Thyroid Cancer

by Biersack, H. J.; Grunwald, F.

• ISBN13: 9783540223092
• ISBN10: 3540223096
• Edition: 2nd
• Format: Hardcover
• Copyright: 2005-08-15
• Publisher: Springer Verlag

Summary

Thyroid Cancer describes all current diagnostic techniques, including FDG-PET and MRI. In recent years these modalities have documented hitherto hidden radioiodine-negative metastases, thus improving surgical therapy. The whole gamut of treatment, including surgery, radioiodine therapy, percutaneous radiation therapy and medical management, is covered. In some 10% of differentiated thyroid cancers, the well-known treatment tools of surgery and radioiodine therapy are not sufficient. New treatment modalities such as high-dose radioiodine therapy, redifferentiation therapy with retinoic acid and recombinant TSH are therefore highlighted. In a special section devoted to medullary thyroid cancer, new imaging procedures such as octreotide scintigraphy are described. The second edition includes two new chapters, on I-124 PET and dosimetry. Other chapters have been modified particularly in view of the new UICC classification, with special regard to the definition of T1 tumors.

Table of Contents

PART I Basics
1 The Changing Epidemiology of Thyroid Cancer	3	(26)
R. GÖRGES
1.1 Basic Epidemiological Problems in Thyroid Cancer	3	(3)
1.2 General Epidemiological Data for Thyroid Cancer	6	(3)
1.3 Prognosis	9	(2)
1.4 Thyroid Malignancy Entities with Special Features	11	(5)
1.4.1 Papillary Micro carcinoma	11	(1)
1.4.2 Hürthle Cell Carcinoma	12	(1)
1.4.3 Histological Variants of Papillary Thyroid Cancer	13	(1)
1.4.4 Poorly Differentiated (Insular) Thyroid Carcinoma	14	(1)
1.4.5 Anaplastic Carcinoma	14	(1)
1.4.6 Medullary Thyroid Carcinoma	15	(1)
1.4.7 Thyroid Lymphoma	15	(1)
1.4.8 Secondary Tumors	16	(1)
1.5 Changes in Epidemiology	16	(4)
1.6 Summary	20	(1)
References	21	(8)
2 Histopathology, Immunohistochemistry, and Molecular Biology	29	(28)
F. HOFSTÄDTER
2.1 Introduction	29	(1)
2.2 Principles of Histopathological Diagnosis and Classification	29	(5)
2.2.1 The Rules and Their Problems	29	(1)
2.2.2 Papillary Carcinoma	30	(1)
2.2.3 Follicular Carcinoma	31	(2)
2.2.4 Anaplastic (Undifferentiated) Carcinoma	33	(1)
2.2.5 Medullary (C-cell) Carcinoma	33	(1)
2.3 Histopathology and Prognosis	34	(5)
2.3.1 Histopathology and Prognostic Scores	34	(2)
2.3.2 Histological Subtypes Influencing Prognosis	36	(3)
2.4 Histo/Cytopathology in Preoperative and Intraoperative Diagnosis (Problem of Frozen Section)	39	(1)
2.5 Auxiliary Techniques (Cytometry, Immunohistochemistry, Molecular Pathology)	39	(1)
2.6 Preoperative Diagnosis (Fine Needle Aspiration Biopsy)	40	(1)
2.7 Prognosis	41	(1)
2.8 Pathogenesis	42	(6)
2.8.1 Anatomical Histogenesis	43	(1)
2.8.2 Molecular Pathogenesis	43	(1)
