Combining Reflectance Confocal Microscopy, Optical Coherence Tomography and Ex-Vivo Fluorescence Confocal Microscopy for Margin Assessment in Basal Cell Carcinoma Excision.

INTRODUCTION: Recent developments of noninvasive, high-resolution imaging techniques, such as reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), have enhanced skin cancer detection and precise tumor excision particularly in highly aggressive and poorly defined basal cell carcinomas (BCCs). OBJECTIVES: The aim of this pilot study is to assess the feasibility and reproducibility of a systematic clinical workflow combining noninvasive (RCM-OCT) and invasive fluorescence confocal microscopy (FCM) imaging modalities in pre- and intra-surgical evaluations of the lateral and deep margins of BCC. METHODS: Superficial incisions were made 2 mm beyond the clinical-dermoscopic BCC margins. Lateral margins were then explored with OCT and RCM. In positive margins, a further cut was made 2 mm distal from the previous. A final RCM/OCT-based double-negative margin was drawn around the entire perimeter of the lesion before referring to surgery. The freshly excised specimen was then examined with FCM (ex-vivo) for the evaluation of the deep margin. Histopathologic examination eventually confirmed margin involvement. RESULTS: The study included 22 lesions from 13 patients. At the end of the study, 146 margins-106 negative (73%) and 40 positive (27%) at RCM/OCT-were collected. The RCM/OCT margin evaluation showed an overall sensitivity of 100% and a specificity of 96.3%. The overall positive margins diagnostic accuracy was 98.2%. Reproducibility was evaluated on recorded images and the raters showed a substantial inter-observer agreement on both RCM (κ = 0.752) and OCT images (κ = 0.724). CONCLUSIONS: The combined RCM/OCT/FCM ex-vivo approach noninvasively facilitates the presurgical and intrasurgical lateral and deep margin assessment of poorly defined BCCs.

Dermoscopic, Histological, Confocal Microscopy Correlation of Atypical-Dysplastic Melanocytic Nevi.

INTRODUCTION: The term "atypical melanocytic nevus" (AMN) is used as a synonym for dysplastic nevus (DN) in clinical practice. Although the criteria for diagnosis of AMN/DN by the Agency for Research on Cancer helps to differentiate AMN/DN from common acquired nevi, they do not have high degrees of specificity, as they are similar to those used for the diagnosis of melanoma. OBJECTIVES: In this retrospective study we evaluated the correlation and diagnostic concordance of dermoscopy, confocal microscopy, and histological examination in 50 AMN. METHODS: A graded scale was used to compare histological examination with dermoscopy and confocal microscopy. Low magnification histological images of only the central part of lesions were examined. This allowed histological diagnoses based almost exclusively on architectural criteria instead of simultaneously architectural and cytological, as in the global histological examination. RESULTS: Our data demonstrate that the diagnostic accuracy of dermoscopy and confocal microscopy diagnosis of the clinical aspects of AMN/DN as nevi or melanomas tends to be equivalent, being fair for nevi and excellent for melanomas. The total percentage of AMN suggested that the accuracy of confocal microscopy in the diagnosis of melanoma (86.7%) is greater than that of dermoscopy (73.3%). CONCLUSIONS: This study demonstrated that diagnostic assessments of AMN/DN by dermoscopy and confocal microscopy are accurate and often coincide with those of histological examination and that their combined use helps to better manage and monitor these patients by facilitating early detection of melanomas and reducing unnecessary excisions of benign melanocytic lesions.

Melanoma clinicopathological groups characterized and compared with dermoscopy and reflectance confocal microscopy.

BACKGROUND: Dermoscopic and reflectance confocal microscopy (RCM) correlations between morphologic groups of melanoma have not yet been described. OBJECTIVE: Describe and compare dermoscopic and RCM features of cutaneous melanomas with histopathological confirmation. METHODS: Single center, retrospective analysis of consecutive melanomas evaluated with RCM (2015-2019). Lesions were clinically classified as typical, nevus-like, amelanotic/nonmelanoma skin cancer (NMSC)-like, seborrheic keratosis (SK)-like and lentigo/lentigo maligna (LM)-like. Presence or absence of common facial and nonfacial melanoma dermoscopic and RCM patterns were recorded. Clusters were compared with typical lesions by multivariate logistic regression. RESULTS: Among 583 melanoma lesions, significant differences between clusters were evident (compared to typical lesions). Observation of dermoscopic features (>50% of lesions) in amelanotic/NMSC-like lesions consistently displayed 3 patterns (atypical network, atypical vascular pattern + regression structures), and nevus-like and SK-like lesions and lentigo/LM-like lesions consistently displayed 2 patterns (atypical network + regression structures, and nonevident follicles + heavy pigmentation intensity). Differences were less evident with RCM, as almost all lesions were consistent with melanoma diagnosis. LIMITATIONS: Small SK-like lesions sample, single RCM analyses (no reproduction of outcome). CONCLUSION: RCM has the potential to augment our ability to consistently and accurately diagnose melanoma independently of clinical and dermoscopic features.

