Reflectance Confocal Microscopy and Dermoscopy for the Diagnosis of Solitary Hypopigmented Pink Lesions: A Narrative Review.

Diagnosing solitary pink skin lesions poses a significant challenge due to the scarcity of specific clinical and dermoscopic criteria. Several benign lesions, such as cherry angioma, clear cell acanthoma, dermal nevus, keloid, hypertrophic scar, and Spitz nevus, often exhibit similar clinical and dermoscopic features. This similarity extends to some malignant lesions, including basal cell carcinoma, actinic keratosis, and amelanotic melanoma, making differentiation difficult. Recent studies highlight the enhanced diagnostic accuracy of reflectance confocal microscopy (RCM), which offers increased sensitivity and specificity compared to dermoscopy alone for diagnosing skin cancer. This study aims to summarize the application of dermoscopy and RCM in distinguishing between benign and malignant pinkish-reddish skin lesions. The integration of RCM with traditional dermoscopic techniques improves the ability to accurately identify and differentiate these lesions. However, it is crucial to note that for any suspicious lesions, a final diagnosis must be confirmed through surgical excision and histopathological evaluation. This comprehensive approach ensures accurate diagnosis and appropriate treatment, highlighting the importance of combining advanced imaging techniques in clinical practice.

Line-field confocal optical coherence tomography: Characteristic hints for the diagnosis of scarring alopecia due to lupus erythematodes: A preliminary study.

INTRODUCTION: Lupus erythematosus (LE) is an inflammatory autoimmune disease, that can affect the skin to varying degree. In particular, discoid LE (DLE) and the rare form of lupus panniculitis/profundus are associated with scarring alopecia. The heterogeneity of the clinical, dermatoscopic, and histologic presentation poses a major challenge to the clinician in the diagnosis and differential diagnosis of other forms of scarring alopecia. OBJECTIVE: While noninvasive imaging techniques using optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) have proven to be helpful in the diagnosis of scarring alopecia in the context of LE, this study aimed to investigate line-field confocal OCT (LC-OCT) to identify characteristic features of cicatricial alopecia in LE. METHODS: Fifteen patients with cicatricial alopecia in LE were included and the most affected/inflamed areas of the scalp were prospectively examined. In analogy to histopathology and previously reported criteria in RCM, all images were evaluated according to seven established criteria and underwent descriptive analyses. RESULTS: LC-OCT revealed characteristic features of cicatricial alopecia, such as lymphocytic interface dermatitis (14/15; 93.3%) and basal cell vacuolization (13/15; 86.7%). The most impressive feature was the occurrence of prominent hyperreflective fibers in 14/15 patients (93.3%). CONCLUSION: LC-OCT imaging can noninvasively detect morphologic criteria such as lymphocytic and vacuolar interface dermatitis of cicatricial alopecia due to LE. In particular, the presence of hyperreflective collagen fibers appears to be a characteristic easily recognizable feature that may facilitate differential diagnosis with other forms of cicatricial alopecia. Further studies are mandatory to differentiate other forms of scarring alopecia.

Basosquamous carcinoma: Comprehensive epidemiological, clinical, dermoscopic, and confocal features from a single center institution.

BACKGROUND: Basosquamous carcinoma (BSC) is a rare and aggressive nonmelanoma skin cancer (NMSC) that exhibits features of both BCC and squamous cell carcinoma (SCC). The gold standard for diagnosis is histopathological examination. BSC is often challenging to diagnose and manage due to its mixed histological features and potential for aggressive behavior AIM: To identify specific features aiding clinicians in differentiating BSCs using non-invasive diagnostic techniques. METHODS: We conducted a retrospective descriptive, monocentric study of the epidemiological clinical, dermoscopic, and reflectance confocal microscopy (RCM) features of histopathologically proven BSCs diagnosed between 2010 and 2023. A total of 192 cases were selected. RESULTS: The study population consisted of 17 men (60.9%). Total 95.8% of patients at the time of diagnosis were ≥50 years. BSC occurred in the head and neck area in 124 cases (63.1%) of which 65 (33.9%) were in the H-zone. For 47.4% of patients, BSC presented as a macule with undefined clinical margins (43.3%). Dermoscopic images were available for 98 cases: the most common parameter was the presence of whitish structureless areas (59 [60.2%]), keratin masses (58 [59.2%]), superficial scales, and ulceration or blood crusts (49 [50%] both). Vessels pattern analysis revealed hairpin vessels (exclusively) and linear irregular vessels as the most frequent (55 [56.1%] both). RCM examination was performed in 21 cases which revealed specific SCC features such as solar elastosis (19 [90.5%]), atypical honeycomb pattern (17 [89%]), proliferation of atypical keratinocytes (16 [80%]) combined with BCC' ones as bright tumor islands (12 [57.8%]), and cleft-like dark spaces (11 [53.4%]). DISCUSSION: Our study reflects the largest cohort of BSCs from a single institution. We described an incidence rate of 4.7%, higher than reported in the Literature, with the involvement of patients ≥50years in almost 96% of cases and an overall male predominance. At clinical examination, BSC was described as a hyperkeratotic macule with undefined clinical margins with one or more dermoscopic SCC' features, whereas the presence of typical BCC aspects was observed in less than 10% of cases, differently from what was previously reported. At RCM analysis, BSCs presented with an atypical honeycomb pattern with proliferation of atypical keratinocytes, hyperkeratosis, and in nearly 55% of patients, bright tumor islands with cleft-like dark spaces. CONCLUSION: The distinctive dermoscopic patterns, along with the RCM features aid in the differentiation of BSCs from other NMSCs.

