Ebook Thyroid ultrasound and ultrasound guided FNA (2nd edition): Part 2

(BQ) Part 2 book Thyroid ultrasound and ultrasound guided FNA presents the following contents: Ultrasound in themanagement of thyroid cancer, parathyroid ultrasonography, contrast enhanced ultrasound in the management of thyroid nodules, percutaneous ethanol injection (pei) - thyroid cysts and other neck lesions, laser and radiofrequency ablation procedures,....

surveil-POSTOPERATIVE SURVEILLANCE

FOR THYROID CANCER

Ultrasound has assumed a primary role in the management of patients who have been treated for thyroid cancer In spite of better surgical techniques, the acceptance of total and near-total thyroidectomy, and the increasing use of radioiodine, the mor-tality rate from well-differentiated thyroid cancer has changed very little over the past thirty years Because of its propensity

to occur at any age, even in the very young, and to recur many years later, thyroid cancer must be monitored for the lifetime

of the patient Surveillance of these patients in a cost-effective manner has been a challenge Until the 1990s the only diagnos-tic tool available was a 131I whole body scan (WBS) done after

The sensitivity of a WBS in the early detection of residual, recurrent, or metastatic thyroid cancer is poor This is apparent

111

from the many patients who have increased thyroglobulin (Tg) but negative diagnostic scans who are treated with 131I and have positive post-treatment scans (1–4) Park et al have also shown that the doses of 131I used for WBS can stun the uptake of iodine

in metastatic lesions and interfere with the subsequent ment dose of 131I (5) The expense, poor sensitivity, and risk of stunning with a WBS make it an unsatisfactory test with which

treat-to follow patients with thyroid cancer

In the last decade several new probes have been developed that aid in the early detection of recurrent thyroid cancer These include: (1) sensitive, reliable, reproducible Tg assays that biochemically detect the earliest sign of cancer

allows scanning and Tg stimulation without thyroid hormone withdrawal; and (3) high-resolution ultrasound of the postop-erative neck to identify early lymph node recurrence Using these new tools, especially neck ultrasound combined with UG FNA of suspicious lymph nodes, has greatly improved the sen-sitivity of cancer surveillance in these patients Hopefully, their use will result in lower mortality from thyroid cancer

Physical examination of the neck of a patient who has gone a thyroidectomy for thyroid cancer is seldom helpful in the

under-early detection of a recurrence The scar tissue following surgery,

combined with the propensity of metastatic lymph nodes to lie deep in the neck beneath the sternocleidomastoid muscle, make palpation of enlarged lymph nodes in the neck difficult Even lymph nodes several centimeters in diameter are often not palpable High-resolution ultrasound has solved this problem

by proving to be a very sensitive method to find and locate early recurrent cancer and lymph node metastasis Frasoldati et al (6) studied 494 patients with a history of low risk well-differentiated thyroid cancer by a withdrawal WBS, stimulated Tg, and ultra-sound, and found by at least one test that 51 had had a recurrence The WBS was positive in 23 patients (45%), the Tg was positive in

34 patients (67%), and the ultrasound with FNA was positive in

48 patients (94%) Since most thyroid cancer metastasizes to the neck, it is rare for it to spread elsewhere without neck lymph node involvement Therefore, neck ultrasound has proven to be the most sensitive test available in locating early recurrent disease, even before serum Tg is elevated

ULTRASOUND OF THE POSTOPERATIVE NECK

Identifying and evaluating lymph nodes should be done with high-resolution ultrasound using a 10–15MHz transducer with power Doppler capability to assess vascularity When performing

ULTRASOUND MANAGEMENT OF THYROID CANCER 113

ultrasound of the neck in a patient who has undergone a roidectomy, one sees that the carotid artery and jugular vein have migrated medially close to the trachea, and that the thy-roid bed has been filled with a varying amount of hyperechoic connective tissue that appears white (dense) on ultrasound This serves well in demarcating a recurrence of cancer or a metastatic lymph node, which will appear dark or hypoechoic Someone unfamiliar with the appearance of the postoperative neck on ultrasound should begin by examining the neck of someone who underwent a thyroidectomy or hemithyroidectomy for benign disease This allows one to become accustomed to the neck structures and the altered anatomy of the postopera-tive neck without worrying about recurrent thyroid cancer.The commonest areas for detecting cancer are the thyroid bed and the jugular chain of lymph nodes, but metastatic lymph nodes may occur anywhere in the neck In performing ultra-sound looking for metastatic lymph nodes, the entire length

thy-of the internal jugular vein from the head thy-of the clavicle up

to the mandible is searched, paying close attention to the area between the carotid artery and the jugular vein Special attention should be given to the thyroid bed and the central compartment medial to the common carotid artery Malignant paratrachael lymph nodes in this area are likely to metastasize more quickly to the mediastinum and lungs

