Metastatic papillary thyroid carcinoma

Diagnosis with an elevated thyroglobulin level and negative RAI whole body scan.

Issue: October 2008

ByStephanie L. Lee, MD, PhD, ECNU

A 62-year-old woman is referred for evaluation of persistently elevated thyroglobulin levels consistent with metastatic papillary thyroid carcinoma. The patient presented with an incidental nodule found on exam by her primary care physician in January 2007. An ultrasound-guided fine needle aspiration biopsy was consistent with a papillary thyroid carcinoma.

A total thyroidectomy was performed in March 2007. During the surgery the tumor was found to have macroscopic invasion into strap muscles and the left recurrent laryngeal nerve. In addition to the total thyroidectomy, the patient had a central neck (level VI) node dissection, tumor shaved off the recurrent laryngeal nerve, and strap muscles involved with tumor excised. Pathology showed a multifocal papillary thyroid cancer in a 3.5 cm tumor in the left thyroid lobe and 0.8 cm focus in right thyroid lobe, both with extension into extrathyroidal soft tissue and lymphovascular invasion. Tumor was noted to focally extend to the surgical margins. A third 0.5 cm foci of papillary microcarcinoma was found in the right lobe with hyalinization and extensive dystrophic calcifications. Four of six paratracheal and pretracheal lymph nodes removed contained papillary thyroid carcinoma. The patient’s overall AJCC classification is T4N1aM0.

Stephanie L. Lee

She was treated with 150 mCi I-131 with her post therapy scan showing uptake only the thyroid bed. She had moderately severe mucositis after the radioiodine treatment that resolved over two weeks. Over the next year, her thyroglobulin levels continued to be remain elevated between 3.5-8.2 ng/mL with negative thyroglobulin antibodies and T4 suppression of her TSH to 0.01 uU/mL consistent with tumor persistence. One year after her I-131 therapy, a 2-Deoxy-2-[18F] fluoro-D-glucose PET scan was performed while she was taking her levothyroxine suppression therapy and did not reveal any areas of abnormal FDG activity. The patient was referred for further evaluation.

An office ultrasound with a high frequency ultrasound linear probe did not reveal any abnormal adenopathy or mass in the neck. She was allowed to become hypothyroid and an I-123 diagnostic whole body scan was performed with 2mCi of I-123. Her TSH was 40.8 with an elevated thyroglobulin of 41.3 ng/mL and thyroglobulin antibody of < 20.

The scan revealed a linear area of uptake in the left lower neck but no other focal area of uptake was seen (Figure 1). After swallowing water, the uptake diminished consistent with physiological esophageal retention of the I-123. The following day, the patient had a hypothyroid PET/diagnostic quality CT scan without contrast that demonstrated an abnormal FDG hypermetabolic activity in a right retrotracheal lymph node at the level of the thoracic inlet that coincided with a 1.5 cm lymph node deep in the right neck (Figure 2). The node was located low in Level VI adjacent to the trachea, posterior to the right carotid artery and jugular vein and just anterior to the pre-vertebral fascia. This secluded location prevented biopsy with either ultrasound or CT guidance. The patient was admitted and 50 mCi of I-131 was administered. This dose was selected because of her severe mucositis that occurred with her initial radioactive iodine therapy. A one week post-therapy scan did not reveal any persistent abnormal uptake in the PET-positive neck mass.

Figure 1: I-123 Whole Body Scan
Figure 1. I-123 Whole Body Scan. The patient was hypothyroid with a TSH of 40 uU/mL. Whole body scintigraphy was performed 24 hours after a 2 mCi dose of I-123. The linear uptake (red arrow) in the left neck resolved after the patient swallowed water consistent with esophageal retention of the isotope. Normal physiological uptake into the nasopharynx (blue arrow) and the gastrointestinal tract/bladder (green arrows) is also seen.

This patient poses a common problem of persistent measurable thyroglobulin levels with no abnormal uptake on a radioiodine whole body scan after the initial surgical and radioiodine ablation treatments. The first diagnostic test should be a high frequency neck ultrasound exam because local adenopathy is often the site of recurrence of papillary thyroid carcinoma. In this case, the neck ultrasound, euthyroid PET/CT scan and hypothyroid I-123 whole body scans were unrevealing for tumor but with hypothyroidism her PET/CT scan revealed increased metabolic activity of the tumor allowing for localization with this imaging modality.

Although there has not been rigorous testing, expert opinions suggest TSH stimulation of tumor will increase thyroid cancer detection on PET scans since TSH stimulates thyrocyte metabolism, glucose transport, and glycolysis. A small randomized study has demonstrated that rTSH stimulation improves the detectability of occult thyroid metastases with FDG PET, compared with scans performed on TSH suppression. When tumor cannot be detected after recombinant TSH stimulated or euthyroid radioiodine or PET/CT scans, repeat scans should be considered with hypothyroidism (TSH >25-30 uU/mL). The TSH stimulation of hypothyroidism is prolonged compared to recombinant human TSH injections and may allow for increase in metabolism and iodine uptake necessary for detection.

Figure 2. Transverse FDG PET and CT scans of the neck. A. CT scan of the transverse neck. A 1.5 node (blue arrow) is found posterior to the trachea and anterior to the pre-vertebral fascia approximately 1 cm above the clavicular heads. B. Fused FDG PET and CT scans of the neck. The hypermetabolic mass shown in red with a SUV max of 7.6 (red arrow) co-localizes with the retrotracheal node found on CT scan.

Finally, the 2006 ATA Guidelines for the Management of Thyroid Nodules and Cancers suggests than when tumor cannot be located with conventional imaging including MRI, CT scan, US scan of the neck and PET/CT scan, then a single therapy with 100-150 mCi of I-131 with a post therapy can may be performed for localization. There is no utility for repeated I-131 therapies if the post therapy scan is negative as with this patient. Radioiodine treatment in patients with a prior negative radioiodine whole body scan is for localization but not for meaningful reduction in tumor burden. There are many reasons for false positive PET scans including inflammation, therefore, a hypermetabolic mass on a PET/ CT scan must be confirmed to be thyroid malignancy by either evidence of radioactive iodine uptake or cytological or pathological confirmation after biopsy. Because of the location of the mass, an open biopsy was performed and confirmed that mass was a node containing well-differentiated papillary thyroid carcinoma.

Stephanie L. Lee, MD, PhD, is an Associate Chief in the Section of Endocrinology, Diabetes and Nutrition and an Associate Professor of Medicine at Boston University School of Medicine and Boston Medical Center.

For more information:

Chin BB, Patel P, Cohade C, et al. Recombinant human thyrotropin stimulation of fluoro-D-glucose positron emission tomography uptake in well-differentiated thyroid carcinoma. J Clin Endocrinol Metab. 2004;89:91-95.

Cooper DS, Doherty GM, Haugen BR, et al. The American Thyroid Association Guidelines Taskforce. Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2006;16:109-142.

Leboulleux S, Schroeder PR, Schlumberger M, Ladenson PW. The role of PET in follow-up of patients treated for differentiated epithelial thyroid cancers. Nat Clin Pract Endocrinol Metab. 2007;3:112-121.