2.8.2.1 Genetics	43	(1)
2.8.2.2 Malignant Transformation	44	(1)
2.8.2.3 Mechanisms of Invasion and Metastasis	46	(1)
2.8.2.4 Cell Cycle Regulation	46	(1)
2.8.2.5 Cytogenetics and Clonality	47	(1)
2.8.2.6 Receptor Activation	48	(1)
2.8.2.7 Telomerase	48	(1)
References	48	(9)
3 Familial Differentiated Carcinoma of the Thyroid	57	(14)
M.R. CARLISLE and I.R. MCDOUGALL
3.1 Introduction	57	(1)
3.2 Etiology of Non-Medullary Thyroid Cancers	57	(2)
3.3 Could "Familial" Thyroid Cancers Be a Chance Finding?	59	(1)
3.4 Genetics and Associated Syndromes	60	(5)
3.4.1 Molecular Genetics of Familial Thyroid Cancer	62	(2)
3.4.2 Natural History of Familial Thyroid Cancer	64	(1)
3.5 Clinical Implications of Familial Nonmedullary Thyroid Cancer	65	(1)
3.5.1 Primary Treatment	65	(1)
3.5.2 Screening of Families	65	(1)
References	66	(5)
4 The Diagnosis of Thyroid Cancer	71	(12)
C. REINERS
4.1 Prevalence/Risk Assessment	71	(1)
4.2 Findings/Symptoms	71	(1)
4.3 Ultrasonography	72	(1)
4.4 Scintigraphy	73	(3)
4.5 Fine-Needle Aspiration Biopsy	76	(3)
4.6 Additional Diagnostic Procedures	79	(1)
References	80	(3)
5 The Current Surgical Approach to Non-Medullary Thyroid Cancer	83	(12)
O. GIMM and H. DRALLE
5.1 Introduction	83	(1)
5.2 Prognostic Factors	84	(1)
5.3 Surgical Treatment	85	(4)
5.3.1 Technique	85	(1)
5.3.2 Primary Therapy	85	(1)
5.3.2.1 Thyroid Gland	85	(1)
5.3.2.1.1 Differentiated Thyroid Carcinoma	85	(1)
5.3.2.1.2 Undifferentiated Thyroid Carcinoma	86	(1)
5.3.2.1.3 Rare Types of Thyroid Cancer	87	(1)
5.3.2.2 Extrathyroidal Tumor Extension	87	(1)
5.3.2.3 Lymph Nodes	88	(1)
5.3.2.4 Distant Metastases	88	(1)
5.3.3 Completion Thyroidectomy	89	(1)
5.3.4 Recurrent Disease	89	(1)
References	89	(6)
PART II Differentiated Thyroid Cancer
6 Radioiodine Therapy for Thyroid Cancer	95	(32)
M. DIETLEIN, D. MOKA, and H. SCHICHA
6.1 Introduction	95	(1)
6.2 Radioiodine Ablation and Radioiodine Therapy	96	(7)
6.2.1 Ablation of Residual Thyroid Tissue	96	(1)
6.2.2 Ablative Dose	97	(3)
6.2.3 In Which Patients Is Ablation Unnecessary?	100	(1)
6.2.4 Radioiodine Therapy for Thyroid Cancer	101	(1)
6.2.5 Radioiodine Therapy with Negative Radioiodine Scan	101	(1)
6.2.6 Radioiodine Therapy in Patients on Maintenance Hemodialysis	102	(1)
6.3 Prognostic Factors and Therapeutic Strategies in Metastatic Thyroid Cancer	103	(7)
6.3.1 Lymph Node Metastases	103	(1)
6.3.2 Pulmonary Metastases	104	(2)
6.3.3 Bone Metastases	106	(2)
6.3.4 Brain Metastases	108	(1)
6.3.5 Locally Invasive Thyroid Cancer	109	(1)
6.4 Optimizing the Therapeutic and Diagnostic Capabilities of ¹³¹I	110	(6)
6.4.1 Thyroid-Stimulating Hormone Stimulation	110	(1)
6.4.2 Administration of Recombinant Human Thyrotropin	110	(2)
6.4.3 Low-Iodine Diet	112	(1)
6.4.4 Optimal Diagnostic Scan Dose	113	(1)
