Abstract

Virtual microscopy (VM) holds promise to reduce subjectivity as well as intra- and inter-observer variability for the histopathological evaluation of prostate cancer. We evaluated (i) the repeatability (intra-observer agreement) and reproducibility (inter-observer agreement) of the 2014 Gleason grading system and other selected features using standard light microscopy (LM) and an internally developed VM system, and (ii) the interchangeability of LM and VM. Two uro-pathologists reviewed 413 cores from 60 Swedish men diagnosed with non-metastatic prostate cancer 1998–2014. Reviewer 1 performed two reviews using both LM and VM. Reviewer 2 performed one review using both methods. The intra- and inter-observer agreement within and between LM and VM were assessed using Cohen’s kappa and Bland and Altman’s limits of agreement. We found good repeatability and reproducibility for both LM and VM, as well as interchangeability between LM and VM, for primary and secondary Gleason pattern, Gleason Grade Groups, poorly formed glands, cribriform pattern and comedonecrosis but not for the percentage of Gleason pattern 4. Our findings confirm the non-inferiority of VM compared to LM. The repeatability and reproducibility of percentage of Gleason pattern 4 was poor regardless of method used warranting further investigation and improvement before it is used in clinical practice.

Highlights

  • Virtual microscopy (VM) holds promise to reduce subjectivity as well as intra- and inter-observer variability for the histopathological evaluation of prostate cancer

  • In the International Society of Urological Pathology (ISUP) 2014 revision, it was, among other things, recommended that cribriform pattern, fused glands and poorly formed glands should be graded as Gleason pattern 4, presence of comedonecrosis and single cells indicates Gleason pattern 5­ 13, and that percentage of Gleason pattern 4 should be recorded for all Gleason score 7 ­cores[14]

  • Our study is unique in that we evaluated the interchangeability of VM and light microscopy (LM) for cribriform pattern, poorly formed glands, comedonecrosis, percentage of Gleason pattern 4, and intraductal and mucinous carcinoma, inflammation, high-grade prostatic intraepithelial neoplasia (HGPIN) and postatrophic hyperplasia (PAH)

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Summary

Introduction

Virtual microscopy (VM) holds promise to reduce subjectivity as well as intra- and inter-observer variability for the histopathological evaluation of prostate cancer. We evaluated (i) the repeatability (intra-observer agreement) and reproducibility (inter-observer agreement) of the 2014 Gleason grading system and other selected features using standard light microscopy (LM) and an internally developed VM system, and (ii) the interchangeability of LM and VM. Interchangeability of LM and VM has been demonstrated for primary and secondary Gleason pattern, Gleason score, tumour length and perineural ­invasion[6,23,24,25], but not for different Gleason related characteristics (i.e. poorly formed glands, cribriform pattern, comedonecrosis and the percentage of Gleason pattern 4) or for other histopathological characteristics

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