VOLUME 33 䡠 NUMBER 32 䡠 NOVEMBER 10 2015
JOURNAL OF CLINICAL ONCOLOGY
Intraluminal Superior Vena Cava Metastasis in a Patient With Poorly Differentiated Thyroid Carcinoma Introduction Poorly differentiated thyroid carcinoma (PDTC) is a clinical entity that exists on the spectrum between well-differentiated thyroid carcinoma (WDTC) and anaplastic thyroid carcinoma (ATC). The role of nuclear imaging in the management of PDTC is evolving. Approximately 85% of PDTCs are able to concentrate radioactive iodine (RAI).1 It is postulated that as the disease dedifferentiates, its ability to concentrate RAI may be lost, but its ability to take up fluorodeoxyglucose (FDG) increases.2 Hence, throughout the course of an individual patient’s illness, the use of various imaging modalities may change. We report a case of poorly differentiated thyroid carcinoma with an intraluminal superior vena cava metastasis diagnosed by FDG– positron emission tomography (PET). Case Report In 2009, a 75-year-old woman presented with symptomatic anemia and during investigation developed rapidly progressive dysphagia. Her medical history included type II diabetes mellitus, hypertension, and depression. Ultrasonography of her thyroid showed multiple poorly defined nodules and enlarged cervical lymph nodes. The overall appearance favored malignancy. She required partial left hemithyroidectomy for airway protection. Histology revealed thyroid transcription factor 1–positive, thyroglobulin-positive, poorly differentiated primary thyroid carcinoma with infiltration of adjacent soft tissue/muscle. Postoperative thyroid scan revealed right-sided residual functioning thyroid tissue. Computed tomography (CT) chest, abdomen/pelvis, and brain revealed no distant metastatic disease but showed a residual right thyroid mass. The patient underwent urgent postoperative radiotherapy to the right thyroid lobe (50 Gy in 25 fractions) with near-complete resolution of the mass. A completion thyroidectomy was performed and histology revealed a small focus of papillary carcinoma and a bizarre follicular adenoma. Her postoperative serum thyroglobulin level was elevated (4,512 g/L), which prompted a whole-body iodine-123 scan. This revealed two foci of residual uptake: one in the right thyroid bed, and a second in either a remnant of the thyroglossal tract or a separate cervical lymph node. Radioactive iodine was administered (4 GBq iodine-131). Six months later, the patient developed progressive cough, voice change, stridor, and dysphagia. Serum thyroglobulin level had increased to 5,437.4 g/L. An iodine-123 scan showed no evidence of local recurrence or distant metastases. Magnetic resonance imaging of the neck and thoracic inlet revealed an adducted right vocal cord and nonspecific changes consistent with previous radiotherapy. FDG-PET scan showed multiple metabolically active subcentimeter lung nodJournal of Clinical Oncology, Vol 33, No 32 (November 10), 2015: pp e119-e121
D I A G N O S I S
I N
O N C O L O G Y
ules and an intensely avid 22 ⫻ 24 ⫻ 63–mm superior vena cava (SVC) mass (Figs 1 and 2). Subsequent CT SVC venogram confirmed an intraluminal mass (Fig 3) and multiple pulmonary nodules. The mass was treated with radiotherapy (30 Gy in 10 fractions) with improvement in the patient’s symptoms and reduction in her thyroglobulin level to 422.9 g/L. Repeat CT revealed residual 7-mm intraluminal lesion extending from the brachiocephalic vein through to the SVC. Repeat FDG-PET scan showed complete metabolic response in the SVC metastasis. Discussion PDTCs are a heterogeneous group of tumors that fall between WDTC and ATC in terms of their morphology and biologic behavior. The 5-year survival of PDTC is 60% to 85%, lower than that of WDTC but far superior to that of ATC.3 PDTC accounts for 4% to 7% of thyroid cancers; it is more common in women and typically presents between the ages 55 and 64 years.3
Fig 1.
© 2014 by American Society of Clinical Oncology
Downloaded from jco.ascopubs.org on November 15, 2015. For personal use only. No other uses without permission. Copyright © 2015 American Society of Clinical Oncology. All rights reserved.
e119
Murphy et al
Fig 2.
PDTC was first described in 1983 and gained official recognition as a separate clinical entity when it was included in the WHO classification of thyroid tumors in 2004.4,5 In 2006, an international consensus meeting of thyroid pathologists produced the Turin proposal, a definition of PDTC based on its morphology, growth patterns, and presence of high-grade features.6 More recent research identified RAS mutations as the predominant molecular alteration in PDTC, setting it farther apart from WDTC.7,8 Despite this, there is still no unifying set of diagnostic criteria by which PDTC is defined. The difficulty defining PDTC has contributed to a lack of consensus regarding optimal assessment and treatment of this disease. The majority of patients have locally advanced disease at diagnosis and, ideally, total thyroidectomy with lymph node dissection is firstline management.2,3,9 A definite role for external-beam radiotherapy (EBRT) or systemic treatment with RAI or chemotherapy has not been established. On the basis of a 2007 literature review, Sanders et al10 recommend that EBRT be considered in patients with tumors larger than 4 cm, extrathyroidal extension, or lymph node metastases.10 EBRT has not been shown to improve overall survival, but it may have a role in controlling local disease in patients with incomplete resection or unresectable disease.2-4 In our case, EBRT was used successfully to control residual disease in the right thyroid before completion thyroidectomy and later to treat the symptomatic intraluminal
Fig 3. e120
© 2014 by American Society of Clinical Oncology
SVC metastasis. PDTC has a higher rate of distant relapse than WDTC and as such may warrant systemic treatment after initial surgery.11 Distant metastases are present in 37% of patients at diagnosis and will develop in more than 50% of patients over the course of their disease.9 Most deaths result from metastases, and although treatment with RAI has not been shown to increase survival, it may help to control distant disease.2,3,9,12 The role of chemotherapy is based largely on studies of ATC and has not been established in the management of PDTC. Benefit has only been seen in isolated case reports or short case series.13,14 In this case, the development of a symptomatic SVC metastasis was paralleled by an increase in serum thyroglobulin. Despite this, our patient’s RAI scan was negative, and FDG-PET was required to identify the site of her recurrence. False-negative RAI scans occur and likely result from tumor dedifferentiation with subsequent loss of the iodine symporter.2 FDG-PET is able to detect distant metastases in 71% of patients with a history of PDTC, increasing thyroglobulin levels and negative RAI imaging.15 FDG-PET is also useful in planning radiotherapy and assessing response to treatment.16 PDTCs usually metastasizes to lung, bone, and brain. Intravascular metastases from thyroid cancers are rare, with only a handful of cases reported in the literature.17-20 This case underscores the use of FDG-PET in localizing disease when there is a high suspicion of recurrence and negative RAI imaging.
Caitlin Murphy Albury Base Hospital, Albury, New South Wales; Border Medical Oncology, Wodonga, Victoria, Australia
Heinrich Schwalb Albury Base Hospital, Albury, New South Wales, Australia
Sam Berlangieri Austin Hospital, Heidelberg, Victoria, Australia
Richard Eek Albury Base Hospital, Albury, New South Wales; Border Medical Oncology, Wodonga, Victoria, Australia
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest. REFERENCES 1. Patel KN, Shaha AR: Poorly differentiated and anaplastic thyroid cancer. Cancer Control 13:119-127, 2006 2. Hannallah J, Rose J, Guerrero MA: Comprehensive literature review: Recent advances in diagnosing and managing patients with poorly differentiated thyroid carcinoma. Int J Endocr 2013:317487, 2013 3. Pacini F, Castagna MG, Brilli L, et al: Thyroid cancer: ESMO clinical practice guidelines for diagnosis, treatment, and follow-up. Ann Oncol 23:vii110-vii119, 2012 4. Sakamoto A, Kasai N, Sugano H: Poorly differentiated carcinoma of the thyroid: A clinicopathologic entity for a high-risk group of papillary and follicular carcinomas. Cancer 52:1849-1855, 1983 5. Volante M, Papotti M: Poorly differentiated thyroid carcinoma: 5 years after the 2004 classification of endocrine tumours. Endocr Pathol 21:1-6, 2010 6. Volante M, Collini P, Nikiforov YE, et al: Poorly differentiated thyroid carcinoma: The Turin proposal for the use of uniform diagnostic criteria and an algorithmic diagnostic approach. Am J Surg Pathol 31:1256-1264, 2007 7. Volante M, Rapa I, Papotti M: Poorly differentiated thyroid carcinoma: Diagnostic features and controversial issues. Endocr Pathol 19:150-155, 2008 8. Volante M, Rapa I, Gandhi M, et al: RAS mutations are the predominant molecular alteration in poorly differentiated thyroid carcinomas and bear prognostic impact. J Clin Endocrinol Metab 94:4735-4741, 2009 9. Ibrahimpasic T, Ghossein R, Carlson D, et al: Poorly differentiated thyroid carcinoma presenting with gross extrathyroidal extension: 1986-2009 Memorial Sloan-Kettering Cancer Centre experience. Thyroid 23:997-1002, 2013 JOURNAL OF CLINICAL ONCOLOGY
Downloaded from jco.ascopubs.org on November 15, 2015. For personal use only. No other uses without permission. Copyright © 2015 American Society of Clinical Oncology. All rights reserved.
Diagnosis in Oncology
10. Sanders EM Jr, LiVolsi VA, Brierley J, et al: An evidence-based review of poorly differentiated thyroid cancer. World J Surg 31:934-945, 2007 11. Katsuhiro T, Sonoo J, Saito W, et al: Analysis of clinical outcome of patients with poorly differentiated thyroid carcinoma. ISRN Endocrinol 2011:308029, 2011 12. Jung TS, Kim TY, Kim KW, et al: Clinical features and prognostic factors for survival in patients with poorly differentiated thyroid carcinoma and comparison to the patients with aggressive variants of papillary thyroid carcinoma. Endocr J 54:265-274, 2007 13. Crouzeix G, Michels JJ, Sevin E, et al: Unusual short-term complete response to two regimens of cytotoxic chemotherapy in a patient with poorly differentiated thyroid carcinoma. J Clin Endocr Metab 97:3046-3050, 2012 14. Siironen P, Hagstro¨m J, Ma¨enp¨a¨a H, et al: Anaplastic and poorly differentiated thyroid carcinoma: Therapeutic strategies and treatment outcome of 52 consecutive patients. Oncology 79:400-408, 2010 15. Wang W, Larson SM, Fazzari M, et al: Prognostic value of [18F]fluorodeoxyglucose positron emission tomographic scanning in patients with thyroid cancer. J Clin Endocr Metab 85:1107-1113, 2008
16. Abraham T, Scho¨der H: Thyroid cancer: Indications and opportunities for positron emission tomography/computed tomography imaging. Semin Nucl Med 41:121-138, 2011 17. Choi SH, Chung KW, Min HS, et al: Intravascular metastasis at the internal jugular vein from follicular thyroid carcinoma. J Ultrasound Med 29:659-662, 2010 18. Bertoldi EG, Severo MD, Scheffel RS, et al: Left atrial metastases of poorly differentiated thyroid carcinoma diagnosed by echocardiography and magnetic resonance imaging: Case report and review of literature. Echocardiography 29:E30-E33, 2012 19. Osborne RF, Zandifar H, Gupta R: Thyroid carcinoma with intravascular metastasis to the internal jugular vein. Ear Nose Throat J 90:568-570, 2011 20. Stickel JS, Mayer F, Vollmer JP, et al: Ventricular thrombus and thrombocytopaenia as first presentation anaplastic thyroid carcinoma. J Clin Oncol 31:e194-e196, 2013
DOI: 10.1200/JCO.2013.51.8753; published online ahead of print at www.jco.org on April 21, 2014
■ ■ ■
www.jco.org
© 2014 by American Society of Clinical Oncology
Downloaded from jco.ascopubs.org on November 15, 2015. For personal use only. No other uses without permission. Copyright © 2015 American Society of Clinical Oncology. All rights reserved.
e121
JOURNAL OF CLINICAL ONCOLOGY
Intraluminal Superior Vena Cava Metastasis in a Patient With Poorly Differentiated Thyroid Carcinoma Introduction Poorly differentiated thyroid carcinoma (PDTC) is a clinical entity that exists on the spectrum between well-differentiated thyroid carcinoma (WDTC) and anaplastic thyroid carcinoma (ATC). The role of nuclear imaging in the management of PDTC is evolving. Approximately 85% of PDTCs are able to concentrate radioactive iodine (RAI).1 It is postulated that as the disease dedifferentiates, its ability to concentrate RAI may be lost, but its ability to take up fluorodeoxyglucose (FDG) increases.2 Hence, throughout the course of an individual patient’s illness, the use of various imaging modalities may change. We report a case of poorly differentiated thyroid carcinoma with an intraluminal superior vena cava metastasis diagnosed by FDG– positron emission tomography (PET). Case Report In 2009, a 75-year-old woman presented with symptomatic anemia and during investigation developed rapidly progressive dysphagia. Her medical history included type II diabetes mellitus, hypertension, and depression. Ultrasonography of her thyroid showed multiple poorly defined nodules and enlarged cervical lymph nodes. The overall appearance favored malignancy. She required partial left hemithyroidectomy for airway protection. Histology revealed thyroid transcription factor 1–positive, thyroglobulin-positive, poorly differentiated primary thyroid carcinoma with infiltration of adjacent soft tissue/muscle. Postoperative thyroid scan revealed right-sided residual functioning thyroid tissue. Computed tomography (CT) chest, abdomen/pelvis, and brain revealed no distant metastatic disease but showed a residual right thyroid mass. The patient underwent urgent postoperative radiotherapy to the right thyroid lobe (50 Gy in 25 fractions) with near-complete resolution of the mass. A completion thyroidectomy was performed and histology revealed a small focus of papillary carcinoma and a bizarre follicular adenoma. Her postoperative serum thyroglobulin level was elevated (4,512 g/L), which prompted a whole-body iodine-123 scan. This revealed two foci of residual uptake: one in the right thyroid bed, and a second in either a remnant of the thyroglossal tract or a separate cervical lymph node. Radioactive iodine was administered (4 GBq iodine-131). Six months later, the patient developed progressive cough, voice change, stridor, and dysphagia. Serum thyroglobulin level had increased to 5,437.4 g/L. An iodine-123 scan showed no evidence of local recurrence or distant metastases. Magnetic resonance imaging of the neck and thoracic inlet revealed an adducted right vocal cord and nonspecific changes consistent with previous radiotherapy. FDG-PET scan showed multiple metabolically active subcentimeter lung nodJournal of Clinical Oncology, Vol 33, No 32 (November 10), 2015: pp e119-e121
D I A G N O S I S
I N
O N C O L O G Y
ules and an intensely avid 22 ⫻ 24 ⫻ 63–mm superior vena cava (SVC) mass (Figs 1 and 2). Subsequent CT SVC venogram confirmed an intraluminal mass (Fig 3) and multiple pulmonary nodules. The mass was treated with radiotherapy (30 Gy in 10 fractions) with improvement in the patient’s symptoms and reduction in her thyroglobulin level to 422.9 g/L. Repeat CT revealed residual 7-mm intraluminal lesion extending from the brachiocephalic vein through to the SVC. Repeat FDG-PET scan showed complete metabolic response in the SVC metastasis. Discussion PDTCs are a heterogeneous group of tumors that fall between WDTC and ATC in terms of their morphology and biologic behavior. The 5-year survival of PDTC is 60% to 85%, lower than that of WDTC but far superior to that of ATC.3 PDTC accounts for 4% to 7% of thyroid cancers; it is more common in women and typically presents between the ages 55 and 64 years.3
Fig 1.
© 2014 by American Society of Clinical Oncology
Downloaded from jco.ascopubs.org on November 15, 2015. For personal use only. No other uses without permission. Copyright © 2015 American Society of Clinical Oncology. All rights reserved.
e119
Murphy et al
Fig 2.
PDTC was first described in 1983 and gained official recognition as a separate clinical entity when it was included in the WHO classification of thyroid tumors in 2004.4,5 In 2006, an international consensus meeting of thyroid pathologists produced the Turin proposal, a definition of PDTC based on its morphology, growth patterns, and presence of high-grade features.6 More recent research identified RAS mutations as the predominant molecular alteration in PDTC, setting it farther apart from WDTC.7,8 Despite this, there is still no unifying set of diagnostic criteria by which PDTC is defined. The difficulty defining PDTC has contributed to a lack of consensus regarding optimal assessment and treatment of this disease. The majority of patients have locally advanced disease at diagnosis and, ideally, total thyroidectomy with lymph node dissection is firstline management.2,3,9 A definite role for external-beam radiotherapy (EBRT) or systemic treatment with RAI or chemotherapy has not been established. On the basis of a 2007 literature review, Sanders et al10 recommend that EBRT be considered in patients with tumors larger than 4 cm, extrathyroidal extension, or lymph node metastases.10 EBRT has not been shown to improve overall survival, but it may have a role in controlling local disease in patients with incomplete resection or unresectable disease.2-4 In our case, EBRT was used successfully to control residual disease in the right thyroid before completion thyroidectomy and later to treat the symptomatic intraluminal
Fig 3. e120
© 2014 by American Society of Clinical Oncology
SVC metastasis. PDTC has a higher rate of distant relapse than WDTC and as such may warrant systemic treatment after initial surgery.11 Distant metastases are present in 37% of patients at diagnosis and will develop in more than 50% of patients over the course of their disease.9 Most deaths result from metastases, and although treatment with RAI has not been shown to increase survival, it may help to control distant disease.2,3,9,12 The role of chemotherapy is based largely on studies of ATC and has not been established in the management of PDTC. Benefit has only been seen in isolated case reports or short case series.13,14 In this case, the development of a symptomatic SVC metastasis was paralleled by an increase in serum thyroglobulin. Despite this, our patient’s RAI scan was negative, and FDG-PET was required to identify the site of her recurrence. False-negative RAI scans occur and likely result from tumor dedifferentiation with subsequent loss of the iodine symporter.2 FDG-PET is able to detect distant metastases in 71% of patients with a history of PDTC, increasing thyroglobulin levels and negative RAI imaging.15 FDG-PET is also useful in planning radiotherapy and assessing response to treatment.16 PDTCs usually metastasizes to lung, bone, and brain. Intravascular metastases from thyroid cancers are rare, with only a handful of cases reported in the literature.17-20 This case underscores the use of FDG-PET in localizing disease when there is a high suspicion of recurrence and negative RAI imaging.
Caitlin Murphy Albury Base Hospital, Albury, New South Wales; Border Medical Oncology, Wodonga, Victoria, Australia
Heinrich Schwalb Albury Base Hospital, Albury, New South Wales, Australia
Sam Berlangieri Austin Hospital, Heidelberg, Victoria, Australia
Richard Eek Albury Base Hospital, Albury, New South Wales; Border Medical Oncology, Wodonga, Victoria, Australia
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest. REFERENCES 1. Patel KN, Shaha AR: Poorly differentiated and anaplastic thyroid cancer. Cancer Control 13:119-127, 2006 2. Hannallah J, Rose J, Guerrero MA: Comprehensive literature review: Recent advances in diagnosing and managing patients with poorly differentiated thyroid carcinoma. Int J Endocr 2013:317487, 2013 3. Pacini F, Castagna MG, Brilli L, et al: Thyroid cancer: ESMO clinical practice guidelines for diagnosis, treatment, and follow-up. Ann Oncol 23:vii110-vii119, 2012 4. Sakamoto A, Kasai N, Sugano H: Poorly differentiated carcinoma of the thyroid: A clinicopathologic entity for a high-risk group of papillary and follicular carcinomas. Cancer 52:1849-1855, 1983 5. Volante M, Papotti M: Poorly differentiated thyroid carcinoma: 5 years after the 2004 classification of endocrine tumours. Endocr Pathol 21:1-6, 2010 6. Volante M, Collini P, Nikiforov YE, et al: Poorly differentiated thyroid carcinoma: The Turin proposal for the use of uniform diagnostic criteria and an algorithmic diagnostic approach. Am J Surg Pathol 31:1256-1264, 2007 7. Volante M, Rapa I, Papotti M: Poorly differentiated thyroid carcinoma: Diagnostic features and controversial issues. Endocr Pathol 19:150-155, 2008 8. Volante M, Rapa I, Gandhi M, et al: RAS mutations are the predominant molecular alteration in poorly differentiated thyroid carcinomas and bear prognostic impact. J Clin Endocrinol Metab 94:4735-4741, 2009 9. Ibrahimpasic T, Ghossein R, Carlson D, et al: Poorly differentiated thyroid carcinoma presenting with gross extrathyroidal extension: 1986-2009 Memorial Sloan-Kettering Cancer Centre experience. Thyroid 23:997-1002, 2013 JOURNAL OF CLINICAL ONCOLOGY
Downloaded from jco.ascopubs.org on November 15, 2015. For personal use only. No other uses without permission. Copyright © 2015 American Society of Clinical Oncology. All rights reserved.
Diagnosis in Oncology
10. Sanders EM Jr, LiVolsi VA, Brierley J, et al: An evidence-based review of poorly differentiated thyroid cancer. World J Surg 31:934-945, 2007 11. Katsuhiro T, Sonoo J, Saito W, et al: Analysis of clinical outcome of patients with poorly differentiated thyroid carcinoma. ISRN Endocrinol 2011:308029, 2011 12. Jung TS, Kim TY, Kim KW, et al: Clinical features and prognostic factors for survival in patients with poorly differentiated thyroid carcinoma and comparison to the patients with aggressive variants of papillary thyroid carcinoma. Endocr J 54:265-274, 2007 13. Crouzeix G, Michels JJ, Sevin E, et al: Unusual short-term complete response to two regimens of cytotoxic chemotherapy in a patient with poorly differentiated thyroid carcinoma. J Clin Endocr Metab 97:3046-3050, 2012 14. Siironen P, Hagstro¨m J, Ma¨enp¨a¨a H, et al: Anaplastic and poorly differentiated thyroid carcinoma: Therapeutic strategies and treatment outcome of 52 consecutive patients. Oncology 79:400-408, 2010 15. Wang W, Larson SM, Fazzari M, et al: Prognostic value of [18F]fluorodeoxyglucose positron emission tomographic scanning in patients with thyroid cancer. J Clin Endocr Metab 85:1107-1113, 2008
16. Abraham T, Scho¨der H: Thyroid cancer: Indications and opportunities for positron emission tomography/computed tomography imaging. Semin Nucl Med 41:121-138, 2011 17. Choi SH, Chung KW, Min HS, et al: Intravascular metastasis at the internal jugular vein from follicular thyroid carcinoma. J Ultrasound Med 29:659-662, 2010 18. Bertoldi EG, Severo MD, Scheffel RS, et al: Left atrial metastases of poorly differentiated thyroid carcinoma diagnosed by echocardiography and magnetic resonance imaging: Case report and review of literature. Echocardiography 29:E30-E33, 2012 19. Osborne RF, Zandifar H, Gupta R: Thyroid carcinoma with intravascular metastasis to the internal jugular vein. Ear Nose Throat J 90:568-570, 2011 20. Stickel JS, Mayer F, Vollmer JP, et al: Ventricular thrombus and thrombocytopaenia as first presentation anaplastic thyroid carcinoma. J Clin Oncol 31:e194-e196, 2013
DOI: 10.1200/JCO.2013.51.8753; published online ahead of print at www.jco.org on April 21, 2014
■ ■ ■
www.jco.org
© 2014 by American Society of Clinical Oncology
Downloaded from jco.ascopubs.org on November 15, 2015. For personal use only. No other uses without permission. Copyright © 2015 American Society of Clinical Oncology. All rights reserved.
e121
