcinoma (PTC) is the most common, accounting for approximately 75% to 80% of thyroid cancers. PTC is multifocal in approximately 20% of cases and more common in females than males. PTC usually presents before age 40 years, often with cervical nodal metastases. It is also the most common thyroid malignancy in children. PTC has the best prognosis and highest survival rate of all thyroid cancers, reaching a 20-year survival rate of approximately 90% to 95%. Other types of thyroid carcinoma include follicular carcinoma (10%–20%), medullary carcinoma (5%–10%), and anaplastic carcinoma
Fig. 2. Normal lymph nodes. (A) Lymph node with smooth, homogeneous, hypoechoic cortex (arrow), and central echogenic fatty hilum. (B) Another lymph node demonstrating normal central hilar flow (arrow).
The Role of Sonography in Thyroid Cancer
Table 1 Cervical nodal stations: numeric classification Nodal Station
Location
IA IB II
Submental lymph nodes Submandibular lymph nodes Internal jugular vein chain from base of skull to the inferior border of the hyoid bone A: Anterior to the internal jugular vein B: Posterior the internal jugular vein Internal jugular vein chain from the inferior border of the hyoid bone to the inferior border of the cricoid cartilage Internal jugular vein chain from the inferior border of the cricoid cartilage to the supraclavicular fossa Posterior triangle lymph nodes, posterior to the sternocleidomastoid muscle A: From the skull base to the inferior border of the cricoid cartilage B: From the inferior border of the cricoid cartilage to the clavicle Central compartment nodes from the hyoid bone to the suprasternal notch Central compartment nodes inferior to the suprasternal notch in the superior mediastinum
III IV V
VI VII
Note: The lateral compartments (II–V) are separated from the central compartments (I, VI, and VII) by the medial edge of the common carotid artery. From Som PM, Curtin HD, Mancuso AA. An imaging-based classification for the cervical nodes designed as an adjunct to recent clinically based nodal classifications. Arch Otolaryngol Head Neck Surg 1999;125(4):391; with permission.
(1%–2%).5 Follicular thyroid carcinoma most often affects women in the 6th decade of life and may present with metastatic lesions to bone, brain, lung, and liver via hematogenous spread. FNA biopsy (FNAB) cannot differentiate between follicular adenoma and carcinoma and surgical
resection is required to make this distinction. Medullary thyroid carcinoma arises from the parafollicular cells (C cells) of the thyroid gland. It is often familial in origin (vs sporadic) and is associated with multiple endocrine neoplasia type 2 syndrome in 10% to 20% of cases. Patients present with
Fig. 3. Diagram of the neck nodal stations. (From Som PM, Curtin HD, Mancuso AA. An imaging-based classification for the cervical nodes designed as an adjunct to recent clinically based nodal classifications. Arch Otolaryngol Head Neck Surg 1999;125(4):394; with permission.)
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Table 2 Imaging protocols for thyroid and cervical lymph node examinations Thyroid imaging protocol Transducer Linear 7–15 MHz (curved lower-frequency transducer as needed) Gland Lobes: anterior-posterior measurements dimension, width, longitudinal dimension Isthmus: anterior-posterior dimension Nodules Measurement of each nodule in three dimensions; color Doppler interrogation of nodule Cervical lymph node imaging protocol Transducer Linear 7–15 MHz (curved lower-frequency transducer as needed) Nodes Each nodal station evaluated on each side of the neck Documentation of abnormal lymph nodes: Size measured in three dimensions Color Doppler interrogation of node
elevated calcitonin levels due to the secretion of calcitonin by the parafollicular cells. Anaplastic thyroid carcinoma is the rarest and most aggressive of the primary thyroid carcinomas, often fatal. Its dismal prognosis carries a 5-year survival rate of only 5%.6 There is often local invasion of the adjacent soft tissues, trachea, and lymph nodes. Risk factors for the development of thyroid carcinoma include a history of neck irradiation and a family history of thyroid cancer. Additional risk factors that increase the probability of cancer within a given thyroid nodule include age under 30 years or over 60 years and male gender.7 Nodules greater than 2 cm also are reported to have an increased risk of cancer (Fig. 4).8 Lymphomatous involvement of the thyroid is rare, accounting for less than 5% of thyroid malignancies. It may present as a manifestation of generalized lymphoma or be primary to the thyroid gland, usually a non-Hodgkin lymphoma. Hashimoto thyroiditis is a risk factor for the development of thyroid lymphoma. Metastatic disease to the thyroid is also uncommon; primary malignancies include lung, breast, and renal cell carcinomas as well as melanoma.6
Fig. 4. PTC. This nodule measured 5.2 cm and was found in a 17-year-old girl who presented with neck swelling. The patient’s age and the size of the nodule increased the probability of this nodule being malignant.
Thyroid Nodules Thyroid nodules are common in the United States; it has been estimated that approximately 50% of the adult population has thyroid nodules, although less than 7% of these nodules prove malignant.6 US features suspicious for malignancy are reviewed in this section. They are also summarized in Table 3. Calcification Calcification within the thyroid may be classified as microcalcification, coarse calcification, or peripheral rim calcification. Although calcification may be seen in both benign and malignant processes of the thyroid, it is the US feature most commonly associated with malignancy. Of these various types, microcalcifications are the most specific for thyroid malignancy, with a specificity of up to 95%.6 Microcalcifications are most commonly found in PTC and appear as tiny punctate echogenic foci within the nodule (Fig. 5). Due to their small size, they usually do not demonstrate posterior acoustic shadowing. Colloid may also appear on US as tiny echogenic foci but tends to appear linear and demonstrates posterior ring-down or comet-tail artifact (Fig. 6).9 Making this distinction can be difficult, however, and biopsy should be performed for indeterminate foci and for those foci lacking the comet-tail artifact. Furthermore, the presence of the ring-down artifact does not necessarily preclude contemplating biopsy; microcalcifications and colloid may coexist in the same nodule. Coarse calcification and peripheral rimlike calcification may also be seen with thyroid malignancies; however, they also may be found in multinodular thyroids or goiters. Due to their larger size,
The Role of Sonography in Thyroid Cancer
Table 3 Diagnostic criteria: sonographic features suggestive of malignancy US Feature
Comment
Calcification
Micro-, macro-, coarse, peripheral (especially micro) Especially if very hypoechoic More common in anaplastic and lymphoma
Solid hypoechoic nodule Local invasion
Edge refraction shadow Taller than wide
Nodule anterior-posterior dimension greater than width
Irregular margins Adjacent suspicious lymph nodes Size >2 cm Posterior acoustic shadowing
confers a higher risk of malignancy. Benign nodules may also be hypoechoic; therefore, evaluation for additional suspicious features, such as calcification, should be performed. If no other suspicious features are present, these hypoechoic nodules can be biopsied when of sufficient size (discussed later). Follicular neoplasms (adenoma and carcinoma) can also appear as solid, well-marginated, hypoechoic nodules with thin hypoechoic halos10 and central linear hypoechoic striations or areas (Fig. 8). Because the distinction between follicular adenoma and carcinoma can only be made based on vascular and capsular invasion, the diagnosis can only be made by surgical resection. As such, once a nodule is diagnosed as a follicular neoplasm via FNAB, surgical management is the next step. Local invasion Anaplastic thyroid carcinoma and thyroid lymphoma may present as large, rapidly growing masses. The masses may be discrete or infiltrative. Extracapsular extension into the soft tissues is common with invasion into the trachea, neck vessels, and strap muscles. There is usually associated cervical lymphadenopathy.
these calcifications demonstrate posterior acoustic shadowing (Fig. 7). Coarse calcifications may be seen in PTC; however, they are more commonly associated with medullary thyroid carcinoma.6 Nodules with coarse calcifications necessitate FNAB.
