Radioactive iodine uptake in a mediastinal mass

Issue: August 2008

ByStephanie L. Lee, MD, PhD, ECNU

A 28-year-old woman was referred for the evaluation of metastatic papillary thyroid carcinoma in the anterior mediastinum. The patient found a mass in the right neck about nine months ago. Biopsy of the right lateral, level V, lymph node revealed metastatic papillary thyroid carcinoma.

Stephanie L. Lee

After a total thyroidectomy and modified radical neck dissection, a multifocal well-differentiated papillary thyroid carcinoma was found in both lobes of the thyroid with the largest tumor measuring 1.2 cm and in 14 cervical lymph nodes. She received 150 mCi of I-131 therapy and a post-therapy scan (see figure 1) showed physiological I-131 in her nasopharynx, thyroid remnant and a discrete uptake in the anterior mediastinum. A computed tomography scan (see figure 2) and a magnetic resonance imaging scan (see figure 3) demonstrated an anterior mediastinal mass. Her thyroglobulin declined after the radioactive iodine treatment but remained detectable after six months. This patient’s thyroglobulin level was unreliable tumor marker because of positive serum thyroglobulin antibodies.

A hypothyroid 2 mCi I-131 whole body scan demonstrated no abnormal uptake. Repeat CT scan of the neck and chest showed a stable mediastinal mass and no cervical adenopathy or pulmonary masses. Four months later, she was referred for evaluation because of the suspicion of metastatic papillary thyroid carcinoma; her thyroglobulin antibodies failed to decline after initial treatment and the persistent mediastinal mass. Review of her radiological studies revealed the typical appearance of a thymus on the post-therapy whole body scan, CT scan and MRI scan. During a routine diagnostic ultrasound of the neck, a 3 x 2 x 1.5 cm cystic mass was found posterior to the right carotid artery and internal jugular vein. Fine needle aspiration biopsy revealed a thyroglobulin level of > 300 ng/mL and cytology consistent with metastatic papillary thyroid carcinoma. After the node resection, the thyroglobulin level decreased to 0.2 ng/mL and the thyroglobulin antibody level became unmeasurable.

Figure 1. I-131 post-therapy whole body scintigraphy.
Scintigraphy performed seven days after 150 mCi of therapeutic I-131 with anterior and posterior views. Physiologic secretion of I-131 was identified in the nasopharynx (yellow arrow) and thyroid remnant (blue arrow). Focal uptake was also identified in the anterior mediastinum (red arrow). No other site of radioiodine uptake suggestive of metastatic disease was noted.

Role of thymus

The thymus is a lymphoid organ with a role in cellular immunity to induce lymphocyte maturation of T-helper cells (CD-4) and cytotoxic suppressor cells (CD-8). Developmentally, the thymus descends from the third branchial arch caudally to the anterior mediastinum along with the inferior pair of parathyroid glands. This developmental pattern explains the occasional localization of an inferior parathyroid adenoma within or near the thymus in the anterior mediastinum.

Contrary to common teaching, the thymus does not involute after birth but grows reaching its largest size at puberty. The average size of the thymus in children between the ages of 6 and 19 years on CT scan is 1.1 cm. With advancing age, the thyroid is replaced by fibrofatty tissues and decreases in size and weight but does not disappear. The average size of the thymus in adults over the age of 50 years on CT scan is 0.5 cm while on MRI scan the average size is 1.5 to 2 cm. The difference in size is likely because the fatty infiltration makes the margins of the thymus easier to detect on MRI scan. The thymus on a CT scan (see figure 2) and a MRI scan (see figure 3) is a bilobed or triangular mass with straight or concave borders in the anterior mediastinum located anterior to the proximal ascending aorta, pulmonary outflow tract and the superior vena cava. The thymus on CT scan has attenuation lower than muscle because of the fatty infiltration (see figure 2). The thymus on MRI scan appears homogeneous with signal intensity slightly greater than muscle on T1-weighted images and close to that of fat on T2-weighted images. Diffuse symmetric thymus enlargement may occur as a result of thymic hyperplasia or lymphoid hyperplasia.

Figure 2. CT scan without contrast of the thorax.
The thymus is a low attenuation triangular mass with smooth borders (red arrow) in the anterior mediastinum. The thyroid is located anterior to the aorta and main pulmonary arterial trunk in the axial view (panel A) and superior to the heart in the coronal view (panel B). Aorta: Ao. Liver: L. Heart: H.

Figure 3. MRI scan without contrast of the thorax.
The thymus is a hypodense, triangular mass (red arrow) in the anterior mediastinum is located anterior to the aorta in the axial view of the thorax.

Source: Stephanie L. Lee

Thymic hyperplasia is associated with autoimmune diseases including myasthenia gravis, Hashimoto’s thyroiditis, Addison’s disease and Graves’ disease. Lymphoid hyperplasia occurs after a systemic stress such as chemotherapy, radiation therapy and thermal burns. Thymic enlargement should be distinguished from a thymoma or thymic carcinoma, which usually appears as a mass rather than diffuse thymus enlargement. The thymus only rarely is a metastatic site for differentiated thyroid carcinoma. Although I-131 whole body scanning is generally specific in localizing metastatic foci of differentiated thyroid carcinoma, non-thyroidal uptake has been reported in the thymus. I-131 trapping in the thymus was first described by Braverman but Schlumberger proved I-131 localized to the thymus after guidance with a hand-held gamma probe and thymectomy. Uptake in the area of the thymus gland should be evaluated carefully, as recurrent thyroid cancer occasionally occurs in level VII nodes beneath the manubrium. The thymus histology was normal without evidence of metastatic differentiated thyroid carcinoma and negative for thyroglobulin immunostaining. Although the differential for radioactive iodine uptake in to the anterior mediastinum may be a result of metastases to mediastinal nodes and rarely to the thymus, clinicians must be aware the mediastinal uptake of radioiodine occurs in thymus especially in younger patients but may occur in patients of all ages as the thymus persists in most adults.

In this patient, the radioactive iodine uptake in the mediastinum was a false positive result while a high frequency ultrasound imaging provided a more sensitive and accurate localization of persistent and recurrent papillary thyroid carcinoma in the neck.

Stephanie L. Lee, MD, PhD, is an Associate Professor of Medicine at Boston University School of Medicine and Director of Endocrine Clinic, and the Robert Dawson Evans Clinician at the Boston Medical Center.

For more information:

Nishino M, Ashiku SK, Kocher ON, et al. The thymus: a comprehensive review. Radiographics. 2006;26:335-348.

Vermiglio F, Baudin E, Travagli JP, et al. Iodine concentration by the thymus in thyroid carcinoma. J Nucl Med. 1996;27:1830-1836.

Veronikis IE, Simkin P, Braverman LE. Thymic uptake of iodine-131 in the anterior mediastinum. J Nucl Med. 1996;37:991-992.