Maria Elisabetta Greco

Dear Editor, Spindle cell lipoma (SCL) is a benign adipocytic neoplasm first characterized by Enzinger and Harvey, classically arising in the posterior neck, shoulder, and upper back of middle-aged to older men. Histologically, it is defined by a variable admixture of mature adipocytes, bland spindle cells, rope-like collagen, and myxoid matrix. The adipocytic component, however, may be minimal or entirely absent, creating a diagnostically deceptive low-fat or fat-free phenotype.

Background: Guselkumab, a selective interleukin-23 inhibitor, is effective in moderate-to-severe plaque psoriasis, but real-world long-term data in elderly patients remain limited. Objective: To evaluate the long-term effectiveness of guselkumab in elderly patients with moderate-to-severe psoriasis in a real-world setting. Methods: This retrospective, multicenter study included 102 patients aged 65 years or older treated with guselkumab across seven Italian centers. PASI scores and PASI 75/90/100 responses were assessed as observed cases at weeks 4, 16, 28, and 52, and annually up to 4 years, with last-observation-carried-forward and non-responder imputation as sensitivity analyses. Subgroups by biologic experience and BMI were analyzed. Results: Mean PASI decreased from 12.4 to 0.3 at week 52, remaining low through year 4 (p < 0.001). At week 52 and year 4, PASI 90 was achieved by 89.7% and 86.5%, and PASI 100 by 79.3% and 73.0%, respectively. Responses were comparable between biologic-naïve and biologic-experienced patients. Obese patients had higher baseline PASI; after adjustment for baseline severity, responses did not differ from non-obese patients. Conclusions: Guselkumab was associated with high and durable PASI improvement in elderly patients, regardless of prior biologic exposure or body weight. The retrospective design and absence of systematic safety data warrant cautious interpretation.

Background/Objectives: The incidence of melanoma in situ (MIS) has increased markedly in several high-income countries, often outpacing invasive melanoma without a proportional rise in mortality. This divergence has raised concerns regarding overdiagnosis, defined as the detection of biologically indolent disease that would not have caused harm if left untreated. This review aims to synthesize contemporary evidence on the overdiagnosis of MIS, focusing on epidemiological patterns, screening-related detection, pathological interpretation, quantitative estimates, and clinical consequences. Methods: A narrative review with systematic search elements was conducted using a structured approach informed by PRISMA principles. PubMed was searched for studies published between January 2017 and March 2026, and eligible studies were selected based on relevance to melanoma overdiagnosis, MIS incidence, screening, and diagnostic variability. Results: The literature consistently demonstrates that increases in melanoma incidence are largely driven by MIS and thin invasive lesions rather than advanced disease. Screening and surveillance preferentially increase detection of low-risk lesions, while variability in dermatopathological interpretation contributes to diagnostic drift. Quantitative studies suggest that a substantial proportion of MIS diagnoses may represent overdiagnosis, exceeding 60–80% in some settings. All of this entails significant direct and indirect social costs in several countries. Conclusions: Overdiagnosis of MIS is a significant and multifactorial phenomenon. MIS represents a heterogeneous entity, and future strategies should focus on improving diagnostic precision, risk stratification, and minimizing harm associated with unnecessary diagnosis.

Urticaria is a mast cell-mediated disorder commonly encountered in women of reproductive age, making its interaction with pregnancy clinically relevant. Gestation induces profound hormonal and immunologic adaptations—including shifts between Th1/Th17 and Th2/Treg responses and sustained exposure to sex steroids and placental hormones—that can modulate mast cell reactivity. As a result, chronic urticaria (CU) shows heterogeneous behavior during pregnancy: approximately half of patients improve, one third worsen, and the remainder remain stable. Pregnancy also presents several urticaria-like dermatoses, notably polymorphic eruption of pregnancy (PEP/PUPPP), atopic eruption of pregnancy (AEP) and pemphigoid gestationis (PG), as well as rare hormone-induced hypersensitivity reactions. Additionally, systemic disorders such as intrahepatic cholestasis of pregnancy (ICP), chronic kidney disease–associated pruritus and urticarial vasculitis may mimic urticaria but differ markedly in prognosis, maternal–fetal risk and management. Given this complexity, accurate diagnosis requires integration of temporal pattern, lesion morphology and duration, distribution, systemic features and targeted investigations, as outlined in the diagnostic algorithm proposed. Most pregnancy-specific eruptions are benign, whereas PG, ICP and urticarial vasculitis warrant prompt recognition due to potential fetal implications. Management of CU in pregnancy generally follows standard guidelines, with second-generation H1-antihistamines as first-line therapy and omalizumab reserved for severe refractory cases.

Vitiligo is a chronic autoimmune depigmenting disorder. Ruxolitinib 1.5% cream is currently the only therapy specifically approved for its treatment. In addition, clinical guidelines recommend off label standard therapies, including topical corticosteroids (TCS), topical calcineurin inhibitors (TCI), phototherapy (narrowband UVB or excimer devices), and selected off-label systemic regimens. This review summarizes the scientific evidence on approved and guideline-recommended treatments for adult vitiligo, using a PRISMA-based approach. Only English-language articles published between 2000 and 2025 were included. Interventions comprised approved therapies and standard treatments recommended by guidelines. Outcomes evaluated were changes in Facial and Total Vitiligo Area Scoring Index (F-VASI/T-VASI), quality of life, and safety. Risk of bias was assessed using the Risk of Bias 2 (RoB 2) tool for randomized controlled trials (RCTs) and the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) for non-randomized studies. Ruxolitinib cream demonstrated superior F-VASI responses compared with vehicles in phase II-III RCTs. Evidence supports the efficacy of potent or very potent TCS, TCI, and NB-UVB or targeted 308-nm devices in localized disease. Systemic regimens show benefits in selected clinical scenarios, although supporting evidence remains heterogeneous. Treatment selection should be individualized based on disease activity, extent, anatomical site, and patient preferences.

Background: Eczematous dermatitis refers to a group of inflammatory skin disorders—including seborrheic, atopic, and contact dermatitis—characterized by epidermal barrier dysfunction and chronic inflammation. Disrupting the itch–scratch cycle and reversing microscopic skin changes are key to improving patient outcomes and quality of life. Aims: This study aimed to assess the clinical and microscopic effects of a topical medical device containing N-butanoyl glutathione (GSH-C4) and hyaluronic acid in patients with inflammatory eczematous dermatitis, combining clinical scores with in vivo confocal and OCT imaging. Methods: A prospective clinical trial enrolled 30 patients with active eczematous lesions. Participants applied a GSH-C4/hyaluronic acid-based product (GSEBA^®) for 28 days. Clinical improvement was evaluated at baseline, day 14, and day 28 using the Investigator’s Global Assessment (IGA), a Visual Analog Scale (VAS) for itching, and a self-reported index of disease impact on quality of life (IDL). Microscopic changes were assessed using optical coherence tomography (OCT) and reflectance confocal microscopy (RCM). Results: After 28 days, the mean IGA score improved from 2.48 to 0.18 (p < 0.001), VAS itching score decreased from 4.52 to 0.32 (p < 0.001), and IDL dropped from 4.86 to 0.79 (p < 0.001). RCM analysis showed significant reductions in key inflammatory features such as spongiosis, vesiculation, and inflammatory infiltrate. OCT revealed a significant decrease in vascularization at 150 μm depth, with no change in collagen density. Conclusions: The GSH-C4/hyaluronic acid-based mousse (GSEBA^®) demonstrated strong clinical efficacy and excellent tolerability in managing eczematous dermatitis. It effectively reduced both symptoms and microscopic markers of inflammation without compromising dermal structure.

