ABPath Neuropathology cheat sheet

Cortex is 6 laminae; layer III (external pyramidal) and V (internal pyramidal) give rise to corticofugal projections; layer IV is the principal thalamic recipient layer.

Brodmann areas: 4 = primary motor (precentral), 17 = primary visual (striate, calcarine), 41/42 = primary auditory, 44/45 = Broca, 22 = Wernicke.

Internal capsule: anterior limb between caudate and putamen; posterior limb between thalamus and lentiform nucleus; genu lies between them.

Basal ganglia circuitry: striatum (caudate + putamen) receives cortical input, projects to globus pallidus/SNr via direct (facilitatory) and indirect (inhibitory) pathways.

Hippocampal formation: subiculum to CA1 to CA3 to dentate gyrus (excitatory trisynaptic loop); CA1 and subiculum are most vulnerable to hypoxia.

Brainstem levels: midbrain at superior colliculus/red nucleus; pons at middle cerebellar peduncle; medulla at inferior olive and pyramidal decussation.

Cranial nerve nuclei: III/IV in midbrain, V-VIII in pons, IX-XII in medulla; LMN lesions cause ipsilateral weakness and atrophy.

Circle of Willis: anterior communicating artery joins ACAs; posterior communicating artery joins ICA to PCA; PICA arises from vertebral artery.

CSF pathway: lateral ventricles to foramina of Monro to third ventricle to aqueduct of Sylvius to fourth ventricle to foramina of Luschka/Magendie to subarachnoid space.

Glioblastoma: IDH-wildtype astrocytic tumor with necrosis and/or microvascular proliferation; grade 4 by definition in adults.

Oligodendroglioma requires both IDH mutation and 1p/19q codeletion; classic histology shows perinuclear halos and chicken-wire vasculature.

Meningioma grading: grade 1 typical; grade 2 if brain invasion, >=4 mitoses/10 HPF, or 3 of 5 atypical features (sheet-like growth, small cells, macronucleoli, hypercellularity, necrosis).

Alzheimer disease: Braak neurofibrillary tangle stage plus Thal amyloid plaque phase plus CERAD neuritic plaque score establish ABC level.

Lewy body disease: alpha-synuclein inclusions; brainstem-predominant, limbic, or neocortical distribution; cortical Lewy bodies are less distinct on H&E.

Prion disease: spongiform change, neuronal loss, gliosis; definite diagnosis requires Western blot or immunohistochemistry for PrP-res.

CNS lymphoma: large B-cell lymphoma, perivascular angiocentric infiltrate; consider EBV in immunocompromised patients.

Intraoperative consultation: fresh frozen section for tumor vs. infection vs. demyelination; crush artifact and ice crystals limit interpretation.

Tumor grading per WHO CNS5 integrates histology with molecular markers (IDH, 1p/19q, H3 K27M, MYCN, CDKN2A/B).

MGMT promoter methylation predicts temozolomide benefit in glioblastoma; testing is by methylation-specific PCR or pyrosequencing.

Turnaround time metrics: intraoperative consultation usually within 20-30 minutes; final report within 24-48 hours for routine specimens.

Specimen retention and biobanking require IRB approval and informed consent; HIPAA applies to any PHI in reports.

Proficiency testing: CAP/CLIA requires documented competency for immunohistochemistry and molecular assays with periodic validation.

Autopsy consent and brain-only autopsy protocols differ from hospital autopsy; neuropathologist may perform limited brain removal with next-of-kin consent.

Quality assurance: peer review of 10% of cases, discrepancy conferences, and root-cause analysis for diagnostic errors.

Research ethics: use of human tissue in research requires IRB oversight; de-identified specimens may qualify for exemption.

Brain biopsy: sample at enhancing rim, avoid necrotic center; fresh tissue for frozen section and molecular studies.

Muscle biopsy: orient longitudinally, snap-freeze in isopentane cooled in liquid nitrogen; avoid formalin for enzyme histochemistry.

Nerve biopsy: usually sural nerve; requires glutaraldehyde for electron microscopy and oriented longitudinal sections.

Enucleation: orient with optic nerve margin; sample tumor, sclera, choroid, and optic nerve stump; retinoblastoma requires fresh tissue for genetics.

CSF cytology: prepare cytospin and cell block; sensitivity for leptomeningeal metastasis is highest with repeat sampling.

Skeletal muscle stains: H&E, Gomori trichrome, NADH, SDH, COX, PAS, and ATPase at pH 4.3/4.6/9.4 for fiber typing.

Peripheral nerve pathology: teased fiber preparations and semithin sections assess myelin thickness and axonal loss.

Ocular pathology: corneal buttons require orientation and endothelial assessment; lens specimens for cataract show cortical and nuclear changes.

Inflammation: acute (neutrophils) vs. chronic (lymphocytes, plasma cells); granulomas contain epithelioid histiocytes and giant cells.

Neoplasia: benign vs. malignant by differentiation, growth pattern, invasion, and metastasis; grade vs. stage distinction.

Cell injury: reversible swelling and fatty change; irreversible injury shows mitochondrial and membrane damage with necrosis or apoptosis.

Amyloid: Congo red shows apple-green birefringence under polarized light; thioflavin T fluoresces.

Thrombosis: Virchow triad is stasis, endothelial injury, and hypercoagulability; emboli commonly lodge in the middle cerebral artery.

Immunohistochemistry principles: antigen retrieval, avidin-biotin or polymer detection; false positives from endogenous peroxidase or biotin.

Hemodynamic pathology: ischemia causes coagulative necrosis in most organs, liquefactive necrosis in brain.

Genetics: autosomal dominant vs. recessive inheritance; mosaicism and penetrance affect phenotype expression.