CNS Pathology (Tumors, Degenerative, Infections) MCQs

Pathology · 117 free questions with answers & explanations.

1. A 50-year-old patient has a cerebral tumor biopsy showing microvascular proliferation, geographic necrosis with pseudopalisading, and high mitotic rate. Molecular analysis reveals EGFR amplification, PTEN loss, and TERT promoter mutation. IDH mutation is absent. This tumor is classified as:
2. Autopsy of an 80-year-old with Parkinson's disease reveals depigmentation of the substantia nigra. Microscopy shows eosinophilic intracytoplasmic inclusions in surviving neurons. These inclusions are composed primarily of which abnormally aggregated protein?
3. A 45-year-old presents with a well-circumscribed cerebellar mass. Histology shows a biphasic pattern with compact bipolar cells in Rosenthal fiber-rich areas alternating with loose microcystic areas containing eosinophilic granular bodies. BRAF V600E or BRAF-KIAA1549 fusion is characteristic. This is a:
4. In Creutzfeldt-Jakob disease (CJD), the hallmark neuropathological triad includes spongiform change, neuronal loss, and reactive gliosis. The infectious prion protein (PrPSc) causes disease by:
5. A 45-year-old man presents with seizures. MRI shows a 4 cm frontal lobe lesion with no ring enhancement, minimal edema, and calcification. The WHO 2021 CNS classification assigns this to the oligodendroglioma category. Which COMBINED molecular requirement defines oligodendroglioma in the 2021 WHO CNS classification?
6. A 70-year-old woman presents with progressive memory loss, visuospatial difficulties, and then parkinsonism. She dies 2 years later. Autopsy shows neuronal loss in the substantia nigra, locus coeruleus, and cerebral cortex. Immunohistochemistry with anti-alpha-synuclein antibody shows Lewy bodies in cortical neurons and dorsal vagal nucleus. Which clinical-pathological classification is this?
7. A 25-year-old immunocompetent man develops fever, confusion, and seizures. CSF shows lymphocytic pleocytosis, elevated protein, normal glucose. Brain MRI shows bilateral temporal lobe and insular signal abnormality on FLAIR. Serum and CSF anti-NMDAR (anti-GluN1) antibody is positive. This condition is most commonly associated with which underlying neoplasm in women?
8. The 2021 WHO Classification of CNS Tumors made a paradigm shift in glioma classification. Under the new classification, IDH-mutant astrocytomas are graded by specific molecular criteria. Which molecular alteration, when present in an IDH-mutant astrocytoma, automatically upgrades it to WHO grade 4 even without microvascular proliferation or necrosis?
9. In Alzheimer disease, the pathological cascade hypothesis implicates amyloid-β (Aβ) as the initiating event. BACE1 (β-secretase) and γ-secretase are the enzymes generating Aβ from APP. Normally, α-secretase cleaves APP within the Aβ sequence, preventing Aβ formation. This normal cleavage produces:
10. Progressive multifocal leukoencephalopathy (PML) affects immunosuppressed patients, especially those with AIDS or on natalizumab. The causative virus and its target cell type in the CNS are:
11. A 35-year-old with a grade 2 glioma shows IDH1 R132H mutation and 1p/19q co-deletion. Per WHO 2021 CNS5 classification, this tumor is classified as:
12. In Parkinson's disease, the intraneuronal inclusions (Lewy bodies) in substantia nigra neurons contain aggregated α-synuclein. The biochemical mechanism of α-synuclein aggregation involves:
13. A 70-year-old man with rapidly progressive dementia (weeks-months) and myoclonus has a brain biopsy showing spongiform vacuolation of the neuropil without inflammatory infiltrate, gliosis, and neuronal loss. 14-3-3 protein is positive in CSF. The definitive diagnostic confirmation requires:
14. According to the 2021 WHO Classification of CNS Tumors, a diffuse glioma in a 30-year-old with IDH1 R132H mutation and 1p/19q codeletion is classified as:
15. Tau protein pathology is central to several neurodegenerative diseases. In Alzheimer's disease, tau forms neurofibrillary tangles predominantly composed of hyperphosphorylated tau with which isoform predominance?
