Dermato

Background: Biotin (vitamin B7) is widely marketed and used as an over-the-counter supplement for hair, skin, and nails, despite uncertainty about its clinical benefit for alopecia and hair growth. While overt biotin deficiency can be associated with hair changes, clinically meaningful deficiency is uncommon in individuals consuming a balanced diet, and published findings on biotin status in hair loss populations are inconsistent. Methods: This is a systematic review following PRISMA. A search was conducted in PubMed/MEDLINE (PROSPERO: CRD420251274919) for human studies evaluating biotin (alone or in combination) and including hair outcomes. The synthesis was qualitative due to clinical and methodological heterogeneity. Results: Ten studies were included. Across controlled and quasi-experimental interventions, biotin monotherapy did not show consistent benefit on objective hair growth outcomes; when improvements were reported, they typically occurred in combined regimens and were difficult to attribute specifically to biotin. Studies showed mixed findings on “low” biotin levels in hair loss populations, whereas controlled studies in telogen effluvium found no significant differences in serum biotin versus controls. No serious adverse events attributable to biotin were identified; however, high-dose biotin may interfere with immunoassays, potentially leading to clinically relevant false laboratory results. Conclusions: Current evidence does not support routine biotin supplementation for alopecia in the absence of documented deficiency, although it may be considered in scenarios with risk or confirmation of deficiency/malabsorption. Full article

The skin serves as a primary defensive barrier to protect the body from environmental contaminants, infections and trauma. Unfortunately, skin barrier’s structural and functional integrity can be compromised, disrupted or impaired due to a combination of internal and external factors, making it vulnerable and often leading to a wide range of skin conditions characterized by dryness, heightened sensitivity, and increased susceptibility to damage and infections. In addition, the integrity of the skin barrier tends to deteriorate progressively with age. As people age, their skin naturally changes and can also be compromised by a plethora of factors that reduce its strength and resilience. The aging skin becomes thinner and more sensitive, coinciding with a variety of structural–functional alterations, decreased levels of natural moisturizing factor (NMF), lipid content and hydration, increased transepidermal water loss (TEWL), altered skin surface pH (pHss) and microbiome diversity. All these age-related skin integrity alterations make the skin drier, flakier, itchy, and fragile, and more susceptible to damage and breakdown, thus diminishing its ability to effectively protect, repair and heal efficiently. Identifying skin integrity issues before they progress will foster positive outcomes through effective preventive measures. Hence, it is important to understand the impact of skincare formulations on skin integrity in compromised aging skin. A well-considered, evidence-based approach to skincare can provide cleansing, moisturizing and protective benefits, while aiding the reduction in skin integrity issues like dry and itchy skin, sensitive skin, bruising, skin tears, pressure injuries (PIs), lower leg ulcers and moisture-associated skin damage (MASD). Managing skin integrity in compromised aging skin begins with gentle skin cleansing, adequate moisturization and protective barrier care to ensure the skin’s function is maximized. Full article

Hidradenitis suppurativa (HS) is a chronic inflammatory dermatosis characterized by recurrent nodules, abscesses, and sinus tract formation in intertriginous skin. Although HS is increasingly recognized as an autoinflammatory condition rather than a classical infection, antimicrobial therapies remain central to disease management, implicating a potential role for the cutaneous microbiome in disease activity. Recent advances in culture-independent sequencing techniques have enabled more detailed characterization of microbial communities in HS, revealing consistent alterations in microbial composition and diversity. Compared with healthy skin, HS lesions exhibit reduced microbial diversity, depletion of commensal organisms such as Cutibacterium acnes, and enrichment of anaerobic bacteria including Prevotella, Porphyromonas, and Finegoldia. These alterations are more pronounced in chronic, tunnel-forming disease and are frequently associated with biofilm formation, which may contribute to treatment resistance and persistent inflammation. Microbiome changes have also been observed beyond overtly lesional skin, suggesting a broader field effect. Evidence regarding extracutaneous microbial compartments, particularly the gut microbiome, remains limited and heterogeneous, while methodological variability in sampling, sequencing, and treatment exposure continues to complicate cross-study comparisons. Emerging data further suggest that immune-targeted therapies, including biologic and small-molecule agents, may indirectly influence microbial community structure through modulation of the inflammatory milieu. Collectively, the available evidence supports cutaneous dysbiosis as a characteristic feature of HS that may potentially interact bidirectionally with immune dysfunction. Future longitudinal, multi-omic studies integrated with clinical phenotyping will be critical to clarify causal relationships and to determine whether microbiome modulation can be leveraged to improve therapeutic outcomes in HS. Full article