DermoGAN: multi-task cycle generative adversarial networks for unsupervised automatic cell identification on in-vivo reflectance confocal microscopy images of the human epidermis.

Significance: Accurate identification of epidermal cells on reflectance confocal microscopy (RCM) images is important in the study of epidermal architecture and topology of both healthy and diseased skin. However, analysis of these images is currently done manually and therefore time-consuming and subject to human error and inter-expert interpretation. It is also hindered by low image quality due to noise and heterogeneity. Aim: We aimed to design an automated pipeline for the analysis of the epidermal structure from RCM images. Approach: Two attempts have been made at automatically localizing epidermal cells, called keratinocytes, on RCM images: the first is based on a rotationally symmetric error function mask, and the second on cell morphological features. Here, we propose a dual-task network to automatically identify keratinocytes on RCM images. Each task consists of a cycle generative adversarial network. The first task aims to translate real RCM images into binary images, thus learning the noise and texture model of RCM images, whereas the second task maps Gabor-filtered RCM images into binary images, learning the epidermal structure visible on RCM images. The combination of the two tasks allows one task to constrict the solution space of the other, thus improving overall results. We refine our cell identification by applying the pre-trained StarDist algorithm to detect star-convex shapes, thus closing any incomplete membranes and separating neighboring cells. Results: The results are evaluated both on simulated data and manually annotated real RCM data. Accuracy is measured using recall and precision metrics, which is summarized as the F 1 -score. Conclusions: We demonstrate that the proposed fully unsupervised method successfully identifies keratinocytes on RCM images of the epidermis, with an accuracy on par with experts' cell identification, is not constrained by limited available annotated data, and can be extended to images acquired using various imaging techniques without retraining.

Intradermal Delivery of Calcium Hydroxylapatite With Fractionated Ablation.

OBJECTIVES: The absorption of biostimulatory particulate matter following its application to fractional skin defects remains poorly understood, and even less is known about its in vivo impact in terms of tissue integration. The objectives of this study are twofold: (1) to evaluate the potential of calcium hydroxylapatite (CaHA) to penetrate through skin treated with a fractional laser; and (2) to assess the effectiveness of clinical laser scanning microscopy technologies in monitoring the effects of such treatment over time. METHODS: One area on a volunteer's arm was treated with a fractional erbium laser (Sciton Inc., Palo Alto, CA), while a second area received the same laser treatment followed by CaHA topical application. We used reflectance confocal microscopy (RCM) and multiphoton microscopy (MPM) to noninvasively image beneath the surface of the treated skin to study and monitor the effects of these treatments within 1 h of treatment and at four additional time points over a 6-week period. RESULTS: One hour posttreatment, at different depths beneath the skin surface, MPM and RCM provided similar visualizations of laser-induced channels. In skin treated by both laser and CaHA, these two imaging methods provided complementary information. RCM captured the lateral and depth distribution of CaHA microspheres and were seen as bright spheres as they became incorporated into the healing tissue. MPM, meanwhile, visualized the CaHA microparticles as dark shadow spheres within the laser-induced channels and encroaching healing tissue. Furthermore, MPM provided critical information about collagen regeneration around the microspheres, with the collagen visually marked by its distinct second harmonic generation (SHG) signal. CONCLUSIONS: This observational pilot study demonstrates that CaHA, a collagen stimulator used as a dermal filler, can not only be inserted into the dermis after fractional laser treatment but remains in the healing skin for at least 6 weeks posttreatment. The noninvasive imaging techniques RCM and MPM successfully captured the presence of CaHA microspheres mid-dermis during the healing phase. They also demonstrated new collagen production around the microspheres, highlighting the effectiveness of these imaging approaches in monitoring such treatment over time.

