The Role of Sonographyin Thyroid Cancer

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

� 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 manage-ment 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 nodulesand cervical lymph nodes.

� US is routinely used in the postoperative surveillance of the neck for tumor recurrence in the thyroidbed or nodal stations.

INTRODUCTION

According to the National Cancer Institute, anestimated 63,000 cases of thyroid cancer will bediagnosed in 2014.1 When pathologically welldifferentiated and diagnosed early, the disease ishighly treatable and can be curable. The 5-yearrelative survival rate of most types of stage Ithyroid cancer approaches 100%.2

US is used routinely in the diagnosis and man-agement of thyroid cancer, from initial detectionand diagnosis to preoperative planning to post-operative surveillance. This review discussesthe various roles of sonography in managingpatients with thyroid cancer and reviews the sono-graphic appearance of thyroid cancer and nodalmetastases.

om

NORMAL ANATOMY AND IMAGINGTECHNIQUE

The thyroid gland is a bilobed gland that sitsatop the trachea within the anterior-inferior neck

Russell H. Morgan Department of Radiology and RadioMedicine, 601 North Caroline Street, Baltimore, MD 212* Corresponding author. 601 North Caroline Street, JHOE-mail address: scoquia1@jhmi.edu

Radiol Clin N Am - (2014) -–-http://dx.doi.org/10.1016/j.rcl.2014.07.0070033-8389/14/$ – see front matter � 2014 Elsevier Inc. All

(Fig. 1). The isthmus connects the right and leftthyroid lobes. Each lobe measures approximately4 to 6 cm in length and less than 2 cm in widthand in the anterior-posterior dimension.3 Thenormal isthmus measures less than 6 mm in theanterior-posterior dimension. The normal gland ishomogeneous in echotexture and hyperechoiccompared with the adjacent strap muscles (seeFig. 1).

After documentation of any thyroid lesion thathas suspicious features for primary thyroid cancer,the cervical lymph nodes are imaged. A normallymph node has an elongated shape (a 2:1 ratiobetween length and short-axis dimensions) anddemonstrates an echogenic fatty hilum. Vascularflow is seen entering into the lymph node via thefatty hilum (Fig. 2) and the cortex is symmetricallyhypoechoic.

The neck can be divided into nodal levels orstations by anatomic landmarks. The numericclassification system of the neck nodal stations isoutlined in Table 1 and depicted in Fig. 3.4 Usingthis classification, the neck can be divided into

logical Science, Johns Hopkins University School of87, USAC 3142, Baltimore, MD 21287.

rights reserved. radiologic.th

eclinics.c

Fig. 1. Normal sonographic appearance of the thyroid.The thyroid (arrows) sits atop the trachea (T) and isa bilobed structure echogenic to the adjacentmuscula-ture (M).

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central and lateral neck compartments. Stations I,VI, and VII are considered central neck compart-ments and stations II to V are considered lateralneck compartments. The medial edge of the com-mon carotid artery serves as a landmark to dividethe central from the lateral compartment. Thedistinction between the central and lateral neckcompartments is important for the surgical man-agement of thyroid cancer if nodal metastasesare present (discussed later).

IMAGING PROTOCOLSThyroid

The thyroid gland is imaged with a linear high-frequency transducer (7–15 MHz). Occasionally,if the thyroid gland is enlarged, a curved, lower-frequency transducer may be used to fully imagethe thyroid.The right and left thyroid lobes are imaged in the

transverse and sagittal planes. Anterior-posteriordimension, width, and length are measured atthe mid thyroid gland. The isthmus is measuredin the anterior-posterior dimension. Nodules, ifpresent, are measured in the transverse and

Fig. 2. Normal lymph nodes. (A) Lymph node with smooth,echogenic fatty hilum. (B) Another lymph node demonstr

sagittal planes in three dimensions and evaluatedwith color Doppler to document vascularity.

Cervical Lymph Nodes

The neck nodes are imaged with the same trans-ducers as the thyroid: a high-frequency lineartransducer for most of the nodal stations and oc-casionally 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 abnormallymph nodes. Normal-appearing lymph nodescan be documented for each level, with the fattyhilum included in the image. Measurement ofsonographically normal-appearing lymph nodesis not necessary. Abnormal lymph nodes (dis-cussed later) should be imaged and measured inthe transverse and sagittal planes. The nodesalso should be interrogated with color DopplerUS to assess for abnormal and disorganized bloodflow.General imaging protocols for the thyroid gland

and cervical lymph nodes are summarized inTable 2.

