Thyroid Cancer. With 51 Figures and 30 Tables. Springer

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1 H.-J. Biersack F. Griinwald (Eds.) Thyroid Cancer With 51 Figures and 30 Tables Springer

2 PART 1 Basics 1 The Changing Epidemiology of Thyroid Cancer 3 R. GORGES 1.1 Basic Epidemiological Problems in Thyroid Cancer General Epidemiological Data for Thyroid Cancer Prognosis Thyroid Malignancies with Special Features Papillary Microcarcinoma Hiirthle Cell Carcinoma Tall Cell Variant of Papillary Thyroid Cancer Poorly Differentiated (Insular) Thyroid Carcinoma Anaplastic Carcinoma Medullary Thyroid Carcinoma Thyroid Lymphoma Secondary Tumors Changes in Epidemiology Summary 20 References 20 2 Histopathology, Immunohistochemistry, and Molecular Biology 27 F. HOFSTADTER 2.1 Introduction Principles of Histopathological Diagnosis and Classification The Rules and Their Problems Papillary Carcinoma Follicular Carcinoma Anaplastic (Undifferentiated) Carcinoma Medullary (C-cell) Carcinoma Histopathology and Prognosis Histopathology and Prognostic Scores Histological Subtypes Influencing Prognosis 34

3 VIII Contents 2.4 Histo/Cytopathology in Preoperative and Intraoperative Diagnosis (Problem of Frozen Section) Auxiliary Techniques (Cytometry, Immunohistochemistry, Molecular Pathology) Preoperative Diagnosis (Fine Needle Aspiration Biopsy, FNAB) Prognosis Pathogenesis Anatomical Histogenesis Molecular Pathogenesis Genetics Malignant Transformation Mechanisms of Invasion and Metastasis Cell Cycle Regulation Cytogenetics and Clonality Receptor Activation Telomerase 45 References 45 3 Familial Differentiated Carcinoma of the Thyroid 55 M.R. CARLISLE and I.R. MCDOUGALL 3.1 Introduction Etiology of Non-Medullary Thyroid Cancers Could "Familial" Thyroid Cancers Be a Chance Finding? Association Between Thyroid Cancer and Familial Cancer Syndromes Molecular Genetics of Familial Thyroid Cancer Mode of Inheritance Natural History of Familial Thyroid Cancer Clinical Implications of Familial Differentiated Thyroid Cancer Primary Treatment Screening of Families 63 References 63 4 The Diagnosis of Thyroid Cancer 69 C. REINERS 4.1 Prevalence/Risk Assessment Findings/Symptoms Ultrasonography Scintigraphy Fine-Needle Aspiration Biopsy Additional Diagnostic Procedures 77 References 78

4 IX 5 The Current Surgical Approach to Non-Medullary Thyroid Cancer 81 O. GIMM and H. DRALLE 5.1 Introduction Prognostic Factors Surgical Treatment Technique Primary Therapy Thyroid Gland Extrathyroidal Tumor Extension Lymph Nodes Distant Metastases Completion Thyroidectomy Recurrent Disease 87 References 87 PART 2 Differentiated Thyroid Cancer 6 Radioiodine Therapy for Thyroid Cancer 93 M. DIETLEIN, D. MOKA, and H. SCHICHA 6.1 Introduction Radioiodine Ablation and Radioiodine Therapy Ablation of Residual Thyroid Tissue Ablative Dose In Which Patients Is Ablation Unnecessary? Radioiodine Therapy for Thyroid Cancer Radioiodine Therapy with Negative Radioiodine Scan Radioiodine Therapy in Patients on Maintenance Hemodialysis Prognostic Factors and Therapeutic Strategies in Metastatic Thyroid Cancer Lymph Node Metastases Pulmonary Metastases Bone Metastases Brain Metastases Locally Invasive Thyroid Cancer Optimizing the Therapeutic and Diagnostic Capabilities of 131 I Thyroid-Stimulating Hormone Stimulation Administration of Recombinant Human Thyrotropin Low-Iodine Diet Optimal Diagnostic Scan Dose 110

