Previous radiotherapy increases the efficacy of cemiplimab in the treatment of locally advanced and metastatic cutaneous squamous cell carcinoma: a retrospective analysis.

BACKGROUND: Cemiplimab, a PD-1 inhibitor approved in 2018 for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (cSCC) who are ineligible for curative therapies, lacks clarity regarding the optimal patient selection despite its known efficacy. OBJECTIVE: This retrospective study aims to assess the real-world treatment patterns and outcomes in patients with cSCC at our institution. METHODS: A retrospective analysis of consecutively treated patients with cemiplimab for cSCC was conducted. Progression-Free Survival (PFS) and Overall Survival (OS) were evaluated alongside clinical-pathologic characteristics. RESULTS: 45 patients were included, of which 73.3% were male with a median age of 77 years. After 18 months of median follow-up median PFS and OS were not reached with a mean of 21.3 months ± 2.2 months and 25.3 ± 2.1 months, respectively. Univariate and multivariate analyses revealed significant correlations only between PFS and previous radiotherapy (p-values: 0.043 and 0.046, respectively). LIMITATIONS: limitations include its retrospective nature, the low number of patients analyzed and the potential for inherent biases. CONCLUSIONS: The study reveals a significant association between prior radiotherapy and improved PFS in cemiplimab-treated cSCC, suggesting the potential for combining radiotherapy with cemiplimab. Further exploration of this combined approach is warranted.

Dermatitis Artefacta: A Retrospective Descriptive Study on 46 Patients.

INTRODUCTION: Self-induced dermatoses are self-inflicted skin lesions, whose occurrence patient denies responsibility for. OBJECTIVES: The aim of this study was to retrospectively investigate all the clinical records of dermatitis artefacta (DA) in order to put special focus on: a) epidemiological aspects; b) location, shape and additional features of the lesions; c) availability of psychiatric details in the records. METHODS: A retrospective observational descriptive study on 46 patients affected by dermatitis artefacta was conducted from January 2015 to March 2021. The only inclusion criterion was clinical or histological diagnosis of DA in patients for which we had clinical images. RESULTS: The most frequent type of lesions were erosions/excoriations and ulcers (14/46, 30.4% and 13/46, 28.3% respectively) followed by ecchymoses (9/46, 19.5%), vasculitis-like lesions (5/46, 10.9%), crusted plaques (3/46, 6.5%), scales (1/46, 2.2%) and erythema (1/46, 2.2%). Thirty-three percent of the medical records generically referred to the presence of psychiatric disorder, but none of them included a specific psychiatric diagnosis. CONCLUSIONS: In our study the main dermatologic lesions observed in DA were represented by excoriations and ulcers and that the shape and location of the lesions are essential for a correct diagnosis.

All for one: Collaboration between dermatologist, radiation oncologist and radiologist in the clinical management of "difficult to treat" non melanoma skin cancer.

This series introduces the clinical management of difficult-to-treat non-melanoma skin cancers (NMSCs) through a multidisciplinary approach, emphasizing the integration of dermoscopy and Ultra high-frequency ultrasound (UHFUS) for accurate diagnosis and treatment planning, particularly in cases referred for radiotherapy (RT). Dermoscopy aids in diagnosing both pigmented and non-pigmented skin lesions, guiding treatment margins and reducing the benign-to-malignant biopsy ratio. UHFUS provides valuable insights into tumor size, depth, and vascularity, complementing clinical evaluations and assisting in RT planning. Three challenging cases are presented, highlighting the pivotal role of dermoscopy and UHFUS in decision-making and treatment optimization. Collaboration between dermatologists, radiation oncologists, and radiologists enhances diagnostic accuracy, tailoring treatment plans to individual patient needs and preferences, ultimately improving patient outcomes and experience. The integration of these imaging techniques holds promise for optimizing non-surgical treatments like RT and monitoring treatment progress, offering a personalized approach to NMSC management.

The Role of Sentinel Node Biopsy in the Era of Adjuvant Therapy for Melanoma.

