Reflectance Confocal Microscopy and Molecular Correlation in Atypical Melanocytic Lesions

November 29, 2025 updated by: Francesca Farnetani, University of Modena and Reggio Emilia

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

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.

Study Overview

Status

Recruiting

Conditions

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.

Study Type

Observational

Enrollment (Estimated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • Mo
      • Modena, Mo, Italy, 41125
        • Recruiting
        • Dermatology Department, University Hospital of Modena
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

N/A

Sampling Method

Non-Probability Sample

Study Population

Approximately 200 melanocytic lesions from adult patients (age ≥18 years) scheduled for surgical excision due to dermoscopic suspicion of atypical nevus or early-stage melanoma will be included. Patients of all genders are eligible. Lesions will be evaluated using routine clinical assessment, dermoscopy, and Reflectance Confocal Microscopy (RCM). Histopathological evaluation will be performed on all excised lesions. Molecular analysis via Next-Generation Sequencing (NGS) will be performed on lesions with available tissue, and not all lesions may undergo NGS. Participants are recruited consecutively at the Videomicroscopy and Confocal Clinic, Dermatology Department, University Hospital of Modena.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Diagnostic relevance of RCM features in atypical melanocytic lesions
Time Frame: through study completion, an average of 1 year
Evaluation of the presence of atypical cells (>20 µm, dendritic or round, suprabasal or at the dermoepidermal junction level) and disarrangement of the dermoepidermal junction (non-edged papillae, chaotic patterns, architectural irregularity) using Reflectance Confocal Microscopy (RCM), and comparison with histopathological diagnosis.
through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Differential gene expression profiles distinguishing nevi and early-stage melanomas
Time Frame: through study completion, an average of 1 year
Quantitative assessment of molecular features obtained through genomic/molecular analysis to identify patterns that distinguish benign nevi from early-stage melanomas. Data will be summarized as differential expression levels and/or frequency of molecular alterations.
through study completion, an average of 1 year

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation between RCM morphological patterns and NGS-derived molecular signatures
Time Frame: through study completion, an average of 1 year

Outcome Measure Description

Quantitative correlation analysis between:

RCM morphological features, measured using Reflectance Confocal Microscopy (RCM) (e.g., presence of atypical cells, dermoepidermal junction disarrangement, architectural irregularity), summarized as categorical imaging features, and

NGS-derived molecular signatures, measured through Next-Generation Sequencing (NGS), including identification of specific genes showing differential expression or genomic alterations, not only presence/absence of alterations.

The reported outcome will be the correlation coefficient between imaging-defined RCM patterns and gene-level molecular profiles identified through NGS.

Unit of Measure:

Correlation coefficient (r value)

Measurement Tools:

Reflectance Confocal Microscopy (RCM) for morphological features

Next-Generation Sequencing (NGS) for molecular signatures
through study completion, an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Modena and Reggio Emilia

Collaborators

European Union

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2023

Primary Completion (Estimated)

December 31, 2025

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

November 19, 2025

First Submitted That Met QC Criteria

November 29, 2025

First Posted (Actual)

December 11, 2025

Study Record Updates

Last Update Posted (Actual)

December 11, 2025

Last Update Submitted That Met QC Criteria

November 29, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UNIMORE-DERM-2025-01

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Melanoma (Skin Cancer)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Sweden

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe