NEUROPATHOLOGY TRAINING MANUAL
Detailed Educational Objectives
Neuroanatomy / Histology
Disease of Muscle and Peripheral Nerve
Glial Tumors
Non-Glial Tumors of the CNS
Pediatric Tumors of the CNS
Developmental Abnormalities
Hydrocephalus
Metabolic Disease
Demyelinating
Vascular Diseases
Hypoxia / Ischemia Adult and Pediatric
Acute and Chronic Viral Infections
Non-Viral Infections
Neurodegenerative Diseases
Forensic Neuropathology
Ophthalmic Pathology
Neuroanatomy / Histology  top
  1. Know the major morphological, ultrastructural, and immunohistochemical characteristics of the neuroectodermal and mesenchymal cellular constituents of the nervous system.
  2. Know the histologic and cytologic structure of the specialized regional organs of the nervous system: the pineal gland, pituitary gland, circumventricular organs, optic nerves, olfactory tracts and bulbs, and filum terminale.
  3. Know the principal reactions shown by each nervous system cell type to aging, disease, and neoplastic transformation.
  4. Know the appropriate use of special histochemical and immunohistochemical stains.
  5. Know the major levels of the nervous system and the signs and symptoms produced by lesions at these different levels. Know the difference between an intra-axial versus an extra-axial lesion.
  6. Know how to distinguish between a lesion of the peripheral and central nervous system using clinical information.
  7. Know how to distinguish extradural, intradural extramedullary, and intramedullary spinal cord processes, and the implications of this distinction.
  8. Know the anatomical basis of visual field abnormalities.
  9. Know the major motor, sensory, and cognitive consequences of lesions of the frontal, parietal, occipital, and temporal lobes, and limbic system.
Disease of Muscle and Peripheral Nerve  top
  1. Know the rationale for performing, and the technique for processing, skeletal and peripheral nerve biopsies.
  2. Know the algorithm for microscopic analysis of skeletal muscle and peripheral nerve biopsy including paraffin and frozen sections, teased fibers and EM.
  3. Know what is relevant and important clinical history for evaluating peripheral nerve and muscle biopsies.
  4. Know the differential diagnosis of major histopathological findings in neuromuscular disease (e.g. mitochondrial, congential, toxic neuropathies and myopathies, and muscle proteinopathies).
  5. Know how to distinguish primary from secondary demyelination.
  6. Know how to recognize the histopathologic features of vasculitis and the clinical implications of this diagnosis.
  7. Know how to recognize the histopathologic features of major peripheral neuropathies.
Glial Tumors  top
  1. Know the basis of and correlate current and past classifications of diffuse gliomas (Three-tiered vs. Four-tiered systems).
  2. Know the limitations and similarities of current classification systems (St. Anne-Mayo and WHO 2000).
  3. Know the epidemiology, clinical presentation and neuroradiology of common glial neoplasms.
  4. Know useful diagnostic features of gliomas on touch, smear, and frozen preparations and paraffin histology.
  5. Know the diagnostic histologic features of glial neoplasms.
  6. Know the immunohistochemical profile of astrocytic, oligodendroglial and ependymal tumors..
  7. Know the different prognostic significance of glioma variants.
  8. Know methods for quantifying the proliferation index of a glial tumor.
  9. Know how to recognize common diagnostic dilemmas and the means of resolving them: (astrocytoma vs. reactive gliosis, astrocytoma vs. demyelinating disease).
  10. Know typical genetic alterations of different glioma types and grades and the therapeutic implications associated with particular genetic alterations in some subtypes of gliomas.
  11. Know familial cancer syndromes in which glial neoplasms occur.
  12. Know histopathologic definitions of glial neoplasms.
  13. Know the diagnostic criteria for anaplastic versus non-anaplastic glial tumors.
  14. Know how to recognize common glial neoplasms occurring in NF-1 and Tuberous Sclerosis.
Non-Glial Tumors of the CNS  top
  1. Know how to recognize histologic patterns of meningiomas with prognostic significance, as well as those patterns that present potential diagnostic confusion with other tumors.
  2. Know how to discuss the current WHO criteria for meningioma grading, and its major differences from earlier grading schemes.
