Reflectance confocal microscopy as noninvasive tool for monitoring tirbanibulin efficacy in actinic keratosis.

Actinic keratosis (AK) is a common precancerous condition found on sun-damaged skin. Tirbanibulin 1 % ointment has been approved for the topical treatment of non-hyperkeratotic facial and scalp Olsen grade I AKs over a contiguous area of 25 cm2 with a daily application for 5 consecutive days. Our aim was to investigate the use of in vivo RCM in the assessment of the response of AKs treated with tirbanibulin, as it has never been described in the published Literature. A total of 10 AKs in 10 consecutive outpatients were enrolled in the present study in May 2023. The follow-up visit was scheduled after 30 days from last application of tirbanibulin ointment. At follow-up visit, a complete response was described by clinical, dermoscopic and in vivo RCM examination in 10 out of 10 lesions, with a recovery of stratum corneum, decrease in atypical honeycomb pattern and changes in dermal collagen. All patients were followed up for at least 8 months and further recurrences were not registered. Based on our experience, we confirm the efficacy and safety of tirbanibulin in treating AKs and the usefulness of RCM in vivo examination for the therapeutic monitoring of such lesions, even in a very early stage.

Association of miR-146a-5p and miR-21-5p with Prognostic Features in Melanomas.

BACKGROUND: Cutaneous melanoma (CM) is one of the most lethal tumors among skin cancers and its incidence is rising worldwide. Recent data support the role of microRNAs (miRNAs) in melanoma carcinogenesis and their potential use as disease biomarkers. METHODS: We quantified the expression of miR-146a-5p and miR-21-5p in 170 formalin-fixed paraffin embedded (FFPE) samples of CM, namely 116 superficial spreading melanoma (SSM), 26 nodular melanoma (NM), and 28 lentigo maligna melanoma (LMM). We correlated miRNA expression with specific histopathologic features including Breslow thickness (BT), histological subtype, ulceration and regression status, and mitotic index. RESULTS: miR-146a-5p and miR-21-5p were significantly higher in NM compared to SSM and LMM. The positive correlation between miR-146a-5p and miR-21-5p expression and BT was confirmed for both miRNAs in SSM. Considering the ulceration status, we assessed that individual miR-21-5p expression was significantly higher in ulcerated CMs. The increased combined expression of the two miRNAs was strongly associated with ulceration (p = 0.0093) and higher mitotic rate (≥1/mm2) (p = 0.0005). We demonstrated that the combination of two-miRNA expression and prognostic features (BT and ulceration) can better differentiate cutaneous melanoma prognostic groups, considering overall survival and time-to-relapse clinical outcomes. Specifically, miRNA expression can further stratify prognostic groups among patients with BT ≥ 0.8 mm but without ulceration. Our findings provide further insights into the characterization of CM with specific prognostic features. The graphical abstract was created with BioRender.com.

Molecular Characterization of Advanced-Stage Melanomas in Clinical Practice Using a Laboratory-Developed Next-Generation Sequencing Panel.

Cutaneous melanoma is one of the most lethal tumors among skin cancers, characterized by complex genetic and molecular alterations that result in uncontrolled cell proliferation and metastatic spread. Next-generation sequencing (NGS) enables the simultaneous examination of numerous genes, making this molecular technique essential for melanoma diagnosis, prognostic stratification, and therapy planning. Herein, we present the experience with our laboratory-designed NGS panel for the routine assessment of advanced-stage melanoma. A total of 260 specimens of advanced-stage melanomas were evaluated utilizing a laboratory-developed multi-gene NGS panel, which allowed the investigation of 229 amplicons in 25 oncogene/oncosuppressor genes. The NGS panel proved to be a reliable tool, failing to produce results in only 1.2% of the samples tested. BRAF and TERT were the two more commonly altered genes in 44.0% and 59.9% of samples, respectively. In 59.3% of the mutated cases, at least two concomitant variants were detected. In eight cases, both primary lesion and metastatic disease were analyzed by NGS. In all specimens (8/8, 100%), a perfect concordance in variants harbored by the primary and recurrence lesions was observed. Finally, this study described the validity of a laboratory-developed multi-gene NGS panel built specifically for advanced-stage melanomas in ordinary clinical practice.

The importance of caregivers for patients with advanced basal cell carcinoma treated with hedgehog-pathway inhibitors: an observational prospective study.

