title: Intraductal carcinoma of the prostate: interobserver reproducibility survey of 39 urologic pathologists.
abstract: The diagnosis of intraductal carcinoma (IDC) of the prostate remains subjective because 3 sets of diagnostic criteria are in use. An internet survey was compiled from 38 photomicrographs showing duct proliferations: 14 signed out as high-grade prostatic intraepithelial neoplasia (HGPIN), 17 IDC, and 7 invasive cribriform/ductal carcinoma. Each image was assessed for the presence of 9 histologic criteria ascribed to IDC. Thirty-nine respondents were asked to rate images as (1) benign/reactive, (2) HGPIN, (3) borderline between HGPIN and IDC, (4) IDC, or (5) invasive cribriform/ductal carcinoma. Intraclass correlation coefficient was 0.68. There was 70% overall agreement with HGPIN, 43% with IDC, and 73% with invasive carcinoma (P < .001, χ(2)). Respondents considered 19 (50%) of 38 cases as IDC candidates, of which 5 (26%) had a two-thirds consensus for IDC; two-thirds consensus for either borderline or IDC was reached in 9 (47%). Two-thirds consensus other than IDC was reached in the remaining 19 of 38 cases, with 15 supporting HGPIN and 4 supporting invasive carcinoma. Findings that differed across diagnostic categories were lumen-spanning neoplastic cells (P < .001), 2× benign duct diameters (P < .001), duct space contours (round, irregular, and branched) (P < .001), papillary growth (P = .048), dense cribriform or solid growth (both P = .023), and comedonecrosis (P = .015). When the 19 of 38 images that attained consensus for HGPIN or invasive carcinoma were removed from consideration, lack of IDC consensus was most often attributable to only loose cribriform growth (5/19), central nuclear maturation (5/19), or comedonecrosis (3/19). Of the 9 histologic criteria, only 1 retained significant correlation with a consensus diagnosis of IDC: the presence of solid areas (P = .038). One case that attained IDC consensus had less than 2× duct enlargement yet still had severe nuclear atypia and nucleomegaly. Six fold nuclear enlargement was not significant (P = .083), although no image had both 6× nuclei and papillary or loose cribriform growth: a combination postulated as sufficient criteria for IDC. Finally, 20.5% of respondents agreed that an isolated diagnosis of IDC on needle biopsy warrants definitive therapy, 20.5% disagreed, and 59.0% considered the decision to depend upon clinicopathologic variables. Although IDC diagnosis remains challenging, we propose these criteria: a lumen-spanning proliferation of neoplastic cells in preexisting ducts with a dense cribriform or partial solid growth pattern. Solid growth, in any part of the duct space, emerges as the most reproducible finding to rule in a diagnosis of IDC. Comedonecrosis is a rarer finding, but in most cases, it should rule in IDC. Duct space enlargement to greater than 2× the diameter of the largest, adjacent benign spaces is usually present in IDC, although there may be rare exceptions.
authors.affiliation: Medical College of Wisconsin, Milwaukee, WI. Electronic address: kaiczkowski@mcw.edu.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Iczkowski
authors.affiliation: Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lars
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authors.affiliation: Bostwick Laboratories, Orlando, FL.
authors.forename: Jun
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authors.affiliation: Medical College of Wisconsin, Milwaukee, WI.
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authors.lastname: Harding-Jackson
authors.affiliation: Universitat Autónoma de Barcelona, Barcelona, Spain.
authors.forename: Ferran
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authors.affiliation: State University of Campinas (Unicamp), Campinas, Brazil.
authors.forename: Athanase
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authors.affiliation: Cabinet de Pathologie, Amiens, France.
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authors.lastname: Camparo
authors.affiliation: Indiana University, Indianapolis, IN.
authors.forename: Liang
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authors.affiliation: TissuPath, Mount Waverley, Victoria, Australia.
authors.forename: David
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authors.affiliation: Pitié-Salpêtrière Hospital Université Pierre et Marie Curie, Paris, France.
authors.forename: Eva M
authors.initials: EM
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authors.affiliation: Hospital Pathology Associates, PA, Minneapolis, MN.
authors.forename: Milton W
authors.initials: MW
authors.lastname: Datta
authors.affiliation: University of Toronto, Toronto, ON, Canada.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Evans
authors.affiliation: University Hospital of Wales, Cardiff, United Kingdom.
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authors.lastname: Griffiths
authors.affiliation: University of Texas MD Anderson Cancer Center, Houston, TX.
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authors.affiliation: University of Zurich, Zurich, Switzerland.
authors.forename: Seife
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authors.lastname: Hailemariam
authors.affiliation: University of Wisconsin, Madison, WI.
authors.forename: Wei
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authors.affiliation: Yale University, New Haven, CT.
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authors.initials: PA
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authors.affiliation: University of Colorado, Aurora, CO.
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authors.initials: FG
authors.lastname: La Rosa
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authors.forename: Antonio
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authors.affiliation: Case Western Reserve University, Cleveland, OH.
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authors.lastname: Magi-Galluzzi
authors.affiliation: Dalhousie University, Halifax, NS, Canada.
authors.forename: Jennifer
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authors.lastname: Merrimen
authors.affiliation: Polytechnic University of the Marche Region, Ancona, Italy.
authors.forename: Rodolfo
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authors.lastname: Montironi
authors.affiliation: Emory University, Atlanta, GA.
authors.forename: Adeboye O
authors.initials: AO
authors.lastname: Osunkoya
authors.affiliation: Loyola University, Maywood, IL.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Picken
authors.affiliation: Medical College of Wisconsin, Milwaukee, WI.
authors.forename: Nagarjun
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authors.lastname: Rao
authors.affiliation: Life Sciences Research Institute, Miraca Life Sciences, Irving, TX.
authors.forename: Rajal B
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authors.lastname: Shah
authors.affiliation: Christie Hospital, Manchester, United Kingdom.
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Shanks
authors.affiliation: The Methodist Hospital, Houston, TX.
authors.forename: Steven S
authors.initials: SS
authors.lastname: Shen
authors.affiliation: Kansas University Medical Center, Kansas City, KS.
authors.forename: Ossama W
authors.initials: OW
authors.lastname: Tawfik
authors.affiliation: University of Washington, Seattle, WA.
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: True
authors.affiliation: University of Toronto, Toronto, ON, Canada.
authors.forename: Theodorus
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authors.lastname: Van der Kwast
authors.affiliation: University Hospital of Wales, Cardiff, United Kingdom.
authors.forename: Murali
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authors.lastname: Varma
authors.affiliation: Baylor College of Medicine, Houston, TX.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Wheeler
authors.affiliation: Ohio State University, Columbus, OH.
authors.forename: Debra L
authors.initials: DL
authors.lastname: Zynger
authors.affiliation: Medical College of Wisconsin, Milwaukee, WI.
authors.forename: Natasha
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mesh_terms: D002285:Carcinoma, Intraductal, Noninfiltrating / Q000473:pathology*; D003937:Diagnosis, Differential; D006306:Health Surveys; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D015588:Observer Variation; D010820:Physicians; D011379:Prognosis; D019048:Prostatic Intraepithelial Neoplasia / Q000473:pathology; D011471:Prostatic Neoplasms / Q000473:pathology*; D015203:Reproducibility of Results
keywords: Cribriform; High-grade prostatic intraepithelial neoplasia; Interobserver variability; Intraductal carcinoma; Prostate; Solid; Survey