Edge refraction shadow Posterior acoustic shadowing from the edges of a solid nodule has also been associated with PTC. It is thought that the fibrotic reaction around the edge of the tumor is responsible for the edge refraction shadow.10
Solid hypoechoic nodule Thyroid nodules may be completely cystic or solid or a combination of both. Likewise, thyroid nodules may be hyperechoic, isoechoic, or hypoechoic to the remainder of the thyroid parenchyma. Most PTCs are hypoechoic and nearly all medullary thyroid carcinomas are hypoechoic.10 Some investigators believe the extremely hypoechoic nodule
Other features suggesting malignancy in thyroid nodules Additional suspicious features include nodules that are taller than they are wide,11 have irregular shape or margins,11 demonstrate posterior acoustic shadowing in the absence of edge refraction, or are accompanied by sonographically suspicious lymph nodes, such as lymph nodes with
Fig. 5. (A, B) Examples of microcalcification. Multiple punctate echogenic foci (arrows) are seen within each of the hypoechoic nodules. Both of these nodules are markedly hypoechoic with irregular borders. These nodules were pathologically proved to be PTC.
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Fig. 6. Example of colloid within a predominately cystic thyroid nodule. The punctate echogenic foci demonstrate comet-tail artifact (arrow).
calcification, cystic change, or abnormally increased or disorganized blood flow. A more detailed discussion of the sonographic findings suspicious for cervical lymph node metastasis from thyroid carcinoma follows. Although these features can be seen in thyroid malignancies, they are by no means pathognomonic; benign nodules may also demonstrate these features. The differential diagnosis of thyroid nodules is found in Table 4. Therefore, when nodules present with features suspicious or suggestive of malignancy, these should proceed to biopsy when of sufficient size. Size criteria for biopsy Multiple guidelines for FNAB of thyroid nodules exist because multiple medical specialties and
Fig. 7. Coarse calcification. Hypoechoic nodule with slightly indistinct and irregular border demonstrates a cluster of coarse echogenic calcifications demonstrating posterior acoustic shadowing (arrow). Pathology was PTC.
Fig. 8. Hypoechoic nodule. The nodule is well defined and homogeneously hypoechoic with a thin hypoechoic halo. FNA resulted in pathology of follicular neoplasm. The patient was scheduled for lobectomy for definitive diagnosis.
organizations are involved in the care of patients with thyroid nodules. These include recommendations from the American Thyroid Association (ATA), the Society of Radiologists in Ultrasound, and the American Association of Clinical Endocrinologists (AACE).5,12,13 Regardless of the recommending body, the guidelines take into account the nodule’s sonographic appearance as well as size. In addition, the ATA uses clinical risk stratification, providing differing guidelines for high-risk and low-risk patients. In general, for low-risk patients, the various guidelines recommend biopsy of solid nodules at sizes greater than 1 to 1.5 cm and mixed cystic and solid nodules at sizes greater than 1.5 to 2 cm. The ATA decreases its minimum size threshold to 5 mm in high-risk patients who have nodules with suspicious features or nodules accompanied by suspicious lymph nodes, whereas the AACE decreases its size threshold below 1.0 cm if there are suspicious sonographic features present. Due to the multitude of guidelines available, it may be confusing as to which specific recommendations to follow. Each department or practice should meet with the referring endocrinologists and surgeons to decide which of the guidelines is to be used by all members of the clinical team to provide seamless care to patients. Pitfalls of thyroid US in the detection of nodules Parathyroid adenomas may be confused with thyroid nodules. Most parathyroid adenomas are extrathyroidal in location; evaluation for the echogenic thyroid capsule separating the adenoma from the thyroid tissue is helpful in making this distinction. Parathyroid adenomas are usually located posterior to the mid gland or inferior to the thyroid gland (Fig. 9A). Adenomas are quite vascular and obtain their vascular supply from the thyroid (see Fig. 9B).
The Role of Sonography in Thyroid Cancer
Table 4 Differential diagnosis of thyroid nodules Diagnosis Benign Adenomatoid nodule Follicular adenoma Hashimoto thyroiditis Parathyroid adenoma Malignant PTC Follicular thyroid carcinoma Medullary thyroid carcinoma Anaplastic thyroid carcinoma Lymphoma Metastatic disease
Comment
Surgical excision is required to differentiate adenoma from carcinoma Lymphocytic thyroiditis can be used as alternative nomenclature Most are extrathyroidal in location; evaluate for capsule separating lesion from thyroid; correlate with parathyroid hormone level
Treat with systemic therapy rather than thyroidectomy
Note that benign and malignant nodules may have overlapping appearances and can only be differentiated by FNAB. Different pathology laboratories may use slightly different cytologic descriptions.
Hashimoto thyroiditis may also present with nodules. The nodules are usually subcentimeter in size (typically 2–3 mm and less than 6 mm) and numerous (termed micronodulation or giraffe pattern), however, causing diffuse heterogeneity of the gland. This diffuse heterogeneity may also create the appearance of larger nodules. The borders of these apparent lesions are indistinct, however. Moreover, because it is an autoimmune process, prominent reactive cervical lymph nodes, usually in level VI, may be present and could be confused as suspicious lymph nodes. These lymph nodes, however, usually have fatty hila and maintain the morphologic appearance of a benign lymph node. A truly discrete nodule, however, in a patient with Hashimoto thyroiditis should be viewed with concern
because these patients are at increased risk for both lymphoma and PTC. Management of multiple thyroid nodules Patients sometimes present with multiple nodules, which may pose a dilemma regarding which nodules to biopsy. Regardless of the number of nodules present, the risk of thyroid cancer in a patient is unchanged.5 Furthermore, it has been found that although a majority of cancers found in patients with multinodular thyroids are within the dominant nodule, approximately one-third of the cancers are found in the nondominant nodule.5 Therefore, each nodule should be evaluated independently, evaluating for suspicious features and then triaging the nodules for biopsy in the order of most suspicious features and then by size.