IMAGING FINDINGS AND PATHOLOGYTypes of Thyroid Cancer

There are several types of primary thyroid cancer.Papillary thyroid carcinoma (PTC) is the mostcommon, accounting for approximately 75% to80% of thyroid cancers. PTC is multifocal inapproximately 20% of cases and more commonin females than males. PTC usually presentsbefore age 40 years, often with cervical nodal me-tastases. It is also themost common thyroid malig-nancy in children. PTC has the best prognosis andhighest survival rate of all thyroid cancers, reach-ing a 20-year survival rate of approximately 90%to 95%. Other types of thyroid carcinoma includefollicular carcinoma (10%–20%), medullary carci-noma (5%–10%), and anaplastic carcinoma

homogeneous, hypoechoic cortex (arrow), and centralating normal central hilar flow (arrow).

Table 1Cervical nodal stations: numeric classification

Nodal Station Location

IA Submental lymph nodes

IB Submandibular lymph nodes

II Internal jugular vein chain from base of skull to the inferior border of the hyoid boneA: Anterior to the internal jugular veinB: Posterior the internal jugular vein

III Internal jugular vein chain from the inferior border of the hyoid bone to the inferiorborder of the cricoid cartilage

IV Internal jugular vein chain from the inferior border of the cricoid cartilage to thesupraclavicular fossa

V Posterior triangle lymph nodes, posterior to the sternocleidomastoid muscleA: From the skull base to the inferior border of the cricoid cartilageB: From the inferior border of the cricoid cartilage to the clavicle

VI Central compartment nodes from the hyoid bone to the suprasternal notch

VII Central compartment nodes inferior to the suprasternal notch in the superiormediastinum

Note: The lateral compartments (II–V) are separated from the central compartments (I, VI, and VII) by the medial edge ofthe common carotid artery.

From Som PM, Curtin HD, Mancuso AA. An imaging-based classification for the cervical nodes designed as an adjunct torecent clinically based nodal classifications. Arch Otolaryngol Head Neck Surg 1999;125(4):391; with permission.

The Role of Sonography in Thyroid Cancer 3

(1%–2%).5 Follicular thyroid carcinomamost oftenaffects women in the 6th decade of life and maypresent with metastatic lesions to bone, brain,lung, and liver via hematogenous spread. FNAbiopsy (FNAB) cannot differentiate between fol-licular adenoma and carcinoma and surgical

Fig. 3. Diagram of the neck nodal stations. (From Som PMtion for the cervical nodes designed as an adjunct to recentHead Neck Surg 1999;125(4):394; with permission.)

resection is required to make this distinction. Med-ullary thyroid carcinoma arises from the parafollic-ular cells (C cells) of the thyroid gland. It is oftenfamilial in origin (vs sporadic) and is associatedwith multiple endocrine neoplasia type 2 syndromein 10% to 20% of cases. Patients present with

, Curtin HD, Mancuso AA. An imaging-based classifica-clinically based nodal classifications. Arch Otolaryngol

Table 2Imaging protocols for thyroid and cervicallymph node examinations

Thyroid imaging protocol

Transducer Linear 7–15 MHz (curvedlower-frequencytransducer as needed)

Glandmeasurements

Lobes: anterior-posteriordimension, width,longitudinal dimension

Isthmus: anterior-posteriordimension

Nodules Measurement of eachnodule in threedimensions; color Dopplerinterrogation of nodule

Cervical lymph node imaging protocol

Transducer Linear 7–15 MHz (curvedlower-frequencytransducer as needed)

Nodes Each nodal stationevaluated on each side ofthe neck

Documentation ofabnormal lymph nodes:Size measured in threedimensions

Color Dopplerinterrogation of node

Fig. 4. PTC. This nodule measured 5.2 cm and wasfound in a 17-year-old girl who presented with neckswelling. The patient’s age and the size of the noduleincreased the probability of this nodule beingmalignant.

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elevated calcitonin levels due to the secretion ofcalcitonin by the parafollicular cells. Anaplasticthyroid carcinoma is the rarest and most aggres-sive of the primary thyroid carcinomas, often fatal.Its dismal prognosis carries a 5-year survival rateof only 5%.6 There is often local invasion of theadjacent soft tissues, trachea, and lymph nodes.Risk factors for the development of thyroid

carcinoma include a history of neck irradiationand a family history of thyroid cancer. Additionalrisk factors that increase the probability of cancerwithin a given thyroid nodule include age under30 years or over 60 years and male gender.7 Nod-ules greater than 2 cm also are reported to havean increased risk of cancer (Fig. 4).8

Lymphomatous involvement of the thyroid israre, accounting for less than 5% of thyroid malig-nancies. It may present as a manifestation ofgeneralized lymphoma or be primary to the thyroidgland, usually a non-Hodgkin lymphoma. Hashi-moto thyroiditis is a risk factor for the developmentof thyroid lymphoma. Metastatic disease to thethyroid is also uncommon; primary malignanciesinclude lung, breast, and renal cell carcinomas aswell as melanoma.6

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 ma-lignant.6 US features suspicious for malignancyare reviewed in this section. They are also summa-rized in Table 3.

