Isoechoic thyroid nodules not always ‘low risk,’ benign

Issue: August 2017

ByStephanie L. Lee, MD, PhD, ECNU

A 59-year-old Hispanic man was referred to the endocrine clinic by the otolaryngology department for a thyroid mass. The patient had no prior history of head and neck radiation, but 2 years earlier, a 1-cm mass was discerned on physical exam “near the thyroid” without additional evaluation. He had no family history of thyroid cancer.

An ultrasound of the neck performed in the endocrine clinic showed a well- defined heterogeneous, isoechoic nodule, greater than 6.5 cm x 4 cm x 5.5 cm, in an otherwise normal thyroid gland (Figures 1 and 2). No abnormal nodes or masses were noted in the bilateral central or lateral neck, levels II, III, IV, V and VI. A rough estimate showed approximately 1.5 cm of rightward tracheal deviation without obvious tracheal narrowing at the level of the thyroid (Figure 2).

Risk classification

Figure 1. Thyroid ultrasound. (A) Right transverse view. (B) Right sagittal view. An isoechoic nodule replaces the right lobe of the thyroid. The nodule has smooth, well-defined margins with a very heterogeneous echotexture. No microcalcifications are evident, and the nodule had grade 3 vascular flow by Doppler (not shown).

This nodule was classified as “low risk” based on the 2015 American Thyroid Association guideline. A fine-needle biopsy was performed because the low-risk nodule was larger than 2 cm in greatest dimension. The cytology was Bethesda VI, malignant with follicular cells showing enlarged nuclei, nuclear groves, vesicular chromatin, membrane-bound nucleoli and syncytial, tridimensional cell groups consistent with papillary thyroid carcinoma.

Because of the discrepancy of the low-risk ultrasound designation and the Bethesda VI cytology, a ThyroSeqV.2 test was performed that showed a triple mutation: NRAS mutation (p.Q61R, c.182A>G), TERT promoter mutation (c.1-124C>T; C228T), ElF1AX mutation (c.371G>C; p.G124A). The RAS mutation is associated with an approximately 80% risk for cancer, usually a follicular variant of papillary carcinoma, but it also occurs, rarely, in follicular thyroid carcinoma. The presence of a TERT mutation is associated with a higher risk for distant metastases and disease persistence. The finding of the triple mutations confers an approximately 99% risk for cancer and raised the possibility of a thyroid cancer with a more aggressive biological behavior.

Preoperative imaging, laboratory tests

Based on the increased risk for aggressive behavior, the patient had preoperative CT imaging of the neck for surgical planning. The CT scan of the neck showed a well-encapsulated, heterogeneously enhancing mass, measuring 5.2 cm x 5.8 cm x 4.6 cm, within the right thyroid gland without evidence of infiltration of the surrounding soft tissues or encasement of the surrounding structures (Figure 3). The trachea was deviated to the left without significant narrowing, and the right common carotid and jugular vein were shifted to the right without evidence of associated stenosis or narrowing. There was no evidence of local invasion or cervical lymphadenopathy.

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The patient’s thyroid function was normal with thyroid-stimulating hormone level 2.01 uIU/mL (reference range, 0.35-4.9 uIU/mL). A total thyroidectomy with a prophylactic bilateral central neck dissection showed an 8 cm x 3.5 cm x 3.5 cm poorly differentiated thyroid carcinoma without evidence of capsular or lymphovascular invasion and with no extrathyroidal extension or adenopathy.

Figure 2. Thyroid ultrasound. (A) Midline transverse view. (B) Left transverse view. The isoechoic nodule in the right thyroid lobe has a well-defined margin seen in both views. The isthmus and left lobe (B) of the thyroid are normal in size and echotexture in the transverse view. An estimate of the left tracheal deviation can be determined when the linear ultrasound probe is placed visually at anatomic midline in transverse orientation to the trachea. The distance between the midline of the image (*) and the middle of the trachea (+) is measured (dotted blue line: 2 cm). In addition, no tracheal compression is evident at the level of the thyroid.

Ultrasound risk stratification

Thyroid ultrasound is used to stratify the risk for cancer in thyroid nodules to determine whether a fine-needle biopsy is necessary. In interpreting ultrasound images, thyroid cancer is associated with microcalcifications, hypoechogenicity compared with the surrounding thyroid or strap muscles, irregular margins (defined as either infiltrative, microlobulated or spiculated), and a shape taller than wide measured on a transverse view. Ultrasound characteristics that are highly specific for thyroid cancer (median > 90%) are microcalcifications, irregular margins and tall shape.

What is not well-understood are the features that are specific for classical papillary thyroid carcinoma, whereas follicular thyroid carcinoma and follicular variant of papillary thyroid carcinoma exhibit differences in sonographic features. These tumors are more likely to be isoechoic to hyperechoic (52%-65%), noncalcified, round (width greater than anterioposterior dimension) nodules with regular smooth margins (39%) or halo (25%) and no microcalcifications.

Figure 3. CT scan with contrast. (A) Axial view. (B) Coronal view. A well-encapsulated mass is seen in the right thyroid lobe (red arrow) with heterogeneous enhancement with contrast. The left thyroid lobe and isthmus enhance normally with contrast (blue arrows). The mass displaces the trachea to the left without invasion or compression. The right internal jugular vein and the right carotid artery (yellow arrows) are displaced by the mass to the right without stenosis or encasement by the tumor. Abbreviations: CA = carotid artery; JV = jugular vein; TR = trachea

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However, isoechoic/hyperechoic nodules can be aggressive, poorly differentiated thyroid cancers as illustrated by this patient. In a group of 30 poorly differentiated thyroid cancers, the mean age of the patient was 53.7 years (range, 14-73 years) with a large solitary (80%) tumor with a mean size of 3.6 cm (range, 0.6-10 cm), heterogeneous echogenicity (93.3%), circumscribed margin (63.3%), oval to round shape (63.3%) and hypoechogenicity (60%). It is important for the endocrinologist to know that 15% to 20% of thyroid cancers are isoechoic or hyperechoic on ultrasound, and these are generally follicular thyroid carcinoma or follicular variant of papillary thyroid carcinoma.

References:
Hahn SY, et al. J Ultrasound Med. 2016;doi:10.7863/ultra.15.09058 35:1873-9.
Haugen BR, et al. Thyroid. 2016;doi:10.1089/thy.2015.0020.
Jeh SK, et al. Korean J Radiol. 2007;doi:10.3348/kjr.2007.8.3.192.
Kim DS, et al. J Ultrasound Med. 2009;doi:10.7863/jum.2009.28.12.1685.

For more information:
Stephanie L. Lee, MD, PhD, ECNU, is an Endocrine Today Editorial Board Member. She is associate professor of medicine and director of thyroid health in the Section of Endocrinology, Diabetes and Nutrition at Boston Medical Center. She can be reached at Boston Medical Center, 88 E. Newton St., Boston, MA 02118; email: stephanie.lee@bmc.org.

Disclosure: Lee reports no relevant financial disclosures.