PA34.1-3,PA35.1 | Nervous System & Eye — Graded Quiz

A 3-year-old child presents with fever and a petechial rash progressing to purpura over 6 hours. He develops neck stiffness and photophobia. Lumbar puncture: opening pressure 300 mmH₂O; appearance turbid; WBC 18,000/µL (95% neutrophils); glucose 15 mg/dL (blood glucose 90 mg/dL); protein 280 mg/dL; Gram stain shows gram-negative diplococci. Despite IV antibiotics, he deteriorates over 24 hours with bilateral adrenal haemorrhage on CT. Which organism is responsible, what is the mechanism of adrenal haemorrhage, and which meningitis complication accounts for the observed coagulopathy?

A 42-year-old HIV-positive patient (CD4 count 45 cells/µL) presents with 3 weeks of progressive headache, mild confusion, and low-grade fever. CSF: opening pressure 380 mmH₂O; WBC 20 cells/µL (predominantly lymphocytes); glucose mildly decreased; protein mildly elevated; India ink preparation shows encapsulated yeast cells. Cryptococcal antigen is strongly positive. Which pathological mechanism best explains why this organism produces raised intracranial pressure without a proportionate inflammatory response, and why the India ink preparation highlights the organism?

A 60-year-old man presents with a 3-month history of progressive right temporal headache, personality change, and mild left hemiparesis. MRI shows a large ring-enhancing mass in the right temporal lobe with central necrosis and extensive surrounding oedema. The mass crosses the corpus callosum ('butterfly' appearance). Biopsy shows: pseudopalisading necrosis (tumour cells piling around areas of necrosis), glomeruloid microvascular proliferation, and pleomorphic astrocytes with irregular hyperchromatic nuclei. IDH status is wild-type. MGMT promoter is unmethylated. Which statement MOST accurately predicts this patient's prognosis and the rationale for MGMT testing?

A 35-year-old man undergoes frontal lobe biopsy for a mass lesion. Histology shows uniform round-to-oval nuclei with clear cytoplasmic halos ('fried-egg' appearance), a delicate branching capillary network ('chicken-wire' pattern), and focal calcification. Mitoses are rare. FISH confirms deletion of chromosomes 1p and 19q. The pathologist grades this WHO Grade 2. Which statement MOST accurately explains why the 1p/19q codeletion is therapeutically important and why this tumor is in the frontal lobe?

A 58-year-old woman undergoes craniotomy for a parasagittal mass causing progressive right leg weakness. Intraoperatively, the tumor appears to arise from and compress the brain from outside, with a dural attachment. It is rubbery, highly vascular, and separates cleanly from brain parenchyma. Post-operative histology shows: meningothelial whorls, psammoma bodies (laminated calcifications), and cells with oval nuclei and pale chromatin. No necrosis; Ki-67 2%. Which statement about the cell of origin, WHO grade, and the most important management decision MOST accurately reflects this tumor?

A 9-year-old boy presents with 2 months of early morning vomiting, headache, and progressive gait ataxia. MRI shows a midline posterior fossa mass in the cerebellar vermis, filling the fourth ventricle and causing obstructive hydrocephalus. Histology shows sheets of small round blue cells (SRBC) with scant cytoplasm, high nuclear-to-cytoplasmic ratio, and Homer Wright rosettes (tumour cells arranged around central neuropil fibrils). Synaptophysin is positive; GFAP is focally positive. Which statement MOST accurately classifies this tumor, explains its location preference, and identifies the most important route of spread?

A 60-year-old woman with a known history of breast carcinoma presents with 2 weeks of progressive bifrontal headache, confusion, and a new onset seizure. MRI (with contrast) shows multiple small enhancing lesions at the grey-white junction of both cerebral hemispheres. Histology of one lesion shows a nest of pleomorphic cells forming glands, surrounded by reactive gliosis; the cells are GFAP-negative and ER-positive. No Homer Wright rosettes or palisading necrosis is seen. Which feature most reliably distinguishes this lesion from a primary brain tumor, and why does metastatic carcinoma preferentially locate to the grey-white junction?

A 28-year-old woman with neurofibromatosis type 2 (NF2) develops bilateral sensorineural hearing loss. MRI shows bilateral enhancing masses at the cerebellopontine angles. Histology of the resected right-sided mass shows: spindle cells arranged in two patterns — compact elongated bipolar cells forming fascicles with Verocay bodies (Antoni A areas) and loosely textured myxoid tissue with few cells (Antoni B areas). S100 is strongly positive. Which cell of origin, chromosome, and key functional consequence of NF2 gene loss MOST accurately explains this tumor?

A 3-year-old boy is brought by his parents after a GP noticed a white reflex from the right eye (leukocoria) in a dark room photograph. On examination, visual acuity is reduced in the right eye. MRI shows an intraocular mass with calcification. Enucleation is performed. Histology shows sheets of small round blue cells with hyperchromatic nuclei. Two types of rosettes are identified: Type 1 — tumour cells arranged around a central lumen (Flexner-Wintersteiner rosettes); Type 2 — tumour cells arranged around neuropil fibrils (Homer Wright rosettes). Genetic testing shows a germline RB1 mutation on one allele. Which statement MOST accurately applies the two-hit hypothesis to predict this child's risk for a second tumour, and what is the mechanism of the RB1 protein in normal cell cycle regulation?

A pathologist examining an enucleated eye from a 2-year-old identifies two distinct rosette patterns on haematoxylin and eosin staining. Pattern 1: tumour cells (small, round, hyperchromatic) arranged in a ring around a central empty-appearing lumen with no neuropil — cells show apical specialisation resembling photoreceptor inner segments. Pattern 2: concentric rings of tumour cells around a central tangle of eosinophilic neuropil fibrils, with no lumen. A third field shows tumour cells forming a flower-like cluster without any central structure. What are the correct names and significance of these three structural patterns, and which one is most specific for retinoblastoma?

A 55-year-old man presents with 3 weeks of progressive encephalopathy and fever. He is an immunocompetent farmer who recently travelled through the Ohio River Valley region of the USA (a histoplasmosis-endemic region). CSF analysis shows: lymphocytic pleocytosis, mildly elevated protein, mildly low glucose. Serum cryptococcal antigen is negative. Brain MRI shows leptomeningeal enhancement. Culture is pending. The attending physician considers three pathogens: Cryptococcus neoformans, Histoplasma capsulatum, and Mycobacterium tuberculosis. Which CSF finding pattern would MOST reliably distinguish tubercular meningitis from both fungal causes in this setting?

A 55-year-old woman with a previously resected parietal meningioma (Simpson Grade II) returns 4 years later with a recurrent mass. Original biopsy showed 2 mitoses/10 HPF and meningothelial whorls with psammoma bodies — graded WHO Grade 1 at the time. Repeat biopsy of the recurrent mass shows: brain parenchyma infiltrated by meningioma cell nests (brain invasion), 6 mitoses/10 HPF, focal sheeting architecture, and small cell change. Ki-67 is 9%. According to WHO 2021 CNS tumour classification, what grade is this recurrent tumour, and which single histological finding alone — independent of mitotic count — is sufficient to upgrade any meningioma to WHO Grade 2?