Dermatopathology最新文献

{"title":"Quantifying the Interplay Between PRAME Expression and Classical Morphology: A Multivariable Analysis of 954 Suspected Melanocytic Lesions.","authors":"Frank Friedrich Gellrich, Alaska Kistner, Jakob Nikolas Kather, Narmin Ghaffari Laleh, Claudia Günther, Cosima Hufnagel, Sarah Hobelsberger, Jörg Laske, Stefan Beissert, Daniela Aust, Gustavo Baretton, Nick Reidow, Mildred Sergon","doi":"10.3390/dermatopathology13030035","DOIUrl":"10.3390/dermatopathology13030035","url":null,"abstract":"<p><p>The integration of immunohistochemical biomarkers like PRAME (Preferentially Expressed Antigen in Melanoma) into the histomorphological assessment of melanocytic lesions is gaining prominence. While PRAME's diagnostic value is widely recognized, its independent weight compared directly to classical morphology remains underexplored in large, challenging cohorts. This retrospective study quantifies the diagnostic utility of PRAME alongside traditional histomorphology in a high-risk cohort of 954 primary melanocytic lesions (335 nevi, 215 melanomas in situ, 404 invasive melanomas) where PRAME was clinically requested to resolve diagnostic ambiguity. Using Firth's penalized likelihood regression, a baseline diagnostic model utilizing 13 histomorphological features was established and subsequently integrated with PRAME expression. The pure morphology baseline model demonstrated a high cross-validated area under the curve (AUC) of 0.969. As a standalone marker, PRAME achieved an AUC of 0.895, with a diffuse expression score of 4+ yielding peak specificity (94.3%) and moderate sensitivity (77.9%). Integrating PRAME into the morphological model significantly enhanced diagnostic accuracy (AUC: 0.980; <i>p</i> < 0.001), establishing PRAME as a dominant independent predictor of malignancy alongside core features like junctional atypia and upward melanocytes (Odds Ratio 19.08 for Score 4+). Analysis of discordant cases revealed that completely PRAME-negative melanomas were morphologically indistinguishable from typical PRAME-positive melanomas. Conversely, diffusely PRAME-positive (4+) nevi exhibited significantly higher rates of upward migrating melanocytes, constituting a critical diagnostic pitfall. In conclusion, while classic histomorphology remains the indispensable gold standard in dermatopathology, PRAME functions as a highly objective, reproducible tie-breaker. The synergistic integration of PRAME with morphological assessment effectively resolves diagnostic ambiguity and maximizes diagnostic confidence in challenging melanocytic lesions.</p>","PeriodicalId":42885,"journal":{"name":"Dermatopathology","volume":"13 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13510435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148833075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surgical Management of Cutaneous Neoplasms: Biopsy Strategies, Margin Assessment, and Special Considerations.","authors":"Maged Daruish, Catherine M Stefanato","doi":"10.3390/dermatopathology13030034","DOIUrl":"10.3390/dermatopathology13030034","url":null,"abstract":"<p><p>There has been a rising incidence of both melanoma and non-melanoma skin cancers, requiring knowledge of effective management techniques. This review aims to provide a structured approach to biopsy selection, surgical excision, and margin assessment for common cutaneous neoplasms.</p>","PeriodicalId":42885,"journal":{"name":"Dermatopathology","volume":"13 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13511405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148833135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Halo Nevus as a Self-Limited Model of Melanocyte Autoimmunity: Bridging Vitiligo, Immune Resolution, and Tumor Immunology-A Narrative Review.","authors":"Giulio Tosti","doi":"10.3390/dermatopathology13030033","DOIUrl":"10.3390/dermatopathology13030033","url":null,"abstract":"<p><p>Halo nevus (HN), also known as Sutton nevus or leukoderma acquisitum centrifugum, is a melanocytic lesion characterized by a depigmented halo surrounding a central nevus. Although HN is a benign dermatological condition, increasing evidence indicates that HN represents a dynamic in vivo model of melanocyte-directed immune response with relevant implications for autoimmunity, pigmentary disorders, melanoma regression, and tumor immunosurveillance. The pathogenesis is primarily mediated by CD8+ cytotoxic T lymphocytes via interferon-γ-driven pathways, leading to targeted destruction of melanocytes. However, recent studies have highlighted the importance of immune regulatory mechanisms, including PD-L1-expressing neutrophils and FOXP3+ regulatory T cells, which limit excessive immune-mediated damage and may contribute to the self-limited course and repigmentation observed in some lesions. Additional cytotoxic mediators, particularly