Fig. 9. Parathyroid adenoma. (A) The inferior parathyroid gland is typically located posterior and inferior to the thyroid. The echogenic thyroid capsule (arrow) separates the parathyroid adenoma (P) from the thyroid. (B) The parathyroid adenoma is quite vascular and receives its blood supply from the thyroid gland. Unlike the central hilar flow of a lymph node, the flow within a parathyroid adenoma is peripheral/polar in distribution.
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Coquia et al Thyroid Nodule Fine-Needle Aspiration Biopsy Biopsy and cytologic evaluation Thyroid nodules can be sampled via US guidance or by palpation; however, in this day and age, they should be sampled with US guidance. After sterilization of the skin at the needle entrance site and administration of local anesthesia, FNA samples are obtained with small-gauge needles with a bevel tip, typically 25 or 26 gauge. Pathologic evaluation can be performed on site or the samples can be transported to a laboratory for off-site testing. The presence of at least 6 groups of benign follicular cells, with each group containing at least 10 cells, is required for a specimen to be considered adequate and benign, per the Bethesda System criteria.14 Other alternative criteria for adequacy include the presence of abundant colloid (suggesting a benign macrofollicular nodule) or enough cells to suggest an alternative diagnosis, such as lymphocytic (or Hashimoto) thyroiditis or atypia. Aspirated thyroid nodules are classified as benign, atypia of undetermined significance/follicular lesion of undetermined significance (AUS/ FLUS), follicular neoplasm, suspicious for malignancy, or malignant, per the Bethesda System classification.14 Approximately 10% of thyroid FNAs from most laboratories are read, however, as nondiagnostic or inadequate.14 Management Benign nodules are managed conservatively with clinical and imaging follow-up whereas nodules classified as follicular neoplasm, suspicious for malignancy, or malignant go on to surgical management. Nodules classified as AUS/FLUS fall into an indeterminate category, comprising between 3% and 6% of total diagnoses.14 In these cases, repeat FNA is recommended. However, 20% of these nodules remain AUS after repeat biopsy. The risk of malignancy in these nodules is between 5% and 15%.14 To avoid diagnostic surgery for what may ultimately be a benign nodule, FNA samples can be sent for genomic testing. The Afirma Gene Expression Classifier (AGEC) from Veracyte (South San Francisco, California) classifies these cytologically indeterminate nodules as either benign or malignant, with a 95% negative predictive value.15 To minimize the need for a third FNA specifically just to perform this test, additional FNA passes are obtained at the time of the second FNA for AGEC testing. This material is then reserved and analyzed in the event that the repeat (or second) FNA is also called indeterminate. A nodule classified as benign on AGEC is managed just as a nodule classified as benign on cytology, with
imaging and clinical follow-up.15 A benign AGEC result, therefore, negates the necessity of performing surgery for diagnosis of cytologically indeterminate nodules. At one center, the number of diagnostic surgeries performed for these nodules dropped 10-fold after the implementation of AGEC testing, and 1 surgery was avoided for every 2 AGEC tests performed.15 A suspicious for malignancy AGEC result correlates to a greater than 50% risk of malignancy for the nodule, and surgery should be performed for pathologic diagnosis.
Preoperative Evaluation for Cervical Nodal Metastases Current best surgical practice in the United States recommends central lymph node dissection at the time of thyroidectomy as well as lateral neck dissection if there are confirmed metastatic cervical lymph nodes. Therefore, prior to thyroidectomy, the cervical lymph nodes should be evaluated for lymph node metastases both with palpation and US; if abnormal lymph nodes are suspected, FNA should be performed. Stulak and colleagues16 in 2006 reported a sensitivity and specificity of 83.5% and 97.7% of preoperative US in the detection of lateral nodal metastasis in newly diagnosed thyroid cancer patients, respectively. Hence, a systematic sonographic evaluation of the neck nodes is performed bilaterally to identify suspicious nodes. US features of suspicious nodes Benign sonographic morphologic features of lymph nodes include the presence of an echogenic fatty hilum, central regular hilar vascular flow, and elongated shape. Deviations from this appearance should be considered abnormal. A node demonstrating cystic change or the presence of calcification (mimicking the appearance of the primary tumor) has been shown to be 100% specific for metastatic disease.17 Increased or eccentric irregular vascularity, round shape and/or loss of the normal elongated shape, hyperechogenicity of the node relative to the adjacent strap muscles, and loss of a fatty hilum are all features of abnormal lymph nodes. A summary of suspicious features is in Box 1, and examples of suspicious nodes are given in Figs. 10–12. Metastatic disease from other primaries, however, such as squamous cell carcinoma, can produce cystic degeneration of a lymph node. Management of suspicious nodes Unlike the guidelines for thyroid nodule biopsy, no specific size criteria are commonly used in regard to lymph node biopsy. Some institutions may have
The Role of Sonography in Thyroid Cancer
Box 1 Sonographic features suspicious for lymph node metastasis Cystic change Calcification Peripheral, increased, irregular, or eccentric vascularity Loss of the normal elongated shape (less than 2:1 ratio between long axis and short axis) or round shape Hyperechogenicity of the lymph node relative to adjacent strap muscle Loss of fatty hilum Irregular, asymmetrically thickened cortex
their own size cutoff (ie, biopsy lymph nodes 8 mm or larger), formed by consensus between their surgeons, endocrinologists, and radiologists. For example, at the authors’ institution, because of the high specificity of lymph nodes containing calcification or cystic areas in predicting metastatic disease, these are biopsied regardless of size. Those that are abnormal but do not contain these features are usually biopsied when 8 mm in size. Lymph nodes that are homogeneously hypoechoic without an echogenic fatty hilum present and do not demonstrate any other suspicious features may be followed, with biopsy for those that demonstrate interval growth or interval
Fig. 10. Cystic replacement of a cervical lymph node. The lymph node is enlarged and has a large anechoic component, causing increased through transmission, compatible with cystic change (C). A small area of residual soft tissue is seen within the node (arrow). A punctate echogenic focus is seen within the soft tissue, compatible with calcification.
Fig. 11. Calcifications within a lymph node. Multiple echogenic foci (arrow) are seen within a lymph node (arrowheads), compatible with calcification. The lymph node is also round, another suspicious feature. The node was biopsied, with pathology of metastatic PTC.
development of additional suspicious features. Again, this particular management step may be based on the consensus between the referring physicians and the radiologists. Suspicious lymph nodes can be biopsied preoperatively to confirm the necessity for lateral neck dissection at the time of thyroidectomy. Because these nodes are usually not palpable, they are sampled under US guidance, using the same technique as described for FNA of thyroid nodules. If the lymph node is cystic, such that it yields insufficient cells for diagnosis, the fluid can be aspirated and sent for thyroglobulin. Alternatively a surgeon may choose to proceed to surgery and remove the suspicious lymph nodes at the time of thyroidectomy. To help the surgeon find the nodes intraoperatively, preoperative
Fig. 12. Abnormal lymph node vascularity. Instead of central hilar flow, there is peripheral vascularity, which is increased. A fatty hilum is also not seen. This was biopsied with pathology of metastatic PTC.
