Dermatopathology doi: 10.3390/dermatopathology13030042

Authors: Mar Llamas-Velasco Eduardo Rozas-Muñoz Angel Fernandez-Flores Maria-Teresa Fernandez-Figueras

Skin biopsy is one of the most valuable diagnostic procedures in dermatology, particularly when clinical findings alone are insufficient to establish a diagnosis. However, obtaining an accurate histopathological diagnosis depends on multiple steps, and errors at any stage of the biopsy pathway may compromise the final result. This review synthesizes current evidence and available guidelines on best practices for skin biopsy, integrating the practical experience of four internationally recognized dermatopathologists to address areas where evidence is limited or poorly standardized. The review covers biopsy planning, selection of the optimal biopsy site and technique, specimen handling and fixation, grossing and laboratory processing, prevention of technical artifacts, the use of ancillary diagnostic techniques, and clinicopathological correlation, with particular attention to challenging anatomical sites and complex diseases. Diagnostic accuracy depends on obtaining a representative specimen, maintaining high technical standards throughout tissue processing, providing adequate clinical information, and ensuring close communication between the clinician and the dermatopathologist. In selected cases, multidisciplinary review is required to reach a definitive diagnosis. Adherence to these principles can optimize diagnostic yield, reduce avoidable errors, and ultimately improve patient care.

Dermatopathology doi: 10.3390/dermatopathology13030041

Authors: Qing Xie Di Bao Tao Ruan Kuangzheng Zhu Dawei Liu Tiecheng Zhong

Background: Psoriasis is a chronic inflammatory skin disease due to genetic susceptibility and multiple environmental factors. Transient receptor potential vanilloid 4 (TRPV4) is a calcium channel extensively expressed throughout the body with multiple functions. However, the role of TRPV4 in imiquimod (IMQ)-induced -psoriasis progression remains unclear although it is ubiquitously expressed in skin tissues and participates in cutaneous mechano- and thermo-sensation. Methods: Both in vivo and in vitro studies were performed in murine skin tissue and isolated cells. TRPV4 expression, autophagy, and Akt/mTOR phosphorylation were assessed by Western blot and reactive oxygen species (ROS) generation was examined by MitoSOX staining. Cytokine levels were measured by ELISA and cell proliferation was determined by CCK staining. The severity of psoriasis was also checked by psoriasis severity index (PSI), scale and thickness scoring and microscopic observations. Results: IMQ-induced psoriasis was remarkably attenuated in TRPV4 knockout mice compared with their wild-type counterparts, accompanied by reduced expression of several inflammatory cytokines. Deletion of TRPV4 diminished ROS production and Akt/mTOR phosphorylation. In vitro experiments showed that IMQ caused a concentration-dependent increase in autophagy, characterized by an initial increasing phase followed by a declining phase in primary keratinocytes. IMQ-induced autophagic activity was enhanced via Calmodulin/Akt pathway suppression while weakened by CaMKKβ/AMPK pathway inhibition. Moreover, blockade of the Calmodulin/Akt pathway significantly reduced IMQ-induced ROS production and psoriasis severity, whereas inhibition of the CaMKKβ/AMPK pathway exacerbated IMQ-induced psoriasis progression through ROS accumulation. Conclusions: Both CaMKKβ/AMPK and Calmodulin/Akt signaling pathways, as downstream components of TRPV4, are involved in IMQ-induced psoriasis: lower IMQ dosage activates AMPK, thereby preventing psoriasis by ROS clearance, whereas higher IMQ dosage activates Calmodulin and exacerbates psoriasis. Our findings reveal the potential values of targeting TRP-related channels in IMQ-induced psoriasis.

Dermatopathology doi: 10.3390/dermatopathology13030040

Authors: Dieter Metze Kira Süßmuth

We are grateful for the commentary by Ángel Fernández-Flores on our concept of “desmosomal-type acantholysis”, a distinct histologic form of acantholysis associated with mutations in genes encoding desmosomal proteins [...]

Dermatopathology doi: 10.3390/dermatopathology13030039

Authors: Ángel Fernández-Flores

We read with great interest the article by Metze et al [...]

Dermatopathology doi: 10.3390/dermatopathology13030038

Authors: Christoph Müller Harald Kittler Mathias Drach

Optical imaging technologies are increasingly reshaping the interface between clinical dermatology and dermatopathology. In vivo reflectance confocal microscopy (IV-RCM), line-field confocal optical coherence tomography (LC-OCT), and ex vivo confocal microscopy (EV-CM) provide tissue-level morphological information without the need for conventional histopathologic processing or with substantially reduced processing times. These technologies have enabled the concept of the “virtual biopsy” and are increasingly integrated into diagnostic workflows. However, their clinical value cannot be understood solely through conventional diagnostic performance metrics such as sensitivity and specificity. Rather, their impact depends on how the information they generate is incorporated into sequential diagnostic pathways and clinical decision-making processes. This review summarizes the principles, current applications, diagnostic performance, limitations, and future prospects of IV-RCM, LC-OCT, and EV-CM. We discuss the complementary strengths of these modalities and propose a systems perspective in which imaging technologies are viewed as components of diagnostic ecosystems linking clinical examination, dermatoscopy, pathology, surgery, and computational decision support. Emerging developments in artificial intelligence, multimodal imaging, and digital pathology are likely to further strengthen these connections and expand the role of optical imaging in dermatology and dermatopathology.

Dermatopathology doi: 10.3390/dermatopathology13030037

Authors: Anne Welfringer-Morin Stéphanie Leclerc-Mercier

Vasculitis encompasses a heterogeneous group of diseases characterized by the inflammation of blood vessels. In children, the diagnosis of vasculitis with cutaneous involvement relies on a combination of clinical evaluation, histopathological examination, and, in some cases, genetic investigations. Diagnosing pediatric vasculitis remains particularly challenging due to overlapping clinical manifestations, variable disease courses, and the evolving nature of histological features. Histopathological assessment aims to confirm inflammation of the vessel walls—either readily visible at low magnification or requiring serial sections—and to characterize the inflammatory infiltrate and other key features that aid in classifying the vasculitis subtype. Accurate diagnosis requires ongoing dialog and collaboration among multiple specialists. In this article, we present the clinical and histopathological features of the most common pediatric vasculitides—including IgA vasculitis and polyarteritis nodosa—as well as newly recognized entities such as COVID-19-associated vasculitis and monogenic vasculitides.

Dermatopathology doi: 10.3390/dermatopathology13030036

Authors: Martin Manole Iuliu Gabriel Cocuz Alexandru-Constantin Ioniță Maria Baldea Carla-Antonia Peterdeak Adrian Horațiu Sabău Maria-Cătălina Popelea Emőke Andrea Szász Andreea Raluca Cozac-Szőke Andreea Cătălina Tinca Diana Maria Chiorean Ovidiu Simion Cotoi

Background/Objectives: Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer (NMSC) and represents the leading cause of NMSC-related deaths. Despite its growing global burden, comprehensive epidemiological and clinicopathological data from Easter Europe remains limited. This study aimed to evaluate the epidemiological, clinical, histopathological, and surgical characteristics of cSCC diagnosed before, during and after the COVID-19 pandemic. Methods: We conducted a retrospective, descriptive observational study including 332 lesions diagnosed between January 2017 and December 2025 at the Clinical Pathology Department of the Mureș Clinical County Hospital. Demographic, epidemiological, topographic, histopathologic, surgical, and volumetric parameters were analyzed. Tumours were stratified into low-, high-, and very-high-risk categories according to the National Comprehensive Cancer Network (NCCN) criteria. Results: The cohort demonstrated a significant male predominance (n = 193 vs. n = 139; p = 0.0355), with females presenting a higher median age (77 vs. 75; p = 0.0489). Lesions were predominantly located in the head and neck region (n = 216; p < 0.0001), which was significantly associated with very-high-risk tumours (p = 0.0051). Low-risk tumours accounted for 62.35% of cases, while high-risk and very-high-risk lesions comprised 19.88% and 17.77%, respectively (p < 0.0001). Ulcerations were strongly associated with very-high-risk tumours (p < 0.0001). Poor differentiation was more frequent outside the head and neck region (p < 0.0001) and varied significantly across the pandemic periods (p = 0.0349). Tumoral and excision volumes were higher in very-high-risk (p = 0.0070; p = 0.0004) and ulcerated tumours (p < 0.001), with a peak in volume during the COVID-19 period (p < 0.0001). A decrease through the years of diagnosis was observed in tumoral volumes (r = −0.2295; p < 0.0001) and patients showed a weak positive correlation with diagnosis year (r = +0.13; p = 0.019). Conclusions: The study provides an epidemiological and clinicopathological characterization of cSCC within one of the largest Romanian cohorts to date. Tumour aggressiveness was primarily driven by histopathological and topographical features rather than demographic factors. While the COVID-19 pandemic did not induce persistent changes in tumour risk profiles or surgical outcomes, it influenced diagnosis timing and tumour burden. These findings highlight the importance of incorporating temporal and emerging systemic factors, such as pandemics, and infectious events, into future epidemiological models to improve preparedness, early detection, future treatment schemes, and risk stratification in cSCC.

