Sonidegib is a Hedgehog pathway inhibitor (HHI) used as a first-line systemic treatment for patients with advanced basal cell carcinoma (aBCC). Alopecia is reported as a frequent adverse event (AE), occurring in 49% of patients. Forty-five patients with aBCC were treated with sonidegib between December 2022 and December 2023; among them, 11/45 patients developed alopecia. Trichoscopic features included yellow dots, black dots, exclamation mark hairs, and broken hairs. Upon LC-OCT examination, yellow dots were seen as dilated follicular dark spaces containing malted, nonhomogeneous material and outlined by bright collarets. Black dots corresponded to normal-sized follicular ostia filled with bright, homogeneous material and cadaverized hair. Exclamation mark hairs were short, dark dysmorphic hairs with different sizes of proximal and distal ends, and broken hairs were short dysmorphic hairs. LC-OCT may provide additional insights into early signs and clinical evolution of sonidegib-induced alopecia in patients with aBCC.

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.

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.

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.

Background: Mohs micrographic surgery (MMS) is the preferred surgical approach for high-risk basal cell carcinoma (BCC). Pre-surgical tumor margins delineation with line field confocal optical coherence tomography (LC-OCT) is expected to reduce MMS stages number. Objective: to investigate the effectiveness of LC-OCT preoperative evaluation of high-risk BCC margins in reducing the number of MMS stages to achieve tumor clearance. Patients and methods: high-risk BCC patients undergoing MMS at Policlinico A. Gemelli Foundation, IRCCS - Rome during January 2018 - December 2022. The LC-OCT group included patients undergoing preoperative lateral tumor margin demarcation by clinical, dermoscopic, and LC-OCT examination; patients in the control group underwent preoperative lateral tumor margin demarcation by clinical and dermoscopic examination only. LC-OCT imaging was compared to MMS histopathological sections. Results: 63 facial high-risk BCCs from 60 patients, mean age of 68.3 years (SD 11.9). The LC-OCT and the control group included 22 and 41 BCCs, respectively. LC-OCT imaging showed almost perfect agreement with histopathology for low- versus high-risk of recurrence BCC histopathological subtypes discrimination (Cohen's kappa 0.88). We reported a significant difference in the mean number of MMS stages between the LC-OCT and the control group (1.23 +/- 0.43 SD, and 1.89 +/- 1.05 SD, respectively; p-value =0.007). At univariate regression analysis, LC-OCT preoperative mapping of BCC tumor margins significantly reduced patients' risk of undergoing >1 MMS stage (crude odds ratio [ORc]: 0.3 95% CI 0.1-0.8, p-value =0.032). Conclusion: LC-OCT preoperative evaluation of high-risk BCC margins significantly reduced the number of MMS stages to achieve tumor clearance.

Background/Objectives: Hidrocystomas, eccrine and apocrine, are rare cystic lesions that form benign tumors of the sweat glands. This study aimed to describe the clinical features of hidrocystomas and evaluate the role of non-invasive imaging techniques, including dermoscopy, Line-field Confocal Optical Coherence Tomography (LC-OCT), Reflectance Confocal Microscopy (RCM), and Ultra-High-Frequency Ultrasound (UHFUS), in their diagnosis. Methods: In total, seven cases of hidrocystomas were collected from the Dermatologic Clinic of the University of Siena, Italy. Predefined dermoscopic, LC-OCT, RCM, and UHFUS features were retrospectively described. Results: Overall, hidrocystomas were located on the face, mainly presenting as blue/purple-bluish translucent papules (71%). Dermoscopic examination revealed a homogeneous purple-bluish color (71%), white pale halo (71%), and shiny globules at the periphery (57%). LC-OCT identified a hyporeflective cupoliform round structure in the dermis with a bright and thick contour, while UHFUS showed a round structure in the dermis filled with hypoechoic content. Conclusions: Non-invasive imaging techniques could significantly enhance the diagnostic accuracy of hidrocystomas, aid in differentiation from other lesions, and minimize unnecessary biopsies.

BACKGROUND:Porokeratosis variants are relatively rare and can be clinically misdiagnosed with several common papulokeratotic mimickers. Line-field confocal optical coherence tomography (LC-OCT) is a new technology able to explore the skin in vivo up to a depth of 500 µm. OBJECTIVES:To investigate the role of LC-OCT in the diagnosis of many porokeratosis variants in a preliminary study. METHOD:In total, 130 LC-OCT images were obtained from 98 patients, 45 affected by a porokeratosis variant (69 images) and 53 with a mimicker condition (61 images). RESULTS:We found almost perfect interobserver agreement for LC-OCT image interpretation and perfect correspondence with the findings from histological slides. In addition, a series of morphological in vivo and three-dimensional features related to the cornoid lamella were detected by LC-OCT that were not visible from the histology. CONCLUSIONS:This device can be proposed to assist with rapid bedside noninvasive differentiation of porokeratosis variants from their mimickers, possibly sparing incisional biopsy in patients where the diagnosis is uncertain.