FIG 8.1 Normal postoperative left neck Note that the common carotid artery and the internal jugular vein have migrated medially next

to the trachea The vein is anterior to the artery but closely adhered to

it Hyperechoic connective tissue has filled in the thyroid bed

The normal neck contains approximately 300 lymph nodes Except for the pharyngeal area, they are usually less than 0.5 cm in their short axis and flattened or oval in the trans-verse view of the neck, with a long axis two or more times the short axis If they become inflamed or hyperplastic, they enlarge but generally maintain this flattened or oval shape High-resolution ultrasound often shows a white line of fat and intranodal blood vessels running through the center of the

lymph node referred to as a hilar line The hilar line is present

in most benign lymph nodes greater than 0.5cm and is also more prominent in older patients A hilar line is seldom seen

in malignant lymph nodes Because lymph node hyperplasia

is so common in the neck, only those lymph nodes >0.5cm

in the short axis are usually biopsied Those with a short axis 0.5cm (0.8cm in the pharyngeal area) or less should have their location marked and be reexamined in six months Metastatic lymph nodes generally have a fuller or more rounded appear-ance in the transverse view with a short/long axis ratio >0.5 Postoperative ultrasound surveillance for cancer is done in the transverse view, since all lymph nodes may appear elongated

in the longitudinal view

In addition to a rounded shape and the absence of a hilar line, there are other ultrasound findings that suggest a lymph node is malignant (7) (Table 8.1) The internal jugular vein

FIG 8.2 Normal postoperative right neck In this patient the vein remains lateral to the artery, but still lies adjacent to it The strap mus-cles (sm) have helped fill in the space left by removal of the thyroid

ULTRASOUND MANAGEMENT OF THYROID CANCER 115

remains lateral or migrates anterior next to the carotid artery

in the postoperative neck Since metastatic nodes commonly

occur in proximity to the jugular vein or in the carotid sheath,

any deviation of the jugular vein away from the carotid artery

strongly suggests malignancy The entire length of the vessels

should be surveyed closely with particular attention given to

any area where the artery and vein diverge

In addition to causing deviation of the internal jugular

vein, malignant lymph nodes tend to compress the vein and

cause a partial obstruction to blood flow Benign lymph nodes

rarely do this until they become quite large

Calcifications in the lymph node, either

microcalcifica-tions or amorphous calcium with shadowing, are indicative

FIG 8.3 Benign lymph node The normal neck contains scores of

lymph nodes, some of which are easily seen with ultrasound This

lymph node (calipers) appears benign because it is flat with a short/

long axis ratio <0.5

TABLE 8.1 Neck lymph node characteristics

Short/Long Axis <0.5 >0.5

Hilar line Present Absent

Jugular Deviation or Compression Absent Present

Microcalcifications Absent Present

Cystic Necrosis Absent Present

Vascularity Central Chaotic/peripheral

of malignancy Cystic necrosis within the lymph node, often recognized because of distal enhancement, is another sign of metastatic involvement with thyroid cancer, although it may also occur with tuberculosis.

FIG 8.5 Power Doppler of the previous lymph node shows zation of the hilum, which contains small arterioles Note there is no vascularization seen in the periphery of the node

vasculari-FIG 8.4 This lymph node beneath the sternocleidomastoid muscle (scm) is slightly more oval but still maintains a short/long axis ratio

<0.5 It also has a distinct hilar line (arrow), a strong indication that

it is benign

ULTRASOUND MANAGEMENT OF THYROID CANCER 117

Power Doppler is very useful in evaluating lymph nodes because

of its sensitivity to arteriolar blood flow Normal nodes generally show only hilar vascularization, but malignant nodes have chaotic vascularization throughout the cortex This is due to the recruitment

of vessels into the periphery of the node (8, 9)

FIG 8.6 Malignant lymph node This lymph node (calipers) is slightly more rounded, with a short/long axis ratio > 0.5 in the transverse view Note the absence of a hilar line, which makes this node suspicious An

UG FNA was needed to confirm malignancy

FIG 8.7 Same lymph node in longitudinal view It appears more benign in this view because it is flatter; even malignant lymph nodes can be long in longitudinal view Therefore, always take the short/long axis measurement in the transverse view

Characteristics that were helpful in deciding if a thyroid nodule is benign or malignant may not apply to lymph nodes For example, metastatic lymph nodes may have sharp borders until they become quite large Both normal and malignant lymph nodes are generally hypoechoic compared to thyroid,

FIG 8.9 Same lymph node (calipers) in longitudinal view shows pression of the jugular vein against the carotid UG FNA confirmed malignancy

com-FIG 8.8 On transverse view, this small rounded lymph node (calipers) without a hilar line is in close proximity to the great vessels

ULTRASOUND MANAGEMENT OF THYROID CANCER 119

but they have varying degrees of echogenicity Early papillary metastases are sometimes dense and may be relatively hyper-echoic As they enlarge up to 1cm they develop cystic necrosis and become hypoechoic Therefore, echogenicity may not be helpful in determining malignancy Matting of lymph nodes

FIG 8.10 This 0.5cm lymph node (calipers) lies between the carotid and the jugular Its location and shape (short/long axis ratio >1) strongly suggest that it is malignant, which was confirmed by UG FNA

