Gleason grade 4 prostate adenocarcinoma patterns: an interobserver agreement study among genitourinary pathologists

Charlotte F. Kweldam, Daan Nieboer, Ferran Algaba, Mahul B. Amin, Dan M. Berney, Athanase Billis, David G. Bostwick, Lukas Bubendorf, Liang Cheng, Eva Compérat, Brett Delahunt, Lars Egevad, Andrew J. Evans, Donna E. Hansel, Peter A. Humphrey, Glen Kristiansen, Theodorus H. van der Kwast, Cristina Magi-Galluzzi, Rodolfo Montironi, George J. NettoHemamali Samaratunga, John R. Srigley, Puay H. Tan, Murali Varma, Ming Zhou, Geert J.L.H. van Leenders

Research output: Contribution to journalArticlepeer-review

86 Scopus citations


Aims: To assess the interobserver reproducibility of individual Gleason grade 4 growth patterns. Methods and results: Twenty-three genitourinary pathologists participated in the evaluation of 60 selected high-magnification photographs. The selection included 10 cases of Gleason grade 3, 40 of Gleason grade 4 (10 per growth pattern), and 10 of Gleason grade 5. Participants were asked to select a single predominant Gleason grade per case (3, 4, or 5), and to indicate the predominant Gleason grade 4 growth pattern, if present. ‘Consensus’ was defined as at least 80% agreement, and ‘favoured’ as 60–80% agreement. Consensus on Gleason grading was reached in 47 of 60 (78%) cases, 35 of which were assigned to grade 4. In the 13 non-consensus cases, ill-formed (6/13, 46%) and fused (7/13, 54%) patterns were involved in the disagreement. Among the 20 cases where at least one pathologist assigned the ill-formed growth pattern, none (0%, 0/20) reached consensus. Consensus for fused, cribriform and glomeruloid glands was reached in 2%, 23% and 38% of cases, respectively. In nine of 35 (26%) consensus Gleason grade 4 cases, participants disagreed on the growth pattern. Six of these were characterized by large epithelial proliferations with delicate intervening fibrovascular cores, which were alternatively given the designation fused or cribriform growth pattern (‘complex fused’). Conclusions: Consensus on Gleason grade 4 growth pattern was predominantly reached on cribriform and glomeruloid patterns, but rarely on ill-formed and fused glands. The complex fused glands seem to constitute a borderline pattern of unknown prognostic significance on which a consensus could not be reached.

Original languageEnglish (US)
Pages (from-to)441-449
Number of pages9
Issue number3
StatePublished - Sep 1 2016


  • Gleason grading
  • interobserver variability
  • prostate cancer

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology


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