Diagnosis of Skin Cancer: From the Researcher Bench to the Patient's Bedside.

The overall incidence and prevalence of skin cancer have shown a significant increase worldwide in the last several decades [...].

Multispectral Imaging Analysis of Skin Lesions in Patients with Neurofibromatosis Type 1.

Neurofibromatosis type 1 (NF1) is a rare disease, affecting around 1 in 3500 individuals in the general population. The rarity of the disease contributes to the scarcity of the available diagnostic and therapeutic approaches. Multispectral imaging is a non-invasive imaging method that shows promise in the diagnosis of various skin diseases. The device utilized for the present study consisted of four sets of narrow-band LEDs, including 526 nm, 663 nm, and 964 nm for diffuse reflectance imaging and 405 nm LEDs, filtered through a 515 nm long-pass filter, for autofluorescence imaging. RGB images were captured using a CMOS camera inside of the device. This paper presents the results of this multispectral skin imaging approach to distinguish the lesions in patients with NF1 from other more common benign skin lesions. The results show that the method provides a potential novel approach to distinguish NF1 lesions from other benign skin lesions.

Optically Guided High-Frequency Ultrasound to Differentiate High-Risk Basal Cell Carcinoma Subtypes: A Single-Centre Prospective Study.

BACKGROUND: Basal cell carcinoma (BCC) is the most common type of skin cancer in the Caucasian population. Currently, invasive biopsy is the only way of establishing the histological subtype (HST) that determines the treatment options. Our study aimed to evaluate whether optically guided high-frequency ultrasound (OG-HFUS) imaging could differentiate aggressive HST BCCs from low-risk tumors. METHODS: We conducted prospective clinical and dermoscopic examinations of BCCs, followed by 33 MHz OG-HFUS imaging, surgical excision, and a histological analysis. We enrolled 75 patients with 78 BCCs. In total, 63 BCCs were utilized to establish a novel OG-HFUS risk classification algorithm, while 15 were employed for the validation of this algorithm. The mean age of the patients was 72.9 ± 11.2 years. Histology identified 16 lesions as aggressive HST (infiltrative or micronodular subtypes) and 47 as low-risk HST (superficial or nodular subtypes). To assess the data, we used a one-sided Fisher's exact test for a categorical analysis and a Receiver Operating Characteristic (ROC) curve analysis to evaluate the diagnostic accuracy. RESULTS: OG-HFUS distinguished aggressive BCC HSTs by their irregular shape (p < 0.0001), ill-defined margins (p < 0.0001), and non-homogeneous internal echoes (p = 0.004). We developed a risk-categorizing algorithm that differentiated aggressive HSTs from low-risk HSTs with a higher sensitivity (82.4%) and specificity (91.3%) than a combined macroscopic and dermoscopic evaluation (sensitivity: 40.1% and specificity: 73.1%). The positive and negative predictive values (PPV and NPV, respectively) for dermoscopy were 30.2% and 76.8%, respectively. In comparison, the OG-HFUS-based algorithm demonstrated a PPV of 94.7% and an NPV of 78.6%. We verified the algorithm using an independent image set, n = 15, including 12 low-risk and 3 high-risk (high-risk) with two blinded evaluators, where we found a sensitivity of 83.33% and specificity of 91.66%. CONCLUSIONS: Our study shows that OG-HFUS can identify aggressive BCC HSTs based on easily identifiable morphological parameters, supporting early therapeutic decision making.

Dermoscopic Patterns of Genodermatoses: A Comprehensive Analysis.

(1) Background: Genodermatoses are a clinically and genetically heterogenous group of inherited skin disorders. Diagnosing inherited skin diseases is a challenging task due to their rarity and diversity. Dermoscopy is a non-invasive, easily accessible, and rapid tool used in dermatology not only for diagnostic processes but also for monitoring therapeutic responses. Standardized terminologies have been published for its proper use, reproducibility, and comparability of dermoscopic terms. (2) Methods: Here, we aimed to investigate dermoscopic features in various genodermatoses by conducting a systematic review and comparing its results to our own findings, data of patients diagnosed with genodermatoses at the Department of Dermatology, Venereology and Dermatooncology, Semmelweis University. (3) Results: Our systematic search provided a total of 471 articles, of which 83 reported both descriptive and metaphoric dermoscopic terminologies of 14 genodermatoses. The literature data were then compared to the data of 119 patients with 14 genodermatoses diagnosed in our department. (4) Conclusion: Dermoscopy is a valuable tool in the diagnosis of genodermatoses, especially when symptoms are mild. To enable the use of dermoscopy as an auxiliary diagnostic method, existing standardized terminologies should be extended to more genodermatoses.

