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.

Assessment of Frontal Hemispherical Lateralization in Plaque Psoriasis and Atopic Dermatitis.

BACKGROUND: Each brain hemisphere plays a specialized role in cognitive and behavioral processes, known as hemispheric lateralization. In chronic skin diseases, such as plaque psoriasis (Pso) and atopic dermatitis (AD), the degree of lateralization between the frontal hemispheres may provide insight into specific connections between skin diseases and the psyche. This study aims to analyze the hemispherical lateralization, neurovegetative responses, and psychometric characteristics of patients with Pso and AD. METHODS: The study included 46 patients with Pso, 56 patients with AD, and 29 healthy control (Ctrl) subjects. The participants underwent frontal electroencephalogram (EEG) measurement, heart rate variability (HRV) assessment, and psychological tests. Statistical analyses were performed using ANOVA, with Bonferroni correction applied for multiple comparisons. RESULTS: This study shows a significant right-lateralized prefrontal activity in both AD patients (p < 0.001) and Pso patients (p = 0.045) compared with Ctrl, with no significant difference between the AD and Pso groups (p = 0.633). AD patients with right-hemispheric dominant prefrontal activation exhibited increased inhibition and avoidance markers, while Pso patients showed elevated sympathetic nervous system activity. CONCLUSION: Psychophysiological and psychometric data suggest a shared prevalence of right-hemispheric dominance in both AD and Pso patient groups. However, the findings indicate distinct psychodermatological mechanisms in AD and Pso.

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.

Do budget constraints limit access to health care? Evidence from PCI treatments in Hungary.

Under Hungary's single payer health care system, hospitals face an annual budget cap on most of their diagnoses-related group based reimbursements. In July 2012, percutaneous coronary intervention (PCI) treatments of acute myocardial infarction were exempted from that hospital level budget cap. We use countrywide individual-level patient data from 2009 to 2015 to map the effect of such a quasi-experimental change in monetary incentives on health provider decisions and health outcomes. We find that direct admissions into PCI-capable hospitals increase, especially in central Hungary, where there are several hospitals which can compete for patients. The proportion of PCI treatments at PCI-capable hospitals, however, does not increase, and neither does the number of patient transfers from non-PCI hospitals to PCI-capable ones. We conclude that only patient pathways, plausibly influenced by hospital management, were affected by the shift in incentives, while physicians' treatment decisions were not. While average length of stay decreased, we do not find any effect on 30-day readmissions or in-hospital mortality.

[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.

Correlation of systemic involvement and presence of pathological skin calcification assessed by ex vivo nonlinear microscopy in Pseudoxanthoma elasticum.

Pseudoxanthoma elasticum (PXE (OMIM 264800)) is an autosomal recessive connective tissue disorder mainly caused by mutations in the ABCC6 gene. PXE results in ectopic calcification primarily in the skin, eye and blood vessels that can lead to blindness, peripheral arterial disease and stroke. Previous studies found correlation between macroscopic skin involvement and severe ophthalmological and cardiovascular complications. This study aimed to investigate correlation between skin calcification and systemic involvement in PXE. Ex vivo nonlinear microscopy (NLM) imaging was performed on formalin fixed, deparaffinized, unstained skin sections to assess the extent of skin calcification. The area affected by calcification (CA) in the dermis and density of calcification (CD) was calculated. From CA and CD, calcification score (CS) was determined. The number of affected typical and nontypical skin sites were counted. Phenodex + scores were determined. The relationship between the ophthalmological, cerebro- and cardiovascular and other systemic complications and CA, CD and CS, respectively, and skin involvement were analyzed. Regression models were built for adjustment to age and sex. We found significant correlation of CA with the number of affected typical skin sites (r = 0.48), the Phenodex + score (r = 0.435), extent of vessel involvement (V-score) (r = 0.434) and disease duration (r = 0.48). CD correlated significantly with V-score (r = 0.539). CA was significantly higher in patients with more severe eye (p = 0.04) and vascular (p = 0.005) complications. We found significantly higher CD in patients with higher V-score (p = 0.018), and with internal carotid artery hypoplasia (p = 0.045). Significant correlation was found between higher CA and the presence of macula atrophy (ß = - 0.44, p = 0.032) and acneiform skin changes (ß = 0.40, p = 0.047). Based on our results, the assessment of skin calcification pattern with nonlinear microscopy in PXE may be useful for clinicians to identify PXE patients who develop severe systemic complications.

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.

STIs during the COVID-19 Pandemic in Hungary: Gonorrhea as a Potential Indicator of Sexual Behavior.

The social distancing measures introduced due to the COVID-19 pandemic may have affected the sexual behavior of the population. We collected data retrospectively from the National STD Center of Hungary. The overall patient influx data of the STD Center and the number of patients diagnosed with syphilis, chlamydia, and gonorrhea infections were assessed in the three-month period of 2020 when the strict governmental lockdown was introduced in Hungary. Data were compared to the pre- and post-lockdown quarters of 2020 and matched to the respective quarters of 2018 and 2019. The number of patients diagnosed with syphilis and chlamydia infections in 2020 during the lockdown decreased compared to 2018 and 2019, while the number of gonorrhea cases increased. The lower number of STI screenings resulted in a significant decrease in asymptomatic syphilis and chlamydia case numbers. However, the growing number of gonorrhea cases in 2020 during lockdown highlights that sexual behavior remained unchanged regardless of restrictions. Therefore, gonorrhea may be considered as an indicator of STI incidences during the pandemic.

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.

Cutaneous Reactions to COVID-19 Vaccines in a Monocentric Study: A Case Series.

After coronavirus disease 2019 (COVID-19) caused a global pandemic, vaccines were rapidly developed to control the spread of the virus. Although they were effective in most of the cases at protecting people from becoming seriously ill and being hospitalized, they showed side effects, too. Among other adverse vaccine reactions, cutaneous eruptions following SARS-CoV-2 have been described in the literature, but they are not well-characterized yet. We described the morphology and timing of the spectrum of cutaneous reactions following most of the COVID-19 vaccines available in Italy, which were observed in outpatients referred to our non-invasive diagnostic clinic. Most of these reactions appeared after the second or third COVID-19 vaccine dose (most of them after mRNA COVID-19 vaccines). Our data support that cutaneous reactions to COVID-19 vaccination are generally self-limited; in addition, history of allergic reaction to a specific food, medicine or vaccine should not discourage vaccination in the general population, although patients with immune dysregulation should be accurately selected and monitored. Further research is necessary to better assess the true prevalence and preventive measures of skin reactions to COVID-19 vaccination.

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.