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Researchers Assess Diagnostic Criteria for Canine Glioma

Golden retriever
Photo by Josef Reckziegel on Unsplash

For Immediate Release

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

Gliomas are a family of tumors that occur in the brain and spinal cord and comprise 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 features that help 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 achieve diagnostic consensus.

“The CBTC system of diagnostic criteria could be very useful not only in the clinical diagnosis of canine patients, but also in enabling inter-institutional research collaboration, since it has everyone speaking the same language, diagnostically speaking,” says Gregory Krane, co-lead author of the paper, a veterinary pathologist currently working at Moderna and former Ph.D. student at NC State. “To that end, we wanted to conduct a real-world assessment of the system.”

Krane obtained 85 glioma samples taken from dogs examined at NC State between 2006 and 2018. Five pathologists – one M.D. neuropathologist, two veterinary neuropathologists, and two veterinary pathologists without subspecialty training in neuropathology – separately examined the samples using the CBTC guidelines.

There are three types of canine glioma: oligodendroglioma, astrocytoma or undefined glioma. Each of these subtypes can be further classified as low or high-grade based on certain microscopic features. The pathologists utilized both microscopy and immunohistochemistry to analyze the samples.

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

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

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

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

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

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

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Note to editors: An abstract follows.

“Inter-pathologist Agreement on Diagnosis, Classification and Grading of Canine Glioma”

DOI: 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: Online July 22, 2022 in Veterinary and Comparative Oncology

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

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