Surgery continues to represent the central curative modality for melanoma despite major advances in systemic immunotherapy and targeted treatments. Contemporary surgical strategies aim to maintain oncologic safety while minimizing functional and aesthetic morbidity through optimized excision margins, highly selective use of sentinel lymph node biopsy (SLNB), and the omission of routine completion lymph node dissection (CLND). Rapid integration of neoadjuvant and adjuvant immunotherapies has begun to redefine surgical indications, timing, and extent—particularly for intermediate-stage and locoregionally advanced disease. Parallel innovations in Mohs micrographic surgery, reconstructive flap design, lymphatic reconstruction, and minimally invasive techniques further broaden the possibilities for individualized intervention. This expanded review synthesizes current evidence, ongoing controversies, and emerging trends that are shaping the future of melanoma surgery, highlighting how precision oncology, immunologic profiling, and technological advances are transforming the surgeon’s role and enabling more tailored, less invasive, and outcome-focused management. Full article

Background: Conventional therapies for moderate-to-severe inflammatory acne include topical agents, systemic antibiotics, hormonal treatments, and oral isotretinoin. However, increasing resistance of Cutibacterium acnes to antibiotics and the potential adverse effects of systemic agents have prompted growing interest in non-pharmacological alternatives such as fractional microneedling radiofrequency (RF-MN), recently introduced in the clinical practice. Objective: This report of five cases aims to document the clinical benefits and safety of RF-MN using the Focus Dual^® device in the treatment of moderate-to-severe inflammatory acne vulgaris. Methods: Five patients (2 male, 3 female; aged 19–28 years; Fitzpatrick skin types II–III) with moderate-to-severe acne were treated with two RF-MN sessions at 4-week intervals using the Focus Dual^® device (Med & Tech, Occhiobello (RO), Italy). Acne severity was assessed using the Face Global Acne Grading System (F-GAGS) and the 5-point Global Improvement Score (GIS), with evaluations performed by two independent blinded raters (G.P and O.R). Standardized photographic documentation and lesion counting were conducted at baseline (T0) and 4 weeks after the second session (T2). All individual F-GAGS scores for each of the five patients showed a reduction from baseline to T2, as consistently assessed by both evaluators. Two patients improved from moderate to mild acne, one improved from severe to moderate, and one remained mild. GISs indicated clinical improvement ranging from Grade 1 to Grade 2 in all cases, with individual improvements between 8.33% and 37.93%. No adverse events were reported during treatment or follow-up. Conclusions: RF-MN appears to be a promising therapeutic option for moderate-to-severe inflammatory acne, providing clinical improvement and reduction in acne severity without adverse effects. Prospective studies with a larger sample are needed to confirm these preliminary results and support the potential role of RF-MN as an adjunctive or standalone treatment in patients with limited tolerance or response to conventional therapies. Full article

Sensitive Skin Syndrome (SSS) is a worldwide condition characterized by sensory symptoms such as stinging, burning, and itching, often without visible signs. This pilot study investigated individuals with self-reported SSS, focusing on the specific skin conditions, motivations and barriers for seeking medical attention. SSS individuals were divided into two groups: those who consulted a doctor (n = 16) and those who did not (n = 10). While SSS symptom severity was similar in both groups, those with greater severity were five times more likely to seek medical help. Key symptoms prompting consultations included morphological symptoms (papules, macules), sensory symptoms (itch, discomfort), and inflammatory symptoms (redness, rash). Notably, altered sensation and macules/papules showed the strongest trends towards influencing care-seeking behavior. Differences in anatomical sites affected were significant, with the head and face having the highest odds of doctor visits. Barriers to care included high specialist costs, travel distances, and a lack of remote consultation options, particularly for rural residents. Although treatments recommended by healthcare providers often fell short of expectations, partially effective options were more acceptable when endorsed by doctors. Subjects reported improvements within weeks of starting new treatments, though many remained only partially satisfied. This study highlights important aspects of SSS and its entanglement with other skin conditions, as well as how individuals navigate their symptoms and make treatment decisions amidst their sufferings. Full article

