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.

Skin Imaging of Juvenile Xanthogranuloma: In Vivo Diagnosis by Line-Field Confocal Optical Coherence Tomography.

A 15-year-old boy presented with a yellowish, asymptomatic nodule on the left forearm, which developed in the last year. A diagnosis of juvenile xanthogranuloma was confirmed with histopathology. Line-field confocal optical coherence tomography (LC-OCT), a new skin imaging technique, was performed prior to surgery, showing a strong correspondence with histopathological sections. As juvenile xanthogranuloma is a benign disorder of the pediatric age, LC-OCT may represent an alternative to surgery for achieving a fast diagnosis in uncertain cases.

Comparison of reflectance confocal microscopy and line-field optical coherence tomography for the identification of keratinocyte skin tumours.

BACKGROUND: Reflectance confocal microscopy (RCM) and line-field confocal optical coherence tomography (LC-OCT) are non-invasive imaging devices that can help in the clinical diagnosis of actinic keratosis (AK) and cutaneous squamous cell carcinoma (SCC). No studies are available on the comparison between these two technologies for the identification of the different features of keratinocyte skin tumours. OBJECTIVES: To compare RCM and LC-OCT findings in AK and SCC. METHODS: A retrospective multicenter study was conducted. Tumours were imaged with RCM and LC-OCT devices before surgery, and the diagnosis was confirmed by histological examinations. LC-OCT and RCM criteria for AK/SCC were identified, and their presence/absence was evaluated in all study lesions. Gwet AC1 concordance index was calculated to compare RCM and LC-OCT. RESULTS: We included 52 patients with 33 AKs and 19 SCCs. Irregular epidermis was visible in most tumours and with a good degree of agreement between RCM and LC-OCT (Gwet's AC1 0.74). Parakeratosis, dyskeratotic keratinocytes and both linear dilated and glomerular vessels were better visible at LC-OCT than RCM (p < 0.001). Erosion/ulceration was identified with both methods in more than half of the cases with a good degree of agreement (Gwet AC1 0.62). CONCLUSIONS: Our results suggest that both LC-OCT and hand-held RCM can help clinicians in the identification of AK and SCC, providing an in vivo and non-invasive identification of an irregular epidermis. LC-OCT proved to be more effective in identifying parakeratosis, dyskeratotic keratinocytes and vessels in this series.

Real-Time Confocal Imaging for Hidradenitis Suppurativa: Description of Morphological Aspects and Focus on the Role of Follicular Ostia.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory skin disease involving the follicular unit. Growing evidence suggests a crucial role of hyperkeratosis, infundibular plugging and perifolliculitis in its pathogenesis. OBJECTIVES: To characterize the microscopic morphology of open comedos using in vivo reflectance confocal microscopy (RCM) and define alterations occurring in HS normal-appearing perilesional skin compared to healthy skin of a control group, discussing therefore microscopic differences. MATERIALS AND METHODS: Twenty patients (11 males, 9 females; aged 19-51 years) affected by HS were recruited. RCM was performed on open comedos of axillary/inguinal regions and on normal-appearing skin areas distant at least 1.5 cm from HS lesions. Ten healthy individuals (6 males, 4 females) were included as control group. RESULTS: RCM aspects of 78 open comedos were explored, observing circular/ovoidal structures disclosing a hyperrefractive amorphous material (72/78, 92.3%) within the infundibular cavity surrounded with a bright (51/78, 65.4%) and regular (52/78, 66.2%) border. Follicular ostia of HS perilesional skin (n = 541) compared to follicular ostia of a control group (n = 321) were characterized by a larger infundibular diameter (183.4 vs. 85.8 µm) and diverged in terms of material collected inside infundibula (44.5 vs. 21%) and keratinization of the border (47.6 vs. 25.5%). CONCLUSION: In vivo characterization of open comedos and the recognition of microscopic subclinical alterations of HS normal-appearing skin, compared to healthy skin, could add further insights into the definition of biological events leading to HS manifestations, including the dysregulated process of keratinization.

Real-Life Experience with Sonidegib for Locally Advanced Basosquamous Carcinoma: A Case Series.

