Researchers assess diagnostic criteria for canine glioma

By on August 15, 2022 0

A multi-institutional team led by researchers at North Carolina State University found that using recently published criteria for the diagnosis of canine glioma resulted in strong diagnostic consensus among pathologists. The results not only pave the way for more standardized diagnostic criteria for dogs with brain tumors, but also create a useful baseline to support larger interagency studies that could help dogs and humans with glioma.

Gliomas are a family of tumors that occur in the brain and spinal cord and account for 30-40% of intracranial tumors in dogs. Humans can suffer from these same tumors; however, in human medicine, physicians have a diagnostic algorithm based on molecular and microscopic characteristics that helps them identify and agree on the subtype and grade (or severity) of glioma.

Dogs did not have a similar set of standards until 2018, when the Comparative Brain Tumor Consortium (CBTC) created a set of diagnostic criteria aimed at helping veterinary pathologists reach diagnostic consensus.

“The CBTC diagnostic criteria system could be very useful not only for the clinical diagnosis of canine patients, but also to enable inter-institutional research collaboration, since everyone speaks the same language, from a diagnostic point of view,” says Gregory Krane, co-lead author of the paper, a veterinary pathologist currently working at Moderna and a former Ph.D. student at NC State. “To that end, we wanted to do a real-world system evaluation. »

Krane obtained 85 glioma specimens from dogs examined at NC State between 2006 and 2018. Five pathologists — one MD neuropathologist, two veterinary neuropathologists, and two veterinary pathologists with no subspecialty training in neuropathology — separately reviewed the specimens using the guidelines of the CBTC.

There are three types of canine glioma: oligodendroglioma, astrocytoma or indefinite glioma. Each of these subtypes can further be classified as low or high based on certain microscopic characteristics. Pathologists used both microscopy and immunohistochemistry to analyze the samples.

Consensus was defined as three or more of five pathologists agreeing on tumor subtype and grade. A consensus diagnosis was obtained for 71 of 85 cases (84%).

Keith Shockley, co-first author of the study and a biostatistician at the National Institute of Environmental Health Sciences (NIEHS), helped perform advanced statistical analysis on the diagnoses to obtain a kappa statistic, which estimates the degree of agreement between different evaluators beyond what would be predicted by chance alone.

The kappa statistic is regularly used in human studies to quantify diagnostic consensus, primarily in the fields of pathology and radiology. Agreement levels for the kappa statistic are defined as weak, slight, medium, moderate, substantial, near perfect, and perfect. The kappa statistic for the CBTC criteria was moderate, which was similar to most human glioma studies.

“These results show that the CBTC system is just as reliable as those used in human studies,” says Krane. “Hopefully, this will support multi-institutional studies with large caseloads, so we can begin to leverage our data to help advance diagnostic and treatment options for canine and human glioma patients.”

“The study also shows that even with detailed diagnostic criteria, consensus among pathologists is often not 100%. For a clinical setting, practitioners must be comfortable speaking with their pathologist if the diagnosis is n is not compatible with the rest of the clinical picture, and in the context of research, investigators can strengthen their studies by incorporating groups of pathologists into the diagnostic examination.

The study appears in Veterinary and comparative oncology and was funded by the NIEHS and the College of Veterinary Medicine at North Carolina State University. Christopher Mariani, professor of neurology and neurosurgery at the NC State College of Veterinary Medicine, is the book’s corresponding author.

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Note to Editors: A summary follows.

“Inter-pathologist agreement on the diagnosis, classification and grading of canine glioma”

DO I: 10.1111/vco.12853

Authors: Gregory A. Krane, Debra A. Tokarz; Matthew Breen, Christopher L. Mariani, North Carolina State University; Keith R. Shockley, David E. Malarkey, Heather L. Jensen; National Institute of Environmental Health Sciences; Andrew D. Miller, Cornell University; C. Ryan Miller, University of Alabama at Birmingham; Kyathanahalli S. Janardhan, Integrated Laboratory Systems
Published: Posted on July 22, 2022 in Veterinary and comparative oncology

Summary:
Histopathological evaluation of tumors is a subjective process, but studies of interpathologist agreement are rare in veterinary medicine. The Comparative Brain Tumor Consortium (CBTC) recently published diagnostic criteria for canine gliomas. Our objective was to assess the degree of inter-pathologist agreement on canine intracranial gliomas, using the CBTC diagnostic criteria in a cohort of eighty-five samples from dogs with an archival diagnosis of intracranial glioma. Five pathologists independently reviewed the H&E and immunohistochemistry sections and provided diagnosis and grade. Percent agreement and kappa statistics were calculated to measure interpathologist agreement between pairs and among the whole group. A consensus diagnosis of glioma subtype and grade was obtained for 71/85 (84%) cases. For these cases, the percent agreement on combined diagnosis (subtype and grade), subtype only, and grade only was 66%, 80%, and 82%, respectively. The Kappa statistics for the same were 0.466, 0.542, and 0.516, respectively. Kappa statistics for oligodendroglioma, astrocytoma, and indefinite glioma were 0.585, 0.566, and 0.280 and were 0.516 for low-grade and high-grade tumors. Kappa statistics among pathologist pairs for the combined diagnosis ranged from 0.352 to 0.839. 8% of archived oligodendrogliomas and 61% of archived astrocytomas were reclassified as another entity after examination. Inter-pathologist agreement using the CBTC guidelines for canine glioma was moderate overall, but ranged from fair to near perfect between pairs of pathologists. Concordance was similar for oligodendrogliomas and astrocytomas but lower for indefinite gliomas. These results are similar to the agreement of pathologists in studies of human gliomas and with other tumor entities in veterinary medicine.