- Email: [email protected]
Metastases to the thyroid gland—a report of six cases
EUROPEAN
JOURNAL
OF
INTERNAL MEDICINE ELSEVIER
European
Journal
of Internal
Medicine
14 (2003)
377-379 www.elsevier.com/locate/ejim
Brief report
Metastases to the thyroid gland-a
report of six cases
Mark De Ridder”‘*, Alexandra B.L. Sermeusb, Daniel Urbainb, Guy A. Storme” “Oncology Center, University hGastroenterology, Department
Hospital of Internal
(AZ-VUB), Medicine,
Received
Vrije Universiteit Brussel, Laarbeeklaan 101, B- 1090 Brussels. Belgium University Hospital (AZ-VUB). Vrije Universiteit Brussel, Brussels, Belgium
10 February
2003;
accepted
10 April
2003
Abstract The associationof an asymptomatic mass,normal thyroid function, and a cold nodule can occur months to yearsafter a primary cancer. should include ruling out other metastases and fine-needle aspiration cytology. We report six cases of secondary thyroid cancer. Two of the patients in our series presented with hyperthyroidism, which may be due to invasion and disruption of thyroid follicles. 0 2003 Elsevier B.V. All rights reserved.
Work-up
Keywords:
Adjuvant
radiotherapy:
Hyperthyroidism;
Surgery;
Thyroid
cancer;
1. Introduction Metastases to the thyroid gland receive little attention in discussions on thyroid cancer. However, the appearance of a nodule in the thyroid of a patient with a history of cancer often causes a dilemma. Such a lesion may be benign, it may be a new primary cancer requiring thyroidectomy, or it may be a metastasis from the original neoplasm and constitute the first evidence of disseminated disease. In this report, records of the Oncology Center AZ-VUB were reviewed for all patients who were diagnosed with histologically proven metastases to the thyroid from January 1982 to December 2002.
2. Case reports All six patients presented with an enlarged thyroid or a mass in the thyroid. Thyroid function was normal in four patients, while two patients presented with hyperthyroidism. Thyroid scintigraphy showed three patients to have a dominant cold nodule and two to have a multinodular *Corresponding E-mail address:
author. Tel.: +32-2-477-6144; fax: +32-2-477-6212. [email protected] (M. De Ridder).
0953-6205/03/$ - see front doi:10.1016/S0953-6205(03)00115-8
matter
0
2003 Elsevier
B.V. All rights
reserved
Thyroid
metastases
goiter; it was not performed in one patient. Fine-needle aspiration was not done in any of these patients. A primary cancer elsewhere had previously only been diagnosed in two patients (Table 1). One had a left hemicolectomy because of a Dukes C sigmoid carcinoma 86 months prior to thyroidectomy; the other had a right nephrectomy because of renal cell carcinoma 16 months prior to being diagnosed as having metastases to the thyroid. In four patients the primary cancer was diagnosed shortly after the metastases to the thyroid were found. Two of them had a renal cell carcinoma, one had an invasive ductal breast carcinoma, and one had a head and neck cancer. Only two patients presented other distant metastases at the time their secondary thyroid cancer was diagnosed (patient Nos. 3 and 4, Table 1). Four patients were treated by total thyroidectomy and two were treated by hemithyroidectomy. None of the patients received postoperative radiotherapy or chemotherapy. Tamoxifen was postoperatively given to the breast cancer patient. Pathological examination showed five patients to have multiple nodules of metastatic neoplasm and only one to have a single lesion in the thyroid. Of the three patients with renal cell carcinoma, two developed a local relapse in the thyroid lodge. One of them had initially been treated with a hemithyroidectomy and presented a
378
M. De Ridder
et al. I European
Journal
of Internal
Medicine
14 (2003)
377-379
Table 1 Patient characteristics Patient number
Primary site
Time from primary site treatment to thyroid involvement (months)
Type of surgical resection
Time from surgical resection to local relapse (months)
Survival surgery
1 2 3 4 5 6
Renal cell Renal cell Renal cell Breast Head & neck Siemoid
16 0 0 0 0 86
Hemithyroidectomy Thyroidectomy Thyroidectomy Hemithyroidectomy Thyroidectomy Thvroidectomv
7 26 No local No local 2 3
209 (still alive) 97 (still alive) 4 19 4 12
metastatic growth in the remaining thyroid lobe 7 months later. This was treated by completion of the hemithyroidectomy to a total thyroidectomy, and the patient had no more local relapses. The other patient relapsed 26 months after surgery, when other distant metastases had already developed. The mass progressively grew, became symptomatic, and was recently treated by radiotherapy. Both patients are still alive, 209 and 97 months, respectively, after secondary thyroid cancer was diagnosed. The third patient with renal cell carcinoma, who already had distant metastases at diagnosis, died within 4 months. The breast cancer patient died within 2 years because of disseminated disease. Autopsy revealed no relapse in the thyroid lodge. Two patients, with head and neck cancer and sigmoid cancer, respectively, died within 1 year due to local mutilating relapses in the thyroid lodge. One initially had a metastasis that extended beyond the capsule of the thyroid; the other had a tumor located near the section margin.
