1. The Normal Pituitary Gland...... 1 Gross Anatomy...... 1 Vascular Supply ...... 4 Nerve Supply ...... 7 Embryology and Developmental Disorders ...... 7 Microscopic and Functional Anatomy...... 10 Hypothalamus and Neurohypophysis ...... 10 Adenohypophysis...... 13 Other Peptides in the Adenohypophysis...... 32 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...... 48 Flow Cytometry...... 48 Molecular Analysis ...... 49 A Practical Approach to the Diagnosis of a Pituitary Tumor...... 49 3. Pituitary Neuroendocrine Tumors...... 55 Epidemiology...... 55 Classification ...... 58 Functional Classification...... 58 Anatomic or Radiologic Classification...... 58 Histologic and Immunohistochemical Classification ...... 62 Ultrastructural Classification...... 63 Clinicopathologic Classificiation...... 64 Tumors Causing ACTH Excess...... 65 Clinical Features...... 65 Biochemical Findings...... 66 Radiologic Findings...... 67 Gross Findings...... 67 Microscopic Findings ...... 68 Differential Diagnosis...... 75 Treatment and Prognosis ...... 75

ix Tumors of the Pituitary Gland

Tumors Causing Growth Hormone Excess ...... 76 Clinical Features...... 76 Biochemical Findings...... 77 Radiologic Findings...... 78 Gross Findings...... 79 Microscopic Findings ...... 80 Differential Diagnosis...... 90 Treatment and Prognosis ...... 91 Tumors Causing Prolactin Excess...... 92 Clinical Features...... 92 Biochemical Findings...... 94 Radiologic Findings...... 94 Gross Findings...... 95 Microscopic Findings ...... 95 Differential Diagnosis...... 105 Treatment and Prognosis ...... 106 Tumors 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 Tumors Causing Gonadotropin Excess ...... 115 Clinical Features...... 115 Biochemical Findings...... 116 Radiologic Findings...... 116 Gross Findings...... 116 Microscopic Findings ...... 116 Differential Diagnosis...... 119 Treatment and Prognosis ...... 120 Clinically Nonfunctioning Adenohypophysial Cell Tumors...... 121 Clinical Features...... 121 Biochemical Findings...... 121 Radiologic Findings...... 121 Microscopic Findings ...... 121 Differential Diagnosis...... 134 Treatment and Prognosis ...... 135

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Unusual Plurihormonal and Multiple Tumors ...... 135 Clinical Features...... 135 Biochemical Findings...... 135 Radiologic Findings...... 135 Microscopic Findings ...... 135 Differential Diagnosis...... 136 Treatment and Prognosis ...... 136 Pituitary Apoplexy...... 136 Clinical Features...... 136 Pathogenesis...... 136 Gross and Microscopic Findings ...... 136 Differential Diagnosis...... 137 Treatment and Prognosis ...... 137 Ectopic Tumors...... 137 Pathogenesis of Pituitary Tumors...... 138 Clonality Studies ...... 139 Pituitary Tumor Susceptibility Genes ...... 139 Endocrine-Specific Mechanisms: Hormone Regulatory Pathways ...... 141 Classic Oncogenic Signals...... 146 Dysregulated Growth Factors and their Receptors ...... 147 Epigenetically Silenced Tumor Suppressors in Sporadic Pituitary Tumors. . . . 148 Epigenetic Alterations in Pituitary Tumors...... 150 Implications for Therapy ...... 151 4. Pituitary Carcinoma ...... 175 Pathogenesis ...... 175 Clinical Features...... 176 Radiologic Findings ...... 176 Morphologic Findings ...... 176 Treatment and Prognosis...... 181 5. Pituitary Blastoma ...... 183 Pathogenesis ...... 183 Clinical Features...... 183 Radiologic Findings ...... 183 Morphologic Findings ...... 183 Treatment and Prognosis...... 186 6. Tumors of the Hypothalamus and Neurohypophysis...... 187 Hypothalamic Hamartoma ...... 187 Gangliocytoma and Ganglioglioma...... 189 Neurocytoma...... 194

xi Tumors of the Pituitary Gland

Paraganglioma ...... 198 Pituicytoma and its Variants ...... 201 Other Sellar Gliomas ...... 206 Meningiomas...... 209 Schwannomas...... 211 7. Craniopharyngioma ...... 219 Pathogenesis ...... 219 Clinical Features...... 219 Biochemical Findings...... 220 Radiologic Findings ...... 220 Gross Findings ...... 221 Microscopic Findings...... 221 Differential Diagnosis...... 225 Treatment and Prognosis...... 227 Malignant Craniopharyngioma...... 228 8. Germ Cell Tumors ...... 231 Clinical Features...... 231 Radiologic Findings ...... 231 Biochemical Findings...... 231 Microscopic Findings...... 231 Differential Diagnosis...... 234 Treatment and Prognosis...... 234 9. Hematologic Tumors ...... 237 Lymphoma and Leukemia...... 237 Histiocytoses...... 239 10. Mesenchymal and Vascular Tumors...... 247 Chordomas...... 247 Vascular Tumors...... 250 Tumors of Fibrous Tissue, Fat, Bone, and Cartilage ...... 250 11. Metastatic Neoplasms...... 255 Epidemiology...... 255 Clinical Features...... 255 Radiologic Findings ...... 255 Microscopic Findings...... 255 Differential Diagnosis...... 258 Treatment and Prognosis...... 259 12. Tumor-Like Lesions of the Sella Turcica...... 263 Hyperplasias ...... 263 Cysts ...... 269

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Inflammatory Lesions...... 271 Lymphocytic Hypophysitis...... 272 Idiopathic Granulomatous Hypophysitis ...... 278 Xanthomatous Hypophysitis...... 279 IgG4-Related Hypophysitis (Inflammatory Pseudotumor)...... 281 Miscellaneous Tumor-Like Lesions...... 281 Aneurysms...... 281 Meningoencephalocele ...... 282 Hamartomas ...... 282 Bone Lesions...... 283 Index ...... 293

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