Intraductal carcinoma of the prostate: Interobserver reproducibility survey of 39 urologic pathologists

Kenneth A. Iczkowski, Lars Egevad, Jun Ma, Nicholas Harding-Jackson, Ferran Algaba, Athanase Billis, Philippe Camparo, Liang Cheng, David Clouston, Eva M. Comperat, Milton W. Datta, Andrew G. Evans, David F. Griffiths, Charles C. Guo, Seife Hailemariam, Wei Huang, Peter A. Humphrey, Zhong Jiang, Hillel Kahane, Glen KristiansenFrancisco G. La Rosa, Antonio Lopez-Beltran, Gregory T. MacLennan, Cristina Magi-Galluzzi, Jennifer Merrimen, Rodolfo Montironi, Adeboye O. Osunkoya, Maria M. Picken, Nagarjun Rao, Rajal B. Shah, Jonathan H. Shanks, Steven S. Shen, Ossama W. Tawfik, Lawrence D. True, Theodorus Van Der Kwast, Murali Varma, Thomas M. Wheeler, Debra L. Zynger, Natasha Sahr, David G. Bostwick

Research output: Contribution to journalArticle

19 Citations (Scopus)

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, X2). 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 IDCwas reached in 9 (47%). Two-thirds consensus other than IDCwas 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.

Original languageEnglish (US)
Pages (from-to)333-342
Number of pages10
JournalAnnals of Diagnostic Pathology
Volume18
Issue number6
DOIs
StatePublished - Jan 1 2014

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Carcinoma, Intraductal, Noninfiltrating
Prostate
Prostatic Intraepithelial Neoplasia
Growth
Ductal Carcinoma
Pathologists
Surveys and Questionnaires
Carcinoma
Adenocarcinoma
Carcinoma in Situ
Needle Biopsy

Keywords

  • Cribriform
  • High-grade prostatic intraepithelial neoplasia
  • Interobserver variability
  • Intraductal carcinoma
  • Prostate
  • Solid
  • Survey

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Iczkowski, K. A., Egevad, L., Ma, J., Harding-Jackson, N., Algaba, F., Billis, A., ... Bostwick, D. G. (2014). Intraductal carcinoma of the prostate: Interobserver reproducibility survey of 39 urologic pathologists. Annals of Diagnostic Pathology, 18(6), 333-342. https://doi.org/10.1016/j.anndiagpath.2014.08.010

Intraductal carcinoma of the prostate : Interobserver reproducibility survey of 39 urologic pathologists. / Iczkowski, Kenneth A.; Egevad, Lars; Ma, Jun; Harding-Jackson, Nicholas; Algaba, Ferran; Billis, Athanase; Camparo, Philippe; Cheng, Liang; Clouston, David; Comperat, Eva M.; Datta, Milton W.; Evans, Andrew G.; Griffiths, David F.; Guo, Charles C.; Hailemariam, Seife; Huang, Wei; Humphrey, Peter A.; Jiang, Zhong; Kahane, Hillel; Kristiansen, Glen; La Rosa, Francisco G.; Lopez-Beltran, Antonio; MacLennan, Gregory T.; Magi-Galluzzi, Cristina; Merrimen, Jennifer; Montironi, Rodolfo; Osunkoya, Adeboye O.; Picken, Maria M.; Rao, Nagarjun; Shah, Rajal B.; Shanks, Jonathan H.; Shen, Steven S.; Tawfik, Ossama W.; True, Lawrence D.; Van Der Kwast, Theodorus; Varma, Murali; Wheeler, Thomas M.; Zynger, Debra L.; Sahr, Natasha; Bostwick, David G.

In: Annals of Diagnostic Pathology, Vol. 18, No. 6, 01.01.2014, p. 333-342.