Dermatopathology doi: 10.3390/dermatopathology13030035

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

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; p < 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.

Dermatopathology doi: 10.3390/dermatopathology13030034

Authors: Maged Daruish Catherine M. Stefanato

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.

Dermatopathology doi: 10.3390/dermatopathology13030033

Authors: Giulio Tosti

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.

Dermatopathology doi: 10.3390/dermatopathology13030032

Authors: Michail Sofopoulos

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.

Dermatopathology doi: 10.3390/dermatopathology13030031

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

Background: 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. Methods: Twenty-seven patients with melanocytic lesions at different stages that were surgically removed were retrospectively selected; clinical-pathological and dermoscopic data were collected. Results: 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. Conclusions: 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.

Dermatopathology doi: 10.3390/dermatopathology13030030

Authors: Kristijan Jovanović Tamara Umeljic Sočević Milos Stepovic Jovana Milosavljević Jovica Tomović Miroslav M. Sovrlić Marko Folić Miloš N. Milosavljević Dalibor Jovanović Nevena Folić

Background/Objectives: 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. Case presentation: 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. Conclusions: 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.

Dermatopathology doi: 10.3390/dermatopathology13030029

Authors: Charlotte C. Fuchs Bastian Stoffers Stephan A. Braun Almut Böer-Auer

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 Treponema pallidum IHC and PCR. Of 48 biopsies, 42 (88%) were positive by T. pallidum–specific PCR, whereas IHC identified 45 (94%; p = 0.04). Organisms were denser in primary syphilis (p = 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, Treponema pallidum 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.

Dermatopathology doi: 10.3390/dermatopathology13030028

Authors: Philippe Drabent Nicolas Macagno Sylvie Fraitag

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.

Dermatopathology doi: 10.3390/dermatopathology13020027

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

Aim: This study aimed to identify the clinical and pathological features of primary cutaneous melanomas in young patients, comparing them with those of older patients. Materials and Methods: 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. Results: 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 (p = 0.0003), a brisk inflammatory infiltrate (p = 0.0061), a pT1–pT2 pathological stage (p = 0.0183), decreased mitotic activity (p = 0.0186), decreased Breslow index (p = 0.0301), and female sex (p = 0.022). Conclusions: 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.

Dermatopathology doi: 10.3390/dermatopathology13020026

Authors: Phatcharawat Chirasuthat Supaporn Suwanchote Tanaporn Borriboon

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.

Dermatopathology doi: 10.3390/dermatopathology13020025

Authors: Muhammad N. Mahmood Eunice Y. Chow

Melanocytic nevi exhibiting perineuriomatous differentiation are rare and pose significant diagnostic challenges due to their low incidence and morphological resemblance to other cutaneous spindle-cell lesions, including desmoplastic melanoma. In this report, we describe the clinical, dermoscopic, microscopic, and immunohistochemical features of a perineuriomatous melanocytic nevus on the right mid-forearm of a 73-year-old Caucasian man. Given the scarcity of reported cases, documenting additional examples is crucial for refining clinicopathological diagnostic criteria. Accurate identification relies on thorough histopathological and immunohistochemical assessment. By presenting the current case, we aim to enhance diagnostic accuracy and raise awareness of this uncommon nevus. A clearer understanding of these characteristics will help dermatologists and dermatopathologists identify this nevus and distinguish it from other cutaneous spindle-cell proliferations.

Dermatopathology doi: 10.3390/dermatopathology13020024

Authors: Philippe Drabent Anne Welfringer Alejandro A. Gru Thierry J. Molina Sylvie Fraitag

Cutaneous hematologic neoplasms in children are relatively rare and encompass a wide range of lymphoproliferative and myeloproliferative disorders. This review explores and updates the classification, clinical presentation, diagnostic challenges, histopathology, and management of pediatric lymphomas, lymphoproliferations, and leukemias that may be seen in the skin. The most frequent of them are lymphomatoid papulosis (LyP) and mycosis fungoides (MF), and are discussed first, with a particular focus on differential diagnosis and overlaps with benign lesions—mainly pityriasis lichenoides—which raises questions regarding the delineation of these entities and their potential interconnection. It is important to underline that most cutaneous lymphoproliferations are indolent in children: primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder, subcutaneous panniculitis-like T-cell lymphoproliferation (non-associated with HAVCR2 mutations), primary cutaneous marginal zone lymphoproliferative disorder, and EBV-related lymphoproliferative disorders. However, aggressive hematologic malignancies, although rarer, must not be missed; these are mostly leukemias (but not all forms) and blastic plasmacytoid dendritic cell neoplasm. We emphasize the importance of clinical–pathological correlation, with clonality studies playing a crucial role in some cases. Management strategies are briefly reviewed, ranging from skin-directed therapies like phototherapy and corticosteroids to systemic treatments for more aggressive forms of leukemia cutis and lymphomas.

Dermatopathology doi: 10.3390/dermatopathology13020023

Authors: Jade Nasser Eldin Elias El Tayar Ossama Abbas Jag Bhawan

Cutaneous pseudolymphomas are benign reactive lymphoid proliferations that often mimic cutaneous lymphomas both clinically and histologically. A diverse array of inflammatory, infectious, and drug-induced dermatoses can closely resemble cutaneous T-cell lymphomas (CTCLs), particularly mycosis fungoides (MFs), posing significant diagnostic challenges. These mimickers may show histopathological features such as epidermotropism, dense lymphocytic infiltrates, or even clonality, making accurate differentiation crucial to avoid overtreatment. This review endeavors to comprehensively discuss the clinicopathologic features of the various inflammatory and infectious dermatoses that may simulate CTCL, drawing on illustrative examples across disease categories. By highlighting important comparative features and emphasizing the importance of clinicopathologic correlation, this review outlines practical strategies for distinguishing true lymphoma from its inflammatory mimics.

Dermatopathology doi: 10.3390/dermatopathology13020022

Authors: Andreea Cătălina Tinca Andreea Raluca Cozac-Szoke Ovidiu Simion Cotoi

Inflammatory skin diseases are characterized by complex interactions between immune pathways, epidermal barrier function, and environmental triggers, leading to distinct clinical and histopathological features. This narrative review aims to integrate current knowledge on the cutaneous immune microenvironment across major inflammatory skin diseases, including atopic dermatitis, psoriasis, hidradenitis suppurativa, and vitiligo. A comprehensive literature search was conducted using PubMed, Web of Science, and Scopus, focusing on studies published between 2021 and early 2026. The findings highlight disease-specific immune signatures, such as Th2-driven inflammation in atopic dermatitis, IL-23/Th17 axis activation in psoriasis, neutrophil-dominated responses in hidradenitis suppurativa, and cytotoxic T-cell-mediated melanocyte destruction in vitiligo. These molecular pathways are closely reflected in histopathological patterns, emphasizing the link between morphology and immunopathogenesis. Advances in targeted therapies, including biologics and Janus kinase inhibitors, demonstrate the clinical relevance of these pathways and support a transition toward mechanism-based treatment strategies. Dermatopathology is increasingly contributing to precision medicine approaches by supporting correlations between tissue features, immune pathways, and potential therapeutic targets. This review provides a framework for improved disease stratification and for the development of personalized treatment strategies in inflammatory skin diseases.

Dermatopathology doi: 10.3390/dermatopathology13020021

Authors: Gerardo Cazzato Anna Colagrande Antonietta Cimmino Lucia Lospalluti Aurora Demarco Caterina Foti Paolo Romita Francesca Arezzo Vera Loizzi Paola Parente Leonardo Resta Giuseppe Ingravallo

The authors would like to make the following corrections to this published paper [...]

Dermatopathology doi: 10.3390/dermatopathology13020020

Authors: Irena Janković Goran Stevanović Toma Kovačević Dimitrije Janković Dimitrije Pavlović

Background and Objectives: Sentinel lymph node biopsy (SLNB) is increasingly used for high-risk, clinically node-negative cutaneous squamous cell carcinoma (cSCC), yet pathological reporting remains binary, lacking morphological stratification. The prognostic relevance of nodal tumor burden subtypes—isolated tumor cells (ITC), micrometastases, and macrometastases—is well established in melanoma and breast cancer but remains uncharacterized in cSCC. We aimed to describe the morphological spectrum of sentinel lymph node involvement in a consecutive institutional cohort and determine whether primary tumor characteristics predict the extent of nodal colonization. Materials and Methods: We conducted a retrospective-observational study at Clinical Center Niš (Serbia) including 35 consecutive clinically N0 high-risk cSCC patients who underwent SLNB using a dual-tracer protocol (99mTc-labeled albumin and methylene blue). Sentinel nodes were processed by serial sectioning with hematoxylin-eosin and pancytokeratin (AE1/AE3) immunohistochemistry. Deposits were classified as ITC (≤0.2 mm), micrometastases (>0.2–2.0 mm), or macrometastases (>2.0 mm). Clinicopathologic predictors were evaluated using the Mann–Whitney U test, Fisher’s exact test, the Kruskal–Wallis test, and the Spearman rank correlation test. Results: SLN involvement was identified in 12 of 35 patients (34.3%). Among positive cases, ITC accounted for 6 patients (50.0%), micrometastases for 5 (41.7%), and macrometastasis for 1 (8.3%)—minimal nodal disease constituting 91.7% of positive findings. No primary tumor feature—including diameter, thickness, grade, perineural invasion, or lesion multiplicity—significantly distinguished ITC from overt metastatic deposits. Patients with ITC showed numerically higher median tumor thickness (8.0 mm) than those with micrometastases (4.0 mm), though this did not reach significance (Kruskal–Wallis p = 0.065). Conclusions: SLN positivity in high-risk cSCC is morphologically heterogeneous, with minimal nodal disease predominating. Primary tumor features do not reliably stratify the extent of nodal colonization. Structured tumor-burden reporting—distinguishing ITC, micrometastases, and macrometastases—should be adopted as standard practice to enable meaningful prognostic comparisons and inform individualized management.

Dermatopathology doi: 10.3390/dermatopathology13020019

Authors: Angel Fernandez-Flores José Luis Martínez-Amo

Granuloma annulare is a non-infectious granulomatous dermatosis with a probable pathogenic mechanism of delayed-type hypersensitivity, in which the dermal histiocytic granulomatous infiltrate is usually accompanied by a lesser component of lymphocytes. Although there are more common clinical and histopathological patterns of presentation, there are less well-known variants that may pose significant diagnostic challenges by mimicking other inflammatory cutaneous processes or even neoplastic conditions. One of the rarest forms of granuloma annulare is the pseudolymphomatous variant, in which the lymphocytic component is not only highly prominent but may, in some cases, partially or completely obscure the histiocytic component itself. This feature, together with the fact that the clinical presentation of this variant is often atypical—frequently lacking the characteristic annular morphology of conventional granuloma annulare—renders the diagnosis particularly challenging. From an immunohistochemical standpoint, the infiltrates described are predominantly composed of T cells, with only a sparse and scattered B-cell component. In this article, we present a case of granuloma annulare with a pseudolymphomatous B-cell component (PAX5+, CD79+) and minimal T-cell involvement, observed in a 4 mm skin nodule located on the shoulder of a 48-year-old male. This case therefore broadens the concept of pseudolymphomatous granuloma annulare to include infiltrates predominantly composed of B lymphocytes.

Dermatopathology doi: 10.3390/dermatopathology13020018

Authors: Janmesh D. Patel Pooja A. Shet Sara E. Dahle Joshua M. Schulman Marat D. Kazak

An 86-year-old man presented with a slowly enlarging, subject to chronic mechanical irritation, pedunculated keratotic papule on the plantar tip of the right hallux in the setting of severe peripheral arterial disease. Excision was deferred until after endovascular revascularization to reduce the risk of nonhealing and limb complications, after which the lesion was removed without wound sequelae. Histopathology demonstrated a conical papule with a central collagenous core and an overlying cap of compact hyperkeratosis. This case highlights key clinicopathologic features that distinguish acral keratotic tumors and underscores the importance of perfusion optimization when planning elective excision on an ischemic limb.

Dermatopathology doi: 10.3390/dermatopathology13020017

Authors: Dieter Metze Kira Süßmuth Clemens Metze Vinzenz Oji Heiko Traupe

Desmosomes are specialized cell–cell junctions that play a crucial role in maintaining the structural integrity of both cornifying and non-cornifying epithelium. Disruption of desmosomal cohesion in autoimmune, infectious, and other diseases is typically associated with acantholysis, often leading to intraepidermal blisters and erosions. In recent decades, genetic mutations have been identified that impair desmosomal integrity to varying degrees, giving rise to a spectrum of genodermatoses. These conditions, which include palmoplantar keratoderma, epidermolysis bullosa, and ichthyoses, can range from mild to severe, with some forms being syndromic and life-threatening. We investigated dermatopathologic changes in patients with mutations in genes encoding desmosomal proteins seen in consultations at our genodermatoses unit. A series of cases, including keratosis palmoplantaris areata et striata (striated palmoplantar keratoderma type 1), Carvajal–Huerta syndrome, severe dermatitis–multiple allergies–metabolic wasting (SAM) syndrome, ectodermal dysplasia–skin fragility syndrome, and inflammatory peeling skin disease, was examined histologically and, when necessary, immunohistochemically. Findings from our cohort were compared with histopathological consultation cases from our dermatopathology laboratory and previously published cases in the literature. Through these observations, we defined a distinct form of acantholysis associated with desmosomal protein mutations, which we term “desmosomal-type acantholysis.” We outline the spectrum of this newly characterized pattern and highlight its differences from conventional forms of acantholysis. Furthermore, for the first time, we describe incidental cases where “desmosomal-type acantholysis” appears sporadically in solitary acanthoma and in association with a melanocytic nevus.

Dermatopathology doi: 10.3390/dermatopathology13020016

Authors: Nazario Pesce Giorgia Di Marco Giorgio Stabile Antonio Podo Brunetti Alessandro Russo Stefania Guida Rongioletti Franco

Blastomycosis-like pyoderma (BLP) is a rare chronic inflammatory dermatosis characterized by exuberant vegetative and verrucous plaques, most frequently associated with bacterial colonization, particularly Staphylococcus aureus. Owing to its striking clinical and histopathological resemblance to squamous cell carcinoma (SCC) and other granulomatous or hyperplastic dermatoses, BLP represents a well-recognized diagnostic pitfall, often leading to delayed diagnosis or unnecessary surgical management. We report an unusual case of bilateral auricular BLP in a 58-year-old apparently immunocompetent woman, initially misdiagnosed as SCC. Comprehensive clinicopathological reassessment revealed pseudoepitheliomatous hyperplasia, intraepidermal neutrophilic microabscesses, and a dense mixed inflammatory infiltrate, findings consistent with a reactive rather than neoplastic process. Microbiological cultures confirmed Staphylococcus aureus, supporting the final diagnosis of BLP and guiding effective antimicrobial therapy. To better contextualize this rare presentation, we reviewed all previously reported cases of BLP, summarizing available clinical, histopathological, microbiological, and therapeutic data. This case further raises the possibility of an association between BLP and systemic inflammatory conditions, as the patient subsequently developed severe colitis, highlighting the potential role of immune dysregulation and the gut–skin axis in disease pathogenesis or a possible temporal association, without allowing causal inference. Beyond inflammatory bowel disease, blastomycosis-like pyoderma has been reported in association with a variety of systemic and immune-mediated conditions, including diabetes mellitus, hematologic malignancies, HIV infection, chronic renal failure, autoimmune disorders, and prolonged immunosuppressive therapies. These associations support the concept that BLP represents a hyperinflammatory reaction pattern occurring in the setting of altered immune surveillance rather than a purely infectious disease. Accurate recognition and management of BLP require careful integration of clinical features, histological findings, and microbiological results. Increased awareness of its diverse presentations is essential to avoid misdiagnosis and to ensure appropriate, conservative treatment.