5 6.4.5 Redifferentiation Therapy and Future Therapeutic Options Ill Lithium Ill Further Optimization of 131 I Imaging Ill Diuretic-Enhanced 131 I Clearance Side Effects of 131 I Therapy Radiation Thyroiditis Painless Neck Edema Sialadenitis Taste Dysfunction Gastrointestinal Symptoms Testicular Function and Male Fertility Ovarian Function and Female Fertility Pregnancy Outcome Bone Marrow Suppression Leukemia Solid Tumors Pulmonary Fibrosis Neurologic Complications Parathyroid Dysfunction Radiation Considerations in the Treatment of Thyroid Cancer 117 References Percutaneous Radiation Therapy 121 C. PUSKAS, M. BlERMANN, N. WlLLICH, and O. SCHOBER 7.1 Surgical Therapy and Lymph Node Staging Lymph Node Status and Prognosis Indications for External Radiotherapy Gross Residual Disease and Local Recurrence Distant Metastases Anaplastic Carcinoma Adjuvant Radiotherapy Radiation Treatment Protocols Side Effects ; Review Studies Demonstrating No Beneficial Effect of Percutaneous Radiotherapy Studies Demonstrating Beneficial Effects of Percutaneous Radiotherapy Inauguration of a Prospective Multicenter Trial 128 References 128

6 XI 8 Thyroid Cancer: Treatment with Thyroid Hormone 131 P.-M. SCHUMM-DRAEGER 8.1 Introduction Rationale of Thyroid Hormone Therapy Effects on Thyroid Growth Effects on Differentiation of Thyroid Cells Optimal Level of TSH Suppression in Patients with Differentiated Thyroid Cancer Treatment with Thyroid Hormones Pharmacology of Thyroid Hormones (Levothyroxine, L-T4) Optimal Dosage and Adjustment of L-T4 in Thyroid Cancer Patients According to Disease Status Important Side Effects of L-T4 Suppressive Therapy Side Effects of L-T4 Therapy: Bone Side Effects of L-T4 Therapy: Heart Conclusion 136 References Treatment with Cytotoxic Drugs 139 B.SALLER 9.1 Introduction Results of Chemotherapy in Differentiated Thyroid Carcinoma Monotherapy Combination Chemotherapy Results of Chemotherapy in Poorly Differentiated and Anaplastic Thyroid Carcinoma Chemotherapy Combined Modality Treatment Treatment Protocols Including Chemotherapy with Single Cytotoxic Drugs Treatment Protocols Including Combination Chemotherapy Drugs with In Vitro Anti-Tumor Effects Mechanisms of Resistance Against Cytotoxic Drugs Future Directions in Chemotherapy of Thyroid Cancer, Current Suggestions for Management 148 References 149

7 XII Contents 10 Redifferentiation Therapy of Thyroid Carcinomas with Retinoic Acid 153 D. SIMON 10.1 Introduction Biological Effects of Retinoic Acids Retinoids in Cancer Treatment Thyroid-Specific Effects of Retinoids Thyroid-Specific Functions Differentiation Proliferation Basis for Therapeutic Approach Results of a Clinical Pilot Study Conclusion and Perspectives 159 References Follow-up of Patients with Well-Differentiated Thyroid Cancer 165 B. SHAPIRO and M.D. GROSS 11.1 Introduction The Follow-up of Patients with Thyroid Cancer Assessing the Risk of Morbidity and Mortality Postoperative Evaluation of Thyroid Cancer Postoperative Laboratory Evaluation and Imaging Radioiodine Other Agents Used to Image Thyroid Cancer Thyroglobulin Follow-up Therapy After Thyroidectomy Ablation of Thyroid Remnants Follow-up Intervals After Successful Ablation Thyroid Hormone Replacement in the Thyroid Cancer Patient Radioiodine Therapy for Recurrent/ Metastatic Thyroid Cancer Radioiodine-Negative Thyroid Cancer Summary 177 References Functional Imaging of Thyroid Cancer 181 F. GRUNWALD 12.1 Introduction Tracers Thallium Chloride MIBI and Other 99m Tc-Labeled Tracers F-Fluorodeoxyglucose nl In-Octreotide 185

