1. ¹Department of Pathology, Stanford University, Stanford, CA, USA
2. ²Applied Statistician, Markham, Ontario, Canada
3. ³Department of Pathology, Jewish General Hospital, Montreal, Quebec, Canada
4. ⁴Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada
5. ⁵Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
6. ⁶Department of Pathology, Mount Sinai Medical Center, New York, NY, USA
7. ⁷Department of Pathology, St Clare's Hospital, St Johns, Newfoundland, Canada
8. ⁸Department of Pathology, Cooper Health, Camden, NJ, USA
9. ⁹Department of Pathology, Columbia University, New York, NY, USA
10. ¹⁰Department of Pathology, University of Utah, Salt Lake City, UT, USA
11. ¹¹Department of Pathology, Fox Chase Cancer Center, Philadelphia, PA, USA

Correspondence: Dr FP O'Malley, MB, FRCPC, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Ave., Toronto, Canada M5G1X5. E-mail: fomalley@mtsinai.on.ca

Received 20 June 2005; Revised 12 August 2005; Accepted 13 August 2005; Published online 9 December 2005.

Abstract

The United States National Cancer Institute Breast/Ovarian Cancer Family Registry is the largest international Registry of this type; over 37 724 individuals have been enrolled to date. One activity of this Registry is the semicentralized pathologic review of tumors from all probands. Given the semicentralized nature of the review, this study was undertaken to determine the reproducibility, source(s) of classification discrepancies and stratagems to circumvent discrepancies for histologic subtyping and grading of invasive breast cancer among the reviewing pathologists. A total of 13 pathologists reviewed 35 invasive breast cancers and classified them by primary and secondary histologic type, Nottingham grade and score. Lymph–vascular space invasion, circumscribed margins, syncytial growth and lymphocytic infiltrate were also evaluated. A training session using a separate set of slides was conducted prior to the study. General agreement, in terms of category-specific 's and percent agreement, and accuracy of classification relative to a reference standard were determined. Classification of histologic subtype was most consistent (and accurate) for mucinous carcinoma (=1.0), followed by tubular (=0.8) and lobular subtypes (=0.8). Classification of medullary subtype was moderate (=0.4), but additional evaluation of degree of lymphocytic infiltrate, syncytial growth and circumscribed margins identified most cases. Category-specific 's were moderate to good for Nottingham grade (=0.5–0.7), with the greatest agreement obtained in categorizing grade I (=0.7), and grade III tumors (=0.7). A flexible classification strategy that employs individual and combined criteria provides good interobserver agreement for invasive breast cancers with uniform, unambiguous histology and compensates for classification discrepancies in the more histologically ambiguous or heterogeneous cancers.