Case Report
Amy L. Cummings, MD; Melanie Goldfarb, MD, FACS ABSTRACT Objective: Axillary lymph nodes (ALNs) are a rare manifestation of thyroid carcinoma; only 16 cases are in the published literature. This study adds two additional patients, one involving differentiated papillary thyroid carcinoma (PTC) and one case involving medullary thyroid carcinoma (MTC). The limited information on this topic in the literature is also reviewed. Methods: In case 1, a 56-year-old female diagnosed in 2004 with stage IV PTC (lung and rib metastases) underwent total thyroidectomy (TTx) and received radioiodine and antineoplastics for progression in the lung, liver, and chest wall (2008-2011). In 2012, screening mammography detected multiple axillary masses corresponding to ALNs on magnetic resonance imaging. After fine-needle aspiration biopsy demonstrated metastatic PTC, the patient underwent right ALN dissection and is currently with stable disease. In case 2, a 59-year-old male diagnosed in 2011 with stage III MTC underwent TTx and bilateral modified lymph node (LN) dissection for cervical LN metastases. Three months later, a positron emission tomography scan revealed hypermetabolic ALNs confirmed by excisional biopsy as metastatic MTC. A completion left
Submitted for publication August 14, 2013 Accepted for publication October 4, 2013 From the Division of Breast/Soft Tissue and Endocrine Surgery, Keck School of Medicine of the University of Southern California, 1510 San Pablo Street, Los Angeles, California. Address correspondence to Dr. Melanie Goldfarb, Assistant Professor of Surgery, Endocrine Surgery, University of Southern California, Keck School of Medicine, 1510 San Pablo Street, Suite 412K, Los Angeles, CA 90033. Email: [email protected]. Published as a Rapid Electronic Article in Press at http://www.endocrine practice.org on November 18, 2013. DOI:10.4158/EP13339.CR To purchase reprints of this article, please visit: www.aace.com/reprints. Copyright © 2014 AACE.
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ALN dissection and supraclavicular LN excision was performed and the patient is currently with stable disease. Results: Sixteen reports of ALN metastases from thyroid cancer exist in the literature: 11 PTC, 2 mucoepidermoid carcinoma variants, and 1 each of follicular thyroid carcinoma, MTC, and poorly differentiated mucin-producing adenocarcinoma. This study reports the second case of MTC metastatic to ALNs. Conclusion: Thyroid cancer ALN metastases are rare representations of distant metastatic disease. Complete surgical resection remains the standard of care for all MTC metastases and for DTC patients with local symptoms or otherwise stable disease that can tolerate the operation. (Endocr Pract. 2014;20:e34-e37) Abbreviations: ALN = axillary lymph node; DTC = differentiated thyroid carcinoma; MTC = medullary thyroid carcinoma; PTC = papillary thyroid carcinoma; TTx = total thyroidectomy Tg = thyroglobulin INTRODUCTION Thyroid carcinomas typically follow an indolent course, with excellent long-term survival rates. However, a small subset exhibit highly malignant behavior. Larger primary tumor size, extracapsular extension, older age, certain histological variants, and distant metastases have all been identified as risk factors for poorer prognosis, often with a cumulative effect (1). Axillary lymph nodes (ALNs) are rarely mentioned as sites of thyroid carcinoma metastases, although 16 case reports have been published describing this finding, as exhibited in Table 1 (2-16). This study contributes two additional cases, including only the second medullary thyroid carcinoma (MTC) metastasis to ALNs ever reported. The cases presented here are compared to those cases reported in the literature.
Abbreviations: ALN = axillary lymph node; B/l = bilateral; CEA = carcinoembryonic antigen; dx = diagnostic scan; FTC = follicular thyroid carcinoma; L = left; MAC = mucinproducing adenocarcinoma; MEC = mucoepidermoid carcinoma; R = right; SCLN = supraclavicular lymph node; SL-i = sialyl Lewisx-i; SMECE = sclerosing mucoepidermoid carcinoma with eosinophilia; Tg = thyroglobulin; TTx = thyroidectomy. *Age at initial diagnosis of thyroid cancer. †Distant metastases include any known sites beyond head and neck soft tissues present at time of ALN metastases. ‡At time of ALN metastases, post designates value after axillary dissections. §Results after axillary dissection, unless otherwise noted.
