ABPath Neuropathology Subspecialty: Diagnostic Reasoning Guide Study Guide

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At the edge of a destructive lesion, identify whether GFAP-positive stellate cells are the abnormal population or reactive astrocytes surrounding another process. In a tumor, assess architecture and other differentiation evidence, including possible ependymal differentiation.

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In a young adult with an infiltrative glial tumor and negative R132H staining, consider sequence-based IDH assessment when the differential remains compatible with an IDH-mutant tumor.

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Report retained GFAP-positive astrocytes and reduced perivascular AQP4 separately. These observations assess different proteins and can coexist within an injured region.

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Compare myelin staining with an axonal preparation in a pale white matter lesion. Then use cellular changes, distribution, and etiologic evidence to distinguish possible causes.

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An astrocytic-appearing, GFAP-positive tumor still requires the relevant IDH and chromosome-arm assessment before assignment to an adult diffuse glioma entity.

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A glioma block contains a small viable focus beside extensive necrosis. Select the viable tumor-rich area rather than extracting indiscriminately from the entire block.

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When explaining white matter injury in a very premature infant, identify the immature oligodendroglial population instead of describing only destruction of established adult myelin.

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Identify focal necrosis, macrophage-rich organization, cavitation, or focal scars within a broader glial response when assessing premature periventricular white matter. Relate the focal lesion's stage to the surrounding diffuse injury.

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A narrow hemispheric defect connects ventricular and pial surfaces. Cortical gray matter along its margins supports schizencephaly even when the margins are nearly apposed.

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An epilepsy resection contains disorganized cortex, dysmorphic neurons, and unequivocal balloon cells. This cellular combination supports FCD IIb rather than IIa.

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Assess adjacent temporal cortex independently when a resection demonstrates hippocampal sclerosis. Convincing dyslamination supplies the additional evidence needed for the associated cortical diagnosis.

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Marked neuronal depletion and gliosis in both CA1 and CA4 support type 1. Assess adjacent cortical architecture independently before adding an associated dysplasia diagnosis.

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Progressive unilateral hemispheric atrophy with worsening focal seizures and cortical lymphocytic inflammation supports consideration of Rasmussen encephalitis. Earlier active regions may contain more T cells and microglial nodules, while longstanding regions may predominantly show neuronal loss and glial scarring.

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Trace ring-shaped amyloid deposits to recognizable vessel walls and record parenchymal plaques separately. This preserves the distinction between angiopathy and tissue plaque burden.

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Record extensive occipital leptomeningeal involvement and mild frontal parenchymal involvement as separate findings instead of averaging them into an unexplained global impression.

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Examine small cortical vessels specifically for capillary amyloid when assessing a region with prominent arteriolar deposits. Document whether the capillary compartment is involved.

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Describe circumferential amyloid separately from wall splitting, luminal thrombi, and adjacent hemorrhage. The second group supplies evidence of associated vasculopathy.

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Use APP-positive swollen profiles as evidence of disturbed axonal transport, then evaluate their distribution and possible traumatic or nontraumatic mechanisms.

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A small white matter block is negative after a short survival interval. Describe that sampled finding while considering whether relevant pathways and evolving lesions were adequately represented.

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In an immunocompromised patient, demyelination with enlarged oligodendroglial nuclei and bizarre astrocytes should prompt JC virus assessment rather than a tumor diagnosis based only on atypia.

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Progressive focal deficits and strongly compatible imaging despite negative initial PCR justify continued targeted evaluation rather than immediate exclusion of PML.

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New enhancement and worsening deficits after treatment initiation in established PML should raise consideration of immune-reconstitution inflammation while alternative causes are evaluated.

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Round yeast forms with clear surrounding spaces acquire a distinct mucicarmine-positive external coat. This supports recognition of cryptococcal capsules in the tissue.

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Perivascular AQP4 loss with astrocytic injury and limited myelin destruction supports an astrocyte-centered process rather than requiring advanced demyelination before recognizing the mechanism.

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AQP4 depletion in an inflammatory focus with preserved myelin and vasculocentric immune deposition provides stronger mechanistic evidence than depletion within extensively destroyed tissue.

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A symmetric central pontine lesion with myelin depletion, macrophages, and many retained axons should be correlated with sodium changes and other osmotic or systemic disturbances.

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A patient with prolonged poor intake develops confusion and gait dysfunction. Consider and promptly address thiamine deficiency despite an absent alcohol history or ocular findings.

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In a malnourished patient, sample mammillary bodies and relevant periventricular regions when examining symmetric petechial or congestive lesions. Distinguish active hemorrhagic injury from an older atrophic lesion.

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Relate small, gliotic mammillary bodies to the broader periventricular lesion pattern and nutritional history. Persistent inability to form new memories after acute confusion improves supports assessment for Korsakoff syndrome.