Dermatopathology doi: 10.3390/dermatopathology13020015

Authors: Maroun Bou Zerdan Kevin T. Jamouss Alexandre Maalouf Rita Moukarzel Tanishq Chhabra Daniel J. Zaccarini Dean Pavlick Natalie Danziger Jeffrey Ross

Cutaneous adnexal carcinomas (CACs) comprise a diverse group of malignant tumors that show morphological differentiation toward one of the four main adnexal structures in normal skin: hair follicles, sebaceous glands, sweat-apocrine glands, and sweat-eccrine glands. These tumors can arise sporadically or may be associated with rare genetic syndromes. A total of 276 CACs cases underwent hybrid capture-based comprehensive genomic profiling (CGP) to assess all classes of genomic alterations (GA). Sequencing data were used to determine microsatellite instability (MSI) status, tumor mutational burden (TMB), genomic loss of heterozygosity (gLOH), genomic ancestry, and COSMIC mutational signatures. PD-L1 expression was evaluated by immunohistochemistry (TPS; Dako 22C3). Statistical analyses were performed using Fisher’s exact test, with false discovery rate correction via the Benjamini–Hochberg method. Sequencing was performed on primary cutaneous tumors in 131 cases (47.4%) and on local recurrence or metastatic site biopsies in 145 cases (52.5%). Across all groups, there was a male predominance (64–81%) and similar mean ages (59–63 years), with apocrine (APO) tumors occurring in older patients than eccrine (ECC) tumors (72 vs. 62 years; p = 0.001). Histologically, 173 tumors (62.7%) were sweat gland-derived (SWT), 55 (19.9%) sebaceous gland-derived (SEB), 14 (5.1%) hair follicle-derived (HRF), and 34 (12.3%) unclassified (UNK). Among SWT tumors, 150 (86.7%) were eccrine and 23 (13.3%) apocrine. SWT tumors included digital papillary adenocarcinomas (DPA, 6.9%), mucinous carcinomas (MC, 6.3%), porocarcinomas (POR, 11.0%), spiradenocarcinomas (SPR, 8.1%), syringoadenocarcinomas (SRNG, 5.8%), and 77 (44.5%) unclassified cases. The number of GA per tumor was highest in SEB compared with SWT tumors (7.9 vs. 4.9; p = 0.005) and lowest in DPA (2.1 vs. 5.0 in non-DPA; p = 0.03). No differences in ancestry distribution were observed. Compared with SWT tumors, SEB tumors exhibited higher frequencies of RB1 (38.2% vs. 8.1%; p < 0.0001) and TP53 alterations (76.4% vs. 43.4%; p = 0.0002), suggesting potential neuroendocrine differentiation. MC tumors showed significantly higher PTCH1 alterations than non-MC tumors (36.4% vs. 1.8%; p = 0.044). MSI-high status was most frequent in SEB tumors compared with all other groups (15.7% vs. 1.2%; p = 0.005), and gLOH > 16% was also more common in SEB than SWT tumors (19.6% vs. 7.2%; p = 0.081). The MMR signature occurred more frequently in SEB than SWT tumors (32.0% vs. 2.1%; p = 0.005). Mean TMB was elevated across most CACs types, ranging from 10.4 mutations/Mb in HRF to 38.8 mutations/Mb in MC, with the exceptions of APO (2.7 mut/Mb; p = 0.001) and DPA (1.4 mut/Mb; p = 0.003). PD-L1 expression was generally low and did not differ significantly between SWT and SEB tumors (37.0% vs. 33.3%; NS). Given the limited data on CAC treatment, this study provides a catalog of commonly observed GA. SEB tumors exhibited the highest frequency of genomic alterations. Prospective clinical trials are needed to determine the prognostic and predictive value of CAC-specific biomarkers for immune checkpoint inhibitor (ICI) response, which is essential for integrating novel therapies into the evolving treatment landscape.

Dermatopathology doi: 10.3390/dermatopathology13010013

Authors: Isabelle Moulonguet Marie Caucanas Sophie Goettmann

Longitudinal melanonychia (LM) results from the deposition of pigment in the nail plate due to increased melanocytic activity within the nail matrix. Recent publications on this topic have helped clarify the main clinical, histological, and evolutionary characteristics of pediatric LM and provide guidance for its appropriate management. In this review, we will examine the literature on the subject. LM is far less common in children than in adults and is most often caused by benign nail matrix lesions. Pediatric LM has specific clinical and histopathologic features, and many of the clinical warning signs used in adults are not applicable to children. Pediatric lesions may show atypical cytologic and even architectural features yet still follow a benign clinical course. Spontaneous regression of LM is common in children, with fading and narrowing of the pigmented band, or even complete disappearance. The vast majority of pediatric LM cases can be managed conservatively with regular follow-up, including clinical photography and onychoscopy.

Dermatopathology doi: 10.3390/dermatopathology13010014

Authors: Francesco Fortarezza Anna Poputchikova Federica Pezzuto Christian Ciolfi Vincenza Guzzardo Paolo Del Fiore Gerardo Cazzato Franco Bassetto Mauro Alaibac Angelo Paolo Dei Tos

PRAME (Preferentially Expressed Antigen in Melanoma) is increasingly used as an immunohistochemical marker in the evaluation of melanocytic lesions; however, its expression in benign melanocytic proliferations remains incompletely characterized. This study investigated PRAME expression in melanoacanthomas, with particular emphasis on its relationship with ultraviolet exposure and chronic solar damage. A consecutive series of melanoacanthomas was retrospectively analyzed. Melanocytes were identified and quantified using SOX10 immunohistochemistry, while PRAME-positive melanocytes were counted and graded semiquantitatively according to nuclear staining intensity. PRAME expression was correlated with lesion site (photoexposed versus non-photoexposed skin) and with the degree of solar elastosis. Eighty-four cases were evaluated, of which 25 (29.8%) showed at least focal PRAME positivity in melanocytes. Overall melanocytic density assessed by SOX10 did not differ significantly between photoexposed and non-photoexposed lesions. Similarly, stratification based on total PRAME-positive melanocyte counts, irrespective of staining intensity, revealed no significant association with photoexposure. In contrast, analysis restricted to melanocytes with strong nuclear PRAME expression demonstrated a significant enrichment in photoexposed lesions compared with non-photoexposed sites (p < 0.01). Moreover, high-intensity PRAME expression showed a positive association with increasing grades of solar elastosis. These findings indicate that strong PRAME expression in melanoacanthoma could be associated with chronic sun damage and may reflect non-specific, ultraviolet-related modulation rather than malignant transformation, underscoring the importance of contextual interpretation of PRAME immunohistochemistry in diagnostic practice.

Dermatopathology doi: 10.3390/dermatopathology13010012

Authors: Francoise Plantier Fiona Lewis

Biopsies are only performed in less than 1% of all consultations dedicated to paediatric genital dermatology. The objectives of this paper are to review and clarify the histopathological features of the conditions most often biopsied: first, lichen sclerosus, which has a peak incidence in childhood and progresses over years; secondly, pigmented lesions, including atypical genital naevi and common naevi in the context of lichen sclerosus, both histologically differential diagnoses of melanoma, which probably does not present in childhood. And finally, Crohn’s disease, which is a cause of vulval oedema or genital ulceration.