Table 1 Summary of Reported Cases of Thyroid Carcinomas Metastatic to Axillary Lymph Nodes
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CASE REPORT Case 1 A 56-year-old Bangladeshi female who initially presented with heat intolerance and weight loss underwent total thyroidectomy (TTx) and radioiodine therapy in 2004 for stage IV papillary thyroid carcinoma (PTC) (lung and bone metastases). She was treated in 2008 and 2009 with vascular endothelial growth factor antisense, lapatinib, vinorelbine, and triapine for progression to the liver, followed by treatment with sorafenib in 2011 and 2012 for spread to the chest wall. In 2012, screening mammography detected a right breast mass with subsequent magnetic resonance imaging revealing multiple bulky, enhancing level I ALNs. Fine-needle aspiration biopsy demonstrated metastatic PTC; the corresponding thyroglobulin (Tg) level was 1,859 ng/mL. The patient underwent a right axillary node dissection, with 2 of 28 positive lymph nodes (LNs) showing a well-differentiated follicular variant of PTC. The postsurgical Tg level was 583 ng/mL. The patient was then started on P7170 (a phosphoinositide 3-kinase inhibitor) and has had persistent, stable disease for the past several months. Case 2 A 59-year-old Hispanic male that presented with a painful, enlarging neck mass, weight loss, and diarrhea underwent a TTx and bilateral modified neck dissection in 2011 for stage III MTC (1.8-cm left-sided tumor; 37 of 63 positive left-neck lymph nodes [LNs]; 0 of 92 positive right-neck LNs). The patient’s calcitonin level decreased from 5,237 pg/nL to 687 pg/nL postoperatively, and he was started on vandetanib. Three months later, the patient’s calcitonin levels trended up to 989 pg/nL, at which time an (18F)-fluorodeoxyglucose positron emission tomography/ computed tomography scan revealed hypermetabolic LNs in the left axilla. Excisional biopsy revealed metastatic MTC in 9 of 10 ALNs, at which time the patient’s serum calcitonin level was 2,113 pg/mL. The patient underwent a completion left ALN dissection, with 14 of 40 positive ALNs and excision of the left supraclavicular LNs. The patient’s postoperative calcitonin level was 436 pg/mL. He has had no progression or recurrence for 9 months. DISCUSSION The pathophysiology of thyroid carcinoma metastatic to the axilla remains elusive. Current hypotheses that account for tumor dissemination from the cervical nodal basin to the ALN basin include direct communication between the cervical and axillary lymphatic systems, hematogenous dissemination, or retrograde dissemination to regional lymphatic channels (17). A review of all known cases of thyroid carcinoma metastatic to ALN (Table 1)
supports extensive cervical metastases and/or previous neck dissection in all cases of ALN metastases where this information is documented, which may favor lymphatic over hematogenous spread. Interestingly, the only cases of metastases to ALNs contralateral to a corresponding tumor mass occurred in poorly differentiated tumor variants (11,15), which may support hematologic spread, although given the small number of cases, this could be entirely coincidental. There are no known cases to date in which an ALN metastasis occurred in the absence of extensive cervical disease. Of the 18 cases of thyroid cancer metastatic to ALNs reported to date and detailed in Table 1, differentiated thyroid carcinoma (DTC) was the most common (13 of 18 cases had PTC or follicular thyroid carcinoma), men and women were equally represented, and there was a mix of Tg-producing and non-Tg-producing tumors. All poorly differentiated variants had ALN metastases detected at presentation or within 7 months of diagnosis. Nearly all patients (88.9%) had at least one feature associated with poorer prognosis, including age greater than 45 years at diagnosis, tumor size greater than 4 cm, and/or the presence of multiple sites of distant metastases. Both MTC patients that developed ALNs did so at diagnosis and at 3 months, whereas most DTC patients developed ALN metastases years after diagnosis (mean, 11.8 years; range, 5 to 41 years). Not surprisingly, those patients with worse outcomes tended to have widely metastatic disease at presentation and a lack of known surgical intervention, whereas those who were disease-free at last follow-up had only limited metastases and underwent definitive surgical intervention. CONCLUSION Thyroid cancer metastatic to ALNs is a rare representation of distant metastatic disease. These metastases can present at the time of diagnosis in poorly