Theoretical, Investigative, and Administrative Neuropathology
Beyond the microscope
This domain tests laboratory operations, quality, and research literacy - areas candidates often neglect.
Concepts to understand:
- Specimen handling and turnaround: fixation time affects IHC and molecular results; formalin overfixation impairs DNA/RNA quality.
- Quality assurance: proficiency testing, peer review, discrepancy review, and documentation of critical results.
- Regulatory frameworks: CLIA/CAP accreditation concepts, validation of new assays (sensitivity, specificity, concordance), and chain of custody for forensic or research specimens.
- Research methods: sensitivity vs specificity, positive/negative predictive value, and how prevalence changes PPV. Understand bias and confounding in observational studies.
- Bioinformatics basics: variant interpretation, tumor mutational burden, and the difference between germline and somatic findings.
Traps:
- Confusing sensitivity (true positives among diseased) with PPV (true positives among test-positives).
- Forgetting that prevalence alters predictive value but not sensitivity/specificity.
- Assuming a validated assay transfers across platforms without bridging studies.
Rule of thumb: For any test question, write the 2×2 table. If prevalence rises, PPV rises and NPV falls, while sensitivity and specificity stay fixed. For administrative questions, the safest answer usually emphasizes documentation, validation, and peer review.
Worked example: A new CSF biomarker has 90% sensitivity and 90% specificity. In a high-prevalence clinic, PPV is high; in a screening population, PPV collapses. This explains why the same test performs differently across settings - a common exam trap.