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.

Dermatoscopy and reflectance confocal microscopy for basal cell carcinoma diagnosis and diagnosis prediction score: A prospective and multicenter study on 1005 lesions.

BACKGROUND: Basal cell carcinoma (BCC) is usually diagnosed by clinical and dermatoscopy examination, but diagnostic accuracy may be suboptimal. Reflectance confocal microscopy (RCM) imaging increases skin cancer diagnostic accuracy. OBJECTIVE: To evaluate additional benefit in diagnostic accuracy of handheld RCM in a prospective controlled clinical setting. METHODS: A prospective, multicenter study in 3 skin cancer reference centers in Italy enrolling consecutive lesions with clinical-dermatoscopic suspicion of BCC (ClinicalTrials.gov: NCT04789421). RESULTS: A total of 1005 lesions were included, of which 474 histopathologically confirmed versus 531 diagnosed by clinical-dermatoscopic-RCM correlation, confirmed with 2 years of follow-up. Specifically, 740 were confirmed BCCs. Sensitivity and specificity for dermatoscopy alone was 93.2% (95% CI, 91.2-94.9) and 51.7% (95% CI, 45.5-57.9); positive predictive value was 84.4 (95% CI, 81.7-86.8) and negative predictive value 73.3 (95% CI, 66.3-79.5). Adjunctive RCM reported higher rates: 97.8 (95% CI, 96.5-98.8) sensitivity and 86.8 (95% CI, 82.1-90.6) specificity, with positive predictive value of 95.4 (95% CI, 93.6-96.8) and negative predictive value 93.5 (95% CI, 89.7-96.2). LIMITATIONS: Study conducted in a single country. CONCLUSIONS: Adjunctive handheld RCM assessment of lesions clinically suspicious for BCC permits higher diagnostic accuracy with minimal false negative lesions.

Lentigo maligna and lentigo maligna melanoma in patients younger than 50†years: a multicentre international clinical-dermoscopic study.

BACKGROUND: Lentigo maligna/lentigo maligna melanoma (LM/LMM) is usually diagnosed in older patients, when lesions are larger. However, it is important to detect it at an earlier stage to minimize the area for surgical procedure. OBJECTIVES: To determine and define clinical, dermoscopic and reflectance confocal microscopy (RCM) features of LM/LMM in patients < 50 years old. METHODS: This was a multicentre study involving tertiary referral centres for skin cancer management. The study included cases of consecutively excised LM/LMM arising in patients < 50 years of age with a histopathological diagnosis of LM/LMM and a complete set of clinical and dermoscopic images; RCM images were considered when present. RESULTS: In total, 85 LM/LMM of the face from 85 patients < 50 years were included in the study. A regression model showed a direct association with the size of the lesion (R2 = 0.08; P = 0.01) and with the number of dermoscopic features at diagnosis (R2 = 0.12; P < 0.01). In a multivariable analysis, an increasing number of dermoscopic features correlated with increased patient age (P < 0.01), while the presence of grey colour was a predictor of younger age at diagnosis (P = 0.03). RCM revealed the presence of melanoma diagnostic features in all cases (pagetoid cells and atypical nesting). CONCLUSIONS: LM is not a disease limited to older people as previously thought. LM presenting in young adults tends to be smaller and with fewer dermoscopic features, making its diagnosis challenging. Careful evaluation of facial pigmented lesions prior to cosmetic procedures is imperative to avoid incorrectly treating early LM as a benign lesion.

Skin ageing: Clinical aspects and in vivo microscopic patterns observed with reflectance confocal microscopy and optical coherence tomography.

