Multi-site bone marrow core biopsy improves diagnostic accuracy in dogs with hematologic disease

Abstract

Background Spatial heterogeneity within bone marrow significantly affects diagnostic accuracy in human and veterinary medicine, where single-site sampling may fail to detect focal disease processes. However, optimal bone marrow sampling strategies for canine hematologic disease diagnosis remain unclear, representing a critical knowledge gap in veterinary diagnostic pathology. We hypothesized that multi-site bone marrow core sampling would provide superior diagnostic accuracy compared to current single-site sampling standards in canine patients. The primary aim was to evaluate diagnostic capture probability of sampling one to four bone marrow sites in dogs with suspected hematologic disease.

Methods and findings Sixteen dogs with suspected hematologic disease underwent bone marrow trephine biopsies from four anatomical locations (bilateral proximal humerus and iliac crest) using the ARROW OnControl Powered Driver system. Two board-certified clinical pathologists independently evaluated 64 masked bone marrow samples. Diagnostic accuracy was assessed using truth set methodology, with statistical analysis including mixed-effects logistic regression and bootstrap confidence intervals. Multi-site core sampling significantly improved diagnostic capture probability. Moving from one to two sites increased diagnostic accuracy from 76.6% to 94.8% under the permissive rule (18.2% improvement, P < 0.0001), and from 28.1% to 47.9% when both pathologists agreed (19.8% improvement). Significant site-specific differences were observed in myeloid-to-erythroid ratios and megakaryocyte counts. Overall, 13.3% of samples were nondiagnostic, with modest inter-pathologist agreement (κ=0.30, 42% agreement).

Conclusions Multi-site bone marrow core sampling provides clinically meaningful improvements in diagnostic accuracy for canine hematologic diseases, with the greatest benefit achieved by adding a second sampling site to current single-site protocols.