differentiated tumors and MTC but most commonly develop many years later in DTC patients. Although the exact pathophysiology remains uncertain, surgical resection with a complete axillary dissection is associated with improved outcomes and should likely remain the standard of care for all MTC metastases and for DTC patients with local symptoms or otherwise stable disease that can tolerate the operation (18,19). ACKNOWLEDGMENT Dr. Goldfarb conceived of, designed, and supervised the study. Drs. Goldfarb and Cummings acquired, analyzed, and interpreted the data and wrote the manuscript. Dr. Goldfarb critically revised the manuscript for important intellectual content. The results of this study
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were presented as a poster at the American Association of Clinical Endocrinologists 22nd Annual Scientific and Clinical Congress in Phoenix, Arizona, in May 2013. DISCLOSURE The authors have no multiplicity of interest to disclose. Dr. Goldfarb had full access to all of the data in the study and assumes responsibility for the integrity of the data and the accuracy of the data analysis. REFERENCES 1. Mazzaferri EL, Young RL. Papillary thyroid carcinoma:
a 10 year follow-up report of the impact of therapy in 576 patients. Am J Med. 1981;70:511-518. 2. Elboga U, Kalender E, Yilmaz M, Celen YZ, Aktolun C. Axillary lymph node metastasis of papillary thyroid carcinoma detected by FDG PET/CT in a thyroglobulin-positive patient with negative whole-body 131I scan. Clin Nucl Med. 2012;37:1120-1122. 3. Chiofalo MG, Losito NS, Fulciniti F, et al. Axillary node metastasis from differentiated thyroid carcinoma with Hürthle and signet ring cell differentiation. A case of disseminated thyroid cancer with peculiar histologic findings. BMC Cancer. 2012;12:55. 4. Krishnamurthy A, Vaidhyanathan A. Axillary lymph node metastasis in papillary thyroid carcinoma: report of a case and review of the literature. J Cancer Res Ther. 2011; 7:220-222. 5. Angeles-Angeles A, Chable-Montero F, MartinezBenitez B, Albores-Saavedra J. Unusual metastases of papillary thyroid carcinoma: report of 2 cases. Ann Diagn Pathol. 2009;13:189-196. 6. Kepenekci I, Demirkan A, Cakmak A, Tug T, Ekinci C. Axillary lymph node metastasis as a late manifestation of papillary thyroid carcinoma. Thyroid. 2009;19:417-419. 7. Nakayama H, Wada N, Masudo Y, Rino Y. Axillary lymph node metastasis from papillary thyroid carcinoma: report of a case. Surg Today. 2007;37:311-315.
8. Ers V, Galant C, Malaise J, Rahier J, Daumerie C. Axillary lymph node metastasis in recurrence of papillary thyroid carcinoma: a case report. Wien Klin Wochenschr. 2006;118:124-127. 9. Koike K, Fujii T, Yanaga H, et al. Axillary lymph node recurrence of papillary thyroid microcarcinoma: report of a case. Surg Today. 2004;34:440-443. 10. Shehadeh NJ, Vernick J, Lonardo F, et al. Sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid: a case report and review of the literature. Am J Otolaryngol. 2004;25:48-53. 11. Lal G, Brennan TV, Hambleton J, Clark OH. Coagulopathy, marantic endocarditis, and cerebrovascular accidents as paraneoplastic features in medullary thyroid cancer—case report and review of the literature. Thyroid. 2003;13:601-605. 12. Lal G, Ituarte P, Duh Q, Clark O. The axilla as a rare site of metastatic thyroid cancer with ominous implications. Presented at: 74th annual meeting of the American Thyroid Association, October 10-13, 2002; Los Angeles, CA. 13. Minagawa A, Iitaka M, Suzuki M, et al. A case of primary mucoepidermoid carcinoma of the thyroid: molecular evidence of its origin. Clin Endocrinol (Oxf). 2002;57: 551-556. 14. Ueda S, Takahashi H, Akehi S, Nakata T, Satoh N, Kimura S. A case of recurrent thyroid cancer metastasizing to axillary lymph nodes 7 years after the initial thyroidectomy. J Japanese Pract Surg Soc. 1996;57:2934-2937. 15. Mizukami Y, Nakajima H, Annen Y, Michigishi T, Nonomura A, Nakamura S. Mucin-producing poorly differentiated adenocarcinoma of the thyroid. A case. Pathol Res Pract. 1993;189:608-612; discussion 612-615. 16. Shelley WB, Beerman H, Enterline HT. Metastatic thyroid carcinoma. JAMA. 1973;226:173-174. 17. Sherman SI. Thyroid carcinoma. Lancet 2003;361:501-511. 18. American Thyroid Association Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, Doherty GM, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009;19:1167-1214. 19. Goffredo P, Sosa JA, Roman SA. Differentiated thyroid cancer presenting with distant metastases: a population analysis over two decades. World J Surg. 2013;37:1599-1605.