Sentinel lymph node biopsy (SLNB) is a surgical procedure aimed to detect nodal metastases in patients with clinically occult disease. Since the advent of new systemic therapies, its role in melanoma has been extensively debated over the last years. In this article, three possible scenarios are discussed, considering the SLNB impact on the management of melanoma patients. First, pT1b and pT2a patients with negative SLNB (stages IA and IB) and those with positive SLNB (stage IIIA) would all not benefit from adjuvant treatment. Therefore, SLNB might be avoided in these categories of patients. Second, in IIB and IIC, melanoma patients are already candidates for adjuvant treatment; therefore, SLNB in patients with T3b, T4a, or T4b melanoma would not change treatment decisions. On the other end of the spectrum, patients with pT2b and pT3a melanomas (clinical stage IIA) represent the only two groups whose management would be significantly affected by the SLNB status, being adjuvant therapy only indicated for SLN-positive patients. Further studies are needed to investigate which melanoma patient deserves SLNB.

Tacrolimus in Solution as an Option to Inflammatory Conditions of the Scalp.

INTRODUCTION: Several dermatological diseases lead to inflammatory conditions of the scalp. Most of these afflictions are recalcitrant and require long term maintenance treatment. OBJECTIVES: We present a case series where topical tacrolimus was used in a solution vehicle for these conditions. METHODS: A total of 22 patients (aged 24-90 years) with confirmed diagnosis of lichen planus pilaris (LPP), discoid lupus (DL), frontal fibrosing alopecia (FFA), erosive pustulosis of the scalp (EPS) or folliculitis decalvans (FD) were evaluated and treated with tacrolimus solution (0.1%) applied twice daily for 1 month, then once daily for another month and alternate days for 4 months. Efficacy was evaluated by an investigator global assessment, clinical and dermoscopic evaluation at weeks 4, 8 and 24. The safety assessment included monitoring of all adverse events. RESULTS: The study included 13 patients with LPP, 2 with DL, 2 with FD, 2 with EPS and 3 with AFF. After 1 month, 14 patients (63.6%) had a good response and 7 (31.8%) had excellent response. After 2 months, 16 patients (72.7%) had excellent response, and this response was persistent after 6 months of treatment. CONCLUSIONS: Tacrolimus in solution, even if not yet commercially available, was an effective and well tolerated alternative for the maintenance treatment of inflammatory conditions of the scalp.

Stardust Pattern as Evolution of Pigmented Spitz Nevi During Childhood.

INTRODUCTION: Spitz nevi (SN) are benign melanocytic proliferations frequently occurring in children. Some pigmented SN with a starburst pattern evolve into the "stardust" one, which is characterized by a central, black to gray, hyperpigmented area and remnants of a brown network at the periphery. These dermoscopy changes are often the first alert to induce excision. OBJECTIVES: The aim of this study is to enlarge the case series of stardust SN in children, in order to increase confidence with this new dermoscopic pattern and reduce unnecessary excisions. METHODS: This retrospective observational study was conducted with SN cases received from IDS members. The inclusion criteria were: clinical and/or histopathologic diagnosis of Spitz naevus with starburst appearance in children <12 years old, availability of a dermoscopic image at baseline and after follow-up of at least 1 year, availability of patient data. The dermoscopic images and their changes over time were assessed by three evaluators in consensus. RESULTS: 38 SN were enrolled, with a median age of 7 years and a median FUP duration of 15,5 months. Comparing the evolution with time of FUP, no significant differences were found between growing and involuting lesions in terms of patient age and sex, location and palpability of lesions. CONCLUSIONS: The long follow-up reported in our study could really support the concept of benignity of changing SN. A conservative approach is acceptable for nevi showing the stardust pattern, because it may be considered a physiological evolution of pigmented Spitz nevus, and urgent surgeries could be avoided.

Junctional Nevus and Early Melanoma on Sun-Damaged Skin of the Head/Neck: a Clinico-Pathologic Challenge.

INTRODUCTION: Melanoma on the head/neck area can show subtle clinical, dermoscopic and histologic features at early stages, being difficult to differentiate from junctional nevi. OBJECTIVES: This case series aims to raise awareness on the topic of misdiagnosis of early lentigo maligna as junctional nevi. METHODS: From the databases of three pigmented lesion clinics in Italy, Australia, and France, we retrieved all cases of lesions of the head/neck area with an initial histopathologic diagnosis of junctional nevus (JN) or dysplastic junctional nevus (DJN) which subsequently recurred and were ultimately diagnosed as melanoma. Moreover, we also retrieved those cases with an initial diagnosis of JN/DJN made on a partial biopsy that were diagnosed as melanoma after complete surgical removal. RESULTS: Here we report 14 cases in which the initial histologic diagnosis was junctional nevus or dysplastic junctional nevus. The lesions recurred over time with a final diagnosis of lentigo maligna. CONCLUSIONS: Clinicians should critically question a given histologic diagnosis of junctional or dysplastic junctional nevus on the head/neck area if the clinical or dermoscopic features are discordant. Clinico-pathologic correlation is the best way to increase diagnostic accuracy and optimize management for the patient.