FIG 8.11 Although this lymph node (arrow) measures only 2.5mm, its location and shape lead to UG FNA, and Tg was found in the needle washout, confirming metastatic thyroid cancer

FIG 8.13 Transverse view of a metastatic lymph node (calipers) in right neck beneath the sternocleidomastoid muscle (scm) and lateral

to the carotid artery The node is impinging upon the jugular vein (J) The short/long axis ratio is >0.5 and no hilar line is seen UG FNA had positive cytology, and Tg was found in the needle washout

occurs with malignancy but is not a helpful sign, since it is also seen with inflammation or in patients who have had radiation

FIG 8.12 This irregular rounded lymph node (arrow) was discovered because of the separation of the jugular from the carotid The calcifica-tion at 3:00 o’clock indicates it is malignant, but UG FNA is necessary before surgery

ULTRASOUND MANAGEMENT OF THYROID CANCER 121

Because the sonographic features of malignant lymph nodes are not always present, and there is overlap in the ultrasound appearance of benign and malignant lymph nodes, UG FNA

of suspicious lesions is essential for a definitive diagnosis and

FIG 8.14 Longitudinal view of the same lymph node (calipers), ing partial obstruction of the jugular vein In this view, the short/long axis ratio is <0.5, emphasizing the need to measure the short/long ratio

show-in the transverse view

FIG 8.15 This markedly heterogeneous lymph node (calipers) contains scattered calcifications indicating metastatic papillary carcinoma

before recommending surgery Lymph nodes with a short axis

>0.5cm (>0.8cm in pharyngeal area), with a short/long axis ratio

>0.5, and that do not have a hilar line must have an UG FNA

FIG 8.17 This rounded lymph node (calipers) without a hilar line is hypoechoic and has begun to develop cystic necrosis Liquid formation within a solid lymph node is often first suspected because of distal enhancement (arrow)

FIG 8.16 This 2cm rounded lymph node in the right neck is 80% cystic; note the distal enhancement Although occasionally seen in tuberculosis, cyst formation within a lymph node usually indicates metastatic papillary carcinoma

ULTRASOUND MANAGEMENT OF THYROID CANCER 123

FIG 8.18 This metastatic lymph node, less than 1cm in size, contains cystic necrosis on the medial side which is hypoechoic (calipers) and shows enhancement The other side (arrow) is solid and hyperechoic

UG FNA of the hypoechoic area yielded negative cytology, but high levels of Tg in needle washout—a finding not unusual if there is cystic necrosis

FIG 8.19 Typical small metastatic lymph node (calipers) near the jugular vein (J) Note the rounded shape with a short/long axis of 1, absence of a hilar line, calcification (white arrow), and enhancement (black arrow), indicating early cystic necrosis

UG FNA of a suspicious lymph node in the neck is carried out in the same manner as an UG FNA of a thyroid nodule with aspirate slides prepared and sent for cytology interpretation

FIG 8.21 Ultrasound of a 16-year old-female one year ectomy Power Doppler of a small lymph node (arrow) found in the central compartment between the trachea and the left carotid shows chaotic vascularization

post-thyroid-FIG 8.20 Power Doppler of previous lymph node shows chaotic cularization of the periphery of the node, rather than the normal hilar vascular pattern Although cytology from the FNA was negative, a high level of Tg was found in the needle washout

vas-ULTRASOUND MANAGEMENT OF THYROID CANCER 125

FIG 8.22 Larger lymph node found in the lateral compartment of the same patient Power Doppler again shows an abnormal pattern with recruitment of vessels into the cortex of the lymph node

FIG 8.23 2cm nonpalpable lymph node (calipers) in 47-year-old male seven years post-thyroidectomy Enhancement distal to the node (arrow) indicates cystic necrosis has started FNA found negative cytol-ogy, but very high levels of Tg in the needle washout

Lymph node cytology is sometimes difficult to interpret (10) However, thyroid cancer metastases contain Tg, which can be measured and used as a tissue marker Therefore, the biopsy

FIG 8.25 A 1cm lymph node (1) and a 0.5cm lymph node (2) in the lateral neck are both rounded without a hilar line Both nodes had papillary cancer at surgery.

needle(s) is then washed with 1cc normal saline and the out sent for Tg assay (11, 12) A normal saline control is also sent for Tg assay Since most patients are on thyroid hormone suppression, serum Tg is usually low or non-detectable, and

wash-FIG 8.24 Ultrasound of 54-year-old female 36 years after her ectomy reveals a paratrachael lymph node (arrow) in the right central compartment Note that the short/long axis is >1 and several calcifica-tions are seen, indicating malignancy FNA showed positive cytology, but Tg in needle washout was negative, demonstrating the need to do both tests when lymph nodes are biopsied

thyroid-ULTRASOUND MANAGEMENT OF THYROID CANCER 127

the material in the needle is diluted approximately a dredfold to a thousandfold; therefore finding a Tg >10 in the needle washout is considered positive for malignancy Because the intracellular Tg is not exposed to circulating anti-TgAB, a positive test for anti-TgAB in the serum does not interfere with

hun-FIG 8.26 Ultrasound of a 57-year-old female 13 years after a ectomy shows a small oval node (calipers) in the left central com-partment that is suspicious

