Line-Field Confocal Optical Coherence Tomography: A New Skin Imaging Technique Reproducing a "Virtual Biopsy" with Evolving Clinical Applications in Dermatology.

BACKGROUND: Line-field confocal optical coherence tomography is a novel technology able to reproduce a "virtual biopsy" of the skin. The aim of this review is to explore the application of line-field confocal optical coherence tomography (LC-OCT) in various skin diseases, covering skin cancers, inflammatory and infectious skin diseases, genetic diseases, cosmetic procedures, and less common disorders. METHODS: Study selection was conducted based on LC-OCT and using pertinent MeSh terms, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines from inception to March 2024; to evaluate the quality and risk of bias of studies, Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used. RESULTS: the search retrieved 154 papers according to the selection criteria; after removing publications by one or more of the exclusion criteria, a total of 96 studies were found to be suitable for the analysis. CONCLUSIONS: Increasing evidence supports the use of LC-OCT as an adjunctive diagnostic tool for the in vivo diagnosis of a variety of skin tumors. As this device can be considered a "bridge" between dermoscopy and histopathology, widening applications in numerous fields of clinical dermatology, including inflammatory skin disease treatment, presurgical mapping, cosmetic procedures, and monitoring of non-invasive therapies, have been explored.

Line-field confocal optical coherence tomography for the differential diagnosis of porokeratosis from clinical simulators: a preliminary study.

Porokeratosis variants are relatively rare and can be clinically misdiagnosed with several common papulo-keratosic simulators. Line-field confocal optical coherence tomography (LC-OCT) is a new technology able to explore the skin in vivo up to 500µm depth. In this preliminary study we aimed to investigate the role of LC-OCT in the diagnosis of many porokeratosis variants. A total of 54 patients (28 was affected by one among 13 porokeratosis variants, 26 had a simulator condition) were examined at lesional and perilesional sites in vertical and horizontal view. We found an almost perfect interobserver agreement in LC-OCT images interpretation and a perfect correspondence with histologic slides. In addition, a series of morphologic in vivo and 3D features related to the cornoid lamella were detected by LC-OCT, not visible under histology. This device can be proposed for rapid bed-side non-invasive differentiation of porokeratosis variants from their simulators, possibly sparing incisional biopsy in doubtful cases.

North-south differences in incidence and surveillance of cutaneous malignant melanoma in Italy.

BACKGROUND: In Italy, the incidence of cutaneous malignant melanoma is two-fold higher in the north than in the south. This gradient might be associated with differences in incidence trends and disease surveillance. We compared the time trends in incidence rates, mortality rates, dermatologic office visit rates and skin biopsy rates between the Emilia-Romagna Region (northern Italy) and the Sicily Region (southern Italy). METHODS: The cancer registries of Parma, Modena, Ferrara and Romagna (current population, 2,606,465) and Catania-Messina-Enna, Siracusa and Ragusa (2,775,019) provided incidence and mortality records for the years 2008-2017. The records of outpatient services delivered in public health facilities were obtained from the two Regional Administrations. Trends in rates were assessed with the estimated average annual percent change. North-south differences were expressed as age-standardised rate ratios. RESULTS: In the context of a generalised increasing incidence trend, which was more moderate in the female population of the Sicily Region, the standardised rate ratios were: 5.31 (males) and 5.20 (females) for in situ cutaneous malignant melanoma; 2.10 and 2.07 for invasive cutaneous malignant melanoma, with an excess incidence concentrated in lesions ⩽1.00 mm thick (3.58 and 3.05); 3.00 and 2.44 for dermatologic office visits; and 5.25 and 5.02 for skin biopsies. Mortality was stable in both Regions. CONCLUSIONS: In the Emilia-Romagna Region, as compared with the Sicily Region, a higher incidence of cutaneous malignant melanoma -especially of in situ and early invasive cutaneous malignant melanoma- coexisted with a higher level of clinical surveillance. The question of the direction of the cause-effect relationship between increased incidence and increased diagnostic scrutiny remains open.

Pattern Analysis of Benign and Malignant Atypical Melanocytic Skin Lesions of Palms and Soles: Variations of Dermoscopic Features According to Anatomic Site and Personal Experience.