16. A 25-year-old patient has a spinal cord tumor. Histology shows elongated bipolar cells with hair-like processes arranged in a biphasic pattern (loose microcystic areas alternating with compact Rosenthal fiber-rich areas). Ki-67 is 1%. The diagnosis and molecular marker expected is:
17. A 45-year-old man presents with new-onset seizures. MRI shows a cortical-based mass with heterogeneous signal. Histology reveals glial neoplasm with a dual neuronal-glial differentiation, Rosenthal fibers absent, eosinophilic granular bodies present, and BRAF V600E mutation. According to WHO 2021 CNS tumor classification, the diagnosis is:
18. Alpha-synuclein (αSyn) protein misfolds and aggregates forming Lewy bodies in Parkinson disease. The distinct pathological difference between Lewy body dementia (DLB) and Parkinson disease with dementia (PDD) is primarily based on:
19. A 35-year-old HIV patient (CD4+ count 45 cells/μL) develops progressive confusion, headache, and fever. CSF analysis shows India ink positive encapsulated yeast, elevated CSF opening pressure, low glucose, and minimal pleocytosis. Which virulence factor of Cryptococcus neoformans directly inhibits phagocytosis and prevents complement opsonization?
20. The WHO 2021 CNS tumor classification now requires molecular diagnosis. An adult with a diffuse glioma with IDH1 mutation, ATRX loss, and 1p/19q intact is classified as:
21. A 70-year-old man with progressive dementia has autopsy findings of neurofibrillary tangles in the entorhinal cortex and hippocampus, amyloid plaques, and cortical atrophy. The protein within neurofibrillary tangles is:
22. A brain biopsy from an HIV-positive patient with CD4 <50 cells/μL shows enlarged oligodendrocytes with ground-glass nuclei and reactive astrocytes with bizarre nuclear forms (Creutzfeldt cells), no inflammatory infiltrate, and multiple foci of demyelination. This is most consistent with:
23. A 35-year-old presents with seizures and a cortical lesion. MRI shows a well-circumscribed T2-hyperintense mass with no gadolinium enhancement. Biopsy shows moderate cellularity with atypical glial cells, rare mitoses, no necrosis, and no microvascular proliferation. Molecular testing reveals IDH1 R132H mutation and 1p/19q co-deletion. According to WHO 2021 CNS classification, this tumor is classified as:
24. Autopsy of a 78-year-old with clinical Alzheimer's dementia shows neurofibrillary tangles in the entorhinal cortex and hippocampus (Braak stage III–IV). The tau protein in neurofibrillary tangles is hyperphosphorylated at specific serine/threonine residues. Which kinase is most consistently implicated in pathological tau hyperphosphorylation in Alzheimer's disease?
25. A 25-year-old immunocompetent man develops progressive encephalopathy with personality change over weeks. CSF shows mild lymphocytosis. Brain biopsy shows widespread neuronal vacuolation with intranuclear eosinophilic Cowdry type A inclusions in cortical neurons. Electron microscopy reveals enveloped icosahedral virions. PCR of CSF is positive for herpes simplex virus type 1. The characteristic pattern of herpes encephalitis involving which specific brain regions differentiates it from other encephalitides?
26. WHO 2021 CNS tumor classification introduced integrated molecular-morphological diagnoses. Glioblastoma, IDH-wildtype, CNS WHO grade 4, requires at least ONE of three molecular criteria (even without necrosis or microvascular proliferation). Which three molecular features define IDH-wildtype glioma as glioblastoma per WHO 2021?
27. Creutzfeldt-Jakob disease (CJD) and other prion diseases share a common pathological hallmark. The characteristic 'spongiform change' in prion diseases is caused by:
28. A biopsy from the temporal lobe of a 70-year-old with progressive dementia shows neurofibrillary tangles (NFTs) and senile plaques. NFTs in Alzheimer disease are composed primarily of:
29. According to the WHO Classification of Tumors of the Central Nervous System (5th edition, 2021), a 35-year-old patient with IDH1 R132H mutation, 1p/19q codeletion, and TERT promoter mutation, with an oligodendroglial morphology on histology, is classified as which entity and grade?
