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Thymic Hyperplasia Presenting as a False Positive Whole Body I131 Scan in a Patient With Well-Differentiated Thyroid Carcinoma: A Case Report and Review of the Literature

Peralta, Maylene C.I. MD*†; Emanuele, Nicholas V. MD*†; Gordon, Donald L. MD*; Spies, Stuart MD‡; Camacho, Pauline M. MD*

Case Report
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This case report describes a woman who had persistent I131 whole body scan uptake after thyroidectomy and two radioactive iodine ablation therapies for papillary cancer despite absence of thyroglobulin. The patient was a 44-year-old female who presented in another institution with a one cm right thyroid nodule. Fine needle aspiration biopsy was interpreted as a follicular neoplasm. A near total thyroidectomy was done revealing three foci of papillary carcinoma, follicular variant (0.8 cm tumor in the isthmus and two additional microscopic foci). The patient received ablation radiotherapy with 28.9 millicuries (mCi) one month after surgery. A follow up whole body scan six months later showed two or three foci of functioning thyroid tissue in the neck. A second ablation therapy with 100.9 mCi was administered. Seven days later, follow-up whole body scan showed large uptake in the mediastinum. Suppressed and stimulated thyroglobulin levels were undetectable. She then presented in our institution. Chest CT showed a possible mediastinal soft tissue density. Repeat chest CT 6 months later showed an increase in the anterior mediastinal soft tissue density. Thoracotomy and thymectomy were performed. Histopathology was consistent with thymic hyperplasia. No thyroid tissue was found and the tissue stained negative for thyroglobulin. Thymic hyperplasia can cause a false positive uptake in the mediastinum. In the absence of thyroglobulin elevation in a patient with well-differentiated thyroid carcinoma, a positive I131 scan may be of nonthyroidal origin.

*From the Division of Endocrinology and Metabolism, Loyola University Chicago, Chicago, Illinois.

From the VA Hines Hospital, Chicago, Illinois.

From the Department of Radiology, Northwestern University, Evanston, Illinois.

The authors thank Dr. Cesar Reyes, Hines VA Department of Pathology for photography of slides.

Address correspondence and reprint requests to: Pauline M. Camacho, M.D., Division of Endocrinology and Metabolism, Bldg 117, Room 11, Loyola University Medical Center, 2160 South First Ave., Maywood, IL 60153. Telephone: 708 216-8634; Fax: 708 216-5936; E-mail: pcamach@lumc.edu

The whole body radioidine I131 scan is an important component in the postoperative management of differentiated thyroid carcinomas. A positive scan is generally caused by residual thyroid tissue, recurrent or persistent tumor or metastasis. The most sensitive imaging is achieved after a therapeutic dose of I131. However, with increased sensitivity, there may be decreased specificity. We present a patient in whom thymic hyperplasia was responsible for a positive posttherapy I131 scan and review previously reported causes of false positive whole body I131 scans.

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CASE REPORT

A 44-year-old white female underwent near-total thyroidectomy for thyroid carcinoma. Histopathology revealed a 0.8 cm follicular variant of papillary carcinoma in the isthmus and two additional microscopic foci of carcinoma in the left lobe. There was no evidence of vascular, capsular or lymphatic invasion. A postoperative whole body scan (WBS) 1 month later showed residual uptake in the neck. Radioactive iodine (28.9 mCi I131) was administered. Follow-up WBS 6 months later demonstrated 2–3 foci of functioning thyroid tissue in the neck. Serum thyroglobulin (TG) level was undetectable. The patient was given 100.9 mCi I131 therapy. Posttherapy scan revealed moderate-sized, spherical, midline, retrosternal uptake (Figure 1). This distribution of radioactivity was not seen on the scan before the second therapeutic dose of I131. Subsequent CT scan of the chest was equivocal for increased soft tissue density in the mediastinum. Positron emission tomography (PET) imaging with 18F FDG (fluourodeoxyglucose) verified the mediastinal uptake, thought to be from the thymus gland. Six months later, a chest CT was repeated showing increased prominence of the soft tissue density (Figure 2). The patient opted for surgical removal of the mass. Mediastinostomy and thymectomy was performed revealing benign lymphoid hyperplasia of the thymus. No thyroid tissue was present (Figure 3, 4). Immunohistochemical stain for thyroglobulin was negative. Follow-up WBS using a non-therapeutic dose of I131 did not show any isotope.

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DISCUSSION

I131 WBS and TG levels are useful tools for the detection of functioning metastases in patients with differentiated thyroid carcinoma [1–2]. TG level determination has both high sensitivity (88%) and specificity (99%) in the recognition of metastases [2,3]. However, I131 WBS has high specificity (80–100%) but less sensitivity, 45–57% in papillary cancer and 60% for follicular cancer [1,3–6,8].

False positive I131 body scans have been reported from contaminated body secretions such as saliva retained in the esophagus, galactorrhea, pathologic transudates, and inflammation as seen in skin burns [1,12,16]. Neoplasms of nonthyroidal origin, such as lymphoepithelial cyst, gastric adenocarcinoma [35], Warthin tumor [17], primary lung adenocarcinoma [31], or undifferentiated bronchogenic carcinoma [33], have also been reported to cause false positive WBS [12]. Table 1 shows causes of false positive WBS based on a review of MEDLINE 1966–2002.

Several reports have shown that the thymus whether hyperplastic (one case) or nonhyperplastic (four cases), can be the cause of an increased mediastinal uptake on WBS [1,24–29]. It has been observed among patients of relatively young age (19–44 years). They also have CT scans showing enlarged thymus without other abnormalities, and low to absent serum TG after thyroid hormone withdrawal [1]. Among the most common causes of false positive uptake in the chest are disorders involving the esophagus such as achalasia, Zenkers diverticulum, hiatal hernia, and Barrett esophagus. However, our patient’s clinical presentation was not compatible with these conditions. Radiologic imaging including a chest CT scan failed to reveal any other abnormality except a hyperplastic thymus.

Lin [43] reported a case of false positive anterior mediastinal I131 uptake caused by thymic hyperplasia. There were atypical CT features such as lobulated lesion edges that made it suspicious for metastases. Histopathology showed cystic degeneration of thymic Hassall bodies, and was negative for metastatic thyroid cells. Hassall bodies are composed of epithelial cells that resemble keratinocytes. During physiological involution, Hassall bodies decrease in number but increase in size and finally degenerate into corneal cysts [42,44]. It has been proposed that the iodine-trapping property of the thymic cystic corpuscles maybe compared with the thyroid follicles. Both have spherical basic architecture containing a cluster of epithelial cells in the periphery and proteinaceous material in the center. Although the iodine containing protein in the thyroid colloid is thyroglobulin, its equivalent in the cystic Hassall bodies is unknown. It may be a keratin-related protein that gives a similar iodine trapping property. Thymic uptake of iodine is low as compared with iodine uptake by the thyroid; therefore, thymic visualization requires high doses of I131 given for therapeutic purposes [7,24–27,45].

Because there have been more cases of thymic uptake in patients with normal thymus glands than thymic hyperplasia after posttherapy I131 scans, uptake in this location must always be assessed as to the potential of it not being thyroid tissue. Verifying this, we failed to find thyroid tissue in our case of thymic uptake of I131 either histologically or by thyroglobulin staining.

In summary, we present the second case of thymic hyperplasia causing a falsely positive posttherapy I131 scan. Typical thymic histology and absent thyroglobulin staining of the thymus confirmed the lack of thyroid cells.

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