Grading of Lesions

Abstract

The diagnosis of a non-neoplastic lesion is usually based on subjective morphologic characteristics of the lesion, which are published and/or based on the pathologist’s training and experiences. Naturally occurring lesions in most animal species typically follow an age-related progression of extent and severity in a specific tissue. Induced lesions often follow doseand timerelated progression. The changes in a lesion with time or dose are often reported according to general guidelines at the pathologist’s place of employment for reporting of the grading of lesions, namely, extent of the lesion in the tissue and severity of the lesion itself. The reporting usually depends on the computer system used and requirements for the study. Yet few publications have established guidelines for the grading of natural or induced lesions (Shackelford et al. 2002), although many have reported graded lesions in animals and humans. We are not aware of any government regulatory agency that requires grading of lesions. The Society of Toxicologic Pathology best practices guidelines for toxicologic histopathology (Crissman et al. 2004) recommend that ‘‘for common lesions in a species or strain of animal, it is important to know if the experimental treatment alters severity. The pathologist should use a severity grading system that allows for an appropriate severity classification, as treatment may affect incidence or severity. Toxicologic lesions are found in a continuous spectrum of severity and are often on a borderline in any classification system. Therefore, severity grading systems should be: (1) definable, (2) reproducible, and (3) meaningful.’’ The lack of any requirement or guidelines on the use of grading can result in difficulty in a clear understanding of the pathology report, especially if read by nonpathologists. The question arises as to whether or not lesions in all tissues are always graded in a report, or are those mentioned only in specific tissues such as kidney and liver also graded? Should grading only be used selectively and not always, or should it be standard for all tissues? Is the extra work involved of use, and is it cost effective? How does grading contribute to the overall quality of the pathology report? The grading of lesions should depend on the organ or tissue, anatomic structure, type of lesion, natural progression of the lesion, and dose relatedness of the lesion. Some organs would require more than one type of grading system for natural or induced lesions. The kidney has various anatomic subunits, such as glomeruli, tubules, and blood vessels, each of which can require a different type of grading system. Pathologists can be lumpers or splitters for diagnosing lesions in an organ. For example, aging nephropathy can be an average grading for the extent and severity of involvement of any portion of the nephron and kidney. Splitters can grade the glomerular lesion, tubular lesions, and grades of inflammation, as examples. Our new ‘‘INHAND’’ liver nomenclature gives an example of grading for non-neoplastic liver lesions (Thoolen et al 2010). There are many examples of grading of spontaneous or induced lesions in the kidney and other tissues in both animals (Bruner et al. 2010; Grim et al. 2009; Hard et al. 2011; Hard and Khan 2004; NTP 2007) and humans (Caballero et al. 2001). Suggested methods for statistical analysis of subjectively graded lesions have been reported in these and many other papers. Holland and Holland (in this issue) review various methods for grading and its statistical evaluation. They suggest that the best approach may be an ‘‘ordering method,’’ whereby the slides are all coded and placed in groups of grades, which are subsequently decoded. The pathologist then makes a judgment on the lesions after a statistical test is performed. It seems to be a valuable method, but it perhaps requires more work than the usual, less formalized methods of grading. Computerized image analysis may in some cases represent the ultimate method for reporting and grading lesions of any type (Boyce et al. 2010; Maximova et al. 2009; Potts et al. 2010). It is not subjective or based on the pathologist’s opinion of the diagnosis and grading of a lesion, but rather, it is based on the computerized appearance of the lesion and its cell components, using computer analysis possibly supplemented by immunohistochemistry. Presently, regulatory agencies in many nations do not require the grading of lesions, and little is defined for this step with regard to quality in pathology reporting (Isaacs 2007). When regulators read reports of the toxicologic pathology of a chemical in animals and then read about the grading of lesions, they often ask questions as to the methods used and the significance of the grading results. They can also be confused