Ann Thorac Surg 1999;67:856-857
© 1999 The Society of Thoracic Surgeons
Case Reports
Thyroid lung metastasis diagnosed 47 years after thyroidectomy1
Peter Fonseca, MD, PhDa
a Department of Cardiothoracic Surgery, National Naval Medical Center, Bethesda, Maryland, USA
Accepted for publication September 14, 1998.
Address reprint requests to Dr Fonseca, 505 Couch Avenue, Suite 250, St. Louis, MO 63122
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Abstract
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A 75-year-old woman underwent excision of a middle lobe lung nodule that contained a separate, isolated focus of metastatic papillary thyroid carcinoma. A thyroid lobectomy for papillary cancer had been performed 47 years earlier. This interval is believed to be the longest time from initial diagnosis to identification of distant lung metastasis reported. The pertinent published reports are reviewed and methods of surveillance discussed.
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Introduction
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Well-differentiated thyroid metastases to the lung are known to occur many years after the initial presentation for thyroid carcinoma. The incidence of metastases has been reported to be high. With prolonged follow-up of greater than 20 years, metastases to the cervical lymph nodes occur in 35% to 80% of patients and distant metastases, including the lung, in 10% to 40% [1]. The longest interval between thyroid resection and differentiated thyroid lung metastases previously reported has been 30 years [2].
The patient was a 75-year-old woman who was noted to have a middle lobe nodule on the screening chest x-ray film. A computed tomographic scan confirmed a 2-cm right middle lobe lung lesion (Fig 1). The patient was asymptomatic and had been in good health.
The past medical history was notable for thyroid malignancy. In 1950, at the age of 28, she had a right thyroid lobectomy and isthmusectomy performed for papillary thyroid carcinoma, with right radical neck dissection (4 of 17 lymph nodes positive for metastases). Subsequent radiation therapy delivered a total of 21 Gy to the neck. Twenty-six years later, the patient noted enlargement of the left lobe of the thyroid. Technetium and iodine scans indicated a cold nodule, and left thyroid completion lobectomy was performed for a benign follicular adenoma. She has subsequently received maintainence therapy with Synthroid, with no evidence of tumor recurrence as monitored by serum thyroglobulin levels.
She presented again at the age of 75 with a right middle lobe lung nodule. Pathologic analysis of the lung specimen showed necrotizing bronchial and peribronchial inflammation with granulomatous inflammation and a separate focus of well-defined metastatic thyroid cancer less than 2 mm in diameter (hematoxylin and eosin staining). There was no inflammatory response around the tumorlet, and immunoperoxidase staining (identifying the presence of thyroglobulin with antibodies causing a peroxidase reaction) of the thyroid tissue was reactive only in the small area of previously identified thyroid cells (Fig 2). The serum thyroid-stimulating hormone assay and thyroglobulin levels were negligible, and the levothyroxine level was normal.
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Fig 2. Reactive immunoperoxidase stain for thyroglobulin in papillary tumor (central dark staining cells) within lung tissue of resected specimen, separate from lung nodule. (Hematoxylin and eosin; x40 before 46.9% reduction.)
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Comment
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A long follow-up interval is required to assess treatment for well-differentiated thyroid carcinoma because of its prolonged course and very slow growth rate. McConahey and colleagues [3], in a retrospective study of 859 patients with papillary thyroid cancer, found distant metastatic lesions in 40 (5%). The lungs were the leading site of involvement in 76%, followed by the mediastinum in 24%, bone in 23%, and brain in 15%.
Compared with patients with cervical lymph node recurrence, patients with distant spread carry a poorer prognosis. Of 32 patients whose first postoperative recurrence occurred in cervical nodes, none died of thyroid cancer. However, the mortality rate in patients with a distant metastatic site was 36% by 5 years and 65% by 20 years, with the most common cause of thyroid cancer death being pulmonary metastatic disease [2].
The presentation of lung metastases has been reported to be from 5 to 30 years after the initial diagnosis of thyroid cancer [1, 2]. Approximately 25% of first relapses occurred after 20 years of complete remission [2].
It has been repeatedly documented that chest radiography does not detect all pulmonary metastases and that scintigraphy with iodine 131 may demonstrate tumor that is not radiographically detectable [1]. Neither iodine 131 scintigraphy nor routine chest x-ray film alone will reveal all cases of pulmonary metastases. In addition, unlike most lung nodules, nodular lung metastases from papillary thyroid carcinoma may demonstrate no change in size on the chest x-ray film for 25 years [4].