CalcificationCalcification within the thyroid may be classifiedas microcalcification, coarse calcification, or peri-pheral rim calcification. Although calcification maybe seen in both benign and malignant processesof the thyroid, it is the US feature most commonlyassociated with malignancy. Of these varioustypes, microcalcifications are the most specificfor thyroid malignancy, with a specificity of up to95%.6 Microcalcifications are most commonlyfound in PTC and appear as tiny punctate echo-genic foci within the nodule (Fig. 5). Due to theirsmall size, they usually do not demonstrate poste-rior acoustic shadowing. Colloid may also appearon US as tiny echogenic foci but tends to appearlinear and demonstrates posterior ring-down orcomet-tail artifact (Fig. 6).9 Making this distinctioncan be difficult, however, and biopsy should beperformed for indeterminate foci and for thosefoci lacking the comet-tail artifact. Furthermore,the presence of the ring-down artifact doesnot necessarily preclude contemplating biopsy;microcalcifications and colloid may coexist in thesame nodule.Coarse calcification and peripheral rimlike

calcification may also be seen with thyroid malig-nancies; however, they also may be found in multi-nodular thyroids or goiters. Due to their larger size,

Table 3Diagnostic criteria: sonographic featuressuggestive of malignancy

US Feature Comment

Calcification Micro-, macro-,coarse, peripheral(especially micro)

Solid hypoechoicnodule

Especially if veryhypoechoic

Local invasion More common inanaplastic andlymphoma

Edge refractionshadow

Taller than wide Nodule anterior-posteriordimension greaterthan width

Irregular margins

Adjacent suspiciouslymph nodes

Size >2 cm

Posterior acousticshadowing

The Role of Sonography in Thyroid Cancer 5

these calcifications demonstrate posterior acous-tic shadowing (Fig. 7). Coarse calcifications maybe seen in PTC; however, they are more com-monly associated with medullary thyroidcarcinoma.6 Nodules with coarse calcificationsnecessitate FNAB.

Solid hypoechoic noduleThyroid nodules may be completely cystic or solidor a combination of both. Likewise, thyroid nodulesmay be hyperechoic, isoechoic, or hypoechoicto the remainder of the thyroid parenchyma. MostPTCs are hypoechoic and nearly all medullarythyroid carcinomas are hypoechoic.10 Some inves-tigators believe the extremely hypoechoic nodule

Fig. 5. (A, B) Examples of microcalcification. Multiple punthe hypoechoic nodules. Both of these nodules are markewere pathologically proved to be PTC.

confers ahigher risk ofmalignancy.Benign nodulesmay also be hypoechoic; therefore, evaluationfor additional suspicious features, such as calcifi-cation, should be performed. If no other suspiciousfeatures are present, these hypoechoic nodulescan be biopsied when of sufficient size (discussedlater).

Follicular neoplasms (adenoma and carcinoma)can also appear as solid, well-marginated, hypoe-choic nodules with thin hypoechoic halos10 andcentral linear hypoechoic striations or areas(Fig. 8). Because the distinction between follicularadenoma and carcinoma can only be made basedon vascular and capsular invasion, the diagnosiscan only be made by surgical resection. As such,once a nodule is diagnosed as a follicularneoplasm via FNAB, surgical management is thenext step.

Local invasionAnaplastic thyroid carcinoma and thyroid lym-phoma may present as large, rapidly growingmasses. The masses may be discrete or infiltra-tive. Extracapsular extension into the soft tissuesis common with invasion into the trachea, neckvessels, and strap muscles. There is usually asso-ciated cervical lymphadenopathy.

Edge refraction shadowPosterior acoustic shadowing from the edges of asolid nodule has also been associated with PTC. Itis thought that the fibrotic reaction around theedge of the tumor is responsible for the edgerefraction shadow.10

Other features suggesting malignancy inthyroid nodulesAdditional suspicious features include nodulesthat are taller than they are wide,11 have irregularshape or margins,11 demonstrate posterior acous-tic shadowing in the absence of edge refraction, orare accompanied by sonographically suspiciouslymph nodes, such as lymph nodes with

ctate echogenic foci (arrows) are seen within each ofdly hypoechoic with irregular borders. These nodules

Fig. 6. Example of colloid within a predominatelycystic thyroid nodule. The punctate echogenic focidemonstrate comet-tail artifact (arrow).

Fig. 8. Hypoechoic nodule. The nodule is well definedand homogeneously hypoechoic with a thin hypoe-choic halo. FNA resulted in pathology of follicularneoplasm. The patient was scheduled for lobectomyfor definitive diagnosis.