  3. Know the role of immunohistochemistry and electron microscopy in the work-up of pituitary adenomas.
  4. Know how to recognize the major phenotypes of CNS lymphoma and lymphoproliferative disorders, the populations at risk, viral associations, and the role of ancillary studies.
  5. Know the anatomical, pathologic, and prognostic characteristics of chordoma vs. chondrosarcoma.
  6. Be able to discuss the differential diagnosis of sellar/suprasellar, pineal region, and intraventricular mass lesions.
  7. Be able to discuss the differential diagnosis for spinal tumors in the extradural, intradural extramedullary, and intramedullary compartments.
  8. Know how to distinguish between schwannomas and neurofibromas, and recognize pathologic patterns with potential clinical impact, as well as those patterns that present potential diagnostic confusion with more aggressive entities.
  9. Know how to discuss the differential diagnosis and work-up of malignant peripheral nerve sheath tumor, and know the clinical setting where CNS leiomyosarcoma enters the differential.
  10. Know the common primary sites for tumors metastatic to the brain, understand the role of immunohistochemistry in the work up of metastatic lesions, and be aware of less common metastases of younger patients such as alveolar soft part sarcoma and choriocarcinoma.
  11. Know the genetics, CNS, skin, ophthalmic, visceral and osseous manifestations of: neurofibromatosis types 1 & 2, tuberous sclerosis, Cowden’s syndrome, Gorlin’s syndrome, hereditary polyposis, Li Fraumeni syndrome, and MEN1, 2a, and 2b.
Pediatric Tumors of the CNS  top
  1. Know the most common type and location of pediatric brain tumors.
  2. Know the two most common clinical presentations.
  3. Know the differential diagnosis of CNS lesions causing seizures in children.
  4. Know the differential diagnosis of supratentorial pediatric brain tumors.
  5. Know the pediatric CNS neoplasms that are not usually biopsied before treatment.
Developmental Abnormalities  top
  1. Know the most common pathologic manifestations of neural tube defects.
  2. Know the risk factors associated with neural tube defects and the effects of folate on neural tube defects.
  3. Know the association between midline facial abnormalities and holoprosencephaly.
  4. Know the spectrum of brain pathology in holoprosencephaly.
  5. Know the main malformations affecting the cerebellum.
  6. Know the pathologic spectrum of neuronal migration disorders.
  7. Be aware of the mutations associated with neuronal migration disorders and the relationship between specific mutations and patterns of dysmorphogenesis.
  8. Know criteria for grading of cortical dysplasia.
  9. Know the genetic syndromes with migration defects and tumors.
  10. Know the difference between syringomyelia and hydromyelia.
  11. Know how to distinguish ischemic lesions from malformative lesions.
Hydrocephalus  top
  1. Know and be able to trace the formation, circulation and absorption of cerebrospinal fluid.
  2. Know the anatomic structure and physiologic function of the blood-brain-CSF barrier system.
  3. Know the definition and structural basis of communicating and non communicating hydrocephalus and hydrocephalus ex-vacuo.
  4. Know clinical signs and symptoms of increased intracranial pressure.
  5. Know the effects of increased intracranial pressure on the contents of the cranial cavity.
Metabolic Disease  top
  1. Know the pathogenesis of hepatolenticular degeneration (Wilson’s disease).
  2. Know the neurologic manifestations of Wernicke-Korsakoff syndrome.
  3. Know the pathogenesis of central pontine myelinolysis.
  4. Know the clinicopathologic basis of subacute combined degeneration.
  5. Know the neurologic complications of uncontrolled diabetes mellitus.
  6. Know the pathogenesis of kernicterus.
  7. Know the clinical and pathologic features of phenylketonuria.
  8. Know the classifications and pathology associated with inborn errors of metabolism (lysosomal storage disorders, glycogen storage disorders, gangliosidoses, sphingolipidoses, mucopolysaccharidoses, etc.).
Demyelinating  top
  1. Know the structure and function of myelin, and the electrophysiological consequence of myelin loss.
  2. Know the difference between central and peripheral myelin.
  3. Understand why diseases may afflict central myelin, peripheral myelin, or both central and peripheral myelin.
  4. Understand the difference between dysmyelinating versus demyelinating disease.
  5. Know the gross and microscopic features of multiple sclerosis, and how these correlate with the clinical course of the disease.