3. Discussion Thyroid metastases are thought to be rare. However, autopsy findings of malignancy metastatic to the thyroid gland vary from 1.9 to 9.5% in three large series, each examining over 1000 patients who died of cancer [l-3]. The more painstaking the pathological study of the thyroid, the more frequent becomes the rate of thyroid involvement. In the study by Shimaoka et al., the greatest incidence was for malignant melanoma (39%/o>,followed by carcinoma of the breast (21%), kidney (12%), and lung (11%) [2]. Only 5% of those metastases were described as a thyroidal mass or enlargement in the clinical record. In accordance with this, only a small number of patients followed at the Oncology Center AZ-VUB (six in 20 years) had ante-mortem histologically proven metastases to the thyroid. Many thyroid metastases were undoubtedly overlooked because metastatic involvement of the thyroid gland is infrequently sought and is often overshadowed by the classic sites where metastases are found. In our series, renal cell carcinoma was the most common primary cancer. Thyroid metastases present themselves as an asymptomatic mass or with symptoms such as dysphagia, dyspnea, and dysphonia or even as a thyroiditis-like picture [4-71.
relapse relapse
after (months)
The interval between primary site treatment and secondary disease varies with the course of the primary cancer, but it has been reported to be as high as 26 years [8]. Thyroid function mostly remains normal, although cases of hypothyroidism due to destruction of the thyroid gland have been described [9]. In contrast, we report two cases that presented with hyperthyroidism. This may be caused by invasion and disruption of thyroid follicles by rapid metastatic growth. A similar phenomenon is characteristic in the course of a de Quervain’s thyroiditis, where the initial thyroid inflammation damages thyroid follicles and activates proteolysis of the thyroglobulin stored within the follicles. This results in an unregulated release of large amounts of thyroxine (T4) and triiodethyronine (T3) into the circulation and, consequently, hyperthyroidism [lo]. Thyroid scintigraphy usually shows a dominant cold nodule and sometimes a multinodular goiter [4,7]. One patient in our series had a multinodular goiter as an underlying thyroid abnormality. Willis observed as early as in 1931 that adenomatous and other abnormal areas of thyroid tissue are predisposed to the establishment of metastatic neoplasms, and he postulated that this predisposition depends on chemical and metabolic changes [ 1 I]. With the establishment of fine-needle aspiration cytology of the thyroid gland as a reliable diagnostic tool [8,12], we propose applying this safe and simple procedure to all patients with a history of cancer in whom a thyroid nodule or enlargement causes a diagnostic dilemma. If isolated metastatic cancer to the thyroid is found, surgical resection should be considered since it often prolongs disease-free survival and may, on occasion, be curative [4,5,8]. Based on the high number of relapses in the thyroid lodge and their mutilating potential, we advise the use of postoperative radiotherapy if metastases invade the capsule of the thyroid or are found near the section margin. In conclusion, every new thyroid mass in a patient with a previous history of malignancy should be considered to be secondary thyroid cancer.
Acknowledgements M.De R. is a fellow of the ‘Fonds voor Wetenschappelijk Onderzoek-Vlaanderen’ .
