Thyroid Neoplasms (eBook)

Cover 1
Thyroid Neoplasms 4
Contents 6
Preface 8
List of contributors 10
Gene rearrangements in thyroid cancer 12
Introduction 12
RET/PTC Rearrangement 12
The RET proto-oncogene 12
Structure of RET/PTC oncogenes 13
Consequences of RET/PTC fusion and activation in thyroid cells 13
Prevalence in thyroid tumors 15
Association with age and radiation exposure 16
Genotype-phenotype correlation 17
Characterization of breakpoint sites and possible mechanisms of RET/PTC rearrangement 17
PAX8–PPAR. Rearrangement 21
Structure 21
Prevalence in thyroid tumors 21
Biological function of PAX8– PPAR. and possible mechanisms of transformation 23
Concluding remarks 23
Acknowledgments 24
References 24
Molecular markers of thyroid nodules 30
Introduction 30
Telomerase 30
Galectin-3 32
Thyroid peroxidase 34
Oncofetal fibronectin 35
Ret/PTC 35
Pax8-PPAR· 36
Nm23 37
High-mobility group I(Y) protein-HMGI(Y) 37
Ceruloplasmin 38
Cytokeratin 19 38
GLUT 1 39
CA 19-9, CD15 and HMBE-1 39
CD30 39
CD97 40
Epithelial membrane antigen, Leu-7 (CD57), epidermal growth factor receptor 40
Cyclooxygenase-2 41
Conclusion 42
References 42
Ultrasound in the diagnosis and management of thyroid cancer 46
Ultrasound analysis of thyroid nodules 47
Echogenecity 47
Margins 49
Calcifications 49
Vascularity 51
Cervical lymphadenopathy 51
Other nodule characteristics 51
Ultrasound-guided FNA 54
Ultrasound in the post-operative surveillance of thyroid cancer 55
Summary 58
References 58
Controversies in the use of radioiodine for remnant ablation and therapy of thyroid carcinoma 60
Introduction 60
131I Thyroid remnant ablation 60
Rationale for thyroid remnant ablation 60
Decreased cancer recurrence after 131I ablation 61
Decrease in cancer-specific death after 131I ablation 63
Simplified patient follow-up and early detection of disease 63
Scan sensitivity after 131I ablation 64
Serum Tg during TSH suppression 65
Accuracy of serum Tg during TSH stimulation 65
Resolution of interfering antithyroglobulin antibodies 66
Psychological comfort 66
Candidate patients for remnant ablation 67
DTC surgery as it relates to remnant ablation 67
Initial thyroid surgery 67
Completion thyroidectomy 68
Selection of patients for 131I remnant ablation 69
Patient preparation for remnant ablation 70
Stable iodine depletion 70
Low-iodine diet 70
Stable iodine from CT, angiography, and ERCP contrast 71
TSH stimulation 71
Thyroid hormone withdrawal (THW) 71
Recombinant human TSH (rhTSH) 72
Diagnostic whole body scan (DxWBS) 73
Utility 73
Stunning 73
131I dose for remnant ablation 74
Definition of complete ablation and selection of patients for repeat 131I ablation 75
131I Therapy of differentiated thyroid carcinoma 76
131I Dosing for tumor therapy 77
Empiric fixed doses 77
Maximum safety limit of the 131I dose established by dosimetry 78
Quantitative tumor dosimetry 78
Renal insufficiency 79
Children 79
Lithium 79
Elevated serum Tg levels and negative diagnostic 131I scans 80
CNS or vertebral metastases 82
125I 83
Retinoic acid 83
Conclusion 83
References 84
Thyroglobulin measurements in thyroid cancer evaluation and surveillance 94
Thyroglobulin physiology 94
Clinical utility of serum Tg measurement 95
Serum Tg reference range values¹ 95
Clinical utility of serum Tg in different stages of managing DTC 97
Pre-operative serum Tg measurements 97
Acute post-operative period (first 6 months) 98
Early post-operative period (6– 24 months) 99