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Coquia et al US can be used to mark the suspicious nodes on the skin. In more complex cases, intraoperative US guidance can be provided.
Postoperative Surveillance After thyroidectomy, in conjunction with laboratory follow-up and nuclear medicine radioiodine imaging, the neck is evaluated routinely with US for the development of nodal metastases. The initial US examination should be performed in the first 6 to 12 months and then periodically depending on a patient’s risk for recurrence and thyroglobulin level.12 The frequency and length of surveillance may also be dependent on the institution, endocrinologist, or surgeon. The risk of recurrence either within the thyroid bed or within the cervical lymph nodes in PTC has been reported to between 15% and 25%.18 The postoperative neck can be divided into lateral and central compartments (right lateral neck, right central neck, left lateral neck, and left central neck), discussed previously. Disease found in each separate compartment leads to its own separate neck dissection. Therefore, if multiple abnormal nodes are present in multiple compartments, a suspicious node from each compartment should be sampled to accurately plan surgical management and decrease the extent of the neck dissection. Identification of thyroid cells within the lymph node is confirmatory for lymph node metastasis. In the event the lymph node sampling is nondiagnostic or indeterminate for metastatic disease, the lymph node can be aspirated and the sample sent for thyroglobulin assay. It is particularly helpful to aspirate and analyze the fluid within small cystic areas. A thyroglobulin level in a lymph node greater than the serum thyroglobulin level is diagnostic for metastatic disease. Pitfalls in the postoperative surveillance period In one study, approximately 34% of postoperative patients were found to have small thyroid bed nodules.18 Of these nodules, only a small percentage (9%) increased in size during the median 3-year follow-up period, growing at a rate of 1.3 mm/y. Furthermore, only one-third of those proved malignant demonstrated interval growth. This behavior demonstrates the slow indolent nature of papillary thyroid cancer. Therefore, many small nodules in the thyroid bed without suspicious features can be observed over time. In addition to recurrence, other masses can be seen in the surgical bed on postoperative examinations, such as residual thyroid tissue, scarring/ fibrosis, and suture granulomas. Residual thyroid tissue may be focal and can be vascular, features
that make it difficult to differentiate from recurrence by imaging. FNA can be performed to differentiate the mass as either malignant (compatible with recurrence) or benign (normal residual thyroid tissue). Scarring in the postsurgical bed can be nonspecific in appearance but typically is nonvascular and elongated, blending into the adjacent fat and muscle. These areas can also be observed over time for interval increase in size or development of suspicious features that prompt biopsy. Suture granulomas can present as focal masses within the thyroid bed. The sonographic appearance of suture granulomas has been described as a hypoechoic lesion with central echogenic lines or foci.19 Although echogenic foci within a lesion may suggest microcalcification and, therefore, imply recurrence, features that support suture granuloma include centrality of the foci, paired foci, and foci larger than 1 mm.19 Suture granulomas also tend to regress or resolve over time.19 Suture granulomas also may present within the neck, buried within the sternocleidomastoid muscle or subcutaneous tissue. Neuromas may also be seen within the neck, typically presenting as hypoechoic masses in close relation to the carotid artery. Traumatic neuromas may develop after neck dissection.20 Because many of these masses in the thyroid bed and neck can demonstrate either no growth or minimal growth over time, it is important to correlate with a patient’s thyroglobulin level over time because this may indicate residual or progressive disease. Alcohol ablation of lymph node metastases As an alternative to surgical management, alcohol (ethanol) ablation can be performed in the treatment of cervical lymph node metastases, especially in patients who are either poor surgical candidates or those who wish to avoid surgery. The ethanol is administered through percutaneous injection under US guidance.21
SUMMARY US plays a crucial role in the diagnosis and management of patients with thyroid cancer. Not only is it the best imaging modality for the detection of suspicious thyroid nodules and cervical nodal metastases but also the imaging modality of choice to provide guidance during the performance of thyroid and nodal biopsies. Knowledge of the sonographic anatomy of the thyroid gland and nodal stations as well as features commonly seen in malignant thyroid nodules and nodal metastases and experience with the use of the
The Role of Sonography in Thyroid Cancer latest state-of the art high-resolution US equipment is imperative to its effective use in the evaluation of thyroid cancer patients. A summary of the pearls, pitfalls, and variants and what radiologists need to know is found in Boxes 2 and 3. Many groups of physicians (radiologists, surgeons, and endocrinologists) are involved in the care of patients with thyroid cancer and the recommendations and management steps discussed in this article may vary by institution. Therefore, multidepartmental collaboration and meetings are essential to keeping a practice up to date to ensure satisfaction of the referring physicians and providing optimal patient care.
Box 2 Pearls, pitfalls, and variants Hashimoto thyroiditis can present with diffuse small nodules (
KEY POINTS
INTRODUCTION According to the National Cancer Institute, an estimated 63,000 cases of thyroid cancer will be diagnosed in 2014.1 When pathologically well differentiated and diagnosed early, the disease is highly treatable and can be curable. The 5-year relative survival rate of most types of stage I thyroid cancer approaches 100%.2 US is used routinely in the diagnosis and management of thyroid cancer, from initial detection and diagnosis to preoperative planning to postoperative surveillance. This review discusses the various roles of sonography in managing patients with thyroid cancer and reviews the sonographic appearance of thyroid cancer and nodal metastases.
NORMAL ANATOMY AND IMAGING TECHNIQUE The thyroid gland is a bilobed gland that sits atop the trachea within the anterior-inferior neck
(Fig. 1). The isthmus connects the right and left thyroid lobes. Each lobe measures approximately 4 to 6 cm in length and less than 2 cm in width and in the anterior-posterior dimension.3 The normal isthmus measures less than 6 mm in the anterior-posterior dimension. The normal gland is homogeneous in echotexture and hyperechoic compared with the adjacent strap muscles (see Fig. 1). After documentation of any thyroid lesion that has suspicious features for primary thyroid cancer, the cervical lymph nodes are imaged. A normal lymph node has an elongated shape (a 2:1 ratio between length and short-axis dimensions) and demonstrates an echogenic fatty hilum. Vascular flow is seen entering into the lymph node via the fatty hilum (Fig. 2) and the cortex is symmetrically hypoechoic. The neck can be divided into nodal levels or stations by anatomic landmarks. The numeric classification system of the neck nodal stations is outlined in Table 1 and depicted in Fig. 3.4 Using this classification, the neck can be divided into
Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 601 North Caroline Street, Baltimore, MD 21287, USA * Corresponding author. 601 North Caroline Street, JHOC 3142, Baltimore, MD 21287. E-mail address: [email protected] Radiol Clin N Am - (2014) -–http://dx.doi.org/10.1016/j.rcl.2014.07.007 0033-8389/14/$ – see front matter Ó 2014 Elsevier Inc. All rights reserved.
radiologic.theclinics.com
Thyroid nodules are commonly detected on ultrasound (US). Specific sonographic features are found in many malignant nodules and lymph nodes. Identification of cervical nodal metastasis is important for accurate staging and surgical management of de novo thyroid cancer. Pathologic diagnosis of a thyroid nodule requires fine-needle aspiration (FNA). US accurately provides imaging guidance for FNA of indeterminate or suspicious thyroid nodules and cervical lymph nodes. US is routinely used in the postoperative surveillance of the neck for tumor recurrence in the thyroid bed or nodal stations.