M. De Ridder
et al. I European
Journal
References PI
Abrams HL, Spiro R, Goldstein N. Metastases in carcinoma: analysis of 1000 autopsied cases. Cancer 1950;3:74-85. JW. Metastatic neoplasms in the PI Shimaoka K, Sokal JE, Pi&en Cancer thyroid gland: pathological and clinical findings. 1962;15:557-65. S. Cancer in Molmo 1958-1969: an autopsy [31 Berge T, Lundberg study. Acta Path01 Microbial Scand Suppl 1977;260:1-235. A, Cederquist E, Ingemansson S, Akerman [41 Ericsson M, Biorklund M. Surgical treatment of metastatic disease in the thyroid gland. J Surg Oncol 1981;17:15-23. metastatic to the thyroid: a diagnostic problem. 151 Ivy HK. Cancer Mayo Clin hoc 1984;59:856-9. mimicked by PI Tibaldi JM, Shapiro LE, Mahadevia PS. Thyroiditis metastatic carcinoma to the thyroid. Mayo Clin Proc 1986;5:399400.
of Internal
Medicine
14 (2003)
377-379
379
M, Sermeus ABL, Van de Steene J, Storme GA. [71 De Ridder Metastatic colon cancer to a multinodular goiter. J Clin Oncol 2001;19:3572-4. 181Nakhjavani MK, Gharib H, Goellner JR, van Heerden JA. Metastasis to the thyroid gland. A report of 43 cases. Cancer 1997:79:574-g. EB, Eng YF, Unger AH. Metastatic infiltration [91 Sirota DK. Goldfield of the thyroid gland causing hypothyroidism. J Mt Sinai Hosp N Y 1968;35:242-5. of thyroiditis. Diagnostic UOI Hamburger JI. The various presentations considerations. Ann Intern Med 1986;104:219-24. [Ill Willis RA. Metastatic tumours in the thyroid gland. Am J Path01 1931;7:187-208. WV Smith SA, Gharib H, Goellner JR. Fine-needle aspiration: usefulness for diagnosis and management of metastatic carcinoma to the thyroid. Arch Intern Med 1987;147:31 l-2.
JOURNAL
OF
INTERNAL MEDICINE ELSEVIER
European
Journal
of Internal
Medicine
14 (2003)
377-379 www.elsevier.com/locate/ejim
Brief report
Metastases to the thyroid gland-a
report of six cases
Mark De Ridder”‘*, Alexandra B.L. Sermeusb, Daniel Urbainb, Guy A. Storme” “Oncology Center, University hGastroenterology, Department
Hospital of Internal
(AZ-VUB), Medicine,
Received
Vrije Universiteit Brussel, Laarbeeklaan 101, B- 1090 Brussels. Belgium University Hospital (AZ-VUB). Vrije Universiteit Brussel, Brussels, Belgium
10 February
2003;
accepted
10 April
2003
Abstract The associationof an asymptomatic mass,normal thyroid function, and a cold nodule can occur months to yearsafter a primary cancer. should include ruling out other metastases and fine-needle aspiration cytology. We report six cases of secondary thyroid cancer. Two of the patients in our series presented with hyperthyroidism, which may be due to invasion and disruption of thyroid follicles. 0 2003 Elsevier B.V. All rights reserved.
Work-up
Keywords:
Adjuvant
radiotherapy:
Hyperthyroidism;
Surgery;
Thyroid
cancer;
1. Introduction Metastases to the thyroid gland receive little attention in discussions on thyroid cancer. However, the appearance of a nodule in the thyroid of a patient with a history of cancer often causes a dilemma. Such a lesion may be benign, it may be a new primary cancer requiring thyroidectomy, or it may be a metastasis from the original neoplasm and constitute the first evidence of disseminated disease. In this report, records of the Oncology Center AZ-VUB were reviewed for all patients who were diagnosed with histologically proven metastases to the thyroid from January 1982 to December 2002.
2. Case reports All six patients presented with an enlarged thyroid or a mass in the thyroid. Thyroid function was normal in four patients, while two patients presented with hyperthyroidism. Thyroid scintigraphy showed three patients to have a dominant cold nodule and two to have a multinodular *Corresponding E-mail address:
author. Tel.: +32-2-477-6144; fax: +32-2-477-6212. [email protected] (M. De Ridder).
