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Consider metastatic disease to the thyroid in patients with history of cancer
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A 58-year-old Vietnamese man with stage IV non–small cell lung cancer, which was diagnosed in 2007, presented to the ED with several days of hoarseness and worsening dysphagia for solid foods.
A recent 18F-fluorodeoxyglucose PET/CT scan obtained to restage his lung cancer after treatment with carboplatinum/taxol and whole brain radiation therapy demonstrated increased metabolic activity diffusely throughout a newly enlarged thyroid gland with new hypermetabolic cervical, mediastinal, inguinal and retroperitoneal lymph nodes (figure 1A).
 Miguel Ariza |
 Stephanie L. Lee |
On review of systems, he reported poor appetite with a 13-lb weight loss in two weeks. He otherwise denied other symptoms suggestive of hypothyroidism or hyperthyroidism. He did not have a personal or family history of thyroid disease or neck radiation. On physical exam, he was cachectic and afebrile, with a normal pulse and blood pressure. His thyroid gland was firm, nontender, approximately 45 g, without focal nodules and with palpable nonmobile bilateral cervical lymph nodes in the jugular chain. He did not have a fine tremor and his deep tendon reflexes were normal.
Laboratory testing showed subclinically elevated thyroid function studies with a thyroid-stimulating hormone <0.01 IU/L (range, 0.35-5.5), total triiodothyronine 152 ng/dL (range, 60-181) and free thyroxine 1.6 ng/dL (range, 0.89-1.8). Thyroid ultrasound showed an enlarged heterogeneous, hypoechoic and hypovascular thyroid gland without focal nodules (figures 2A and 2B). Bilateral lateral cervical lymphadenopathy in levels III (figure 2C) and IV was also noted, with the largest lymph nodes measuring 2 cm.
Although the diffusely enlarged hypoechoic thyroid and thyrotoxicosis suggested Graves’ hyperthyroidism, the appearance of a nonvascular thyroid with pathologic adenopathy made Graves’ disease an unlikely diagnosis. A nuclear thyroid I-123 uptake and scan showed a poorly imaged gland with uptake of 2.6% at four hours and 0.7% at 24 hours, consistent with a subacute thyroiditis or a destructive process and eliminating Graves’ disease as a cause of the elevated thyroid hormone levels (figure 1B).
Fine-needle aspiration biopsy
The patient was referred to the endocrine service and a fine-needle aspiration (FNA) biopsy of the thyroid gland was performed on the right thyroid lobe and a right level III cervical lymph node. The FNA of the thyroid was sent for standard cytology, flow cytometry and immunohistochemical stains. The node biopsy was examined with standard cytology, with thyroglobulin levels measured from a needle washout. Cytology of the right thyroid and cervical node was consistent with a poorly differentiated metastatic NSCLC.
Immunohistochemistry of the cell block obtained from the right thyroid FNA was negative for thyroglobulin and positive for carcinoembryonic antigen staining. S-100 and thyroid transcription factor-1 stains were inconclusive. Flow cytometry was not consistent with lymphoma. The needle washout from the node FNA was negative for thyroglobulin.
Metastases to the thyroid gland are uncommon but tend to be more frequent in patients aged 60 years and older. The incidence rate in autopsy studies varies from 1.25% to 24%. The lung was the most common primary tumor, followed by the esophagus, breast, kidney and malignant melanoma. Within pulmonary malignancies, adenocarcinoma is the most common to metastasize to the thyroid gland, followed by squamous cell, small-cell and large-cell carcinomas.
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Photos courtesy of: Stephanie L. Lee, MD, PhD |
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It is important to establish the distinction between metastatic disease to the thyroid and a primary thyroid carcinoma, as treatment options and prognosis are different. Poorly differentiated thyroid malignancies, medullary thyroid carcinoma and metastatic lesions to the thyroid may be difficult to distinguish cytologically. Cytologically, the findings of epithelial differentiation such as mucin production or keratinization should raise the suspicion for metastatic disease.
Immunohistochemical stains may help in distinguishing primary thyroid cancers from the common metastatic carcinomas. Immunostains for thyroglobulin are specific for thyroid follicular epithelial carcinomas but can be negative in poorly differentiated and anaplastic thyroid carcinomas. Thyroid transcription factor-1 stain is positive in thyroid and pulmonary carcinomas. Medullary thyroid carcinomas may be immunoreactive for thyroid transcription factor-1, chromogranin and calcitonin. Carcinoembryonic antigen is expressed in a variety of cancers, including medullary thyroid carcinoma, colon, gastric, breast and lung. Renal cell carcinoma and CD-10 are relatively specific and sensitive immunostains for renal cell carcinoma. S-100 stain is positive in malignant melanomas.
Role of 18F-fluorodeoxyglucose PET
18F-fluorodeoxyglucose PET has an established role in thyroid cancer management, particularly in patients who have thyroglobulin positive and iodine negative tumors. Because of its lack of specificity, however, it is not indicated for the routine evaluations of thyroid nodules. Nevertheless, 18F-fluorodeoxyglucose PET can be a useful study if one suspects metastatic disease to the thyroid gland.
Focal uptake of 18F-fluorodeoxyglucose in a thyroid nodule occurs when the tissue is hypermetabolic with high glucose utilization. An 18F-fluorodeoxyglucose-positive thyroid nodule has a high risk of carcinoma of about 35%, either from a primary thyroid carcinoma or metastatic disease. The risk for aggressive carcinoma is increased when a high metabolic activity is measured by the standard uptake values. Diffuse 18F-fluorodeoxyglucose PET uptake, as in this patient, can be found in normal variants, Graves’ disease and Hashimoto’s thyroiditis, but this pattern does not necessarily exclude a diffuse infiltration of metastatic tumor, such as in this case.
Metastatic disease to the thyroid should always be considered in patients with a thyroid nodule and a history of cancer. Our case also illustrates that metastatic disease to the thyroid gland should also be considered in a patient with a diffuse 18F-fluorodeoxyglucose PET uptake and a history of existing malignancy, even though this pattern is most frequently seen with chronic thyroiditis. The thyrotoxicosis and very low thyroid uptake were consistent with a subacute thyroiditis or destructive process. The FNA demonstrated that this was a case of thyroid destruction with release of excess thyroid hormone caused by metastatic spread of aggressive metastatic lung cancer to the thyroid.
It was recommended by the endocrine service to place the patient on thyroid hormone therapy because of the evidence of aggressive progression of the lung carcinoma diffusely in the thyroid. Upon discharge from the hospital, the patient and his family met with his oncologist and opted for hospice care.
Miguel Ariza, MD, is a Fellow in Endocrinology, and Stephanie L. Lee, MD, PhD, is Associate Professor of Medicine and Associate Chief, both in the Section of Endocrinology, Diabetes and Nutrition at Boston University Medical Center.
For more information:
- Chen YK. Nuc Med Commun. 2007;28:117-122.
- Kurata S. Ann Nucl Med. 2007;21:325-330.
- Lin SY. Chin Med J. 2002;65:101-105.
- Papi G. Clin Endocrinol. 2007;66:565-571.