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Renal cell carcinoma with metastasis to the thyroid gland
Urologic Oncology 5 (2000) 173–175
Original article
Renal cell carcinoma with metastasis to the thyroid gland Shailesh U. Pitale, M.D.a,*, Glen W. Sizemore, M.D.a, Rima Bakhos, M.D.b, Steven A. DeJong, M.D.c, Robert C. Flanigan, M.D.d, Nicholas V. Emanuele, M.D.a a
Division of Endocrinology and Metabolism, Loyola University Medical Center, 2160 S. First Avenue, Maywood, IL 60153, USA b Department of Pathology, Loyola University Medical Center, 2160 S. First Avenue, Maywood, IL 60153, USA c Department of Surgery, Loyola University Medical Center, 2160 S. First Avenue, Maywood, IL 60153, USA d Department of Urology, Loyola University Medical Center, 2160 S. First Avenue, Maywood, IL 60153, USA Received 16 January 1999; received in revised form 18 August 1999; accepted 13 November 1999.
Abstract Cancers that metastasize to the thyroid gland are uncommon. Metastasis to the thyroid gland has been reported in renal cell carcinoma (RCC), breast cancer, lung cancer, gastrointestinal malignancies, malignant melanoma, sarcoma, hematologic malignancies, and other genitourinary cancers. A computer search of the records of the department of pathology at Loyola University Medical Center was done to determine the number of thyroidectomies performed between 1988 and 1998. A detailed review of the clinical records of patients with metastasis to the thyroid gland from RCC was done. A total of 941 thyroidectomies were performed between 1988 and 1998. Metastasis to the thyroid gland was seen in six cases (0.64%). Three of these six cases had metastasis from RCC. The interval between the diagnosis of the primary RCC and the thyroid metastasis was 2 to 10 years. Two of these three patients had an adenomatous thyroid gland. Metastases to the thyroid, though relatively rarely diagnosed clinically as a cause of thyroid nodule, must be considered in the differential diagnosis of thyroid nodule, particularly in patients who have a history of RCC. © 2000 Elsevier Science Inc. All rights reserved. Keywords: Renal cell carcinoma; Hypernephroma; Thyroid metastasis
1. Introduction
2. Case reports
Cancers that metastasize to the thyroid gland are uncommon. In more than 20,000 thyroidectomies at the Mayo Clinic over a period of 21 years, only 10 cases (0.05%) were reported to have metastasized to the thyroid gland [1]. Metastasis to the thyroid gland has been reported in renal cell carcinoma (RCC), breast cancer, lung cancer, gastrointestinal malignancies, malignant melanoma, sarcoma, hematologic malignancies, and other genitourinary cancers. At Loyola University Medical Center, 941 thyroidectomies were performed between 1988 and 1998. Metastasis to the thyroid gland was seen in 6 cases (0.64%). The primary malignancies in these cases were adenocarcinoma of the lung (1 patient), lymphoma (2 patients), and RCC (3 patients). We present the three cases of thyroid metastasis from RCC, review the problem, and suggest a change of follow-up strategy for RCC.