Background: This study aimed to assess the prevalence of PD-L1 protein expression in dermatofibrosarcoma protuberans (DFSP) to provide insights into the potential use of immune checkpoint inhibitors. Methods: We retrospectively analyzed formalin-fixed, paraffin-embedded primary DFSP specimens (n = 17). Diagnoses were confirmed by two senior dermatopathologists according to guideline criteria, including diffuse CD34 positivity and storiform spindle cell morphology. All cases represented conventional DFSP without fibrosarcomatous transformation. PD-L1 immunohistochemistry was carried out using a rabbit monoclonal antibody (ab205921, clone 28-8; Abcam). Only membranous staining in viable tumor cells was scored as a tumor proportion score (TPS), where >1% was considered positive. Any cytoplasmic staining without convincing membranous accentuation was not scored. PD-L1 staining in tumor-infiltrating immune cells was recorded separately. Five pleomorphic dermal sarcomas served as positive controls. Results: The median age was 62 years (IQR 55–74); 12 patients were men and 5 were women. The primary sites were trunk (59%), upper extremity (35%), and lower extremity (6%); immunosuppression was present in 18%. By FNCLCC, 82% of tumors were G1 and 18% were G2; no G3 tumors were identified. All DFSPs were PD-L1-negative in DFSP cells (TPS ≤ 1%) and in tumor-infiltrating lymphocytess. Among controls, 3/5 pleomorphic dermal sarcomas were PD-L1-positive with the expected membranous pattern and variable intensity. Conclusions: PD-L1 expression was absent in this cohort of conventional, predominantly low-grade DFSP, suggesting that classic DFSP is generally not an ideal candidate for PD-1/PD-L1-directed checkpoint blockade. These conclusions should not be extrapolated to fibrosarcomatous DFSP or metastatic disease, where PD-L1 expression has been reported. Selective PD-L1 testing may still be warranted in clinically aggressive scenarios (e.g., fibrosarcomatous transformation, unresectable recurrence, or metastasis). Full article

Introduction: Myxoid liposarcoma (MLPS) is a rare soft tissue sarcoma comprising 5–10% of adult cases, most often in the thigh. Diagnosis is challenging due to nonspecific imaging findings and resemblance to benign lesions. Case Report: A 42-year-old male presented with a painless, enlarging upper right medial thigh mass. CT and ultrasound suggested a complex solid lesion, possibly benign. Outpatient surgical excision revealed a red, gelatinous, non-encapsulated mass. Frozen section suggested a myxomatous spindle cell tumor. Final pathology confirmed MLPS FNCLCC grade 2 (intermediate grade) with DDIT3 rearrangement on fluorescence in situ hybridization (FISH). Margins were negative but close. Postoperative PET scan and Signatera MRD assay were negative for metastasis. Given the tumor’s size (>10 cm) and known radiosensitivity, adjuvant radiotherapy (60–66 Gy) was initiated. Discussion: MLPS features myxoid stroma, plexiform vasculature, and, in high-grade tumors, a round cell component. The FUS::DDIT3 fusion gene is diagnostic. While MRI offers superior soft tissue characterization, definitive diagnosis requires pathology and molecular testing. Surgical excision with negative margins remains standard, with radiotherapy recommended for large tumors or close margins to reduce recurrence. This case highlights the limitations of preoperative imaging and the value of intraoperative pathology in guiding management. Conclusions: Early recognition, accurate diagnosis, and tailored multimodal treatment are essential for MLPS. Given the potential for recurrence, late extrapulmonary metastases, long-term surveillance with imaging, and molecular assays are critical for optimizing outcomes. Full article