Background: The differential diagnosis of atypical melanocytic skin lesions localized on palms and soles represents a diagnostic challenge: indeed, this spectrum encompasses atypical nevi (AN) and early-stage melanomas (EN) displaying overlapping clinical and dermoscopic features. This often generates unnecessary excisions or delayed diagnosis. Investigations to date were mostly carried out in specific populations, focusing either on acrolentiginous melanomas or morphologically typical acquired nevi. Aims: To investigate the dermoscopic features of atypical melanocytic palmoplantar skin lesions (aMPPLs) as evaluated by variously skilled dermatologists and assess their concordance; to investigate the variations in dermoscopic appearance according to precise location on palms and soles; to detect the features with the strongest association with malignancy/benignity in each specific site. Methods: A dataset of 471 aMPPLs-excised in the suspect of malignancy-was collected from 10 European Centers, including a standardized dermoscopic picture (17×) and lesion/patient metadata. An anatomical classification into 17 subareas was considered, along with an anatomo-functional classification considering pressure/friction, (4 macroareas). A total of 156 participants (95 with less than 5 years of experience in dermoscopy and 61 with ≥than 5 years) from 17 countries performed a blinded tele-dermoscopic pattern analysis over 20 cases through a specifically realized web platform. Results: A total of 37,440 dermoscopic evaluations were obtained over 94 (20%) EM and 377 (80%) AN. The areas with the highest density of EM compared to AN were the heel (40.3% EM/aMPPLs) of the sole and the "fingers area" (33%EM/aMPPLs) of the palm, both characterized by intense/chronic traumatism/friction. Globally, the recognition rates of 12 dermoscopic patterns were non statistically different between 95 dermatology residents and 61 specialists: aMPPLs in the plantar arch appeared to be the most "difficult" to diagnose, the parallel ridge pattern was poorly recognized and irregular/regular fibrillar patterns often misinterpreted. Regarding the aMPPL of the "heel area", the parallel furrow pattern (p = 0.014) and lattice-like pattern (p = 0.001) significantly discriminated benign cases, while asymmetry of colors (p = 0.002) and regression structures (p = 0.025) malignant ones. In aMPPLs of the "plantar arch", the lattice-like pattern (p = 0.012) was significant for benignity and asymmetry of structures, asymmetry of colors, regression structures, or blue-white veil for malignancy. In palmar lesions, no data were significant in the discrimination between malignant and benign aMPPLs. Conclusions: This study highlights that (i) the pattern analysis of aMPPLs is challenging for both experienced and novice dermoscopists; (ii) the histological distribution varies according to the anatomo-functional classification; and (iii) different dermoscopic patterns are able to discriminate malignant from benign aMPPLs within specific plantar and palmar areas.

Impact of Attachment Style and Temperament Traits on the Quality of Life of Patients with Psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease with manifestations that go beyond the visual manifestation, and include psychological aspects. Some mental disorders or personality traits in psoriasis patients have also been highlighted, such as a negative or problematic attitude towards life, impulsive or avoidant behavior, and lower satisfaction with life. The aim of our cross-sectional study was to explore the associations between adult attachment, temperament, and quality of life of patients with psoriasis. METHODS: A sample of 75 patients with psoriasis was evaluated with the Attachment Style Questionnaire (ASQ) to study adult attachment, the Temperament Evaluation of Memphis, Pisa, and San Diego Auto-questionnaire (TEMPS-A) to study temperament traits, and the Dermatology Life Quality Index (DLQI) to study the impact of dermatological diseases on patients' lives. RESULTS: Depressive, cyclothymic, and irritable temperaments were found to be significantly positively associated with a need for approval and preoccupation with relationships subscales of the ASQ. The severity of skin disease effect on the patient's life was higher in women than in men. Moreover, a statistically significant effect of the need for approval subscale of the ASQ was found. The positive correlation between the severity of skin disease effect on the patient's life with a need for approval was statistically significant and stronger in women than in men. CONCLUSIONS: A better understanding of the impact of mental comorbidities on psoriasis and vice versa places an ever-greater responsibility on dermatologists involved in the management of psoriasis to recognize these problems and collaborate with psychologists and psychiatrists to help these patients.

Italian National Registry of Alopecia Areata: an epidemiological study of 699 Italian patients.

