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.

Editor's Highlights - August 2024.

Pigmentary and hair disorders have a significant cosmetic and psychological impact. In the August issue of the Journal, we highlight the use of reflectance confocal microscopy in diagnosing and monitoring treatment responses in patients with melasma. We will also discuss new therapeutic approaches involving oral melatonin and a combination of glutathione and resveratrol for melasma. Additionally, the ongoing revolution in alopecia treatment with oral low-dose minoxidil will be spotlighted, including the circumstances under which media attention has contributed to the growing interest in oral minoxidil prescriptions.

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.

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.

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.

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.

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 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.

Microneedle fractional radiofrequency associated with drug delivery for facial atrophic acne scars and skin rejuvenation.

Microneedle fractional radiofrequency (MFRF) has been used to improve photoaging and scars. This study aimed to evaluate the efficacy and safety of MFRF with basic fibroblast growth factor (bFGF) for facial atrophic acne scars and skin rejuvenation by blinded visual evaluation, self-report, and reflective confocal microscopy (RCM). Fifteen subjects were randomized to the MFRF with bFGF group and fifteen to the MFRF group. All subjects underwent three-session therapy and a follow-up period. Significant group differences were in ECCA, global improvement score, satisfaction, and downtime before and after treatment. Combination therapy could be more effective than monotherapy for acne scars and facial rejuvenation. In addition, RCM can be used to observe the changes in skin collagen before and after treatment in evaluating cosmetic efficacy.

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.

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.

Correlation between super-high magnification (400x) dermoscopy and reflectance confocal microscopy for the diagnosis of melanosis and other pigmented genital lesions.

The clinical diagnosis of pigmented genital lesions is challenging. Reflectance confocal microscopy (RCM) is effective for diagnosis but is limited in its application due to elevated costs. A more affordable dermatoscope with a 400x magnification (D400) has recently been brought to market. The aim of our study was to compare these two imaging techniques for the analysis of pigmented genital tumours. An observational, prospective and mono-centric study was carried out from October 2017 to May 2019, in which clinical, dermatoscopic (20x and 400x) and RCM data from 207 pigmented genital lesions were collected. The images generated via D400 and RCM were analysed by three expert investigators. Similarities between the criteria observed using D400 and RCM were evaluated by each investigator. In total, 207 lesions were included: 183 melanosis, 19 nevi, one basal cell carcinoma (BCC), two condylomas and two melanomas in situ. Our series correlates well with data found in the literature especially for the distribution of different lesions, their topography, and their aspect using x20 dermatoscopy and RCM. Pattern and cell criteria defined using RCM largely paralleled those observed with D400 for all three investigators. Correlation between D400 and RCM was moderate to strong with regards to the identification of the ring pattern and clustered round cells, strong for dendritic and plump cells, and perfect for isolated round cells and spindle cells. D400 is an easy-to-use, cost-effective alternative for the analysis of pigmented genital lesions, particularly for melanosis.

The Importance of In Vivo Reflectance Confocal Microscopy in a Case of Desmoplastic Melanoma.

Desmoplastic melanoma accounts for 5% of all cases of melanoma, but its diagnosis can be difficult due to its frequent clinical presentation with amelanotic lesions. Histologically, spindled melanocytes surrounded by a collagenous stroma are observed. Compared with other types of melanoma, the desmoplastic types presents greater local aggression, and is more prone to local recurrence, but has a lower risk of lymph node metastasis. Early detection, accurate staging, and proper surgical management are the main factors associated with higher survival rates in melanoma patients. Reflectance confocal microscopy (RCM) has proven to be a valuable imaging tool in the diagnosis of skin neoplasms, being useful for orientating practitioners towards the diagnosis of melanoma and indicating the necessity of performing a diagnostic biopsy. We present the case of 52-year-old woman, who presented to the dermatology department with an irregular, dark-colored plaque in the right deltoid region. Dermoscopy showed asymmetry with an atypical network and some areas of regression. RCM revealed pagetoid cells in the upper epidermis, cell atypia, non-edged papillae, dermal inflammation, and nucleated cells in the dermis, which are highly suggestive of melanoma. A biopsy was also performed. A histopathology exam confirmed the diagnosis of superficially spreading melanoma with a desmoplastic component, and revealed a Breslow index of 0.9 mm, Clark level IV, an absence of mitoses, angiolymphatic invasion and regression, and complete excision. The CT and PET-CT scans were negative. A biopsy of the axillary sentinel lymph node was conducted, with a negative result obtained, establishing the IB stage of the disease. The patient will remain under follow-up to look for a recurrence or a new primary melanoma.

Ex Vivo Confocal Laser Scanning Microscopy in Rare Skin Diseases.

While ex vivo confocal laser scanning microscopy has previously demonstrated its utility in most common skin diseases, its use in the assessment of dermatological entities with lower incidence remains unexplored in most cases. We therefore aimed to evaluate the diagnostic efficacy of some rare skin tumors as well as a few inflammatory skin diseases, that have not yet been studied in ex vivo confocal laser scanning microscopy. A total of 50 tissue samples comprising 10 healthy controls, 10 basal cell carcinoma, 10 squamous cell carcinoma, and 20 rare skin conditions were imaged using the newest generation ex vivo confocal microscopy (Vivascope 2500 M-G4, Vivascope GmbH, Munich, Germany). Three blinded investigators were asked to identify characteristic features of rare skin disorders and distinguish them from more common skin diseases in the ex vivo confocal microscopy images. Our findings present the capability of ex vivo confocal microscopy to display distinctive morphologic patterns in common and rare skin diseases. As might be expected, we found a strong correlation between imaging experience and diagnostic accuracy. While the imaging inexperienced dermatohistopathologist reached 60% concordance, the imaging-trained dermatologist obtained 88% agreement with dermatohistopathology. The imaging-trained dermatohistopathologist achieved concordance up to 92% with gold-standard dermatohistopathology. This study highlights the potential of ex vivo confocal laser scanning microscopy as a promising adjunct to conventional dermatohistopathology for the early and precise identification of rare dermatological disorders.

