Wednesday, September 3, 2008

Thyroid US - malignant criteria

What are the Ultrasound Criteria for Fine-Needle Aspiration Cytology of Nonpalpable Thyroid Nodules?

SJ Mandel

Nat Clin Pract Endocrinol Metab.  2006;2(7):372-373.  ©2006 Nature Publishing Group
Posted 08/03/2006

Synopsis

Background: Widespread use of ultrasound to assess thyroid disease has led to an increased number of clinically unapparent, nonpalpable nodules being identified. Although many of these nodules are benign, malignancy cannot be excluded without further testing by fine-needle aspiration cytology (FNAC).
Objective: To evaluate whether ultrasound criteria can be used to identify malignant nodules and, therefore, limit the number of patients undergoing unnecessary FNAC.
Design and Intervention: This study evaluated patients referred to the thyroid unit at the University of Brescia, Italy, a geographic region with endemic goiter. Inclusion criteria included normal thyroid function, ultrasound identification of a solid, nonpalpable nodule and no previous diagnosis of thyroid malignancy. Ultrasound was performed using a real-time scanner and the following parameters were assessed: echographic dimension (anteroposterior and transverse diameter), echogenicity, calcification, lesion margins (well-defined or blurred), and vascularity pattern. FNAC was performed using 25-gauge needles and lesions were classified as benign, suspicious, or malignant. Patients with suspicious or malignant cytology underwent surgery; those with benign nodules received follow-up ultrasound after 6 months.
Outcome Measures: The main outcome measures were ultrasound and FNAC.
Results: A total of 701 nodules were examined; 327 were solitary and 374 were embedded in a multinodular goiter. FNAC identified 108 (15.4%) of the nodules as suspicious or malignant. Histology after surgery confirmed that 67 of these were carcinomas (50 papillary, 15 follicular, and 2 medullary) and 41 were adenomas. Extracapsular growth was present in 8 carcinomas and was predicted by ultrasound in one case. Additionally, lymph node metastases were detected in 16 carcinomas, 3 of which were predicted by ultrasound. When ultrasound parameters were related to histology, malignant nodules were more likely than benign nodules to present with an anteroposterior to transverse diameter ratio (A/T)≥1 (83.6% versus 18.5%; P <0.001). A similar trend was observed for the other sonographic criteria, although no single parameter identified a subset of patients requiring FNAC. Carcinomas presented with a solid, hypoechoic appearance in 79.1% of cases, blurred margins in 47.8%, microcalcification in 73.1%, and intranodular vascularity in 56.7%. All variables were found to be independent risk factors for malignancy (odds ratio 2.6�22.4). Combining an A/T≥1 with at least one of these variables gave the greatest sensitivity (83.6%) and specificity (91.9%), limiting the need for FNAC to only 15.9% of the nodules.
Conclusion: Combining an A/T≥1 with at least one other sonographic criterion to predict which nonpalpable nodules are malignant could be an effective tool to select patients for FNAC, reducing the number of unnecessary procedures currently performed.

Commentary

Before the introduction of high-frequency ultrasound for evaluating the thyroid gland, nonpalpable nodules were detected in about 6% of the adult population; however, ultrasound now detects such nodules in more than half of the general population aged over 50 years. As only 4-7% of nodules are malignant, the challenge for clinicians is to devise a rational strategy to differentiate lesions that require surgical excision from those that can be followed medically.[1,2] Before diagnostic ultrasound, the decision to perform FNAC was based predominantly upon nodule size. With ultrasound imaging, however, the number of nodules that meet any specific size cutoff has increased. In an attempt to provide a framework for triaging nodules for FNAC according to the highest risk of malignancy, sonographic features of nodules associated with thyroid cancer have been identified.[3]

The results from Cappelli et al. are consistent with previously published sensitivity and specificity estimates for ultrasound criteria already known to be associated with thyroid cancer. The current analysis is restricted to solid, nonpalpable nodules, although the findings should apply to palpable nodules as well. The authors do not, however, provide the interobserver variability for characterization of both nodule sonographic features and diameter measurement, and they also exclude partially cystic nodules, which are quite common (up to 50% of all nonpalpable nodules); thus, applicability might be somewhat limited.

The authors also endeavor to add another sonographic feature to the list, namely an A/T≥1; however, why should the shape of a nodule matter? The ratio of surface area to volume is maximized by a spherical shape, optimizing exposure of the tumor cells to nutrients. By considering all three dimensions of a nodule (anteroposterior, transverse, and longitudinal) to calculate shape as the ratio of the longest to shortest diameter, the least spherical nodules―defined as a long-to-short axis ratio of >2.5―were found to be benign.[4] The current report only calculates the ratio of two of these three dimensions, so might not truly reflect nodule shape. Nevertheless, Cappelli et al. found that an A/T ≥1 has both high specificity (82%) and sensitivity (84%) for detection of thyroid cancer, the latter of which is significantly higher than the 33% sensitivity previously reported for this feature.[3] The use of an A/T ≥1, therefore, requires additional validation, including an analysis of interobserver variation in nodule diameter measurement, before it can be used widely to select nodules for FNAC.