Dermatopathology doi: 10.3390/dermatopathology13010011

Authors: Yara Alhusaini Abdulaziz Almufadhi Naif Alzahrani Nawaf Alqahtani Ohoud Aljarbou

Granular cell tumors are uncommon neoplasms of neural origin that may involve the skin and often present with nonspecific clinical features, making diagnosis challenging. Cutaneous granular cell tumors rarely exhibit overlying hypertrichosis, a finding that may obscure their clinical recognition. In this report, we describe a rare case of a primary cutaneous granular cell tumor with prominent overlying terminal hair growth in an adult patient. A 27-year-old woman presented with a slowly enlarging, firm, pigmented plaque on the upper back associated with pruritus and increased hair growth. Histopathologic examination revealed sheets of large polygonal cells with abundant granular eosinophilic cytoplasm, and immunohistochemical staining was positive for S100, SOX10, CD68, and calretinin, confirming the diagnosis. The lesion was completely excised with no evidence of malignancy. To our knowledge, this represents the second reported instance of a cutaneous granular cell tumor associated with hypertrichosis and the first described in an adult. It underscores the importance of clinicopathologic correlation in evaluating unusual cutaneous lesions and expands the spectrum of recognized presentations of cutaneous granular cell tumors.

Dermatopathology doi: 10.3390/dermatopathology13010010

Authors: Madeleine Kelly Crystal Williams Robert Miller

Chromoblastomycosis is a chronic mycosis of the skin and subcutaneous tissue typically caused by traumatic inoculation of dematiaceous fungi of the Herpotrichiellaceae. A 59-year-old male presented with a 12-month history of an asymmetrical, scaly plaque on the left forearm that has been slowly increasing in size. Past medical history included atrial fibrillation on apixaban, hypertension and a cardiac stent. A 4 mm punch biopsy of the left forearm revealed superficial dermal fibrosis with mild pseudoepitheliomatous hyperplasia and granulomatous inflammation with scattered multinucleate histiocytes. There were giant cells with dark brown, somewhat round, yeast-like structures, some with internal septation exhibiting moderate staining for PAS, compatible with Medlar bodies suggestive of chromoblastomycosis. The patient was on rosuvastatin, rendering itraconazole not a possible treatment option, and instead the patient underwent curettage and cautery with two bouts of cryotherapy freeze and thaw cycles. A twelve-month follow-up noted a crusted area on the distal aspect of the scar. A shave biopsy of this area revealed pigmented organisms suggesting a recurrence of chromoblastomycosis. A further excisional biopsy was performed, with no evidence of chromoblastomycosis. This case highlights multiple surgical options for the management of chromoblastomycosis in patients where medical management is contraindicated. It highlights the therapeutic challenge of this disease due to frequent recurrence of lesions and that repeat biopsy may be efficacious in monitoring for recurrence.

Dermatopathology doi: 10.3390/dermatopathology13010009

Authors: Kira Süßmuth Vinzenz Oji Jacqueline Bodes Isabelle Jochum Florian Muhs Katalin Komlosi Ingrid Hausser Matthias Schmuth Heiko Traupe Judith Fischer Dieter Metze

Background: Inherited ichthyoses are a heterogeneous group of disorders of cornification caused by mutations in genes encoding epidermal proteins. Clinically, patients with ichthyosis present with erythema, scaling, and occasionally blistering; some subtypes are syndromic. Accurate and timely diagnosis is essential for appropriate management and genetic counseling. Objectives: Diagnosis of ichthyosis typically relies on a combination of clinical features, histopathological and ultrastructural findings, immunohistochemistry, and molecular genetic testing. Dermatopathology can be particularly valuable in three diagnostic scenarios: (i) when the clinical diagnosis of ichthyosis is evident, but the specific subtype remains unclear; (ii) when differential diagnoses such as inflammatory dermatoses need to be excluded; and (iii) when molecular testing is unavailable or yields variants of uncertain significance. However, definitive classification according to current nomenclature requires molecular confirmation. Methods: Despite being a routine diagnostic tool in dermatology, histopathological criteria for ichthyoses remain ill-defined and diagnostically challenging. In this retrospective study, we systematically assessed histological features in 66 patients with confirmed ichthyosis. Results: Our analysis revealed six distinct histological patterns. Based on these, we propose a pattern-based diagnostic algorithm to support the histological classification of ichthyosis subtypes. Limitations: Although some rare subtypes were underrepresented, this cohort represents the largest and most heterogeneous group of molecularly confirmed ichthyosis cases analyzed histologically to date. Conclusions: Our findings highlight the diagnostic value of skin biopsies in inherited ichthyoses. The delineation of characteristic histological patterns and the development of a diagnostic algorithm may facilitate more accurate subtype identification, particularly in settings where genetic testing is limited or inconclusive.

Dermatopathology doi: 10.3390/dermatopathology13010008

Authors: Monia Di Prete Viviana Lora Arianna Lamberti Alessandra Latini Carlo Cota

Rheumatoid nodules are the most common extra-articular manifestation of rheumatoid arthritis. Long-term immunomodulatory therapies, including corticosteroids, used in the management of rheumatoid arthritis are associated with a higher risk of infections. Leishmaniasis is a neglected protozoal infection that may arise in these patients. Cutaneous presentation is the most common and is characterized by a wide spectrum of clinical manifestations and courses, depending on the interplay between species involved and the host’s immune response. Here, we report the rare and intriguing case of a patient with long-standing rheumatoid arthritis, chronically treated with systemic prednisone, whose rheumatoid nodules were colonized by Leishmania major. In this context, therapeutic strategies must be tailored to species and patient factors. This report expands the differential diagnosis of rheumatoid nodule, highlighting the importance of considering opportunistic infections in exuberant presentations, particularly in immunosuppressed patients coming from or travelling in endemic regions. Intracellular pathogens may exploit the localized immunological niche represented by the rheumatoid nodule of an immunocompromised host to survive and replicate undisturbed. It also underscores the value of the clinico-pathological correlation and the importance of integrating molecular analyses to identify unexpected microorganisms that can be hidden by concomitant disease, avoiding misdiagnosis, ensuring timely treatment, and improving patients outcomes.

Dermatopathology doi: 10.3390/dermatopathology13010007

Authors: Gaia Mancuso Igor Salvadè Adam Ogna Brenno Balestra Helmut Beltraminelli

Background: Behçet-like syndrome (BLS) refers to the presence of Behçet’s disease (BD) features occurring in association with distinct clinical–pathological conditions such as inborn errors of immunity, myeloproliferative disorders, infections, or drug exposure. BLS may differ clinically from BD and is increasingly recognized as a separate entity. Distinguishing BLS from primary BD is essential for appropriate management, and studying BLS may provide insights into BD pathogenesis. Objectives: To summarize clinical features, treatments, and genetic abnormalities reported in BLS, we reviewed all published cases up to January 2024. Methods: A systematic search of PubMed, Scopus, and Embase was performed using the terms “Behçet-like syndrome”, “Behçet-like disease”, and “Pseudo-Behçet disease”. We included English-language reports of patients > 12 years old with a defined underlying etiology and Behçet-like manifestations, defined by ≥2 ICBD criteria and/or gastrointestinal involvement, mucosal ulcers, thrombosis, or non-recurrent disease. Epidemiological, clinical, laboratory, histological, and treatment data were extracted and analyzed descriptively. Results: Of 679 publications, 53 met inclusion criteria, comprising 100 patients with BLS. The median age was 44 years (IQR 22–52), with a female predominance (1:2). Fifty-three percent were from non-European countries. A genetic disorder was identified in 70% of cases, while HLA-B51 was present in 10%. Frequent manifestations included skin lesions (68%), fever (56%), intestinal involvement (43%), and joint symptoms (43%). Treatments included glucocorticoids (65%), conventional DMARDs (32%), and biologics (22%), mainly anti-TNF agents. Antiviral/antibiotic therapy was used in 9% and chemotherapy in 15%. Two patients with trisomy-8 MDS underwent allogeneic stem cell transplantation. Conclusions: Diverse conditions—including monogenic diseases, immune defects, myeloproliferative disorders, infections, and drug-related reactions—can produce Behçet-like features. Our findings highlight differences in clinical expression and treatment response across BLS etiologies. Recognizing BLS is essential for appropriate management and may contribute to a deeper understanding of BD pathogenesis and future targeted therapies.

Dermatopathology doi: 10.3390/dermatopathology13010006

Authors: Li Yang Loo Shi Huan Tay Choon Chiat Oh

Cutaneous squamous cell carcinoma (cSCC) is an immunogenic malignancy with variable immune infiltration and inconsistent responses to checkpoint blockade. Tumor-infiltrating lymphocytes (TILs) influence tumor progression and therapeutic outcome, yet their phenotypic and functional diversity across disease contexts remains incompletely understood. This review systematically characterizes the TIL landscape in human cSCC. Following PRISMA 2020 guidelines, PubMed and Embase were searched up to May 2025 and restricted to studies evaluating tumor-infiltrating lymphocytes in human cSCC, using the modified Newcatle–Ottawa score to assess risk of bias. Data were synthesized qualitatively given methodological heterogeneity. 48 studies met inclusion criteria. cSCCs exhibited dense CD3+ infiltrates composed of cytotoxic (CD8+GzmB+, Ki-67+, CD69+) and regulatory (FOXP3+, CCR4+) subsets. Higher CD8+ activity correlated with smaller tumors and longer disease-free survival, whereas FOXP3+ enrichment and TGF-β2 signaling promoted immune evasion. Immunosuppressed patients demonstrated diminished CD8+ density and clonality. Immune modulation with PD-1/PD-L1 blockade, imiquimod, HPV vaccination, or OX40 stimulation enhanced effector function. The cSCC immune microenvironment reflects a balance between cytotoxic and suppressive factors. Harmonizing multimodal immune profiling and integrating spatial context with systemic immune status may advance both prognostic stratification and therapeutic design.

Dermatopathology doi: 10.3390/dermatopathology13010005

Authors: Calla M. Sullivan Dominick DiMaio Scott Lauer Dinesh Pradhan Julie Youngs Kaeli Samson Corey J. Georgesen

Accurate diagnosis of melanomas is crucial for proper evaluation and treatment. One immunohistochemical stain frequently utilized is PRAME (PReferentially expressed Antigen in MElanoma), a tumor-associated antigen expressed in most melanomas. This study aims to evaluate the reproducibility of PRAME scoring performed by dermatopathologists at an academic tertiary referral medical center. A blinded survey was designed featuring 21 melanocytic neoplasms stained with PRAME and H&E. For each case, five dermatopathologists provided a PRAME score from 0–4+, percent PRAME positivity, values for H-score, and a descriptive interpretation. Absolute agreement across raters was assessed using a Kappa statistic for PRAME score and intraclass correlations (ICCs) for H-score and PRAME percentage. Statistical analysis indicated poor inter-rater reliability for PRAME score (Kappa = 0.16), percent PRAME positivity (ICC = 0.31), and H-score (ICC = 0.40). Reporting language varied among pathologists. Our study demonstrated that the interpretation of PRAME immunohistochemistry lacks reproducibility, especially for challenging lesions. This suggests that a more rigorous, defined, and reproducible scoring method should be investigated for equivocal cases. Future studies may explore the utility of artificial intelligence software in the interpretation of PRAME for borderline lesions to improve reliability and standardize scoring.

Dermatopathology doi: 10.3390/dermatopathology13010004

Authors: Padol Chamninawakul Xiaotian Wu Joyce S. S. Lee

Reticulated acanthoma with sebaceous differentiation (RASD) is a rare, benign cutaneous neoplasm. Its variable clinical presentation frequently mimics both benign and malignant entities, posing a significant diagnostic challenge. We report a case of pigmented RASD in a 78-year-old Malay male of Fitzpatrick skin type IV who presented with a 5-year history of an 8 × 5 mm deeply pigmented, asymmetrical nodule on the left upper back, with a 2 mm central raised area showing less pigmentation. The lesion was clinically suspicious for malignant melanoma. Histopathological examination revealed characteristic features of RASD: a broad, plate-like, reticulated and pigmented epidermal proliferation with clusters of mature sebocytes at the bases of anastomosing rete ridges. Following biopsy confirmation, the residual lesion is being managed conservatively with observation. This case demonstrates an unusual heavily pigmented clinical presentation that completely obscured the typical yellowish hue associated with sebaceous differentiation, highlighting pigmented RASD as an important diagnostic pitfall in patients with skin of color. In conclusion, RASD should be included in the differential diagnosis of pigmented cutaneous lesions, especially in patients with skin of color. Recognition of this benign entity can prevent unnecessary aggressive surgical intervention.

Dermatopathology doi: 10.3390/dermatopathology13010003

Authors: Carlo Francesco Tomasini Lorenzo Magnani

Abductive reasoning, or abduction, is a key process in scientific discovery and medical diagnosis. In everyday dermatology and dermatopathology, however, it functions as the practical engine behind differential diagnosis, clinicopathologic correlation, and disciplined pattern recognition. In this paper, we retain the epistemological foundation of abduction but translate it into usable steps for clinicians and dermatopathologists. We distinguish abduction from deduction and induction; separate creative abduction (which generates new concepts) from selective abduction (daily diagnostic choice); and show how both operate within a simple Select-and-Test (ST) Model: select a hypothesis, deduce what else should be true, test against data, and then update. We then reinterpret Ackerman’s algorithmic method of pattern analysis as an operationalization of the ST-Model. Through a couple of concise case vignettes, we illustrate visual and manipulative abduction, nonmonotonic updates, and the role of artifacts (dermoscopy, DIF, stains) as so-called epistemic mediators. Finally, we map contemporary AI tools to selective abduction and propose practical guardrails for fairness, transparency, and accountability. The result is a pragmatic framework that preserves philosophical depth while addressing the daily needs of dermatologists and dermatopathologists in the clinic and at the microscope.

Dermatopathology doi: 10.3390/dermatopathology13010002

Authors: Aysin Kaya Jean-Hilaire Saurat Nathalie Satta Gürkan Kaya

In this study we evaluated the expression of Angiopoietin 1, Angiopoietin 2, and Tie2 by immunohistochemistry in the skin of 10 patients with erythemato telangiectatic and papulopustular rosacea. Significantly increased expression of Tie2 and Angiopoietin 2 in the endothelial cells of the dermal vessels in rosacea skin vs. non-lesional skin (100% and 33.3% for Tie2, and 100% and 50% for Angiopoietin 2) was observed. There was no difference in the expression of Angiopoietin 1 and phosphorylated Tie2 (pTie2) between the lesional skin of rosacea and non-lesional skin.

Dermatopathology doi: 10.3390/dermatopathology13010001

Authors: Rieke Löper Lennart Abels Daniel Otero Baguer Felix Bremmer Michael P. Schön Christina Mitteldorf

Lentigo maligna (LM) is a melanoma in situ with high cumulative sun damage. Histological evaluation of resection margins is difficult and time-consuming. Melanocyte density (MD) is a suitable, quantifiable, and reproducible diagnostic criterion. In this retrospective single-centre study, we investigated whether an artificial intelligence (AI) tool can support the assessment of LM. Training and evaluation were based on MD in Sox-10-stained digitalised slides. In total, 86 whole slide images (WSIs) from LM patients were annotated and used as a training set. The test set consisted of 177 slides. The tool was trained to detect the epidermis, measure its length, and determine the MD. A cut-off of ≥30 melanocytes per 0.5 mm of epidermis length was defined as positive. Our AI model automatically recognises the epidermis and measures the MD. The model was trained on nuclear immunohistochemical signals and can also be applied to other nuclear stains, such as PRAME or MITF. The WSI is automatically visualised by a three-colour heat map with a subdivision into low, borderline, and high melanocyte density. The cut-offs can be adjusted individually. Compared to manually counted ground truth MD, the AI model achieved high sensitivity (87.84%), specificity (72.82%), and accuracy (79.10%), and an area under the curve (AUC) of 0.818 in the test set. This automated tool can assist (dermato) pathologists by providing a quick overview of the WSI at first glance and making the time-consuming assessment of resection margins more efficient and more reproducible. The AI model can provide significant benefits in the daily routine workflow.