Cellulite, or edematous-fibro-sclerotic panniculopathy (EFSP), is a multifactorial condition affecting most postpubertal women, characterized by surface irregularities with significant psychosocial impact. Its pathogenesis involves adipocyte metabolism, fibrous septa, microvascular dysfunction, extracellular matrix (ECM) remodeling, oxidative stress, and low-grade inflammation. Topical therapies remain among the most accessible approaches, acting on specific biological pathways. Osmotic and vSSasomodulatory formulations reduce edema and improve microcirculation, while methylxanthines such as caffeine and aminophylline promote lipolysis and enhance cutaneous blood flow. Retinoids mainly target the ECM, stimulating neocollagenesis and dermal thickening, with greater efficacy in early EFSP. Botanicals, including Centella asiatica, Rosmarinus officinalis, and Ginkgo biloba, provide antioxidant, anti-inflammatory, and venotonic effects. Randomized controlled trials consistently report modest but reproducible benefits: localized circumference reductions and improved elasticity, echogenicity, and orange-peel scores, all with excellent tolerability. Recent innovations, such as lipid nanoparticles, ultradeformable vesicles, and microneedle-assisted delivery, aim to enhance penetration, stability, and sustained bioactivity of established actives. Nonetheless, most studies are small, short-term, and heterogeneous, with limited ability to isolate the role of individual components or control for massage-related effects. Artificial intelligence offers opportunities to standardize outcome measures, optimize formulations, and personalize protocols. Overall, topical therapies are best positioned as safe, biologically active adjuncts within multimodal cellulite management.

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by extreme ultraviolet (UV) sensitivity, predisposing patients to multiple cutaneous malignancies. We present the case of a 26-year-old male with XP diagnosed with three distinct skin cancers: superficial spreading melanoma (SSM), basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). Among these, the melanoma had metastasized. A computed tomography (CT) scan revealed a suspicious pulmonary nodule, prompting further metabolic characterization via positron emission tomography/computed tomography (PET/CT) with ¹⁸F-fluorodeoxyglucose ([¹⁸F]FDG). The scan detected significant hypermetabolism not only in the lung lesion but also in an unsuspected right parotid gland lesion, refining disease staging and guiding treatment decisions. The patient underwent immunotherapy with nivolumab, achieving a complete metabolic response in both metastatic lesions, as confirmed by follow-up PET/CT. This case underscores the critical role of [¹⁸F]FDG PET/CT in staging and treatment monitoring for selected patients with XP, a population in which advanced imaging is rarely employed. Moreover, the patient’s remarkable response to immunotherapy suggests a potential link between XP-related DNA repair defects and increased sensitivity to PD-1 blockade. These findings highlight the importance of integrating metabolic imaging into XP management and warrant further investigation into the immunogenicity of XP-associated malignancies.

Xeroderma Pigmentosum (XP) is a rare autosomal recessive disorder characterized by extreme ultraviolet (UV) sensitivity, predisposing patients to multiple cutaneous malignancies. We present the case of a 26-year-old male with XP diagnosed with three distinct skin cancers: Superficial Spreading Melanoma (SSM), Basal Cell Carcinoma (BCC), and Squamous Cell Carcinoma (SCC). Among these, the melanoma had metastasized. A CT scan revealed a suspicious pulmonary nodule, prompting further metabolic characterization via [18F]FDG PET/CT. The scan detected significant hypermetabolism not only in the lung lesion but also in an unsuspected right parotid gland lesion, refining disease staging and guiding treatment decisions. The patient underwent immunotherapy with nivolumab, achieving a complete metabolic response in both metastatic lesions, as confirmed by follow-up PET/CT. This case underscores the critical role of [18F]FDG PET/CT in staging and treatment monitoring for selected XP patients, a population in which advanced imaging is rarely employed. Moreover, the patient’s remarkable response to immunotherapy suggests a potential link between XP-related DNA repair defects and increased sensitivity to PD-1 blockade. These findings highlight the importance of integrating metabolic imaging into XP management and warrant further investigation into the immunogenicity of XP-associated malignancies.