BACKGROUND: Alopecia areata (AA) is an organ-specific autoimmune disease that affects the hair follicles of the scalp and the rest of the body causing hair loss. Due to the unpredictable course of AA and the different degrees of severity of hair loss, only a few well-designed clinical studies with a low number of patients are available. Also, there is no specific cure, but topical and systemic anti-inflammatory and immune system suppressant drugs are used for treatment. The need to create a global registry of AA, comparable and reproducible in all countries, has recently emerged. An Italian multicentric electronic registry is proposed as a model to facilitate and guide the recording of epidemiological and clinical data and to monitor the introduction of new therapies in patients with AA. METHODS: The aim of this study was to evaluate the epidemiological data of patients with AA by collecting detailed information on the course of the disease, associated diseases, concomitant and previous events, and the clinical response to traditional treatments. Estimate the impact on the quality of life of patients. RESULTS: The creation of the National Register of AA has proven to be a valid tool for recording, with a standardized approach, epidemiological data, the trend of AA, response to therapies and quality of life. CONCLUSIONS: AA is confirmed as a difficult hair disease to manage due to its unpredictable course and, in most cases, its chronic-relapsing course, capable of having a significant impact on the quality of life of patients.

Line-field confocal optical coherence tomography of eyelid margin growths: A case series.

BACKGROUND: The clinical differential diagnosis of lesions arising on the eyelid margin may be challenging and an unneeded surgical approach may have serious functional and aesthetic consequences. Nonetheless, early recognition and treatment of malignant tumors of the eyelid margin is mandatory. Line-field confocal optical coherence tomography (LC-OCT) is a novel tool for the in vivo, real-time skin imaging. OBJECTIVES: The aim of the study was to identify and analyze the LC-OCT features of a series of eyelid margin growths and to correlate these features with the histopathological findings. METHODS: Patients with eyelid margin growths who were scheduled for lesion excision underwent LC-OCT examination. Inclusion criteria were a challenging clinical aspect of the lesions and a clinical history of recent onset (up to 12 months). In all cases, the histopathological examination of the excised lesions was performed for the final diagnosis. RESULTS: A total of 31 lesions located on the upper (13 cases) or lower (18 cases) eyelid margin from 28 consecutive patients (male = 15, female = 13; mean age: 64.7 years, range: 44-87 years) were evaluated and excised. The histopathologic diagnoses were nodular basal cell carcinoma (BCC) (nine cases), squamous cell carcinoma (SCC) (three cases), compound nevus (four cases), dermal nevus (two cases), seborrheic keratosis (four cases), pyogenic granuloma (one case), trichilemmal cyst (three cases), and hidrocystoma (five cases). LC-OCT allowed the in vivo recognition of the main microscopic features of the examined lesions. CONCLUSIONS: LC-OCT represents a promising tool for the evaluation of eyelid margin lesions. Advantages of non-invasive diagnosis particularly relevant in such a sensitive region include a more correct planning of the treatment and, in case of surgery, the most appropriate surgical approach and, importantly, a correct timing of intervention.

Smart e-Skin Cancer Care in Europe During and after the Covid-19 Pandemic: a Multidisciplinary Expert Consensus.

INTRODUCTION: Melanoma is the deadliest of all the skin cancers and its incidence is increasing every year in Europe. Patients with melanoma often present late to the specialist and treatment is delayed for many reasons (delay in patient consultation, misdiagnosis by general practitioners, and/or limited access to dermatologists). Beyond this, there are significant inequalities in skin cancer between population groups within the same country and between countries across Europe. The emergence of the COVID-19 pandemic only aggravated these health deficiencies. OBJECTIVES: The aim was to create an expert opinion about the challenges in skin cancer management in Europe during the post COVID-19 acute pandemic and to identify and discuss the implementation of new technologies (including e-health and artificial intelligence defined as "Smart Skin Cancer Care") to overcome them. METHODS: For this purpose, an ad-hoc questionnaire with items addressing topics of skin cancer care was developed, answered independently and discussed by a multidisciplinary European panel of experts comprising dermatologists, dermato-oncologists, patient advocacy representatives, digital health technology experts, and health technology assessment experts. RESULTS: After all panel of experts discussions, a multidisciplinary expert opinion was created. CONCLUSIONS: As a conclusion, the access to dermatologists is difficult and will be aggravated in the near future. This fact, together with important differences in Skin Cancer Care in Europe, suggest the need of a new approach to skin health, prevention and disease management paradigm (focused on integration of new technologies) to minimize the impact of skin cancer and to ensure optimal quality and equity.