6.4.5 Redifferentiation Therapy and Future Therapeutic Options	114	(1)
6.4.6 Lithium	115	(1)
6.4.7 Further Optimization of ¹³¹I Imaging	115	(1)
6.4.8 Diuretic-Enhanced ¹³¹I Clearance	116	(1)
6.5 Side Effects of ¹³¹I Therapy	116	(6)
6.5.1 Radiation Thyroiditis	116	(1)
6.5.2 Painless Neck Edema	116	(1)
6.5.3 Sialadenitis	116	(1)
6.5.4 Taste Dysfunction	117	(1)
6.5.5 Gastrointestinal Symptoms	117	(1)
6.5.6 Testicular Function and Male Fertility	118	(1)
6.5.7 Ovarian Function and Female Fertility	118	(1)
6.5.8 Pregnancy Outcome	118	(1)
6.5.9 Bone Marrow Suppression	119	(1)
6.5.10 Leukemia	119	(1)
6.5.11 Solid Tumors	120	(1)
6.5.12 Pulmonary Fibrosis	120	(1)
6.5.13 Neurologic Complications	121	(1)
6.5.14 Parathyroid Dysfunction	121	(1)
6.5.15 Lacrimal Gland Dysfunction	121	(1)
6.6 Radiation Considerations in the Treatment of Thyroid Cancer	122	(1)
References	122	(5)
7 124I Positron Emission Tomographic Dosimetry and Positron Emission Tomography/Computed Tomography Imaging in Differentiated Thyroid Cancer	127	(12)
L.S. FREUDENBERG, A. BOCKISCH, and W. JENTZEN
7.1 Introduction	127	(1)
7.2 124I Characteristics	128	(1)
7.3 Metastases Dosimetry Using 124I PET	128	(4)
7.4 PET/CT Imaging with 124I	132	(4)
7.5 Conclusions	136	(1)
References	137	(2)
8 External Beam Radiotherapy	139	(24)
M. BIERMANN, M.K. PIXBERG, A. SCHUCK, N. WILLICH, A. HEINECKE, and O. SCHOBER
8.1 Introduction	139	(1)
8.2 Methods	139	(1)
8.2.1 Literature Search	139	(1)
8.2.2 Statistical Analysis	140	(1)
8.3 Results	140	(15)
8.3.1 Literature Search	140	(8)
8.3.2 Methodological Quality of the Studies	148	(1)
8.3.3 Rationale of RTx	149	(2)
8.3.4 RTx Protocol	151	(1)
8.3.5 Retrospective Studies	151	(1)
8.3.6 Prospective Studies	152	(1)
8.3.7 Toxicity	153	(1)
8.3.8 Guidelines	153	(2)
8.4 Discussion	155	(1)
References	156	(7)
9 Thyroid Cancer: Treatment with Thyroid Hormone	163	(8)
P.-M. SCHUMM-DRAEGER
9.1 Introduction	163	(1)
9.2 Rationale of Thyroid Hormone Therapy	163	(1)
9.3 Effects on Thyroid Growth	164	(1)
9.4 Effects on Differentiation of Thyroid Cells	164	(1)
9.5 Optimal Level of TSH Suppression in Patients with Differentiated Thyroid Cancer	164	(1)
9.6 Treatment with Thyroid Hormones	165	(1)
9.7 Pharmacology of Thyroid Hormones (Levothyroxine, L-T4)	165	(1)
9.8 Optimal Dosage and Adjustment of L-T4 in Thyroid Cancer Patients According to Disease Status	166	(1)
9.9 Important Side Effects of L-T4 Suppressive Therapy	167	(1)
9.9.1 Side Effects of L-T4 Therapy: Bone	167	(1)
9.9.2 Side Effects of L-T4 Therapy: Heart	168	(1)
9.10 Conclusion	168	(1)
References	168	(3)
10 Treatment with Cytotoxic Drugs	171	(1)
B. SALLER
10.1 Introduction	171	(1)
10.2 Results of Chemotherapy in Differentiated Thyroid Carcinoma	171	(3)
10.2.1 Monotherapy	171	(1)
10.2.2 Combination Chemotherapy	172	(1)
10.2.2.1 Doxorubicin and Cisplatin	172	(1)