  6. Know the classification, etiologies, clinical features, and histologic findings of leukodystrophies.
  7. Know about Guillain-Barré syndrome, as a common disease of peripheral myelin characterized by ascending and potentially life-threatening paralysis.
  8. Understand the pathogenesis and clinical features of progressive multifocal leukoencephalopathy (PML).
  9. Know the relationship between systemic disorders and demyelination.
Vascular Diseases  top
  1. Know the anatomical relationships of the major branches of the circle of Willis and the venous sinus system with both skull/dural landmarks and gyral landmarks.
  2. Know the territories of supply of the major arterial branches, and know the parenchymal structures (nuclei and tracts) and major symptoms affected by lesions of these branches, with particular attention to the brainstem syndromes.
  3. Know the most common causes of nontraumatic subarachnoid hemorrhage and intracerebral hemorrhage.
  4. Know the vascular sequelae of systemic hypertension including the locations of lacunes and hypertensive hemorrhages.
  5. Know the clinical and anatomic features of amyloid angiopathy and its pathologic workup.
  6. Know the diagnostic features of temporal arteritis, features suggestive of healed arteritis, and the caliber of vessel usually affected. Know how these differ from primary angiitis of the central nervous system and from polyarteritis nodosa.
  7. Know the clinical, anatomic, and pathologic differences between saccular aneurysms, mycotic aneurysms, and atherosclerotic aneurysms.
  8. Know the radiologic, clinical, gross and microscopic features of arteriovenous malformation, capillary telangiectasia, cavernoma and venous malformation.
  9. Know the mode of inheritance and the tumors/malformations associated with von Hippel-Lindau disease and Sturge-Weber disease.
Hypoxia / Ischemia Adult and Pediatric  top
  1. Know the role of glucose and creatine phosphate in cerebral metabolism under aerobic and anaerobic conditions.
  2. Know the definition of and distinction between: hypoxia, anoxia, ischemia and infarction.
  3. Know the morphologic correlates of ischemia, infarction.
  4. Know the consequences of cerebral ischemia on blood-brain-barrier.
  5. Know the pathophysiologic basis of cerebral autoregulation.
  6. Know the anatomic and physiologic basis of selective vulnerability and how it differs in adult brain and premature brain.
  7. Know how to recognize and distinguish ulegyria, multicystic encephalopathy and hydranencephaly.
  8. Know the pathogenesis of laminar cortical necrosis and arterial border zone infarcts.
  9. Understand the mechanisms that lead to hemorrhagic versus ischemic infarcts.
Acute and Chronic Viral Infections  top
  1. Know the clinical presentation of viral infections of the nervous system and how they depend on host age and immunosuppression.
  2. Know the diagnostic evolution of CNS viral infections.
  3. Know the pathogenesis of the following viral infections of the CNS: HSV, VZV, CMV, HIV, HTLV-1, Arboviruses, PML, Measles, Rubella.
  4. Know the general pathologic features of common CNS viral infections.
  5. Know the most common viral etiologies of meningitis, transverse myelitis, polioencephalitis/myelitis, and leukoencephalitis.
  6. Know the pathogenesis of common viral infections of the PNS.
Non-Viral Infections  top
  1. Know the most common clinical settings in which brain abscesses develop.
  2. Know the organisms most likely to cause meningitis after neurosurgical procedure and after ventriculoperitoneal shunt.
  3. Know the complications of bacterial meningitis.
  4. Know the fungal infections most commonly associated with AIDS.
  5. Know the common causes of immunosuppression in the hospital setting and causes of CNS infections in this population.
  6. Know the epidemiology of neurocysticercosis.
  7. Know the pathogenesis of infections due to acanthamoeba and Naegleria.
Neurodegenerative Diseases  top
  1. Know the basic clinical history and gross appearance of the brain in Alzheimer Disease (AD).
  2. Know the standard sections taken and stains required for assessment of AD and other dementias.
  3. Know the criteria for CERAD, NIA-RI and Braak evaluation of AD.
  4. Know the relationship of AD and Dementia with Lewy Bodies (DLB) and the DLB scoring system.
  5. Know the differential diagnosis of fronto-temporal dementias.
  6. Know the differential diagnosis of Parkinsonism.
  7. Know the differential diagnosis for neurodegenerative diseases characterized by aggregation of tau (tauopathies).
  8. Know the differential diagnosis for neurodegenerative diseases characterized by aggregation of alpha-synuclein (alpha-synucleinopathies).