granulysin, appear to strengthen melanocyte-directed cytotoxicity, while dendritic cells, macrophages, Langerhans cells, neutrophils, and natural killer cells contribute to antigen presentation, tissue remodeling, and immune resolution. HN shares key immunopathogenic features with vitiligo and melanoma regression but differs from both conditions due to its localized, tightly regulated behavior. Moreover, the halo phenomenon is not restricted to melanocytic lesions, supporting the view that it reflects a broader immune pattern rather than a disease-specific entity. This review provides a comprehensive synthesis of the clinical, histopathological, immunological, diagnostic, and translational aspects of halo nevus. Based on the available evidence, we propose a self-limited melanocyte autoimmunity model to explain the characteristic balance between melanocyte destruction, immune regulation, and spontaneous resolution observed in halo nevi.</p>","PeriodicalId":42885,"journal":{"name":"Dermatopathology","volume":"13 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-Melanocytic Histopathological Clues for Melanoma Diagnosis: A Practical Review of Solar Elastosis, Stromal Regression, and Epidermal Reaction Patterns. Do Old-School Clues Still Matter?","authors":"Michail Sofopoulos","doi":"10.3390/dermatopathology13030032","DOIUrl":"10.3390/dermatopathology13030032","url":null,"abstract":"<p><p>Histopathologic melanoma diagnosis extends beyond melanocytic cytology to encompass non-melanocytic features: solar elastosis patterns, stromal regression, adnexal relationships, epidermal reaction patterns, and the host inflammatory response. These \"old school\" low-power clues are particularly valuable on sun-damaged skin, where benign nevi, reactive melanocytic hyperplasia, and melanoma in situ share overlapping features. Quantitative data support two elastosis-based signs: the \"umbrella sign\" (reduced elastosis beneath the lesion's central third; PPV (Positive Predictive Value) for nevus, 96%, and NPV (Negative predictive Value) for melanoma, 74%; calculated from raw cohort data) and the \"purple fiber sign\" (100% specificity, 30% sensitivity for nevus), both from a cohort of 81 actinically damaged lesions. Regression-identified by compressed elastic layers displaced to the reticular dermis, fibrosis, melanophages, and inflammation-aids diagnosis but complicates distinction from surgical scar. The maturation state of tertiary lymphoid structures (TLSs) within the regression zone, ranging from immunosuppressive immature aggregates to anti-tumoral mature structures with germinal centers, may explain the variable prognostic significance of histologic regression. Epidermal hyperplasia over thick melanomas reflects angiogenesis-related changes, while effacement is a practical red flag in spitzoid lesions. Ancillary tests are most productive when morphology has already framed the differential. These non-melanocytic clues remain indispensable as the foundation for rational ancillary testing.</p>","PeriodicalId":42885,"journal":{"name":"Dermatopathology","volume":"13 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring β3-Adrenergic Receptor, HIF-1α, and CD31 Interplay in the Microenvironment of Atypical Melanocytic Lesions.","authors":"Eugenia Belcastro, Giuseppe Nicolò Fanelli, Cristian Fidanzi, Desirèe Fischetti, Riccardo Morganti, Katia De Ieso, Luca Filippi, Antonio Giuseppe Naccarato, Marco Romanelli, Cristian Scatena, Agata Janowska","doi":"10.3390/dermatopathology13030031","DOIUrl":"10.3390/dermatopathology13030031","url":null,"abstract":"<p><p><b>Background:</b> Melanoma incidence is rising rapidly worldwide and stands out due to its high lethality. Despite advances in clinical treatment and in understanding melanoma-sensitive genes and molecular pathogenesis, a specific area of ongoing research is the connection between stress-related β-adrenergic receptors (ARs), hypoxia, and neovascularization in melanoma tumor progression. This exploratory study aimed to investigate the expression of β3-AR, HIF-1α, and CD31 in several cellular subsets of atypical melanocytic lesions and their interplay in promoting melanoma malignancy. <b>Methods:</b> Twenty-seven patients with melanocytic lesions at different stages that were surgically removed were retrospectively selected; clinical-pathological and dermoscopic data were collected. <b>Results:</b> Immunohistochemical and digital evaluation revealed a significant upregulation of β3-AR in malignant melanoma melanocytes and in macrophages from invasive >pT1a melanomas compared to dysplastic nevi. Increased HIF-1α expression in malignant melanocytes and CD31 expression levels in >pT1a melanomas were observed. Ulcerated lesions exhibited a higher percentage of β3-AR, HIF-1α, and CD31 expression. Pearson correlation analysis revealed positive associations among these markers in human malignant melanoma, suggesting a potential relationship between adrenergic signaling, hypoxia, and tumor vascularization. <b>Conclusions:</b> These exploratory findings suggest that β3-AR, HIF-1α, and CD31 may represent interconnected components of the melanoma microenvironment. Unraveling these interactions in larger, independent cohorts and functional studies may provide additional insights into melanoma biology and help define their potential translational relevance.