CNS Pathology Board Review

Comprehensive question-and-answer revision flashcards covering glial biology, neurodegenerative conditions, CNS neoplasms, phakomatoses, vascular pathology, and neuroinfectious diseases.

Which glial cell forms the blood-brain barrier and mediates gliosis after CNS injury?

Astrocyte

Which cell forms myelin in the CNS, and which specialized stain highlights it?

Oligodendrocyte; highlighted by Luxol fast blue stain.

What are the cell lining and function of ependymal cells?

They line the ventricular system and assist in CSF production.

Which clinical conditions are characteristically associated with rod cells, neuronophagia, microglial nodules, and globoid cells?

Rod cells: Neurosyphilis (tertiary syphilis); Neuronophagia: Rabies and polio; Microglial nodules: HIV encephalitis; Globoid cells: Krabbe disease (globoid leukodystrophy).

What are the key genetic loci and chromosomes implicated in early- and late-onset Alzheimer disease?

APP on chromosome $21$, PS1 on chromosome $14$, PS2 on chromosome $1$, and the APOE4 allele of APOE.

Why do individuals with Down syndrome develop premature Alzheimer disease?

Trisomy $21$ provides an extra copy of the APP gene (located on chromosome $21$), leading to excess amyloid-beta accumulation.

What are the two hallmark microscopic lesions of Alzheimer disease, and which stain highlights them?

Neuritic plaques (containing an amyloid-beta core of A-beta $40/42$) and neurofibrillary tangles (composed of hyperphosphorylated tau), demonstrated by Bielschowsky silver stain.

What is cerebral amyloid angiopathy (CAA)?

Deposition of A-beta $40$ within the walls of cerebral blood vessels, leading to vessel wall damage and fragility.

What is the protein constituent of Lewy bodies, and what macroscopic change is seen in Parkinson disease?

Alpha-synuclein; gross examination reveals pallor/depigmentation of the substantia nigra due to loss of dopaminergic neurons.

What are the characteristic gross and microscopic pathological findings of Pick disease?

Gross: Knife-edge gyral atrophy with widening of sulci (frontotemporal lobar degeneration). Microscopic: Pick cells and tau-positive Pick bodies.

What is the genetic mutation, inheritance pattern, and primarily affected brain structure in Huntington disease?

Autosomal dominant CAG trinucleotide repeat expansion in the HTT gene on chromosome $4$, primarily causing atrophy of the caudate nucleus.

What is the underlying pathology, mutated gene, and characteristic inclusion seen in Amyotrophic Lateral Sclerosis (ALS)?

Degeneration of both upper and lower motor neurons (UMN and LMN); linked to mutations in SOD1 (chromosome $21$); characterized microscopically by Bunina bodies.

Which pathognomonic neuronal inclusions are found in rabies, and in which anatomical locations are they most prominent?

Negri bodies (eosinophilic cytoplasmic inclusions), predominantly found in cerebellar Purkinje cells and pyramidal cells of the hippocampus.

What are the diagnostic CSF marker, EEG finding, and PRNP codon polymorphism associated with Creutzfeldt-Jakob disease (CJD)?

CSF: $14-3-3$ protein; EEG: Periodic sharp-wave complexes; PRNP susceptibility: Codon $129$ polymorphism.

Which prion disease is distinct in that it does NOT display a classic spongiform change?

Fatal familial insomnia (FFI)

What is the most common intracranial tumor overall, and what is the most common primary malignant brain tumor in adults?

Metastasis is the most common intracranial neoplasm overall; Glioblastoma (GBM) is the most common primary malignant brain tumor in adults.

What histologic criteria constitute the St. Anne-Mayo grading system for astrocytomas?

A = Atypia, M = Mitosis, E = Endothelial proliferation, N = Necrosis. (Grade 1: $0$ features; Grade 2: $1$ feature; Grade 3: $2$ features; Grade 4: $3$ or $4$ features).

What are the genetic hallmarks, typical site, and microscopic features of pilocytic astrocytoma?

Genetics: BRAF V600E mutation or KIAA1549-BRAF fusion; Site: Cerebellum (cystic cavity with mural nodule in children); Histology: Rosenthal fibers (hair-like, eosinophilic fibers; WHO Grade I).

What are the typical imaging and histopathological findings in glioblastoma (GBM)?

Imaging: Butterfly glioma (crossing corpus callosum); Histology: Serpentine/geographic necrosis with pseudopalisading tumor cells and glomeruloid bodies (microvascular proliferation).