Oral targeted therapy with hedgehog pathway inhibitors has revolutionized the standard of care for patients with advanced basal cell carcinoma (BCC). These patients are frail and elderly, have various comorbidities, and receive pharmacological polytherapy. Moreover, adverse events may have a significant impact on therapeutic adherence, which must be managed by the clinician. We evaluated the impact of caregivers on the treatment of patients with advanced BCC in terms of continuation of therapy over time. All patients included in this observational prospective study had histologically confirmed metastatic or locally advanced BCC (LaBCC) and were treated with hedgehog pathway inhibitors from January 2016 to December 2021 at the Department of Dermatology at the University of Florence, Italy. The collected patient data included: age, sex, BCC site and area of spread; number of cycles, dose, duration and tolerability of therapy; marital status (single, divorced, married/living with a partner, widow/widower); and information such as living with someone, and the presence of any caregivers. Of the 34 patients included, 33 had LaBCC and one metastatic BCC. There were 11 females (32.4%) and 23 males (67.6%). Patients who were married or living with a caregiver -tolerated therapy better than single patients who lived alone. Indeed, patients with married/live-in caregivers and/or those with an adequate caregiver experienced greater therapeutic adherence and tolerance of adverse events. Given the greater therapeutic adherence of patients with live-in caregivers as partners, it is essential to consider patients' marital status. It is advisable to involve the caregiver early on, and there should be a training discussion on the various possible adverse events and the best way to mitigate them. Therapeutic success is linked not only to patients being informed but also to training of caregivers.

Dermoscopy as a Tool for Identifying Potentially Metastatic Thin Melanoma: A Clinical-Dermoscopic and Histopathological Case-Control Study.

Despite being early-stage tumors, thin cutaneous melanomas contribute significantly to mortality and have a rising incidence. A retrospective case-control study was performed to identify clinical-dermoscopic and histopathological variables linked to local and distant metastases in melanomas ≤0.8 mm. Data from 1 January 2000 to 22 June 2022 were analyzed from two Italian skin cancer referral centers. Sixteen patients with ≤0.8 mm melanomas developing metastases were studied compared to controls without metastases over 5 years. Statistical analysis involved Pearson's chi-squared test or Fisher's exact test. Of the 1396 cases, 1.1% progressed. The median diagnosis age was 49 (range 28-83), with 56.3% men and 43.7% women. The torso was the primary tumor site (43.7%). Clinically, lesions were pigmented (>10 mm diameter: 73.3%, ≥3 colors: 80%). Dermoscopically, the common features were white patches (73.3%), atypical vascular patterns (66.5%), blue-gray areas (60%) and absent pigment networks (60%). Histopathologically, all cases had adverse features like regression (87.4%), dermal mitoses (50%), a vertical growth phase (62.5%) and ulceration (12.5%). These findings were statistically significant compared to controls (p < 0.05). In ≤0.8 mm melanomas, specific clinical-dermoscopic traits might indicate higher metastatic potential when paired with adverse histopathological features.

Influence of Vitreous Cortex Remnants on Normal Retinal Anatomy in Eyes with Primary Rhegmatogenous Retinal Detachment.

PURPOSE: To investigate the influence of vitreous cortex remnants (VCRs) removal on normal retinal anatomy in eyes with rhegmatogenous retinal detachment (RRD). DESIGN: Prospective cohort study. SUBJECTS: Patients with primary RRD operated with pars plana vitrectomy (PPV). METHODS: Blue fundus autofluorescence and spectral-domain OCT were obtained preoperatively, and at 1 and 6 months after operation. MAIN OUTCOME MEASURES: Primary outcomes: rate of retinal displacement and outer retinal folds (ORFs) at 1 month after operation. SECONDARY OUTCOMES: continuity of the external limiting membrane (ELM) and ellipsoid zone (EZ), and the logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) at 6 months after operation. RESULTS: One hundred three eyes were included. Intraoperatively, peripheral VCRs (pVCRs) were found in 42 eyes (40.8%) and successfully peeled off from ≥2 quadrants in 37 eyes. Macular VCRs (mVCRs) were detected in 37 (35.9%) and successfully peeled off in 29 eyes. At the end of operation 44.7% and 55.3% of the eyes were tamponaded with 20% sulfur hexafluoride gas and silicone oil 1000 centistokes, respectively. The only variable significantly associated with displacement was the use of gas tamponade versus silicone oil (P = 0.001), whereas no significant association was found between retinal displacement and pVCRs (P = 0.58) or number of quadrants from which pVCRs were peeled off (P = 0.39). At 1 month postoperatively, ORFs were globally detected in 24 eyes (23.3%). Regression analysis showed a direct correlation between ORFs and the intraoperative detection of mVCRs (P = 0.02) and an indirect correlation between ORFs and mVCRs peeling (P = 0.004). Macular VCRs peeling did not influence the continuity of ELM and EZ at the 6-month follow-up (FU). Intraoperative absence of mVCRs (P = 0.0016) and peeling of mVCRs (P = 0.003) were associated with logMAR BCVA ≤0.3 at the 6-month FU. CONCLUSIONS: Peeling of pVCRs did not seem to influence the rate of retinal displacement, whereas peeling of mVCRs was associated with a reduced risk of developing ORFs without detrimental effect on the continuity of ELM/EZ at 6-month FU. The patients without mVCRs detected intraoperatively, or who underwent mVCRs peeling during operation, showed a significantly better visual acuity at the 6-month FU. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Reflectance Confocal Microscopy Combined with Dermoscopy and Histology in the Diagnostic Setting of Pigmented Eccrine Poroma: A Retrospective Study.