Characterization of Acne-Prone Skin with Reflectance Confocal Microscopy and Optical Coherence Tomography and Modifications Induced by Topical Treatment and Probiotic Supplementation.

The evaluation of acne-prone skin and absent-to-mild acne is difficult because this condition is not associated with a clinically definable situation. Previous studies showed that apparently healthy skin in patients with previous episodes of acne shows microcomedos and infundibular hyperkeratosis upon reflectance confocal microscopy (RCM) evaluation. Our aim was to characterize the subclinical and microscopic characteristics of acne-prone skin by means of RCM and dynamic optical coherence tomography (D-OCT) and evaluate microscopic changes induced by treatment. A group of 20 patients received a daily combined treatment over a period of 3 months, consisting of probiotic supplementation with three strains of 109 colony-forming units of Lactobacillus (Lactobacillus reuteri, Lactobacillus casei subsp. rhamnosus, Lactobacillus plantarum) and a combined topical product of azelaic and hydroxypinacolone retinoate (HPR). Clinical evaluations and non-invasive imaging acquisitions using VISIA® System, RCM, and D-OCT were performed at baseline, and after 4 and 12 weeks. The total number of clinically evident non-inflammatory lesions decreased during treatment from 11.5 to 7.3 (p < 0.05). There was also an evident reduction in microscopic acne features at RCM and D-OCT, such as the number of small bright follicles, large bright follicles and vascular threshold density at 300 µm and 500 µm depths. The types and extent of microscopic alterations in acne-prone skin patients may not be evident by clinical scores. Patients with low investigator global assessment (IGA) grades are a heterogeneous population, characterized by different microscopic skin features. Acne-prone skin is susceptible to treatment, and RCM and D-OCT imaging are sensitive tools to objectively monitor subclinical skin changes.

Lentigo maligna and lentigo maligna melanoma in vivo differentiation with dermoscopy and reflectance confocal microscopy: A retrospective, multicentre study.

INTRODUCTION: Dermoscopic predictors of lentigo maligna (LM) and lentigo maligna melanoma (LMM) have been recently reported, but these have not been reported in reflectance confocal microscopy (RCM). OBJECTIVES: (i) To validate dermoscopic predictors for LM/LMM, (ii) to identify RCM patterns in LM and LMM, and (iii) correlations between dermoscopic and RCM features in LM and LMM. MATERIALS AND METHODS: A retrospective, multicentre study of consecutive lesions with histologically proven LM or LMM subtypes of the head and face, with complete sets of dermoscopic and RCM images. RESULTS: A total of 180 lesions were included (n = 40 LMM). Previously reported differential dermoscopic features for LM subtypes were confirmed. Other features significantly associated with LMM diagnosis included irregular hyperpigmented areas, shiny white streaks, atypical vessels and light brown colour at dermoscopy and medusa head-like structures, dermal nests and nucleated cells within the papillae at RCM (p < 0.05). Correlations among LM lesions between dermoscopic and RCM features included brown to-grey dots and atypical cells (epidermis), grey colour and inflammation and obliterated follicles and medusa head-like structures. Among LMM lesions, significant correlations included obliterated follicles with folliculotropism, both irregular hyperpigmented areas and irregular blotches with widespread atypical cell distribution (epidermis), dermal nests and nucleated cells within the papillae (dermis). Irregular blotches were also associated with medusa head-like structures (dermal epidermal junction [DEJ]). CONCLUSIONS: Dermoscopic and RCM features can assist in the in vivo identification of LM and LMM and many are correlated. RCM three-dimensional analysis of skin layers allows the identification of invasive components in the DEJ and dermis.

Identification of Novel Dermoscopic Patterns for "Featureless Melanoma": Clinical-Pathological Correlation.