thyroid-FIG 8.27 Power Doppler of previous lymph node shows a malignant vascular pattern Cytology was negative on FNA, but Tg in needle washout was high, confirming malignancy

the measurement of Tg obtained from lymph nodes, as it does with serum Tg (13) Either a positive cytology report, or find-ing Tg present in the needle washout, confirms the lymph node

is malignant Using either positive cytology or the presence

of Tg as proof of recurrent cancer, Lee et al reported 100%

FIG 8.29 Metastatic lymph node (calipers) in left central ment with short/long axis >1 and no hilar line

compart-FIG 8.28 This lymph node (calipers) was suspicious because of its borderline short/long axis of 0.5 and absent hilum Surgery confirmed metastatic papillary cancer

ULTRASOUND MANAGEMENT OF THYROID CANCER 129

sensitivity and specificity of UG FNA in detecting recurrent thyroid cancer (14) Studies have found the Tg in the needle washout to be more sensitive than cytology in detecting malig-nancy (15) This is probably due to poor cellular material in lymph nodes having cystic necrosis (see Fig 18–20)

FIG 8.30 Another lymph node (calipers) less than 0.5cm that was biopsied because of its shape and location FNA cytology showed papil-lary carcinoma

FIG 8.31 Ultrasound of 50-year-old female 18 years after total thyroidectomy revealed a paratrachael lymph node (calipers) in the central compartment with a short/long axis of 1

Any suspicious lymph nodes should be mapped using the surgical areas defined by the American Joint Commission on Cancer, even if no FNA is done This will allow one to go back and restudy the node at a later date to see if any changes have occurred Mapping of malignant lymph nodes is particularly important when FNA is performed, in order that the surgeon can be directed to the site of the recurrence and plan the sur-gery appropriately A modified lateral neck dissection, rather than removing a few nodes, is usually necessary to return an elevated serum Tg to a nondetectable level.

Routine isotope scanning is no longer an acceptable method of following patients for recurrent thyroid cancer Extrapolating from the Chernobyl experience, early detection using ultrasound offers our best hope of eradicating residual or recurrent disease Ultrasound in conjunction with sensitive Tg monitoring provides endocrinologists with the tools to do this Since 90% of recurrent cancer is initially in the neck, ultra-sound of this area is essential Searching for small hypoechoic lymph nodes or masses in the neck using ultrasound is not difficult, but it does require some effort and patience that is quickly rewarded Annual ultrasound for at least 5 years after surgery, and ultrasound on all patients with detectable serum

Tg or with positive anti-TgAB seems a minimum requirement

if we are to make a significant reduction in the mortality rate

of thyroid cancer

FIG 8.32 Power Doppler of previous lymph node showed peripheral vascular pattern of malignancy FNA cytology was positive and Tg in the needle washout was >10,000

ULTRASOUND MANAGEMENT OF THYROID CANCER 131

ULTRASOUND OF THE PREOPERATIVE NECK

Obviously, if ultrasound is helpful in the management of

thyroid cancer patients after surgery, it should be equally beneficial before surgery Patients who have been selected for

thyroidectomy because of FNA of a nodule or other reasons should be brought back prior to surgery and undergo ultra-sound of the lateral neck and central compartment in a search for suspicious lymph nodes Confirming a malignant lymph node(s) in the lateral neck will extend the surgery beyond a simple thyroidectomy to a modified lateral neck dissection Likewise, finding a malignant lymph node in the central com-partment assures the surgeon that a total thyroidectomy and central node dissection is required

At surgery, well differentiated thyroid cancer involves lymph nodes in 20–50% of patients Using preoperative ultrasound, suspicious lymph nodes are found in 20–30% of patients This discrepancy is in part due to ultrasound not being as sensitive

as surgery in detecting micrometastasis Ultrasound may also

be unable to see enlarged lymph nodes in the central ment because they are hidden by the thyroid gland or pushed behind the trachea Nevertheless, ultrasound will detect most lymph node involvement prior to the initial thyroid surgery One may question the significance of finding preoperative lymph node involvement in these patients Ito studied 560 patients who underwent ultrasound prior to having a thyroid-ectomy for thyroid cancer, and he followed the patients for

compart-an average of ten years (16) The recurrence rate of thyroid cancer was 3.1% in the ultrasound negative patients, but the recurrence rate in the ultrasound positive patients was 24.8% This indicates that recurrence-free survival is definitely worse

if lymph node involvement is present on ultrasound at the time

of the initial surgery

One may still question the need to perform a lateral neck dissection on such patients, unless it can be shown to improve long-term survival Noguchi reported on a series of patients found to have macroscopic lymph node involvement at the time of surgery, who were followed for an average of 40 years (17) The long-term survival rate of the group that underwent

a modified lateral neck dissection (MLND) was 84%, while that of the group not having MLND was only 66% Therefore it appears that MLND does alter the outcome in patients known

to have lateral lymph node metastasis at the time of surgery.Evidence of the value of preoperative ultrasound of the cen-tral compartment is less conclusive It may be less important

