A Multicenter Study Validates the WHO 2022 Classification for Conjunctival Melanocytic Intraepithelial Lesions With Clinical and Prognostic Relevance
Laboratory Investigation, vol. 104, pp. 100281
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.
Authors 19
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Affiliation as printed
National Specialist Ophthalmic Pathology Service, Department of Histopathology, E-Floor, Royal Hallamshire Hospital, Sheffield, UK
National Specialist Ophthalmic Pathology Service, Dept of Histopathology, E-Floor, Royal Hallamshire Hospital, Sheffield S10 2JF UK
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University of Liverpool · Liverpool University Hospitals NHS Foundation Trust
Affiliation as printed
National Specialist Ophthalmic Pathology Service, Liverpool Clinical Laboratories, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK; Liverpool Ocular Oncology Research Group, Department of Molecular and Clinical Cancer Medicine, Institute of System Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
National Specialist Ophthalmic Pathology Service, Liverpool Clinical Laboratories, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK//Liverpool Ocular Oncology Research Group, Department of Molecular and Clinical Cancer Medicine, Institute of System Molecular and Integrative Biology, University of Liverpool, 6 West Derby Street, William Henry Duncan Building, Liverpool L7 8TX, UK
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Affiliation as printed
Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield, UK
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Affiliation as printed
Eye Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany
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Université Paris Sciences et Lettres · Université Paris Descartes · Institut Curie
Affiliation as printed
Department of Translational Research, Institut Curie, Paris Sciences and Lettres Research University, and Faculty of Medicine University of Paris Descartes, Paris, France
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UNSW Sydney · St Vincent's Hospital Sydney
Affiliation as printed
Sydpath, Department of Anatomical Pathology, St Vincent's Hospital, Sydney, New South Wales, Australia; Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
Sydpath, Department of Anatomical Pathology, St Vincent's Hospital, Sydney, New South Wales, Australia
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Thomas Jefferson University · Wills Eye Hospital
Affiliation as printed
Department of Pathology, Wills Eye Hospital, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania; Department of Ophthalmology, Wills Eye Hospital, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania
Department of Ophthalmology, Wills Eye Hospital, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania, USA
Department of Pathology, Wills Eye Hospital, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania, USA
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University of Ottawa · Queen's University
Affiliation as printed
Departments of Ophthalmology and Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada; Departments of Pathology and Laboratory Medicine and Ophthalmology, University of Ottawa, Ottawa, Ontario, Canada
Departments of Ophthalmology and Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada and Departments of Pathology and Laboratory Medicine and Ophthalmology, University of Ottawa, Ottawa, Ontario, Canada
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Oakland University · Beaumont Health · Beaumont Hospital, Royal Oak · Corewell Health William Beaumont University Hospital
Affiliation as printed
Departments of Ophthalmology and Pathology, Oakland University William Beaumont School of Medicine, Rochester, Michigan; Departments of Ophthalmology and Pathology, Corewell Health William Beaumont University Hospital, Royal Oak, Michigan
Departments of Ophthalmology and Pathology, Corewell Health William Beaumont University Hospital, Royal Oak, Michigan, USA
Departments of Ophthalmology and Pathology, Oakland University William Beaumont School of Medicine, Rochester, Michigan
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Emory University · Emory Eye Center
Affiliation as printed
Department of Ophthalmology, Ocular Oncology and Pathology Section, Emory Eye Center, Emory University School of Medicine, Atlanta, Georgia
Department of Ophthalmology, Ocular Oncology and Pathology Section, Emory Eye Center, Emory University School of Medicine, Atlanta, Georgia, USA
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Affiliation as printed
Department of Ophthalmology, Division of Ophthalmic Pathology, University Hospital Bonn, Bonn, Germany
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Affiliation as printed
Department of Pathology and Laboratory Medicine, University of Calgary, Arnie Charbonneau Cancer Institute, Calgary, Alberta, Canada
Department of Pathology and Laboratory Medicine, University of Calgary, Arnie Charbonneau Cancer Institute, Calgary, AB, Canada
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Université Côte d'Azur · Centre Hospitalier Universitaire de Nice · Institut de Recherche sur le Cancer et le Vieillissement de Nice · Hôpital Pasteur
Affiliation as printed
Laboratory of Clinical and Experimental Pathology, Hospital-Related Biobank (BB-0033-00025), Pasteur Hospital, Centre Hospitalier Universitaire de Nice and Institute of Research on Cancer and Aging, FHU OncoAge, Université Côte d'Azur, Nice, France
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Affiliation as printed
Department of Ophthalmology, Division of Ophthalmic Pathology, University Hospital Bonn, Bonn, Germany
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Hôpital Ophtalmique Jules-Gonin · Fondation Asile des Aveugles · University of Lausanne
Affiliation as printed
Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, University of Lausanne, Lausanne, Switzerland
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Thomas Jefferson University · Wills Eye Hospital
Affiliation as printed
Department of Pathology, Wills Eye Hospital, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania; Department of Ophthalmology, Wills Eye Hospital, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania
Department of Ophthalmology, Wills Eye Hospital, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania, USA
Department of Pathology, Wills Eye Hospital, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania, USA
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Robert M. Verdijk Aachen Department of Pathology Section of Ophthalmic Pathology Department of Pathology, Leiden University Medical Centre
Leiden University · Leiden University Medical Center · Erasmus MC
Affiliation as printed
Department of Pathology, Section of Ophthalmic Pathology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
Department of Pathology, Section of Ophthalmic Pathology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands and Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
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University of Copenhagen · Rigshospitalet
Affiliation as printed
Department of Pathology, Eye Pathology Section, and Ophthalmology, Rigshospitalet, University of Copenhagen, Denmark
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Sarah E. Coupland corresponding
University of Liverpool · Liverpool University Hospitals NHS Foundation Trust
Affiliation as printed
National Specialist Ophthalmic Pathology Service, Liverpool Clinical Laboratories, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK; Liverpool Ocular Oncology Research Group, Department of Molecular and Clinical Cancer Medicine, Institute of System Molecular and Integrative Biology, University of Liverpool, Liverpool, UK. Electronic address: s.e.coupland@liverpool.ac.uk
National Specialist Ophthalmic Pathology Service, Liverpool Clinical Laboratories, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK//Liverpool Ocular Oncology Research Group, Department of Molecular and Clinical Cancer Medicine, Institute of System Molecular and Integrative Biology, University of Liverpool, 6 West Derby Street, William Henry Duncan Building, Liverpool L7 8TX, UK
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