Real-World Experience With Topical 5-Fluorouracil 4% (40 mg/g) Cream for the Treatment of Actinic Keratosis.

INTRODUCTION: 5-fluorouracil (5-FU) is one of the most effective topical treatments for actinic keratosis (AK). A new 4% formulation of 5-FU was recently approved in Europe. OBJECTIVES: This study aimed at evaluating 4% 5-FU cream safety and effectiveness in a real-world setting. METHODS: Adult AK patients were retrospectively selected from the University of Campania Dermatology Unit database. Selection criteria included a diagnosis of non-hyperkeratotic, non-hypertrophic AK (Olsen grade I and II) of the face, ears, and/or scalp, treatment with 4% 5-FU once daily for 4 weeks, and at least 3 follow-up visits (4 and 8 weeks after treatment initiation, and 6 months after treatment end). The primary objectives were to evaluate AK lesions improvement at 8 weeks and relapse rate at 6 months. Patient-reported erythema and burning sensation intensity were also assessed at 4 weeks. RESULTS: Ninety-eight patients were included in this analysis (male/female 80/18, mean age 74.7 years). AK lesions improvement at 8 weeks resulted complete or significant in 74.5% and 20.4% of the patients, respectively. At 6 months, 65.3% of the patients did not show AK relapses. Burning sensation at 4 weeks was reported as light, moderate, or absent by 44.9%, 22.4%, and 31.6% of the patients, respectively. Erythema was reported as light, moderate, or absent by 37.8%, 51%, and 10% of the patients, respectively. Burning sensation and erythema disappeared gradually during follow-up. No other side effects were reported. CONCLUSIONS: In this real-world study 4% 5-FU proved to be highly effective for AK lesions clearance with a favorable safety profile.

The current clinical approach to difficult-to-treat basal cell carcinomas.

INTRODUCTION: Basal cell carcinoma (BCC) is the most common malignant tumor in adult white populations. If BCCs are not treated for years, if they cause massive destruction of the surrounding tissues, if they are considered unresectable or not eligible for radiotherapy they become progressively 'locally advanced' (laBCC) or metastatic (mBCC). These tumors are defined as 'difficult-to-treat BCC.' AREAS COVERED: A comprehensive search on PubMed was conducted to identify relevant literature about the several approved and recommended treatment options for the management of difficult-to-treat BCC published from January 2012 to July 2022. Surgical options, radiotherapy, hedgehog inhibitors, immunotherapy, and combined treatments are discussed. The keywords used were basal cell carcinoma; difficult-to-treat BCC; management of difficult-to-treat BCC; surgical therapy; radiotherapy; hedgehog inhibitors; immunotherapy. EXPERT OPINION: Identifying the best approach to DTT BCCs is one of the main challenges for the dermato-oncologist. The introduction of HHI for the treatment of advanced BCCs has revolutionized the clinical management of DTT BCCs. The immune checkpoint inhibitor cemiplimab has been approved for the treatment of locally advanced or metastatic BCC refractory to HHI therapy or in patients intolerant to HHI therapy. Multidisciplinary teams (MDTs) play a key role in managing these complex patients.

Reflectance confocal microscopy in paediatric patients: Applications and limits.

Reflectance confocal microscopy (RCM) is a non-invasive diagnostic tool extensively studied for adult patients. In this retrospective case series conducted at the Dermatology Unit of the University of Campania, Naples, Italy, all patients under 19 years old who were submitted to RCM from January 2011 to December 2021 where evaluated. The aim of the study was to review the most usual indications and possible benefits that it might add for children. Data collection included 215 patients (86 males and 129 females, mean age: 12). Most of the exams (n = 85; 39.5%) were performed for lesions clinically compatible with Spitz nevi, congenital nevi (n = 50 23,2%) and atypical melanocytic lesions (n = 46; 21%) among which two melanomas were detected. RCM can be an useful instrument when evaluating paediatric patients and may help avoid unnecessary biopsy in most cases, representing an additional instrument to improve diagnostic accuracy.

