Thyroid cancer presenting as autonomous thyroid nodule

Issue: September 2015

ByStephanie L. Lee, MD, PhD, ECNU

A 32-year-old woman was referred to the endocrine clinic for abnormal thyroid function, fatigue and depression. Her primary care provider had obtained thyroid function tests to investigate the patient’s depression and inability to lose weight. Results indicated abnormal thyroid function with a suppressed thyroid-stimulating hormone level of 0.02 µU/mL and a low-normal free thyroxine level of 0.81 ng/dL.

An endocrinologist ordered a radioactive iodine (I-123) thyroid scan, which showed normal uptake of 20.1% at 23 hours (Figure 1). The uptake was localized in the lower two-thirds of the right lobe and was suppressed in the left lobe, consistent with an autonomously functioning thyroid nodule (AFTN). An ultrasound was performed at an outside hospital showing a complex, hypoechoic nodule that measured 1.3 cm x 1.3 cm x 0.9 cm.

Figure 1: I-123 nuclear thyroid scan. Increased uptake in the lower portion of the left lobe of the thyroid with reduced uptake in the contralateral right lobe. (A) Anterioposterior view. (B) Left anterior oblique (LAO) view. (C) Right anterior oblique (RAO) view. The 23-hour radioactive iodine uptake of 20.1% in the thyroid gland was within normal limits. RT: right.

The patient was started on methimazole 20 mg daily. She was referred because she was told the antithyroid medication would not help her depression or problems with weight loss. She had no prior or family history of thyroid disease or thyroid cancer, and no history of head and neck radiation.

Imaging, diagnosis

Initially, only the reports of the nuclear thyroid scan and ultrasound were available for review. There was a discrepancy between the size of the nodule reported on the ultrasound (1.3 cm) and the large size of the area of increased iodine uptake (two-thirds of the lobe). We performed a thyroid ultrasound in the office and found the right lobe was normal in size and echotexture.

The left lobe had a hypoechoic nodule with irregular, poorly defined margins (Figure 2). The nodule contained microcalcifications and had vigorous intranodular vascular flow by Doppler analysis (grade 3-4). An ultrasound-guided fine-needle aspiration of this nodule was diagnostic for papillary thyroid carcinoma (Bethesda category VI). The follicular cells had enlarged nuclei, nuclear grooves, powdery vesicular chromatin and membrane-bound nucleoli (Figure 3).

Figure 2: Thyroid ultrasound of the left thyroid lobe. A high-frequency linear probe was used to image the left lobe of the thyroid. (A) Transverse image. (B) Longitudinal image. (C) Longitudinal image with Doppler analysis. The hypoechoic nodule has irregular, poorly defined margins (yellow arrows). The entire nodule had increased intranodular vascularity by Doppler (grade 3-4). The area of hypervascularity helped determine the size of the nodule since the poorly defined nodule margins were hard to detect.

A total thyroidectomy was performed and revealed a 2.5-cm classical papillary thyroid carcinoma with no vascular or capsular invasion. The tumor was positive for the BRAF V600E mutation. During the operation, abnormal nodes were observed posterior to the lobe leading to a bilateral level VI nodal dissection. Three of eight nodes were positive for metastatic papillary thyroid carcinoma.

Screening, confirming malignancy

The current American Thyroid Association management guideline for thyroid nodules and differentiated thyroid cancer suggests that autonomous functioning (hot) thyroid adenomas with hyperthyroidism do not require biopsy. There are scattered case reports that a small percentage of AFTN are thyroid carcinomas. This case alerted clinicians to malignancy because of multiple suspicious sonographic characteristics of tumor (hypoechoic, irregular margins, microcalcifications).

Figure 3: Cytology of the left thyroid nodule. (A) Highly cellular specimen with papillary fronds. (B) Nuclear overlap with nuclear grooves. (C) Enlarged nuclei with intranodular inclusions (red arrow), membrane-bound nuclei (green arrow) and fine, powdery chromatin. The cytology is diagnostic for papillary thyroid carcinoma (Bethesda category VI).

A small retrospective study of 32 patients with hyperthyroidism employed a thyroid ultrasound and radioactive iodine thyroid scan to characterize 42 hyperfunctional nodules. Twenty-five of these nodules had at least one suspicious malignant feature (hypoechoic, taller than wide, irregular margins, evidence of capsular invasion, unilateral adenopathy) and underwent fine-needle aspiration biopsy. Three of 25 (12%) were positive for papillary thyroid carcinoma.

Although not common, a significant number of AFTN may be malignant. It would be reasonable to evaluate patients with AFTN with a thyroid ultrasound as a screen for malignancy. Biopsy should be considered if the ultrasound has suspicious sonographic features.

References:
Bonavita JA, et al. AJR Am J Roentgenol. 2009;doi:10.2214/AJR.08.1820.
Cooper DS, et al. Thyroid. 2009;doi:10.1089/thy.2009.0110.
Lee ES, et al. Korean J Radiol. 2013;doi:10.3348/kjr.2013.14.4.643.

For more information:
Stephanie L. Lee, MD, PhD, ECNU, is an Endocrine Today Editorial Board member. She is Associate Professor of Medicine and Associate Chief, in the Section of Endocrinology, Diabetes and Nutrition 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.