2.1. Case 1
* Corresponding author. Tel.: ⫹1-708-216-5793 or ⫹1-708-216-9219; fax: ⫹1-708-216-5936. E-mail address: [email protected] (S.U. Pitale)
A 59-year-old caucasian female was examined for the presence of a right-sided thyroid nodule 10 years after left radical nephrectomy for RCC. Two months after the nephrectomy, she received interleukin-2 (IL-2) therapy and subsequently underwent left lower lobectomy for pulmonary metastases. Two years prior to the current presentation, she was noted to have a right-sided thyroid nodule on computed tomography (CT) staging, which was not followed. She denied local or systemic symptoms of thyroid disease. On examination, the thyroid gland was normal to palpation. There was no cervical or axillary lymphadenopathy. The remainder of the examination was normal. Total thyroxine was 5.8 mcg/dl (normal range 5.0–12.0 mcg/dl) and thyroid stimulating hormone (TSH) was 1.21 u/ml (normal range 0.20–5.0 u/ ml). Ultrasound guided fine needle aspiration of the right thyroid nodule showed features of follicular neoplasm. Right total and left subtotal thyroidectomy was done and revealed metastatic carcinoma, clear cell type, consistent
1078-1439/00/$ – see front matter © 2000 Elsevier Science Inc. All rights reserved. PII: S1078-1439(00)00 0 6 5 - X
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Pitale et al. / Urologic Oncology 5 (2000) 173–175
with a renal primary located adjacent to the encapsulated follicular adenoma. Additional studies showed several small nonspecific peripheral pleural-based opacities in the right lung, new bilateral adrenal masses (left 5 ⫻ 3 cm, right 2.2 ⫻ 1.2 cm), and a new focus of abnormal density in a lateral left rib. The patient received eight doses of high-dose IL-2 for the metastatic RCC. Followup studies 3 months after the IL-2 therapy revealed an increase in size of the bilateral adrenal masses with no change in the lung opacities. The patient is currently being followed in the oncology clinic. 2.2. Case 2 A 62-year-old caucasian male presented with a left-sided thyroid nodule 6 years after right radical nephrectomy for RCC. He denied local or systemic symptoms of thyroid disease. On examination there was a 2 ⫻ 2 cm left thyroid nodule with no cervical lymphadenopathy and a normal right thyroid lobe. The remainder of the examination was normal. Total thyroxine was 6.2 mcg/dl (normal range 5.0–12.0 mcg/dl), TSH was 0.88 u/ml (normal range 0.2–5.0 u/ ml), and thyroglobulin was 87 ng/ml (normal range ⬍50 ng/ ml). Fine needle aspiration of the nodule revealed metastatic RCC, clear cell type. Total thyroidectomy was performed. The surgical specimen showed metastatic RCC in a multiadenomatous thyroid gland. The patient has declined IL-2 therapy. Post-thyroidectomy he feels well and localizing studies for other metastatic sites are normal. 2.3. Case 3 A 54-year-old caucasian male presented 13 years earlier to an outside hospital with metastatic lesions in the right ischium and pubis from an unknown primary. This was followed by the serendipitous discovery and left total nephrectomy for the RCC (mixed clear cell and papillary RCC). Two years later the patient had metastases to the right acetabulum, right groin, and left lobe of the thyroid. On physical examination there was a 2 ⫻ 2 cm, hard, fixed nodule at the left lobe of the thyroid gland. The right lobe was normal and there was no cervical lymphadenopathy. The remainder of the examination was normal. Total thyroxine was 8.0 mcg/ dl (normal range 5.0–12.0 mcg/dl) and TSH was 3.2 u/ml (normal range 0.2–3.5 u/ml). Ultrasound of the thyroid gland showed a complex mass (3.7 ⫻ 3.3 ⫻ 2.5 cm) in the left lobe of the thyroid extending into the isthmus. Fine needle aspiration of the thyroid mass showed metastatic RCC (mixed clear cell and papillary type). The patient underwent total thyroidectomy and received high dose IL-2 therapy for the metastatic RCC. He has been lost to follow up.