Like previous reports, this study has explored sonographic criteria to identify nodules with a high cancer risk. Implicitly understood is that most nodules are not malignant. As the absolute number of detected thyroid nodules increases, the most beneficial analysis would be one that attempted to identify a subset of nodules lacking all the suspicious sonographic features for which FNAC might be omitted. Over 2 decades ago, Simeone and colleagues wrote "...the exact role of ultrasound is still to be defined ... the traditional use of ultrasound to separate cystic from solid lesions is probably outdated".[5] Although we now understand much more about ultrasound imaging of thyroid nodules, this statement remains true today. We must, therefore, begin to apply sonographic criteria to identify nodules for which FNAC is not indicated, as well as those for which it might be.

Practice Point

Sonographic features of thyroid nodules might identify lesions with a high risk of malignancy

TGD cyst

Insidious Swelling in the Neck of a 45-Year-Old Man

Background

Figure 1.
Figure 1.
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Figure 2.
Figure 2.
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A 45-year-old man presents to his primary care physician (PCP) complaining of gradual swelling in his anterior neck over the past 6 months. At first, he thought nothing of the swelling, expecting it go away on its own; however, over the past 2 months, it has become more noticeable. The patient has become concerned that the swelling may be caused by cancer. He has not experienced any pain in the area of the swelling, nor has he experienced fevers. Additionally, he denies any difficulty in swallowing and any alteration of his voice. There are no problems with his breathing. The patient has no history of trauma, and he denies any significant personal medical history. The family history is unremarkable. He is not currently taking any medications, he does not smoke, and he does not use any illicit substances. He is a social drinker.

On physical examination, the patient is afebrile and has a pulse of 72 bpm, a blood pressure of 130/82 mm Hg, a respiratory rate of 12 breaths/min, and a normal oxygen saturation while breathing room air. He is well-developed and well-appearing. Examination of the anterior neck reveals a nontender, nonerythematous, fluctuant mass measuring approximately 10 × 8 cm in the midline of the lower neck, with slight extension to the right side of the midline. The mass moves up and down when the patient swallows, and it slightly displaces anteriorly with protrusion of the tongue. No cervical lymphadenopathy is appreciated. The lung fields are clear bilaterally, without any evidence of stridor or wheeze. The heart has a regular rate and rhythm, without murmurs, and the abdomen is soft and nontender, without evidence of masses. The cranial nerves are intact, and the remainder of the neurologic exam is unrevealing as well.

Some routine laboratory blood tests, which include a complete blood cell (CBC) count and an electrolyte panel, are sent, as well as a rapid assay for thyroid function tests. All of the laboratory investigations, including the thyroid studies, are within normal limits. An ultrasound of the neck is obtained (Figure 1). As a follow-up, a computed tomography (CT) scan of the neck is also performed for further evaluation (Figure 2).


What is the diagnosis?

Hint: This is the most common congenital anomaly resulting in a midline neck mass.
Cystic vascular abnormality
Cervical teratoma
Ectopic thyroid
Thyroglossal duct cyst

Discussion

Figure 1.
Figure 1.
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Figure 2.
Figure 2.
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The ultrasound image in Figure 1 shows a large cystic mass anterior to the thyroid gland (arrowheads). The contrast-enhanced CT scan (Figure 2) demonstrates that same predominantly midline cystic mass extending anteriorly to the thyroid gland and under the strap muscles, without any evidence of ectopic thyroid tissue. The findings are consistent with the diagnosis of a thyroglossal duct cyst. This diagnosis is the most common etiology for a midline neck mass. Thyroglossal duct cysts usually occur between the hyoid bone and the thyroid gland, and they represent up to 70% of congenital neck anomalies. Thyroglossal duct cysts are second only to lymphadenopathy as the most common cause of a neck mass.[4,5]

The cysts usually appear in the midline and can be present anywhere along the line of fetal descent from the foramen cecum to the level of the thyroid gland. From an embryologic perspective, the thyroid gland develops during the third week of life as an outgrowth of the floor of the primitive pharynx. The primitive thyroid then descends from the foramen cecum to its mature position in the anterior neck through the thyroglossal duct. The thyroglossal duct is normally resorbed by 7 to 10 weeks of fetal life. Abnormal persistence of the thyroglossal tract accompanied by mucus production from the endothelial lining of the tract leads to the development of a thyroglossal duct cyst. Approximately 7% of the population has thyroglossal duct remnants, and the distribution is equal among males and females. The cysts are usually found in children or adults younger than age 30 years, but they can develop in adults of any age. In recent years, a number of older patients, including patients in their 80s and 90s, have presented with thyroglossal duct cysts. There are 4 general types of thyroglossal duct cysts: thyrohyoid (61% of cases), suprahyoid (24%), suprasternal (13%), and intralingual (2%).[2,3,4,5]