What is the defining molecular signature and classic microscopic appearance of oligodendroglioma?

IDH mutation accompanied by $1p/19q$ co-deletion; microscopically displays sheets of cells with clear halos ('fried-egg' appearance) and a branching 'chicken-wire' capillary network.

What histone mutation characterizes diffuse midline glioma, and what is its typical prognosis?

H3 K27M mutation (histone H3); associated with a uniformly poor prognosis.

What are the common anatomical sites, genetic alterations, and histological features of ependymoma?

Sites: Infratentorial (fourth ventricle) and supratentorial; Genetics: NF2 (chromosome $22$) or RELA fusion (chromosome $11$ supratentorial); Histology: Perivascular pseudorosettes.

Which malignant pediatric cerebellar tumor is WHO Grade IV and characterized by Homer Wright rosettes?

Medulloblastoma (molecular subgroups: WNT, SHH, Group 3, Group 4; WNT carries the best prognosis).

What are the gender predominance, hormone receptor status, and classic microscopic hallmarks of meningioma?

Female predominance; Progesterone receptor (PR) positive; Histology: Concentric whorling of meningothelial cells and calcified psammoma bodies.

What does the 'Mi S M E' mnemonic stand for in relation to Neurofibromatosis type 2 (NF2)?

Mi = Multiple intracranial tumors, S = Schwannoma, M = Meningioma, E = Ependymoma.

What gene mutation defines atypical teratoid/rhabdoid tumor (ATRT), and where does it typically present?

Mutation in SMARCB1 (also known as INI1 or SNF5); typically located in the posterior fossa of young children.

What microscopic feature characterizes dysembryoplastic neuroepithelial tumor (DNET)?

'Floating neurons' within pools of mucinous extracellular matrix (a benign cause of chronic intractable epilepsy).

What is the most common histology, associated virus, and microscopic distribution of primary CNS lymphoma in immunocompromised patients?

Diffuse large B-cell lymphoma (DLBCL); associated with Epstein-Barr virus (EBV) and HIV; shows an angiocentric pattern with concentric reticulin rings.

Which cranial nerve and angle are affected by vestibular schwannoma, and what histological patterns are seen?

Arises from CN VIII at the cerebellopontine angle (CPA); exhibits Antoni A areas (hypercellular with Verocay bodies) and Antoni B areas (hypocellular, myxoid).

What is the embryologic origin, key gene mutation, and histological hallmark of craniopharyngioma?

Remnant of Rathke pouch; CTNNB1 (beta-catenin) mutation; displays peripheral palisading, stellate reticulum, and wet keratin (cholesterol-rich 'machine-oil' fluid).

Which cerebellar vascular tumor is associated with von Hippel-Lindau (VHL) disease on chromosome 3p?

Hemangioblastoma (histologically rich in capillary networks and lipid-laden foamy stromal cells).

What CNS lesions are associated with Tuberous Sclerosis (TSC1 on chr 9, TSC2 on chr 16)?

Cortical tubers and subependymal giant cell astrocytoma (SEGA).

What is the underlying cause, typical affected brain region, and microscopic pathology of Wernicke encephalopathy?

Thiamine (vitamin B1) deficiency; causes hemorrhagic necrosis and capillary proliferation in the mammillary bodies and periventricular areas.

What is the most common intracranial site of hypertensive intracerebral hemorrhage, and what microvascular lesions cause it?

Basal ganglia (specifically the putamen), resulting from the rupture of Charcot-Bouchard microaneurysms.

Where do the majority of berry (saccular) aneurysms occur, and what fatal acute complication do they precipitate upon rupture?

Anterior communicating artery of the circle of Willis; rupture causes subarachnoid hemorrhage (SAH).

What are the characteristic MRI and CSF findings in multiple sclerosis?

MRI: Periventricular demyelinating plaques oriented along venules (Dawson fingers); CSF: Oligoclonal IgG bands.

Which lobe of the brain is characteristically involved in Herpes Simplex Encephalitis, and what intranuclear inclusion is present?

Temporal lobe (necrotizing, hemorrhagic encephalitis); Cowdry type A eosinophilic intranuclear inclusions.

What is the classic diagnostic morphology and stain for Cryptococcus neoformans infection in the CNS?

India ink preparation (or mucicarmine) showing encapsulated budding yeast cells surrounded by a wide gelatinous, clear halo.