Research output: Contribution to journalArticle

Iczkowski, KA, Egevad, L, Ma, J, Harding-Jackson, N, Algaba, F, Billis, A, Camparo, P, Cheng, L, Clouston, D, Comperat, EM, Datta, MW, Evans, AG, Griffiths, DF, Guo, CC, Hailemariam, S, Huang, W, Humphrey, PA, Jiang, Z, Kahane, H, Kristiansen, G, La Rosa, FG, Lopez-Beltran, A, MacLennan, GT, Magi-Galluzzi, C, Merrimen, J, Montironi, R, Osunkoya, AO, Picken, MM, Rao, N, Shah, RB, Shanks, JH, Shen, SS, Tawfik, OW, True, LD, Van Der Kwast, T, Varma, M, Wheeler, TM, Zynger, DL, Sahr, N & Bostwick, DG 2014, 'Intraductal carcinoma of the prostate: Interobserver reproducibility survey of 39 urologic pathologists', Annals of Diagnostic Pathology, vol. 18, no. 6, pp. 333-342. https://doi.org/10.1016/j.anndiagpath.2014.08.010
Iczkowski, Kenneth A. ; Egevad, Lars ; Ma, Jun ; Harding-Jackson, Nicholas ; Algaba, Ferran ; Billis, Athanase ; Camparo, Philippe ; Cheng, Liang ; Clouston, David ; Comperat, Eva M. ; Datta, Milton W. ; Evans, Andrew G. ; Griffiths, David F. ; Guo, Charles C. ; Hailemariam, Seife ; Huang, Wei ; Humphrey, Peter A. ; Jiang, Zhong ; Kahane, Hillel ; Kristiansen, Glen ; La Rosa, Francisco G. ; Lopez-Beltran, Antonio ; MacLennan, Gregory T. ; Magi-Galluzzi, Cristina ; Merrimen, Jennifer ; Montironi, Rodolfo ; Osunkoya, Adeboye O. ; Picken, Maria M. ; Rao, Nagarjun ; Shah, Rajal B. ; Shanks, Jonathan H. ; Shen, Steven S. ; Tawfik, Ossama W. ; True, Lawrence D. ; Van Der Kwast, Theodorus ; Varma, Murali ; Wheeler, Thomas M. ; Zynger, Debra L. ; Sahr, Natasha ; Bostwick, David G. / Intraductal carcinoma of the prostate : Interobserver reproducibility survey of 39 urologic pathologists. In: Annals of Diagnostic Pathology. 2014 ; Vol. 18, No. 6. pp. 333-342.
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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, X2). 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 IDCwas reached in 9 (47{\%}). Two-thirds consensus other than IDCwas 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.",
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TY - JOUR

T1 - Intraductal carcinoma of the prostate

T2 - Interobserver reproducibility survey of 39 urologic pathologists

AU - Iczkowski, Kenneth A.

AU - Egevad, Lars

AU - Ma, Jun

AU - Harding-Jackson, Nicholas

AU - Algaba, Ferran

AU - Billis, Athanase

AU - Camparo, Philippe

AU - Cheng, Liang

AU - Clouston, David

AU - Comperat, Eva M.

AU - Datta, Milton W.

AU - Evans, Andrew G.

AU - Griffiths, David F.

AU - Guo, Charles C.

AU - Hailemariam, Seife

AU - Huang, Wei

AU - Humphrey, Peter A.

AU - Jiang, Zhong

AU - Kahane, Hillel

AU - Kristiansen, Glen

AU - La Rosa, Francisco G.

AU - Lopez-Beltran, Antonio

AU - MacLennan, Gregory T.

AU - Magi-Galluzzi, Cristina

AU - Merrimen, Jennifer

AU - Montironi, Rodolfo

AU - Osunkoya, Adeboye O.

AU - Picken, Maria M.

AU - Rao, Nagarjun

AU - Shah, Rajal B.

AU - Shanks, Jonathan H.

AU - Shen, Steven S.

AU - Tawfik, Ossama W.

AU - True, Lawrence D.

AU - Van Der Kwast, Theodorus

AU - Varma, Murali

AU - Wheeler, Thomas M.

AU - Zynger, Debra L.

AU - Sahr, Natasha

AU - Bostwick, David G.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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, X2). 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 IDCwas reached in 9 (47%). Two-thirds consensus other than IDCwas 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.

AB - 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, X2). 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 IDCwas reached in 9 (47%). Two-thirds consensus other than IDCwas 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.

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KW - Interobserver variability

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KW - Prostate

KW - Solid

KW - Survey

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