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calcification, cystic change, or abnormally in-creased or disorganized blood flow. A moredetailed discussion of the sonographic findingssuspicious for cervical lymph node metastasisfrom thyroid carcinoma follows.Although these features can be seen in thyroid

malignancies, they are by no means pathogno-monic; benign nodules may also demonstratethese features. The differential diagnosis of thyroidnodules is found in Table 4. Therefore, when nod-ules present with features suspicious or sugges-tive of malignancy, these should proceed tobiopsy when of sufficient size.

Size criteria for biopsyMultiple guidelines for FNAB of thyroid nodulesexist because multiple medical specialties and

Fig. 7. Coarse calcification. Hypoechoic nodulewith slightly indistinct and irregular border demon-strates a cluster of coarse echogenic calcificationsdemonstrating posterior acoustic shadowing (arrow).Pathology was PTC.

organizations are involved in the care of patientswith thyroid nodules. These include recommenda-tions from the American Thyroid Association(ATA), the Society of Radiologists in Ultrasound,and the American Association of Clinical Endocri-nologists (AACE).5,12,13 Regardless of the recom-mending body, the guidelines take into accountthe nodule’s sonographic appearance as well assize. In addition, the ATA uses clinical risk stratifi-cation, providing differing guidelines for high-riskand low-risk patients. In general, for low-riskpatients, the various guidelines recommendbiopsy of solid nodules at sizes greater than 1 to1.5 cm and mixed cystic and solid nodules at sizesgreater than 1.5 to 2 cm. The ATA decreases itsminimum size threshold to 5 mm in high-risk pa-tients who have nodules with suspicious featuresor nodules accompanied by suspicious lymph no-des, whereas the AACE decreases its sizethreshold below 1.0 cm if there are suspicioussonographic features present.Due to the multitude of guidelines available,

it may be confusing as to which specific recom-mendations to follow. Each department or practiceshould meet with the referring endocrinologistsand surgeons to decide which of the guidelinesis to be used by all members of the clinical teamto provide seamless care to patients.

Pitfalls of thyroid US in the detection ofnodulesParathyroid adenomas may be confused withthyroid nodules. Most parathyroid adenomas areextrathyroidal in location; evaluation for the echo-genic thyroid capsule separating the adenomafrom the thyroid tissue is helpful in making thisdistinction. Parathyroid adenomas are usuallylocated posterior to the mid gland or inferior tothe thyroid gland (Fig. 9A). Adenomas are quitevascular and obtain their vascular supply fromthe thyroid (see Fig. 9B).

Table 4Differential diagnosis of thyroid nodules

Diagnosis Comment

Benign

Adenomatoid nodule

Follicular adenoma Surgical excision is required to differentiate adenoma fromcarcinoma

Hashimoto thyroiditis Lymphocytic thyroiditis can be used as alternative nomenclature

Parathyroid adenoma Most are extrathyroidal in location; evaluate for capsule separatinglesion from thyroid; correlate with parathyroid hormone level

Malignant

PTC

Follicular thyroid carcinoma

Medullary thyroid carcinoma

Anaplastic thyroid carcinoma

Lymphoma Treat with systemic therapy rather than thyroidectomyMetastatic disease

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.

The Role of Sonography in Thyroid Cancer 7

Hashimoto thyroiditis may also present withnodules. The nodules are usually subcentimeterin size (typically 2–3 mm and less than 6 mm)and numerous (termed micronodulation or giraffepattern), however, causing diffuse heterogeneityof the gland. This diffuse heterogeneity mayalso create the appearance of larger nodules.The borders of these apparent lesions are indis-tinct, however. Moreover, because it is an auto-immune process, prominent reactive cervicallymph nodes, usually in level VI, may be presentand could be confused as suspicious lymph no-des. These lymph nodes, however, usually havefatty hila and maintain the morphologic appear-ance of a benign lymph node. A truly discretenodule, however, in a patient with Hashimotothyroiditis should be viewed with concern

Fig. 9. Parathyroid adenoma. (A) The inferior parathyroidthyroid. The echogenic thyroid capsule (arrow) separates tparathyroid adenoma is quite vascular and receives its blohilar flow of a lymph node, the flow within a parathyroid

because these patients are at increased risk forboth lymphoma and PTC.

Management of multiple thyroid nodulesPatients sometimes present with multiple nodules,which may pose a dilemma regarding which nod-ules to biopsy. Regardless of the number of nod-ules present, the risk of thyroid cancer in apatient is unchanged.5 Furthermore, it has beenfound that although a majority of cancers foundin patients with multinodular thyroids are withinthe dominant nodule, approximately one-third ofthe cancers are found in the nondominant nodule.5

Therefore, each nodule should be evaluated inde-pendently, evaluating for suspicious features andthen triaging the nodules for biopsy in the orderof most suspicious features and then by size.

gland is typically located posterior and inferior to thehe parathyroid adenoma (P) from the thyroid. (B) Theod supply from the thyroid gland. Unlike the centraladenoma is peripheral/polar in distribution.