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Cervical Lymph Nodes
Fig. 1. Normal sonographic appearance of the thyroid. The thyroid (arrows) sits atop the trachea (T) and is a bilobed structure echogenic to the adjacent musculature (M).
central and lateral neck compartments. Stations I, VI, and VII are considered central neck compartments and stations II to V are considered lateral neck compartments. The medial edge of the common carotid artery serves as a landmark to divide the central from the lateral compartment. The distinction between the central and lateral neck compartments is important for the surgical management of thyroid cancer if nodal metastases are present (discussed later).
IMAGING PROTOCOLS Thyroid The thyroid gland is imaged with a linear highfrequency transducer (7–15 MHz). Occasionally, if the thyroid gland is enlarged, a curved, lowerfrequency transducer may be used to fully image the thyroid. The right and left thyroid lobes are imaged in the transverse and sagittal planes. Anterior-posterior dimension, width, and length are measured at the mid thyroid gland. The isthmus is measured in the anterior-posterior dimension. Nodules, if present, are measured in the transverse and
The neck nodes are imaged with the same transducers as the thyroid: a high-frequency linear transducer for most of the nodal stations and occasionally a curved transducer for the lower and, therefore, deeper level IV and VI lymph nodes. Each nodal station within the neck is evaluated to assess for the presence of normal or abnormal lymph nodes. Normal-appearing lymph nodes can be documented for each level, with the fatty hilum included in the image. Measurement of sonographically normal-appearing lymph nodes is not necessary. Abnormal lymph nodes (discussed later) should be imaged and measured in the transverse and sagittal planes. The nodes also should be interrogated with color Doppler US to assess for abnormal and disorganized blood flow. General imaging protocols for the thyroid gland and cervical lymph nodes are summarized in Table 2.
IMAGING FINDINGS AND PATHOLOGY Types of Thyroid Cancer There are several types of primary thyroid cancer. Papillary thyroid carcinoma (PTC) is the most common, accounting for approximately 75% to 80% of thyroid cancers. PTC is multifocal in approximately 20% of cases and more common in females than males. PTC usually presents before age 40 years, often with cervical nodal metastases. It is also the most common thyroid malignancy in children. PTC has the best prognosis and highest survival rate of all thyroid cancers, reaching a 20-year survival rate of approximately 90% to 95%. Other types of thyroid carcinoma include follicular carcinoma (10%–20%), medullary carcinoma (5%–10%), and anaplastic carcinoma
Fig. 2. Normal lymph nodes. (A) Lymph node with smooth, homogeneous, hypoechoic cortex (arrow), and central echogenic fatty hilum. (B) Another lymph node demonstrating normal central hilar flow (arrow).
The Role of Sonography in Thyroid Cancer
Table 1 Cervical nodal stations: numeric classification Nodal Station
Location
IA IB II
Submental lymph nodes Submandibular lymph nodes Internal jugular vein chain from base of skull to the inferior border of the hyoid bone A: Anterior to the internal jugular vein B: Posterior the internal jugular vein Internal jugular vein chain from the inferior border of the hyoid bone to the inferior border of the cricoid cartilage Internal jugular vein chain from the inferior border of the cricoid cartilage to the supraclavicular fossa Posterior triangle lymph nodes, posterior to the sternocleidomastoid muscle A: From the skull base to the inferior border of the cricoid cartilage B: From the inferior border of the cricoid cartilage to the clavicle Central compartment nodes from the hyoid bone to the suprasternal notch Central compartment nodes inferior to the suprasternal notch in the superior mediastinum
III IV V
VI VII
Note: The lateral compartments (II–V) are separated from the central compartments (I, VI, and VII) by the medial edge of the common carotid artery. From Som PM, Curtin HD, Mancuso AA. An imaging-based classification for the cervical nodes designed as an adjunct to recent clinically based nodal classifications. Arch Otolaryngol Head Neck Surg 1999;125(4):391; with permission.
(1%–2%).5 Follicular thyroid carcinoma most often affects women in the 6th decade of life and may present with metastatic lesions to bone, brain, lung, and liver via hematogenous spread. FNA biopsy (FNAB) cannot differentiate between follicular adenoma and carcinoma and surgical
resection is required to make this distinction. Medullary thyroid carcinoma arises from the parafollicular cells (C cells) of the thyroid gland. It is often familial in origin (vs sporadic) and is associated with multiple endocrine neoplasia type 2 syndrome in 10% to 20% of cases. Patients present with
Fig. 3. Diagram of the neck nodal stations. (From Som PM, Curtin HD, Mancuso AA. An imaging-based classification for the cervical nodes designed as an adjunct to recent clinically based nodal classifications. Arch Otolaryngol Head Neck Surg 1999;125(4):394; with permission.)
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Table 2 Imaging protocols for thyroid and cervical lymph node examinations Thyroid imaging protocol Transducer Linear 7–15 MHz (curved lower-frequency transducer as needed) Gland Lobes: anterior-posterior measurements dimension, width, longitudinal dimension Isthmus: anterior-posterior dimension Nodules Measurement of each nodule in three dimensions; color Doppler interrogation of nodule Cervical lymph node imaging protocol Transducer Linear 7–15 MHz (curved lower-frequency transducer as needed) Nodes Each nodal station evaluated on each side of the neck Documentation of abnormal lymph nodes: Size measured in three dimensions Color Doppler interrogation of node
elevated calcitonin levels due to the secretion of calcitonin by the parafollicular cells. Anaplastic thyroid carcinoma is the rarest and most aggressive of the primary thyroid carcinomas, often fatal. Its dismal prognosis carries a 5-year survival rate of only 5%.6 There is often local invasion of the adjacent soft tissues, trachea, and lymph nodes. Risk factors for the development of thyroid carcinoma include a history of neck irradiation and a family history of thyroid cancer. Additional risk factors that increase the probability of cancer within a given thyroid nodule include age under 30 years or over 60 years and male gender.7 Nodules greater than 2 cm also are reported to have an increased risk of cancer (Fig. 4).8 Lymphomatous involvement of the thyroid is rare, accounting for less than 5% of thyroid malignancies. It may present as a manifestation of generalized lymphoma or be primary to the thyroid gland, usually a non-Hodgkin lymphoma. Hashimoto thyroiditis is a risk factor for the development of thyroid lymphoma. Metastatic disease to the thyroid is also uncommon; primary malignancies include lung, breast, and renal cell carcinomas as well as melanoma.6
Fig. 4. PTC. This nodule measured 5.2 cm and was found in a 17-year-old girl who presented with neck swelling. The patient’s age and the size of the nodule increased the probability of this nodule being malignant.
