Alessandro Di Stefani

Line‐field confocal optical coherence tomography (LC‐OCT) is an emerging non‐invasive imaging technique that provides real‐time vertical, horizontal, and three‐dimensional visualization of the skin at near‐cellular resolution. We systematically reviewed the available evidence on LC‐OCT in melanocytic lesions to identify diagnostic features associated with melanoma and to clarify its current clinical role. MEDLINE/PubMed, Scopus, Embase, and Web of Science were searched from inception to September 2026 in accordance with PRISMA recommendations. Thirty‐two studies were included, encompassing cutaneous melanoma, lentigo maligna, and facial pigmented lesions, benign and atypical melanocytic lesions, and mucosal melanoma. Across studies, melanoma‐associated findings included irregular or disorganized epidermal architecture, numerous or pleomorphic pagetoid cells, disruption or blurring of the dermoepidermal junction, atypical dermal nests, and clefting. In lentigo maligna and facial melanoma, peri‐adnexal atypia and follicular involvement emerged as particularly relevant features, whereas mucosal melanoma was characterized by diffuse pagetoid spread, epithelial disarray, atypical junctional cells, and discohesive melanocytic nests. Benign lesions more often showed preserved epidermal architecture, a well‐defined junction, organized nests, and a regular wave‐like dermal pattern. However, substantial overlap was observed with atypical nevi, spitzoid lesions, blue nevi, melanosis, and other intermediate entities. Although selected studies reported promising diagnostic performance, the evidence remains heterogeneous and is largely based on small, descriptive cohorts. LC‐OCT may therefore serve as a useful adjunct in clinically or dermoscopically equivocal melanocytic lesions, but prospective multicenter validation and assessment of reproducibility are required before widespread routine implementation. image

Cutaneous lupus erythematosus (CLE) encompasses a heterogeneous group of autoimmune skin manifestations that often overlap clinically with other inflammatory dermatoses, particularly rosacea. While histopathology remains the gold standard, its invasiveness limits routine and longitudinal use. Line‐field confocal optical coherence tomography (LC‐OCT) is an emerging non‐invasive imaging modality capable of providing real‐time, near‐histological resolution of skin architecture. In this single‐center cross‐sectional observational study, 45 patients (30 CLE: 16 acute, 5 subacute, 9 chronic; 15 rosacea) underwent LC‐OCT imaging of active lesions. Images were independently evaluated using predefined criteria reflecting histopathological features. LC‐OCT identified key histopathological correlates of CLE in vivo. Interface dermatitis features (including dermoepidermal junction disruption, basal cell vacuolization and band‐like inflammatory infiltrate) were highly prevalent in ACLE and SCLE, while chronic CLE was characterized by epidermal atrophy, hyperkeratosis, fibrosis and adnexal destruction. In contrast, rosacea exhibited a vascular and folliculocentric pattern with frequent peri‐adnexal inflammation and Demodex infestation, without interface changes. Interobserver agreement was substantial to excellent for most criteria. In the ACLE versus rosacea comparison, interface dermatitis features like band‐like DEJ infiltrate, DEJ disruption, basal vacuolization and apoptotic bodies were associated with ACLE. Conversely, rosacea exhibited a vascular‐folliculocentric profile with peri‐infundibular infiltrates and Demodex mites. In conclusion, LC‐OCT enables non‐invasive visualization of disease‐specific microarchitectural patterns in CLE, reflecting both inflammatory and chronic remodelling changes. In this pilot study, it shows potential in differentiating CLE from rosacea and may support diagnosis, staging and treatment monitoring in clinical practice. Larger, multicenter studies are required to confirm the role of LC‐OCT in the non‐invasive diagnosis of CLE.

Introduction: The recent approval of pembrolizumab and nivolumab for the adjuvant treatment of stage IIB–IIC cutaneous melanoma (CM) significantly improved the relapse-free survival probability of this patient population. Real-life data suggest that not all stage IIB and IIC CM patients will invariably undergo disease progression. There is a growing need for accurate patients’ selection for whom adjuvant therapy is expected to be beneficial. The aim of this study was to investigate the baseline clinical and histopathological features associated with tumor recurrence in stage II CM patients in an Italian tertiary referral center. Methods: Patients’ clinical features and histopathological tumor characteristics were recorded at the time of melanoma diagnosis. Non-recurrent patients were defined based on a ≥5-year follow-up period; time to disease recurrence was calculated as the time from the diagnosis of the primary tumor until first evidence of melanoma relapse. Results: A total of 103 stage II CM patients, with a median follow-up of 6.2 years, were included. Twenty-one of 103 (20.4%) patients recurred, of whom 15/21 (71.4%) showed disease progression to stage IV disease. Breslow thickness was significantly associated with CM recurrence, with a 70% increased probability of melanoma relapse per each unit increase in Breslow thickness (mm) (OR = 1.7; 95% CI: 1.05–2.7; p = 0.029). Histopathological evidence of ulceration and the mitotic rate did not show a significant association with melanoma progression. Breslow thickness was also associated with a reduced time from melanoma diagnosis to recurrence per each unit increase (mm) (p = 0.032) and with shorter disease-free survival probability (HR: 1.47; 95% CI: 1.05–2.06; p = 0.025). Conclusion: Breslow thickness is a relevant prognostic factor for CM recurrence. Further studies are needed to identify novel prognostic biomarkers.