Long-term monitoring 100
TgAb-negative patients with detectable serum Tg on L-T4 treatment 100
Use of rhTSH for TgAb-negative patients with undetectable serum Tg on L-T4 treatment 102
Serial monitoring of TgAb-positive patients 104
Technical limitations of serum Tg measurement 105
TgAb interference with serum Tg measurements 106
TgAb measurement in DTC patients 107
Tg mRNA determinations in peripheral blood 108
Between-method biases 109
Suboptimal sensitivity 109
Between-run assay precision 110
High-dose ’hook’ effects 110
Summary 111
References 112
The role of fluoro-deoxy glucose (FDG) positron emission tomography (PET) in the management of differentiated thyroid cancer 118
History of FDG-PET and thyroid cancer 118
Use of FDG-PET to detect occult metastases 119
FDG-PET evaluation of thyroid nodules and incidentalomas 122
Does the TSH level affect FDG-PET outcome? 123
Does FDG-PET provide information about the biology of the tumor? 123
Sensitivity of FDG-PET lesions to radioactive iodine therapy 124
Summary 125
References 125
Preclinical studies of chemotherapy for undifferentiated thyroid carcinoma 128
Introduction 128
DNA-damaging agents 128
Antimetabolites 129
Tezacitabine 129
Gemcitabine 129
Multimeric gemcitabine monophosphate 130
Antimicrotubule agents 130
Paclitaxel 130
2-Methoxyestradiol 131
Vinorelbine 131
Mitogenic signaling blockers 132
4,5-Dianilinophthalimide 133
Pyrazolo-pyrimidine PP1 133
Manumycin 134
Lonafarnib (SCH66336) 136
Angiogenesis inhibitors 138
TNP-470 138
Combretastatin A-4 phosphate 139
Manumycin 139
Imatinib mesylate (STI571, Gleevec®, CGP 57148B) 140
Gene therapy 140
Adenovirus expressing wild-type p53 140
Thyroid-specific expression of prodrug/suicide genes 143
ONYX-015 (an E1B-defective adenovirus) 143
Redifferentiation therapy 143
Azacitidine 144
Trichostatin A 144
Retinoic acids 145
Vitamin D analog 145
Miscellaneous agents 145
Bovine seminal ribonuclease 145
Apigenin 146
Troglitazone 146
Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) 147
c-myc antisense oligonucleotides 147
Conclusion 147
References 147
Medullary thyroid carcinoma 156
Introduction 156
Genetics of MTC – the men 2 syndromes 157
Diagnosis 160
History and physical examination 160
Serum calcitonin screening 162
Treatment 162
Surgical treatment of palpable disease 162
Management of the parathyroids 163
Management of regional nodes 164
Surgical treatment„preventative thyroidectomy in RET mutation carriers 166
Post-surgical follow-up 167
Persistent or recurrent MTC 168
Treatment of patients with persistent or recurrent medullary thyroid carcinoma 170
Radiation therapy 170
Chemotherapy 172
Cervical reoperation 172
Conclusion 175
References 175
Thyroid neoplasms in children and adolescents 182
Epidemiology 182
Well-differentiated thyroid carcinoma 182
Medullary thyroid carcinoma 184
Anaplastic thyroid carcinoma 184
Pathological features 185
Papillary thyroid carcinoma 185
Follicular thyroid carcinoma 185
Medullary thyroid carcinoma 185
Anaplastaic thyroid carcinoma 185
Clinical features 185
Diagnosis 186
History and physical examination 186
Blood studies 187
Radionuclide imaging 188
Ultrasonography 188
Thyroid hormone suppression 189
Biopsy 189
Treatment of thyroid carcinoma 189
Well-differentiated thyroid carcinoma 189
LT4 therapy 192
Other therapies 192
Follow-up 192
Prognosis 193
Medullary thyroid carcinoma 194
Prognosis 194
Anaplastic thyroid carcinoma 194
Prognosis 195
References 195