Few studies have combined high-resolution, non-invasive imaging, such as standardized clinical images, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), for age-related skin change characterization according to age groups. This study aimed to correlate clinical manifestations of ageing with skin cytoarchitectural background observed with high-resolution, non-invasive imaging according to age-related skin pattern distribution. A set of 140 non-pathological facial skin images were retrospectively retrieved from a research database. Subjects, aged between 20 and 89, were divided into 7 age groups. Clinical features were explored with VISIA, including hyperpigmentation, skin texture, wrinkles, pores and red areas, quantified and expressed as automated absolute scores. Previously described RCM and OCT epidermal and dermal features associated with ageing were investigated. All features were assessed for distribution and correlation among age groups. Significant direct correlations between age and clinical features were proven for cutaneous hyperpigmentation, skin texture, wrinkles and red areas. As age advances, RCM epidermal irregular honeycomb and mottled pigmentation are more frequently observed and collagen is more frequently coarse, huddled and curled, while the epidermis in OCT is thickened and the dermal density is decreased with more disrupted collagen fibres. RCM and OCT feature changes correlate directly and indirectly as well as correlating directly and indirectly with standardized clinical images. Clinical manifestations of ageing correlate with skin cytoarchitectural background observed with RCM and OCT. In conclusion, complimentary information between standardized clinical images and high-resolution, non-invasive imaging will assist in the development of future studies dedicated to skin ageing assessment and treatment effectiveness.

Interstitial lung disease in microscopic polyangiitis and granulomatosis with polyangiitis: demographic, clinical, serological and radiological features of an Italian cohort from the Italian Society for Rheumatology.

OBJECTIVES: Interstitial lung disease (ILD) has been described as a possible pulmonary involvement in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV), mainly granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Aim of this cross-sectional Italian national study was to describe demographic, clinical and serological profile of ILD related to MPA and GPA and investigate possible correlations between radiologic patterns of ILD and vasculitis features. METHODS: We enrolled 95 consecutive patients with AAV-ILD, 56 affected by MPA (58.9%) and 39 by GPA (41.1%). RESULTS: NSIP was the most frequently detected ILD pattern, observed in c-ANCA patients in 60.9% of cases, followed by UIP pattern mainly observed in p-ANCA patients (47.7%, p=0.03). ILD represented the first clinical manifestation, preceding vasculitis diagnosis in 22.1% of cases and, globally, ILD was already detectable at AAV diagnosis in 66.3% of patients. The diagnosis of ILD preceded that of AAV in 85.7% of p-ANCA positive-patients, while only one patient with c-ANCA developed ILD before AAV (p= 0.039). Multivariate analysis confirmed the correlation of UIP pattern with p-ANCA-positivity and a diagnosis of ILD before AAV, also when adjusted for age and sex. CONCLUSIONS: Our study confirms that UIP is a frequent pattern of lung disease in AAVILD patients. Our results also suggest that ILD can represent an early complication of AAV but also occur in the course of the disease, suggesting the need of a careful evaluation by both pulmonologist and rheumatologist to achieve an early diagnosis. Further prospective studies are needed to define ILD prevalence and evolution in AAV patients.

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.

Dendritic cells in reflectance confocal microscopy are a clue for early melanoma diagnosis in extrafacial flat pigmented melanocytic lesions.

Differential diagnosis of extrafacial flat pigmented lesions with dermoscopic reticular and/or homogeneous pattern is challenging. Dendritic cells upon reflectance confocal microscopy (RCM) still represent a pitfall. This study aims to determine the role of dendritic cells upon RCM in the epidermis and dermo-epidermal junction (DEJ), together with common RCM features for melanoma and nevi, in dermoscopically equivocal extrafacial flat pigmented lesions. A retrospective evaluation of RCM images of melanocytic extrafacial flat pigmented lesions with reticular and/or homogeneous dermoscopic pattern and with histopathological diagnosis, was performed. A multivariate model of RCM features was used to obtain a score of independent risk factors. A total of 698 lesions were included. Increasing patient age, epidermal dendritic cells, many dendritic cells in the DEJ (>30%) and many (>5/mm2 ) round atypical cells were independent risk factors for melanoma. Edged papillae and melanophages were indicative of nevus. A score based on these features was developed to assist in melanoma differential diagnosis. The RCM observation of abundant (>30%) dendritic cells in the DEJ is highly suggestive of malignity. This independent risk factor should also be considered for improved differential diagnosis of extrafacial melanoma.