30. A 65-year-old man presents with rapidly progressive dementia, myoclonus, visual hallucinations, and cerebellar ataxia over 6 weeks. CSF 14-3-3 protein is positive; MRI DWI shows cortical ribboning and basal ganglia signal change. Autopsy shows spongiform change (vacuolation of the neuropil), neuronal loss, gliosis, and PrP immunostaining. Which of the following best explains the molecular basis of neurodegeneration in this disease?
31. In Alzheimer's disease, the amyloid cascade hypothesis posits that Aβ42 peptide accumulation is the primary pathogenic event. Which enzyme generates Aβ42, and why is Aβ42 more amyloidogenic than Aβ40?
32. A 35-year-old woman undergoes brain MRI for new-onset seizures. A 3 cm frontal lobe mass is found with T2/FLAIR hyperintensity, minimal enhancement, and no significant mass effect. Biopsy shows a diffusely infiltrating glioma with IDH1 R132H mutation, intact ATRX, and 1p/19q codeletion. Per WHO 2021 CNS classification, this tumour is best classified as:
33. In Alzheimer's disease pathogenesis, amyloid-beta (Abeta) plaques form from sequential cleavage of amyloid precursor protein (APP). In the amyloidogenic pathway, APP is first cleaved by beta-secretase (BACE1), then by gamma-secretase. The critical difference between the amyloidogenic and non-amyloidogenic pathways lies in which of the following?
34. A 35-year-old patient with a frontal lobe tumour undergoes resection. Histology shows infiltrating glioma with moderate cellularity, nuclear atypia, no necrosis, and no microvascular proliferation. IDH1 R132H IHC is positive. FISH shows co-deletion of 1p/19q. MGMT promoter is methylated. According to the WHO 2021 CNS classification, what is the diagnosis and grade?
35. Autopsy of a 78-year-old patient with Parkinson's disease shows brainstem and cortical Lewy bodies. The major component of Lewy bodies is alpha-synuclein. Which post-translational modification of alpha-synuclein is most critical for its aggregation into pathological amyloid fibrils?
36. A 25-year-old immunocompetent patient develops rapidly progressive headache, fever and meningismus. CSF shows: opening pressure 280 mmH2O, turbid appearance, 800 cells/mm3 (90% neutrophils), protein 350 mg/dL, glucose 20 mg/dL (serum glucose 90 mg/dL). India ink is negative. Gram stain shows gram-positive diplococci. Which virulence factor of the causative organism most critically enables evasion of complement-mediated lysis?
37. A 35-year-old man undergoes MRI for seizures showing a diffuse T2/FLAIR hyperintense mass involving the cortex and white matter of the left frontal lobe with minimal enhancement. Biopsy reveals a diffuse glioma with IDH1 R132H mutation, 1p/19q co-deletion, and TERT promoter mutation. According to WHO 2021 CNS classification, what is the diagnosis and grade?
38. In prion diseases (transmissible spongiform encephalopathies), what is the molecular basis for the species barrier, and how does variant CJD (vCJD) arising from bovine BSE overcome the normal human species barrier?
39. Progressive multifocal leukoencephalopathy (PML) is caused by JC virus reactivation in immunocompromised patients. Which cell types are preferentially infected, and what is the pathological consequence of this tropism?
40. The WHO CNS Tumor Classification 2021 requires molecular parameters for accurate glioma diagnosis. An adult with IDH-wildtype glioma showing EGFR amplification, TERT promoter mutation, and +7/-10 chromosomal pattern is classified as:
41. A 70-year-old man presents with rapidly progressive dementia, myoclonus, and characteristic EEG changes (periodic sharp wave complexes). CSF 14-3-3 protein is positive, and RT-QuIC assay is positive. The pathological hallmark of this disease involves which molecular mechanism of neurodegeneration?