Thyroid Nodules Thyroid nodules are common in the United States; it has been estimated that approximately 50% of the adult population has thyroid nodules, although less than 7% of these nodules prove malignant.6 US features suspicious for malignancy are reviewed in this section. They are also summarized in Table 3. Calcification Calcification within the thyroid may be classified as microcalcification, coarse calcification, or peripheral rim calcification. Although calcification may be seen in both benign and malignant processes of the thyroid, it is the US feature most commonly associated with malignancy. Of these various types, microcalcifications are the most specific for thyroid malignancy, with a specificity of up to 95%.6 Microcalcifications are most commonly found in PTC and appear as tiny punctate echogenic foci within the nodule (Fig. 5). Due to their small size, they usually do not demonstrate posterior acoustic shadowing. Colloid may also appear on US as tiny echogenic foci but tends to appear linear and demonstrates posterior ring-down or comet-tail artifact (Fig. 6).9 Making this distinction can be difficult, however, and biopsy should be performed for indeterminate foci and for those foci lacking the comet-tail artifact. Furthermore, the presence of the ring-down artifact does not necessarily preclude contemplating biopsy; microcalcifications and colloid may coexist in the same nodule. Coarse calcification and peripheral rimlike calcification may also be seen with thyroid malignancies; however, they also may be found in multinodular thyroids or goiters. Due to their larger size,
The Role of Sonography in Thyroid Cancer
Table 3 Diagnostic criteria: sonographic features suggestive of malignancy US Feature
Comment
Calcification
Micro-, macro-, coarse, peripheral (especially micro) Especially if very hypoechoic More common in anaplastic and lymphoma
Solid hypoechoic nodule Local invasion
Edge refraction shadow Taller than wide
Nodule anterior-posterior dimension greater than width
Irregular margins Adjacent suspicious lymph nodes Size >2 cm Posterior acoustic shadowing
confers a higher risk of malignancy. Benign nodules may also be hypoechoic; therefore, evaluation for additional suspicious features, such as calcification, should be performed. If no other suspicious features are present, these hypoechoic nodules can be biopsied when of sufficient size (discussed later). Follicular neoplasms (adenoma and carcinoma) can also appear as solid, well-marginated, hypoechoic nodules with thin hypoechoic halos10 and central linear hypoechoic striations or areas (Fig. 8). Because the distinction between follicular adenoma and carcinoma can only be made based on vascular and capsular invasion, the diagnosis can only be made by surgical resection. As such, once a nodule is diagnosed as a follicular neoplasm via FNAB, surgical management is the next step. Local invasion Anaplastic thyroid carcinoma and thyroid lymphoma may present as large, rapidly growing masses. The masses may be discrete or infiltrative. Extracapsular extension into the soft tissues is common with invasion into the trachea, neck vessels, and strap muscles. There is usually associated cervical lymphadenopathy.
these calcifications demonstrate posterior acoustic shadowing (Fig. 7). Coarse calcifications may be seen in PTC; however, they are more commonly associated with medullary thyroid carcinoma.6 Nodules with coarse calcifications necessitate FNAB.
Edge refraction shadow Posterior acoustic shadowing from the edges of a solid nodule has also been associated with PTC. It is thought that the fibrotic reaction around the edge of the tumor is responsible for the edge refraction shadow.10
Solid hypoechoic nodule Thyroid nodules may be completely cystic or solid or a combination of both. Likewise, thyroid nodules may be hyperechoic, isoechoic, or hypoechoic to the remainder of the thyroid parenchyma. Most PTCs are hypoechoic and nearly all medullary thyroid carcinomas are hypoechoic.10 Some investigators believe the extremely hypoechoic nodule
Other features suggesting malignancy in thyroid nodules Additional suspicious features include nodules that are taller than they are wide,11 have irregular shape or margins,11 demonstrate posterior acoustic shadowing in the absence of edge refraction, or are accompanied by sonographically suspicious lymph nodes, such as lymph nodes with
Fig. 5. (A, B) Examples of microcalcification. Multiple punctate echogenic foci (arrows) are seen within each of the hypoechoic nodules. Both of these nodules are markedly hypoechoic with irregular borders. These nodules were pathologically proved to be PTC.
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Fig. 6. Example of colloid within a predominately cystic thyroid nodule. The punctate echogenic foci demonstrate comet-tail artifact (arrow).
calcification, cystic change, or abnormally increased or disorganized blood flow. A more detailed discussion of the sonographic findings suspicious for cervical lymph node metastasis from thyroid carcinoma follows. Although these features can be seen in thyroid malignancies, they are by no means pathognomonic; benign nodules may also demonstrate these features. The differential diagnosis of thyroid nodules is found in Table 4. Therefore, when nodules present with features suspicious or suggestive of malignancy, these should proceed to biopsy when of sufficient size. Size criteria for biopsy Multiple guidelines for FNAB of thyroid nodules exist because multiple medical specialties and
Fig. 7. Coarse calcification. Hypoechoic nodule with slightly indistinct and irregular border demonstrates a cluster of coarse echogenic calcifications demonstrating posterior acoustic shadowing (arrow). Pathology was PTC.
Fig. 8. Hypoechoic nodule. The nodule is well defined and homogeneously hypoechoic with a thin hypoechoic halo. FNA resulted in pathology of follicular neoplasm. The patient was scheduled for lobectomy for definitive diagnosis.
organizations are involved in the care of patients with thyroid nodules. These include recommendations from the American Thyroid Association (ATA), the Society of Radiologists in Ultrasound, and the American Association of Clinical Endocrinologists (AACE).5,12,13 Regardless of the recommending body, the guidelines take into account the nodule’s sonographic appearance as well as size. In addition, the ATA uses clinical risk stratification, providing differing guidelines for high-risk and low-risk patients. In general, for low-risk patients, the various guidelines recommend biopsy of solid nodules at sizes greater than 1 to 1.5 cm and mixed cystic and solid nodules at sizes greater than 1.5 to 2 cm. The ATA decreases its minimum size threshold to 5 mm in high-risk patients who have nodules with suspicious features or nodules accompanied by suspicious lymph nodes, whereas the AACE decreases its size threshold below 1.0 cm if there are suspicious sonographic features present. Due to the multitude of guidelines available, it may be confusing as to which specific recommendations to follow. Each department or practice should meet with the referring endocrinologists and surgeons to decide which of the guidelines is to be used by all members of the clinical team to provide seamless care to patients. Pitfalls of thyroid US in the detection of nodules Parathyroid adenomas may be confused with thyroid nodules. Most parathyroid adenomas are extrathyroidal in location; evaluation for the echogenic thyroid capsule separating the adenoma from the thyroid tissue is helpful in making this distinction. Parathyroid adenomas are usually located posterior to the mid gland or inferior to the thyroid gland (Fig. 9A). Adenomas are quite vascular and obtain their vascular supply from the thyroid (see Fig. 9B).