Dermatopathology doi: 10.3390/dermatopathology12040043

Authors: Sumeyye Ozer Priya Agarwal Noah Musolff Brendan Plann-Curley Gizem Cosgun Helen Yanyu Sun Babar Rao

Melanoma is a highly aggressive skin cancer primarily linked to ultraviolet (UV) radiation. However, the potential role of ionizing radiation from radiotherapy in melanoma development remains unclear. This review synthesizes data from epidemiologic studies and case reports on melanoma after radiation exposure. Evidence indicates that childhood radiotherapy, even at low doses, is associated with an increased melanoma risk, plausibly reflecting the heightened radiosensitivity of developing melanocytes. Occupational radiation exposure, particularly in earlier eras with insufficient shielding, also appears to elevate risk. In patients exposed to radiation in adulthood, findings are mixed: large population datasets suggest a modest increase in melanoma following therapeutic radiation, whereas some case–control analyses do not demonstrate a clear dose–response relationship. UV radiation promotes melanomagenesis through direct DNA photoproducts driving characteristic C>T transitions at dipyrimidine sites, alongside oxidative stress and local immune modulation that facilitate malignant transformation. Collectively, individuals with prior radiotherapy, especially those irradiated in childhood, should be considered at increased melanoma risk and may benefit from long-term, targeted surveillance of irradiated fields. Awareness of this association between radiation exposure and melanoma may also support clinicopathologic correlation during the diagnostic evaluation of melanocytic lesions. Future work should define dose–response relationships in contemporary radiotherapy methods, characterize molecular signatures of ionizing radiation-associated melanomas, and establish evidence-based surveillance strategies for high-risk cohorts.

Dermatopathology doi: 10.3390/dermatopathology12040042

Authors: Dorra Guermazi Sarina Khemchandani Samer Wahood Cuong Nguyen Elie Saliba

Melanoma subtyping plays a vital role in histopathological diagnosis, informing prognosis and, in some cases, guiding targeted therapy. However, conventional histologic classification is constrained by inter-rater reliability, morphologic overlap, and the underrepresentation of rare subtypes. Deep learning (DL)—particularly convolutional neural networks (CNNs)—presents a compelling opportunity to enhance diagnostic precision and reproducibility through automated analysis of histopathologic slides. This review examines the clinical importance and diagnostic challenges of melanoma subtyping, outlines core DL methodologies in dermatopathology, and synthesizes current advances in applying DL to subtype classification. Pertinent limitations including dataset imbalance, a lack of interpretability, and domain generalizability are discussed. Additionally, emerging directions such as multimodal integration, synthetic data generation, federated learning, and explainable AI are highlighted as potential solutions. As these technologies mature, DL holds considerable promise in advancing melanoma diagnostics and supporting more personalized, accurate, and equitable patient care.

Dermatopathology doi: 10.3390/dermatopathology12040041

Authors: Vincent Kimpe David Alvarez Martinez Sébastien Menzinger Gürkan Kaya

A 56-year-old patient presented to our dermatology clinic with asymmetric hyperpigmentation on her lower lip, which had developed over the previous six to twelve months. Her medical history included kidney and pancreas transplants, requiring chronic immunosuppression, and two lip filler injections with hyaluronic acid (HA). Clinical examination revealed irregular pigmented macules limited strictly to the lower lip. Histological analysis showed epidermal melanosis, pigmentary incontinence, solar elastosis, and amorphous dermal HA deposits, without evidence of melanocytic hyperplasia or granulomatous inflammation.

Dermatopathology doi: 10.3390/dermatopathology12040040

Authors: Alessandro Serrone Chiara Rustichelli Gian Luca Fadda Giuseppe Riva Massimo Rizzo Giovanni Cavallo

We report the case of a 16-year-old girl presenting with a painless, clinically stable subcutaneous swelling of the nasal dorsum with a three-year history. Despite an extensive multidisciplinary diagnostic work-up—including dermatological, otorhinolaryngological, and radiological evaluations (ultrasound, CT, and MRI)—the nature of the lesion remained indeterminate. In order to achieve a definitive diagnosis while preserving the nasal profile aesthetics, the mass was entirely excised via an endoscope-assisted closed rhinoseptoplasty approach. Histopathological analysis revealed a spindle cell lipoma characterized by CD34 positivity and a Ki-67 proliferation index of less than 1%. This finding is extremely rare in terms of both anatomical location and patient age. The present case highlights the crucial role of histopathological examination in establishing the correct diagnosis, supported by a multidisciplinary assessment.

Dermatopathology doi: 10.3390/dermatopathology12040039

Authors: Siddharth Venigalla Tanvir K. Dhaliwal Anvita Anumolu Lena Rafey Arturo P. Saavedra David D. Limbrick

Encephalocraniocutaneous lipomatosis (ECCL) is a rare congenital neurocutaneous disorder characterized by ocular, skin, and central nervous system manifestations. Despite its recognizable clinical features, such as nevus psiloliparus, histopathologic characterization of ECCL remains limited in the dermatopathology literature, and diagnosis is often clinical. This scarcity of published histopathological descriptions makes diagnostic confirmation challenging and underscores the value of synthesizing the available evidence. This comprehensive review synthesizes reported histopathological findings across cutaneous manifestations highlighting key tissue-level features that may aid diagnostic confirmation. Additionally, we review the emerging role of molecular diagnostics, particularly the identification of mosaic activating mutations in FGFR-1 and KRAS, which have been implicated in ECCL pathogenesis. By integrating clinicopathologic correlations with molecular insights, this review aims to enhance our dermatopathological understanding of ECCL, bolstering diagnostic reasoning and clinical decision making for this rare neurocutaneous condition.

Dermatopathology doi: 10.3390/dermatopathology12040038

Authors: Wickramasinghe Mudiyanselage Sithma Nilochana Wickramasinghe Primali Rukmal Jayasooriya Balapuwaduge Ranjit Rigobert Nihal Mendis Tommaso Lombardi

Background/Objectives: Oral focal mucinosis (OFM) and solitary cutaneous focal mucinosis (SCFM) are rare, benign lesions characterized by localized mucin deposition in the stromal connective tissue. While both share similar histological features, they occur in distinct anatomical sites and clinical contexts and have not been directly compared in the literature. Method: This study presents a case series of 39 OFM cases diagnosed over 25 years, supplemented by a literature review of previously reported OFM cases, and compares the combined data with published cases of SCFM. The literature-based analysis included 116 OFM cases published in four articles and 138 cases of SCFM published in five articles. Demographic and clinical data were extracted and analyzed, including age, sex, lesion location, size, duration, symptoms, clinical impression, treatment, and recurrence. Results: The mean age of OFM patients was 41 years, with a slight female predominance, most commonly affecting the gingiva. SCFM cases were more common in males, with a higher mean age of 52 years and frequent occurrence on the extremities and trunk. Both lesions were predominantly asymptomatic and managed by conservative excision. Due to its rare occurrence and nonspecific clinical presentation, both entities were frequently clinically misdiagnosed. Conclusions: In conclusion, this is the first study to directly compare OFM with SCFM and represents the largest series of OFM reported to date. The study provides new comparative insights into SCFM and OFM, highlighting differences in age, gender, lesion site, size, and symptomatology. SCFM predominantly affects older males on the extremities, whereas OFM occurs in younger females, mainly in the gingiva, with larger, sometimes symptomatic lesions, and with a very low recurrence rate.