INTRODUCTION: Diagnosis of melanoma can be very difficult because of its phenotypic and histological heterogeneity. Difficult-to-diagnose melanoma can be represented by mucosal melanoma, pink lesions, amelanotic melanoma (amelanotic lentigo maligna, amelanotic acral melanoma, desmoplastic melanoma), melanoma arising on sun-damaged facial skin, and "featureless melanoma". OBJECTIVES: The aim of the study was to improve the identification of featureless melanoma (scoring 0-2 according to the 7-point-checklist) describing the variegated dermoscopic features and their histopathological correlation. METHODS: Study samples included all melanomas excised based on clinical and/or dermoscopic findings in the period between January 2017 and April 2021. Before excisional biopsy, all lesions were recorded by means of digital dermoscopy at the department of Dermatology. Only lesions with a diagnosis of melanoma and a high quality of dermoscopic images were included in this study. After clinical and dermoscopic evaluation of 7-point checklist score, single dermoscopic and histological features were considered for lesions with a score of 2 or lower and a diagnosis of melanoma (corresponding to dermoscopic featureless melanoma). RESULTS: A total of 691 melanomas fulfilled inclusion criteria and were retrieved from the database. The 7-point checklist evaluation identified 19 "negative-featureless" melanoma. The 100% of the lesions with score 1 showed a globular pattern. CONCLUSIONS: Dermoscopy is still the best diagnostic method for melanoma. The 7-point checklist provides a simplification of standard pattern analysis because of the algorithm based on a scoring system and the lower number of features to recognize. In the daily practice it is more comfortable for many clinicians to keep in mind a list of principles that may help in the decision.

Multiparametric ultrasound images of three different cases of schwannoma of the peripheral nervous system.

This case image illustrates the importance of new sonographic applications such as superb microvascular imaging and shear wave elastography; as showed, they improve the diagnostic recognition of peripheral nerve lesion thanks to a better definition of vascularity and measure of stiffness.

The combination of oral and topical photoprotection with a standardized Polypodium leucotomos extract is beneficial against actinic keratosis.

INTRODUCTION: This study describes a prospective, multicentre, randomized controlled, open-label study with three arms aimed at studying the differences between: [Cnt], self-administered sun protection; [T], topical treatment; and [TO], topical + oral treatment; for the management of Actinic Keratosis (AK) in a cohort of subjects of advanced age displaying severe actinic damage (SAD). METHODS: Treatments administered to groups [T] and [TO] had a common component, which is a botanical extract, Fernblock, with demonstrated photoprotective activity. RESULTS: In total, 131 subjects were distributed randomly in the three groups, and followed up clinically at three separate time points, beginning of the study (t = 0) and after 6 and 12 months. Analysis of clinical data and examination using reflectance confocal microscopy (RCM) revealed that group [T] and [TO] displayed decreased clinical AK and field cancerization parameters, including the number of new lesions, and reduced the need for additional interventions in these patients. RCM revealed normalization of the keratinocyte layer. Improvements in AK and field cancerization parameters were greatest in the group [TO], suggesting that topical and oral photoprotection improves the clinical and anatomical outcome compared to control conditions. CONCLUSIONS: The combination of topical and oral immune photoprotection provides an advantage compared to topical photoprotection alone.

Atopic Dermatitis and Ulcerative Colitis Successfully Treated with Upadacitinib.

Background and Objectives: JAK inhibitors entered current clinical practice as treatment for several immune-related diseases and, recently, for atopic dermatitis. These drugs target the Janus Kinase intracellular cascade, rendering them suitable for treating both Th1 and Th2 immune-mediated responses. Materials and Methods: We report the case of a 36-year-old male patient presenting an overlap of ulcerative colitis, a Th1-related disease, and atopic dermatitis, a Th2-mediated condition. Treatment with upadacitinib was initiated, and laboratory and instrumental follow-ups were carried out for 8 months. Results: The complete and persistent clinical remission of both conditions was observed at a low dose of 15 mg of upadacitinib, even though ulcerative colitis guidelines usually recommend a dosage of 45 mg. No serious adverse responses to therapy were reported. Conclusions: Upadacitinib may be the most suitable management strategy in subjects with coexisting severe conditions mediated by Th1 inflammation, such as ulcerative colitis, and by Th2 cytokines, such as atopic dermatitis.

Human Monkeypox-A Global Public Health Emergency.