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An adequately sampled brain with Thal phase 3 receives A2. Determine neurofibrillary stage and neuritic plaque density independently before integrating the complete result.

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Braak stage IV produces B2 even if amyloid deposition is relatively limited. Preserve this independent staging result before applying the overall classification matrix.

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Extensive diffuse deposits with sparse neuritic plaques yield C1 from the neuritic assessment. Total amyloid abundance should not inflate that component.

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A3/B3/C1 is intermediate, whereas A3/B3/C2 is high. A2/B2/C1 is intermediate. Relate the resulting tissue classification to cognition and accompanying pathology.

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Alpha-synuclein-positive neuronal inclusions and neurites support Lewy-related pathology. Assess their distribution and other lesions before assigning their relationship to dementia or motor dysfunction.

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Preserve separate findings of intermediate Alzheimer change, alpha-synuclein-positive inclusions, and vascular lesions when discussing a patient's cognitive and motor course.

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Without confirmatory tissue examination, a compatible progressive neuropsychiatric syndrome and positive CSF RT-QuIC support probable disease. Spongiform change with neuronal loss and gliosis supplies relevant morphology; abnormal PrP assessment provides specific tissue confirmation.

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Rapidly progressive dementia with myoclonus and cerebellar signs, positive CSF 14-3-3 during an eight-month illness, and no alternative diagnosis meets this probable-disease pathway. The separate RT-QuIC pathway does not require this same combination of two clinical features.

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A diffuse thalamic glioma loses H3 K27me3 in tumor nuclei while endothelial nuclei retain it. Investigate the underlying alteration instead of assuming a particular sequence variant.

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Round nuclei and delicate vessels in an IDH-mutant diffuse glioma justify assessment of whole-arm 1p/19q status before the integrated entity is assigned.

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Review probe coverage and obtain arm-wide assessment before accepting an apparent codeletion in a tumor whose other findings favor astrocytic differentiation.

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A molecularly established oligodendroglioma with frequent mitoses, proliferating multilayered microvessels, and necrosis supports grade 3 rather than reassignment to astrocytoma.

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An IDH-mutant astrocytoma with unequivocal tumor necrosis has a histologic basis for grade 4 while retaining its IDH-mutant astrocytoma identity.

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Assign grade 4 when validated testing demonstrates the qualifying homozygous deletion in an established IDH-mutant astrocytoma, despite less aggressive histologic appearances.

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Use a suitable targeted or sequence-based method when the exact IDH variant must be established rather than inferring it from a methylation class.

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Multiple CNS hemangioblastomas with retinal involvement and a renal mass warrant communication of suspected VHL and syndrome-focused hereditary evaluation.

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For a young patient or a histologically low-grade tumor with one such finding, extend characterization rather than assigning glioblastoma from that marker alone. Assess IDH and H3 alterations, relevant MAPK or other drivers, copy-number patterns, and DNA methylation classification. Competing entities include diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype; H3-altered diffuse gliomas; MAPK-altered low-grade gliomas; pleomorphic xanthoastrocytoma; and high-grade astrocytoma with piloid features.

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Clarify whether a BRAF result represents a fusion or point mutation before relating it to a proposed tumor type or choosing additional testing.

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A negative test restricted to one fusion partner should prompt review of coverage when morphology and location continue to support a fusion-defined ependymoma.

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A confirmed hormone-negative PitNET with convincing TPIT expression supports corticotroph lineage rather than a null-cell designation based only on absent hormones.

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A confirmed PitNET with negative hormone stains and clear nuclear SF1 expression should retain its supported gonadotroph classification.

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Complete transcription-factor assessment when an initial report calls a hormone-negative tumor null cell without examining lineage markers.

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Years of difficulty gripping and rising from a chair should guide interpretation of an inflammatory biopsy with few additional distinctive findings.

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Longstanding finger-flexor and knee-extensor weakness with endomysial inflammation remains compatible with IBM even when sampled sections lack rimmed vacuoles.

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For suspected metabolic or mitochondrial disease, reserve adequate unfixed tissue for histochemistry and biochemical studies before placing a small residual portion in formalin.

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Orient fibers appropriately, freeze promptly using the receiving laboratory's method, and maintain frozen tissue on suitable transport material without allowing thawing.

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A longstanding inherited demyelinating neuropathy with a duplication containing PMP22 supports the increased-dosage mechanism of CMT1A.

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Repeated palsies after leaning on elbows or crossing legs fit a pressure-susceptibility phenotype when paired with a pathogenic reduced-function PMP22 result.

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Tumor posterior to the lamina with an uninvolved cut end should be reported as postlaminar invasion with a negative optic nerve margin.

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Do not document hereditary disease as excluded solely because a child has unilateral retinoblastoma and no affected relatives. Incorporate appropriate genetic assessment.

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Replace same-day sequential glass and digital interpretations with an adequate washout before treating agreement as evidence of diagnostic performance.