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Thyroid Nodule Fine-Needle Aspiration Biopsy

Biopsy and cytologic evaluationThyroid nodules can be sampled via US guidanceor by palpation; however, in this day and age,they should be sampled with US guidance. Aftersterilization of the skin at the needle entrance siteand administration of local anesthesia, FNAsamples are obtained with small-gauge needleswith a bevel tip, typically 25or 26 gauge. Pathologicevaluation can be performed on site or the samplescan be transported to a laboratory for off-sitetesting. The presence of at least 6 groups of benignfollicular cells, with each group containing at least10 cells, is required for a specimen to be consid-ered adequate and benign, per the BethesdaSystem criteria.14 Other alternative criteria for ade-quacy include the presence of abundant colloid(suggesting a benign macrofollicular nodule) orenough cells to suggest an alternative diagnosis,such as lymphocytic (or Hashimoto) thyroiditis oratypia. Aspirated thyroid nodules are classified asbenign, atypia of undetermined significance/follic-ular lesion of undetermined significance (AUS/FLUS), follicular neoplasm, suspicious for malig-nancy, or malignant, per the Bethesda Systemclassification.14 Approximately 10% of thyroidFNAs from most laboratories are read, however,as nondiagnostic or inadequate.14

ManagementBenign nodules are managed conservatively withclinical and imaging follow-up whereas nodulesclassified as follicular neoplasm, suspicious formalignancy, or malignant go on to surgical man-agement. Nodules classified as AUS/FLUS fallinto an indeterminate category, comprising be-tween 3% and 6% of total diagnoses.14 In thesecases, repeat FNA is recommended. However,20% of these nodules remain AUS after repeatbiopsy. The risk of malignancy in these nodules isbetween 5% and 15%.14

To avoid diagnostic surgery for what may ulti-mately be a benign nodule, FNA samples can besent for genomic testing. The Afirma Gene Expres-sion Classifier (AGEC) from Veracyte (South SanFrancisco, California) classifies these cytologicallyindeterminate nodules as either benign or malig-nant, with a 95% negative predictive value.15

To minimize the need for a third FNA specificallyjust to perform this test, additional FNA passesare obtained at the time of the second FNA forAGEC testing. This material is then reserved andanalyzed in the event that the repeat (or second)FNA is also called indeterminate. A nodule classi-fied as benign on AGEC is managed just as anodule classified as benign on cytology, with

imaging and clinical follow-up.15 A benign AGECresult, therefore, negates the necessity of per-forming surgery for diagnosis of cytologically inde-terminate nodules. At one center, the number ofdiagnostic surgeries performed for these nodulesdropped 10-fold after the implementation ofAGEC testing, and 1 surgery was avoided forevery 2 AGEC tests performed.15 A suspiciousfor malignancy AGEC result correlates to a greaterthan 50% risk of malignancy for the nodule, andsurgery should be performed for pathologicdiagnosis.

Preoperative Evaluation for Cervical NodalMetastases

Current best surgical practice in the United Statesrecommends central lymph node dissection at thetime of thyroidectomy as well as lateral neckdissection if there are confirmed metastatic cervi-cal lymphnodes. Therefore, prior to thyroidectomy,the cervical lymph nodes should be evaluated forlymph node metastases both with palpation andUS; if abnormal lymph nodes are suspected, FNAshould be performed. Stulak and colleagues16 in2006 reported a sensitivity and specificity of83.5% and 97.7% of preoperative US in the detec-tion of lateral nodal metastasis in newly diagnosedthyroid cancer patients, respectively. Hence, asystematic sonographic evaluation of the necknodes is performedbilaterally to identify suspiciousnodes.

US features of suspicious nodesBenign sonographic morphologic features oflymph nodes include the presence of an echo-genic fatty hilum, central regular hilar vascularflow, and elongated shape. Deviations from thisappearance should be considered abnormal.A node demonstrating cystic change or the

presence of calcification (mimicking the appear-ance of the primary tumor) has been shown to be100% specific for metastatic disease.17 Increasedor eccentric irregular vascularity, round shapeand/or loss of the normal elongated shape, hyper-echogenicity of the node relative to the adjacentstrap muscles, and loss of a fatty hilum are allfeatures of abnormal lymph nodes. A summary ofsuspicious features is in Box 1, and examples ofsuspicious nodes are given in Figs. 10–12.Metastatic disease from other primaries, how-

ever, such as squamous cell carcinoma, can pro-duce cystic degeneration of a lymph node.

Management of suspicious nodesUnlike the guidelines for thyroid nodule biopsy, nospecific size criteria are commonly used in regardto lymph node biopsy. Some institutions may have

Fig. 11. Calcifications within a lymph node. Multipleechogenic foci (arrow) are seen within a lymph node(arrowheads), compatiblewith calcification. The lymphnode is also round, another suspicious feature. Thenode was biopsied, with pathology of metastatic PTC.

