A Multicenter Study Validates the WHO 2022 Classification for Conjunctival Melanocytic Intraepithelial Lesions With Clinical and Prognostic Relevance

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  • Hardeep Singh Mudhar
  • Yamini Krishna
  • Simon Cross
  • Claudia Auw-Haedrich
  • Raymond Barnhill
  • Svetlana Cherepanoff
  • Ralph Eagle
  • James Farmer
  • Robert Folberg
  • Hans Grossniklaus
  • Martina C. Herwig-Carl
  • Martin Hyrcza
  • Sandra Lassalle
  • Karin U. Loeffler
  • Alexandre Moulin
  • Tatyana Milman
  • Robert M. Verdijk
  • Heegaard, Steffen
  • Sarah E. Coupland

Several nomenclature and grading systems have been proposed for conjunctival melanocytic intraepithelial lesions (C-MIL). The fourth "WHO Classification of Eye Tumors" (WHO-EYE04) proposed a C-MIL classification, capturing the progression of noninvasive neoplastic melanocytes from low- to high-grade lesions, onto melanoma in situ (MIS), and then to invasive melanoma. This proposal was revised to the WHO-EYE05 C-MIL system, which simplified the high-grade C-MIL, whereby MIS was subsumed into high-grade C-MIL. Our aim was to validate the WHO-EYE05 C-MIL system using digitized images of C-MIL, stained with hematoxylin and eosin and immunohistochemistry. However, C-MIL cases were retrieved from 3 supraregional ocular pathology centers. Adequate conjunctival biopsies were stained with hematoxylin and eosin, Melan-A, SOX10, and PReferentially expressed Antigen in Melanoma. Digitized slides were uploaded on the SmartZoom platform and independently scored by 4 ocular pathologists to obtain a consensus score, before circulating to 14 expert eye pathologists for independent scoring. In total, 105 cases from 97 patients were evaluated. The initial consensus diagnoses using the WHO-EYE04 C-MIL system were as follows: 28 benign conjunctival melanoses, 13 low-grade C-MIL, 37 high-grade C-MIL, and 27 conjunctival MIS. Using this system resulted in 93% of the pathologists showing only fair-to-moderate agreement (kappa statistic) with the consensus score. The WHO-EYE05 C-MIL system (with high-grade C-MIL and MIS combined) improved consistency between pathologists, with the greatest level of agreement being seen with benign melanosis (74.5%) and high-grade C-MIL (85.4%). Lowest agreements remained between pathologists for low-grade C-MIL (38.7%). Regarding WHO-EYE05 C-MIL scoring and clinical outcomes, local recurrences of noninvasive lesions developed in 8% and 34% of the low- and high-grade cases. Invasive melanoma only occurred in 47% of the cases that were assessed as high-grade C-MIL. This extensive international collaborative study is the first to undertake a comprehensive review of the WHO-EYE05 C-MIL scoring system, which showed good interobserver agreement and reproducibility.

Original languageEnglish
Article number100281
JournalLaboratory investigation; a journal of technical methods and pathology
Volume104
Issue number1
Number of pages9
ISSN0023-6837
DOIs
Publication statusPublished - 2024
Externally publishedYes

Bibliographical note

Publisher Copyright:
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

    Research areas

  • conjunctival melanoma, conjunctival melanoma in situ, digital pathology, high-grade conjunctival melanocytic intraepithelial lesions, immunohistochemistry, low-grade conjunctival melanocytic intraepithelial lesions

ID: 381236622