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Variability in diagnostic threshold for comedo necrosis among breast pathologists: implications for patient eligibility for active surveillance trials of ductal carcinoma in situ

Abstract

Active surveillance trials for low-risk ductal carcinoma in situ (DCIS) are in progress in the United States and Europe. In some of these trials, the presence of comedo necrosis in the DCIS has been an exclusion criterion for trial entry. However, the minimum amount of necrosis required by pathologists for a diagnosis of comedo necrosis is not well-defined. We surveyed 35 experienced breast pathologists to assess their diagnostic threshold for comedo necrosis. Pink circles representing necrosis ranging in extent from 10 to 80% of the duct diameter were superimposed on eight replicate histologic images of a single duct involved by low nuclear grade, solid pattern DCIS. These images were circulated by e-mail to the participating pathologists who were asked to select the image that represents the minimum amount of necrosis that they require for a diagnosis of comedo necrosis. Among the 35 participants, the minimum extent of the duct diameter required for a diagnosis of comedo necrosis was 10% for 4 pathologists, 20% for 5, 30% for 11, 40% for 7, 50% for 6, 60% for 1 and 70% for 1. There was no single threshold about which more than one-third of the pathologists agreed met the minimal criteria for comedo necrosis. We conclude that even among experienced breast pathologists, the threshold for comedo necrosis is highly variable. Our findings highlight the need for a standardized definition of comedo necrosis as a trial criterion, and more generally where it may be used as a marker of increased risk of recurrence for therapeutic decision making.

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Acknowledgements

We would like to acknowledge the breast pathologists who participated in our survey in addition to authors B.H. and S.S., without whom this study would not have been possible.Constance Albarracin, The University of Texas MD Anderson Cancer Center, Houston, TX.Kimberly Allison, Stanford University School of Medicine, Stanford, CA. Sunil Badve, Indiana University School of Medicine, Indianapolis, IN. Gabrielle Baker, Beth Israel Deaconess Medical Center, Boston, MA. Ira Bleiweiss, Hospital of the University of Pennsylvania, Philadelphia, PA. Jane Brock, Brigham and Women’s Hospital, Boston, MA. Edi Brogi, Memorial Sloan Kettering Cancer Center, New York, NY. Laura Collins, Beth Israel Deaconess Medical Center, Boston, MA. James Connolly, Beth Israel Deaconess Medical Center, Boston, MA. Yunn-Yi Chen, University of California San Francisco, San Francisco, CA. David Dabbs, Magee-Womens Hospital, Pittsburgh, PA. Susan Feinberg, Montefiore Medical Center, Bronx, NY.Hannah Gilmore, University Hospitals Cleveland Medical Center, Cleveland, OH. Thomas Gudewicz, Massachusetts General Hospital, Boston, MA. Xufei Hong, Brigham and Women’s Faulkner Hospital, Boston, MA. Timothy Jacobs, Virginia Mason Medical Center, Seattle, WA. Shabnam Jaffer, Mount Sinai Hospital, New York, NY. Kristen Jensen, Stanford University School of Medicine, Stanford, CA. Erinn Downs Kelly, Cleveland Clinic, Cleveland, Ohio.Gregor Krings, University of California San Francisco, San Francisco, CA. Melinda Lerwill, Massachusetts General Hospital, Boston, MA.Susan Lester, Brigham and Women’s Hospital, Boston, MA. Jonathan Marotti, Dartmouth-Hitchcock Medical Center, Lebanon, NH. Melissa Murray, Memorial Sloan Kettering Cancer Center, New York, NY. Juan Palazzo, Thomas Jefferson University Hospital, Philadelphia, PA. Liza Quintana, Beth Israel Deaconess Medical Center, Boston, MA. Mara Rendi, University of Washington, Seattle, WA. Jordi Rowe, Cleveland Clinic, Cleveland, OH. Dennis Sgroi, Massachusetts General Hospital, Boston, MA. Sandra Shin, Albany Medical College, Albany, NY. Donald Weaver, University of Vermont, Burlington, VT. Hannah Wen, Memorial Sloan Kettering Cancer Center, New York, NY. Tad Wieczorek, Brigham and Women’s Faulkner Hospital, Boston, MA.

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The authors declare that they have no conflict of interest.

Correspondence to Beth T. Harrison.

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