Optical Coherence Tomography as a Valuable Tool for the Evaluation of Cutaneous Kaposi Sarcoma Treated with Imiquimod 5% Cream.

Kaposi sarcoma (KS) is a rare disease that was not frequently identified before the widespread occurrence of AIDS. Even today, it remains a challenge for physicians to diagnose, particularly in its early stages, often requiring referral to specialists and further investigations. Dermoscopy, a non-invasive imaging technique, reveals a distinctive rainbow pattern that strongly indicates KS. Moreover, advanced imaging tools like optical coherence tomography (OCT) can provide additional information though specific disease-related patterns have not been fully established yet. These emerging techniques show promise in facilitating early diagnosis of skin-related KS and monitoring the effectiveness of treatments. However, biopsy remains the definitive method for confirming the disease. In this study, we present two cases of cutaneous Kaposi sarcoma, documented using OCT, both before and after treatment with imiquimod 5% cream. The study highlights the potential of OCT in evaluating disease progression and treatment response, as well as the usefulness of dermoscopy in detecting early indicators of KS. By integrating these advanced imaging techniques, the diagnosis and management of cutaneous KS could be improved, leading to timely interventions and better patient outcomes.

Real-World Experience with Cemiplimab Treatment for Advanced Cutaneous Squamous Cell Carcinoma-A Retrospective Single-Center Study.

BACKGROUND: The systemic treatment of advanced cutaneous squamous cell carcinoma (cSCC) has seen significant developments in recent years. The anti-PD1 inhibitor cemiplimab has demonstrated efficacy in clinical trials, but real-world data are still limited. Here, we aimed to evaluate the efficacy and the safety of cemiplimab in a real-world clinical setting. METHODS: A retrospective analysis was carried out for all patients who received at least two doses of cemiplimab at our department between February 2020 and January 2023. Progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), the disease control rate (DCR) and adverse events (AEs) were evaluated. RESULTS: Twenty-five patients were included with a median age of 78 (65-82) years. The median treatment duration was 48 (16-72) weeks. Five (20%) patients were immunocompromised. Sixteen patients (64%) developed AEs, including 36% serious AEs (SAEs) of grade ≥ 3. Six patients (24%) were withdrawn from treatment due to the occurrence of AEs. Among the 25 patients, 52% showed an objective response (3 complete and 10 partial responses), 76% had controlled disease and 24% experienced progression. Among the five immunocompromised patients, the ORR was 60%, while the DCR was 80%. CONCLUSIONS: This retrospective real-world study revealed that locally advanced or metastatic cSCC could be effectively treated with cemiplimab even in elderly, polymorbid and immunocompromised patients.

A Cross-Sectional Study of the Dermatological Manifestations of Patients with Fabry Disease and the Assessment of Angiokeratomas with Multimodal Imaging.

Fabry disease (FD) is a multisystemic X-linked lysosomal storage disease that presents with angiokeratomas (AKs). Our objective was to investigate the clinical and morphologic features of AKs and to present two experimental techniques, multispectral imaging (MSI) and non-linear microscopy (NLM). A thorough dermatological examination was carried out in our 26 FD patients and dermoscopic images (n = 136) were evaluated for specific structures. MSI was used for the evaluation of AKs in seven patients. NLM was carried out to obtain histology samples of two AKs and two hemangiomas. Although AKs were the most common manifestation, the majority of patients presented an atypical distribution and appearance, which could cause a diagnostic challenge. Dermoscopy revealed lacunae (65%) and dotted vessels (56%) as the most common structures, with a whitish veil present in only 25%. Autofluorescence (405 nm) and diffuse reflectance (526 nm) images showed the underlying vasculature more prominently compared to dermoscopy. Using NLM, AKs and hemangiomas could be distinguished based on morphologic features. The clinical heterogeneity of FD can result in a diagnostic delay. Although AKs are often the first sign of FD, their presentation is diverse. A thorough dermatological examination and the evaluation of other cutaneous signs are essential for the early diagnosis of FD.