Efficacy of Siltuximab and 1,927 nm Fractional Laser for the Treatment of Cutaneous Manifestations in Castleman's Disease: The Role of Dermoscopy and Reflectance Confocal Microscopy for Lesion Evaluation.

Introduction: Multicentric Castleman's disease (MCD) with cutaneous involvement has rarely been discussed in dermatologic literature, with few reports. Cutaneous lesions in MCD may induce deep scars, causing a significant impact in the daily life of the patients. The treatment of Castleman's disease (CD) is usually a challenge, especially in case of cutaneous involvement. Case Presentation: We report the case of a 35-year-old Caucasian man with a 3-year-old history of MCD with cutaneous involvement that we treated with a combined therapy characterized by siltuximab and 1,927 nm fractional laser. The patient showed a therapeutic response, characterized by a reduction of systemic symptoms and cutaneous manifestations. Conclusion: We believe that the combination of siltuximab and 1,927 nm fractional laser might have a synergistic beneficial role in patients with cutaneous iMCD and maximize esthetic outcomes. Anyway, additional evidence is needed to validate our findings.

Evaluation of linear dermatoses by reflectance confocal microscopy in children.

Lichen striatus (LS), linear psoriasis (LPs), linear cutaneous lupus erythematosus (LCLE) and linear lichen planus (LLP) often have similar clinical manifestations, which makes clinical diagnosis with the naked eye difficult; therefore, they are easily misdiagnosed. The purpose of this study was to determine whether reflectance confocal microscopy (RCM) is helpful in differentiating between these four linear dermatoses in children. This retrospective study included 14 patients with LS, nine with LPs, eight with LCLE and 12 with LLP. All patients were analysed using RCM, and biopsies were collected from lesions previously imaged by RCM. For LS, the dermal papillary rings were partially absent, but when present, manifested with small, homogeneously round, bright cells and occasionally highly refractive plump cellular structures, aggregated in clusters. LPs exhibited dark cyst-like structures with small, bright, round cells aggregated at the epidermal level; at the dermal-epidermal junction, homogeneously distributed, enlarged, faint dermal papillary rings and numerous enlarged low-refractive canalicular structures were observed in the superficial dermis. LCLE and LLP exhibited similar manifestations, including epidermal disarray, almost total absence of dermal papillary rings, and various sized refractive structures densely distributed in the dermis. The key distinguishing features of LCLE were the different sized structures mainly clustered around hair follicles, while LLP demonstrated dense structures with a scattered distribution. RCM may be used to distinguish between the key features of LS, LPs, LCLE and LLP in children.

Exploring the Utilization of Imaging Modalities in the Diagnosis of Basal Cell Carcinoma: A Scoping Review.

Basal cell carcinoma (BCC) is a common skin cancer that occurs due to various genetic and environmental factors. Diagnosis is made by a combination of clinical appearance, biopsy, imaging, and histopathological analysis. This review describes the current array of imaging modalities available to physicians to aid in the diagnosis of BCC. It is important to stay up-to-date with improvements in diagnostic screening, and knowledge of these options is instrumental in providing the best care to patients. Embase, Medline Industries, and PubMed were searched for articles within the past 10 years based on a search query that looked for imaging modalities used in the diagnosis and evaluation of a variety of dermatologic conditions. The search was further refined to focus on BCC and satisfy the inclusion/exclusion criteria determined by the authors. The research process was detailed in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses diagram. Dermoscopy is a non-invasive in vivo microscopic technique used to evaluate skin lesions. Features of dermoscopy cannot be visualized with the naked eye, and studies found that dermoscopy increased diagnostic accuracy. Reflectance confocal microscopy (RCM) examines skin morphology, and recent studies found that 100% of patients with BCC had tumor-free margins when diagnosed with RCM. It allows for a one-stop-shop for diagnosis. Optical spectroscopy samples multiple sites without removing tissue. It helps detect subtle biophysical differences, allowing for earlier diagnosis. High-frequency ultrasound (HFUS) helps determine tumor size, structure, depth of invasion and spread. Studies found statistically significant positive correlations between depth of spread and HFUS readings. Optical coherence tomography takes cross-sectional images to analyze histopathology and morphology. It produces high-resolution images, confers slightly more accurate results than a biopsy, and expedites the treatment process through an earlier diagnosis without a biopsy.These results will advance the fields of dermatology and radiology as they describe unique uses for these imaging modalities. There are a variety of ways to use microscopy, and these techniques may be applied to many different lesions and help revolutionize the diagnosis and treatment of skin cancer and other lesions without the need for multiple, sometimes disfiguring surgical procedures. With the increase in diagnostic accuracy and decrease in diagnosis time, advanced imaging studies will become an integral part of dermatologic diagnosis and be included in future management and treatment plans, especially in the case of BCC.