3. Discussion Metastases to the thyroid gland have been reported in patients with RCC, breast cancer, lung cancer, gastrointestinal cancers, malignant melanoma, sarcomas, hematologic
malignancies, and other genitourinary cancers. Metastasis to the thyroid from distant cancer is rarely diagnosed clinically. Autopsy studies report a higher incidence (2–17%) of metastasis to the thyroid gland in patients who die of any cancer [2–5]. In the autopsy series of 1,980 cases reported by Shimaoka et al. [5], the incidence of metastasis to the thyroid from distant cancers was 9.5%. The potential for RCC to metastasize to the thyroid gland (proportion of patients with RCC having metastasis to the thyroid gland) in that study was 12%. The incidence of metastasis to the thyroid reported in clinical series is much lower than in the autopsy studies. Long and Black [6] reported a 0.4% incidence of metastasis to the thyroid in a total of 1,000 patients. Wychulis et al. [1] reported the occurrence of metastasis to the thyroid in 10 of 20,262 thyroidectomy cases (0.05%). At our institution 6 of 941 cases of thyroidectomy (0.64%) had metastasized to the thyroid gland from a distant malignancy. Primary malignancies in these patients were RCC (3 patients), lymphoma (2 patients), and adenocarcinoma of the lung (1 patient). The difference in the reported incidence of metastasis to the thyroid between clinical and autopsy studies could be due to either: (1) selection bias or the difference in the baseline characteristics of the study cohort or (2) compulsive thoroughness of a directed microscopic autopsy examination that specifically looked for micrometastasis versus clinical series with a less thorough, nearly incidental discovery of metastasis in a gland removed for many clinical reasons. Metastasis to an adenomatous thyroid gland was reported in 2 of 7 patients by Green et al. [7]. Our first two patients had an adenomatous thyroid gland. This could very well be due to the common occurrence of subclinical adenomatous changes in the thyroid gland. Linton et al. [8] postulated that low oxygen and iodine levels in the adenomatous gland were responsible for making the thyroid susceptible to metastasis from distant cancers. Willis [9] suggested decreased blood flow through an abnormal gland to be responsible for increased predisposition for metastasis from distant cancers. RCC has a variable natural history. The pre-invasive phase is thought to last 13 to 20 years [10]. Metastasis to the thyroid gland has been reported to be present at the initial diagnosis of RCC [11]. The longest interval between the diagnosis of RCC and metastasis to the thyroid gland reported in the literature is 18 years [12]. In a study by Czech et al. [13], the mean interval between the diagnosis of primary RCC and thyroidectomy was 6 years, 10 months. Our first patient had pulmonary metastases 2 months after nephrectomy. This was followed by thyroid and possible adrenal metastasis approximately 10 years after the diagnosis and treatment of the primary tumor. The thyroid nodule noted 2 years prior to the diagnosis of thyroid metastasis was probably a benign adenoma followed by subsequent metastasis of RCC. Our second patient had thyroid metastasis 6 years postnephrectomy for RCC. The third patient’s initial presentation was with distant me-
Pitale et al. / Urologic Oncology 5 (2000) 173–175
tastasis of the RCC followed in 2 years with metastasis to the thyroid gland. As expected, the clinical outcome of patients with isolated metastasis to the thyroid gland is significantly better than those with multiple systemic metastases [13,14]. Aggressive surgical management of the isolated thyroid metastasis is recommended in patients with RCC with no evidence of metastases elsewhere [14]. Thyroidectomy may be done in patients with multiple systemic metastases from RCC if the thyroid metastasis causes treacheal compression [14]. Fine needle aspiration of the thyroid gland may be used to diagnose metastatic RCC when clinical suspicion warrants, as shown by Halbauer et al. [15]. Lung metastasis are seen in 50% of patients with metastastic RCC [10]. A CT scan of the chest is commonly done in these patients. If we accept the metastatic potential of RCC to the thyroid to be as high as 12%, as shown by Shimaoka et al. [5], and believe that CT might detect a significant percentage of these lung metastases, then we suggest that it might be appropriate for the chest CT to become a thyroid-chest CT. In conclusion, we believe that: (1) Metastases to the thyroid, though relatively rarely diagnosed clinically as a cause of thyroid nodule, must be considered in the differential diagnosis of thyroid nodule, particularly in patients who have a history of RCC, and (2) a history of a remote RCC increases the possibility that a thyroid nodule could represent late metastasis from RCC.