INTRODUCTION: Pigmented eccrine poroma (PEP) is a unique variant of a benign adnexal tumor known as eccrine poroma. Distinguishing PEPs from other pigmented lesions can be challenging due to overlapping clinical and dermoscopic features. OBJECTIVES: To provide a comprehensive analysis of the dermoscopic, confocal (RCM), and histological features of PEPs. METHODS: We undertook a retrospective study of the clinical, dermoscopic, RCM and histopathological features of PEPs that were surgically excised and histopathologically recognized. Data on epidemiological, clinical, dermoscopic, RCM and histopathological features were collected from the databases of the Skin Cancer Unit, IRCCS Policlinico di Sant' Orsola, between January 2021 and May 2023. RESULTS: The study population consisted of 61 patients, including 34 females (55.7%) and 27 males (44.3%). Dermoscopic examination of 61 PEPs revealed the presence of irregular borders (55.7%), milia-like cysts (50.8%), brown pseudo-network (41%), cerebriform pattern (34.4%), comedo-like openings (29.5%), atypical vessels (26.2%), glomerular vessels (18%), fingerprint-like perifollicular structures (8.2%), dots (4.9%) and dotted vessels (4.9%). RCM imaging was collected from 11 cases and showed mostly well-defined tumor nests with small cells in 100% of cases, bright structures in the upper dermis representing melanocytes and melanophages (63.6%), dark round spaces within the tumor nests (54.5%), well-demarcated borders of the nest (45.5%) and dilated and prominent vessels in upper dermis (27.3%). Histopathological pattern analysis revealed PEP sensu stricto (PEPss) as the most frequent (54.1%). CONCLUSIONS: The distinctive dermoscopic patterns, along with the confocal features aid in the differentiation from other pigmented lesions.

Assessment of Vulvar Intraepithelial Neoplasia (VIN) Grades Based on Dermoscopic Features: A Diagnostic Study.

INTRODUCTION: Vulvar intraepithelial neoplasia (VIN) is a vulvar skin lesion considered a precursor of vulvar squamous cell carcinoma. No characteristics have been discovered to date that allows us to differentiate between grades of VIN, such as correlating the thickness of involvement of the epithelium (VIN1, VIN2, and VIN3) to the dermoscopic pattern. OBJECTIVES: The aim of this study was to correlate the clinical and dermoscopic features of VIN cases with histopathological findings, with the purpose of identifying dermoscopic characteristics that allow us to differentiate between different grades of VIN. METHODS: A retrospective study of the clinical and dermoscopic characteristics of VINs was recruited. Clinical and dermoscopic characteristics, as well as histopathology data, were gathered from patients at two Dermatology Units in Italy during the period spanning from January 2020 to December 2021. RESULTS: The study population consisted of 20 patients with a histologically confirmed diagnosis of VIN. The mean age of patients at the time of diagnosis was 55 years. At the dermoscopic level, VIN1 was characterized by a homogeneous erythematous area that completely involved the entire lesion, with a vascular pattern consisting of regular glomerular vessels. VIN3, was characterized by the presence of compact milky white areas that involved almost the entire lesion. VIN2 was characterized by the presence of non-compact white areas that allowed homogeneous erythematous areas to be seen transparently, without other distinguishing aspects. CONCLUSIONS: Although a definitive diagnosis and grading of VIN remains confirmed only histopathologically, our study shows how dermoscopy may aid the differential diagnosis between the different grades of VIN; the presence of a compact milky white area that involves nearly the entire lesion should be interpreted as an alarming feature, while homogeneous erythematous areas or a glomerular vascular pattern are more typical of the first stage of this neoplasia.

Tolerance of sonidegib after intolerance of vismodegib-Experience in two patients with nevoid basal cell carcinoma syndrome (Gorlin syndrome).

Nevoid basal cell carcinoma syndrome (NBCCS, Gorlin syndrome) is a rare genetic condition characterized by the early development of numerous cutaneous basal cell carcinomas (BCCs). Although most BCCs are surgically treated with total resection, some of the lesions may proceed to a locally advanced or metastatic stage. Systemic treatment with a hedgehog inhibitors (HHIs) such as Vismodegib or Sonidegib is indicated in this population. We report cases of two patients with confirmed diagnoses of NBCCS. Both patients had undergone multiple surgical excisions and had been treated with oral Vismodegib 150 mg/day for a locally advanced tumour. They both discontinued the therapy due to its specific adverse effects (AEs) and are now being treated with oral Sonidegib, which has had better tolerability and a complete response. The aims of this report was to demonstrate the efficacy of HHI treatment with Sonidegib in patients with NCBBS who had previously treated with Vismodegib but discontinued it because of its specific AEs. Our experience in two patients shows that Sonidegib can be considered in Gorlin patients intolerant but responding to Vismodegib.