Normal findings on the chest x-ray film appear to confer a survival advantage in those patients with metastatic lung lesions. Schlumberger and associates [5] presented data on 141 patients with lung metastases. They reported that the overall survival rate was 30% at 15 years in patients with distant metastases but 95% in patients with normal findings on the chest x-ray film and 55% in patients with micronodular lung metastases.
Serum thyroglobulin measurement should be performed routinely as part of the follow-up visit. This glycoprotein is a secretory product produced only by thyroid tissue. A detectable thryoglobulin level warrants further investigation, beginning with a total body scan. Negative findings on the total body scan do not preclude the existence of metastases, and additional attempts to localize thyroid tissue should be made, including neck ultrasound, neck and thoracic computed tomographic scans, and a 100-mCi iodine-131 whole-body scans. These modalities will help to identify those patients with lung metastases and normal chest x-ray findings. It should also be noted that a normal thyroglobulin level, as in our patient, does not exclude a metastatic focus.
The treatment recommended is radioactive iodine. Samaan and colleagues [6] reported a 5-year pulmonary metastatic survival rate of 61% for patients with positive radioactive uptake on the scan and 29% for patients with no uptake. The appearance of micronodular metastases on the chest x-ray film and the ability of the lesions to concentrate radioiodine confer improved prognosis when treated with radioactivity. Emphasis should therefore be placed on early detection and treatment [5].
The cause of arrest of metastatic growth in papillary thyroid carcinoma is unknown. It may be due to long tumor doubling time or to phases of dormancy during the course of the cancer. The doubling time of pulmonary metastases of differentiated thyroid cancers is among the longest observed, and growth arrest has occurred without irradiation or suppressive chemotherapy [7].
A fascinating aspect of the present case is that this small, isolated focus of excised thyroid tissue was an incidental finding. Were it not for the granulomatous lesion excised, the thyroid tumorlet would not have been identified. One can conjecture as to whether this tissue was present since the original operation (a period of growth arrest) or was a recent metastatic deposition within the lung. Although the patient had sporadic thyroglobulin and chest x-ray follow-up since her thyroid operations, the tumorlet identified is clearly below the detection sensitivity of current radiographic techniques. In addition, her serum test results did not indicate recurrence.
Although the mechanism is unclear for delayed presentation of papillary thyroid metastatic lesions, it nevertheless occurs. The present case demonstrates one such occurrence 47 years after initial diagnosis and is believed to be the longest interval recorded. Such patients must be followed up for their entire lifetime.
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Footnotes
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1 The views expressed in this article are those of the author and do not reflect the official policy or position of the Department of Navy, Department of Defense, or the US Government. 
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References
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Worm A.M., Holten I., Taaning E. Nuclear imaging of pulmonary metastases in thyroid carcinoma. Acta Radiol Oncol 1980;19:401-403.[Medline]
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Tubiana M., Schlumberger M., Rougier P., et al. Long term results and prognostic factors in patients with differentiated thyroid carcinoma. Cancer 1985;55:794-804.[Medline]
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McConahey W.M., Hay I.D., Woolner L.B., van Heerden J.A., Taylor W.F. Papillary thyroid cancer treated at the Mayo Clinic, 1946 through 1970: initial manifestations, pathologic findings, therapy and outcome. Mayo Clin Proc 1986;61:978-996.[Medline]
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Kressel H.Y., Gamsu G., Kalifa L.G., Webb W.R. Prolonged growth arrest of pulmonary metastases in papillary thyroid carcinoma. West J Med 1978;129:424-429.[Medline]
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Schlumberger M., Tubiana M., de Vathaire F., et al. Long term results of treatment of 283 patients with lung and bone metastases from differentiated thyroid carcinoma. J Clin Endocrinol Metab 1986;63:960-967.[Abstract/Free Full Text]
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Samaan N.A., Schultz P.N., Haynie T.P., Ordonez N.G. Pulmonary metastasis of differentiated thyroid carcinoma: treatment results in 101 patients. J Clin Endocrinol Metab 1985;60:376-380.[Abstract/Free Full Text]
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Charbit A., Malaise E., Tugiana M. Relations between the pathological nature and the growth rate of human tumours. Eur J Cancer 1971;7:307-315.
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Abstract
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