175
References [1] Wychulis AR, Beahrs OH, Woolner LB. Metastasis of carcinoma to the thyroid gland. Ann Surg 1964;160:169–77. [2] Abrams HL, Spiro R, Goldstein N. Metastases in carcinoma: Analysis of 1,000 autopsied cases. Cancer 1950;3:74–85. [3] Mortensen JD, Woolner LB, Bennett WA. Secondary malignant tumors of thyroid gland. Cancer 1956;9:306–9. [4] Rice CO. Microscopic metastases in thyroid gland. Am J Pathol 1934;10:407–12. [5] Shimaoka K, Sokal JE, Pickren JW. Metastatic neoplasms in the thyroid gland. Cancer 1962;15:557–65. [6] Long GC, Black BM. Metastatic hypernephroma of thyroid. Mayo Clin Proc 1945;20:43–8. [7] Green LK, Ro JY, Mackay B, Ayala AG, Luna MA. Renal cell carcinoma metastatic to the thyroid. Cancer 1989;63:1810–5. [8] Linton RR, Barney JD, Moorman HD, Lerman J. Metastatic hypernephroma of the thyroid gland. Surg Gynecol Obstet 1946;83:493–8. [9] Willis RA. Metastatic tumors in the thyroid gland. Am J Pathol 1931; 197:187–208. [10] Holland JM. Cancer of the kidney—natural history and staging. Cancer 1973;32:1030–42. [11] Gault EW, Leung THW, Thomas DP. Clear cell renal carcinoma masquerading as thyroid enlargement. J Pathol 1974;113:21–5. [12] Siekierska-Hellman M, Sworczak K, Lewczuk A, Blaut K, Boj E. Renal cell carcinoma with solitary metastases appearing during 18 years of follow-up. Postgrad Med 1997;73:582–4. [13] Czech JM, Lichtor TR, Carney JA, Van Heerden JA. Neoplasms metastatic to the thyroid gland. Surg Gynecol Obstet 1982;155:503–5. [14] Burge JP, Blalock JB. Metastastic hypernephroma of the thyroid gland. Am J Surg 1967;113:387–9. [15] Halbauer M, Kardum-Skelin I, Vranesic D, Crepinko I. Aspiration cytology of renal cell carcinoma metastatic to the thyroid. Acta Cytol 1991;35:443–6.
Original article
Renal cell carcinoma with metastasis to the thyroid gland Shailesh U. Pitale, M.D.a,*, Glen W. Sizemore, M.D.a, Rima Bakhos, M.D.b, Steven A. DeJong, M.D.c, Robert C. Flanigan, M.D.d, Nicholas V. Emanuele, M.D.a a
Division of Endocrinology and Metabolism, Loyola University Medical Center, 2160 S. First Avenue, Maywood, IL 60153, USA b Department of Pathology, Loyola University Medical Center, 2160 S. First Avenue, Maywood, IL 60153, USA c Department of Surgery, Loyola University Medical Center, 2160 S. First Avenue, Maywood, IL 60153, USA d Department of Urology, Loyola University Medical Center, 2160 S. First Avenue, Maywood, IL 60153, USA Received 16 January 1999; received in revised form 18 August 1999; accepted 13 November 1999.