Introduction: Basosquamous carcinoma is an uncommon subtype of basal cell carcinoma (BCC), characterized by aggressive local growth and metastatic potential, that mainly develops on the nose, perinasal area, and ears, representing 1.2-2.7% of all head-neck keratinocyte carcinomas. Although systemic therapy with hedgehog inhibitors (HHIs) represents the first-line medical treatment in advanced BCC, to date, no standard therapy for advanced basosquamous carcinoma has been established. Herein, we reported a case series of patients affected by locally advanced basosquamous carcinomas, who were treated with HHIs. Case Presentation: Data of 5 patients receiving HHIs for locally advanced basosquamous carcinomas were retrieved (2 women and 3 males, age range: 63-89 years, average age of 77 years). Skin lesions were located on the head-neck area; in particular, 4 tumors involved orbital and periorbital area and 1 tumor developed in the retro-auricular region. A clinical response was obtained in 3 out of 5 patients (2 partial responses and 1 complete response), while disease progression was observed in the remaining 2 patients. Hence, therapy was interrupted, switching to surgery or immunotherapy. Conclusion: Increasing evidence suggests considering HHIs for large skin tumors developing in functionally and cosmetically sensitive areas, in patients with multiple comorbidities, although their use for basosquamous carcinoma require more exploration, large cohort populations, and long follow-up assessment.

In Vivo Reflectance Confocal Microscopy Applied to Acral Melanocytic Lesions: A Systematic Review of the Literature.

Background: Acral melanocytic lesions often pose a diagnostic and therapeutic challenge for many clinicians. Reflectance confocal microscopy (RCM) is an imaging technique widely used for the assessment of skin cancers. The aim of this review is to explore the applicability of RCM for the diagnosis of nevi and melanoma on the acral sites. Methods: Study selection was conducted based on the application of RCM for acral melanocytic lesions. All types of articles (original articles, short reports, and single case reports) were included in the analysis following PRISMA updated guidelines. Results: The search retrieved 18 papers according to the selection criteria; after removing duplicate records and additional articles by one or more of the exclusion criteria, a total of seven studies were carefully evaluated. Conclusions: RCM seems a valuable and useful additional tool for the diagnosis of acral melanocytic lesions, and its use may decrease the need for invasive procedures to some extent. Visualization of deeper layers may be achieved through mechanical removal of the superficial stratum corneum.

LC-OCT for early diagnosis and characterization of dermatologic adverse events to oncologic drugs and correlation to histopathology.

BACKGROUND: Targeted and immune therapies have recently been associated with the occurrence of multiple cutaneous toxicities, often challenging to differentiate by clinical examination alone without histology. Line-field confocal optical coherence tomography (LC-OCT) is a non-invasive and innovative imaging technique that has been shown to be almost as effective as histology in diagnosing several skin conditions. Our study aimed to assess the effectiveness of LC-OCT in predicting the clinical evolution of early maculopapular eruptions related to antineoplastic targeted therapy and immunotherapy. METHODS: In the period between May 2023 and December 2023, consecutive patients with clinical cutaneous maculopapular reactions caused by oncologic targeted therapy or immunotherapy were enrolled at the dermatologic outpatient clinic of the Fondazione Policlinico A. Gemelli IRCCS, Rome. Patients underwent clinical dermatological examination, video-dermoscopy, LC-OCT, and incisional skin biopsy of a target cutaneous lesion. To investigate the evolutionary pattern of maculopapular lesions (psoriasic eruption, lichenoid eruption, eczematous eruption, bullous eruption), LC-OCT and histopathological images have been compared based on specific characteristics (hyperkeratosis, acanthosis, spongiosis; papillomatosis; lichenoid inflammatory infiltrate; presence of intraepidermal/subepidermal cleavage plan with formation of a bulla). RESULTS: Eighteen patients were included in this study (11 males, 7 females, median age 64.5). LC-OCT demonstrated an overall concordance with histology of 77.8%, with a Cohen's Kappa of 0.69 (P < 0.0001). Sensitivity exceeded 70%, and specificity was ≥88.2%. The Area Under the Curve (AUC) ranged from 0.9 to 1 for psoriasis and lichenoid eruption and from 0.7 to 0.9 for eczematous and bullous eruption. CONCLUSIONS: LC-OCT appears to be a promising tool for the early differential diagnosis of adverse skin reactions related to targeted therapy and immunotherapy, offering the potential to avoid skin biopsies in fragile cancer patients.