Confluent and reticulated papillomatosis (CRP) is a rare acquired keratinization disorder. We report a 29‐year‐old woman with a 3‐year history of mildly pruritic hyperpigmented papules on the back, flanks, abdomen, and groin, coalescing centrally into plaques with a peripheral reticulated pattern. Dermoscopy showed a cerebriform sulci‐and‐gyri‐like network. LC‐OCT revealed a markedly thickened hyperreflective stratum corneum, increased epidermal thickness, and a strongly undulated dermal–epidermal junction; a hyperreflective basal band may also be appreciable if consistently visible on the image set. Histopathology showed orthokeratotic hyperkeratosis, focal acanthosis, papillomatosis, and increased basal pigmentation, confirming the diagnosis of CRP. In this case, LC‐OCT identified in vivo optical features corresponding to key histopathologic criteria of CRP and may support noninvasive clinicopathologic correlation.

Background: Patients with locally advanced (la) and metastatic (m) cutaneous squamous cell carcinoma (CSCC) for which curative surgery or radiation is not available may benefit from treatment with anti–programmed cell death 1 (PD‐1) monoclonal antibody cemiplimab. The predictive and prognostic role of hematological markers in such patients remains unclear. Type of Study: A real‐life retrospective cohort study was conducted to evaluate the role of hematological inflammatory parameters as predictive and prognostic factors in patients with laCSCC and mCSCC who underwent first‐line treatment with cemiplimab. Methods: Lymphocyte–monocyte ratio (LMR), neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), albumin, creatinine, systemic immune–inflammation index (SII), and LDH were measured prior to cemiplimab therapy and subsequently at the first follow‐up visit. To evaluate independent prognostic factors, the 12‐month time‐dependent performance was assessed using the incident/dynamic receiver operating characteristic (ROC) framework implemented with a nearest‐neighbor estimator. Model performance metrics, including Harrell’s C‐index and the time‐dependent area under the curve (AUC), were quantified with 95% confidence intervals. Results: A total of 43 CSCC patients including 37 (86.1%) with laCSCC and 6 (14.0%) with mCSCC were retrospectively enrolled. After a median of 33.1 weeks (8.4 months) of exposure to cemiplimab, ORR was 72% (31/43), including 41.9% (13/31) complete responses and 58.1% (18/31) partial responses; stable disease was observed in 9.7% (3/31). The median progression‐free survival (PFS) was 6.4 months (IQR, 3.9–14.7 months). Overall, 7% of patients discontinued therapy due to adverse events (Grade 3 renal insufficiency and liver toxicity). We identified a significant inverse association between NLR change from baseline to first on‐treatment visit (ΔNLR) and PFS (Coeff = −0.25; 95% CI [jackknife] = −0.45–0.05, p = 0.014), showing higher ΔNLR score in patients with shorter PFS. The ΔNLR was associated with a 36% higher chance of progression (HR = 1.36, 95% CI = 0.97–1.89, p = 0.073), adjusted for age, systemic inflammatory index, and sex. Decision curve analysis showed a modest net benefit of the ΔNLR‐based model across a broad range of threshold probabilities (approximately 7%–49%), without identification of a clinically optimal decision threshold. Conclusion: Our study suggests that ΔNLR may serve as an exploratory prognostic indicator in patients with laCSCC and mCSCC.

Background: Line-field confocal optical coherence tomography (LC-OCT) is an innovative non-invasive imaging technique recently introduced in dermatology. Its use has been established particularly in the diagnosis of skin cancer. The LC-OCT description of basal cell carcinoma (BCC) criteria has served for the conduction of retrospective evaluations on its diagnostic performance, which demonstrated its utility in diagnosis and subtyping BCC. However, prospective studies performed at patients’ bedside are currently lacking in this field. Objective: The objective of the study was to provide parameters of LC-OCT diagnostic performance for BCC derived from a prospective study performed at patients’ bedside. Methods: Lesions clinically equivocal for BCC were prospectively included. Dermoscopic and LC-OCT diagnoses were obtained at the patients’ bedside by an expert observer prior to surgical excision or biopsy. Results: A total of 214 lesions (163 BCCs and 51 BCC imitators) belonging to 119 patients were included. For the differentiation of BCC from BCC-imitators, LC-OCT had the same sensitivity as dermoscopy (98%) but a better specificity (90% vs. 37%). For the discrimination of superficial BCC from other BCC subtypes, LC-OCT had an increased sensitivity and specificity compared to dermoscopy (72% vs. 62%, and 97% vs. 84%, respectively). Conclusions: This prospective study showed that the diagnostic performance for BCC diagnosis and subtyping can be remarkedly increased by LC-OCT compared to dermoscopic examination alone. Our data encourages the inclusion of LC-OCT in the diagnostic process and management of equivocal lesions for BCC.