Efficacy and safety of sonidegib for the management of basal cell carcinoma: a drug safety evaluation.

INTRODUCTION: Surgery is the standard management for most of basal cell carcinomas (BBCs). In some cases, also radiotherapy may be a valuable weapon as well as ablative and topical treatments. However, all these approaches may be limited by some tumor features. In this scenario, locally advanced BCCs (laBCC) and metastatic BCC, also defined as 'difficult-to-treat' BCC, remain the real treatment challenge. New knowledge on BCC pathogenesis, particularly the Hedgehog (HH) pathway, led to the development of new selective therapies such as vismodegib and sonidegib. In particular, sonidegib is an orally administered small molecules, which inhibits the HH signaling pathway through the binding to SMO receptor, recently approved for the management of adult patients with laBCC who are not amenable to curative surgery or radiation therapy. AREAS COVERED: The purpose of this review is to analyze and discuss the efficacy and safety of sonidegib for the management of BCC, to provide a broad perspective on the currently available data. EXPERT OPINION: Sonidegib is a valuable weapon for the management of difficult-to-treat BCC. Current data showed promising results in terms of effectiveness and safety. However, more studies are needed to underline its role in BCC management, also considering the presence of vismodegib, and to investigate its use in a long-term period.

Line-field confocal optical coherence tomography in melanocytic and non-melanocytic skin tumors.

INTRODUCTION: Line-field confocal optical coherence tomography (LC-OCT) is a recently introduced, non-invasive skin imaging technique combining the technical advantages of reflectance confocal microscopy and conventional OCT in terms of isotropic resolution and in-tissue penetration. Several studies have been published so far about the use of LC-OCT in melanocytic and non-melanocytic skin tumors. The aim of this review was to summarize the currently available data on the use of LC-OCT for benign and malignant melanocytic and non-melanocytic skin tumors. EVIDENCE ACQUISITION: We searched scientific databases for any literature published up to 30th April 2023 and concerning the use of LC-OCT for melanocytic and non-melanocytic skin tumors. Identified papers were evaluated, and relevant information was extracted. EVIDENCE SYNTHESIS: A total of 29 studies were found including original articles, short reports, and letters to the Editor: 6 applied to melanocytic skin tumors, 22 to non-melanocytic skin tumors and 1 to both. The use of LC-OCT increased the diagnostic accuracy for melanocytic and non-melanocytic skin lesions. The highest diagnostic performance was found for basal cell carcinoma (BCC), but significant improvements in the diagnostic accuracy were also detected for the differentiation of actinic keratosis (AK) from squamous cell carcinoma (SCC) and of melanoma from nevi. The LC-OCT features of other skin tumors were also described and successfully correlated with histopathology. CONCLUSIONS: LC-OCT proved to increase the diagnostic accuracy for melanocytic and non-melanocytic skin lesions, thanks to the combination of high resolution/penetration, 3D reconstructions, and integrated dermoscopy. Although BCC seems the most suitable tumors for LC-OCT examination, the device is extremely performant for the differentiation of AK from SCC and the discrimination of melanoma from nevi as well. Additional studies on diagnostic performance and new investigations about the presurgical assessment of tumor margins with LC-OCT and its association with human and artificial intelligence algorithms are in progress.

Inflammatory and infectious skin diseases in line-field confocal optical coherence tomography: state of the art.

Line-field confocal optical coherence tomography (LC-OCT) is a new non-invasive dermatological imaging device. We summarized the available data on the use of LC-OCT for inflammatory and infectious diseases. In February 2023, we searched for all articles concerning the use of LC-OCT in inflammatory and infectious diseases. A total number of 14 papers were found and evaluated, and relevant information was extracted. LC-OCT can reveal architectural changes in the skin. Inflammatory cells are barely visible. It can highlight the level of fluid accumulation, the thickness of different epidermal layers, and the presence of ''foreign bodies'' such as parasites.