Reflectance Confocal Microscopy and Molecular Correlation in Atypical Melanocytic Lesions

Official title

Evaluation of Reflectance Confocal Microscopy (RCM) Features in Surgically Excised Atypical Melanocytic Lesions and Their Correlation With Next-Generation Sequencing (NGS) Patterns

Overview

This observational, prospective cohort study aims to evaluate the diagnostic relevance of Reflectance Confocal Microscopy (RCM) features in atypical melanocytic lesions scheduled for surgical excision, and to correlate these imaging features with molecular profiles obtained through Next-Generation Sequencing (NGS). Approximately 200 consecutive lesions, including atypical nevi and early-stage melanomas, will be analyzed from patients attending the Videomicroscopy and Confocal Clinic at the Dermatology Department of the University Hospital of Modena. The primary objective is to assess the diagnostic significance of RCM features-specifically atypical cells and disarrangement of the dermoepidermal junction (DEJ)-for early detection of melanoma. Secondary objectives include correlating RCM morphological patterns with NGS-derived genetic alterations and identifying molecular signatures that differentiate early-stage melanomas from benign nevi. All procedures are performed as part of routine clinical care, including dermoscopic and confocal evaluation, surgical excision, histopathology, and molecular analysis on formalin-fixed, paraffin-embedded blocks. Data will be anonymized, securely stored, and analyzed to determine associations between imaging and genetic variables. This study integrates morphological and molecular data to refine diagnostic workflows and improve early melanoma detection.

Detailed description

Background and Rationale

Reflectance confocal microscopy (RCM) is a non-invasive imaging technique that allows in vivo evaluation of the skin with near-histologic resolution. Integrating RCM into clinical dermatology has been shown to reduce unnecessary excisions of benign lesions and improve diagnostic accuracy compared with dermoscopy alone.

Next-Generation Sequencing (NGS) enables the identification of key genetic mutations in atypical nevi and melanomas, providing valuable insights into their biological behavior and potential malignant transformation.

This study aims to evaluate the correlation between characteristic RCM features and molecular findings obtained through NGS in melanocytic lesions already scheduled for surgical excision, to improve early diagnosis of melanoma and risk classification.

Objectives Primary Objective

To assess the diagnostic relevance of characteristic RCM features - specifically atypical cells and DEJ disarrangement - in melanocytic lesions already scheduled for surgical excision due to dermoscopic suspicion of atypical nevus or melanoma.

Secondary Objectives

To correlate RCM morphological features with molecular profiles obtained through NGS in both nevi and early-stage melanomas, comparing the genetic and morphologic patterns between these two groups.

To identify distinctive biological and molecular signatures that may differentiate early-stage melanomas from benign nevi, providing potential markers for early diagnosis and risk stratification.

Funding Statement

This study is funded by the European Union - NextGenerationEU, through the Italian Ministry of University and Research (MUR) under PNRR - M4C2-I1.3 Project PE\_00000019 HEAL ITALIA, CUP E93C22001860006.

Primary outcome measures

• Diagnostic relevance of RCM features in atypical melanocytic lesions [Time frame: through study completion, an average of 1 year]

Secondary outcome measures (1)

• Differential gene expression profiles distinguishing nevi and early-stage melanomas [Time frame: through study completion, an average of 1 year]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years
• Presence of cutaneous lesions with dermoscopic and reflectance confocal microscopy suspicion of melanocytic neoplasia, already scheduled for surgical excision
• Written informed consent obtained

Exclusion criteria

• Age < 18 years
• Lesions not scheduled for excision or with uncertain dermoscopic diagnosis
• Lack of informed consent

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Study design

Observational model

Cohort

Study locations

Italy · 1 center

• Dermatology Department, University Hospital of Modena — Modena

Publications

• Mesbah Ardakani N. Dysplastic/Clark naevus in the era of molecular pathology. Australas J Dermatol. 2019 Aug;60(3):186-191. doi: 10.1111/ajd.13019. Epub 2019 Mar 10. PMID 30854639
• Piepkorn MW, Barnhill RL, Elder DE, Knezevich SR, Carney PA, Reisch LM, Elmore JG. The MPATH-Dx reporting schema for melanocytic proliferations and melanoma. J Am Acad Dermatol. 2014 Jan;70(1):131-41. doi: 10.1016/j.jaad.2013.07.027. Epub 2013 Oct 28. PMID 24176521
• Ferrara G, Argenziano G, Soyer HP, Corona R, Sera F, Brunetti B, Cerroni L, Chimenti S, El Shabrawi-Caelen L, Ferrari A, Hofmann-Wellenhof R, Kaddu S, Piccolo D, Scalvenzi M, Staibano S, Wolf IH, De Rosa G. Dermoscopic and histopathologic diagnosis of equivocal melanocytic skin lesions: an interdisciplinary study on 107 cases. Cancer. 2002 Sep 1;95(5):1094-100. doi: 10.1002/cncr.10768. PMID 12209696
• Kozubek J, Ma Z, Fleming E, Duggan T, Wu R, Shin DG, Dadras SS. In-depth characterization of microRNA transcriptome in melanoma. PLoS One. 2013 Sep 4;8(9):e72699. doi: 10.1371/journal.pone.0072699. eCollection 2013. PMID 24023765
• Sadrolashrafi K, Cotter DG. Not Your Mother's Melanoma: Causes and Effects of Early Melanoma Diagnosis. Dermatopathology (Basel). 2022 Nov 27;9(4):368-378. doi: 10.3390/dermatopathology9040043. PMID 36547217
• Navarrete-Dechent C, DeRosa AP, Longo C, Liopyris K, Oliviero M, Rabinovitz H, Marghoob AA, Halpern AC, Pellacani G, Scope A, Jain M. Reflectance confocal microscopy terminology glossary for nonmelanocytic skin lesions: A systematic review. J Am Acad Dermatol. 2019 May;80(5):1414-1427.e3. doi: 10.1016/j.jaad.2018.12.007. Epub 2018 Dec 8. PMID 30529706
• Pellacani G, Farnetani F, Gonzalez S, Longo C, Cesinaro AM, Casari A, Beretti F, Seidenari S, Gill M. In vivo confocal microscopy for detection and grading of dysplastic nevi: a pilot study. J Am Acad Dermatol. 2012 Mar;66(3):e109-21. doi: 10.1016/j.jaad.2011.05.017. Epub 2011 Jul 13. PMID 21742408
• Argenziano G, Catricala C, Ardigo M, Buccini P, De Simone P, Eibenschutz L, Ferrari A, Mariani G, Silipo V, Sperduti I, Zalaudek I. Seven-point checklist of dermoscopy revisited. Br J Dermatol. 2011 Apr;164(4):785-90. doi: 10.1111/j.1365-2133.2010.10194.x. Epub 2011 Mar 10. PMID 21175563

Identifiers

NCT: NCT07277920 · UNIMORE-DERM-2025-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