FIG 8.33 Preoperative ultrasound of a patient seen for a thyroid ule in the right lobe (N) revealed a large cystic lymph node in the right lateral neck (box) Note the short/long axis >0.5, absent hilum, and abnormal vascularity Although FNA of the lymph node had negative cytology, Tg in needle washout was positive.

nod-FIG 8.34 Preoperative ultrasound of patient with a thyroid nodule (N) whose FNA was positive for papillary cancer shows a suspicious lymph node (calipers) adjacent to the lower pole of the thyroid A central node dissection at the time of surgery revealed that this was metastatic papillary cancer

ULTRASOUND MANAGEMENT OF THYROID CANCER 133

because many endocrine surgeons now routinely perform

a central node dissection at the time of the thyroidectomy Preoperative ultrasound of the central compartment is much less sensitive than it is in the lateral neck, for the reasons men-tioned above Preoperative FNA of central compartment lymph nodes is fraught with the risk of contamination if the needle inadvertently passes through the thyroid, which might cause a false positive cytology and/or Tg in the washout It is generally recommended that the central compartment be examined

at the time of lateral neck ultrasound Because 70–90% of positive lymph nodes in the central neck are not seen by ultra-sound before the thyroid is removed, a “negative” ultrasound examination is of no value Suspicious lymph nodes should be reported to the surgeon, but FNA is not recommended

SUMMARY

The critical importance of ultrasound in thyroid cancer agement is recognized in the 2006 Management Guidelines for Patients with Thyroid Cancer published by the American Thyroid Association Recommendation 21 is that all patients undergoing surgery for thyroid cancer have a preoperative ultrasound of the neck for lymph nodes Recommendations 46 and 48 are that routine whole body scans be abandoned, and that periodic ultrasound of the neck be used for the followup of thyroid cancer patients Implementation of these recommen-dations by endocrinologists may ultimately lead to a reduction

man-in the rate of recurrence of thyroid cancer and to an man-increase

in the long-term survival of patients

References

1 Pineda J, Lee T, Ain K et al (1995) Iodine-131 therapy for thyroid cancer patients with elevated thyroglobulin and negative diagnostic scan J Clin Endocrinol Metab 80:1488–1492

2 Schumberger M, Arcangioli O, Piekarski J et al (1988) Detection and treatment of lung metastases of differentiated thyroid carcinoma in patients with normal chest x-ray J Nucl Med 29:1790–1794

3 Torre E, Carballo M, Erdozain R, Lienas L, Iriarte M, Layana J (2004) Prognostic value of thyroglobulin and I-131 whole-body scan after initial treatment of low –risk differentiated thyroid cancer Thyroid 14:301–306

4 Pacini F, Lari R, Mazzeo S (1985) Diagnostic value of a single serum thyroglobulin determination on and off thyroid suppressive therapy

in the follow-up of patients with differentiated thyroid cancer Clin Endocrinol 23:405–411

5 Park H, Perkins O, Edmondson J (1994) Influence of diagnostic radioiodines on the uptake of ablative dose of iodine-131 Thyroid 4:49–54

6 Frasoldati A, Presenti M, Gallo M, Coroggio A, Salvo D, Valcavi R (2003) Diagnosis of neck recurrences in patients with differenti-ated thyroid carcinoma Cancer 97:90–96

7 Ahuja A, Ying M, Phil M, King A, Yuen HY (2001) Lymph node hilus—gray scale and power Doppler sonography of cervical nodes J Ultrasound Med 20:987–992

8 Ahuja A, Ying M, Yuen H, Metreweli C (2001) Power Doppler sonography of metastatic nodes from papillary carcinoma of the thyroid Clinical Radiology 56:284–288

9 Ahuja A, Ying M (2002) An overview of neck node sonography Investigative Radiology 37:333–342

10 Ballantone R, Lombardi C, Raffaelli M, Traini E, Crea C, Rossi

E et al (2004) Management of cystic thyroid nodules: the role

of ultrasound-guided fine-needle aspiration biopsy Thyroid 14:43–47

11 Frasoldati A, Toschi E, Zini M, Flora M, Caroggio A, Dotti C et al (1999) Role of thyroglobulin measurement in fine-needle aspira-tion biopsies of cervical lymph nodes in patients with differenti-ated thyroid cancer Thyroid 9:105–111

12 Pacini F, Fugazzola I, Lippi F, Ceccarelli C, Centoni R, Miccoli P, Elisei R, Pinchera A (1992) Detection of thyroglobulin in the nee-dle aspirates of nonthyroidal neck masses: a clue to the diagnosis

of metastatic differentiated thyroid cancer J Clin Endocrinol Metab 74:1401–1404

13 Baskin HJ (2004) Detection of recurrent papillary thyroid noma by thyroglobulin assessment in the needle washout after fine-needle aspiration of suspicious lymph nodes Thyroid 14:959–963

carci-14 Lee M, Ross D, Mueller P, Daniels G, Dawson S, Simeone J (1993) Fine-needle biopsy of cervical lymph nodes in patients with thy-roid cancer: a prospective comparison of cytopathologic and tis-sue marker analysis Radiology 187:851–854