The role of reflectance confocal microscopy in the diagnosis of eccrine poroma: A retrospective case-control study.

Eccrine poroma (EP) is a rare benign adnexal tumor that may mimic benign or malignant tumors and differential diagnosis may be difficult under clinical and dermoscopic examination. Reflectance confocal microscopy (RCM) examination may add important information to diagnosis and subsequent management of solitary lesions for which dermoscopy can be challenging. The aim of the present study was to investigate features of EP at RCM in order to detect the characteristics that might aid in the differential diagnosis of EP versus other solitary lesions (benign or malignant). Secondary objective was to correlate the resulting features with histopathological findings. This monocentric retrospective observational case-control study included all EPs registered with RCM between January 2007 and May 2018. Control cases were benign or malignant lesions similar in clinical appearance, morphology, and dermoscopic features to EPs. RCM evaluators were blinded to clinical-dermoscopic images and to final histopathological diagnoses. Finally, RCM-histopathological correlation was performed. A total of 11 EPs and 33 controls were included in the present study. Among RCM parameters, "cords without palisading," "dark holes," "prominent vascularization" and "abundant stroma" resulted positively associated with EP in univariate analysis. RCM features correspond to the histopathological diagnosis of EP in 97% of cases, as illustrated by the cluster analysis. An excellent correlation between diagnostic features of conventional histopathology and RCM was observed. RCM assists in the differential diagnosis of solitary lesions, allowing to reach a correct diagnosis of EP through the identification of its four characteristics.

Unusual dermoscopic patterns of basal cell carcinoma mimicking melanoma.

BACKGROUND: Basal cell carcinoma can simulate melanoma and specific dermoscopic criteria have not yet been defined in a large cohort. OBJECTIVE: To identify dermoscopic "trump" characteristics for differential diagnosis, identify cluster groups and assess the clinical impact of this study's findings. METHODS: Retrospective, multicentric comparative study of atypical, non-facial basal cell carcinoma (≥1 seven-point checklist criteria) and melanoma (with at least one BCC criteria) at dermoscopy. Observed dermoscopic features were used to develop a proposed score. Lesion clusters were defined with hierarchical analysis. Clinical impact was assessed with a blinded reader study following this study's results. RESULTS: A total of 146 basal cell carcinoma and 76 melanoma were included. Atypical vascular pattern was common to most lesions (74.5%). Twelve trump features were included in the proposed score (sensitivity 94.1% and specificity 79.5%). Cluster analysis identified 3 basal cell carcinoma and 3 melanoma clusters. Findings improved overall diagnostic accuracy and confidence (26.8% and 13.8%, respectively; p < 0.001). CONCLUSIONS: These findings support the notion that atypical vascular pattern should be considered a shared feature of both melanoma and atypical basal cell carcinoma. Our proposed score improves diagnostic accuracy and confidence. Absence of pigmented features was associated with lower diagnostic accuracy and confidence.

Dynamic dermoscopic and reflectance confocal microscopic changes of melanocytic lesions excised during follow up.

BACKGROUND: Digital dermoscopy follow up (DDF) is useful in improving the recognition of melanoma, catching early changes over time, although benign nevi can also show changes. Reflectance confocal microscopy (RCM) improves accuracy in diagnosing melanoma and decreases the number of unnecessary resections. OBJECTIVE: To evaluate dynamic dermoscopic and RCM changes during follow up of equivocal melanocytic lesions and assess the impact of adjunctive RCM to DDF for melanoma diagnosis. METHODS: A retrospective, multicenter study of extrafacial atypical melanocytic lesions excised during follow up was performed. Morphologic changes were evaluated, comparing dermoscopy and RCM baseline and follow-up images. RESULTS: One hundred thirty-seven atypical melanocytic lesions were studied, including 14 melanomas and 123 benign nevi. Significantly greater changes in DDF of atypical network, regression, atypical streaks, and asymmetrical growth as well as in dynamic RCM of atypical cells and dermal-epidermal junction disarray were noted in melanomas. With adjunctive dynamic RCM and major changes at DDF, sensitivity reached 100%, with 40.6% specificity. LIMITATIONS: Selected series of difficult to recognize lesions, with both DDF and dynamic RCM images. CONCLUSION: Adjunctive dynamic RCM improves early melanoma recognition sensitivity.