Basal cell carcinoma accounts for 75% of skin cancers worldwide and is the most common malignancy in Caucasians. Since chronic ultraviolet exposure is the major risk factor for its development, sun-exposed areas such as the face are frequently affected. The gold-standard treatment is surgical excision. Radiotherapy may be considered in selected cases such as unresectable primary tumors. In some patients, when the risk of a significant functional/cosmetic deficit advises against both surgery and radiotherapy, target therapy (hedgehog pathway inhibitors) can be administered alone or in a neoadjuvant setting, to reduce the tumor size and make it eligible for surgery. Vismodegib as a neoadjuvant treatment before surgery has been investigated in a single, multicentre, open-label, phase II trial (VISMONEO); however, sonidegib has not yet been evaluated in this setting. We report the cases of two patients with locally advanced basal cell carcinoma of the face who achieved complete remission with sonidegib followed by a more limited surgical excision than would have been needed without target therapy.

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.

The reticulated black solar lentigo was initially described by Bolognia et al. in 1992 as a type of solar lentigo.1 Ink spot lentigo (ISL), as commonly known, clinically presents as a solitary dark pigmented macule with ill-defined margins occurring on the back of fair skin individuals. Due to the peculiar appearance and the common association with multiple solar lentigos, ISL may be difficult to differentiate from melanoma.1, 2 Dermoscopy may show criteria similar to those observed in melanocytic lesions as an irregular thick pigment network, angulated lines and rhomboidal structures, and in these cases biopsy should be considered to rule out malignancy.2, 3 The use of noninvasive imaging techniques, like reflectance confocal microscopy (RCM), increases the diagnostic accuracy of equivocal skin lesions, allowing to obtain greater performances than dermoscopy alone.4, 5 A new digital tool, Line-field confocal optical coherence tomography (LC-OCT), is capable to acquire images/videos of skin lesions in multimodal view (vertical and horizontal), creating also immediate 3D cubes.6 Pivotal studies reported promising preliminary data for the in vivo diagnosis of skin cancers.6-8 We report RCM and LC-OCT morphological features of consecutive ISLs, correlating in vivo imaging to histopathology. Twenty-five histopathologically confirmed ISLs of 24 patients (14 M, 10 F, mean age: 48 years old, range: 19–82 years old) were investigated by RCM and LC-OCT from January 2023 to January 2024. ISLs were located on the trunk (10/25, 40%), on the face (7/25, 28%), on the lower extremities (4/25, 16%) and upper extremities (4/25, 16%). Dermoscopy showed atypical (thick, unevenly distributed) pigment network with sharp margins (23/25, 92%), and angulated lines (5/25, 20%) (Figures 1 and 2). RCM mosaics and horizontal sections of LC-OCT displayed densely packed, round to polymorphous edged papillae (24/25, 96%) at dermal-epidermal junction (DEJ), variably associated to bright cords with bulbous projections (19/25, 76%); focal distribution of plump, bright cells in the papillary dermis (20/25, 80%) and keratin-filled invaginations (3/25, 12%) in the upper layers of epidermis (Figure 1). Vertical LC-OCT mode revealed a bright continuous junction (25/25) with evident tubular elongations downward in the dermis (23/25); 3D reconstructions highlighted the presence of architectural changes at the DEJ with a regular epidermis (Figure 2). Criteria indicating melanocytic nature of ISL were not seen either with RCM or with LC-OCT. In our ISLs series, RCM and LC-OCT allowed the clear recognition of typical features associated to a solar lentigo, confirming the benign nature of the lesion.6, 9 The RCM findings are in line with a single case-report recently described by Venturi et al., observing RCM features of ringed pattern with edged papillae, white reticulated collagen, and small inflammatory cells. The recognition of such findings allowed the authors to confirm the diagnosis of ISL with no need of further excisions.9 Compared to RCM, which only provides horizontally oriented images reaching a depth of 150–200 µm, LC-OCT can detect features of skin lesions up to a depth of 500 µm even in vertical and 3D mode, closely resembling a classical histopathological perspective. In this series, the main histopathological criteria of ISL, lentiginous hyperplasia of the epidermis and hyperpigmentation of the basal layer (quite pronounced at the tips of elongated rete ridges) have been clearly recognized with LC-OCT, able to reproduce a "virtual biopsy" that detect in vivo the key clues of this entity. As digital imaging represents a bridge between dermoscopy and histopathology, it has a meaningful diagnostic value for skin lesions of doubtful interpretation, as commonly occur when dealing with ISL.4, 5 The recognition of typical imaging suggestive of a solar lentigo (being ISL a solar lentigo) may increase diagnostic confidence of clinicians, which could in turn optimize their clinical management, as well as reducing unnecessary invasive procedures. Marisa Salvi, Alessandro Di Stefani, and Simone Cappilli: Conceptualization; Gerardo Palmisano and Costantino Ricci: Methodology; Marisa Salvi and Simone Cappilli: Original draft preparation; Alessandro Di Stefani and Ketty Peris: Review and editing; Ketty Peris: Supervision. All authors have read and agreed to the published version of the manuscript. Peris has received consulting fees and honoraria from Abbvie, Almirall, Biogen, Celgene, Janssen Galderma, Novartis, Lilly, Novartis, Pierre Fabre, Sandoz, Sanofi and Sun Pharma outside of the submitted work. The remaining authors declare no conflict of interest. This study was conducted in accordance with the Declaration of Helsinki. All patients in this manuscript have given written informed consent for participation in the study and the use of their deidentified, anonymized, aggregated data and their case details (including photographs) for publication. Ethical Approval: not applicable.