10.2.2.2 Doxorubicin and Bleomicin	173	(1)
10.2.2.3 Doxorubicin and other Cytotoxic Drugs	174	(1)
10.3 Results of Chemotherapy in Poorly Differentiated and Anaplastic Thyroid Carcinoma	174	(3)
10.3.1 Chemotherapy	174	(2)
10.3.2 Combined Modality Treatment	176	(1)
10.3.2.1 Treatment Protocols Including Chemotherapy with Single Cytotoxic Drugs	176	(1)
10.3.2.2 Treatment Protocols Including Combination Chemotherapy	176	(1)
10.4 Drugs with In Vitro Anti-Tumor Effects	177	(1)
10.5 Mechanisms of Resistance Against Cytotoxic Drugs	178	(2)
10.5.1 Overexpression of P-glycoprotein and Multidrug Resistance-Associated Protein	179	(1)
10.5.2 Alterations of DNA Topoisomerases	179	(1)
10.5.3 Alterations of Glutathione and Glutathione S-transferases	180	(1)
10.5.4 Control of Apoptosis	180	(1)
10.6 Future Directions in Chemotherapy of Thyroid Cancer	180	(1)
10.7 Current Suggestions for Management	181	(2)
10.7.1 Differentiated Thyroid Cancer	181	(2)
10.7.2 Poorly Differentiated and Anaplastic Thyroid Carcinoma	183	(1)
References	183	(4)
11 Redifferentiation Therapy of Thyroid Carcinomas with Retinoic Acid	187	(1)
D. SIMON
11.1 Introduction	187	(1)
11.2 Biological Effects of Retinoic Acids	188	(1)
11.3 Retinoids in Cancer Treatment	188	(1)
11.4 Thyroid-Specific Effects of Retinoids	189	(1)
11.4.1 Thyroid-Specific Functions	189	(1)
11.4.2 Differentiation	190	(1)
11.4.3 Proliferation	190	(1)
11.5 Basis for Therapeutic Approach	190	(1)
11.6 Results of a Clinical Pilot Study	191	(2)
11.7 Conclusion and Perspectives	193	(1)
References	194	(5)
12 Follow-up of Patients with Well-Differentiated Thyroid Cancer	199	(1)
B. SHAPIRO, J. FREITAS, and M. GROSS
12.1 Introduction	199	(1)
12.2 The Follow-up of Patients with Thyroid Cancer	199	(16)
12.2.1 Assessing the Risk of Morbidity and Mortality	199	(3)
12.2.2 Postoperative Evaluation of Thyroid Cancer	202	(1)
12.2.3 Postoperative Laboratory Evaluation and Imaging	203	(1)
12.2.3.1 Radioiodine	203	(1)
12.2.3.2 Other Agents Used to Image Thyroid Cancer	206	(1)
12.2.3.3 Thyroglobulin	208	(1)
12.2.4 Follow-up Therapy After Thyroidectomy	209	(1)
12.2.4.1 Ablation of Thyroid Remnants	209	(1)
12.2.4.2 Follow-up Intervals After Successful Ablation	211	(1)
12.2.4.3 Thyroid Hormone Replacement in the Thyroid Cancer Patient	212	(1)
12.2.4.4 Radioiodine Therapy for Recurrent/Metastatic Thyroid Cancer	212	(1)
12.2.4.5 Radioiodine-Negative Thyroid Cancer	213	(2)
12.3 Summary	215	(1)
References	216	(5)
13 Thyroglobulin as Specific Tumor Marker in Differentiated Thyroid Cancer	221	(1)
R. GÖRGES and A. BOCKISCH
13.1 Introduction	221	(2)
13.2 Thyroglobulin Measurement: Methodology and Problems	223	(3)
13.3 Diagnostic Value of Thyroglobulin in the Spectrum of Follow-Up Methods	226	(1)
13.4 Tg Measurement Under Exogenous TSH Stimulation	227	(3)
13.5 Ultrasensitive Thyroglobulin Measurement	230	(2)
13.6 Thyroglobulin Messenger RNA as Alternative Tumor Marker	232	(1)
References	232	(7)
14 Functional Imaging of Thyroid Cancer	239	(1)
F. GRÜNWALD
14.1 Introduction	239	(1)
14.2 Tracers	239	(4)
14.2.1 Thallium Chloride	239	(1)
14.2.2 MIBI and Other 99mTc-Labeled Tracers	240	(1)
14.2.3 18F-Fluorodeoxyglucose	240	(2)
14.2.4 ¹¹¹F-Octreotide	242	(1)
14.3 Clinical Use of Functional Imaging	243	(4)
14.3.1 Presurgical Evaluation	243	(1)
14.3.2 Postsurgical Treatment and Follow-up	244	(3)
References	247	(4)
15 Magnetic Resonance Imaging	251	(1)
J.H. Riss
15.1 Introduction	251	(1)
15.2 Principles of MRI	252	(9)
15.2.1 Physical and Technical Basis of MRI	252	(1)
15.2.1.1 The Magnetic Signal	252	(1)
15.2.1.2 Image Generation: What Are TR and TE? What are T1 and T2?	253	(1)
15.2.1.3 Further Contrast Modifications: Fat Saturation and Contrast Media	255	(1)
15.2.1.3.1 Fat Saturation	255	(1)
15.2.1.3.2 Contrast Media	256	(1)
15.2.2 Safety	257	(1)
15.2.2.1 Safety in the Magnetic Field	257	(1)
15.2.2.2 Safety of Contrast Media	258	(1)
15.2.2.3 Contraindications	258	(1)
15.2.3 Protocol Recommendations for Thyroid Cancer Follow-up	259	(1)
15.2.3.1 Hardware	259	(1)
15.2.3.2 Sequences	259	(1)
15.2.3.3 Planes	260	(1)
15.2.3.4 Covered Anatomic Regions	260	(1)
15.2.3.5 Our Protocol	260	(1)
15.3 Normal MR Anatomy of the Neck, Thyroid, and Upper Mediastinum	261	(6)
15.3.1 Normal Anatomy	261	(1)
15.3.1.1 Neck Compartments	261	(1)
15.3.1.2 Thyroid and Parathyroid Glands	264	(1)
15.3.1.3 Salivary Glands	265	(1)
15.3.1.4 Lymphatic Drainage	266	(1)
15.3.1.5 Upper Anterior Mediastinum	267	(1)
15.3.2 Inconspicuous Anatomy After Thyroidectomy	267	(1)
15.4 Pathologic Changes	267	(13)
15.4.1 Primary Thyroid Cancer	270	(1)
15.4.2 Thyroid Remnants	271	(1)
15.4.3 Recurrent Thyroid Cancer	272	(1)
15.4.4 Pathologic Lymph Nodes	272	(5)
15.4.5 Distant Metastases	277	(1)
15.4.6 Accidental Pathologic Findings	277	(3)
References	280	(3)
16 Thyroid Cancer in Chernobyl Children	283	(1)
C. REINERS, J. BIKO, E.P. DEMIDCHIK, and V. DROZD
16.1 Experiences from the Past	283	(1)
16.2 The Chernobyl Accident	284	(1)
16.3 Thyroid Cancer in Belarus After Chernobyl	284	(2)
16.4 Treatment of Thyroid Cancer in Children from Belarus	286	(3)
16.4.1 Patients	287	(1)
16.4.2 Protocol	288	(1)
16.4.3 Results of Treatment	288	(1)
16.5 Discussion and Conclusions	289	(2)
References	291	(6)
PART III Medullary Thyroid Cancer
17 Diagnosis of Medullary Thyroid Cancer	297	(60)
F. RAUE and K. FRANK-RAUE
17.1 Introduction	297	(1)
17.2 Classification and Epidemiology	297	(1)
17.3 Pathology and Biochemical Markers	298	(1)
17.4 Genetic Abnormalities	299	(3)
17.5 Clinical Syndrome and Diagnostic Procedure	302	(4)