Symptoms and clinical features in patients affected by endolymphatic sac tumor: a systematic review and meta-analysis.

PURPOSE: Most ELST data in the literature are case studies or limited to small cohorts (< 16 patients). We evaluated the main clinical signs observed at endolymphatic sac tumor (ELST) diagnosis in patients with or without Von Hippel-Lindau disease. METHODS: We conducted a comprehensive literature search in PubMed, Scopus, and Web of Science. We included studies with at least 1 patient, of any age, affected by sporadic or VHL-related ELSTs reporting levels of hearing loss and facial nerve function and a comprehensive description of presenting symptoms at ELST diagnosis. We combined data for proportional meta-analysis. p values of 0.05 were considered statistically significant. Methodological quality was evaluated. Analyses were performed with MedCalc 14.8.1 software. RESULTS: A total of 26 studies, including 113 patients and 118 cases of ELSTs were included. Pooled proportion rates (95% CI) of overall hearing loss was 88.7%, (82.4-93.4), severe hearing loss was 21.6% (12.8-32.1) profound hearing loss was 39.8% (28.7-51.5), vertigo/imbalance was 42.0% (33.8-50.5), tinnitus was 61.8% (53.4-69.8) and facial nerve palsy was 30.6% (23.2-38.9). Generally, symptoms were homogeneous or moderately heterogeneous among included studies. CONCLUSION: This is the first systematic review of clinical presentations at ELST diagnosis. The most serious clinical events include profound hearing loss and facial impairment. Fluctuating hearing loss, tinnitus and vertigo are frequently reported and may confound correct and prompt ELST diagnosis.

De Novo Skin Neoplasms in Liver-Transplanted Patients: Single-Center Prospective Evaluation of 105 Cases.

Background and Objectives: Solid-organ transplant recipients (SOTRs) are notably considered at risk for developing cutaneous malignancies. However, most of the existing literature is focused on kidney transplant-related non-melanoma skin cancers (NMSCs). Conflicting data have been published so far on NMSC incidence among liver transplant recipients (LTRs), and whether LTRs really should be considered at lower risk remains controversial. The aim of the present study was to prospectively collect data on the incidence of cutaneous neoplasms in an LTR cohort. Materials and Methods: All LTRs transplanted at the Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit of Modena University Hospital from October 2015 to June 2021 underwent a post-transplant periodic skin check at the Dermatology Unit according to our institutional integrated care pathway. Data on the presence of cutaneous malignant and premalignant lesions were collected at every timepoint. Results: A total of 105 patients were enrolled in the present study. Nearly 15% of the patients developed cutaneous cancerous and/or precancerous lesions during the follow-up period. Almost half of the skin cancerous lesions were basal cell carcinomas. Actinic keratoses (AKs) were observed in six patients. Four patients developed in situ squamous cell carcinomas, and one patient was diagnosed with stage I malignant melanoma. Otherwise, well-established risk factors for the occurrence of skin tumors, such as skin phototype, cumulative sun exposure, and familial history of cutaneous neoplasms, seemed to have no direct impact on skin cancer occurrence in our cohort, as well as an immunosuppressive regimen and the occurrence of non-cutaneous neoplasms. Conclusions: Close dermatological follow-up is crucial for LTRs, and shared protocols of regular skin checks in this particular subset of patients are needed in transplant centers.

COVID-19 spreading across world correlates with C677T allele of the methylenetetrahydrofolate reductase (MTHFR) gene prevalence.