In Vivo Evaluation of Laser-Induced Optical Breakdown (LIOBS) by 1064-nm Nd:YAG Fractional Picosecond Laser With Reflectance Confocal Microscopy and Precise Histopathologic Correlation.

OBJECTIVES: Picosecond lasers with a microlens array can cause laser-induced optical breakdown (LIOBS) and LIC (Intradermal laser-induced cavitation) within high-fluence areas. This study aimed to describe the clinical, reflectance confocal microscopy (RCM), histopathological findings, and the characteristics of vacuoles caused by LIOBS and LIC in individuals with skin types III and IV. MATERIALS AND METHODS: This study was performed on six Chilean healthy volunteers, males and females, aged 35-65 years old with Fitzpatrick skin phototypes III-IV. The laser was applied in the inner proximal area of the nondominant arm. RCM evaluation was performed 24 h later; 48 h later, skin biopsies were performed on the laser-treated areas. Clinical, histological, and RCM findings were recorded. RESULTS: Every individual developed a 10 mm2 area of clinical erythema in the treated area. Under RCM, all six volunteers had hyporeflective spherical structures at the level of the epidermis, consistent with intraepidermal vacuoles. Histopathological evaluation revealed different sizes of vacuoles in both the epidermis and dermis. CONCLUSION: The LIOBS and LIC processes and the secondary production of vacuoles could be highly valuable for effective dermal remodeling treatment and aid in promoting the production of new collagen, elastic fibers, and growth factors that could improve skin texture. These structures were visible under RCM and histopathological evaluation.

Dermoscopic characteristics of Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive, cutaneous tumour with high mortality and frequently delayed diagnosis. Clinically, it often manifests as a rapidly growing erythematous to purple nodule usually located on the lower extremities or face and scalp of elderly patients. There is limited available data on the dermoscopic findings of MCC, and there are no specific features that can be used to definitively diagnose MCC. AIM OF THE STUDY: Here, we aimed to summarize existing published literature on dermatoscopic and reflectance confocal microscopy (RCM) features of MCC. MATERIALS AND METHODS: To find relevant studies, we searched the PubMed and Scopus databases from inception to April 12, 2023. Our goal was to identify all pertinent research that had been written in English. The following search strategy was employed: (" dermoscopy" OR " dermatoscopy" OR " videodermoscopy" OR " videodermatoscopy" OR " reflectance confocal microscopy") AND " Merkel cell carcinoma". Two dermatologists, DK and GE, evaluated the titles and abstracts separately for eligibility. For inclusion, only works written in English were taken into account. RESULTS: In total 16 articles were retrieved (68 cases). The main dermoscopic findings of MCC are a polymorphous vascular pattern including linear irregular, arborizing, glomerular, and dotted vessels on a milky red background, with shiny or non-shiny white areas. Pigmentation was lacking in all cases. The RCM images showed a thin and disarranged epidermis, and small hypo-reflective cells that resembled lymphocytes arranged in solid aggregates outlined by fibrous tissue in the dermis. Additionally, there were larger polymorphic hyper-reflective cells that likely represented highly proliferative cells. CONCLUSION: Dermoscopic findings of MCC may play a valuable role in evaluating MCC, aiding in the early detection and differentiation from other skin lesions. Further prospective case-control studies are needed to validate these results.

Precise Serial Microregistration Enables Quantitative Microscopy Imaging Tracking of Human Skin Cells In Vivo.

We developed an automated microregistration method that enables repeated in vivo skin microscopy imaging of the same tissue microlocation and specific cells over a long period of days and weeks with unprecedented precision. Applying this method in conjunction with an in vivo multimodality multiphoton microscope, the behavior of human skin cells such as cell proliferation, melanin upward migration, blood flow dynamics, and epidermal thickness adaptation can be recorded over time, facilitating quantitative cellular dynamics analysis. We demonstrated the usefulness of this method in a skin biology study by successfully monitoring skin cellular responses for a period of two weeks following an acute exposure to ultraviolet light.

