CONTENTS

1. The Normal ...... 1 Gross Anatomy...... 1 Vascular Supply...... 4 Nerve Supply...... 8 Embryology...... 8 Microscopic and Functional Anatomy...... 10 Hypothalamus and Neurohypophysis...... 10 Adenohypophysis...... 12 Adenohypophyseal Cells...... 17 Localization of Other Peptides in the Adenohypophysis...... 34 2. Methods in Pituitary Pathology...... 41 Gross Examination...... 41 The Autopsy Pituitary...... 41 The Surgical Specimen...... 42 Intraoperative Consultation...... 42 Histology and Immunohistochemistry...... 43 Electron Microscopy...... 47 Tissue Culture...... 47 Flow Cytometry...... 49 Molecular Analysis...... 49 A Practical Approach to the Diagnosis of a Pituitary Tumor...... 49 3. Pituitary Adenomas...... 55 Epidemiology...... 55 Classification Systems...... 58 Functional Classification...... 58 Anatomic or Radiologic Classification...... 58 Histologic Classification...... 61 Immunohistochemical Classification...... 61 Ultrastructural Classification...... 62 Clinicopathologic Classification...... 63 Adenomas Causing Adrenocorticotropic Excess...... 63 Clinical Features...... 63 Biochemical Findings...... 65 Radiologic Findings...... 66 Gross Findings...... 66 Microscopic Findings...... 67

ix Tumors of the Pituitary Gland

Differential Diagnosis...... 74 Treatment and Prognosis...... 75 Adenomas Causing Growth Hormone Excess...... 76 Clinical Features...... 76 Biochemical Findings...... 77 Radiologic Findings...... 78 Gross Findings...... 78 Microscopic Findings...... 78 Differential Diagnosis...... 90 Treatment and Prognosis...... 91 Adenomas Causing Prolactin Excess...... 93 Clinical Features...... 93 Biochemical Findings...... 93 Radiologic Findings...... 94 Gross Findings...... 95 Microscopic Findings...... 95 Differential Diagnosis...... 105 Treatment and Prognosis...... 106 Adenomas Causing Thyrotropin Excess...... 108 Clinical Features...... 108 Biochemical Findings...... 109 Radiologic Findings...... 109 Gross Findings...... 109 Microscopic Findings...... 109 Differential Diagnosis...... 113 Treatment and Prognosis...... 113 Adenomas Causing Gonadotropin Excess...... 113 Clinical Features...... 113 Biochemical Findings...... 114 Radiologic Findings...... 114 Gross Findings...... 114 Microscopic Findings...... 114 Differential Diagnosis...... 117 Treatment and Prognosis...... 118 Clinically Nonfunctioning Adenomas...... 120 Clinical Features...... 120 Biochemical Findings...... 120 Radiologic Findings...... 120 Microscopic Findings...... 120

 Contents

Differential Diagnosis...... 135 Treatment and Prognosis...... 136 Plurihormonal and Double Adenomas...... 136 Clinical Features...... 136 Biochemical Findings...... 137 Radiologic Findings...... 137 Microscopic Findings...... 137 Differential Diagnosis...... 138 Treatment and Prognosis...... 138 Pituitary Apoplexy...... 138 Definition...... 138 Clinical Features...... 139 Differential Diagnosis...... 139 Treatment and Prognosis...... 139 Ectopic Adenomas...... 140 Pathogenesis of Pituitary Adenomas...... 141 Clonality Studies...... 141 Pituitary Tumor Susceptibility Genes...... 142 Endocrine-Specific Mechanisms: Hormone Regulatory Pathways...... 143 Classic Oncogenic Signals...... 149 Dysregulated Growth Factors and Their Receptors...... 149 Epigenetically Silenced Tumor Suppressors in Sporadic Pituitary Tumors...... 150 Chromatin Remodeling in Pituitary Tumors...... 152 Implications for Therapy...... 153 4. Pituitary Carcinoma...... 173 Clinical Features...... 173 Radiologic Findings...... 173 Pathologic Findings...... 173 Pathogenesis...... 174 Treatment and Prognosis...... 178 5. Tumors of the Hypothalamus and Neurohypophysis...... 181 Neuronal Tumors...... 181 ...... 187 ...... 189 Spindle Cell Oncocytoma...... 190 ...... 193 Other Sellar ...... 194 ...... 196

xi Tumors of the Pituitary Gland

Schwannomas...... 198 Granular Cell Tumors...... 200 6. ...... 207 Clinical Features...... 207 Biochemical Findings...... 207 Radiologic Findings...... 207 Gross Findings...... 208 Microscopic Findings...... 208 Pathogenesis...... 212 Differential Diagnosis...... 212 Treatment and Prognosis...... 214 Malignant Craniopharyngioma...... 215 7. Germ Cell Tumors of the Sella Turcica...... 217 Clinical Features...... 217 Biochemical Findings...... 217 Radiologic Findings...... 217 Microscopic Findings...... 217 Differential Diagnosis...... 219 Treatment and Prognosis...... 221 8. Hematologic Tumors of the Sella Turcica...... 223 and ...... 223 Histiocytoses...... 226 9. Mesenchymal and Vascular Tumors of the Sella Turcica...... 233 Chordomas...... 233 Vascular Tumors...... 235 Tumors of the Fibrous Tissue, Fat, Bone, and Cartilage...... 238 10. Metastatic to the Sella Turcica...... 241 Epidemiology...... 241 Clinical Features...... 241 Radiologic Findings...... 241 Microscopic Findings...... 241 Differential Diagnosis...... 243 Treatment and Prognosis...... 246 11. Tumor-Like of the Sella Turcica...... 249 Hyperplasias...... 249 Cysts ...... 256 Inflammatory Lesions...... 258 Lymphocytic Hypophysitis...... 258 Idiopathic Granulomatous Hypophysitis...... 264

xii Contents

Xanthomatous Hypophysitis...... 264 Inflammatory Pseudotumor...... 266 Miscellaneous Tumor-Like Lesions...... 267 Aneurysms...... 267 Meningoencephalocele...... 267 Hamartomas...... 267 Bone Lesions...... 268 Index ...... 277

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