BACKGROUND: Homocysteine assessment has been proposed as a potential predictive biomarker for the severity of COVID-19 infection. The purpose of this review was to analyze the correlation between the prevalence of MTHFR C677 T gene polymorphism and COVID-19 incidence and mortality worldwide. METHODS: Data regarding MTHFR C677 T gene mutation were obtained from the interrogation of the Genome Aggregation Database (genomAD), which is publicly available from the web"https://gnomad.broadinstitute.org." COVID-19 cases, including prevalence and mortality, were obtained from"https://www.worldometers.info/coronavirus" 27 August 2020. RESULTS: There is a clear trend toward the worldwide prevalence of MTHFR 677 T and COVID-19 incidence and mortality. The prevalence of MTHFR 677 T allele in the Latino population, and the incidence and mortality for COVID-19 was higher for this ethnic group than that reported for most other populations globally. Statistical analysis showed a relatively strong correlation between C677 T and death from coronavirus. CONCLUSIONS: Genetic polymorphism of MTHFR C677 T may modulate the incidence and severity of COVID-19 pandemic infection.

Orbital wall decompression in the management of Graves' orbitopathy: a systematic review with meta-analysis.

PURPOSE: To systematically review outcomes of orbital bony wall decompression for Grave's orbitopathy according to the surgical approach. METHODS: A systematic search for studies published in "Ovid MEDLINE", "Web of Science" and "Embase" of patients with surgical treatment of Grave's orbitopathy was performed. The overall postoperative change in Hertel exophthalmometry was calculated by random-effect meta-analysis model with 95% confidence interval (CI). RESULTS: A total of 33 studies, including 1686 patients and 2946 procedures, were included. The weighted mean Hertel value overall reduction was - 4.56 mm (95% CI - 5.05 to - 4.07 mm). According to surgical techniques the reduction was - 4.36 mm (95% CI - 5.22 to - 3.50) for infero-medial technique, - 4.88 mm (- 5.68 to - 4.08) for medial-lateral technique, - 4.32 mm (- 4.80to - 3.84) for lateral technique, - 5.45 mm (- 6.16 to - 4.74) for three-wall technique and - 3.47 mm (- 5.81 to - 1.12) for medial technique. The overall rate of new-onset of primary gaze diplopia was reported in 23 studies. The included procedures were 653 and results were heterogeneous (heterogeneity: Q = 78.8 df = 22, I2 = 72.09%, p < 0.01). The pooled proportion (95% CI) rate of new-onset of primary gaze diplopia was 12% (7-16). CONCLUSION: Our metanalysis highlights that orbital bony wall decompression represents an effective surgical procedure. The three wall approach was associated with the best results in terms of exophthalmos reduction. Data suggest that an exclusive lateral approach may help to avoid the new-onset of primary gaze diplopia during the postoperative period.

Folliculotropism in head and neck lentigo maligna and lentigo maligna melanoma.

BACKGROUND: Lentigo maligna (LM) and lentigo maligna-melanoma (LMM) are histotypes of melanoma arising in skin with cumulative solar radiation damage. The extension of atypical melanocytes to the hair follicle (folliculotropism) is a histopathological feature of LM/LMM. Its role has not been totally clarified, but it may be correlated to treatment response in LM or to progression in LMM. OBJECTIVE: This retrospective, multicentric study aims to identify dermatoscopic features associated with folliculotropism in LMs/LMMs. PATIENTS AND METHODS: We analyzed cases of head and neck LMs/LMMs diagnosed between 2005-2014 at Melanoma Units, University of Bologna/Modena/Florence/Siena (Italy), Nice (France): 25 LMs and 73 LMMs were included. RESULTS: Grey circles (44 %) indicated an isthmic/bulb level of involvement, which were completely absent in the infundibular LM lesions (P = 0.041). In the group of LMMs, light/dark brown pseudonetwork and light brown structureless areas were an indicator of diffuse distribution of malignant melanocytes in the follicular units (P < 0.001 and P = 0.001, respectively), while grey circles indicated focal or diffuse distribution (P < 0.001). CONCLUSIONS: A better understanding of the extension of malignant melanocytes is helpful, aiding clinicians in their decision to perform a radical excision or obtaining a biopsy in the most invasive area of the lesion, which includes potential folliculotropism.

