CONTENTS
1. Peripheral Nerve Tumors: Overview...... 1 Historical Background...... 2 Early Key Investigators ...... 2 Specimen Presentation, Handling, and Assessment...... 6 2. The Normal Peripheral Nervous System ...... 11 Development...... 11 Gross Anatomy ...... 11 Microanatomy ...... 14 Peripheral Nerves...... 14 Sensory and Autonomic Ganglia ...... 20 Interstitial Cells of Cajal...... 25 Specialized Nerve Endings...... 26 Immunohistochemistry...... 28 Ultrastructure...... 30 3. Reactive Lesions...... 33 Traumatic Neuroma...... 33 Localized Interdigital Neuritis ...... 41 Pacinian Neuroma...... 45 Oral Pseudoperineurioma...... 49 Intraneural Injury Neuroma...... 51 Epithelial Sheath Neuroma ...... 52 Ganglion Cyst of Nerve...... 53 Endometriosis of Sciatic Nerve...... 58 Heterotopic Ossification of Nerve (Neuritis Ossificans)...... 60 4. Inflammatory and Infectious Lesions Simulating Tumors of Nerve...... 67 Inflammatory Pseudotumor of Nerve ...... 67 Sarcoidosis of Peripheral Nerve ...... 71 Mycobacterial Pseudotumor...... 73 Leprous Neuropathy...... 75 5. Hyperplastic Lesions...... 81 Palisaded Encapsulated Neuroma...... 81 Multiple Endocrine Neoplasia 2B-Associated Mucosal Neuroma, Mucosal Neuromatosis, and Intestinal Ganglioneuromatosis ...... 87 MEN 2B-Unassociated Neuroma, Ganglioneuroma/Ganglioneuromatosis, and Localized Hypertrophic Neuropathy ...... 95
xi Tumors of the Peripheral Nervous System
Neuroma...... 95 Mucosal Ganglioneuroma and Ganglioneuromatosis...... 98 Localized Hypertrophic Neuropathy...... 101 6. Lipomatosis and Neuromuscular Choristoma of Nerve...... 111 Lipomatosis of Nerve...... 111 Neuromuscular Choristoma ...... 117 7. Schwannoma ...... 129 Conventional Schwannoma...... 129 Cellular Schwannoma ...... 165 Plexiform Schwannoma ...... 178 Congenital and Childhood Plexiform (Multinodular) Cellular Schwannoma. . . . . 184 Melanotic Schwannoma...... 187 8. Neurofibroma...... 211 General Features ...... 211 Genetics...... 212 Clinicopathologic and Anatomic Variants...... 212 Microscopic Findings...... 228 Diagnostically Confusing Microscopic Findings ...... 233 Immunohistochemical Findings ...... 244 Ultrastructural Findings ...... 244 DNA Flow Cytometry ...... 245 Histologic Atypia and Malignant Change...... 245 Tumor of Proposed Neurofibromatous Nature but Unconfirmed ...... 253 Differential Diagnosis...... 253 Treatment and Prognosis...... 259 9. Perineurial Cell Tumors ...... 265 Perineurioma...... 265 Intraneural Perineurioma...... 266 Soft Tissue Perineurioma ...... 274 Intestinal Perineurioma...... 286 Hybrid Benign Peripheral Nerve Sheath Tumors ...... 289 Hybrid Schwannoma/Perineurioma...... 289 Hybrid Reticular (Retiform) Schwannoma/Perineurioma...... 289 Significance of Hybrid Benign PNSTs with Intimately Admixed Phenotypically Different Tumor Cell Types...... 289 Differential Diagnosis...... 292 10. Miscellaneous Benign Neurogenic Tumors ...... 297 Nerve Sheath Myxoma ...... 297
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Benign Granular Cell Tumor...... 305 Ganglioneuroma...... 319 11. Benign and Malignant Non-Neurogenic Tumors...... 347 Benign Non-Neurogenic Tumors...... 347 Lipoma...... 347 Paraganglioma ...... 347 Angiomas of Nerve ...... 350 Glomus Tumor Variants ...... 351 Hemangioblastoma ...... 356 Meningioma ...... 361 Cutaneous Meningioma...... 366 Adrenal Adenoma...... 366 Malignant Non-Neurogenic Tumors ...... 366 Synovial Sarcoma ...... 366 Angiosarcoma ...... 372 Hemangiopericytoma...... 372 Primary Non-Hodgkin Lymphoma ...... 372 Amyloidoma of Nerve ...... 373 12. Malignant Tumors of the Peripheral Nerves ...... 381 Conventional Malignant Peripheral Nerve Sheath Tumors...... 381 Perineurial Cell MPNST...... 414 Variants of Schwann Cell-Derived MPNST ...... 416 Epithelioid MPNST ...... 416 Deep Epithelioid MPNST...... 416 Superficial Epithelioid MPNST ...... 423 Conventional Schwannoma with Epithelioid Malignancy ...... 423 Neurofibroma with Malignant Epithelioid Cell Differentiation ...... 427 MPNST with Divergent Differentiation ...... 429 MPNST with Divergent Mesenchymal Differentiation...... 431 PNST with Divergent Epithelial Differentiation ...... 438 MPNST Arising in Peripheral Neuroblastic Tumors ...... 450 MPNST Presenting in Ganglioneuroma or Ganglioneuroblastoma ...... 450 MPNST Arising in Pheochromocytoma ...... 455 Primitive Neuroectodermal Tumor of Peripheral Nerve ...... 457 Malignant Granular Cell Tumor...... 458 13. Tumors of the Neural Transmitting Mesenchymal Cell Component of the Peripheral Nervous System...... 475 Gastrointestinal Stromal Tumor...... 475
xiii Tumors of the Peripheral Nervous System
14. Secondary Neoplasia...... 491 Metastases and Direct Extension of Neoplasms to Nerve...... 491 Carcinoma ...... 491 Sarcoma ...... 494 Neurotropic Melanoma ...... 495 Lymphoma-Leukemia ...... 502 Miscellaneous Involvement ...... 503 Metastases to Nerve Sheath Tumor ...... 503 15. Neurofibromatosis 1 and 2, and Schwannomatosis...... 507 Neurofibromatosis 1 ...... 507 Neurofibromatosis 2 ...... 521 Schwannomatosis...... 535 Index ...... 545
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