Comparative Pathologists: Ultimate Control Freaks Seeking Validation!

Definable, reproducible, and meaningful are elemental features of grading/scoring systems, while thoroughness, accuracy, and consistency are quality indicators of pathology reports. The expertise of pathologists is significantly underutilized when it is limited to rendering diagnoses. The opportunity to provide guidance on animal model development, experimental design, optimal sample collection, and data interpretation not only contributes to job satisfaction but also, more importantly, promotes validation of the pathology data. Keys to validation include standard operating procedures, experimental controls, and standardized nomenclature applied throughout the experimental design and execution, tissue sampling, and slide preparation, as well as the creation or adaptation and application of semiquantitative grading/scoring systems. Diagnostic drift, thresholds, mental noise, and various diurnal fluctuations strongly influence the repeatability of grading/scoring systems used by the same or different pathologists. Quantitative image analyses are not plagued by the visual and cognitive traps that affect manual semiquantitative grading schemes but may still be affected by technical variables associated with necropsy, tissue sampling, and slide preparation. The validity of a grading scheme is ultimately assessed by its repeatability and biologic relevance, so it is important to correlate scores with comprehensive pathobiology data such as results of antemortem imaging, clinical pathology data, body and organ weights, and histopathologic evaluation of full tissue sets.