Amy L. Cummings, MD; Melanie Goldfarb, MD, FACS ABSTRACT Objective: Axillary lymph nodes (ALNs) are a rare manifestation of thyroid carcinoma; only 16 cases are in the published literature. This study adds two additional patients, one involving differentiated papillary thyroid carcinoma (PTC) and one case involving medullary thyroid carcinoma (MTC). The limited information on this topic in the literature is also reviewed. Methods: In case 1, a 56-year-old female diagnosed in 2004 with stage IV PTC (lung and rib metastases) underwent total thyroidectomy (TTx) and received radioiodine and antineoplastics for progression in the lung, liver, and chest wall (2008-2011). In 2012, screening mammography detected multiple axillary masses corresponding to ALNs on magnetic resonance imaging. After fine-needle aspiration biopsy demonstrated metastatic PTC, the patient underwent right ALN dissection and is currently with stable disease. In case 2, a 59-year-old male diagnosed in 2011 with stage III MTC underwent TTx and bilateral modified lymph node (LN) dissection for cervical LN metastases. Three months later, a positron emission tomography scan revealed hypermetabolic ALNs confirmed by excisional biopsy as metastatic MTC. A completion left
Submitted for publication August 14, 2013 Accepted for publication October 4, 2013 From the Division of Breast/Soft Tissue and Endocrine Surgery, Keck School of Medicine of the University of Southern California, 1510 San Pablo Street, Los Angeles, California. Address correspondence to Dr. Melanie Goldfarb, Assistant Professor of Surgery, Endocrine Surgery, University of Southern California, Keck School of Medicine, 1510 San Pablo Street, Suite 412K, Los Angeles, CA 90033. Email: [email protected]. Published as a Rapid Electronic Article in Press at http://www.endocrine practice.org on November 18, 2013. DOI:10.4158/EP13339.CR To purchase reprints of this article, please visit: www.aace.com/reprints. Copyright © 2014 AACE.
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ALN dissection and supraclavicular LN excision was performed and the patient is currently with stable disease. Results: Sixteen reports of ALN metastases from thyroid cancer exist in the literature: 11 PTC, 2 mucoepidermoid carcinoma variants, and 1 each of follicular thyroid carcinoma, MTC, and poorly differentiated mucin-producing adenocarcinoma. This study reports the second case of MTC metastatic to ALNs. Conclusion: Thyroid cancer ALN metastases are rare representations of distant metastatic disease. Complete surgical resection remains the standard of care for all MTC metastases and for DTC patients with local symptoms or otherwise stable disease that can tolerate the operation. (Endocr Pract. 2014;20:e34-e37) Abbreviations: ALN = axillary lymph node; DTC = differentiated thyroid carcinoma; MTC = medullary thyroid carcinoma; PTC = papillary thyroid carcinoma; TTx = total thyroidectomy Tg = thyroglobulin INTRODUCTION Thyroid carcinomas typically follow an indolent course, with excellent long-term survival rates. However, a small subset exhibit highly malignant behavior. Larger primary tumor size, extracapsular extension, older age, certain histological variants, and distant metastases have all been identified as risk factors for poorer prognosis, often with a cumulative effect (1). Axillary lymph nodes (ALNs) are rarely mentioned as sites of thyroid carcinoma metastases, although 16 case reports have been published describing this finding, as exhibited in Table 1 (2-16). This study contributes two additional cases, including only the second medullary thyroid carcinoma (MTC) metastasis to ALNs ever reported. The cases presented here are compared to those cases reported in the literature.
Abbreviations: ALN = axillary lymph node; B/l = bilateral; CEA = carcinoembryonic antigen; dx = diagnostic scan; FTC = follicular thyroid carcinoma; L = left; MAC = mucinproducing adenocarcinoma; MEC = mucoepidermoid carcinoma; R = right; SCLN = supraclavicular lymph node; SL-i = sialyl Lewisx-i; SMECE = sclerosing mucoepidermoid carcinoma with eosinophilia; Tg = thyroglobulin; TTx = thyroidectomy. *Age at initial diagnosis of thyroid cancer. †Distant metastases include any known sites beyond head and neck soft tissues present at time of ALN metastases. ‡At time of ALN metastases, post designates value after axillary dissections. §Results after axillary dissection, unless otherwise noted.