The Role of Sonography in Thyroid Cancer
Table 4 Differential diagnosis of thyroid nodules Diagnosis Benign Adenomatoid nodule Follicular adenoma Hashimoto thyroiditis Parathyroid adenoma Malignant PTC Follicular thyroid carcinoma Medullary thyroid carcinoma Anaplastic thyroid carcinoma Lymphoma Metastatic disease
Comment
Surgical excision is required to differentiate adenoma from carcinoma Lymphocytic thyroiditis can be used as alternative nomenclature Most are extrathyroidal in location; evaluate for capsule separating lesion from thyroid; correlate with parathyroid hormone level
Treat with systemic therapy rather than thyroidectomy
Note that benign and malignant nodules may have overlapping appearances and can only be differentiated by FNAB. Different pathology laboratories may use slightly different cytologic descriptions.
Hashimoto thyroiditis may also present with nodules. The nodules are usually subcentimeter in size (typically 2–3 mm and less than 6 mm) and numerous (termed micronodulation or giraffe pattern), however, causing diffuse heterogeneity of the gland. This diffuse heterogeneity may also create the appearance of larger nodules. The borders of these apparent lesions are indistinct, however. Moreover, because it is an autoimmune process, prominent reactive cervical lymph nodes, usually in level VI, may be present and could be confused as suspicious lymph nodes. These lymph nodes, however, usually have fatty hila and maintain the morphologic appearance of a benign lymph node. A truly discrete nodule, however, in a patient with Hashimoto thyroiditis should be viewed with concern
because these patients are at increased risk for both lymphoma and PTC. Management of multiple thyroid nodules Patients sometimes present with multiple nodules, which may pose a dilemma regarding which nodules to biopsy. Regardless of the number of nodules present, the risk of thyroid cancer in a patient is unchanged.5 Furthermore, it has been found that although a majority of cancers found in patients with multinodular thyroids are within the dominant nodule, approximately one-third of the cancers are found in the nondominant nodule.5 Therefore, each nodule should be evaluated independently, evaluating for suspicious features and then triaging the nodules for biopsy in the order of most suspicious features and then by size.
Fig. 9. Parathyroid adenoma. (A) The inferior parathyroid gland is typically located posterior and inferior to the thyroid. The echogenic thyroid capsule (arrow) separates the parathyroid adenoma (P) from the thyroid. (B) The parathyroid adenoma is quite vascular and receives its blood supply from the thyroid gland. Unlike the central hilar flow of a lymph node, the flow within a parathyroid adenoma is peripheral/polar in distribution.
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Coquia et al Thyroid Nodule Fine-Needle Aspiration Biopsy Biopsy and cytologic evaluation Thyroid nodules can be sampled via US guidance or by palpation; however, in this day and age, they should be sampled with US guidance. After sterilization of the skin at the needle entrance site and administration of local anesthesia, FNA samples are obtained with small-gauge needles with a bevel tip, typically 25 or 26 gauge. Pathologic evaluation can be performed on site or the samples can be transported to a laboratory for off-site testing. The presence of at least 6 groups of benign follicular cells, with each group containing at least 10 cells, is required for a specimen to be considered adequate and benign, per the Bethesda System criteria.14 Other alternative criteria for adequacy include the presence of abundant colloid (suggesting a benign macrofollicular nodule) or enough cells to suggest an alternative diagnosis, such as lymphocytic (or Hashimoto) thyroiditis or atypia. Aspirated thyroid nodules are classified as benign, atypia of undetermined significance/follicular lesion of undetermined significance (AUS/ FLUS), follicular neoplasm, suspicious for malignancy, or malignant, per the Bethesda System classification.14 Approximately 10% of thyroid FNAs from most laboratories are read, however, as nondiagnostic or inadequate.14 Management Benign nodules are managed conservatively with clinical and imaging follow-up whereas nodules classified as follicular neoplasm, suspicious for malignancy, or malignant go on to surgical management. Nodules classified as AUS/FLUS fall into an indeterminate category, comprising between 3% and 6% of total diagnoses.14 In these cases, repeat FNA is recommended. However, 20% of these nodules remain AUS after repeat biopsy. The risk of malignancy in these nodules is between 5% and 15%.14 To avoid diagnostic surgery for what may ultimately be a benign nodule, FNA samples can be sent for genomic testing. The Afirma Gene Expression Classifier (AGEC) from Veracyte (South San Francisco, California) classifies these cytologically indeterminate nodules as either benign or malignant, with a 95% negative predictive value.15 To minimize the need for a third FNA specifically just to perform this test, additional FNA passes are obtained at the time of the second FNA for AGEC testing. This material is then reserved and analyzed in the event that the repeat (or second) FNA is also called indeterminate. A nodule classified as benign on AGEC is managed just as a nodule classified as benign on cytology, with
imaging and clinical follow-up.15 A benign AGEC result, therefore, negates the necessity of performing surgery for diagnosis of cytologically indeterminate nodules. At one center, the number of diagnostic surgeries performed for these nodules dropped 10-fold after the implementation of AGEC testing, and 1 surgery was avoided for every 2 AGEC tests performed.15 A suspicious for malignancy AGEC result correlates to a greater than 50% risk of malignancy for the nodule, and surgery should be performed for pathologic diagnosis.
Preoperative Evaluation for Cervical Nodal Metastases Current best surgical practice in the United States recommends central lymph node dissection at the time of thyroidectomy as well as lateral neck dissection if there are confirmed metastatic cervical lymph nodes. Therefore, prior to thyroidectomy, the cervical lymph nodes should be evaluated for lymph node metastases both with palpation and US; if abnormal lymph nodes are suspected, FNA should be performed. Stulak and colleagues16 in 2006 reported a sensitivity and specificity of 83.5% and 97.7% of preoperative US in the detection of lateral nodal metastasis in newly diagnosed thyroid cancer patients, respectively. Hence, a systematic sonographic evaluation of the neck nodes is performed bilaterally to identify suspicious nodes. US features of suspicious nodes Benign sonographic morphologic features of lymph nodes include the presence of an echogenic fatty hilum, central regular hilar vascular flow, and elongated shape. Deviations from this appearance should be considered abnormal. A node demonstrating cystic change or the presence of calcification (mimicking the appearance of the primary tumor) has been shown to be 100% specific for metastatic disease.17 Increased or eccentric irregular vascularity, round shape and/or loss of the normal elongated shape, hyperechogenicity of the node relative to the adjacent strap muscles, and loss of a fatty hilum are all features of abnormal lymph nodes. A summary of suspicious features is in Box 1, and examples of suspicious nodes are given in Figs. 10–12. Metastatic disease from other primaries, however, such as squamous cell carcinoma, can produce cystic degeneration of a lymph node. Management of suspicious nodes Unlike the guidelines for thyroid nodule biopsy, no specific size criteria are commonly used in regard to lymph node biopsy. Some institutions may have
The Role of Sonography in Thyroid Cancer
Box 1 Sonographic features suspicious for lymph node metastasis Cystic change Calcification Peripheral, increased, irregular, or eccentric vascularity Loss of the normal elongated shape (less than 2:1 ratio between long axis and short axis) or round shape Hyperechogenicity of the lymph node relative to adjacent strap muscle Loss of fatty hilum Irregular, asymmetrically thickened cortex
their own size cutoff (ie, biopsy lymph nodes 8 mm or larger), formed by consensus between their surgeons, endocrinologists, and radiologists. For example, at the authors’ institution, because of the high specificity of lymph nodes containing calcification or cystic areas in predicting metastatic disease, these are biopsied regardless of size. Those that are abnormal but do not contain these features are usually biopsied when 8 mm in size. Lymph nodes that are homogeneously hypoechoic without an echogenic fatty hilum present and do not demonstrate any other suspicious features may be followed, with biopsy for those that demonstrate interval growth or interval
Fig. 10. Cystic replacement of a cervical lymph node. The lymph node is enlarged and has a large anechoic component, causing increased through transmission, compatible with cystic change (C). A small area of residual soft tissue is seen within the node (arrow). A punctate echogenic focus is seen within the soft tissue, compatible with calcification.
