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Chapter 8 Ultrasound in the Management of Thyroid Cancer H. Jack Baskin INTRODUCTION The strategic value of ultrasound in the postoperative surveillance of patients with thyroid cancer and in the preoperative surgical planning of patients undergoing thyroid cancer surgery has become increasingly appreciated over the past decade. In this chapter we will focus on how to recognize and differentiate malignant lymph nodes from benign lymphadenopathy. Once you become familiar with the appearance of metastatic lymph nodes in thyroid cancer, you will find that ultrasound is a more specific tool for separating benign from malignant lymph nodes than it is for separating benign and malignant thyroid nodules. However, we still must rely on ultrasound-guided FNA for a definitive diagnosis. 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 mortality 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 diagnostic tool available was a 131I whole body scan (WBS) done after withdrawing the patient from thyroid hormone replacement. The sensitivity of a WBS in the early detection of residual, recurrent, or metastatic thyroid cancer is poor. This is apparent 111 112 H.J. BASKIN 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 treatment dose of 131I (5). The expense, poor sensitivity, and risk of stunning with a WBS make it an unsatisfactory test with which 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 recurrence; (2) development of recombinant TSH (rhTSH) that allows scanning and Tg stimulation without thyroid hormone withdrawal; and (3) high-resolution ultrasound of the postoperative 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 sensitivity 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 undergone a thyroidectomy for thyroid cancer is seldom helpful in the 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 ultrasound, 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 thyroidectomy, one sees that the carotid artery and jugular vein have migrated medially close to the trachea, and that the thyroid 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 postoperative 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 ultrasound looking for metastatic lymph nodes, the entire length of the internal jugular vein from the head 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. 114 H.J. BASKIN 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 muscles (sm) have helped fill in the space left by removal of the thyroid. 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 transverse 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 appearance 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 ULTRASOUND MANAGEMENT OF THYROID CANCER 115 TABLE 8.1. Neck lymph node characteristics Benign Short/Long Axis Hilar line Jugular Deviation or Compression Microcalcifications Cystic Necrosis Vascularity <0.5 Present Absent Absent Absent Central Malignant >0.5 Absent Present Present Present Chaotic/peripheral 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. 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 microcalcifications or amorphous calcium with shadowing, are indicative 116 H.J. BASKIN 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. FIG. 8.5. Power Doppler of the previous lymph node shows vascularization of the hilum, which contains small arterioles. Note there is no vascularization seen in the periphery of the node. 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. ULTRASOUND MANAGEMENT OF THYROID CANCER 117 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. 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). 118 H.J. BASKIN FIG. 8.8. On transverse view, this small rounded lymph node (calipers) without a hilar line is in close proximity to the great vessels. FIG. 8.9. Same lymph node (calipers) in longitudinal view shows compression of the jugular vein against the carotid. UG FNA confirmed malignancy. 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, ULTRASOUND MANAGEMENT OF THYROID CANCER 119 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. but they have varying degrees of echogenicity. Early papillary metastases are sometimes dense and may be relatively hyperechoic. 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 120 H.J. BASKIN FIG. 8.12. This irregular rounded lymph node (arrow) was discovered because of the separation of the jugular from the carotid. The calcification at 3:00 o’clock indicates it is malignant, but UG FNA is necessary before surgery. 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.