Rosacea is a chronic skin condition characterized by persistent inflammation, manifesting primarily on the face and causing redness, papules, pustules, and phymatous changes. The etiology of rosacea is multifactorial, with immune system factors playing a crucial role in its pathogenesis. The scientific literature contains an increasing number of studies that suggest a correlation between rosacea and the gut microbiota. Small intestinal bacterial overgrowth (SIBO) is defined as an excessive proliferation of potentially pathogenic bacteria within the small intestine of the gastrointestinal system. Multiple factors have been posited to explain the pathogenesis of rosacea, and the presence of SIBO has been identified as a potential factor in its occurrence. A decrease in the Lactobacillus genus, Prevotella copri, Lachnospiraceae, and Faecalibacterium within the gut microbiota may initiate inflammation related to rosacea. These bacterial species are crucial for regulating the intestinal mucosa. The findings indicate that there is an increase in Bacteriodes, Acidaminococcus, Megasphaera, and Ruminococcus in the gut microbiome of patients with rosacea. Probiotics can be advantageous for managing the intestinal microbiome, while Rifaximin treatment has shown efficacy in addressing inflammatory rosacea lesions associated with SIBO. The present review has been undertaken with the objective of enhancing our comprehension of SIBO in rosacea. The emphasis has been placed on the pathogenetic mechanisms and the shift in the gut microbiota that will lead to understanding probiotic benefits and therapy options in rosacea patients. Full article

Background/Objectives: Metformin, a widely used antidiabetic drug, has recently gained attention in dermatology due to its pleiotropic effects. Given the high prevalence, chronicity, and therapeutic challenges of several dermatological conditions, there is growing interest in repurposing metformin as a topical agent with anti-inflammatory, antioxidant, metabolic, and regenerative properties. This narrative review aimed to synthesize and critically analyze the available preclinical and clinical evidence regarding the mechanisms of action, efficacy, safety, and therapeutic potential of topical metformin across different skin disorders. Methods: A literature search was conducted in PubMed and complementary databases for studies published between 2015 and 2025 addressing topical metformin in dermatology, including experimental, observational, interventional, and review articles. Results: The findings indicate that topical metformin has been associated with beneficial biological effects in conditions such as melasma, photoaging, wound healing, psoriasis, acne, skin cancer, and hair disorders, largely through AMPK activation, modulation of inflammation and oxidative stress, inhibition of melanogenesis, enhancement of tissue regeneration, and regulation of immune and metabolic pathways, although evidence remains predominantly preclinical and methodologically heterogeneous. Conclusions: Topical metformin represents a promising investigational multifunctional dermatological agent; however, its clinical translation depends on well-designed randomized controlled trials with standardized formulations, adequate sample sizes, and long-term follow-up to establish its efficacy, safety, and optimal therapeutic protocols. Full article

Background/Objectives. Ultraviolet B (UVB) radiation is a key etiological factor for skin cancer, inducing oxidative stress, DNA damage and apoptosis. Nicotinamide (NAM), a NAD⁺ precursor, has shown photoprotective properties, although the mechanisms underlying this effect have not been fully elucidated. This study sought to elucidate the role of NAM in counteracting UVB-induced oxidative damage in HaCaT cells and to assess the contribution of NAD⁺ metabolism to these effects. Methods. HaCaT were exposed to low-dose UVB irradiation (40 mJ/cm²) and treated with NAM (25 μM), alone or in combination with the NAMPT inhibitor FK866 (1 nM) for 4 and 24 h. Oxidative stress, lipid peroxidation and DNA damage were evaluated by DCFDA assay, TBARS assay and comet assay, respectively. Cell proliferation, cell cycle progression and apoptosis were assessed using Ki67 immunofluorescence, flow cytometry analysis and Annexin V/PI staining. Transcriptional activity for oxidative stress- and apoptosis-related markers was analyzed by RT-qPCR. Results. NAM significantly reduced UVB-induced ROS production at both 4 and 24 h post-irradiation in an NAD⁺-dependent manner, as demonstrated by the reversal of its effects following NAMPT inhibition. NAM also decreased oxidative DNA damage accompanied by reduced OGG1 expression, a marker of oxidative stress. Moreover, NAM restored HaCaT proliferation and reduced early apoptosis, particularly at 24 h post-UVB exposure. These protective effects were mediated by NAD⁺. Conclusions. Our results show that NAM confers robust protection to HaCaT cells from UVB-induced oxidative stress and cellular damage, largely mediated by NAD⁺-dependent pathways, supporting its potential role as a systemic photoprotective agent in skin cancer prevention. Full article

