When to biopsy: A taller-than-wide nodule lacking worrisome sonographic features

Issue: February 2013

Two patients were sent to the endocrine clinic for the evaluation of a thyroid nodule. A 67-year-old female was sent for an asymptomatic 1-cm thyroid nodule found during an MRI for neck pain. A 28-year-old female was referred because of a 2-cm thyroid nodule felt during an initial evaluation for infertility.

They had no history of head and neck radiation and no family history of thyroid disease, including thyroid cancer.

The patients were unaware of the thyroid nodule and had no symptoms of dysphagia, change in voice or anterior neck pressure. The 1-cm nodule could not be felt, whereas the larger 2-cm nodule was easily palpable in the left lobe. The nodule was mobile and nontender. Neither woman had palpable adenopathy in the neck. Laboratory testing showed both women had normal thyroid-stimulating hormone values <1.9 mU/L.

Stephanie L. Lee

Both women had a thyroid ultrasound, including a nodal survey of the neck. There were no abnormal or enlarged nodes seen in the bilateral neck in levels 2, 3, 4, 5 or 6.

Nodule features

The older woman had a heterogeneous, minimally hypoechoic/isoechoic 0.9 cm x 0.6 cm x 0.3 cm (sagittal x anteroposterior x transverse) nodule in the left lobe of an otherwise normal thyroid (Figures 1A and 1B). This nodule had a shape that is taller than wide, defined as an anteroposterior/transverse diameter (A/T) ratio >1 in the transverse view. This nodule had an A/T ratio of 2 with a border that was blurred, suggesting varying thickness. There were a few nonshadowing hyperechoic foci that were not punctate and appeared to be posterior to microcytic areas of the nodule. The nodule did not have any vascular flow by Doppler (grade 1) and no calcification.

The younger woman had a mostly isoechoic/hyperechoic 2.9 cm x 2.4 cm x 2 cm (sagittal x anteroposterior x transverse) nodule in the left lobe of an otherwise normal-appearing thyroid (Figures 1C and 1D). The margins of this nodule were well defined. The nodule had an A/T ratio of 1.2 with peripheral and low-volume intranodular vascular flow (grade 3) by Doppler and no calcification. This nodule also contained nonshadowing hyperechoic foci that were not punctate and were posterior to microcytic areas of the nodule.

Characteristics of concern

The generally accepted sonographic characteristics of thyroid nodules that are concerning for malignancy include solid composition, hypoechogenicity, intranodular vascular flow, micro- and macro-calcification, blurred margins, capsular invasion and hypermetabolic rate on F-18 fluorodeoxyglucose (FDG) PET scan.

Figure 1. Thyroid ultrasound of taller-than-wide nodules (blue arrows). A. Transverse image of the older woman’s nodule showed a small left lobe nodule with an A/T ratio of 2. B. Sagittal image of the older woman’s nodule showing the blurred margin and now vascular flow by Doppler (grade 1). C. Transverse image of the younger woman’s nodule with an isoechoic/hyperechoic nodule with an A/T ratio of 1.2. D. Doppler shows this nodule has peripheral and scant intranodular vascular flow (grade 3). CA: Carotid artery. E: Esophagus.

Source: Stephanie L. Lee, MD, PhD

The shape of a nodule is also independently associated with the risk for thyroid cancer. Cappelli and colleagues found that an A/T ratio >1 was associated with thyroid cancer with a sensitivity of 84% and a specificity of 82%. The taller-than-wide (A/T >1) shape plus two additional worrisome sonographic features (hypoechoic, micro-calcifications, blurred margins and increased intranodular vascular flow) will detect thyroid cancer with a sensitivity of 99% but a specificity of 57%. This group has suggested that biopsy should be performed when a nodule is found with this characteristic on ultrasound. For our patients, the older woman had a <1 cm nodule with a blurred margin and A/T >1 but no other risk factors such as radiation, adenopathy or family history of thyroid cancer. It was elected to watch.

Patient follow-up

After 18 months, the nodule grew in largest dimension to 1.4 cm and developed micro-calcifications. The nodule was biopsied with ultrasound guidance and found to be a papillary thyroid carcinoma. After thyroidectomy, she was found with a unifocal 1.2-cm papillary thyroid carcinoma with classical papillary histology, no invasion, no nodes and BRAF mutation negative. She was not treated with radioactive iodine. She is disease-free after 3 years.

The younger patient had an ultrasound-guided biopsy at the time of the initial visit and was found to have a papillary thyroid carcinoma. After thyroidectomy, she was found to have a unifocal 2.5-cm papillary thyroid carcinoma with classic histology, minimal capsular invasion, two metastatic perithyroidal nodes and BRAF mutation positive. She received 50 mCi radioactive iodine remnant ablation with a post-therapy whole-body scan showing only a small thyroid remnant. She is disease-free after 2 years.

Ultrasound characteristics of these two cases emphasize that thyroid malignancy occurs in nodules that do not have the usual worrisome characteristics of hypoechogenicity, vigorous intranodular vascularity or calcification. Both of these nodules were isoechoic to hyperechoic but had the characteristic of being taller than wide. It is important that clinicians include this characteristic of A/T ratio >1 in the transverse view when describing the ultrasound appearance of a nodule and use it in the decision to biopsy that nodule, regardless of the lack of other sonographic features of malignancy.

References:

Cappelli C. Clin Endocrinol. 2005;63:689-693.
Cappelli C. Eur J Endocrinol. 2006;155:27-31.
Kim EK. AJR Am J Roentgenol. 2002;178:687-691.

For more information:

Stephanie L. Lee, MD, PhD, is associate professor of medicine, diabetes and nutrition and associate professor of medicine at Boston Medical Center. Lee can be reached at Boston Medical Center, 88 E. Newton St., Endocrinology Evans 201, Boston, MA 02118; email: stephanie.lee@bmc.org. Lee reports no relevant financial disclosures.