Fig. 11. Calcifications within a lymph node. Multiple echogenic foci (arrow) are seen within a lymph node (arrowheads), compatible with calcification. The lymph node is also round, another suspicious feature. The node was biopsied, with pathology of metastatic PTC.
development of additional suspicious features. Again, this particular management step may be based on the consensus between the referring physicians and the radiologists. Suspicious lymph nodes can be biopsied preoperatively to confirm the necessity for lateral neck dissection at the time of thyroidectomy. Because these nodes are usually not palpable, they are sampled under US guidance, using the same technique as described for FNA of thyroid nodules. If the lymph node is cystic, such that it yields insufficient cells for diagnosis, the fluid can be aspirated and sent for thyroglobulin. Alternatively a surgeon may choose to proceed to surgery and remove the suspicious lymph nodes at the time of thyroidectomy. To help the surgeon find the nodes intraoperatively, preoperative
Fig. 12. Abnormal lymph node vascularity. Instead of central hilar flow, there is peripheral vascularity, which is increased. A fatty hilum is also not seen. This was biopsied with pathology of metastatic PTC.
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Postoperative Surveillance After thyroidectomy, in conjunction with laboratory follow-up and nuclear medicine radioiodine imaging, the neck is evaluated routinely with US for the development of nodal metastases. The initial US examination should be performed in the first 6 to 12 months and then periodically depending on a patient’s risk for recurrence and thyroglobulin level.12 The frequency and length of surveillance may also be dependent on the institution, endocrinologist, or surgeon. The risk of recurrence either within the thyroid bed or within the cervical lymph nodes in PTC has been reported to between 15% and 25%.18 The postoperative neck can be divided into lateral and central compartments (right lateral neck, right central neck, left lateral neck, and left central neck), discussed previously. Disease found in each separate compartment leads to its own separate neck dissection. Therefore, if multiple abnormal nodes are present in multiple compartments, a suspicious node from each compartment should be sampled to accurately plan surgical management and decrease the extent of the neck dissection. Identification of thyroid cells within the lymph node is confirmatory for lymph node metastasis. In the event the lymph node sampling is nondiagnostic or indeterminate for metastatic disease, the lymph node can be aspirated and the sample sent for thyroglobulin assay. It is particularly helpful to aspirate and analyze the fluid within small cystic areas. A thyroglobulin level in a lymph node greater than the serum thyroglobulin level is diagnostic for metastatic disease. Pitfalls in the postoperative surveillance period In one study, approximately 34% of postoperative patients were found to have small thyroid bed nodules.18 Of these nodules, only a small percentage (9%) increased in size during the median 3-year follow-up period, growing at a rate of 1.3 mm/y. Furthermore, only one-third of those proved malignant demonstrated interval growth. This behavior demonstrates the slow indolent nature of papillary thyroid cancer. Therefore, many small nodules in the thyroid bed without suspicious features can be observed over time. In addition to recurrence, other masses can be seen in the surgical bed on postoperative examinations, such as residual thyroid tissue, scarring/ fibrosis, and suture granulomas. Residual thyroid tissue may be focal and can be vascular, features
that make it difficult to differentiate from recurrence by imaging. FNA can be performed to differentiate the mass as either malignant (compatible with recurrence) or benign (normal residual thyroid tissue). Scarring in the postsurgical bed can be nonspecific in appearance but typically is nonvascular and elongated, blending into the adjacent fat and muscle. These areas can also be observed over time for interval increase in size or development of suspicious features that prompt biopsy. Suture granulomas can present as focal masses within the thyroid bed. The sonographic appearance of suture granulomas has been described as a hypoechoic lesion with central echogenic lines or foci.19 Although echogenic foci within a lesion may suggest microcalcification and, therefore, imply recurrence, features that support suture granuloma include centrality of the foci, paired foci, and foci larger than 1 mm.19 Suture granulomas also tend to regress or resolve over time.19 Suture granulomas also may present within the neck, buried within the sternocleidomastoid muscle or subcutaneous tissue. Neuromas may also be seen within the neck, typically presenting as hypoechoic masses in close relation to the carotid artery. Traumatic neuromas may develop after neck dissection.20 Because many of these masses in the thyroid bed and neck can demonstrate either no growth or minimal growth over time, it is important to correlate with a patient’s thyroglobulin level over time because this may indicate residual or progressive disease. Alcohol ablation of lymph node metastases As an alternative to surgical management, alcohol (ethanol) ablation can be performed in the treatment of cervical lymph node metastases, especially in patients who are either poor surgical candidates or those who wish to avoid surgery. The ethanol is administered through percutaneous injection under US guidance.21
SUMMARY US plays a crucial role in the diagnosis and management of patients with thyroid cancer. Not only is it the best imaging modality for the detection of suspicious thyroid nodules and cervical nodal metastases but also the imaging modality of choice to provide guidance during the performance of thyroid and nodal biopsies. Knowledge of the sonographic anatomy of the thyroid gland and nodal stations as well as features commonly seen in malignant thyroid nodules and nodal metastases and experience with the use of the
The Role of Sonography in Thyroid Cancer latest state-of the art high-resolution US equipment is imperative to its effective use in the evaluation of thyroid cancer patients. A summary of the pearls, pitfalls, and variants and what radiologists need to know is found in Boxes 2 and 3. Many groups of physicians (radiologists, surgeons, and endocrinologists) are involved in the care of patients with thyroid cancer and the recommendations and management steps discussed in this article may vary by institution. Therefore, multidepartmental collaboration and meetings are essential to keeping a practice up to date to ensure satisfaction of the referring physicians and providing optimal patient care.
Box 2 Pearls, pitfalls, and variants Hashimoto thyroiditis can present with diffuse small nodules (