Background/Objectives: Melanoma remains one of the most malignant types of skin cancer with rising incidence numbers, despite the progress made in the prevention and management of the disease. Recent technological advancements, such as developments in the field of molecular biology, imaging, and artificial intelligence (AI), have led to a paradigm shift in the diagnosis, assessment, and management of melanoma. The current review aims to integrate current research on melanoma, moving beyond the boundaries of conventional histological analysis. Methods: This is a critical appraisal narrative review that focuses on recent studies in the areas of translation research and digital health with regard to melanoma. This research particularly targeted recent studies within the last five years, with landmark studies implicated when appropriate. Evidence was synthesized within the major categories that include epidemiology, early diagnosis, histopathology, predictive biomarkers, genetic/epigenetic changes, AI-assisted diagnostic platforms, and novel therapeutic platforms & targets. Results: Early detection techniques, innovative imaging, and biomarker-guided risk adjustment can improve diagnostic accuracy and prognostic stratification. The potential of AI in dermoscopy, digital pathology, and decision analytical systems is evident, although validation, bias, and integration issues need to be addressed. Advances in immunotherapy, targeted therapies, and novel molecular/immunological targets are expanding and facilitating integrated and personalized management. Conclusions: There is a trend in melanoma research to shift towards an integrated diagnostic platform that involves the use of AI, molecular characterization, and clinical inputs to enable more accurate and personalized diagnoses. To realize this potential, there is a need to validate, collaborate, and address ethics and implementation. Full article

Background/Aims: This study aimed to undertake a systematic literature review to compare the effectiveness of narrowband UVB (nb-UVB) therapy with Psoralen + UVA (PUVA) or Psoralen + UVB treatments in individuals with vitiligo. Methods: A comprehensive search was executed across multiple electronic databases (PubMed, Embase, Cochrane, Scopus, Web of Science, LILACS) and grey literature repositories (Google Scholar, LIVIVO, OpenGrey, ProQuest). Methodological quality was independently assessed by two reviewers employing the Cochrane RoB 2 tool; consensus was achieved through consultation with a third reviewer when necessary. The main efficacy endpoint was repigmentation. Results: From 4758 initial records, four randomized controlled trials that satisfied the inclusion criteria were identified. The aggregated results from these studies indicated that nb-UVB, either alone or combined with psoralen (P-nbUVB), produced better repigmentation outcomes compared to PUVA. Conclusions: Nb-UVB phototherapy demonstrated superior repigmentation efficacy, improved color matching, and a faster clinical response relative to PUVA. The addition of psoralen (P-nbUVB) further enhanced therapeutic outcomes, particularly in VASI scores and in areas typically less exposed to resunlight. Full article

Background and Objectives: Merkel cell carcinoma (MCC) is a rare, aggressive, invasive cutaneous neuroendocrine carcinoma. It commonly affects the skin of the extremities and head and neck regions in elderly patients. In situ MMC represents MMC confined to the epidermis. Incipient MCC is a descriptive term that represents in situ MCC with early focal dermal microinvasion. In situ MCC and incipient MCC have a much better prognosis than MCC. In this study, we aimed to address the clinicopathologic features of early lesions of MCCs, including both incipient and in situ forms. Methods: We conducted a PubMed search using the following keywords: (“Merkel cell carcinoma” OR “Merkel carcinoma” OR “Merkel” OR “MCC”) AND (“in situ” OR “incipient” OR “intraepidermal”) AND (“skin” OR “cutaneous”. The inclusion criteria included (i) human studies, and (ii) case reports and series published in the English language with the above-mentioned search keywords. Studies not meeting all inclusion criteria were excluded. Results: Incipient and in situ MCCs are extremely rare events (15 case reports). They usually appear as tiny (2 mm to 6 mm) erythematous papules or nodules over the skin. Immunohistology (for CK20, EMA, and neuroendocrine markers) was required to establish the diagnosis of these lesions. Conclusions: MCCs carry a significantly high mortality rate due to their aggressive nature. However, for in situ MCC and incipient MCC, local surgical excision is usually curative, and the prognosis is excellent. Therefore, dermatologists and dermatopathologists should remain vigilant for these forms of early lesions of MCCs. This will help with early detection and prompt treatment. Full article