Abstract Cancers that metastasize to the thyroid gland are uncommon. Metastasis to the thyroid gland has been reported in renal cell carcinoma (RCC), breast cancer, lung cancer, gastrointestinal malignancies, malignant melanoma, sarcoma, hematologic malignancies, and other genitourinary cancers. A computer search of the records of the department of pathology at Loyola University Medical Center was done to determine the number of thyroidectomies performed between 1988 and 1998. A detailed review of the clinical records of patients with metastasis to the thyroid gland from RCC was done. A total of 941 thyroidectomies were performed between 1988 and 1998. Metastasis to the thyroid gland was seen in six cases (0.64%). Three of these six cases had metastasis from RCC. The interval between the diagnosis of the primary RCC and the thyroid metastasis was 2 to 10 years. Two of these three patients had an adenomatous thyroid gland. Metastases to the thyroid, though relatively rarely diagnosed clinically as a cause of thyroid nodule, must be considered in the differential diagnosis of thyroid nodule, particularly in patients who have a history of RCC. © 2000 Elsevier Science Inc. All rights reserved. Keywords: Renal cell carcinoma; Hypernephroma; Thyroid metastasis
1. Introduction
2. Case reports
Cancers that metastasize to the thyroid gland are uncommon. In more than 20,000 thyroidectomies at the Mayo Clinic over a period of 21 years, only 10 cases (0.05%) were reported to have metastasized to the thyroid gland [1]. Metastasis to the thyroid gland has been reported in renal cell carcinoma (RCC), breast cancer, lung cancer, gastrointestinal malignancies, malignant melanoma, sarcoma, hematologic malignancies, and other genitourinary cancers. At Loyola University Medical Center, 941 thyroidectomies were performed between 1988 and 1998. Metastasis to the thyroid gland was seen in 6 cases (0.64%). The primary malignancies in these cases were adenocarcinoma of the lung (1 patient), lymphoma (2 patients), and RCC (3 patients). We present the three cases of thyroid metastasis from RCC, review the problem, and suggest a change of follow-up strategy for RCC.
2.1. Case 1
* Corresponding author. Tel.: ⫹1-708-216-5793 or ⫹1-708-216-9219; fax: ⫹1-708-216-5936. E-mail address: [email protected] (S.U. Pitale)
A 59-year-old caucasian female was examined for the presence of a right-sided thyroid nodule 10 years after left radical nephrectomy for RCC. Two months after the nephrectomy, she received interleukin-2 (IL-2) therapy and subsequently underwent left lower lobectomy for pulmonary metastases. Two years prior to the current presentation, she was noted to have a right-sided thyroid nodule on computed tomography (CT) staging, which was not followed. She denied local or systemic symptoms of thyroid disease. On examination, the thyroid gland was normal to palpation. There was no cervical or axillary lymphadenopathy. The remainder of the examination was normal. Total thyroxine was 5.8 mcg/dl (normal range 5.0–12.0 mcg/dl) and thyroid stimulating hormone (TSH) was 1.21 u/ml (normal range 0.20–5.0 u/ ml). Ultrasound guided fine needle aspiration of the right thyroid nodule showed features of follicular neoplasm. Right total and left subtotal thyroidectomy was done and revealed metastatic carcinoma, clear cell type, consistent
1078-1439/00/$ – see front matter © 2000 Elsevier Science Inc. All rights reserved. PII: S1078-1439(00)00 0 6 5 - X
174
Pitale et al. / Urologic Oncology 5 (2000) 173–175
with a renal primary located adjacent to the encapsulated follicular adenoma. Additional studies showed several small nonspecific peripheral pleural-based opacities in the right lung, new bilateral adrenal masses (left 5 ⫻ 3 cm, right 2.2 ⫻ 1.2 cm), and a new focus of abnormal density in a lateral left rib. The patient received eight doses of high-dose IL-2 for the metastatic RCC. Followup studies 3 months after the IL-2 therapy revealed an increase in size of the bilateral adrenal masses with no change in the lung opacities. The patient is currently being followed in the oncology clinic. 2.2. Case 2 A 62-year-old caucasian male presented with a left-sided thyroid nodule 6 years after right radical nephrectomy for RCC. He denied local or systemic symptoms of thyroid disease. On examination there was a 2 ⫻ 2 cm left thyroid nodule with no cervical lymphadenopathy and a normal right thyroid lobe. The remainder of the examination was normal. Total thyroxine was 6.2 mcg/dl (normal range 5.0–12.0 mcg/dl), TSH was 0.88 u/ml (normal range 0.2–5.0 u/ ml), and thyroglobulin was 87 ng/ml (normal range ⬍50 ng/ ml). Fine needle aspiration of the nodule revealed metastatic RCC, clear cell type. Total thyroidectomy was performed. The surgical specimen showed metastatic RCC in a multiadenomatous thyroid gland. The patient has declined IL-2 therapy. Post-thyroidectomy he feels well and localizing studies for other metastatic sites are normal. 2.3. Case 3 A 54-year-old caucasian male presented 13 years earlier to an outside hospital with metastatic lesions in the right ischium and pubis from an unknown primary. This was followed by the serendipitous discovery and left total nephrectomy for the RCC (mixed clear cell and papillary RCC). Two years later the patient had metastases to the right acetabulum, right groin, and left lobe of the thyroid. On physical examination there was a 2 ⫻ 2 cm, hard, fixed nodule at the left lobe of the thyroid gland. The right lobe was normal and there was no cervical lymphadenopathy. The remainder of the examination was normal. Total thyroxine was 8.0 mcg/ dl (normal range 5.0–12.0 mcg/dl) and TSH was 3.2 u/ml (normal range 0.2–3.5 u/ml). Ultrasound of the thyroid gland showed a complex mass (3.7 ⫻ 3.3 ⫻ 2.5 cm) in the left lobe of the thyroid extending into the isthmus. Fine needle aspiration of the thyroid mass showed metastatic RCC (mixed clear cell and papillary type). The patient underwent total thyroidectomy and received high dose IL-2 therapy for the metastatic RCC. He has been lost to follow up.
