A Revised Diagnostic Classification of Canine Glioma: Towards Validation of the Canine Glioma Patient as a Naturally Occurring Preclinical Model for Human Glioma

Abstract

The National Cancer Institute-led multidisciplinary Comparative Brain Tumor Consortium (CBTC) convened a glioma pathology board, comprising both veterinarian and physician neuropathologists, and conducted a comprehensive review of 193 cases of canine glioma. The immediate goal was to improve existing glioma classification methods through creation of a histologic atlas of features, thus yielding greater harmonization of phenotypic characterization. The long-term goal was to support future incorporation of clinical outcomes and genomic data into proposed simplified diagnostic schema, so as to further bridge the worlds of veterinary and physician neuropathology and strengthen validity of the dog as a naturally occurring, translationally relevant animal model of human glioma. All cases were morphologically reclassified according to a new schema devised by the entire board, yielding a majority opinion diagnosis of astrocytoma (43, 22.3%), 19 of which were low-grade and 24 high-grade, and oligodendroglioma (134, 69.4%), 35 of which were low-grade and 99 were high-grade. Sixteen cases (8.3%) could not be classified as oligodendroglioma or astrocytoma based on morphology alone and were designated as undefined gliomas. The simplified classification scheme proposed herein provides a tractable means for future addition of molecular data, and also serves to highlight histologic similarities and differences between human and canine glioma.

Diagnostic accuracy of stereotactic brain biopsy for intracranial neoplasia in dogs: Comparison of biopsy, surgical resection, and necropsy specimens

“…From the slide material provided for each case in each set, pathologists were asked to provide a neuropathologic diagnosis, and if the assigned diagnosis was neoplastic, that tumors initially be classified and graded according to World Health Organization (WHO) criteria . Two pathologists later were tasked with reclassifying glial tumors after the recent release of the revised classification criteria for dogs, in which gliomas are graded in a binary fashion (high‐ versus low‐grade) . During the review process, pathologists were asked to provide specific reasons for any samples that were determined to be nondiagnostic, and any comments regarding the samples that influenced their diagnostic conclusions.…”

“…Thus, it is not unexpected that more disagreements were noted using the WHO grading system. Pathologists in our study commented that the absence of the hallmark morphologic feature of necrosis in SBB specimens often precluded assignment of a Grade IV astrocytoma or Grade III oligodendroglioma (high‐grade glioma) diagnosis . This may represent a form of sampling bias, because the neurosurgeon performing SBB intentionally avoided necrotic tumor regions, given that obtaining biopsy specimens from necrotic areas accounts for a substantial proportion of nondiagnostic samples in studies of SBB in dogs and humans .…”

“…First, methods to minimize interobserver variability between pathologists classifying tumors were not included in the study design. Although pathologists participating in the study all have experience with brain tumors in dogs and SBB, similar to the results reported here, agreement among experts reviewing glioma histomorphology and grade in dogs and humans has been reported previously as moderate . Incorporation of joint training and multiple specimen review sessions for pathologists has been shown to improve DA and should be considered in future studies .…”

“…This may represent a form of sampling bias, because the neurosurgeon performing SBB intentionally avoided necrotic tumor regions, given that obtaining biopsy specimens from necrotic areas accounts for a substantial proportion of nondiagnostic samples in studies of SBB in dogs and humans . Phenotypic heterogeneity within gliomas is well recognized to present diagnostic challenges to neuropathologists in human and veterinary medicine, especially when considering the sample size limitations inherent to SBB . Our findings further support usage of the revised canine glioma system to streamline and standardize glioma diagnosis in dogs.…”

“…8 Two pathologists later were tasked with reclassifying glial tumors after the recent release of the revised classification criteria for dogs, in which gliomas are graded in a binary fashion (high-versus low-grade). 9 During the review process, pathologists were asked to provide specific reasons for any samples that were determined to be nondiagnostic, and any comments regarding the samples that influenced their diagnostic conclusions. At least 6 weeks lapsed between a pathologist's review of each of the slide sets.…”