Background/Objectives: Acute generalized exanthematous pustulosis (AGEP) is a severe drug-induced cutaneous reaction characterized by the abrupt onset of sterile pustules, fever, neutrophilia, and a T cell-mediated type IVd hypersensitivity response. This narrative review synthesizes current evidence on pharmacological triggers, immunopathogenic mechanisms, diagnostic criteria, and differential diagnosis to provide a clinically oriented framework. Methods: A comprehensive literature search was conducted in PubMed/MEDLINE, Scopus, ScienceDirect, and SpringerLink for studies published between 2000 and 2025, complemented by selected clinical reference sources. Studies addressing clinical features, immunological pathways, pharmacovigilance signals, and diagnostic tools for AGEP were included. Synthesis of Evidence: β-lactam antibiotics remain the most frequent triggers, while increasing associations have been reported with hydroxychloroquine, targeted therapies, immune checkpoint inhibitors, psychotropic agents, and vaccines. Immunopathogenesis is driven by IL-36 activation, CXCL8/IL-8–mediated neutrophil recruitment, and IL36RN mutations, explaining overlap with pustular psoriasis. Diagnostic accuracy improves through integration of drug latency, clinical morphology, histopathology, biomarkers, and standardized tools such as the EuroSCAR score. Conclusions: AGEP is a complex pustular reaction induced by diverse drugs and amplified by IL-36-mediated inflammation. Accurate diagnosis requires a multidimensional approach supported by structured algorithms and robust pharmacovigilance to identify evolving drug-associated patterns. Full article

Background/Objectives: Acne is a common skin condition that is characterized by the manifestation of comedones, erythematous papules, pustules, and nodules over follicular areas. A huge contributing factor in the pathogenesis is colonization by Cutibacterium acnes (C. acnes) (formerly Propionibacterium acnes). Conventional treatments for acne range from topical to systemic agents with variable side effects and safety profiles. Adherence to prescribed treatments for acne is a huge challenge. Method: A quantitative cross-sectional study was conducted among 198 patients with dermatologist-confirmed acne vulgaris at King Abdulaziz University Hospital, Jeddah. Eligible participants had received topical and/or systemic treatment for at least one month. Exclusion criteria included other acne variants and inflammatory follicular disorders. Data on sociodemographics, medical and treatment history, and clinical characteristics were collected using a structured questionnaire. Treatment adherence was assessed with the validated ECOB scale. Associations between adherence and relevant variables were analyzed using Chi-squared and Mann–Whitney tests in SPSS v26, with significance set at p ≤ 0.05. Results: Non-adherence to anti-acne medications was 50.5% and was significantly associated with experiencing side effects, particularly skin dryness, and with moderate acne severity and topical treatment (p ≤ 0.05). No significant associations were found between adherence and demographic or medical history variables. Conclusions: Adherence to acne treatment remains a significant challenge for many patients. Improving patient education, addressing concerns about side effects, and providing practical support may help patients follow their prescribed therapies more consistently. Incorporating tools like the ECOB questionnaire into routine dermatology visits can support ongoing assessment and better management of treatment adherence. Full article

Introduction: Atopic dermatitis (AD) is driven by complex pathways that mediate inflammation and pruritus. The pathophysiology of AD’s disease involves multiple pathways. Interleukin-13 (IL-13) is considered a major cytokine in Th2-type inflammation, responsible for changing the epidermal barrier and producing chronic inflammation, whereas interleukin-31 (IL-31) is considered a major inducer of pruritus. The exact correlation of each of these cytokines with disease severity in children with AD appears to vary across studies. This study was therefore designed to evaluate whether IL-13 and IL-31 levels contribute complementarily or independently to the overall clinical severity of AD in the Moroccan pediatric population and to analyze the correlation between serum IL-13 and IL-31 levels and investigate their correlation with disease severity in a pediatric cohort. Methods: A total of 52 children with moderate to severe AD were included. The severity of the disease was measured using the SCORing Atopic Dermatitis (SCORAD) index. Serum levels of IL-13 and IL-31 were measured by Enzyme-Linked Immunosorbent Assay (ELISA). Results: The IL-13 serum level showed a considerable positive correlation with the SCORAD score (r_s = 0.7, p < 0.0001). On the other hand, IL-31 levels revealed no correlation with SCORAD (r_s = 0.07, p = 0.62) but were positively correlated with pruritus intensity (r_s = 0.91, p < 0.001). Conclusion: Our results support the presence of different pathophysiological axes in pediatric AD, where IL-13 functions as a reliable biomarker of inflammatory severity. IL-31 acts as a systemic marker of the pruritic pathway. Full article