  9. Know the basic clinical history, gross appearance and microscopic findings of Parkinson Disease, amyotrophic lateral sclerosis, Huntington Disease and Progressive Supranuclear Palsy.
  10. Know the major prion protein disorders including clinical history, gross and microscopic appearance, and special handling precautions for Creutzfeldt-Jakob Disease.
Forensic Neuropathology  top
  1. Know the neuropathology of sudden infant death syndrome (SIDS) and the possible neuropathologic findings that are associated with SIDS.
  2. Know how to recognize and describe specific constellations of patterns of craniocerebral injury that are characteristic of fatal, non-accidental trauma in childhood.
  3. Know the possible neuropathological findings in sudden unexpected death in epilepsy (SUDEP), especially in relation to describing gross and microscopic features of cerebral dysmorphisms and/ or neocortical dysplasia.
  4. Know the putative mechanisms of death in SUDEP.
  5. Know the different pathologic findings in brain trauma with emphasis on blunt force, translational force, acceleration and deceleration craniocerebral injuries.
  6. Know the mechanisms of trauma of the central nervous system in relation to the distinct anatomy of the skull, intracranial cavity, brain and spinal column.
  7. Know the possible complications and sequelae of trauma to the brain with emphasis on timing of a forensic event and the sequential occurrence of such complications and sequelae.
  8. Know the most common causes, vessels, and mechanisms associated with the following: epidural hematoma, subdural hematoma, subarachnoid hemorrhage, intraparenchymal hemorrhage, and petechial hemorrhages.
  9. Know the differences between a contusion and an infarct. What are the characteristic locations of contusions with different types of injury?
  10. Know the signs and symptoms of fractures involving the base of the skull?
  11. Know how to teach the anatomic relationships, gross findings, synonyms for, and clinical symptomatology associated with subfalcine, transtentorial, and foramen magnum herniation.
  12. Know how to discuss the gross and microscopic findings of diffuse axonal injury, and special stains that may be employed.
  13. Know the most common fatal inadvertent therapeutic misadventures that are encountered in neurological and neurosurgical medicine.
  14. Know basic medicolegal syntax, e.g. forensic significance and consequence of findings, cause of death, manner of death, inquest, deposition, expert witness, expert opinion.
  15. Know basic courtroom etiquette and protocol by witnessing at least one oral deposition or one pre-trial inquest and one court room testimony given by a Forensic Pathologist.
Ophthalmic Pathology  top
  1. Know how to identify, orient, and systematically examine enucleation specimens, with emphasis on selecting appropriate plane of section for neoplastic, traumatic/forensic, and phthisical eyes.
  2. Know the importance of clinician-pathologist and pathologist-histotechnician communication, particularly with regard to achieving proper orientation of corneal and conjunctival biopsies.
  3. Know normal appearance of ocular structures submitted to pathology.
  4. Know how to distinguish common pathologic responses in the eye that disrupt visual function from incidental age-related and artifactual changes.
  5. Know how to identify diagnostic features of corneal dystrophies and degenerations.
  6. Know how to discuss endothelial, inflammatory, and pressure-related causes of bullous keratopathy.
  7. Know natural history of uveal and adnexal melanomas.
  8. Know how to evaluate and report pigmented lesions of the eye with an understanding of the pertinent prognostic issues.
  9. Know the most pertinent margin to examine in retinoblastoma enucleations, and be able to list common clinical mimics.
  10. Know how to recognize pathologic sequelae of diabetes, end-stage glaucoma, and penetrating/perforating trauma.
  11. Know how to list the characteristic anterior segment, posterior segment, and optic nerve lesions associated with child/infant abuse, and to discuss non-traumatic medical conditions (if any) that can lead to similar findings.
  12. Know the differential diagnosis and proper handling of orbital biopsies.