0953-6205/03/$ - see front doi:10.1016/S0953-6205(03)00115-8
matter
0
2003 Elsevier
B.V. All rights
reserved
Thyroid
metastases
goiter; it was not performed in one patient. Fine-needle aspiration was not done in any of these patients. A primary cancer elsewhere had previously only been diagnosed in two patients (Table 1). One had a left hemicolectomy because of a Dukes C sigmoid carcinoma 86 months prior to thyroidectomy; the other had a right nephrectomy because of renal cell carcinoma 16 months prior to being diagnosed as having metastases to the thyroid. In four patients the primary cancer was diagnosed shortly after the metastases to the thyroid were found. Two of them had a renal cell carcinoma, one had an invasive ductal breast carcinoma, and one had a head and neck cancer. Only two patients presented other distant metastases at the time their secondary thyroid cancer was diagnosed (patient Nos. 3 and 4, Table 1). Four patients were treated by total thyroidectomy and two were treated by hemithyroidectomy. None of the patients received postoperative radiotherapy or chemotherapy. Tamoxifen was postoperatively given to the breast cancer patient. Pathological examination showed five patients to have multiple nodules of metastatic neoplasm and only one to have a single lesion in the thyroid. Of the three patients with renal cell carcinoma, two developed a local relapse in the thyroid lodge. One of them had initially been treated with a hemithyroidectomy and presented a
378
M. De Ridder
et al. I European
Journal
of Internal
Medicine
14 (2003)
377-379
Table 1 Patient characteristics Patient number
Primary site
Time from primary site treatment to thyroid involvement (months)
Type of surgical resection
Time from surgical resection to local relapse (months)
Survival surgery
1 2 3 4 5 6
Renal cell Renal cell Renal cell Breast Head & neck Siemoid
16 0 0 0 0 86
Hemithyroidectomy Thyroidectomy Thyroidectomy Hemithyroidectomy Thyroidectomy Thvroidectomv
7 26 No local No local 2 3
209 (still alive) 97 (still alive) 4 19 4 12
metastatic growth in the remaining thyroid lobe 7 months later. This was treated by completion of the hemithyroidectomy to a total thyroidectomy, and the patient had no more local relapses. The other patient relapsed 26 months after surgery, when other distant metastases had already developed. The mass progressively grew, became symptomatic, and was recently treated by radiotherapy. Both patients are still alive, 209 and 97 months, respectively, after secondary thyroid cancer was diagnosed. The third patient with renal cell carcinoma, who already had distant metastases at diagnosis, died within 4 months. The breast cancer patient died within 2 years because of disseminated disease. Autopsy revealed no relapse in the thyroid lodge. Two patients, with head and neck cancer and sigmoid cancer, respectively, died within 1 year due to local mutilating relapses in the thyroid lodge. One initially had a metastasis that extended beyond the capsule of the thyroid; the other had a tumor located near the section margin.
3. Discussion Thyroid metastases are thought to be rare. However, autopsy findings of malignancy metastatic to the thyroid gland vary from 1.9 to 9.5% in three large series, each examining over 1000 patients who died of cancer [l-3]. The more painstaking the pathological study of the thyroid, the more frequent becomes the rate of thyroid involvement. In the study by Shimaoka et al., the greatest incidence was for malignant melanoma (39%/o>,followed by carcinoma of the breast (21%), kidney (12%), and lung (11%) [2]. Only 5% of those metastases were described as a thyroidal mass or enlargement in the clinical record. In accordance with this, only a small number of patients followed at the Oncology Center AZ-VUB (six in 20 years) had ante-mortem histologically proven metastases to the thyroid. Many thyroid metastases were undoubtedly overlooked because metastatic involvement of the thyroid gland is infrequently sought and is often overshadowed by the classic sites where metastases are found. In our series, renal cell carcinoma was the most common primary cancer. Thyroid metastases present themselves as an asymptomatic mass or with symptoms such as dysphagia, dyspnea, and dysphonia or even as a thyroiditis-like picture [4-71.