17.5.1 Sporadic Medullary Thyroid Carcinoma	302	(1)
17.5.2 Hereditary Medullary Thyroid Carcinoma	303	(1)
17.5.2.1 Pheochromocytoma	305	(1)
17.5.2.2 Primary Hyperparathyroidism	305	(1)
17.5.2.3 Multiple Endocrine Neoplasia Type 2B	306	(1)
17.6 Natural History and Prognostic Factors	306	(1)
References	306	(5)
18 Imaging in Medullary Thyroid Cancer	311	(1)
T.M. BEHR and W. BECKER
18.1 Introduction	311	(1)
18.2 Diagnosis and Localization of the Medullary Thyroid Primary Tumor; Presurgical Staging	312	(4)
18.3 Imaging and Disease Localization in the Follow-up of Patients with MTC	316	(10)
18.3.1 Conventional Radiological Techniques (Ultrasonography, X-ray, Computed Tomography, Magnetic Resonance Imaging, Bone Scanning)	316	(2)
18.3.2 Traditional Scintigraphic Techniques [201Tl Chloride, 99mTc-(V)-DMSA, ¹²³/¹³¹-MIBG, etc.]	318	(3)
18.3.3 Modern Nuclear Medical Techniques (Anti-CEA Immunoscintigraphy, Somatostatin Receptor Scintigraphy, Positron Emission Tomography)	321	(5)
18.4 Future Developments: Will Cholecystokinin-B/Gastrin Receptor Scintigraphy Allow for More Sensitive Staging of MTC?	326	(5)
18.5 Conclusion	331	(1)
References	331	(4)
19 Therapy for Medullary Thyroid Cancer	335	(1)
O. GIMM and H. DRALLE
19.1 Introduction	335	(1)
19.2 Sporadic Versus Familial Medullary Thyroid Carcinoma	335	(1)
19.3 Therapy	336	(7)
19.3.1 Surgical Treatment	337	(1)
19.3.1.1 Thyroid Gland	337	(1)
19.3.1.2 Lymph Node Metastases	337	(1)
19.3.1.2.1 Inclusion of the Cervicolateral Compartments	338	(1)
19.3.1.2.2 Inclusion of the Mediastinal Compartment	338	(1)
19.3.1.3 Distant Metastases	339	(1)
19.3.1.4 Reoperation	339	(1)
19.3.2 Special Therapeutic Considerations in Familial MTC	340	(1)
19.3.2.1 Thyroid Gland	340	(1)
19.3.2.2 Lymph Node Metastases	340	(1)
19.3.3 Nonsurgical Treatment Modalities	341	(1)
19.3.3.1 Octreotide	341	(1)
19.3.3.2 Radioactive Iodine	341	(1)
19.3.3.3 External Radiation	342	(1)
19.3.3.4 Chemotherapy	342	(1)
19.3.3.5 Psychological Support	342	(1)
References	343	(4)
20 Follow-up of Medullary Thyroid Cancer	347	(1)
T. SCHILLING and R. ZIEGLER
20.1 Distinction Between Sporadic and Familial Form of Medullary Thyroid Cancer	347	(1)
20.2 Survival in Patients Suffering from MTC	347	(2)
20.3 Sporadic Form of MTC	349	(4)
20.3.1 Calcitonin as a Tumor Marker During Follow-up	349	(1)
20.3.2 Testing the Result of the Primary Operation	349	(2)
20.3.3 Follow-up in General	351	(1)
20.3.4 Follow-up in Patients with No Detectable Calcitonin Postoperatively	351	(1)
20.3.5 Follow-up in Patients with Detectable Calcitonin Postoperatively	351	(1)
20.3.6 Adjuvant Therapy	352	(1)
20.4 Familial Form of MTC (MEN 2)	353	(2)
20.4.1 Screening for Pheochromocytoma and Timing of Surgery	353	(1)
20.4.2 Screening for Primary Hyperparathyroidism	354	(1)
References	355	(2)
Subject Index	357