The differential diagnosis for neck masses can be categorized by the location of the mass itself; the usual categorization is between lateral and midline masses. The most frequent causes of lateral masses are lymphadenopathy, branchial cleft cyst malignancy, cystic lymphangioma, and dermoid and teratoid cysts. Although thyroglossal duct cysts are the most common etiology for midline masses, the differential diagnosis also includes dermoid and teratoid cysts, ectopic thyroid tissue, malignancy, and cystic lymphangiomas.[4]

On radiologic images, thyroglossal duct cysts appear as a cystlike mass along the course of the thyroglossal duct. They must be differentiated from dermoid cysts and lymphangiomas. A dermoid cyst usually contains fat; lymphangioma is most common in infancy or early childhood, and it usually occurs in the posterior triangle of the neck, behind the sternocleidomastoid muscle. A thyroglossal duct cyst must also be differentiated from an ectopic thyroid gland. If an ectopic thyroid gland is mistakenly removed, the patient may require long-term thyroid treatment for hypothyroidism. Often, patients with an ectopic thyroid also have hypothyroidism, and they will have an elevated thyroid-stimulating hormone (TSH) level.[4]

The diagnosis of thyroglossal duct cyst is made on the basis of the clinical history and confirmed with diagnostic imaging. Most patients with thyroglossal duct cysts present with either a history of a slowly growing, asymptomatic mass or of a relatively rapid-growing mass (if the cyst is infected) in the anterior midline of the neck. Frequently, the swelling is exacerbated during an upper respiratory infection. The pathognomonic sign of a thyroglossal duct cyst is that it moves with swallowing and with protrusion of the tongue; however, the mobility of larger cysts may be restricted. Imaging studies, including ultrasonography and CT scanning of the neck, will confirm the diagnosis and help to rule out the presence of a possible ectopic thyroid gland. Thyroid function tests should be obtained to confirm normal thyroid function.[3]

Once diagnosed, thyroglossal duct cysts are removed because they are cosmetically undesirable and have the potential to become infected and undergo malignant transformation. The treatment of choice is the Sistrunk procedure, named after Dr. Walter Ellis Sistrunk and first described in an article in 1920. The procedure, rather than involving a simple excision of the cyst, involves dissecting the central portion of the hyoid bone, with extension of the excision up to the base of the tongue to include excision of a small block of muscle around the foramen cecum. Because of the increased risk of thyroglossal duct carcinoma, some practitioners further recommend the addition of thyroid suppression therapy or a complete thyroidectomy; however, this practice remains controversial. The recurrence rate associated with simple excision of a thyroglossal duct cyst is approximately 50%, whereas the recurrence rate associated with a formal Sistrunk procedure is approximately 5%. The rate of recurrence after a Sistrunk procedure is increased, however, when a thyroglossal duct is ruptured during dissection. A history of previous infection of the cyst, previous incision and drainage procedures, and adherence of the cyst to the skin all increase the risk of rupture during dissection. If the cyst is infected at the time of diagnosis, treatment with antibiotics, such as ampicillin/sulbactam, amoxicillin/clavulanate, or clindamycin, is indicated before surgical excision.[2,4,5,6]

The most common complications of thyroglossal duct cysts are infection with the possibility for abscess formation, spontaneous rupture, and formation of a secondary sinus tract. A Sistrunk procedure mistakenly performed for thyroid ectopia that removes thyroid tissue can cause hypothyroidism. The cysts can compress the trachea and lead to respiratory distress, especially if they are rapidly expanding (although this is not common). Carcinoma is the most feared complication, occurring in about 1% of all cases, with papillary carcinoma accounting for 85-92% of malignancies and follicular carcinoma accounting for the rest. Most patients who develop carcinoma tend to present at a later age. Cancer in a thyroglossal duct cyst seems to be more common in females than in males. The diagnosis of carcinoma arising in a thyroglossal duct cyst is typically made postoperatively by histology.[4,5]

Because the patient in our case presented with a thyroglossal duct cyst which (on clinical grounds) was not infected, he was not given antibiotics. The ultrasound study confirmed the presence of a thyroglossal duct cyst and ruled out the possibility of an ectopic thyroid gland. The patient underwent an elective Sistrunk procedure, with no rupture during dissection. There were no complications. He was discharged from the hospital the following day. Postoperative histologic analysis did not reveal any evidence of malignancy. On follow-up in the clinic 2 weeks later, the patient was noted to be doing well.