Microscopic and functional changes observed with dynamic optical coherence tomography for severe refractory atopic dermatitis treated with dupilumab.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory disease. Recently, dupilumab was approved for moderate-to-severe AD. D-OCT is a noninvasive tool for the characterization of skin diseases. OBJECTIVE: To describe the changes observed with D-OCT in lesional and clinically healthy skin of patients with refractory severe AD under dupilumab treatment. METHODS: We analyzed AD lesions and healthy skin by D-OCT. Clinical scores of AD severity were assessed at baseline (T0) and after 1 and 3 months of treatment (T1, T2). Descriptive statistics, chi-square test, and t test were used to compare the analyzed parameters over time and between AD lesions and clinically healthy skin. RESULTS: At baseline, average EASI was 45.7. During the follow-up, EASI75 and EASI90 were achieved in 57% and 36% of patients at T1 and 100% and 86% of patients at T2, respectively. Lesional skin D-OCT parameters related to epidermal remodeling and inflammation evidenced a significant improvement after 1 month of treatment. In clinically healthy skin, D-OCT parameters improved significantly after 3 months of treatment, especially for collagen remodeling and inflammation. CONCLUSION: The study demonstrates that the clinical improvement of severe AD patients under dupilumab treatment is correlated with specific D-OCT changes of patients' lesional and clinically healthy skin.

The influence of MC1R on dermal morphological features of photo-exposed skin in women revealed by reflectance confocal microscopy and optical coherence tomography.

BACKGROUND: The melanocortin 1 receptor (MC1R) gene is one of the major determinants of skin pigmentation. It is a highly polymorphic gene and some of its polymorphisms have been related to specific skin phenotypes, increased risk of skin cancers and skin photoageing. Currently, its contribution to changes in dermal features in photo-exposed skin is unknown. OBJECTIVE: The main objective of this study is to evaluate the potential correlation between MC1R status and specific healthy photo-exposed skin characteristics. MATERIALS AND METHODS: Skin facial features were estimated by evaluation with standard digital photography with automated features count, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) in 100 healthy women. Skin of the forearms was used as a control. RESULTS: The study found an association between RHC MC1R polymorphisms and dermal features in photo-exposed areas being represented by increased vessel density and pixel density in OCT (P = .025 and P = .001, respectively) and increased coarse collagen in RCM (P = .034), as compared to non-RHC subjects. To our knowledge this is previously unreported. Additionally, previously reported correlations between light hair colour and pigmented spots with MC1R RHC polymorphisms have been confirmed. CONCLUSIONS: Our results suggest the role of RHC MC1R variants in dermal variations of facial skin, as compared to non-RHC variants. To our knowledge this is previously unreported.

Melanoma types by in vivo reflectance confocal microscopy correlated with protein and molecular genetic alterations: A pilot study.

Cutaneous melanoma (CM) is one of the most prevalent skin cancers, which lacks both a prognostic marker and a specific and lasting treatment, due to the complexity of the disease and heterogeneity of patients. Reflectance confocal microscopy (RCM) in vivo analysis is a versatile approach offering immediate morphological information, enabling the identification of four primary cutaneous RCM CM types. Whether RCM CM types are associated with a specific protein and molecular genetic profiles at the tissue level remains unclear. The current pilot study was designed to identify potential correlations between RCM CM types and specific biological characteristics, combining immunohistochemistry (IHC) and molecular analyses. Eighty primary CMs evaluated at patient bedside with RCM (type 1 [19, 24%], type 2 [12, 15%], type 3 [7, 9%] and type 4 [42, 52%]) were retrospectively evaluated by IHC stains (CD271, CD20, CD31, cyclin D1), fluorescence in situ hybridization FISH for MYC gain and CDKN2A loss and molecular analysis for somatic mutations (BRAF, NRAS and KIT). RCM CM types correlated with markers of stemness property, density of intra-tumoral lymphocytic B infiltrate and cyclin D1 expression, while no significant association was found with blood vessel density nor molecular findings. RCM CM types show a different marker profile expression, suggestive of a progression and an increase in aggressiveness, according to RCM morphologies.