Italian Court of Cassation Ruling Decree 30032 of 30 October 2023 discusses a medical malpractice case concerning the diagnosis of dermatofibrosarcoma protuberans and the alleged diagnostic and therapeutic delay. By examining how the ruling frames the role of histopathology in proving pathology benignity, authors prompt to reflect on diagnostic path, the allocation of the burden of proof, and the role of dermatologist’s expertise in professional liability issues. Over a four-year period, five health professionals were involved in a claim concerning an initial diagnosis of an epidermoid cyst and a subsequent diagnosis of dermatofibrosarcoma protuberans. The plaintiff questioned the delay in diagnosis, and the Court of Cassation found two physicians liable because they could not prove that the treated pathology was initially benign. We argue that equating diagnostic correctness exclusively with histological confirmation is unnecessary, both clinically and legally, in typical cases, if the reasoning and findings are adequately documented. Additionally, we examine the value of dermatologists’ experience and the scope of professional competence as measures of liability. Finally, we outline the minimum standards of clinical documentation necessary to make the diagnostic pathway traceable and verifiable. The diagnostic process is a discretionary effort that integrates multiple sources of information, both instrumental and experiential, to reach the most reasonable hypothesis. While histopathology is a crucial tool, it is not the sole gateway to a correct diagnosis of every cutaneous alteration. Adequate disclosure and structured documentation of the diagnostic reasoning are fundamental to the care process and fair assessment of professional responsibility. Full article

Immune checkpoint inhibitors (ICIs), particularly PD-1/PD-L1 antibodies, have significantly improved outcomes in a variety of solid tumors, including urothelial carcinoma. However, their use is frequently associated with immune-related adverse events (irAEs) which frequently affect the skin and mucous membranes. Among these, plasma-cell-rich infiltrates are exceptionally rare. Circumorificial plasmacytosis (COP) is a rare, predominantly reactive condition typically involving mucosal transition zones, with histologic features characterized by dense, polyclonal plasma cell infiltrates and a benign clinical course. Only two case reports have described COP in association with ICI therapy and, to date, transformation or overlap with lymphoproliferative disorders such as marginal zone lymphoma has not been documented. We report the case of an 86-year-old male with urothelial carcinoma who developed a progressive, ulcerated, bleeding lesion of the lower lip during adjuvant nivolumab therapy. Histologic examination revealed a dense subepithelial infiltrate of mature plasma cells and lymphocytes. Direct and indirect immunofluorescence studies were negative, excluding autoimmune blistering disorders. Immunohistochemistry showed a predominance of CD138-positive plasma cells with a moderate kappa light-chain shift, CD19 expression, and absence of CD56, Cyclin-D1, and CD117, arguing against a plasma cell neoplasm. Molecular analysis via multiplex PCR revealed a clonal B-cell population with distinct IgH rearrangements, and some EBV-positive cells were also identified by EBER in situ hybridization. The histopathologic and molecular findings suggested a marginal zone lymphoma-like, plasmacytic proliferation arising in the setting of COP. This case illustrates a rare and diagnostically challenging constellation at the intersection of reactive and clonal B-cell proliferations in the context of ICI therapy. Although the lesion demonstrated features of clonality, the overall low B-cell content, indolent clinical course, and lack of systemic involvement support a reactive, immunodeficiency-associated lymphoproliferation rather than overt lymphoma. This case expands the known spectrum of mucocutaneous irAEs and highlights the need for careful clinicopathologic correlation, including immunophenotyping and molecular diagnostics. Awareness of such rare presentations is essential to avoid overdiagnosis and unnecessary systemic treatment in patients with otherwise indolent lesions. Full article