A Multicenter Study Validates the WHO 2022 Classification for Conjunctival Melanocytic Intraepithelial Lesions With Clinical and Prognostic Relevance
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A Multicenter Study Validates the WHO 2022 Classification for Conjunctival Melanocytic Intraepithelial Lesions With Clinical and Prognostic Relevance. / 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; Coupland, Sarah E.
In: Laboratory investigation; a journal of technical methods and pathology, Vol. 104, No. 1, 100281, 2024.Research output: Contribution to journal › Review › Research › peer-review
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TY - JOUR
T1 - A Multicenter Study Validates the WHO 2022 Classification for Conjunctival Melanocytic Intraepithelial Lesions With Clinical and Prognostic Relevance
AU - Mudhar, Hardeep Singh
AU - Krishna, Yamini
AU - Cross, Simon
AU - Auw-Haedrich, Claudia
AU - Barnhill, Raymond
AU - Cherepanoff, Svetlana
AU - Eagle, Ralph
AU - Farmer, James
AU - Folberg, Robert
AU - Grossniklaus, Hans
AU - Herwig-Carl, Martina C.
AU - Hyrcza, Martin
AU - Lassalle, Sandra
AU - Loeffler, Karin U.
AU - Moulin, Alexandre
AU - Milman, Tatyana
AU - Verdijk, Robert M.
AU - Heegaard, Steffen
AU - Coupland, Sarah E.
N1 - Publisher Copyright: Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - conjunctival melanoma
KW - conjunctival melanoma in situ
KW - digital pathology
KW - high-grade conjunctival melanocytic intraepithelial lesions
KW - immunohistochemistry
KW - low-grade conjunctival melanocytic intraepithelial lesions
U2 - 10.1016/j.labinv.2023.100281
DO - 10.1016/j.labinv.2023.100281
M3 - Review
C2 - 37924948
AN - SCOPUS:85182956039
VL - 104
JO - Laboratory Investigation
JF - Laboratory Investigation
SN - 0023-6837
IS - 1
M1 - 100281
ER -
ID: 381236622