Original Article

Subungual melanoma: molecular analysis of 31 cases from early stage to invasive melanoma

Corresponding Author

Christophe Perrin

[email protected]

orcid.org/0000-0002-6214-3416

Laboratoire Central d'Anatomie Pathologique, Nice University Hospital, Nice, France

Address for correspondence: C Perrin, Laboratoire Central d'Anatomie Pathologique, Hôpital Pasteur, 30, Avenue Voie Romaine, Nice 06001, Cedex 1, France. e-mail: [email protected]

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Michael Coutts,

Michael Coutts

Department of Cellular Pathology, Maidstone Hospital, Kent, UK

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Bérengère Dadone-Montaudié,

Bérengère Dadone-Montaudié

Institute for Research on Cancer and Aging of Nice (IRCAN) CNRS UMR 7284/INSERM U1081, University of Cote d'Azur (UCA), Nice University Hospital, Nice, France

Department of Pathology and Molecular Oncology, Laboratoire d'Oncologie Moléculaire, Nice University Hospital, Nice, France

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Christophe Perrin,

Corresponding Author

Christophe Perrin

[email protected]

orcid.org/0000-0002-6214-3416

Laboratoire Central d'Anatomie Pathologique, Nice University Hospital, Nice, France

Address for correspondence: C Perrin, Laboratoire Central d'Anatomie Pathologique, Hôpital Pasteur, 30, Avenue Voie Romaine, Nice 06001, Cedex 1, France. e-mail: [email protected]

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Michael Coutts,

Michael Coutts

Department of Cellular Pathology, Maidstone Hospital, Kent, UK

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Bérengère Dadone-Montaudié,

Bérengère Dadone-Montaudié

Institute for Research on Cancer and Aging of Nice (IRCAN) CNRS UMR 7284/INSERM U1081, University of Cote d'Azur (UCA), Nice University Hospital, Nice, France

Department of Pathology and Molecular Oncology, Laboratoire d'Oncologie Moléculaire, Nice University Hospital, Nice, France

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First published: 13 August 2024

https://doi.org/10.1111/his.15297

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Abstract

Aims

The distinction between the benign subungual melanocytic lesions and an early lesion of subungual melanoma (SUM) remains a diagnostic challenge. We evaluated the routine diagnostic utility of array Comparative Genomic Hybridization (aCGH) to detect whole-genome copy number variations (CNV) as well as targeted next-generation sequencing (NGS) in SUM.

Methods and Results

This retrospective study included 20 cases of in situ SUM and 11 cases of invasive SUM. Analysis by aCGH detected common oncogene amplifications in all but one case of invasive SUM (n = 10) and in all cases of in situ SUM with a melanocyte count (MC) >45/mm (n = 4 true positive) and the average number of CNV was 8.5. Thirteen remaining cases of in situ SUM gave false negative results (n = 13), owing to a lack of sufficient melanocytes to analyse (median MC of 35.35; range: 10.16–39.5). Molecular analysis failed in four cases (three in situ SUM and one invasive SUM) due to insufficient amounts of DNA. Across the whole cohort, the sensitivity of aCGH was 52%, but when adjusting the cutoff to MC >45/mm, the sensitivity was 93%. Targeted NGS was less informative than aCGH analyses in our series of SUM.

Conclusion

To distinguish malignant from benign lesions, especially in situ SUM versus atypical lentiginous melanocytic proliferations, aCGH analysis should be performed when the MC is above 45 melanocytes per linear millimetre. This pangenomic method can detect oncogene amplifications, as well as a number of CNV >3, which strongly support the diagnosis of malignancy.

Graphical Abstract

To distinguish malignant from benign lesions, especially in situ SUM versus atypical lentiginous melanocytic proliferations, aCGH analysis should be performed when the MC is above 45/mm. This pangenomic method can detect oncogene amplifications, as well as a number of CNV >3, which strongly support the diagnosis of malignancy.

Conflict of interest

None declared.

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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Volume86, Issue2

January 2025

Pages 214-225