3. Discussion Metastases to the thyroid gland have been reported in patients with RCC, breast cancer, lung cancer, gastrointestinal cancers, malignant melanoma, sarcomas, hematologic
malignancies, and other genitourinary cancers. Metastasis to the thyroid from distant cancer is rarely diagnosed clinically. Autopsy studies report a higher incidence (2–17%) of metastasis to the thyroid gland in patients who die of any cancer [2–5]. In the autopsy series of 1,980 cases reported by Shimaoka et al. [5], the incidence of metastasis to the thyroid from distant cancers was 9.5%. The potential for RCC to metastasize to the thyroid gland (proportion of patients with RCC having metastasis to the thyroid gland) in that study was 12%. The incidence of metastasis to the thyroid reported in clinical series is much lower than in the autopsy studies. Long and Black [6] reported a 0.4% incidence of metastasis to the thyroid in a total of 1,000 patients. Wychulis et al. [1] reported the occurrence of metastasis to the thyroid in 10 of 20,262 thyroidectomy cases (0.05%). At our institution 6 of 941 cases of thyroidectomy (0.64%) had metastasized to the thyroid gland from a distant malignancy. Primary malignancies in these patients were RCC (3 patients), lymphoma (2 patients), and adenocarcinoma of the lung (1 patient). The difference in the reported incidence of metastasis to the thyroid between clinical and autopsy studies could be due to either: (1) selection bias or the difference in the baseline characteristics of the study cohort or (2) compulsive thoroughness of a directed microscopic autopsy examination that specifically looked for micrometastasis versus clinical series with a less thorough, nearly incidental discovery of metastasis in a gland removed for many clinical reasons. Metastasis to an adenomatous thyroid gland was reported in 2 of 7 patients by Green et al. [7]. Our first two patients had an adenomatous thyroid gland. This could very well be due to the common occurrence of subclinical adenomatous changes in the thyroid gland. Linton et al. [8] postulated that low oxygen and iodine levels in the adenomatous gland were responsible for making the thyroid susceptible to metastasis from distant cancers. Willis [9] suggested decreased blood flow through an abnormal gland to be responsible for increased predisposition for metastasis from distant cancers. RCC has a variable natural history. The pre-invasive phase is thought to last 13 to 20 years [10]. Metastasis to the thyroid gland has been reported to be present at the initial diagnosis of RCC [11]. The longest interval between the diagnosis of RCC and metastasis to the thyroid gland reported in the literature is 18 years [12]. In a study by Czech et al. [13], the mean interval between the diagnosis of primary RCC and thyroidectomy was 6 years, 10 months. Our first patient had pulmonary metastases 2 months after nephrectomy. This was followed by thyroid and possible adrenal metastasis approximately 10 years after the diagnosis and treatment of the primary tumor. The thyroid nodule noted 2 years prior to the diagnosis of thyroid metastasis was probably a benign adenoma followed by subsequent metastasis of RCC. Our second patient had thyroid metastasis 6 years postnephrectomy for RCC. The third patient’s initial presentation was with distant me-
Pitale et al. / Urologic Oncology 5 (2000) 173–175
tastasis of the RCC followed in 2 years with metastasis to the thyroid gland. As expected, the clinical outcome of patients with isolated metastasis to the thyroid gland is significantly better than those with multiple systemic metastases [13,14]. Aggressive surgical management of the isolated thyroid metastasis is recommended in patients with RCC with no evidence of metastases elsewhere [14]. Thyroidectomy may be done in patients with multiple systemic metastases from RCC if the thyroid metastasis causes treacheal compression [14]. Fine needle aspiration of the thyroid gland may be used to diagnose metastatic RCC when clinical suspicion warrants, as shown by Halbauer et al. [15]. Lung metastasis are seen in 50% of patients with metastastic RCC [10]. A CT scan of the chest is commonly done in these patients. If we accept the metastatic potential of RCC to the thyroid to be as high as 12%, as shown by Shimaoka et al. [5], and believe that CT might detect a significant percentage of these lung metastases, then we suggest that it might be appropriate for the chest CT to become a thyroid-chest CT. In conclusion, we believe that: (1) Metastases to the thyroid, though relatively rarely diagnosed clinically as a cause of thyroid nodule, must be considered in the differential diagnosis of thyroid nodule, particularly in patients who have a history of RCC, and (2) a history of a remote RCC increases the possibility that a thyroid nodule could represent late metastasis from RCC.
175
References [1] Wychulis AR, Beahrs OH, Woolner LB. Metastasis of carcinoma to the thyroid gland. Ann Surg 1964;160:169–77. [2] Abrams HL, Spiro R, Goldstein N. Metastases in carcinoma: Analysis of 1,000 autopsied cases. Cancer 1950;3:74–85. [3] Mortensen JD, Woolner LB, Bennett WA. Secondary malignant tumors of thyroid gland. Cancer 1956;9:306–9. [4] Rice CO. Microscopic metastases in thyroid gland. Am J Pathol 1934;10:407–12. [5] Shimaoka K, Sokal JE, Pickren JW. Metastatic neoplasms in the thyroid gland. Cancer 1962;15:557–65. [6] Long GC, Black BM. Metastatic hypernephroma of thyroid. Mayo Clin Proc 1945;20:43–8. [7] Green LK, Ro JY, Mackay B, Ayala AG, Luna MA. Renal cell carcinoma metastatic to the thyroid. Cancer 1989;63:1810–5. [8] Linton RR, Barney JD, Moorman HD, Lerman J. Metastatic hypernephroma of the thyroid gland. Surg Gynecol Obstet 1946;83:493–8. [9] Willis RA. Metastatic tumors in the thyroid gland. Am J Pathol 1931; 197:187–208. [10] Holland JM. Cancer of the kidney—natural history and staging. Cancer 1973;32:1030–42. [11] Gault EW, Leung THW, Thomas DP. Clear cell renal carcinoma masquerading as thyroid enlargement. J Pathol 1974;113:21–5. [12] Siekierska-Hellman M, Sworczak K, Lewczuk A, Blaut K, Boj E. Renal cell carcinoma with solitary metastases appearing during 18 years of follow-up. Postgrad Med 1997;73:582–4. [13] Czech JM, Lichtor TR, Carney JA, Van Heerden JA. Neoplasms metastatic to the thyroid gland. Surg Gynecol Obstet 1982;155:503–5. [14] Burge JP, Blalock JB. Metastastic hypernephroma of the thyroid gland. Am J Surg 1967;113:387–9. [15] Halbauer M, Kardum-Skelin I, Vranesic D, Crepinko I. Aspiration cytology of renal cell carcinoma metastatic to the thyroid. Acta Cytol 1991;35:443–6.