Dermatopathology doi: 10.3390/dermatopathology12040037

Authors: Christine Sutrisno Desy Pramita Ita Dewi

Neurofibromatosis type 1 (NF1) is a prevalent neurocutaneous illness resulting from mutations in the NF1 gene, usually diagnosed according to clinical criteria set by the National Institutes of Health (NIH). These encompass café-au-lait macules, axillary freckling, Lisch nodules, ocular gliomas, osseous lesions, neurofibromas, and familial history. Atypical instances exhibiting partial or isolated characteristics, such as numerous cutaneous neurofibromas (cNFs) absent other classical manifestations, provide a diagnostic difficulty and may be little acknowledged in clinical environments. We describe a 47-year-old male with several soft, non-tender, pinkish-red papules and nodules dispersed throughout the face, torso, limbs, and back. A solitary café-au-lait macule measuring 3 x 2 cm was seen below the right breast, no axillary or inguinal freckling was observed, Lisch nodules were absent during ophthalmologic examination, and there was no pertinent family history. The histopathological examination of a skin lesion verified the diagnosis of cutaneous neurofibroma. According to the NIH guidelines, the patient did not satisfy the requirements for a conclusive diagnosis of NF1. This instance underscores the clinical intricacy of NF1 spectrum diseases and suggests the potential for mosaic NF1 or a minor phenotypic variation. The existence of several cNFs without systemic involvement undermines the adequacy of existing diagnostic paradigms, particularly in adults who exhibit no early-life signs. The psychosocial challenges linked to widespread cNF distribution highlight the necessity for a comprehensive assessment. Limitations encompass the lack of genetic testing, which would have facilitated the confirmation of the diagnosis and the assessment of probable mosaicism. Isolated cutaneous neurofibromas, devoid of other conventional NF1 characteristics, are an uncommon yet clinically pertinent manifestation. Clinicians must uphold a heightened level of suspicion for aberrant NF1 phenotypes and contemplate further examination, using molecular diagnostics where feasible. Reevaluating diagnostic criteria to include these polymorphisms is essential for prompt identification, effective care, and enhanced patient outcomes.

Dermatopathology doi: 10.3390/dermatopathology12040036

Authors: Pablo Izarra Marwa Zohdy Helmut Beltraminelli Laurence Feldmeyer

Dermatofibromas (DFs) are benign neoplasms of the dermis typically found on the extremities of young adults. In approximately 3–5% of cases, basaloid cell hyperplasia (BCH) is observed overlying DFs. BCH is characterized by the proliferation of basaloid cells within the epidermis. BCH and superficial basal cell carcinoma (BCC) share many histological features, making their differentiation challenging. It is therefore unclear if the proliferation of basaloid cells in DFs represents an inductive process or, conversely, a malignant transformation indicative of BCC. The primary objective of our study was to determine whether BCH can be distinguished from superficial BCC using histology and immunhistological techniques. The histological and immunohistochemical characteristics of 43 DF samples with overlying BCH revealed significant similarities in staining patterns with those of superficial BCC described in the literature. These findings point to the need for innovative methods, such as molecular techniques, to refine diagnostic accuracy.

Dermatopathology doi: 10.3390/dermatopathology12040034

Authors: Sean Lider Chanel Mandap Pavandeep Gill

There are many benign skin neoplasms encountered in dermatopathology practice that can be associated with underlying genetic disorders. Although benign themselves, these lesions can offer insight into the potential for development of internal malignancies in patients with these hereditary syndromes. An astute dermatopathologist will recognize clues that suggest a syndromic association of these lesions, such as the presence of multiple lesions, distinct histologic growth patterns, and the results of ancillary immunohistochemical testing. The dermatopathologist can then guide the referring clinician to obtain additional clinical and family history and, if appropriate, pursue further screening and genetic testing. This review article will provide an overview of the clinical and histologic features associated with select common and uncommon benign skin neoplasms with syndromic associations.

Dermatopathology doi: 10.3390/dermatopathology12040035

Authors: André Aparício Martins José Carlos Cardoso André Pinho

Acroangiodermatitis is an uncommon angioproliferative dermatosis, related to chronic circulatory diseases, such as chronic venous insufficiency and arteriovenous malformations. We describe the case of a 32-year-old healthy male presenting with a pruritic, brownish lesion on the dorsal surface of the left foot, evolving for ten years. Physical examination revealed a brown plaque, with a verrucous surface, on the distal dorsum and medial border of the left foot. Histopathology disclosed a marked neovascularization of the upper dermis, associated with erythrocyte extravasation and hemosiderin deposition. Immunochemistry for HHV-8 was negative. CT angiography revealed multiple serpiginous vessels on the dorsum of the left foot, suggestive of a venous malformation. The diagnosis of acroangiodermatitis was established and the patient started topical corticosteroids and compression stockings, without improvement. Although scarcely described in the literature, treatment with PDL was proposed given the vascular proliferation confined to the papillary dermis. After two sessions, a significant improvement was observed. This case emphasises dermatopathology as the gold standard for the differential diagnosis with Kaposi sarcoma. In addition, it highlights PDL as a promising therapeutic option, based on the superficial histopathological location.

Dermatopathology doi: 10.3390/dermatopathology12040033

Authors: Seraphima S. Sidhom Luke A. Laconi Christopher A. LaFond Steven C. Weindorf

Human herpesvirus-8 (HHV-8)-associated multicentric Castleman disease (MCD) is a rare lymphoproliferative disorder with systemic and cutaneous manifestations that can be diagnostically challenging, especially in immunocompromised patients. We report the case of a 68-year-old man with HIV and biopsy-proven Kaposi sarcoma (KS), who developed progressive fevers, night sweats, weight loss, and fatigue, accompanied by diffuse lymphadenopathy, splenomegaly, and new erythematous and hyperpigmented lesions shortly after intravenous immunoglobulin therapy for Guillain–Barré syndrome. A laboratory evaluation revealed that the patient had elevated total protein and polyclonal hypergammaglobulinemia, without monoclonality. Imaging demonstrated widespread lymphadenopathy and splenomegaly. A core lymph node biopsy showed polytypic plasmacytosis, but was non-diagnostic. Given the ongoing symptoms, an excisional biopsy was performed, revealing regressed germinal centers with increased interfollicular vascularity, mantle zone “onion skinning,” and HHV-8 LANA-1 nuclear positivity, establishing the diagnosis of HHV-8-associated MCD. Rituximab monotherapy was initiated, resulting in clinical improvement, resolution of the constitutional symptoms, and stabilization of ascites. This case highlights the importance of maintaining a high index of suspicion for MCD in patients with KS who develop new systemic or cutaneous findings, the limitations of a core biopsy, and the value of a timely excisional biopsy in guiding diagnosis and treatment.

Dermatopathology doi: 10.3390/dermatopathology12030032

Authors: Ioannis-Alexios Koumprentziotis Evdoxia Panou Antonis Tsimpidakis Maria Gerochristou Theodoros Iliakis Leonidas Marinos Alexander Stratigos Vasiliki Nikolaou

A 27-year-old female with no significant medical or dermatologic history presented with a persistent acneiform eruption on the face. The patient had been treated with multiple topical and systemic anti-acne treatments with no significant improvement over a period of two years. A punch biopsy was performed on the right cheek lesion showing dense lymphocytic infiltrates of the reticular dermis with peri- and intra-follicular distribution.

Dermatopathology doi: 10.3390/dermatopathology12030031

Authors: Lauren Fleshner Alyssa Sayegh Mehmet Fatih Atak Rahim Hirani Banu Farabi Bijan Safai Shoshana Marmon

Despite therapeutic advancements, malignant melanoma remains a leading cause of skin cancer-related mortality, with incidence continuing to rise globally. Traditional prognostic tools offer important clinical guidance but fail to capture the biological heterogeneity of melanoma or reliably predict responses to emerging therapies. In this review, we summarize recent advances in prognostic and predictive molecular biomarkers reported over the past five years. We discuss immunohistochemical and tissue-based markers, circulating biomarkers, microRNAs, and gene expression profiles that enhance risk stratification and inform surveillance strategies. We also review immune-related markers that may predict response to immune-checkpoint inhibitor therapy. