UPDATES IN THE UNDERSTANDING AND MANAGEMENT OF THYROID CANCER Edited by Thomas J. Fahey Updates in the Understanding and Management of Thyroid Cancer Edited by Thomas J. Fahey Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2012 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. 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Publishing Process Manager Masa Vidovic Technical Editor Teodora Smiljanic Cover Designer InTech Design Team First published March, 2012 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechopen.com Updates in the Understanding and Management of Thyroid Cancer, Edited by Thomas J. Fahey p. cm. ISBN 978-953-51-0299-1 Contents Chapter 1 An Epidemiological Analysis of Thyroid Cancer in a Spanish Population: Presentation, Incidence and Survival 1 A. Rego-Iraeta, L. Pérez-Mendez and R.V. García-Mayor Chapter 2 The Functionality of p53 in Thyroid Cancer 33 Debolina Ray, Matthew T. Balmer and Susannah Gal Chapter 3 Glycosylation and Glycoproteins in Thyroid Cancer: A Potential Role for Diagnostics 53 Anna Krześlak, Paweł Jóźwiak and Anna Lipińska Chapter 4 Insulin-Like Growth Factor Receptor Signaling in Thyroid Cancers: Clinical Implications and Therapeutic Potential 91 Geetika Chakravarty and Debasis Mondal Chapter 5 Principles and Application of Microarray Technology in Thyroid Cancer Research 119 Walter Pulverer, Christa Noehammer, Klemens Vierlinger and Andreas Weinhaeusel Chapter 6 Evaluation and Management of Pediatric Thyroid Nodules 147 Melanie Goldfarb and John I. Lew Chapter 7 Papillary Thyroid Cancer in Childhood and Adolescence with Specific Consideration of Patients After Radiation Exposure 163 Yuri Demidchik, Mikhail Fridman, Kurt Werner Schmid, Christoph Reiners, Johannes Biko and Svetlana Mankovskaya Chapter 8 Thyroid Cancer in the Pediatric Population 189 Silva Frieda, Nieves-Rivera Francisco and Laguna Reinaldo VI Contents Chapter 9 Current Innovations and Opinions in the Surgical Management of Differentiated Thyroid Carcinoma 199 Brian Hung-Hin Lang Chapter 10 Sentinel Lymph Node Biopsy in Well Differentiated Thyroid Cancer 217 Tamara Mijovic, Keith Richardson, Richard J. Payne and Jacques How Chapter 11 Preparing Patients for Radioiodine Treatment: Increasing Thyroid Cell Uptake and Accelerating the Excretion of Unbound Radioiodine 235 Milovan Matović Chapter 12 Differentiation Therapy in Thyroid Carcinoma 251 Eleonore Fröhlich and Richard Wahl Chapter 13 Using γ-Camera to Evaluate the In Vivo Biodistributions and Internal Medical Dosimetries of Iodine-131 in Thyroidectomy Patients 283 Sheng-Pin Changlai, Tom Changlai and Chien-Yi Chen Chapter 14 Thyroid Cancer: The Evolution of Treatment Options 295 Hitoshi Noguchi 1 An Epidemiological Analysis of Thyroid Cancer in a Spanish Population: Presentation, Incidence and Survival A. Rego-Iraeta, L. Pérez-Mendez and R.V. García-Mayor Department of Endocrinology, Diabetes, Nutrition and Metabolism, University Hospital of Vigo Spain 1. Introduction Accurate statistics on cancer occurrence and outcome are essential both for the purposes of research and for planning and evaluation programmes for cancer control (Parkin, 2006). Although tumours of thyroid account for only 1% of the overall human cancer burden, they represent the most common malignancies of the endocrine system and pose a significant challenge to pathologists, surgeons and endocrinologists. Among epithelial tumors, carcinomas of follicular cell origin far outnumber those of C-cell origin. The vast majority of carcinomas of follicular cell origin are indolent malignancies with 10 year survivals in excess of 90 %. 1.1 Classification Thyroid follicular epithelial-derived cancers are divided into three categories: papillary cancer, follicular cancer and anaplastic cancer. Papillary and follicular cancers are considered differentiated cancers, and patients with these tumours are often treated similarly despite numerous biologic differences. Most anaplastic (undifferentiated) cancers appear to arise from differentiated cancers. Other malignant diseases of the thyroid include medullary thyroid cancer (which can be familial, either as part of the multiple endocrine neoplasia type 2 syndrome or isolated familial medullary thyroid cancer), primary thyroid lymphoma, or metastases from breast, colon, or renal cancer or melanoma. In countries with adequate iodine intake, differentiated thyroid cancer accounts for more than 85% of all cases, being the most common type papillary (60-80%). Tumor histology is a critical determinant of patient outcomes; differentiated thyroid cancer is associated with the best survival rate and medullary and anaplastic have significantly poorer outcomes (Hundahl et al., 1998). Certain subtypes, such as the tall and columnar cell variants of papillary cancer and the insular variant of follicular cancer are more common in older patients with higher stage disease and have a worse prognosis than usual forms of thyroid cancer. The traditional separation of thyroid cancer into the major groups of papillary, follicular, medullary and undifferentiated (anaplastic) carcinoma, based on morphology and clinical Updates in the Understanding and Management of Thyroid Cancer 2 features, is strongly supported by advances in molecular studies showing the involvement of distinct genes in these four groups, with little overlap (DeLellis & Williams, 2004). 1.2 Staging and prognostic factors Numerous staging systems have been created in an attempt to accurately prognosticate outcomes for individual patients; two careful studies have compared the efficacy of the various staging systems and found that none is superior (Brierley et al., 1997; Sherman et al., 1998). Consequently, the European Thyroid Association (ETA) (Pacini et al., 2006) and the American Thyroid Association (ATA) (Cooper et al., 2009) have recommended the use of the Tumour, Node, Metastasis (TNM) classification of the American Joint Commission on Cancer (AJCC) and the International Union Against Cancer because it is universally available and widely accepted for other disease sites. An interesting feature of the TNM staging system compared to other classifications is the age factor. While the staging of head and neck cancers relies exclusively in the anatomical extent of disease, it is not possible to follow this pattern for the particular group of malignant tumors that arise in the thyroid gland. The effect of age is such significance in behavior and prognosis, that both the histologic diagnosis and the age of the patient are included in the staging system for these tumors. The AJCC classification is based on the TNM system, which relies on assessing three components: (1) extent of the primary tumour (T), (2) absence or presence of regional lymph node metastases (N), and (3) absence or presence of distant metastases (M). The fifth edition (Fleming et al., 1997), (Table 1) was revised as the sixth edition (Greene et al., 2002), (Table 2). A major alteration was the reclassification of tumour staging (T). For differentiated (papillary and follicular) and medullary tumours confined to the parenchyma of the thyroid gland without extrathyroidal extension, there is no evidence to suggest that using a size cut- off of 1 cm provides better prognostic stratification compared with the 2-cm cut-off used for Papillary or Follicular Medullary Anaplastic Stage Age < 45 years Age > 45 years Any age I Any T Any N M0 T1 N0 M0 T1 N0 M0 II Any T Any N M1 T2 N0 M0 T3 N0 M0 T2 N0 M0 T3 N0 M0 T4 N0 M0 III T4 N0 M0 Any T N1 M0 Any T N1 M0 IV Any T Any N M1 Any T Any N M0 Any T Any N Any M Table 1. AJCC TNM classification for thyroid cancer (fifth edition). T1 - Tumor 1 cm or less in greatest dimension limited to the thyroid. T2 - Tumour more than 1 cm, but not more than 4 cm, in greatest dimension limited to the thyroid. T3 - Tumour more than 4 cm in greatest dimension limited to the thyroid. T4 - Tumour of any size extending beyond the thyroid capsule. T4a - Excluded. T4b - Excluded. Regional lymph nodes are the cervical and upper mediastinal lymph nodes. N1a - Metastasis in ipsilateral cervical lymph node(s). N1b - Metastasis in bilateral, midline, or contralateral cervical or mediastinal lymph node (s). M0- no distance metastases; M1- distance metastases. [...]... displays the overall (males and females) crude incidence rates of thyroid cancer in relation to the histological types; the increase in the incidence of thyroid cancer over the three periods of time was primarily due to an increase in papillary cancer incidence After the second period, the incidence of follicular cancer decreased and there was no significant change in the incidence of MTC and anaplastic cancer. .. al in USA (Mitchell et al., 2007), examined trends in surgical therapy for thyroid cancer They hypothesized that if a true increase occurs in the incidence of thyroid cancer, then thyroidectomy, as the primary treatment for thyroid cancer, should also increase during the same period This study reported a regional difference in the incidence of thyroid cancer with an increase in Northeastern and Southern... medullary and papillary cancers of the thyroid Anaplastic cancer and Hürthle cells occurred at older ages Of the total of thyroid cancers, 78.3% of the cases were females and 21.7% outstanding men This female predominance is maintained in all histologic types (Table 4) 10 Updates in the Understanding and Management of Thyroid Cancer 3.1.3 Pathologic Tumor-Node-Metastases (pTNM) distribution Altogether,... than in clinical cancer; they were not related to iodine intake and were exclusively of the papillary type (MPTC) It suggests that a large proportion of the population probably lives with undetected thyroid cancer and fits with the hypothesis of an apparent increase in thyroid cancer incidence Any interpretation of reports of the incidence of papillary thyroid carcinoma must take into account the remarkably... similar to that found in areas with high iodine intake, with a clear predominance of differentiated thyroid carcinoma and a high ratio of papillary to follicular carcinomas As in many other regions and countries, the incidence of thyroid cancer is increasing and this trend is primarily caused by an increase in the incidence of papillary type Our data showing an increase in papillary cancers larger than... crude incidences and ASR show an increasing trend over time In comparison with other European countries, our ASR in the final period of time, 1994-2001, (8.2 per 100,000-year in women and 2.65 in men) is similar to the reports from our 20 Updates in the Understanding and Management of Thyroid Cancer neighbouring countries such as Portugal, France and Italy and is higher than that reported by the IARC... incidence seen in our area together with the good prognosis of this neoplasia can explain the increase in the prevalence of thyroid cancer These data should be taken into account when planning health resources for the management of these patients In the present study, we also performed an analysis of cause–specific survival in our patients diagnosed of thyroid cancer between 1978-2001 In the case of deceased... high prevalence of MPTC in thyroids removed for reasons other than thyroid cancer and in autopsy series (Hedinger & Sobin 1988) In this sense, it is noteworthy, that many cancer registries do not specify the contribution of MPTC to the incidence of thyroid cancer, so differences in the inclusion criteria can cause mistakes in the comparison of the incidences (Teppo & Hakulinen 1998) For these reasons... analyzed the incidence of MPTC and the incidence of papillary cancer not including MPTC (Papillary non MPTC) In the present investigation, we found 245 cases of papillary cancer, of which 95 cases (38.7 %) were MPTC carcinomas (pT1) Remarkably, most of these tumours (91%) were detected incidentally after thyroid surgery performed for reasons other than thyroid cancer Although the incidence of MPTC is increasing... Time trend of thyroid cancer presentation (1978-2001) 3.2 Trends in thyroid surgery A total of 2345 thyroidectomies were performed during the studied period During this period the percentage of the population undergoing a thyroid surgery significantly increased from 13.76 per 100,000 each year (95% CI 12.35–14.56) to 23.83 (95% CI 22.17– 12 Updates in the Understanding and Management of Thyroid Cancer . UPDATES IN THE UNDERSTANDING AND MANAGEMENT OF THYROID CANCER Edited by Thomas J. Fahey Updates in the Understanding and Management of Thyroid Cancer Edited by Thomas. survival for this cancer in EUROCARE-2. Denmark, Germany, The Netherlands, Updates in the Understanding and Management of Thyroid Cancer 6 England, Scotland, Wales and the countries of Eastern. 78.3% of the cases were females and 21.7% outstanding men. This female predominance is maintained in all histologic types (Table 4). Updates in the Understanding and Management of Thyroid Cancer