15 Cignarelli M, Ambrosi A, Marino A, Lamacchia O, Campo M, Picca G (2003) Diagnostic utility of thyroglobulin detection in fine-needle aspiration of cervical cystic metastatic lymph nodes from papillary thyroid cancer with negative cytology Thyroid 13:1163–1167

16 Ito Y,Tomoda C, Uruno T et al (2005) Ultrasonographically and anatomopathologically detectable node metastases in the lat-eral compartment as indicators of worse relapse-free survival in patients with papillary carcinoma World J Surg 29:917–920

17 Noguchi S, Murakami N, Yamashita H et al (1998) Prognostic tors in patients with differentiated thyroid carcinoma Eur J Surg 166:29–33

ANATOMY OF THE PARATHYROID GLANDS

Precise understanding of the normal location and the cal variations of the parathyroid glands is the cornerstone to successful identification of parathyroid adenomas Normal parathyroid glands are ovoid, or bean-shaped, and measure approximately 3 by 5 mm in size with the superior glands being smaller than the inferior glands They have an anatomically distinct vascular supply from that of the thyroid gland Normal parathyroid glands are enveloped in a pad of a fibro-fatty capsule, and are seldom seen on ultrasound (4) However, this capsule may become compressed when the parathyroid enlarges, and is often seen on ultrasound as a hyperechoic line between the thyroid gland and the parathyroid adenoma.Post-mortem examination reveals that four glands are found in 91% of subjects, three glands are found in 5%, and five glands in 4% (5) More supernumerary glands appear to

anatomi-be a rare occurrence (6) The anatomic location of roid glands varies widely due to the embryonic origin of the glands from the 4th and 3rd pharyngeal pouches with eventual migration to the lower neck The superior parathyroid glands

parathy-135

develop in the 4th pharyngeal pouch, and migrate caudally to situate along the upper two thirds of the posterior margin of the thyroid lobes The superior parathyroid glands are more constant in their location in relation to the thyroid gland due

to their common developmental origins The third pharyngeal pouch gives rise to the inferior parathyroid glands and the thy-mus gland and, together, they migrate to the lower neck Forty-four percent of these glands are located within 1 cm of the inferior pole of the thyroid gland, 17% are in close proximity

to the inferior margin of the thyroid gland, 26% are found in relation to the superior portion of the thymus along the thyro-thymic ligament, and 2% remain within the mediastinum por-tion of the thymus (7) Unusual variations in the location of the parathyroid glands include the carotid bifurcation, within

loca-tions Due to these anatomical variations, accurate tive localization becomes crucial for the success of minimally invasive parathyroid surgery

preopera-LOCALIZATION STUDIES

It is important to remember that the diagnosis of PHPT is made

by chemical tests (i.e., elevated serum calcium and mone levels, after ruling out hereditary hypocalcuric hypercal-cemia and other causes of hypercalcemia) Localizing studies are not useful for diagonising PHPT and should be obtained

parathor-after the diagnosis of PHPT has been confirmed The two most

FIG 9.1 Inferior parathyroid adenoma in transverse view

PARATHYROID ULTRASONOGRAPHY 137

widely used studies for locating abnormal parathyroid gland(s) have been 99 Tc MIBI—which is a functional study—and ultra-sonography—an anatomical study The respective studies have their strengths and weaknesses To a practicing endocrinologist, the use of ultrasonography to study a patient with a suspected parathyroid adenoma poses several advantages These include the ease of availability of ultrasound equipment, the lack of ionizing irradiation, the short duration of the procedure, and the

FIG 9.2 Inferior parathyroid adenoma seen in longitudinal view

FIG 9.3 Superior parathyroid adenoma seen in transverse view Note thyroid nodule in anterior lobe

potential cost savings realized by the patient Unfortunately, not all parathyroid adenomas can be visualized by ultrasound Very small adenomas and those located in aberrant locations, such as the mediastinum or posterior to the trachea, are not amenable to ultrasound examination The limitations of parathyroid localization using ultrasonography also include operator variability—however, an experienced sonographer can be expected to identify 85% of parathyroid adenomas Similar results have been reported using 99 Tc MIBI scans

false positive results are sometimes seen with 99 Tc MIBI scans due to thyroid nodules that trap the isotope, UGFNA

of parathyroid adenomas seen with ultrasound have 100% specificity One should also keep in mind that isotope scans

lateralize the adenoma while ultrasound studies localize the

lesion

TECHNIQUE OF PARATHYROID ULTRASOUND

There are many good reasons to perform an ultrasound on

a patient having surgery for hyperparathyroidism Several investigators have shown a 2% incidence of thyroid cancer

in patients with a parathyroid adenoma Not infrequently, a preoperative ultrasound will reveal an unsuspected coexist-ing thyroid nodule, which, after FNA, may alter the entire surgery Finally, ultrasound allows localization of the parathy-roid adenoma in most patients, thereby facilitating minimally invasive surgery