Application of in vivo reflectance confocal microscopy in the diagnosis of Bowen's disease.

Bowen's disease (BD) is a relatively rare early-stage squamous cell carcinoma in situ, most commonly affecting the middle-aged and elderly, and occurring on the skin or mucous membranes of various parts of the body. Its onset is concealed, the course of the disease is chronic, and some patients have malignant tumors outside the skin; therefore, it is necessary to diagnose and evaluate the disease at an early stage. This study aimed to investigate the application of reflectance confocal microscopy (RCM) in the diagnosis of BD. We performed RCM imaging on the lesion site and underwent skin biopsy for histological diagnosis of 92 patients initially diagnosed with BD in clinic. A retrospective analysis of the RCM result as well as the histological examination revealed that after analyzing RCM images, out of 92 biopsy lesions, 61 were diagnosed with BD, of which 54 were consistent with RCM diagnosis. Among the 59 cases diagnosed with BD by RCM, 54 cases were consistent with the histological diagnosis. Afterwards, we analyzed the RCM characteristics in patients with BD verified by biopsy, and compared the RCM images of two different lesions, classic Bowen's disease and pigmented Bowen's disease, and further summarized the key points of BD under RCM. Finally, we focused on the differential characteristics between BD and other skin diseases in RCM. RCM is of great value in the diagnosis of BD. RESEARCH HIGHLIGHTS: A retrospective study of RCM and histological diagnosis in patients with clinical diagnosis of BD. Analyze the RCM characteristics of skin lesions verified by biopsy. RCM is of great value in the diagnosis and differentiation of BD.

Revisiting the standards of cancer detection and therapy alongside their comparison to modern methods.

In accordance with the World Health Organization data, cancer remains at the forefront of fatal diseases. An upward trend in cancer incidence and mortality has been observed globally, emphasizing that efforts in developing detection and treatment methods should continue. The diagnostic path typically begins with learning the medical history of a patient; this is followed by basic blood tests and imaging tests to indicate where cancer may be located to schedule a needle biopsy. Prompt initiation of diagnosis is crucial since delayed cancer detection entails higher costs of treatment and hospitalization. Thus, there is a need for novel cancer detection methods such as liquid biopsy, elastography, synthetic biosensors, fluorescence imaging, and reflectance confocal microscopy. Conventional therapeutic methods, although still common in clinical practice, pose many limitations and are unsatisfactory. Nowadays, there is a dynamic advancement of clinical research and the development of more precise and effective methods such as oncolytic virotherapy, exosome-based therapy, nanotechnology, dendritic cells, chimeric antigen receptors, immune checkpoint inhibitors, natural product-based therapy, tumor-treating fields, and photodynamic therapy. The present paper compares available data on conventional and modern methods of cancer detection and therapy to facilitate an understanding of this rapidly advancing field and its future directions. As evidenced, modern methods are not without drawbacks; there is still a need to develop new detection strategies and therapeutic approaches to improve sensitivity, specificity, safety, and efficacy. Nevertheless, an appropriate route has been taken, as confirmed by the approval of some modern methods by the Food and Drug Administration.

An Update on Non-Invasive Skin Imaging Techniques in Actinic Keratosis-A Narrative Review.

Nonmelanocytic skin cancers (NMSCs) are currently the most common group of human cancers and include all tumors that are not melanomas. Increased exposure to sunlight over the past few years, the lack of regular and proper use of sunscreen, the aging of the population, and better screening techniques are the reasons for the escalation in their diagnosis. Squamous cell carcinoma (SCC) comprises nearly 37% of the tumors in this group and can originate from actinic keratosis (AK), which usually presents as pink, often scaly plaques, usually located on the face or scalp. Advances in dermatoscopy, as well as the development of other non-invasive skin imaging modalities such as high-frequency ultrasound (HFUS), reflectance confocal microscopy (RCM), and optical coherence tomography (OCT), have allowed for greatly increased sensitivity in diagnosing these lesions and monitoring their treatment. Since AK therapy is usually local, and SCCs must be removed surgically, non-invasive imaging methods enable to correctly qualify difficult lesions. This is especially important given that they are very often located on the face, and achieving an appropriate cosmetic result after treatments in this area is very important for the patients. In this review, the authors describe the use of non-invasive skin imaging methods in the diagnosis of actinic keratosis.

Reflectance confocal microscopy for plaque psoriasis therapeutic follow-up during an anti-interleukin-17A monoclonal antibody: an observational study.