42. A 3-year-old child presents with signs of raised intracranial pressure and MRI shows a midline posterior fossa mass with gadolinium enhancement and drop metastases along the spinal cord. Histology shows small blue round cells with Homer Wright (neuroblastic) rosettes and MASH1/ATOH1 expression. Molecular testing shows WNT pathway activation (beta-catenin nuclear accumulation). Per WHO CNS5 2021, this tumor is classified as:
43. A 45-year-old patient's brain tumor shows IDH1 mutation, 1p/19q co-deletion, TERT promoter mutation, and no ATRX loss. According to WHO 2021 CNS tumor classification, this tumor is classified as:
44. A 70-year-old patient has progressive dementia with alpha-synuclein-positive Lewy bodies in the substantia nigra AND cortex, and Alzheimer-type pathology. According to current neuropathological criteria, concurrent Lewy body pathology in the presence of high Alzheimer disease neuropathological change (ADNC) is classified as:
45. A patient develops rapidly progressive dementia with myoclonus and periodic sharp-wave complexes on EEG. CSF real-time quaking-induced conversion (RT-QuIC) assay is positive. Neuropathological examination shows spongiform change in the cortex, neuronal loss, and astrogliosis without inflammatory infiltrate. This is Creutzfeldt-Jakob disease (CJD). The fundamental molecular mechanism is:
46. A 35-year-old presents with seizures. MRI shows a cortical-subcortical mass with 'fried egg' cells on biopsy. Immunostaining is positive for IDH1 R132H, ATRX-negative, and p53 overexpressing. 1p/19q co-deletion is absent. Per WHO 2021 CNS classification, which diagnosis is most appropriate?
47. In Alzheimer disease, the amyloid cascade hypothesis posits that Abeta peptide accumulation is the initiating event. Which enzyme is responsible for the rate-limiting step in Abeta generation, and what is the substrate cleavage site?
48. Progressive multifocal leukoencephalopathy (PML) is caused by JC polyomavirus reactivation. Which CNS cell type is productively infected, causing the hallmark cytopathic changes seen on histology?
49. WHO 2021 CNS tumor classification now integrates molecular markers into diagnoses. IDH-mutant, 1p/19q co-deleted glioma with TERT promoter mutation is classified as:
50. Tau protein pathology is central to several neurodegenerative diseases. In Alzheimer's disease, tau forms neurofibrillary tangles (NFTs). The critical pathological tau modification is:
51. A 55-year-old man presents with a rapidly progressive dementia, myoclonus, and cerebellar ataxia over 8 months. EEG shows periodic sharp wave complexes. Brain biopsy (not typically done antemortem) would show spongiform vacuolation without inflammation and PrP immunopositivity. What is the mechanism of pathogenesis in prion disease?
52. A 40-year-old HIV-positive patient (CD4 count 50/µL) develops subacute encephalopathy. MRI shows non-enhancing, confluent white matter signal changes bilaterally. CSF PCR is positive for JC virus. What is the pathological basis of the white matter changes?
53. A 70-year-old woman with slowly progressive dementia for 3 years. At autopsy, gross examination shows cortical atrophy predominantly in the temporal and parietal lobes with 'knife-blade' gyri. Histology reveals senile plaques (amyloid-beta) and neurofibrillary tangles (hyperphosphorylated tau). Which enzyme generates the amyloid-beta peptide that aggregates in senile plaques?
54. A 35-year-old man with neurofibromatosis type 2 (NF2) develops bilateral acoustic (vestibular) schwannomas. Which molecular alteration drives schwannoma formation in NF2?
55. On brain autopsy of a patient with advanced Alzheimer disease, the neuropathological staging system (Braak and Braak stages) classifies neurofibrillary tangle (NFT) distribution in which order?
56. A 28-year-old AIDS patient (CD4 count 45 cells/µL) presents with headache, confusion, and fever. CSF India ink preparation shows budding encapsulated yeast. Cryptococcus neoformans CNS infection in immunocompromised hosts typically produces which histopathological pattern?
57. IDH1/IDH2 mutations in diffuse gliomas lead to accumulation of which oncometabolite that causes epigenetic dysregulation?
58. Prion diseases (e.g., Creutzfeldt-Jakob disease) are characterized by spongiform encephalopathy. The pathogenic mechanism involves:
59. In Alzheimer's disease, neurofibrillary tangles are composed of abnormally phosphorylated forms of which protein?
60. A 55-year-old man has a contrast-enhancing ring lesion in the white matter on MRI. Biopsy shows necrotic centre with pseudopalisading of tumour cells around it. MGMT promoter methylation status is determined. Methylation of the MGMT promoter is clinically significant because it predicts:
61. A 70-year-old man develops progressive dementia with visuospatial impairment, personality change, and cortical blindness. Autopsy shows spongiform vacuolation, neuronal loss, and gliosis in the cortex without inflammation, and the disease was transmissible to chimpanzees. The fundamental mechanism of prion disease involves:
62. A 25-year-old woman develops sudden-onset psychosis, seizures, and autonomic instability. CSF shows mild lymphocytosis. MRI shows bilateral mesiotemporal signal change. Anti-NMDAR antibodies are detected. What is the pathological target of these antibodies?
63. A 40-year-old patient with IDH-mutant glioblastoma has better prognosis than IDH-wildtype GBM. IDH1/2 mutations produce which oncometabolite that drives epigenetic changes?
64. Lewy bodies in Parkinson disease are intracytoplasmic eosinophilic inclusions composed of misfolded aggregates of which protein?
65. A 25-year-old immunocompetent patient develops acute bacterial meningitis with Gram-positive diplococci on CSF Gram stain. The most common mechanism by which Streptococcus pneumoniae crosses the blood-brain barrier is:
66. A 70-year-old man presents with a 2-year history of progressive dementia, rigidity, and falls. Autopsy shows neuronal loss in the substantia nigra and basal ganglia with pale-staining neuronal cytoplasmic inclusions that are tau-positive. This is most consistent with:
67. Glioblastoma multiforme (GBM) is characterised histologically by necrosis with a distinctive architectural pattern. This pattern is:
68. A 4-year-old presents with cerebellar ataxia, nystagmus, and a posterior fossa mass on MRI. Histology shows pseudorosettes (Homer-Wright rosettes) and small round blue cells with high N:C ratio. The most likely diagnosis is:
69. A 70-year-old with progressive dementia, rigidity, and supranuclear gaze palsy shows tau-positive neurofibrillary tangles predominantly in the subthalamic nucleus, globus pallidus, and periaqueductal gray. Cortical involvement is sparse. This pattern corresponds to:
70. A 50-year-old immunocompetent patient presents with a ring-enhancing lesion in the temporal lobe on MRI. CSF shows lymphocytic pleocytosis, elevated protein, normal glucose. PCR for herpes simplex virus is positive. The pathological hallmark on brain biopsy would be:
71. A 45-year-old man with neurofibromatosis type 2 (NF2) develops bilateral acoustic neuromas. NF2 gene encodes which tumor suppressor protein?
72. In Alzheimer disease, neurofibrillary tangles are composed primarily of:
73. Prion diseases (transmissible spongiform encephalopathies) are characterised by conversion of normal cellular prion protein (PrPC) to the pathological isoform PrPSc. The two isoforms differ in:
74. A 12-year-old boy has a posterior fossa tumor. Biopsy shows Homer Wright rosettes and small round blue cells in a background of neuropil. The diagnosis is:
75. In Alzheimer disease, amyloid plaques are composed predominantly of which peptide fragment, and from which parent protein is it derived?
76. A 40-year-old man has a well-circumscribed cerebellar tumor. Histology shows biphasic pattern with compact Rosenthal fiber–rich areas and loose microcystic areas. The tumor is GFAP positive and WHO grade 1. What is the diagnosis?
77. Lewy bodies, the pathological hallmark of Parkinson's disease, are cytoplasmic inclusions containing aggregated:
78. A 45-year-old man has a brain tumor showing pseudopalisading necrosis, microvascular proliferation, and pleomorphic glial cells. The molecular profile of IDH-wildtype glioblastoma includes:
79. The definitive histological hallmark of Parkinson disease on autopsy is:
80. A 30-year-old HIV-positive man develops progressive focal neurological deficits. MRI shows multiple non-enhancing white matter lesions. CSF PCR is positive for JC virus. Histology of the lesion would show:
81. A 35-year-old woman with neurofibromatosis type 2 (NF2) develops bilateral sensorineural hearing loss and tinnitus. MRI shows bilateral acoustic schwannomas. Which gene mutation underlies this condition?
82. The pathognomonic neuropathological triad of Alzheimer disease includes neurofibrillary tangles, senile plaques, and granulovacuolar degeneration. Neurofibrillary tangles are composed primarily of:
83. A 50-year-old immunocompetent patient develops rapidly progressive dementia with myoclonus, and periodic sharp-wave complexes on EEG. Brain MRI shows cortical ribboning on DWI sequences. CSF real-time quaking-induced conversion (RT-QuIC) test is positive. What is the pathological hallmark of this condition?
84. A 55-year-old woman has a dural-based, extra-axial mass that compresses the brain without invasion. Biopsy shows whorls of meningothelial cells with psammoma bodies and EMA positivity. The cell of origin is:
85. Lewy bodies in Parkinson's disease are intraneuronal cytoplasmic inclusions predominantly composed of which protein?
86. In bacterial meningitis, the exudate fills the subarachnoid space. Which cell type predominates in the CSF in acute purulent meningitis, and which organisms are most commonly responsible in neonates?
87. A 45-year-old woman with NF2 (neurofibromatosis type 2) has bilateral acoustic schwannomas and a meningeal mass. The meningioma on histology shows whorling of meningothelial cells and psammoma bodies. Which WHO grade is most common for meningioma?
88. A 72-year-old woman has progressive memory loss, motor neuron signs, and 14-3-3 protein in CSF. Brain MRI shows cortical ribboning on DWI. She deteriorates rapidly and dies within 6 months. Autopsy shows spongiform vacuolation of cerebral cortex, neuronal loss, astrogliosis, and PrP-immunopositive plaques. The diagnosis is:
89. A 55-year-old man with recurrent glioblastoma (GBM) on temozolomide shows disease progression. Tumor testing reveals MGMT promoter methylation. What is the significance of MGMT methylation in GBM?
90. A 65-year-old man with Parkinson disease has substantia nigra degeneration. The pathological hallmark inclusions are composed predominantly of:
91. In Alzheimer disease, the process of amyloid beta (Aβ) peptide generation from amyloid precursor protein (APP) involves sequential cleavage by two enzymes. The amyloidogenic pathway uses:
92. Glioblastoma (GBM) WHO Grade 4 is the most aggressive primary brain tumour. The WHO 2021 CNS tumour classification now requires molecular testing. Which molecular alteration characterises secondary GBM (arising from lower-grade glioma) and confers a relatively better prognosis compared to primary GBM?
93. A 70-year-old woman with progressive dementia, rigidity, and supranuclear gaze palsy is found to have tau-positive neurofibrillary tangles in the substantia nigra, subthalamic nucleus, and globus pallidus on autopsy with 4-repeat tau isoforms. The diagnosis is:
94. Prion diseases (transmissible spongiform encephalopathies) are caused by conformational conversion of normal cellular prion protein (PrPC) to misfolded scrapie isoform (PrPSc). Which structural change defines the conversion from PrPC to PrPSc?
95. Glioblastoma (WHO grade 4 diffuse astrocytoma, IDH-wildtype) is distinguished pathologically from lower-grade gliomas by which histological features?
96. In Alzheimer disease, the tau protein forms neurofibrillary tangles (NFTs). The specific biochemical change to tau that causes its aggregation is:
97. Progressive multifocal leukoencephalopathy (PML) is caused by reactivation of JC virus in immunocompromised patients. The cell type specifically infected and destroyed, causing demyelination, is:
98. A 55-year-old man presents with rapidly progressive dementia, myoclonus, and visual disturbances. EEG shows periodic sharp wave complexes. Brain biopsy shows spongiform vacuolation of the cortex with gliosis but no inflammatory infiltrate. What is the causative agent?
99. A 45-year-old AIDS patient develops a focal brain lesion. Biopsy shows reactive astrocytes and large cells with multiple enlarged nuclei containing intranuclear inclusions. The pathogen is best identified by which staining?
100. Oligodendroglioma is defined molecularly by co-deletion of chromosomal arms 1p and 19q. This co-deletion has which prognostic and predictive significance?
101. In Parkinson disease, which region of the brain shows the earliest and most severe loss of dopaminergic neurons, and what are the intraeuronal protein aggregates called?