Box 1Sonographic features suspicious for lymphnode metastasis

Cystic change

Calcification

Peripheral, increased, irregular, or eccentricvascularity

Loss of the normal elongated shape (less than2:1 ratio between long axis and short axis) orround shape

Hyperechogenicity of the lymph node relativeto adjacent strap muscle

Loss of fatty hilum

Irregular, asymmetrically thickened cortex

The Role of Sonography in Thyroid Cancer 9

their own size cutoff (ie, biopsy lymph nodes8 mm or larger), formed by consensus betweentheir surgeons, endocrinologists, and radiolo-gists. For example, at the authors’ institution,because of the high specificity of lymph nodescontaining calcification or cystic areas in predict-ing metastatic disease, these are biopsiedregardless of size. Those that are abnormal butdo not contain these features are usually biopsiedwhen 8 mm in size.

Lymph nodes that are homogeneously hypoe-choic without an echogenic fatty hilum presentand do not demonstrate any other suspiciousfeatures may be followed, with biopsy for thosethat demonstrate interval growth or interval

Fig. 10. Cystic replacement of a cervical lymph node.The lymph node is enlarged and has a large anechoiccomponent, causing increased through transmission,compatible with cystic change (C). A small area of re-sidual soft tissue is seen within the node (arrow). Apunctate echogenic focus is seen within the soft tis-sue, compatible with calcification.

development of additional suspicious features.Again, this particular management step may bebased on the consensus between the referringphysicians and the radiologists.

Suspicious lymph nodes can be biopsied preop-eratively to confirm the necessity for lateral neckdissection at the time of thyroidectomy. Becausethese nodes are usually not palpable, they aresampled under US guidance, using the same tech-nique as described for FNA of thyroid nodules. Ifthe lymph node is cystic, such that it yields insuffi-cient cells for diagnosis, the fluid can be aspiratedand sent for thyroglobulin.

Alternatively a surgeon may choose to proceedto surgery and remove the suspicious lymph no-des at the time of thyroidectomy. To help the sur-geon find the nodes intraoperatively, preoperative

Fig. 12. Abnormal lymph node vascularity. Instead ofcentral 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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US can be used to mark the suspicious nodes onthe skin. In more complex cases, intraoperativeUS guidance can be provided.

Postoperative Surveillance

After thyroidectomy, in conjunction with laboratoryfollow-up and nuclear medicine radioiodine imag-ing, the neck is evaluated routinely with US for thedevelopment of nodal metastases. The initial USexamination should be performed in the first 6 to12 months and then periodically depending ona patient’s risk for recurrence and thyroglobulinlevel.12 The frequency and length of surveillancemay also be dependent on the institution, endocri-nologist, or surgeon. The risk of recurrence eitherwithin the thyroid bed or within the cervical lymphnodes in PTC has been reported to between 15%and 25%.18

The postoperative neck can be divided intolateral and central compartments (right lateralneck, right central neck, left lateral neck, and leftcentral neck), discussed previously. Disease foundin each separate compartment leads to its ownseparate neck dissection. Therefore, if multipleabnormal nodes are present in multiple compart-ments, a suspicious node from each compartmentshould be sampled to accurately plan surgicalmanagement and decrease the extent of theneck dissection.Identification of thyroid cells within the lymph

node is confirmatory for lymph node metastasis.In the event the lymph node sampling is nondiag-nostic or indeterminate for metastatic disease,the lymph node can be aspirated and the samplesent for thyroglobulin assay. It is particularly help-ful to aspirate and analyze the fluid within smallcystic areas. A thyroglobulin level in a lymphnode greater than the serum thyroglobulin level isdiagnostic for metastatic disease.

Pitfalls in the postoperative surveillance periodIn one study, approximately 34% of postoperativepatients were found to have small thyroid bed nod-ules.18 Of these nodules, only a small percentage(9%) increased in size during the median 3-yearfollow-up period, growing at a rate of 1.3 mm/y.Furthermore, only one-third of those proved malig-nant demonstrated interval growth. This behaviordemonstrates the slow indolent nature of papillarythyroid cancer. Therefore, many small nodules inthe thyroid bed without suspicious features canbe observed over time.In addition to recurrence, other masses can be

seen in the surgical bed on postoperative exami-nations, such as residual thyroid tissue, scarring/fibrosis, and suture granulomas. Residual thyroidtissue may be focal and can be vascular, features

that make it difficult to differentiate from recur-rence by imaging. FNA can be performed to differ-entiate the mass as either malignant (compatiblewith recurrence) or benign (normal residual thyroidtissue). Scarring in the postsurgical bed can benonspecific in appearance but typically is nonvas-cular and elongated, blending into the adjacent fatand muscle. These areas can also be observedover time for interval increase in size or develop-ment of suspicious features that prompt biopsy.Suture granulomas can present as focal masseswithin the thyroid bed. The sonographic appear-ance of suture granulomas has been describedas a hypoechoic lesion with central echogeniclines or foci.19 Although echogenic foci within alesion may suggest microcalcification and, there-fore, imply recurrence, features that support su-ture granuloma include centrality of the foci,paired foci, and foci larger than 1 mm.19 Suturegranulomas also tend to regress or resolve overtime.19