Scrofuloderma and granuloma annulare-like lesions: Challenges of diagnosing cutaneous tuberculosis in developed countries.

Tuberculosis remains a global health concern, as the increasing levels of urban poverty, higher number of immunodeficient patients and the development of drug resistance threaten the overall efforts made to induce a downward trend for the disease. Scrofuloderma, also known as tuberculosis cutis colliquativa is a subtype of cutaneous tuberculosis. Here we detail a case of a 70-year-old female patient presented with unilateral, left-sided, multiple palpable, painful, ulcerated and purulent cervical nodules, accompanied by persistent generalized erythematous popular granuloma annulare-like skin lesions on the upper extremities. Based on the result of the PCR assay, culture, imaging and histopathological findings, the diagnosis of scrofuloderma was established. To achieve prompt diagnosis and early treatment, it is crucial to include scrofuloderma in the differential diagnosis of ulcerated lesions in developed countries as well, and also be aware of the additional clinical symptoms, such as granuloma annulare-like lesions, possibly accompanying cutaneous tuberculosis.

[Dermoscopy of genodermatoses]. / Dermatoskopie von Genodermatosen.

Genodermatoses are a group of inherited skin diseases whose diagnosis is challenging due to their rarity as well as their clinical and genetic diversity. The majority of genodermatoses are autosomal or X­linked inherited, but mosaic forms are also observed. Genodermatoses comprise various phenotypes ranging from limited cutaneous disease to severe cutaneous and extracutaneous involvement and may also be early warning signs of a multisystemic disorder. Despite recent advances in genetic technology and skin imaging modalities, dermoscopy can be useful for screening, diagnosis, and treatment follow-up. In ectopic mineralization and lysosomal storage disorders (pseudoxanthoma elasticum and Fabry disease, respectively), cutaneous manifestations may indicate involvement of other organs. In keratinization diseases (e.g., ichthyoses) and acantholytic skin fragility disorders (e.g., Darier and Hailey-Hailey disease), dermoscopy may help to assess treatment response by visualizing background erythema, hyperkeratosis, and interkeratinocyte space prominence. Dermoscopy is a noninvasive, easily accessible, useful, in vivo assessment tool that is well established in dermatology to recognize characteristic features of genodermatoses.

Syphilis, the Great Imitator-Clinical and Dermoscopic Features of a Rare Presentation of Secondary Syphilis.

Syphilis is characterized by a wide range of variable clinical symptoms; therefore, it is often referred to as "The Great Imitator". Here, we report the case of a 69-year-old hepatitis-C-positive MSM patient, who was admitted to our clinic due to a solitary firm painless erythematous maculopapular lesion with a central crater-like crust on the upper right thigh that occurred two months prior. The dermoscopy showed an erythematous, copper-colored, oval lesion with diffuse monomorphic dotted and glomerular vessels, central crust, and circular scaling (Biett's sign). The histological findings ruled out neoplasia and described a plasma cell infiltrate and endothelial swelling. Finally, the combination of the dermoscopic image, histological findings and the additionally acquired knowledge about the sexual history of the patient at the second visit led to the diagnosis, which was then confirmed with serological tests. Dermoscopy may become a supportive tool to facilitate the recognition of secondary syphilis; however, the reporting of these atypical cases is crucial to highlight the many faces of the disease so that clinicians consider syphilis as part of the differential diagnosis of non-specific lesions.

Optically Guided High-Frequency Ultrasound Shows Superior Efficacy for Preoperative Estimation of Breslow Thickness in Comparison with Multispectral Imaging: A Single-Center Prospective Validation Study.