Ex vivo fluorescence confocal microscopy: the first application for real-time pathological examination of prostatic tissue.

OBJECTIVE: To report the first application of ex vivo fluorescence confocal microscopy (FCM) - a novel optical technology that is capable of providing fast microscopic imaging of unfixed tissue specimens- in the urological field assessing its diagnostic accuracy for non neoplastic and cancerous prostate tissue (prostatic adenocarcinoma) compared to the 'gold standard' histopathological diagnoses. PATIENTS AND METHODS: In all, 89 specimens from 13 patients with clinically localised prostate cancer were enrolled into the study. All patients underwent robot-assisted laparoscopic radical prostatectomy with fresh prostatic tissue biopsies taken at the end of each intervention using an 18-G biopsy punch. Specimens were randomly assigned to the three collaborating pathologists for evaluation. Intra- and inter-observer agreement was tested by the means of Cohen's κ. The diagnostic performance was evaluated on receiver operating characteristic curve analysis. RESULTS: The overall diagnostic agreement between FCM and histopathological diagnoses was substantial with a 91% correct diagnosis (κ = 0.75) and an area under the curve of 0.884 (95% confidence interval 0.840-0.920), 83.33% sensitivity, and 93.53% specificity. CONCLUSION: FCM seems to be a promising tool for enhanced specimens' reporting performance, given its simple application and very rapid microscopic image generation (<5 min/specimen). This technique may potentially be used for intraoperative pathological specimens' analysis.

Lesions Mimicking Melanoma at Dermoscopy Confirmed Basal Cell Carcinoma: Evaluation with Reflectance Confocal Microscopy.

BACKGROUND: Atypical basal cell carcinoma (BCC), characterized by equivocal dermoscopic features typical of malignant melanoma (MM), can be difficult to diagnose. Reflectance confocal microscopy (RCM) enables in vivo imaging at nearly histological resolution. OBJECTIVES: To evaluate with RCM atypical melanocytic lesions identified in dermoscopy, according to common RCM criteria for the differential diagnosis of BCC, and to identify representative RCM parameters for superficial (sBCCs) and nonsuperficial (nsBCCs) basal cell carcinomas (BCCs). METHODS: A retrospective analysis of consecutive patients evaluated with RCM, selecting excised lesions classified at dermoscopy with ≥1 score from the re visited 7-point checklist, mimicking melanoma, registered between 2010 and 2016. Cluster analysis identified BCC subclassifications. RESULTS: Of 178 atypical lesions, 34 lesions were diagnosed as BCCs with RCM. Lesions were confirmed BCCs with histopathology. Dermoscopic features included atypical network (55.9%) and regression structures (35.5%) associated with sBCCs, and an atypical vascular pattern (58.8%) and irregular blotches (58.8%) with nsBCCs. Hierarchical cluster analysis identified 2 clusters: cluster 1 (100% sBCCs) was characterized by the presence of cords connected to the epidermis (90%, p < 0.001), tumor islands located in the epidermis (100%, p < 0.001), smaller vascular diameter (100%, p < 0.001) and solar elastosis (90%, p = 0.017), and cluster 2 (nsBCCs 85%) was defined by the dermic location of tumor islands (87.5%, p < 0.001) with branch-like structures (70.8%, p = 0.007) and surrounding collagen (83.3%, p = 0.012), peripheral palisading (83.3%, p = 0.012) and coiled vascular morphology (79.2%, p < 0.001) with a larger vascular diameter (50%, p < 0.001). CONCLUSIONS: RCM is able to diagnose BCCs mimicking melanoma at dermoscopy and seems able to identify sBCCs and nsBCCs.