Abstract
The editor and 4 contributing authors set out to provide a basic overview of pathology principles and practices that pertain to the conduct and interpretation of pathology data associated with preclinical safety studies. This overview is intended to provide some insight to toxicologists and other study associated personnel who often review the anatomic or clinical pathologist’s product.
In my view, the preface of this book seems to present pathology assessments/product in a negative context. It does not emphasize the essential value of appropriate pathology observations, data integration, and pathology assessments for preclinical assessment of test article–related changes. Since the audience of this textbook is aimed at study personnel, it would have been appropriate to focus the preface on the value of pathologist tools, practices, and data assessments.
Some chapters of this book present well-written, well-organized, and succinct overviews of specific topics in preclinical research that are pertinent to study personnel. These chapters include principles for documenting pathology data, clinical pathology, adversity (a pathologist’s perspective), and the limitations of pathology and animal models. They have appropriate applicable figures that are supportive of important text concepts. The figures are well integrated into the pertinent factual text. Figure legends in these chapters are well crafted. These sections are an appropriate overview for the targeted audience and do not attempt to oversimplify topics/message. These chapters would certainly provide thoughtful and useful sources of teaching material to educators in the toxicology or toxicologic pathology disciplines. In addition, they are a relevant contemporary framework to communicate basic concepts of pathology practices/challenges/limitations with certain study personnel, sponsors, regulators, and management.
Other chapters of this book, however, are anticipated to be of limited value for the targeted audience. These chapters are less polished and are often not clearly and specifically directed to a preclinical research audience. The presentation of certain topics in these chapters is too superficial, haphazardly arranged, and imprecise for clear and meaningful communication of basic concepts or practices applicable to preclinical research. Some asserted factual statements are inaccurate, and concepts in various sections are notably incomplete. Examples of erroneous and misleading information include statements such as “peer review is required for GLP-compliant studies,” “Generally, most rodent studies will require the examination of a PAS-stained slide of testes to ensure no treatment related findings have occurred,” and “there are no absolute reasons for selecting a particular animal species for systemic toxicity testing.… Non-rodent species may also need to be considered for testing.”
The chapter covering common background lesions in laboratory animal species is inadequate at providing a basic overview of common lesions observed in preclinical studies. The sections pertaining to minipigs, dogs, rabbits, and nonhuman primates are particularly limited in scope. The chapter on basic pathology processes contains a mixture of information gleaned from various references but does not clearly present coherent concepts/processes specifically applicable to preclinical toxicologic pathology findings and terminology. Some terminology in text and figures is archaic, and the use of such terms as macroscopic diagnoses is discouraged in preclinical assessments (eg, dry gangrene of ear tips, liquefactive necrosis of the brain, yellow fatty change in a ruminant liver). Imprecise, casual phrases are used throughout the chapters, particularly in context to gross abnormalities. Examples include “severe cell injury is not difficult to recognize” (associated with a gross image of purulent meningitis), “it is easy to recognize healing,” “an enlarged heart is easy to recognize at necropsy,” and “necrosis is easy to recognize at necropsy.” Pathology processes are rarely as obvious or distinctive on gross assessment as asserted and can often only be made once data from various aspects of the study (including histopathology) are integrated with macroscopic findings. This critical point may be lost on the target audience.
Many figures and figure legends incorporated into certain specific chapters have shortcomings. Quality of photographs in these chapters is inconsistent. Selection of various photographs and legends to present basic concepts in tissue techniques does not clearly demonstrate specific principles/concepts (eg, trimming sheet, quality control, hematoxylin and eosin stain, phosphotungstic acid hematoxylin stain). Figure legends for many photographs, diagrams, and pathologic images in these chapters are extremely brief and omit basic information. Annotations, where employed, are basic and of limited value in pointing out normal vs abnormal tissue. Many of the macroscopic images depict bovine/ruminant abnormalities (eg, yellow fatty change in the ruminant liver, fibrinous inflammation around a ruminant heart, coagulative necrosis in a ruminant kidney) or rare findings in species used in preclinical studies (eg, hemangiosarcoma in a canine lung) rather than “common” findings in common preclinical species. Additional text in figure legends might have clarified that diagnoses were based on microscopic findings rather than by gross assessment as implied in the figure legends. The details for figures and figure legends are more appropriately and clearly covered in other chapters in this textbook. A uniform figure and legend style should have been used throughout the textbook. Because of the shortcomings and inaccuracies in specific chapters, I recommend using other published texts that address the specific topics of necropsy techniques, histology procedures, general pathology/study concepts, and species-specific background pathology.
To conclude, there is useful information in various chapters of this textbook, including those with highlighted flaws. However, one needs to be selective and discerning when using this textbook in totality as a source of information for basic principles of pathology for toxicologists/study personnel. Thus, the utility of this textbook for the intended target audience may be limited.