Melanoma is the most aggressive form of skin cancer that is known for its metastatic potential and has an increasing incidence worldwide. Breslow thickness, which determines the staging and surgical margin of the tumor, is unavailable at initial diagnosis. Novel imaging techniques for assessing Breslow thickness lack comparative data. This study evaluates optically guided high-frequency ultrasound (OG-HFUS) and multispectral imaging (MSI) for preoperative estimation of Breslow thickness and staging. We enrolled 101 patients with histologically confirmed primary melanoma and categorized them based on tumor thickness. Optically guided 33 MHz HFUS and MSI were utilized for the assessment. Our MSI-based algorithm categorized melanomas into three subgroups with a sensitivity of 62.6%, specificity of 81.3%, and fair agreement (κ = 0.440, CI: 0.298-0.583). In contrast, OG-HFUS demonstrated a sensitivity of 91.8%, specificity of 96.0%, and almost perfect agreement (κ = 0.858, CI: 0.763-0.952). OG-HFUS performed better than MSI in estimating Breslow thickness, emphasizing its potential as a valuable tool for melanoma diagnosis and patient management. OG-HFUS holds promise for enhancing preoperative staging and treatment decision-making in melanoma.

Melanoma Detection by Non-Specialists: An Untapped Potential for Triage?

INTRODUCTION: The incidence of melanoma increased considerably in recent decades, representing a significant public health problem. We aimed to evaluate the ability of non-specialists for the preliminary screening of skin lesions to identify melanoma-suspect lesions. MATERIALS AND METHODS: A medical student and a dermatologist specialist examined the total body scans of 50 patients. RESULTS: The agreement between the expert and the non-specialist was 87.75% (κ = 0.65) regarding the assessment of clinical significance. The four parameters of the ABCD rule were evaluated on the 129 lesions rated as clinically significant by both observers. Asymmetry was evaluated similarly in 79.9% (κ = 0.59), irregular borders in 74.4% (κ = 0.50), color in 81.4% (κ = 0.57), and diameter in 89.9% (κ = 0.77) of the cases. The concordance of the two groups was 96.9% (κ = 0.83) in the case of the detection of the Ugly Duckling Sign. CONCLUSIONS: Although the involvement of GPs is part of routine care worldwide, emphasizing the importance of educating medical students and general practitioners is crucial, as many European countries lack structured melanoma screening training programs targeting non-dermatologists.

Anti-PD-1 Monotherapy in Advanced Melanoma-Real-World Data from a 77-Month-Long Retrospective Observational Study.

Real-world evidence plays an important role in the assessment of efficacy and safety of novel therapies. The increasing use of immune checkpoint inhibitors (ICIs) in patients with advanced melanoma has led to notably improved clinical outcomes, while they are also associated with immune-related adverse events (irAEs). The majority of the available data are based on clinical trials, where the investigated subjects often do not adequately represent the general patient population of the everyday practice. Although there is a niche of objective biomarkers for the future treatment response of ICIs, certain studies suggest that irAEs may be predictive. The aim of this study was to carry out a retrospective analysis of treatment data from patients with advanced melanoma, treated with a single anti-PD-1 agent (pembrolizumab or nivolumab) during a 77-month-long period. Treatment efficacy and occurrence of adverse events were analyzed to identify potential predictive markers. Primary and secondary endpoints were the overall survival (OS) and progression-free survival (PFS). In our cohort, we demonstrated that the occurrence of more than one irAE showed a correlation with response to PD-1 ICI therapy and improved the OS and PFS. Our study suggests, that the grade of toxicity of the irAE may affect the survival rate.

Photodynamic Therapy with 5-Aminolevulinic Acid Patch for the Treatment of Actinic Keratosis.

Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) is an emerging treatment option in the care of actinic keratosis (AK). A self-adhesive 5-ALA patch was recently developed that allows a precise PDT procedure. Here, we review the current literature and report the findings of our case series that observed the outcomes and safety of 5-ALA patch PDT. Ten patients with a total of 40 AKs were treated with a single session of conventional or daylight PDT using 5-ALA patch at the Department of Dermatology and Venereology, Sapienza University of Rome or at the European Institute of Oncology, Milan, Italy. Complete response was observed in three patients, while partial response was seen in seven patients. Overall tolerability was good or excellent, with local adverse events observed in four patients. This is the first case series reported where the 5-ALA patch was applied using daylight PDT, and its efficacy and tolerability in the treatment of AK were demonstrated. In conclusion, the self-adhesive 5-ALA patch is a convenient application of PDT that provides a well-tolerated and effective treatment option with satisfactory cosmetic outcomes.

Modeling the efficacy of different anti-angiogenic drugs on treatment of solid tumors using 3D computational modeling and machine learning.

Accurate simulation of tumor growth during chemotherapy has significant potential to alleviate the risk of unknown side effects and optimize clinical trials. In this study, a 3D simulation model encompassing angiogenesis and tumor growth was developed to identify the vascular endothelial growth factor (VEGF) concentration and visualize the formation of a microvascular network. Accordingly, three anti-angiogenic drugs (Bevacizumab, Ranibizumab, and Brolucizumab) at different concentrations were evaluated in terms of their efficacy. Moreover, comprehensive mechanisms of tumor cell proliferation and endothelial cell angiogenesis are proposed to provide accurate predictions for optimizing drug treatments. The evaluation of simulation output data can extract additional features such as tumor volume, tumor cell number, and the length of new vessels using machine learning (ML) techniques. These were investigated to examine the different stages of tumor growth and the efficacy of different drugs. The results indicate that brolucizuman has the best efficacy by decreasing the length of sprouting new vessels by up to 16%. The optimal concentration was obtained at 10 mol m-3 with an effectiveness percentage of 42% at 20 days post-treatment. Furthermore, by performing comparative analysis, the best ML method (matching the performance of the reference simulations) was identified as reinforcement learning with a 3.3% mean absolute error (MAE) and an average accuracy of 94.3%.

Emergency Use and Efficacy of an Asynchronous Teledermatology System as a Novel Tool for Early Diagnosis of Skin Cancer during the First Wave of COVID-19 Pandemic.

Background: After the outbreak of the corona virus disease-19 (COVID-19) pandemic, teledermatology was implemented in the Hungarian public healthcare system for the first time. Our objective was to assess aggregated diagnostic agreements and to determine the effectiveness of an asynchronous teledermatology system for skin cancer screening. Methods: This retrospective single-center study included cases submitted for teledermatology consultation during the first wave of the COVID-19 pandemic. Follow-up of the patients was performed to collect the results of any subsequent personal examination. Results: 749 patients with 779 lesions were involved. 15 malignant melanomas (9.9%), 78 basal cell carcinomas (51.3%), 21 squamous cell carcinomas (13.8%), 7 other malignancies (4.6%) and 31 actinic keratoses (20.4%) were confirmed. 87 malignancies were diagnosed in the high-urgency group (42.2%), 49 malignancies in the moderate-urgency group (21.6%) and 16 malignancies in the low-urgency group (4.6%) (p < 0.0001). Agreement of malignancies was substantial for primary (86.3%; κ = 0.647) and aggregated diagnoses (85.3%; κ = 0.644). Agreement of total lesions was also substantial for primary (81.2%; κ = 0.769) and aggregated diagnoses (87.9%; κ = 0.754). Conclusions: Our findings showed that asynchronous teledermatology using a mobile phone application served as an accurate skin cancer screening system during the first wave of the COVID-19 pandemic.

Preliminary Clinical Experience with a Novel Optical-Ultrasound Imaging Device on Various Skin Lesions.

A compact handheld skin ultrasound imaging device has been developed that uses co-registered optical and ultrasound imaging to provide diagnostic information about the full skin depth. The aim of the current work is to present the preliminary clinical results of this device. Using additional photographic, dermoscopic and ultrasonic images as reference, the images from the device were assessed in terms of the detectability of the main skin layer boundaries and characteristic image features. Combined optical-ultrasonic recordings of various types of skin lesions (melanoma, basal cell carcinoma, seborrheic keratosis, dermatofibroma, naevus, dermatitis and psoriasis) were taken with the device (N = 53) and compared with images captured with a reference portable skin ultrasound imager. The investigator and two additional independent experts performed the evaluation. The detectability of skin structures was over 90% for the epidermis, the dermis and the lesions. The morphological and echogenicity information observed for the different skin lesions were found consistent with those of the reference ultrasound device and relevant ultrasound images in the literature. The presented device was able to obtain simultaneous in-vivo optical and ultrasound images of various skin lesions. This has the potential for further investigations, including the preoperative planning of skin cancer treatment.

Altered Glycosylation of Human Alpha-1-Acid Glycoprotein as a Biomarker for Malignant Melanoma.

A high-resolution HILIC-MS/MS method was developed to analyze anthranilic acid derivatives of N-glycans released from human serum alpha-1-acid glycoprotein (AGP). The method was applied to samples obtained from 18 patients suffering from high-risk malignant melanoma as well as 19 healthy individuals. It enabled the identification of 102 glycan isomers separating isomers that differ only in sialic acid linkage (α-2,3, α-2,6) or in fucose positions (core, antenna). Comparative assessment of the samples revealed that upregulation of certain fucosylated glycans and downregulation of their nonfucosylated counterparts occurred in cancer patients. An increased ratio of isomers with more α-2,6-linked sialic acids was also observed. Linear discriminant analysis (LDA) combining 10 variables with the highest discriminatory power was employed to categorize the samples based on their glycosylation pattern. The performance of the method was tested by cross-validation, resulting in an overall classification success rate of 96.7%. The approach presented here is significantly superior to serological marker S100B protein in terms of sensitivity and negative predictive power in the population studied. Therefore, it may effectively support the diagnosis of malignant melanoma as a biomarker.

Quantitative Multispectral Imaging Differentiates Melanoma from Seborrheic Keratosis.

Melanoma is a melanocytic tumor that is responsible for the most skin cancer-related deaths. By contrast, seborrheic keratosis (SK) is a very common benign lesion with a clinical picture that may resemble melanoma. We used a multispectral imaging device to distinguish these two entities, with the use of autofluorescence imaging with 405 nm and diffuse reflectance imaging with 525 and 660 narrow-band LED illumination. We analyzed intensity descriptors of the acquired images. These included ratios of intensity values of different channels, standard deviation and minimum/maximum values of intensity of the lesions. The pattern of the lesions was also assessed with the use of particle analysis. We found significantly higher intensity values in SKs compared with melanoma, especially with the use of the autofluorescence channel. Moreover, we found a significantly higher number of particles with high fluorescence in SKs. We created a parameter, the SK index, using these values to differentiate melanoma from SK with a sensitivity of 91.9% and specificity of 57.0%. In conclusion, this imaging technique is potentially applicable to distinguish melanoma from SK based on the analysis of various quantitative parameters. For this application, multispectral imaging could be used as a screening tool by general physicians and non-experts in the everyday practice.

Multispectral Imaging Algorithm Predicts Breslow Thickness of Melanoma.

Breslow thickness is a major prognostic factor for melanoma. It is based on histopathological evaluation, and thus it is not available to aid clinical decision making at the time of the initial melanoma diagnosis. In this work, we assessed the efficacy of multispectral imaging (MSI) to predict Breslow thickness and developed a classification algorithm to determine optimal safety margins of the melanoma excision. First, we excluded nevi from the analysis with a novel quantitative parameter. Parameter s' could differentiate nevi from melanomas with a sensitivity of 89.60% and specificity of 88.11%. Following this step, we have categorized melanomas into three different subgroups based on Breslow thickness (≤1 mm, 1-2 mm and >2 mm) with a sensitivity of 78.00% and specificity of 89.00% and a substantial agreement (κ = 0.67; 95% CI, 0.58-0.76). We compared our results to the performance of dermatologists and dermatology residents who assessed dermoscopic and clinical images of these melanomas, and reached a sensitivity of 60.38% and specificity of 80.86% with a moderate agreement (κ = 0.41; 95% CI, 0.39-0.43). Based on our findings, this novel method may help predict the appropriate safety margins for curative melanoma excision.