Correspondence

Diagnosis of Poorly Differentiated Thyroid Cancer with Radioiodine Scanning after Thyrotropin Alfa Stimulation

N Engl J Med 2008; 359:1295-1297September 18, 2008

Article

To the Editor:

Poorly differentiated thyroid cancers are rare and can be difficult for surgeons, endocrinologists, and pathologists to identify.1 These cancers fall into two main histologic categories: insular and other (large cell). Most, but not all, stain with thyroglobulin or thyroid transcription factor 1; those that do not represent particular diagnostic challenges.1-3 We describe a 60-year-old man who presented with bilateral cervical lymphadenopathy and an enlarged thyroid. Biopsy specimens of cervical nodes and the thyroid gland showed features of poorly differentiated adenocarcinoma of unknown primary origin — possibly pulmonary, colorectal, pancreatic, or thyroidal. Immunostaining for thyroglobulin and thyroid transcription factor 1 was negative. The level of serum thyroglobulin at initial presentation was 800 ng per milliliter. No tumor was found outside the neck with diagnostic imaging, including integrated positron-emission tomography and computed tomography (PET–CT) performed after the administration of ¹⁸F-fluorodeoxyglucose. Ultrasonography showed multiple intrathyroidal tumor masses. The patient was unsuccessfully treated with chemotherapy for poorly differentiated adenocarcinoma, which could not be resected because of the extent of the tumor and local invasion.

Since thyrotropin levels were normal, diagnosis of potentially radioiodine-concentrating poorly differentiated thyroid cancer was possible only after stimulation with thyrotropin alfa. After two daily intramuscular injections of 0.9 mg of thyrotropin alfa, thyrotropin levels increased to 91 U per liter and the patient was given 3 mCi of radioiodine orally. A whole-body radioiodine scan obtained 48 hours later showed intense radioiodine uptake in the upper right thyroid lobe, corresponding to a region of normal thyroid tissue identified on ultrasonography and PET–CT. The scan also showed less intense uptake in the lower right lobe and in most of the left lobe, which according to the ultrasonographic and PET–CT findings, were composed entirely of tumor, with a heterogeneous, centrally necrotic tumor on the left (Figure 1Figure 1Imaging Studies of the Head and Neck.). No uptake was seen in the areas of cervical lymphadenopathy. With the diagnosis of poorly differentiated thyroid cancer established, the patient underwent external-beam radiation.

This case shows how stimulation with thyrotropin alfa can be used in a patient with unresectable thyroid cancer to determine the degree of radioiodine concentration in the primary tumor and its metastases. For our patient, this test was critical in establishing the diagnosis of poorly differentiated thyroid cancer, with possible anaplastic transformation of some tumor regions plus metastases that limited the potential usefulness of radioiodine therapy. However, many poorly differentiated thyroid cancers avidly concentrate radioiodine, which has been used successfully to treat such cancers after thyroid resection.1,2,4,5 Our approach of using thyrotropin alfa to stimulate tumoral uptake of radioiodine introduces the possibility of using this treatment even in patients with a thyroid gland that cannot be resected, regardless of the reason.

Malik Juweid, M.D.
Thomas O'Dorisio, M.D.
Mohammed Milhem, M.D.
University of Iowa, Iowa City, IA 52242
malik-juweid@uiowa.edu

Dr. Juweid reports receiving consulting fees from Synarc and lecture fees from Synarc and Zenyaku Kogyo; and Dr. O'Dorisio, consulting fees from InterScience Institute and Novartis, lecture fees from Novartis and Ipsen, and grant support from Novartis and Radiant. No other potential conflict of interest relevant to this letter was reported.

5 References

1. 1

   Sanders EM Jr, LiVolsi VA, Brierley J, Shin J, Randolph GW. An evidence-based review of poorly differentiated thyroid cancer. World J Surg 2007;31:934-945
   CrossRef | Web of Science | Medline

2. 2

   Patel KN, Shaha AR. Poorly differentiated and anaplastic thyroid cancer. Cancer Control 2006;13:119-128
   Medline

3. 3

   Bejarano PA, Nikiforov YE, Swenson ES, Biddinger PW. Thyroid transcription factor-1, thyroglobulin, cytokeratin 7, and cytokeratin 20 in thyroid neoplasms. Appl Immunochem Mol Morphol 2000;8:189-194
   CrossRef | Medline

4. 4

   Tuttle RM, Grewal RK, Larson SM. Radioactive iodine therapy in poorly differentiated thyroid cancer. Nat Clin Pract Oncol 2007;4:665-668
   CrossRef | Web of Science | Medline

5. 5

   Justin EP, Seebold JE, Robinson RA, Walker WP, Gurll NJ, Hawes DR. Insular carcinoma: a distinct thyroid carcinoma with associated iodine-131 localization. J Nucl Med 1991;32:1358-1363
   Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   (2008) Problems Associated with the Use of Thyrogen in Patients with a Thyroid Gland. New England Journal of Medicine 359:16, 1738-1739
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