relapse relapse
after (months)
The interval between primary site treatment and secondary disease varies with the course of the primary cancer, but it has been reported to be as high as 26 years [8]. Thyroid function mostly remains normal, although cases of hypothyroidism due to destruction of the thyroid gland have been described [9]. In contrast, we report two cases that presented with hyperthyroidism. This may be caused by invasion and disruption of thyroid follicles by rapid metastatic growth. A similar phenomenon is characteristic in the course of a de Quervain’s thyroiditis, where the initial thyroid inflammation damages thyroid follicles and activates proteolysis of the thyroglobulin stored within the follicles. This results in an unregulated release of large amounts of thyroxine (T4) and triiodethyronine (T3) into the circulation and, consequently, hyperthyroidism [lo]. Thyroid scintigraphy usually shows a dominant cold nodule and sometimes a multinodular goiter [4,7]. One patient in our series had a multinodular goiter as an underlying thyroid abnormality. Willis observed as early as in 1931 that adenomatous and other abnormal areas of thyroid tissue are predisposed to the establishment of metastatic neoplasms, and he postulated that this predisposition depends on chemical and metabolic changes [ 1 I]. With the establishment of fine-needle aspiration cytology of the thyroid gland as a reliable diagnostic tool [8,12], we propose applying this safe and simple procedure to all patients with a history of cancer in whom a thyroid nodule or enlargement causes a diagnostic dilemma. If isolated metastatic cancer to the thyroid is found, surgical resection should be considered since it often prolongs disease-free survival and may, on occasion, be curative [4,5,8]. Based on the high number of relapses in the thyroid lodge and their mutilating potential, we advise the use of postoperative radiotherapy if metastases invade the capsule of the thyroid or are found near the section margin. In conclusion, every new thyroid mass in a patient with a previous history of malignancy should be considered to be secondary thyroid cancer.
Acknowledgements M.De R. is a fellow of the ‘Fonds voor Wetenschappelijk Onderzoek-Vlaanderen’ .
M. De Ridder
et al. I European
Journal
References PI
Abrams HL, Spiro R, Goldstein N. Metastases in carcinoma: analysis of 1000 autopsied cases. Cancer 1950;3:74-85. JW. Metastatic neoplasms in the PI Shimaoka K, Sokal JE, Pi&en Cancer thyroid gland: pathological and clinical findings. 1962;15:557-65. S. Cancer in Molmo 1958-1969: an autopsy [31 Berge T, Lundberg study. Acta Path01 Microbial Scand Suppl 1977;260:1-235. A, Cederquist E, Ingemansson S, Akerman [41 Ericsson M, Biorklund M. Surgical treatment of metastatic disease in the thyroid gland. J Surg Oncol 1981;17:15-23. metastatic to the thyroid: a diagnostic problem. 151 Ivy HK. Cancer Mayo Clin hoc 1984;59:856-9. mimicked by PI Tibaldi JM, Shapiro LE, Mahadevia PS. Thyroiditis metastatic carcinoma to the thyroid. Mayo Clin Proc 1986;5:399400.
of Internal
Medicine
14 (2003)
377-379
379
M, Sermeus ABL, Van de Steene J, Storme GA. [71 De Ridder Metastatic colon cancer to a multinodular goiter. J Clin Oncol 2001;19:3572-4. 181Nakhjavani MK, Gharib H, Goellner JR, van Heerden JA. Metastasis to the thyroid gland. A report of 43 cases. Cancer 1997:79:574-g. EB, Eng YF, Unger AH. Metastatic infiltration [91 Sirota DK. Goldfield of the thyroid gland causing hypothyroidism. J Mt Sinai Hosp N Y 1968;35:242-5. of thyroiditis. Diagnostic UOI Hamburger JI. The various presentations considerations. Ann Intern Med 1986;104:219-24. [Ill Willis RA. Metastatic tumours in the thyroid gland. Am J Path01 1931;7:187-208. WV Smith SA, Gharib H, Goellner JR. Fine-needle aspiration: usefulness for diagnosis and management of metastatic carcinoma to the thyroid. Arch Intern Med 1987;147:31 l-2.