Confocal Assessment of Pigmented-Mucosal Lesions: A Monocentric, Retrospective Evaluation of Lip and Genital Area.

INTRODUCTION: Pigmentation of lip and/or genitalia is mainly due to the development of benign melanotic macules, with a less occurrence of melanocytic and other non-melanocytic lesions. Mucosal melanoma has worse prognosis compared with cutaneous counterpart, hence identification of atypical features for an early diagnosis is crucial. OBJECTIVES: The aim of this study was to report further data of confocal features characterizing pigmented mucosal lesions of genital area and of the lips and test the diagnostic role of the reflectance confocal microscopy (RCM)lip score. METHODS: Clinical, dermoscopic and RCM images of histologically proven pigmented lesions, involving the genital area (vulva or glans penis) and lip, were retrospectively reviewed. RCM images were evaluated for malignant criteria, and statistical analysis was conducted for categorical variables. RESULTS: Seventy pigmented lesions were included in the study and divided into two groups based on the body area location: lip (17) and genital area (53). Architectural disarray (P = 0.002), dendritic (P = 0.031) and roundish cells in epidermis (P < 0.0001), interpapillary dendritic cells (P = 0.039) and junctional atypical cells (P = 0.002) were associated to genital melanoma. Melanoma involving the lip was characterized by roundish cells in epidermis, a criterion found in one labial benign lesion, only (P = 0.005). Main limitations of the study are the inclusion of low melanomas and the presence of epidermal dendritic cells in melanosis and melanoma, as a confusing factor in imaging. CONCLUSIONS: Dermatologists should consider confocal microscopy as an adjunctive tool to dermoscopy in the differential diagnosis of pigmented mucosal lesions, especially in presence of clinical and dermoscopic findings suspicious for malignancy.

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.

Understanding the Dermoscopic Patterns of Basal Cell Carcinoma Using Line-Field Confocal Tomography.

Basal cell carcinoma (BCC) is the most frequent malignancy in the general population. To date, dermoscopy is considered a key tool for the diagnosis of BCC; nevertheless, line-field confocal optical coherence tomography (LC-OCT), a new non-invasive optical technique, has become increasingly important in clinical practice, allowing for in vivo imaging at cellular resolution. The present study aimed to investigate the possible correlation between the dermoscopic features of BCC and their LC-OCT counterparts. In total, 100 histopathologically confirmed BCC cases were collected at the Dermatologic Clinic of the University of Siena, Italy. Predefined dermoscopic and LC-OCT criteria were retrospectively evaluated, and their frequencies were calculated. The mean (SD) age of our cohort was 65.46 (13.36) years. Overall, BCC lesions were mainly located on the head (49%), and they were predominantly dermoscopically pigmented (59%). Interestingly, all dermoscopic features considered had a statistically significant agreement with the LC-OCT criteria (all p < 0.05). In conclusion, our results showed that dermoscopic patterns may be associated with LC-OCT findings, potentially increasing accuracy in BCC diagnosis. However, further studies are needed in this field.

The Role of Postoperative Radiotherapy in the Management of Dermatofibrosarcoma Protuberans: A Multidisciplinary Systematic Review.

Background: Dermatofibrosarcoma protuberans (DFSP) is a superficial soft tissue sarcoma, and surgical excision is the first-line treatment. The aim of this systematic review is to provide an update about the current indications and clinical results regarding the use of postoperative radiotherapy in DSFP, considering both adjuvant and salvage setting. Methods: We conducted a systematic literature review using the main scientific database, including Cochrane library, Scopus, and PubMed, for any relevant article about the topic, and we considered all available papers without any time restriction. Results: Twenty-two papers, published between 1989 and 2023, were retrieved and considered eligible for inclusion in this review. Regarding the fractionation schedules, most authors reported using standard fractionation (2 Gy/die) with a wide total dose ranging from 50 to 70 Gy. The local control after postoperative radiotherapy was excellent (75-100%), with a median follow-up time of 69 months. Conclusions: After the primary surgical management of DFSP, postoperative radiotherapy may either be considered as adjuvant treatment (presence of risk factors, i.e., close margins, recurrent tumours, aggressive histological subtypes) or as salvage treatment (positive margins) and should be assessed within the frame of multidisciplinary evaluation.