FIG 9.4 Superior parathyroid adenoma seen in longitudinal view

The most common locations (posterior border of the thyroid lobes, tracheoesophogeal groove, thyroid-thymic ligament) are searched first, looking for a hypoechoic mass with the features

of a parathyroid adenoma The following are the most tive sonographic features of parathyroid adenomas

distinc-1 Extrathyroidal Location: The majority of parathyroid

adeno-mas are located adjacent to, but separate from, the posterior aspect of the thyroid It is common to see an indentation made by the parathyroid adenoma on the posterior capsule

of the thyroid gland (Figures 9.4 and 9.10) Look for the echogenic line separating the adenoma from thyroid tissue This represents the compressed fibro-fatty capsule surround-ing the enlarged parathyroid Parathyroid adenomas are completely embedded within the thyroid gland in about 2–5% of cases (9, 10) The incidence of intraglandular loca-tion is higher in patients with multigland disease—in one series, 3% in patients with single-gland disease versus 15%

in those with hyperplasia (10)

2 Hypoechoic and Homogeneous Appearance: The most

typical imaging characteristic of parathyroid adenomas is the homogeneously hypoechoic echogenicity in relation to the thyroid gland (11)

3 Oval, Elongated, Triangular, or Oblong Shapes:

Para-thyroid adenomas conform to the pressures of ing anatomical structures and therefore variation in the shapes is common An excellent method of learning to recognize enlarged parathyroid glands is by performing ultrasound on patients with renal failure These patients frequently have very enlarged parathyroid glands that are easily seen with ultrasound This exercise will allow the beginner to become acquainted with the endless variety of shapes and locations of parathyroid glands

surround-4 Vascular Pedicle and Blood Flow Seen with Doppler:

The presence of an extrathyroidal artery (polar artery) feeding an adenoma may be found in 83% of parathyroid adenomas (12) Besides the visualization of the polar artery,

other patterns such as the vascular arc pattern and diffuse

flow within the adenoma have also been described (13)

PARATHYROID INCIDENTALOMA

Subclinical parathyroid tumors can be incidentally discovered during neck ultrasonography The frequency of observing these incidental tumors is <1% (17, 18) Fine needle aspiration with PTH estimation in syringe washings can identify these lesions

F 9.5 A and B Polar vascular pedicle

FIG 9.6 A Polar blood flow depicted by color flow Doppler.

FIG 9.6 B Dual Polar blood flow depicted by Power Doppler.

F 9.6 C Arc pattern of blood flow.

as parathyroid tumors Their prognosis for developing parathyroidism in the future is presently not known.

hyper-PARATHYROID CYST

Cystic parathyroid adenomas are rare Simple cysts of the athyroid glands without hypercalcemia are occasionally seen during ultrasound assessment of the thyroid Partial cystic change of an adenoma is depicted in Fig 9.15 Syringe washout PTH estimation is useful to prove the origin of these cysts

par-FIG 9.7 Diffuse blood flow seen within adenoma

FIG 9.8 Polar blood flow This adenoma was found within the carotid sheath during surgery

PARATHYROID ULTRASONOGRAPHY 143

FIG 9.9 a, b, and c Parathyroid adenoma visualized along side of incidental thyroid disease (a multinodular goiter b colloid nod-ule c Hashimoto thyroiditis)

ULTRASOUND-GUIDED FNA OF PARATHYROID LESIONS

UGFNA of suspected parathyroid adenomas can be performed

in the office setting, and syringe washings can been submitted for parathormone (PTH) estimation (14, 15) Lesions >1.5 cm

FIG 9.10 Parathyroid adenoma indenting the posterior capsule of the thyroid gland

FIG 9.11 Double adenoma visualized in longitudinal view Note also

PA located within the thyroid gland capsule

PARATHYROID ULTRASONOGRAPHY 145

with obvious ultrasound features of a parathyroid adenoma may not need biopsy confirmation FNA confirmation is most useful when multiple lesions are identified, in which case the lesion with the least identification characteristics of a par-athyroid adenoma should be sampled FNA also allows one to differentiate a parathyroid adenoma from coexistent posterior thyroid nodules (15) (See Fig 9.X) Other situations that are candidates for FNA include suspected parathyroid masses in patients with: 1) prior failed surgery, 2) negative 99 Tc MIBI scans, 3) atypical location, or 4) coexistent multinodular goiter

FIG 9.12 Double inferior parathyroid adenoma in panoramic view The findings were confirmed during surgery

FIG 9.13 Cystic PA

Elevation of intact PTH in syringe washings provides mation with virtually 100% specificity Parathyroid cytology has a very limited role in the diagnosis of parathyroid adeno-mas (15).

confir-The technique of parathyroid FNA is similar to that

of thyroid FNA One or two passes using 27 G needles is recommended Due to the location depth of these lesions, longer needles may be necessary to enable a biopsy to be performed Parathyroid tumors can be mobile and may need a sharp, brief, and abrupt jab to penetrate the cap-sule Parathyroid lesions provide bloody aspirates and the fluid should enter the hub of the needle Absence of bloody aspirate during FNA is typically encountered with non par-athyroid lesions The syringe aspirate can be processed as follows:

1 Make one slide and rinse the remainder of the specimen in

GRAPH 1 Parathyroid hormone (PTH) levels in syringe washing

speci-mens obtained after fineneedle aspiration of parathyroid adenomas of study subjects and proven thyroid nodules as controls, represented in

log scale Findings in the 2 groups were significantly different (p<0.001).