Table 1 Summary of Reported Cases of Thyroid Carcinomas Metastatic to Axillary Lymph Nodes
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CASE REPORT Case 1 A 56-year-old Bangladeshi female who initially presented with heat intolerance and weight loss underwent total thyroidectomy (TTx) and radioiodine therapy in 2004 for stage IV papillary thyroid carcinoma (PTC) (lung and bone metastases). She was treated in 2008 and 2009 with vascular endothelial growth factor antisense, lapatinib, vinorelbine, and triapine for progression to the liver, followed by treatment with sorafenib in 2011 and 2012 for spread to the chest wall. In 2012, screening mammography detected a right breast mass with subsequent magnetic resonance imaging revealing multiple bulky, enhancing level I ALNs. Fine-needle aspiration biopsy demonstrated metastatic PTC; the corresponding thyroglobulin (Tg) level was 1,859 ng/mL. The patient underwent a right axillary node dissection, with 2 of 28 positive lymph nodes (LNs) showing a well-differentiated follicular variant of PTC. The postsurgical Tg level was 583 ng/mL. The patient was then started on P7170 (a phosphoinositide 3-kinase inhibitor) and has had persistent, stable disease for the past several months. Case 2 A 59-year-old Hispanic male that presented with a painful, enlarging neck mass, weight loss, and diarrhea underwent a TTx and bilateral modified neck dissection in 2011 for stage III MTC (1.8-cm left-sided tumor; 37 of 63 positive left-neck lymph nodes [LNs]; 0 of 92 positive right-neck LNs). The patient’s calcitonin level decreased from 5,237 pg/nL to 687 pg/nL postoperatively, and he was started on vandetanib. Three months later, the patient’s calcitonin levels trended up to 989 pg/nL, at which time an (18F)-fluorodeoxyglucose positron emission tomography/ computed tomography scan revealed hypermetabolic LNs in the left axilla. Excisional biopsy revealed metastatic MTC in 9 of 10 ALNs, at which time the patient’s serum calcitonin level was 2,113 pg/mL. The patient underwent a completion left ALN dissection, with 14 of 40 positive ALNs and excision of the left supraclavicular LNs. The patient’s postoperative calcitonin level was 436 pg/mL. He has had no progression or recurrence for 9 months. DISCUSSION The pathophysiology of thyroid carcinoma metastatic to the axilla remains elusive. Current hypotheses that account for tumor dissemination from the cervical nodal basin to the ALN basin include direct communication between the cervical and axillary lymphatic systems, hematogenous dissemination, or retrograde dissemination to regional lymphatic channels (17). A review of all known cases of thyroid carcinoma metastatic to ALN (Table 1)
supports extensive cervical metastases and/or previous neck dissection in all cases of ALN metastases where this information is documented, which may favor lymphatic over hematogenous spread. Interestingly, the only cases of metastases to ALNs contralateral to a corresponding tumor mass occurred in poorly differentiated tumor variants (11,15), which may support hematologic spread, although given the small number of cases, this could be entirely coincidental. There are no known cases to date in which an ALN metastasis occurred in the absence of extensive cervical disease. Of the 18 cases of thyroid cancer metastatic to ALNs reported to date and detailed in Table 1, differentiated thyroid carcinoma (DTC) was the most common (13 of 18 cases had PTC or follicular thyroid carcinoma), men and women were equally represented, and there was a mix of Tg-producing and non-Tg-producing tumors. All poorly differentiated variants had ALN metastases detected at presentation or within 7 months of diagnosis. Nearly all patients (88.9%) had at least one feature associated with poorer prognosis, including age greater than 45 years at diagnosis, tumor size greater than 4 cm, and/or the presence of multiple sites of distant metastases. Both MTC patients that developed ALNs did so at diagnosis and at 3 months, whereas most DTC patients developed ALN metastases years after diagnosis (mean, 11.8 years; range, 5 to 41 years). Not surprisingly, those patients with worse outcomes tended to have widely metastatic disease at presentation and a lack of known surgical intervention, whereas those who were disease-free at last follow-up had only limited metastases and underwent definitive surgical intervention. CONCLUSION Thyroid cancer metastatic to ALNs is a rare representation of distant metastatic disease. These metastases can present at the time