Interleukin-17A therapeutic inhibitors are among the most effective treatment methods for moderate-to-severe plaque psoriasis (PP). Reflectance confocal microscopy is a non-invasive imaging technique already documented to be beneficial in evaluating the follow-up of PP under treatment with topical actives and phototherapy. This study aimed to assess the epidermal and dermal changes associated with psoriasis and its treatment with RCM during systemic secukinumab treatment in patients with moderate-to-severe PP. A pilot study was conducted to evaluate RCM as a non-invasive tool for monitoring secukinumab treatment in patients with PP. For patients receiving secukinumab treatment, lesional skin was selected for RCM imaging, which were recorded at all scheduled times. The RCM evaluation criteria were established based on the histopathological diagnostic criteria for psoriasis. The clinical severity of psoriasis was assessed utilizing the psoriasis area severity index. A total of 23 patients with PP were included in the study. Each patient received 300 mg of subcutaneous secukinumab as induction therapy at baseline and weeks 1-4, followed by maintenance therapy every four weeks. Microscopic confocal changes were observed during the treatment. The results identified early microscopic evidence of the anti-inflammatory activity of secukinumab, which was not detected during the clinical examination. RCM findings correlating with the PASI were used to observe the patient's response to treatment and were identified as follows: acanthosis and parakeratosis, presence of epidermal and dermal inflammatory cells, presence of non-edge dermal papillae, and vascularization in the papillary dermis. This study is the first to demonstrate the use of RCM as an effective tool for non-invasive monitoring of secukinumab therapeutic response at a cellular level in a clinical or research setting. Early detection of RCM parameters associated with secukinumab activity may facilitate the identification of an early treatment response. RCM appears to be capable of providing practical and helpful information regarding follow-up in patients with PP undergoing secukinumab treatment. RCM may also provide novel perspectives on the subclinical evaluation of PP's response to biological therapy.

Analysis of the characteristics of reflectance confocal microscopy images of xanthogranuloma and xanthoma.

BACKGROUND: Both xanthogranuloma and xanthoma clinically manifest as yellowish skin lesions. Historically, the gold standard for diagnosis was skin histopathological examination. Currently, the advent of reflectance confocal microscopy (RCM) offers additional diagnostic support for these diseases by revealing their microscopic features, thereby enhancing the theoretical foundation for diagnosis. OBJECTIVE: This study aimed to elucidate the distinctive characteristics of RCM images in xanthogranuloma and xanthoma, assess their diagnostic value, and investigate the relationship between RCM and histopathological features, ultimately boosting diagnostic accuracy. METHODS: RCM and histopathological examinations were conducted on 13 patients with xanthogranuloma and 12 with xanthoma, recruited from our Dermatology Clinic between August 2022 and November 2023. The study involved analyzing RCM image features and correlating them with histopathological findings. RESULTS: The RCM images of 13 xanthogranuloma and 12 xanthoma cases showed similar features. Xanthogranuloma predominantly exhibited epidermal atrophy and thinning in 6 cases (46.15%). Additionally, in 69.23% of cases, scattered small mononuclear inflammatory cells were infiltrated in the superficial and middle dermis layers. Medium to high refractive cells, predominantly vacuolated and resembling foam, were observed in 61.54% of cases. All cases demonstrated high refractive cells with distinct target-shaped, disc-shaped, horseshoe-like, and flower-ring structures. Concordance rates with histopathological examinations were 69.23, 92.31, 92.31, and 100%, respectively. Regarding xanthoma, epidermal atrophy and thinning occurred in two cases (16.67%), and mononuclear inflammatory cell infiltration was observed in 25% of cases. High refractive cells with the previously mentioned shapes were present in 100% of cases, though only 16.67% displayed these characteristics exclusively. The concordance rates were 66.67, 91.67, 100, and 91.67%, respectively. CONCLUSION: RCM imaging of xanthogranuloma and xanthoma presents distinctive, highly consistent features with their histopathology, offering valuable insights for clinicians in diagnosing and differentiating these conditions.

Successful management of chromoblastomycosis utilizing conventional antifungal agents and imiquimod therapy.