8 XIII 12.3 Clinical Use of Functional Imaging Presurgical Evaluation Postsurgical Treatment and Follow-up 186 References Magnetic Resonance Imaging 193 J.H. RISSE 13.1 Introduction Principles of MRI Physical and Technical Basis The Magnetic Signal Image Generation: What Are TR and TE, and Tl and T2? Further Contrast Modifications: Fat Saturation and Contrast Media Safety Safety in the Magnetic Field Safety of Contrast Media Contraindications Protocol Recommendations for Thyroid Cancer Follow-up Hardware Sequences Planes Covered Anatomic Regions Our Protocol Normal MR Anatomy of the Neck, Thyroid, and Upper Mediastinum Normal Anatomy Neck Compartments Thyroid and Parathyroid Glands Salivary Glands Lymphatic Drainage Upper Anterior Mediastinum Inconspicuous Anatomy After Thyroidectomy Pathologic Changes Primary Thyroid Cancer Thyroid Remnants Recurrent Thyroid Cancer Pathologic Lymph Nodes Distant Metastases Accidental Pathologic Findings 220 References 222

9 XIV Contents 14 Thyroid Cancer in Chernobyl Children 225 C. REINERS, J. BIKO, E.P. DEMIDCHIK, and V. DROZD 14.1 Experiences from the Past The Chernobyl Accident Thyroid Cancer in Belarus After Chernobyl Treatment of Thyroid Cancer in Children from Belarus Patients Protocol Results of Treatment Discussion and Conclusions 231 References 233 PART 3 Medullary Thyroid Cancer 15 Diagnosis of Medullary Thyroid Cancer 239 F. RAUE 15.1 Introduction Classification and Epidemiology Pathology and Biochemical Markers Genetic Abnormalities Clinical Syndrome and Diagnostic Procedure Sporadic Medullary Thyroid Carcinoma Hereditary Medullary Thyroid Carcinoma Pheochromocytoma Primary Hyperparathyroidism Multiple Endocrine Neoplasia Type 2B Natural History and Prognostic Factors 247 References Imaging in Medullary Thyroid Cancer 251 T.M. BEHR and W. BECKER 16.1 Introduction Diagnosis and Localization of the Medullary Thyroid Primary Tumor; Presurgical Staging Imaging and Disease Localization in the Follow-up of Patients with MTC Conventional Radiological Techniques (Ultrasonography, X-ray, Computed Tomography, Magnetic Resonance Imaging, Bone Scanning) Traditional Scintigraphic Techniques [ 201 Tl Chloride, 99m Tc.( V )-DMSA, 123 ' 131 I-MIBG, etc.] 258

10 XV Modern Nuclear Medical Techniques (Anti-CEA Immunoscintigraphy, Somatostatin Receptor Scintigraphy, Positron Emission Tomography) Future Developments: Will Cholecystokinin-B/ Gastrin Receptor Scintigraphy Allow for More Sensitive Staging of MTC? Conclusion 270 References Therapy for Medullary Thyroid Cancer 275 O. GIMM and H. DRALLE 17.1 Introduction Sporadic Versus Familial Medullary Thyroid Carcinoma Therapy Surgical Treatment Thyroid Gland Lymph Node Metastases Distant Metastases Reoperation Special Therapeutic Considerations in Familial MTC Thyroid Gland Lymph Node Metastases Nonsurgical Treatment Modalities Octreotide Radioactive Iodine External Radiation Chemotherapy Psychological Support 282 References Follow-up of Medullary Thyroid Cancer 285 T. SCHILLING and R. ZIEGLER 18.1 Distinction Between Sporadic and Familial Form of Medullary Thyroid Cancer Survival in Patients Suffering from Medullary Thyroid Cancer Sporadic Form of Medullary Thyroid Cancer Calcitonin as a Tumor Marker During Follow-up Testing the Result of the Primary Operation Follow-up in General Follow-up in Patients with No Detectable Calcitonin Postoperatively Follow-up in Patients with Detectable Calcitonin Postoperatively 290

11 XVI Contents Adjuvant Therapy Familial Form of Medullary Thyroid Cancer (Multiple Endocrine Neoplasia Type 2) Screening for Pheochromocytoma and Timing of Surgery Screening for Primary Hyperparathyroidism 292 References 293 Subject Index 295

Glutathione S-transferase, alterations 146 Goiter multinodular 210

Glutathione S-transferase, alterations 146 Goiter multinodular 210 Subject Index A Ablation (see also radioiodine ablation) - follow-up intervals after successful 174 Aclarubicin 140 Adenomatous polyposis, familial 58, 59 Adenovirus, p53-expressing 147 Adrenalectomy 292