Melanocytic or Not? Dermoscopy and Reflectance Confocal Microscopy for Lesions Difficult to Diagnose: A Cross-Sectional Diagnostic Accuracy Study.

BACKGROUND: Different techniques for non-invasive skin examination and early diagnosis of skin lesions are available nowadays, being dermoscopy and reflectance confocal microscopy (RCM) the most diffused ones. Several studies supported the complementary use of dermoscopy and RCM that improves diagnostic accuracy when dealing with melanocytic lesions. OBJECTIVES: To analyze RCM diagnostic accuracy in the differential diagnosis between melanocytic and non-melanocytic lesions. METHODS: This is a cohort selected cross-sectional study conducted at the Dermatology Unit of the University of Campania L. Vanvitelli, Naples, Italy, from 2012 to 2020. We searched the image database for all excised lesions for which the clinical and dermatoscopic differential diagnosis was between melanocytic and non-melanocytic and for which an RCM examination was performed. Sensitivity, specificity, and diagnostic accuracy values were estimated. RESULTS: The study included 53 cases that were found to have disagreement between clinical, histological and RCM diagnosis, of which, in 31 cases the differential diagnosis was melanocytic vs non-melanocytic lesion. The RCM reached a specificity of 87% (95% CI: 0.73-1) and a sensitivity of 62.5% (95% CI: 0.29-0.96) in the present sample. Diagnostic accuracy was 80.6% (95% CI: 0.67-0.94). CONCLUSION: RCM has a high specificity in differentiating between difficult-to-diagnose melanocytic and non-melanocytic lesions.

Diagnosis and Management of Melanoma of the Scalp: A Review of the Literature.

Cutaneous melanoma is a public health issue and the head and neck region is of particular interest, despite accounting for only 9.0% of the total body surface, it harbours 20% of melanoma cases. Data from the literature show that scalp melanomas (SM) carry high mortality rates, with a 10-year survival rate of 60% which lead them to be named as the "invisible killer". Moreover, SMs are more common in the elderly than in young population, and they occur six times more frequently in men than in women. This is probably related to the higher incidence of androgenetic alopecia and a higher cumulative and intermittent ultraviolet damage on the scalp. Histologically, SM is a heterogenous group, including lentiginous melanoma (LM), desmoplastic melanoma, superficial spreading and nodular melanoma. Thin melanomas tend to display an atypical network or pseudo-network and regression in dermoscopy. Blue-white veil, irregular pigmented blotches and an unspecific pattern are most commonly detected in thick lesions. On reflectance confocal microscopy (RCM), the most frequent pattern is irregular meshwork, but also ringed and disarranged pattern have been described. Differential diagnosis includes benign solar lentigo, actinic keratoses, lichen planus like keratosis, melanocytic nevi and blue nevi. All suspicious lesions should be biopsied; therefore, an excisional biopsy with 2 mm margins is usually the best option. The management of SM is the same as for melanoma on other body sites. However, sentinel node biopsy tends to be more challenging, as well as achieving adequate excision margins of the primary tumor. In this review, we summarize clinical, pathologic, dermoscopic and RCM features of SM, and focus on its epidemiology, risk factors and best management options.

KPC-producing Enterobacter aerogenes infection.

BACKGROUND: Enterobacter is a common nosocomial microorganism and its carbapenem's resistance has increased. The management of these cases is unclear. OBJECTIVE: We evaluated 16 patients with KPC-producing Enterobacter aerogenes infections, detailing the site of infection, therapy, clinical and epidemiological data. METHODS: A retrospective and descriptive study. Clinical data were revised and KPC-2 detection was by molecular methods. Risk factors associated with mortality were compared using appropriate tests according to variable type with a significance level of 0.05. RESULTS: The 30-day mortality rate was 37.5% with no association with inadequate treatment. Age (p=0.004) and Charlson score of comorbidities (p=0.048) were independent risk factors associated with death in the multivariate analysis. The odds ratio for age >43 years was 3.00 (95% CI: 1.02-9.32) and for Charlson score >3 was 2.00 (95% CI: 1.08-3.71). Five strains were pan-resistant based on automated susceptibility tests. All patients were treated with monotherapy. CONCLUSION: The clinician should be alert to carbapenem-resistant Enterobacteriaceae infection in older patients with comorbidities. The mortality is high and we believe that prompt and adequate therapy must be employed.