PARATHYROID ULTRASONOGRAPHY 147

If the PTH level is high in the syringe aspirate, the cytology

is not necessary If the PTH level is low in the syringe aspirate, the smear is submitted for cytological analysis The latter technique provides an additional measure of safety in case of sampling a metastatic lymph node either from thyroid or other coincidental occult cancers

Most laboratories in the United States are willing to perform intact PTH estimations in tissue specimens if prior arrangements

FIG 9.14 Biopsy of suspected PA

FIG 9.15 PA located in the proximal portion of thyro-thymic ligament

are made with the supervisor of the lab In our laboratory, the

phenomenon of hook effect has not been detected in over 100

specimens subjected to PTH estimation by the above-described technique, despite the PTH levels being enormously elevated (15)

In summary, most parathyroid adenomas can readily be seen with ultrasound and do not require FNA Sonography provides

an inexpensive method of localizing the lesion prior to surgery without ionizing radiation, and facilitates minimally invasive parathyroid surgery

References

1 Kebebew E, Clark OH (1998) Parathyroid adenoma, hyperplasia and carcinoma: Localization, technical details of primary neck exploration and treatment of hypercalcemic crisis Surg Oncol Clin

N Am 7:721–748

2 Heath H III, Hodgson SF, Kennedy M (1980) Primary roidism: incidence, morbidity and potential economic impact in a community N Engl J Med 302:189–193

hyper3 Udelsman R, Donovan PI (2004) Open minimally invasive roid surgery World J Surg Dec 28(12):1224–6

parathy-4 Gilmore JR (1938) The gross anatomy of parathyroid glands

8 Yeh MW, Barraclough BM, Sidhu SB, Sywak MS, Barraclough

BH, Delbridge LW (2006) Two hundred consecutive parathyroid ultrasound studies by a single clinician: the impact of experience Endocr Pract May-Jun.12(3):257–63

FIG 9.16 Fluid from a parathyroid cyst

11 Kamaya A, Quon A, Jeffrey RB (2006) Sonography of the mal parathyroid gland Ultrasound Q Dec 22(4):253–62

abnor-12 Lane MJ, Desser TS, Weigel RJ, Jeffrey RB Jr (1998) Use of color and power Doppler sonography to identify feeding arteries asso-ciated with parathyroid adenomas AJR Am J Roentgenol Sep 171(3):819–23

13 Wolf RJ, Cronan JJ, Monchik JM (1994) Color Doppler phy: an adjunctive technique in assessment of parathyroid adeno-mas J Ultrasound Med Apr 13(4):303–8

sonogra-14 Doppman JL, Krudy AG, Marx SJ, Saxe A, Schneider P, Norton JA, Spiegel AM, Downs RW, Schaaf M, Brennan ME, Schneider AB, Aurbach GD (1983) Aspiration of enlarged parathyroid glands for parathyroid hormone assay Radiology Jul 148(1):31–5

15 Abraham D, Sharma PK, Bentz J, Gault PM, Neumayer L, McClain

DA (2007) The utility of ultrasound guided FNA of parathyroid adenomas for pre-operative localization prior to minimally inva-sive parathyroidectomy Endocrine Practice Jul/Aug 13(4) pages?

16 Krause UC, Friedrich JH, Olbricht T, Metz K (1996) Association of primary hyperparathyroidism and non-medullary thyroid cancer Eur J Surg Sep 162(9):685–9

17 Pesenti M, Frasoldati A, Azzarito C, Valcavi R (1999) Parathyroid incidentaloma discovered during thyroid ultrasound imaging

J Endocrinol Invest Nov 22(10):796–9

18 Frasoldati A, Pesenti M, Toschi E, Azzarito C, Zini M, Valcavi R (Year?) Detection and diagnosis of parathyroid incidentalomas during thyroid sonography Journal of Clinical Ultrasound 27(9):

492 – 498

sub-of thyroid cancer, which occurs in about 5% sub-of all thyroid ules (4–5) Thus it is essential to improve our diagnostic tools

nod-to avoid the use of unnecessary diagnostic surgery

Brightness-mode US is currently the most accurate ing test to evaluate solitary thyroid nodules or multinodular goiters (6–8) Thyroid US results in improved management for patients, with clinical findings suggestive of thyroid nodules (9) Many patients either have a palpable but not suspicious nodule, or have incidentally revealed but sonographically relevant nodules that warrant fine needle aspiration biopsy (10) Unfortunately, in most cases US characteristics can-not unequivocally distinguish benign and malignant lesions (10–12) Color Doppler US was proposed to evaluate nodule

imag-151

* Department of Endocrine, Metabolic and Digestive Diseases & Department of Diagnostic Imaging Albano (Rome), Italy