102. An IDH-mutant, 1p/19q co-deleted lower-grade glioma in the frontal lobe of a 40-year-old is WHO grade 2 oligodendroglioma. The classic 'fried egg' artifact appearance of oligodendrocytes on formalin-fixed tissue is due to:
103. Creutzfeldt-Jakob disease (CJD) is caused by misfolded prion protein (PrPSc). The primary pathological hallmarks on brain histology are:
104. Glioblastoma (GBM, IDH-wildtype) frequently shows amplification of EGFR with a specific truncation mutation in the extracellular domain. This variant, most commonly amplified in GBM, is:
105. A 55-year-old man presents with seizures and a contrast-enhancing ring lesion in the right temporal lobe on MRI. Biopsy shows hypercellular tumor with nuclear atypia, endothelial proliferation, palisading necrosis, and abundant mitoses. Which genetic alteration confers a relatively better prognosis in tumors of this WHO grade?
106. A 35-year-old woman has an MRI showing a well-demarcated, heavily calcified frontal lobe mass. Biopsy reveals a tumor composed of uniform cells with round nuclei, clear cytoplasm giving a 'fried-egg' appearance, and a chicken-wire vascular pattern. This tumor is most strongly associated with which combined chromosomal deletion?
107. A 7-year-old boy presents with headache and vomiting. MRI reveals a midline cerebellar mass with hydrocephalus. Histology shows sheets of small round blue cells with high nuclear-to-cytoplasmic ratio, brisk mitotic activity, and Homer Wright rosettes. Which therapy targets the pathway most commonly dysregulated in this tumor?
108. A 70-year-old hypertensive man suddenly develops right-sided hemiplegia and aphasia. He dies 5 days later. Autopsy reveals a 4 cm softened, pale yellow, gelatinous area in the left middle cerebral artery territory. Microscopically, the area shows liquefactive necrosis with numerous lipid-laden macrophages (gitter cells). What is the mechanism of this infarct pattern?
109. A 45-year-old woman presents with optic neuritis followed months later by bilateral leg weakness and loss of bladder control. MRI shows periventricular white matter lesions with ovoid plaques perpendicular to the lateral ventricles (Dawson fingers). Histology of an active plaque would show:
110. An 80-year-old woman with slowly progressive dementia, difficulty walking, and urinary incontinence dies. Autopsy shows cortical atrophy predominantly in the frontal and temporal lobes. Microscopically, neuritic plaques (composed of amyloid beta core surrounded by dystrophic neurites) and neurofibrillary tangles (composed of hyperphosphorylated tau) are identified. The neurofibrillary tangles are composed of which specific structural protein?
111. A 65-year-old man develops resting tremor, rigidity, bradykinesia, and postural instability. Biopsy of the substantia nigra would reveal depletion of dopaminergic neurons and intracytoplasmic eosinophilic inclusions. These inclusions are immunoreactive for which protein?
112. A 30-year-old HIV-positive man with CD4 count of 80 cells/µL presents with altered sensorium, fever, and headache. CSF India ink preparation shows encapsulated yeast cells with a thick polysaccharide capsule. The responsible organism typically enters the CNS via which route?
113. A 6-year-old child presents with a cystic sellar/suprasellar mass causing bitemporal hemianopia, short stature, and diabetes insipidus. Biopsy shows a tumor with a peripheral layer of palisading columnar epithelium, central stellate reticulum, and areas of wet keratin (compact squamous epithelium with ghost cells). This is most consistent with:
114. A 50-year-old man develops progressive weakness of hand muscles, fasciculations, hyperreflexia, and dysphagia. MRI shows no compressive lesion. Pathologic examination would show degeneration of both upper and lower motor neurons. Aggregates of which protein are found in the remaining motor neurons?
115. A 28-year-old woman presents with a posterior fossa tumour causing ataxia. MRI shows a cystic cerebellar mass with a mural nodule. Pathology reveals spindle-shaped cells in biphasic pattern with Rosenthal fibres and eosinophilic granular bodies. Which is the most likely diagnosis?
116. In diffuse gliomas, the 2021 WHO CNS Tumor Classification now requires molecular profiling for definitive diagnosis. IDH-mutant astrocytoma is distinguished from IDH-mutant oligodendroglioma by which molecular alteration?
117. Glioblastoma (WHO Grade 4 astrocytoma) shows which combination of histological features that distinguishes it from lower-grade gliomas?