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.

Utility of line-field confocal optical coherence tomography in the pediatric population.

BACKGROUND: In the last decades diagnosis of dermatological diseases has achieved a significant progress with the aid of imaging technologies. In pediatric population dermatologic procedural investigations require special considerations, skill sets, and knowledge. Avoiding unnecessary invasive procedures in children is highly recommended to reduce psychological disturbance and cosmetical scars. Line-field confocal optical coherence tomography (LC-OCT) is an innovative, high-resolution, non-invasive imaging technique, that is proving to be valuable in the diagnosis of different skin conditions. In this study, we aimed to analyze the most common indications for LC-OCT in pediatric age group, discussing its potential role in clinical setting. METHODS: A retrospective review of the medical charts of patients ≤18 years of age, who were performed clinical, dermoscopy and LC-OCT for equivocal skin lesions, was conducted. Diagnostic confidence level was calculated for clinical/dermoscopic diagnosis alone and for combined clinical/dermoscopy and LC-OCT findings, based on a three-point scale ranging from 0% to 100%. RESULTS: Seventy-four skin lesions in 73 patients [(39 (53.4%) females and 34 (46.6%) males, mean age 13.2 (range 5-18 years) years] were investigated with LC-OCT. Diagnosis was established with histopathology in 23/74 (31.1%) cases, while 51/74 (68.9%) skin lesions were monitored over time or treated with topical/physical therapy. High diagnostic confidence increased by 21.6% after LC-OCT assessment, meanwhile reducing low and average score. CONCLUSIONS: LC-OCT may add practical clues for the identification of common skin conditions in pediatric population, improving diagnostic confidence and consequent tailored approach.

Towards AI-driven longevity research: An overview.

While in the past technology has mostly been utilized to store information about the structural configuration of proteins and molecules for research and medical purposes, Artificial Intelligence is nowadays able to learn from the existing data how to predict and model properties and interactions, revealing important knowledge about complex biological processes, such as aging. Modern technologies, moreover, can rely on a broader set of information, including those derived from the next-generation sequencing (e.g., proteomics, lipidomics, and other omics), to understand the interactions between human body and the external environment. This is especially relevant as external factors have been shown to have a key role in aging. As the field of computational systems biology keeps improving and new biomarkers of aging are being developed, artificial intelligence promises to become a major ally of aging research.

Melanocytic Lesions with Peripheral Globules: Proposal of an Integrated Management Algorithm.

INTRODUCTION: A peripheral rim of globules represents a marker of the horizontal growth phase in nevi and is a common feature in children and adolescents. The observation of melanocytic lesions with peripheral globules (MLPGs) in adulthood deserves more attention, since melanoma may exhibit this feature, albeit rarely. Risk-stratified management recommendations considering a global clinical approach are still missing. OBJECTIVES: To analyze current knowledge on MLPGs and propose an integrated management algorithm stratified for age groups. METHODS: We conducted a narrative review of current published data on MLPGs, analyzing clinical dermoscopic and confocal distinguishing features of melanoma from benign nevi. RESULTS: The risk of finding a melanoma when removing an MLPG increases with age, especially in people >55 years old, and is significantly higher in the extremities, head/neck and in case of a single asymmetrical lesion, ≥6 mm in diameter. Dermoscopic features associated with melanoma diagnosis include atypical peripheral globules, asymmetrical distribution, multiple rims as well as the reappearance of globules after prior loss. In addition, wide blue-grey regression areas, atypical networks, eccentric blotches, tan structureless peripheral areas and vascularization are atypical dermoscopic features. Confocal worrisome findings are represented by pagetoid cells within the epidermis, architectural disarrangement and atypical cells of the dermo-epidermal junction with irregular peripheral nests. CONCLUSION: We proposed a multi-step age-stratified management algorithm integrating clinical, dermoscopic and confocal findings that may increase the early recognition of melanoma and avoid surgical excision of benign nevi.