</p>","PeriodicalId":42885,"journal":{"name":"Dermatopathology","volume":"13 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydroxychloroquine-Induced AGEP with Positive Rechallenge: A Case Report and Mini Review of the Literature.","authors":"Kristijan Jovanović, Tamara Umeljic Sočević, Milos Stepovic, Jovana Milosavljević, Jovica Tomović, Miroslav M Sovrlić, Marko Folić, Miloš N Milosavljević, Dalibor Jovanović, Nevena Folić","doi":"10.3390/dermatopathology13030030","DOIUrl":"10.3390/dermatopathology13030030","url":null,"abstract":"<p><strong>Background/objectives: </strong>Hydroxychloroquine is widely used in the treatment of autoimmune and dermatologic diseases; however, it may rarely induce severe cutaneous adverse reactions. Acute Generalized Exanthematous Pustulosis is an uncommon, acute pustular eruption most frequently associated with antibiotics. Hydroxychloroquine-induced AGEP remains relatively rare and diagnostically challenging due to its atypical and prolonged clinical course.</p><p><strong>Case presentation: </strong>We report the case of a 45-year-old woman with rheumatoid arthritis and a complex medical history who developed generalized urticarial and pustular dermatosis following re-exposure to hydroxychloroquine. Notably, the patient had experienced a similar cutaneous reaction after previous exposure to the same medication several years earlier. Ten days after completing a treatment course of hydroxychloroquine, she developed rapidly progressive pruritic erythematous and urticarial plaques that evolved into generalized annular lesions with peripheral scaling and grouped sterile pustules. Laboratory evaluation demonstrated leukocytosis, intermittent eosinophilia, and elevated IgE levels, while the infectious workup was negative. Histopathological examination revealed subcorneal pustules with neutrophilic infiltration, mild spongiosis, and scattered individual eosinophils, perivascular inflammatory infiltrates, findings consistent with AGEP. Retrospective assessment using the EuroSCAR scoring system classified the reaction as probable AGEP, while the Naranjo adverse drug reaction scale supported a probable causal relationship with hydroxychloroquine. Clinical improvement was achieved after withdrawal of the drug and treatment with systemic corticosteroids and supportive therapy.</p><p><strong>Conclusions: </strong>This case highlights the importance of recognizing atypical presentations compatible with hydroxychloroquine-induced probable AGEP and emphasizes the diagnostic value of a positive rechallenge as supportive evidence of drug causality. Early recognition and prompt discontinuation of the offending agent are essential to prevent severe complications and recurrence.</p>","PeriodicalId":42885,"journal":{"name":"Dermatopathology","volume":"13 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnosis of Syphilis in Paraffin-Embedded Skin Biopsies: Comparison of <i>Treponema pallidum</i> Immunohistochemistry and Polymerase Chain Reaction in Primary and Secondary Stages of Disease.","authors":"Charlotte C Fuchs, Bastian Stoffers, Stephan A Braun, Almut Böer-Auer","doi":"10.3390/dermatopathology13030029","DOIUrl":"10.3390/dermatopathology13030029","url":null,"abstract":"<p><p>Syphilis remains one of the most prevalent sexually transmitted infections. Serology is the diagnostic gold standard, but skin biopsies aid in ambiguous cases. Treponemas can be detected in tissue by immunohistochemistry (IHC) and polymerase chain reaction (PCR); however, their comparative performance across disease stages has not been extensively studied. This retrospective study of 48 formalin-fixed, paraffin-embedded (FFPE) skin biopsies from syphilis cases compared <i>Treponema pallidum</i> IHC and PCR. Of 48 biopsies, 42 (88%) were positive by <i>T. pallidum</i>-specific PCR, whereas IHC identified 45 (94%; <i>p</i> = 0.04). Organisms were denser in primary syphilis (<i>p</i> = 0.03) and predominantly involved the lower third of the epidermis. In 7 of 45 biopsies (15%), treponemas were only detected in the dermis (all secondary syphilis). Therefore, <i>Treponema pallidum</i> IHC demonstrated a slight advantage over PCR, but low Treponema density in about 40% and epidermal absence in nearly 20% of secondary syphilis biopsies highlight a substantial risk of overlooking treponemas on IHC. Systematic assessment including endothelium and perivascular areas is essential.