Monkeypox, a viral zoonosis caused by an Orthopoxvirus, is clinically characterized by fever, headache, lymphadenopathy, myalgia, rash and burdened by some complications that can be severe and life threatening. Monkeypox, endemic in some central and west African countries, in tropical areas near equator, rose to the headlines following its recent outbreak in non-endemic countries of Europe and the USA. Thus, the World Health Organization, worried about the growing dimension of the problem, declared monkeypox a global public health emergency. Now, after months of careful observation, the western scientific research is drawing conclusion that African endemic countries represent a reserve pool able to feed, through travelers and sexual networks, the outbreak in non-endemic countries in which high-risk communities such as gay and bisexual men are the most affected. Prevention through vaccination and early diagnosis are the core to breaking the chain of diffusion of this epidemic. Particular attention should be paid to avoid the spread from endemic countries, also implementing the economic investments in their public health system. Information campaigns and assistance to high-risk classes in non-endemic countries are important priorities, however, assuming that specific treatments for this disease are still tentative.

Cutaneous Basal Cell Carcinoma: Does Noninvasive Ventilation Accelerate Tumor Progression?

A 56-year-old woman presented to the emergency to be department with diarrhea, asthenia, cough, and dysgeusia. The patient had chronic obstructive pulmonary disease (COPD) and was found infected with coronavirus disease 2019 (COVID-19). On physical examination, a small basal cell carcinoma (BCC) lesion was identified on her scalp; however, following the administration of noninvasive ventilation, the appearance of both macroscopic and microscopic BCC worsened dramatically. Our findings point to positive pressure noninvasive ventilation used to treat COVID-19 associated with COPD as a possible causative agent for the progression of cutaneous BCC. (SKINmed. 2022;20:463-465).

Varicella-Zoster virus reactivation following severe acute respiratory syndrome coronavirus 2 vaccination or infection: New insights.

INTRODUCTION: Varicella zoster virus (VZV) reactivation has been reported following vaccination for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the real extent remains unknown. METHODS: We conducted a systematic review to summarize evidence of VZV reactivation or infection following SARS-CoV-2 vaccination. Episodes after coronavirus disease-2019 (COVID-19) were also identified. Related articles were identified in PubMed and EMBASE databases till December 31, 2021 using the terms "varicella zoster" and "COVID-19″. PROSPERO Register Number: CRD42021289399. RESULTS: The search revealed 314 articles, of which 55 met the inclusion criteria. VZV manifestations were documented in 179 (82.1%) subjects following SARS-CoV-2 vaccination and in 39 (17.9%) patients with COVID-19. Among the vaccinated, median (IQR) age was 56.5 (42-70) years, and 56.8% were female. Twenty-one (16.8%) were immunosuppressed. The median (IQR) latency time after vaccination was 6 (3-10) days, and 84.4% received mRNA vaccines. VZV reactivation occurred following a first dose (68.2%), a second dose (12.8%) or a booster (0.6%). The most important VZV manifestation was dermatome herpes zoster rash, which accounted for 86.4% of events in vaccinated subjects. Twenty patients (11.3%) presented serious VZV events after vaccination, with Herpes Zoster ophthalmicus (5.6%) and post-herpetic neuralgia (3.4%) predominating. No VZV pneumonia or deaths were recorded. Antiviral prescriptions were made in 96.2% of vaccinated subjects. No significant differences between vaccinated and infected subjects were found. CONCLUSION: This study indicates that the occurrence of VZV reactivation is clinically relevant. However, our findings suggest that COVID-19 vaccination is safe, and remains strongly recommended.

Cardiotoxicity of Chimeric Antigen Receptor T-Cell (CAR-T) Therapy: Pathophysiology, Clinical Implications, and Echocardiographic Assessment.

Contemporary anticancer immunotherapy with chimeric antigen receptor T-cell (CAR-T) therapy has dramatically changed the treatment of many hematologic malignancies previously associated with poor prognosis. The clinical improvement and the survival benefit unveiled the risk of cardiotoxicity, ranging from minimal effects to severe cardiac adverse events, including death. Immunotherapy should also be proposed even in patients with pre-existing cardiovascular risk factors, thereby increasing the potential harm of cardiotoxicity. CAR-T therapy frequently results in cytokine release syndrome (CRS), and inflammatory activation is sustained by circulating cytokines that foster a positive feedback mechanism. Prompt diagnosis and treatment of CAR-T cardiotoxicity might significantly improve outcomes and reduce the burden associated with cardiovascular complications. Clinical and echocardiographic examinations are crucial to perform a tailored evaluation and follow-up during CAR-T treatment. This review aims to summarize the pathophysiology, clinical implications, and echocardiographic assessment of CAR-T-related cardiotoxicity to enlighten new avenues for future research.

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.

Efficacy of prophylactic platelet rich plasma (PRP) following open saphenous vein harvesting in cardiac surgery.

BACKGROUND: Wound infection represents a frequent trouble following open saphenous vein harvesting in cardiac surgery. Platelets' growth factors are crucial for the healing process. Prophylactic platelet rich plasma (PRP) application on leg wound might reduce the incidence of saphenous vein harvest site infections in patients undergoing coronary artery bypass graft surgery (CABG). METHODS: Between January 2009 and December 2020, 987 consecutive patients underwent CABG using saphenous vein as conduit graft and were retrospectively divided into two groups. All patients had standard surgical leg wound closure and wound care, but treatment group received adjunctive topical application of PRP (no-PRP and PRP group, respectively). The primary outcome was wound infection. RESULTS: Saphenous vein harvest site infection rate was similar between PRP (3.5%) and No-PRP (5.2%) group, p = 0.215. The ASEPSIS score was lower for the PRP group (PRP: 3.6 ± 9.1 vs. No-PRP: 5.3 ± 11.2; p = 0.014). Performing a subgroup analysis, the diabetic patients (PRP-DM) group had a lower rate of infection than control group (No-PRP DM) (2.6% vs. 7.7%, p = 0.026). PRP-DM patients had an inferior ASEPSIS score (PRP-DM: 2.7 ± 8.3 vs. No PRP-DM: 7.5 ± 13.2, p < 0.001). CONCLUSIONS: Topical application of autologous PRP on saphenoug vein harvest site might reduce the rate of surgical site infection, with particular benefit among diabetic patients.

Dermoscopy, Reflectance Confocal Microscopy and Optical Coherence Tomography Features of Acne: A Systematic Review.

Noninvasive imaging techniques have recently outlined precise microscopic features of acne elementary lesions and accurate quantifications for disease severity staging and therapeutical efficacy follow-up. The aim of this review is to systematically describe current applications of dermoscopy, reflectance confocal microscopy (RCM), and optical coherence tomography (OCT) in acne vulgaris assessment and management. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. We included studies conducted on human subjects with elementary lesions of acne vulgaris, reporting assessment of the lesions with dermoscopy, RCM, and/or OCT. At present there are few large studies regarding acne and noninvasive imaging techniques, representing the main limitation of this review. Clinical examination represents the first line in acne diagnosis and treatment. However, dermoscopy, RCM, and OCT are further tools that can improve acne classification, monitoring of treatment, and pathophysiologic characterization. In the near future, dermoscopy, RCM, and OCT could become routinely used for the evaluation of acne vulgaris to provide a deeper knowledge of the disease and to guide the clinician in the prescription of tailored treatment protocols based on each patient's characteristics.

Hidradenitis suppurativa: Morphologic and vascular study of nodular inflammatory lesions by means of optical coherence tomography.

Hidradenitis suppurativa (HS) is an inflammatory disease characterized by a recurrent-remission trend and clinical lesions that range from asymptomatic to inflamed, deep-seated nodules with scarring and suppuration. The aim of our study was to identify morphologic and vascular features of HS nodules by means of dynamic optical coherence tomography (D-OCT) and to define if they are correlated to patient endotype and risk of disease progression. A set of standardized clinical pictures and D-OCT images were acquired from 57 inflammatory nodules of 40 patients affected by HS. A set of 20 clinical and D-OCT images were acquired from 20 healthy volunteers as a control group. The comparison of D-OCT features among HS and control group was analysed. The correlation between HS patient endotype and D-OCT features of the lesions was calculated. D-OCT enabled to identify vascular and morphological aspects characterizing HS nodular inflammatory lesions. In addition, several D-OCT features were significantly different among distinct disease endotypes. The characterization of HS nodular inflammatory lesions through D-OCT, corresponding to blood vessel dilation and inflammatory associated hyper-vascularization, may have important clinical consequences in the assessment of HS risk of progression, therapeutic decisions and treatment efficacy monitoring.