of diagnosis in poorly differentiated tumors and MTC but most commonly develop many years later in DTC patients. Although the exact pathophysiology remains uncertain, surgical resection with a complete axillary dissection is associated with improved outcomes and should likely remain the standard of care for all MTC metastases and for DTC patients with local symptoms or otherwise stable disease that can tolerate the operation (18,19). ACKNOWLEDGMENT Dr. Goldfarb conceived of, designed, and supervised the study. Drs. Goldfarb and Cummings acquired, analyzed, and interpreted the data and wrote the manuscript. Dr. Goldfarb critically revised the manuscript for important intellectual content. The results of this study
e37
were presented as a poster at the American Association of Clinical Endocrinologists 22nd Annual Scientific and Clinical Congress in Phoenix, Arizona, in May 2013. DISCLOSURE The authors have no multiplicity of interest to disclose. Dr. Goldfarb had full access to all of the data in the study and assumes responsibility for the integrity of the data and the accuracy of the data analysis. REFERENCES 1. Mazzaferri EL, Young RL. Papillary thyroid carcinoma:
a 10 year follow-up report of the impact of therapy in 576 patients. Am J Med. 1981;70:511-518. 2. Elboga U, Kalender E, Yilmaz M, Celen YZ, Aktolun C. Axillary lymph node metastasis of papillary thyroid carcinoma detected by FDG PET/CT in a thyroglobulin-positive patient with negative whole-body 131I scan. Clin Nucl Med. 2012;37:1120-1122. 3. Chiofalo MG, Losito NS, Fulciniti F, et al. Axillary node metastasis from differentiated thyroid carcinoma with Hürthle and signet ring cell differentiation. A case of disseminated thyroid cancer with peculiar histologic findings. BMC Cancer. 2012;12:55. 4. Krishnamurthy A, Vaidhyanathan A. Axillary lymph node metastasis in papillary thyroid carcinoma: report of a case and review of the literature. J Cancer Res Ther. 2011; 7:220-222. 5. Angeles-Angeles A, Chable-Montero F, MartinezBenitez B, Albores-Saavedra J. Unusual metastases of papillary thyroid carcinoma: report of 2 cases. Ann Diagn Pathol. 2009;13:189-196. 6. Kepenekci I, Demirkan A, Cakmak A, Tug T, Ekinci C. Axillary lymph node metastasis as a late manifestation of papillary thyroid carcinoma. Thyroid. 2009;19:417-419. 7. Nakayama H, Wada N, Masudo Y, Rino Y. Axillary lymph node metastasis from papillary thyroid carcinoma: report of a case. Surg Today. 2007;37:311-315.
8. Ers V, Galant C, Malaise J, Rahier J, Daumerie C. Axillary lymph node metastasis in recurrence of papillary thyroid carcinoma: a case report. Wien Klin Wochenschr. 2006;118:124-127. 9. Koike K, Fujii T, Yanaga H, et al. Axillary lymph node recurrence of papillary thyroid microcarcinoma: report of a case. Surg Today. 2004;34:440-443. 10. Shehadeh NJ, Vernick J, Lonardo F, et al. Sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid: a case report and review of the literature. Am J Otolaryngol. 2004;25:48-53. 11. Lal G, Brennan TV, Hambleton J, Clark OH. Coagulopathy, marantic endocarditis, and cerebrovascular accidents as paraneoplastic features in medullary thyroid cancer—case report and review of the literature. Thyroid. 2003;13:601-605. 12. Lal G, Ituarte P, Duh Q, Clark O. The axilla as a rare site of metastatic thyroid cancer with ominous implications. Presented at: 74th annual meeting of the American Thyroid Association, October 10-13, 2002; Los Angeles, CA. 13. Minagawa A, Iitaka M, Suzuki M, et al. A case of primary mucoepidermoid carcinoma of the thyroid: molecular evidence of its origin. Clin Endocrinol (Oxf). 2002;57: 551-556. 14. Ueda S, Takahashi H, Akehi S, Nakata T, Satoh N, Kimura S. A case of recurrent thyroid cancer metastasizing to axillary lymph nodes 7 years after the initial thyroidectomy. J Japanese Pract Surg Soc. 1996;57:2934-2937. 15. Mizukami Y, Nakajima H, Annen Y, Michigishi T, Nonomura A, Nakamura S. Mucin-producing poorly differentiated adenocarcinoma of the thyroid. A case. Pathol Res Pract. 1993;189:608-612; discussion 612-615. 16. Shelley WB, Beerman H, Enterline HT. Metastatic thyroid carcinoma. JAMA. 1973;226:173-174. 17. Sherman SI. Thyroid carcinoma. Lancet 2003;361:501-511. 18. American Thyroid Association Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, Doherty GM, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009;19:1167-1214. 19. Goffredo P, Sosa JA, Roman SA. Differentiated thyroid cancer presenting with distant metastases: a population analysis over two decades. World J Surg. 2013;37:1599-1605.
