Journal of the European Academy of Dermatology and Venereology

Volume 39, Issue 3 pp. 555-565

SYSTEMATIC REVIEW

In vivo reflectance confocal microscopy role for early to advanced lentigo maligna melanoma spectrum: A systematic review and pooled analysis

Bruna Melhoranse Gouveia,

Corresponding Author

Bruna Melhoranse Gouveia

[email protected]

orcid.org/0000-0002-6322-5675

Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia

Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia

School of Clinical Medicine, Faculty of Medicine & Health, UNSW, Sydney, New South Wales, Australia

Correspondence

Bruna Melhoranse Gouveia, Suite 8, level 3/40 Rocklands Road, Wollstonecraft, NSW 2065, Australia.

Email: [email protected]

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Peter M. Ferguson,

Peter M. Ferguson

Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia

Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia

Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital and NSW Health Pathology, Sydney, New South Wales, Australia

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Serigne N. Lo,

Serigne N. Lo

orcid.org/0000-0001-5092-5544

Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia

Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia

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Helena Collgros,

Helena Collgros

orcid.org/0000-0002-1475-0668

Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia

Sydney Melanoma Diagnostic Centre, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia

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Linda K. Martin,

Linda K. Martin

Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia

School of Clinical Medicine, Faculty of Medicine & Health, UNSW, Sydney, New South Wales, Australia

The Daffodil Centre, The University of Sydney, a Joint Venture with Cancer Council NSW, Sydney, New South Wales, Australia

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Christoph Sinz,

Christoph Sinz

Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia

Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia

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Amelia K. Smit,

Amelia K. Smit

orcid.org/0000-0001-5712-220X

Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia

Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia

The Daffodil Centre, The University of Sydney, a Joint Venture with Cancer Council NSW, Sydney, New South Wales, Australia

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Bruna Gallo,

Bruna Gallo

Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia

Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia

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Genevieve Ho,

Genevieve Ho

orcid.org/0000-0003-3769-8951

Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia

Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia

School of Clinical Medicine, Faculty of Medicine & Health, UNSW, Sydney, New South Wales, Australia

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Amanda Glanz,

Amanda Glanz

Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia

Sydney Melanoma Diagnostic Centre, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia

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Richard A. Scolyer,

Richard A. Scolyer

orcid.org/0000-0002-8991-0013

Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia

Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia

Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital and NSW Health Pathology, Sydney, New South Wales, Australia

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Anne E. Cust,

Anne E. Cust

orcid.org/0000-0002-5331-6370

Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia

Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia

The Daffodil Centre, The University of Sydney, a Joint Venture with Cancer Council NSW, Sydney, New South Wales, Australia

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Pascale Guitera,

Pascale Guitera

Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia

Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia

Sydney Melanoma Diagnostic Centre, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia

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Bruna Melhoranse Gouveia,

Corresponding Author

Bruna Melhoranse Gouveia

[email protected]

orcid.org/0000-0002-6322-5675

Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia

Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia

School of Clinical Medicine, Faculty of Medicine & Health, UNSW, Sydney, New South Wales, Australia

Correspondence

Bruna Melhoranse Gouveia, Suite 8, level 3/40 Rocklands Road, Wollstonecraft, NSW 2065, Australia.

Email: [email protected]

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Peter M. Ferguson,

Peter M. Ferguson

Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia

Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia

Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital and NSW Health Pathology, Sydney, New South Wales, Australia

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Serigne N. Lo,

Serigne N. Lo

orcid.org/0000-0001-5092-5544

Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia

Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia

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Helena Collgros,

Helena Collgros

orcid.org/0000-0002-1475-0668

Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia

Sydney Melanoma Diagnostic Centre, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia

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Linda K. Martin,

Linda K. Martin

Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia

School of Clinical Medicine, Faculty of Medicine & Health, UNSW, Sydney, New South Wales, Australia

The Daffodil Centre, The University of Sydney, a Joint Venture with Cancer Council NSW, Sydney, New South Wales, Australia

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Christoph Sinz,

Christoph Sinz

Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia

Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia

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Amelia K. Smit,

Amelia K. Smit

orcid.org/0000-0001-5712-220X

Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia

Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia

The Daffodil Centre, The University of Sydney, a Joint Venture with Cancer Council NSW, Sydney, New South Wales, Australia

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Bruna Gallo,

Bruna Gallo

Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia

Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia

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Genevieve Ho,

Genevieve Ho

orcid.org/0000-0003-3769-8951

Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia

Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia

School of Clinical Medicine, Faculty of Medicine & Health, UNSW, Sydney, New South Wales, Australia

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Amanda Glanz,

Amanda Glanz

Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia

Sydney Melanoma Diagnostic Centre, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia

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Richard A. Scolyer,

Richard A. Scolyer

orcid.org/0000-0002-8991-0013

Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia

Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia

Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital and NSW Health Pathology, Sydney, New South Wales, Australia

Search for more papers by this author

Anne E. Cust,

Anne E. Cust

orcid.org/0000-0002-5331-6370

Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia

Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia

The Daffodil Centre, The University of Sydney, a Joint Venture with Cancer Council NSW, Sydney, New South Wales, Australia

Search for more papers by this author

Pascale Guitera,

Pascale Guitera

Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia

Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia

Sydney Melanoma Diagnostic Centre, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia

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First published: 13 November 2024

https://doi.org/10.1111/jdv.20389

Registration: PROSPERO registration number 345241 (https://www.crd.york.ac.uk/PROSPEROFILES/345241_STRATEGY_20220708.pdf).

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Abstract

Background

Lentigo maligna (LM) is a growing problem worldwide and the main type of melanoma in situ in some Caucasian populations. It presents as a spectrum from atypical intraepidermal melanocytic proliferation (AIMP) to invasive lentigo maligna melanoma (LMM). Accurate diagnosis and staging are crucial for determining appropriate management strategies.

Objectives

To assess the role of in vivo reflectance confocal microscopy (RCM) in differentiating early and advanced stages of lentigo maligna.

Methods

A systematic search was conducted on Medline, PubMed, Scopus, Web of Science, Proquest Central, Embase, Cochrane and Google Scholar. References of included and excluded studies were reviewed for additional sources. Studies involving RCM for AIMP, LM and LMM diagnosis published until 1 December 2023, were selected for analysis. Publications on other non-invasive imaging techniques, other skin diseases or those addressing only RCM surgical margins and therapeutic response without reporting RCM features were excluded. Each article was reviewed by two experts, with disagreements resolved by a third expert. Data for each RCM feature were pooled, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Features were stratified for architecture, cellular morphology and distribution.

Results

Twenty-seven articles involving 303 lesions were included. Features favouring LM over AIMP included (1) Architecture: the presence of non-edged papillae (OR 4.50, 95% CI 1.92–10.52) and (2) Cellular distribution: widespread pagetoid cells and junctional atypical cells (OR 25.06, 95% CI 4.19–148.45) and junctional nests (OR 18.06, 95% CI 3.04–106.32). Features favouring LMM over LM included (1) Architecture: epidermal disarray (OR 5.03, 95% CI 1.90–13.22), junctional disarray (OR 4.19, 95% CI 1.54–11.33) and destroyed collagen fibres (OR 3.91, 95% CI 1.80–8.44) and (2) cellular distribution: widespread pagetoid and junctional atypical cells (OR 2.71, 95% CI 1.27–5.75) and junctional nests (OR 4.48, 95% CI 2.12–9.43).

Conclusions

This study identifies the RCM features associated with the LM/LMM spectrum.

Graphical Abstract

Key confocal features in LM/LMM progression: Architecture: AIMP: Preserved; LM: Non-edged papillae; LMM: Epidermal/junctional disarray, collagen fibre destruction. Cellular distribution: AIMP: Junctional scattered atypical cells; LM: Widespread pagetoid and junctional atypical cells with junctional nests; LMM: Widespread pagetoid and junctional atypical cells with junctional and dermal nests. Cell Types: AIMP: Dendritic cells with mild atypia; LM/LMM: Dendritic cells with mild atypia, round nucleated cells with marked atypia.

CONFLICT OF INTEREST STATEMENT

RAS has received fees for professional services from Hoffmann-La Roche Ltd., Evaxion, Provectus Biopharmaceuticals Australia, Qbiotics, Novartis, Merck Sharp & Dohme, NeraCare, AMGEN Inc., Bristol-Myers Squibb, Myriad Genetics, GlaxoSmithKline. PG has received honoraria from Metaoptima and fees for professional services from L'Oreal. LKM has received speaking fees from Astra-Zeneca. RAS and AEC are supported by NHMRC Investigator Grants (#2018514 and #2008454). SL and PG are supported by Melanoma Institute Australia. GH was supported by the NHMRC CRE 1135285 and the Lady Mary Fairfax Foundation. BMG was supported by the Melanoma Institute Australia PhD scholarship and Australia Melanoma Research Foundation top-up grant. AKS is supported by an NHMRC Synergy grant (#2009923). LKM is supported by the Warwick L. Morison Professorship in Dermatology UNSW. BG was supported by the Lady Mary Fairfax Foundation/Melanoma Institute Australia Dermatology fellowship. PF, HC, CS and AG have no disclosures.

Open Research

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Volume39, Issue3

March 2025

Pages 555-565