Chromoblastomycosis (CBM), a chronic fungal infection affecting the skin and subcutaneous tissues, is predominantly caused by dematiaceous fungi in tropical and subtropical areas. Characteristically, CBM presents as plaques and nodules, often leading to scarring post-healing. Besides traditional diagnostic methods such as fungal microscopy, culture, and histopathology, dermatoscopy and reflectance confocal microscopy can aid in diagnosis. The treatment of CBM is an extended and protracted process. Imiquimod, acting as an immune response modifier, boosts the host's immune response against CBM, and controls scar hyperplasia, thereby reducing the treatment duration. We present a case of CBM in Guangdong with characteristic reflectance confocal microscopy manifestations, effectively managed through a combination of itraconazole, terbinafine, and imiquimod, shedding light on novel strategies for managing this challenging condition.

Reflectance confocal microscopy for the early diagnosis of herpes zoster.

For herpes zoster (HZ) infection, early diagnosis and treatment are important in order to shorten the course of the disease and reduce sequelae, however, there is a lack of non-invasive diagnostic methods. Reflectance confocal microscopy (RCM) is a non-invasive technique often used to diagnose dyspigmented dermatosis, skin tumours, human papillomavirus infectious dermatosis, etc. To evaluate the clinical value of RCM for the early diagnosis of HZ. We collected RCM images from 30 HZ patients with typical vesicles in order to analyse their features. We then utilized RCM to analyse early lesions of another 12 HZ patients, who presented with localized erythema or papules, but not typical vesicles. In addition, we recruited one patient with HZ and observed the lesions over 14 days also using RCM. RCM images showed that the typical lesions of HZ mainly involved oedema of the spinous layer, intraepidermal blister formation, ballooning multinucleated giant (BMG) cells, and dermal papillary oedema. Among them, BMG cells were of specific diagnostic value. Early lesions of HZ patients without typical vesicles showed BMG cells under RCM. A few BMG cells were observed during the early stage of HZ. However, the number of BMG cells increased significantly as typical clustered blisters gradually appeared in the lesions. With the regression of the lesions, the number of BMG cells decreased gradually. RCM, with the advantages of being non-invasive, rapid, and convenient, has an important role in monitoring the evolution of HZ.

Reflectance confocal microscopy as noninvasive tool for monitoring tirbanibulin efficacy in actinic keratosis.

Actinic keratosis (AK) is a common precancerous condition found on sun-damaged skin. Tirbanibulin 1 % ointment has been approved for the topical treatment of non-hyperkeratotic facial and scalp Olsen grade I AKs over a contiguous area of 25 cm2 with a daily application for 5 consecutive days. Our aim was to investigate the use of in vivo RCM in the assessment of the response of AKs treated with tirbanibulin, as it has never been described in the published Literature. A total of 10 AKs in 10 consecutive outpatients were enrolled in the present study in May 2023. The follow-up visit was scheduled after 30 days from last application of tirbanibulin ointment. At follow-up visit, a complete response was described by clinical, dermoscopic and in vivo RCM examination in 10 out of 10 lesions, with a recovery of stratum corneum, decrease in atypical honeycomb pattern and changes in dermal collagen. All patients were followed up for at least 8 months and further recurrences were not registered. Based on our experience, we confirm the efficacy and safety of tirbanibulin in treating AKs and the usefulness of RCM in vivo examination for the therapeutic monitoring of such lesions, even in a very early stage.

Comparison of Extended Skin Cancer Screening Using a Three-Step Advanced Imaging Programme vs. Standard-of-Care Examination in a High-Risk Melanoma Patient Cohort.

Modern diagnostic procedures, such as three-dimensional total body photography (3D-TBP), digital dermoscopy (DD), and reflectance confocal microscopy (RCM), can improve melanoma diagnosis, particularly in high-risk patients. This study assessed the benefits of combining these advanced imaging techniques in a three-step programme in managing high-risk patients. This study included 410 high-risk melanoma patients who underwent a specialised imaging consultation in addition to their regular skin examinations in outpatient care. At each visit, the patients underwent a 3D-TBP, a DD for suspicious findings, and an RCM for unclear DD findings. The histological findings of excisions initiated based on imaging consultation and outpatient care were compared. Imaging consultation detected sixteen confirmed melanomas (eight invasive and eight in situ) in 39 excised pigmented lesions. Outpatient care examination detected seven confirmed melanomas (one invasive and six in situ) in 163 excised melanocytic lesions. The number needed to excise (NNE) in the imaging consultation was significantly lower than that in the outpatient care (2.4 vs. 23.3). The NNE was 2.6 for DD and 2.3 for RCM. DD, 3D-TBP, or RCM detected melanomas that were not detected by the other imaging methods. The three-step imaging programme improves melanoma detection and reduces the number of unnecessary excisions in high-risk patients.