</p>","PeriodicalId":42885,"journal":{"name":"Dermatopathology","volume":"13 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitotic Proliferative Nodule Within a Giant Congenital Nevus: One Case Report and Updated Review.","authors":"Philippe Drabent, Nicolas Macagno, Sylvie Fraitag","doi":"10.3390/dermatopathology13030028","DOIUrl":"10.3390/dermatopathology13030028","url":null,"abstract":"<p><p>Proliferative nodules (PNs) are benign, well-limited melanocytic proliferations that can occur within congenital nevi, particularly larger ones. Although they may mimic melanoma clinically and histologically, PNs are characterized by a monomorphic, well-defined cell population with peripheral blending with the adjacent nevus cells, and a lack of severe atypias, numerous mitoses (in most instances), necrosis, or inflammation. They generally present at birth or early childhood, and even with cytological atypia, they do not undergo malignant transformation. The risk of malignancy associated with a large/giant congenital nevus is low but increases with size and the presence of multiple satellite lesions. Diagnostic tools, including immunohistochemistry and, in selected cases, molecular techniques such as CGH-array or RNA-seq, can help differentiate atypical PNs from melanoma. Awareness of this entity and its diverse histological features is crucial to avoid over-diagnosis of malignancy and unnecessary interventions. Here we report a case of atypical PNs in a giant congenital nevus and discuss the literature.</p>","PeriodicalId":42885,"journal":{"name":"Dermatopathology","volume":"13 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cutaneous Melanoma in Adolescents and Young Adults Versus Older Patients: Clinical and Histopathological Differences in Western Romania.","authors":"Bianca Roxana Natarâş, Sorina Maria Tăban, Aura Jurescu, Octavia Cornelia Viţa, Remus Florin Cornea, Ioana Hurmuz, Adelina Vidac, Daciana Grujic, Valentin Tudor Popa, Alis Liliana Carmen Dema","doi":"10.3390/dermatopathology13020027","DOIUrl":"10.3390/dermatopathology13020027","url":null,"abstract":"<p><strong>Aim: </strong>This study aimed to identify the clinical and pathological features of primary cutaneous melanomas in young patients, comparing them with those of older patients.</p><p><strong>Materials and methods: </strong>We performed a retrospective study observing the differences with respect to clinical and pathological features in young patients versus older patients. We distributed the cases into two groups: patients < 40 years diagnosed with cutaneous melanoma and patients ≥ 40 years diagnosed with cutaneous melanoma.</p><p><strong>Results: </strong>From the total number of primary cutaneous melanomas diagnosed, 11% of cases were represented by young patients. The clinical and pathological features more frequently associated with cutaneous melanomas in AYAs (adolescents and young adults) were represented by the superficial spreading subtype (<i>p</i> = 0.0003), a brisk inflammatory infiltrate (<i>p</i> = 0.0061), a pT1-pT2 pathological stage (<i>p</i> = 0.0183), decreased mitotic activity (<i>p</i> = 0.0186), decreased Breslow index (<i>p</i> = 0.0301), and female sex (<i>p</i> = 0.022).</p><p><strong>Conclusions: </strong>The most important features of cutaneous melanomas diagnosed in AYA patients were represented by the superficial spreading subtype, the presence of a brisk inflammatory infiltrate, and a pT1-pT2 pathological stage.</p>","PeriodicalId":42885,"journal":{"name":"Dermatopathology","volume":"13 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13298238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148319778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flesh-Colored Papules on the Glans Penis.","authors":"Phatcharawat Chirasuthat, Supaporn Suwanchote, Tanaporn Borriboon","doi":"10.3390/dermatopathology13020026","DOIUrl":"10.3390/dermatopathology13020026","url":null,"abstract":"<p><p>A 23-year-old man reported a 3-year history of slowly growing, slightly itchy, flesh-colored papules on the distal glans penis. He denied any history of trauma or previous treatment. Additionally, he experienced no difficulties with urination, discharge, or erectile function. Upon examination, three firm, dome-shaped papules were found to be attached to the skin but mobile over the underlying tissues. There was no regional lymph node enlargement, hardening, or fluctuation observed. Histopathological analysis revealed a well-defined, encapsulated tumor in the dermis, consisting of spindle cells interspersed with varying numbers of axons.</p>","PeriodicalId":42885,"journal":{"name":"Dermatopathology","volume":"13 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13298525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148319782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}