Document Type
Article
Publication Date
11-3-2023
Abstract
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.
Recommended Citation
Mudhar, Hardeep Singh; Krishna, Yamini; Cross, Simon; Auw-Haedrich, Claudia; Barnhill, Raymond; Cherepanoff, Svetlana; Eagle, Ralph; Farmer, James; Folberg, Robert; Grossniklaus, Hans; Herwig-Carl, Martina C.; Hyrcza, Martin; Lassalle, Sandra; Loeffler, Karin U.; Moulin, Alexandre; Milman, Tatyana; Verdijk, Robert M.; Heegaard, Steffen; and Coupland, Sarah E., "A Multicenter Study Validates the WHO 2022 Classification for Conjunctival Melanocytic Intraepithelial Lesions With Clinical and Prognostic Relevance" (2023). Wills Eye Hospital Papers. Paper 209.
https://jdc.jefferson.edu/willsfp/209
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
37924948
Language
English
Comments
This article is the author's final published version in Laboratory Investigation; A Journal of Technical Methods and Pathology, Volume 104, Issue 1, January 2024, Article number 100281.
The published version is available at https://doi.org/10.1016/j.labinv.2023.100281. Copyright © 2023 THE AUTHORS. Published by Elsevier Inc. on behalf of the United States & Canadian Academy of Pathology.