International Journal of DermatologyEarly View Clinical Correspondence Solitary cutaneous focal mucinosis: In-vivo line-field confocal optical coherence tomography (LC-OCT) features correlate to histopathology Gerardo Palmisano, Gerardo Palmisano UOC di Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A, Gemelli - IRCCS, Rome, Italy Dermatologia, Università Cattolica del Sacro Cuore, Rome, ItalySearch for more papers by this authorSimone Cappilli, Corresponding Author Simone Cappilli [email protected] orcid.org/0000-0001-9813-2391 UOC di Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A, Gemelli - IRCCS, Rome, Italy Dermatologia, Università Cattolica del Sacro Cuore, Rome, ItalySearch for more papers by this authorAnna P. Lugli, Anna P. Lugli UOC di Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A, Gemelli - IRCCS, Rome, Italy Dermatologia, Università Cattolica del Sacro Cuore, Rome, ItalySearch for more papers by this authorAlessandro Di Stefani, Alessandro Di Stefani orcid.org/0000-0001-8283-2633 UOC di Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A, Gemelli - IRCCS, Rome, Italy Dermatologia, Università Cattolica del Sacro Cuore, Rome, ItalySearch for more papers by this authorKetty Peris, Ketty Peris UOC di Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A, Gemelli - IRCCS, Rome, Italy Dermatologia, Università Cattolica del Sacro Cuore, Rome, ItalySearch for more papers by this author Gerardo Palmisano, Gerardo Palmisano UOC di Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A, Gemelli - IRCCS, Rome, Italy Dermatologia, Università Cattolica del Sacro Cuore, Rome, ItalySearch for more papers by this authorSimone Cappilli, Corresponding Author Simone Cappilli [email protected] orcid.org/0000-0001-9813-2391 UOC di Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A, Gemelli - IRCCS, Rome, Italy Dermatologia, Università Cattolica del Sacro Cuore, Rome, ItalySearch for more papers by this authorAnna P. Lugli, Anna P. Lugli UOC di Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A, Gemelli - IRCCS, Rome, Italy Dermatologia, Università Cattolica del Sacro Cuore, Rome, ItalySearch for more papers by this authorAlessandro Di Stefani, Alessandro Di Stefani orcid.org/0000-0001-8283-2633 UOC di Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A, Gemelli - IRCCS, Rome, Italy Dermatologia, Università Cattolica del Sacro Cuore, Rome, ItalySearch for more papers by this authorKetty Peris, Ketty Peris UOC di Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A, Gemelli - IRCCS, Rome, Italy Dermatologia, Università Cattolica del Sacro Cuore, Rome, ItalySearch for more papers by this author First published: 28 February 2024 https://doi.org/10.1111/ijd.17118 Conflict of interest: None. Funding source: None. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1Rongioletti F, Rebora A. Cutaneous mucinoses: microscopic criteria for diagnosis. Am J Dermatopathol. 2001; 23: 257–267. 10.1097/00000372-200106000-00022 CASPubMedWeb of Science®Google Scholar 2Kuo KL, Lee LY, Kuo TT. Solitary cutaneous focal mucinosis: a clinicopathological study of 11 cases of soft fibroma-like cutaneous mucinous lesions. J Dermatol. 2017; 44: 335–338. 10.1111/1346-8138.13523 CASPubMedWeb of Science®Google Scholar 3Chen W, Xie Y, Wang L. A case of papulonodular mucinosis with Sjogren's syndrome. Int J Dermatol. 2022; 61: 621–622. 10.1111/ijd.15981 PubMedWeb of Science®Google Scholar 4Biondo G, Sola S, Pastorino C, Massone C. Clinical, dermoscopic, and histologic aspects of two cases of cutaneous focal mucinosis. An Bras Dermatol. 2019; 94: 334–336. 10.1590/abd1806-4841.20198381 PubMedWeb of Science®Google Scholar 5Suppa M, Palmisano G, Tognetti L, Lenoir C, Cappilli S, Fontaine M, et al. Line-field confocal optical coherence tomography in melanocytic and non-melanocytic skin tumors. Ital J Dermatol Venerol. 2023; 158: 180–189. PubMedGoogle Scholar Early ViewOnline Version of Record before inclusion in an issue ReferencesRelatedInformation

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.

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.

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.