Suture granulomas also may present within theneck, buried within the sternocleidomastoid mus-cle or subcutaneous tissue. Neuromas may alsobe seen within the neck, typically presenting as hy-poechoic masses in close relation to the carotidartery. Traumatic neuromas may develop afterneck dissection.20

Because many of these masses in the thyroidbed and neck can demonstrate either no growthor minimal growth over time, it is important tocorrelate with a patient’s thyroglobulin level overtime because this may indicate residual or pro-gressive disease.

Alcohol ablation of lymph node metastasesAs an alternative to surgical management, alcohol(ethanol) ablation can be performed in the treat-ment of cervical lymph node metastases, espe-cially in patients who are either poor surgicalcandidates or those who wish to avoid surgery.The ethanol is administered through percutaneousinjection under US guidance.21

SUMMARY

US plays a crucial role in the diagnosis andmanagement of patients with thyroid cancer. Notonly is it the best imaging modality for the detec-tion of suspicious thyroid nodules and cervicalnodal metastases but also the imaging modalityof choice to provide guidance during the perfor-mance of thyroid and nodal biopsies. Knowledgeof the sonographic anatomy of the thyroid glandand nodal stations as well as features commonlyseen in malignant thyroid nodules and nodalmetastases and experience with the use of the

Box 3What the radiologist needs to know

� In the adult population, 50% have thyroidnodules, but only 7% are malignant.

� Microcalcification has the highest specificityfor thyroid carcinoma.

� Most malignant nodules are hypoechoic.

� A thyroid nodule biopsy returning a diagnosisof AUS/FLUS should be repeated with addi-tional samples reserved for AGEC genetesting.

� Preoperative US of the neck is performed toevaluate the need for lateral neck dissection.

The Role of Sonography in Thyroid Cancer 11

latest state-of the art high-resolution US equip-ment is imperative to its effective use in theevaluation of thyroid cancer patients. A summaryof the pearls, pitfalls, and variants and what radiol-ogists need to know is found in Boxes 2 and 3.

Many groups of physicians (radiologists, sur-geons, and endocrinologists) are involved in thecare of patients with thyroid cancer and the rec-ommendations and management steps discussedin this article may vary by institution. Therefore,multidepartmental collaboration and meetingsare essential to keeping a practice up to date toensure satisfaction of the referring physiciansand providing optimal patient care.

Box 2Pearls, pitfalls, and variants

� Hashimoto thyroiditis can present withdiffuse small nodules (<6 mm) or diffuse het-erogeneity that can appear like nodules.

� Parathyroid adenomas may be confused withthyroid nodules or lymph nodes due to theirlocation:

� Evaluate for an echogenic line denotingthe thyroid capsule to place the lesion asextrathyroidal in location.

� Parathyroid adenomas are usually locatedposterior to the mid gland and inferior tothe inferior pole of the thyroid.

� Parathyroid adenomas demonstrate polar/peripheral vascular flow from the thyroidrather than central hilar vascular flow oncolor Doppler.

� Microcalcifications within thyroid nodulesmay not demonstrate posterior acousticshadowing.

� Colloid can be confused with microcalcifica-tion: evaluate for comet-tail artifact.

� Rapid growth and invasion of adjacent struc-tures can be seen in anaplastic thyroid carci-noma and lymphoma.

� The presence of cystic change and calcifica-tion in cervical lymph nodes is 100% specificfor metastatic thyroid cancer. Occasionally,metastases from other primaries, mostcommonly squamous cell head and neck can-cer, sometimes cause cystic degeneration incervical lymph nodes.

� The differential diagnosis of thyroid bed andneck masses seen postoperatively other thanrecurrence includes residual thyroid tissue,scarring/fibrosis, scar granuloma, and neu-romas.

� The location and number of lymph nodebiopsies to be performed are determined bythe number of neck compartments showingsuspicious lymph nodes (right and left lateralneck, central neck—if postoperative). At least1 biopsy in each compartment should be per-formed to definitively diagnose metastaticinvolvement prior to surgery.

� In the post-thyroidectomy patient, indetermi-nate or nondiagnostic lymph node biopsies,especially with cystic areas, should be testedfor thyroglobulin.

