Accurately Predict Biological Behavior Proposal of a 2-Tier Histologic Grading System for Canine Cutaneous Mast Cell Tumors to More

Currently, prognostic and therapeutic determinations for canine cutaneous mast cell tumors (MCTs) are primarily based on histologic grade. However, the use of different grading systems by veterinary pathologists and institutional modifications make the prognostic value of histologic grading highly questionable. To evaluate the consistency of microscopic grading among veterinary pathologists and the prognostic significance of the Patnaik grading system, 95 cutaneous MCTs from 95 dogs were 1 Diagnostic Center for Population and Animal Health, College of Veterinary Medicine, Michigan State University, Lansing, Michigan 2 Molecular Pathology Unit, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 3 Amgen, Inc, Seattle, Washington 4 Yager-Best Histovet, Guelph, Ontario, Canada 5 Animal Health Laboratory, University of Guelph, Guelph, Ontario, Canada 6 Charles River Laboratories, Pathology Associates, Illinois 7 Antech Diagnostics, Lake Success, New York 8 Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, Gainesville, Florida 9 Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 10 Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, Georgia 11 Department of Discovery Toxicology, Bristol-Myers Squibb Company, Princeton, New Jersey 12 Department of Comparative Pathobiology, School of Veterinary Medicine, Purdue University, West Lafayette, Indiana 13 Department of Veterinary Pathology, Armed Forces Institute of Pathology, Washington, DC 14 Department of Pathobiology, Faculty of Veterinary Medicine, University of Utrecht, Utrecht, Netherlands 15 Charles River Laboratories Preclinical Services Montreal Inc, Senneville, Quebec, Canada 16 Wyoming State Veterinary Laboratory, Department of Veterinary Sciences, University of Wyoming, Laramie, Wyoming 17 Bridge Pathology Ltd, Bristol, UK 18 Department of Pathology and Infectious Diseases, The Royal Veterinary College, University of London, North Mymms, UK 19 Busch Gardens, Tampa, Florida 20 Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio 21 VDx Veterinary Diagnostics, Davis, California 22 School of Animal and Veterinary Sciences, Charles Sturt University, Wagga Wagga, New South Wales, Australia 23 Center for Comparative Epidemiology, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan yThe author is deceased Corresponding Author: Dr Matti Kiupel, PhD, DACVP, Michigan State University, Department of Pathobiology and Diagnostic Investigation, Diagnostic Center for Population and Animal Health, 4125 Beaumont Road, Room 152A, Lansing, MI 48910 Email: kiupel@dcpah.msu. edu Veterinary Pathology 48(1) 147-155 a The American College of Veterinary Pathologists 2011 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0300985810386469 http://vet.sagepub.com at UNIV OF NEBRASKA LINCOLN on June 4, 2012 vet.sagepub.com Downloaded from graded in a blinded study by 28 veterinary pathologists from 16 institutions. Concordance among veterinary pathologists was 75% for the diagnosis of grade 3 MCTs and less than 64% for the diagnosis of grade 1 and 2 MCTs. To improve concordance among pathologists and to provide better prognostic significance, a 2-tier histologic grading system was devised. The diagnosis of high-grade MCTs is based on the presence of any one of the following criteria: at least 7 mitotic figures in 10 high-power fields (hpf); at least 3 multinucleated (3 or more nuclei) cells in 10 hpf; at least 3 bizarre nuclei in 10 hpf; karyomegaly (ie, nuclear diameters of at least 10% of neoplastic cells vary by at least two-fold). Fields with the highest mitotic activity or with the highest degree of anisokaryosis were selected to assess the different parameters. According to the novel grading system, high-grade MCTs were significantly associated with shorter time to metastasis or new tumor development, and with shorter survival time. The median survival time was less than 4 months for high-grade MCTs but more than 2 years for low-grade MCTs.