� Thryoid bed masses may be stable in size orshow minimal growth over time; correlationwith thyroglobulin levels is imperative toassessing the risk of recurrence when thesonographic appearance is indeterminate.

REFERENCES

1. General information about thyroid cancer. In: thyroid

cancer treatment PDQ. 2014. Available at: http://

www.cancer.gov/cancertopics/pdq/treatment/thyroid/

HealthProfessional. Accessed March 3, 2014.

2. Thyroid cancer survival by type and stage. In: thy-

roid cancer. 2014. Available at: http://www.cancer.

org/cancer/thyroidcancer/detailedguide/thyroid-cancer-

survival-rates. Accessed March 3, 2014.

3. Middleton WD, Kurtz AB, Hertzberg BS. Neck and

chest. In: Ultrasound: The Requisites. St Louis

(MO): Mosby; 2004. p. 244–77.

4. Som PM, Curtin HD, Mancuso AA. An imaging-

based classification for the cervical nodes designed

as an adjunct to recent clinically based nodal classi-

fications. Arch Otolaryngol Head Neck Surg 1999;

125(4):388–96.

5. Frates MC, Benson CB, Chrboneau JW, et al. Man-

agement of thyroid nodules detect at US: Society

of Radiologists in ultrasound consensus conference

statement. Ultrasound Q 2006;22(4):231–8.

Coquia et al12

6. Hoang JK, Lee WK, Lee M, et al. US features of thy-

roid malignancy: pearls and pitfalls. Radiographics

2007;27(3):847–61.

7. Polyzos SA, Kita M, Avramidis A. Thyroid nodules –

Stepwise diagnosis and management. Hormones

2007;6(2):101–19.

8. KamranSC,MarquseeE,KimMI, et al. Thyroid nodule

size andprediction of cancer. JClin EndocrinolMetab

2013;98(2):564–70.

9. BelandMD, Kwon L, Delellis RA, et al. Nonshadowing

echogenic foci in thyroid nodules. J Ultrasound Med

2011;30(6):753–60.

10. Reading CC, Charboneau JW, Hay ID, et al. Sono-

graphy of thyroid nodules: a “classic pattern” diag-

nostic approach. Ultrasound Q 2006;21(3):157–65.

11. Kim JY, Lee CH, Kim SY, et al. Radiologic and path-

ologic findings of nonpalpable thyroid carcinomas

detected by ultrasonography in a Medical Screening

Center. J Ultrasound Med 2008;27(2):215–23.

12. Cooper DS, Doherty GM, Haugen BR, et al. Re-

vised American Thyroid Association Management

Guidelines for patients with thyroid nodules and

differentiated thyroid cancer. Thyroid 2009;19(11):

1167–217.

13. Gharib H, Papini E, Valcavi R, et al. American Asso-

ciation of Clinical Endocrinologists and Associa-

zione Medici Endocrinologi medical guidelines for

clinical practice for the diagnosis and management

of thyroid nodules. Endocr Pract 2006;12(1):63–102.

14. Cibas ES, Ali SZ. The Bethesda system for reporting

thyroid cytopathology. Am J Clin Pathol 2009;132:

658–65.

15. Duick DS, Klopper JP, Diggans JC, et al. The impact

of benign gene expression classifier test results on

the endocrinologist – patient decision to operate

on patients with thyroid nodules with indeterminate

fine-needle aspiration cytopathology. Thyroid 2012;

22(10):996–1001.

16. Stulak JM, Grant CS, Farley DR, et al. Value of pre-

operative ultrasonography in the surgical manage-

ment of initial and preoperative papillary thyroid

cancer. Arch Surg 2006;141:489–96.

17. Shin LK, Olcott EW, Jeffrey RB, et al. Sonographic

evaluation of cervical lymph nodes in papillary

thyroid cancer. Ultrasound Q 2013;29:25–32.

18. Rondeau G, Fish S, Hann LE, et al. Ultrasonograph-

ically detected small thyroid bed nodules identified

after total thyroidectomy for differentiated thyroid

cancer seldom show clinically significant structural

progression. Thyroid 2011;21(8):845–53.

19. Kim JH, Lee JH, Shong YK, et al. Ultrasound fea-

tures of suture granulomas in the thyroid bed after

thyroidectomy for papillary thyroid carcinoma with

an emphasis on their differentiation from locally

recurrent thyroid carcinomas. Ultrasound Med Biol

2009;35(9):1452–7.

20. Huang LF, Weissman JL, Fan C. Traumatic neuroma

after neck dissection: CT characterstics in four

cases. AJNR Am J Neuroradiol 2000;21:1676–80.

21. Lewis BD, Hay ID, Charboneau JW, et al. Percuta-

neous ethanol injection for treatment of cervical

lymph node metastases in patient with papillary

thyroid carcinoma. AJNR Am J Neuroradiol 2002;

178:699–704.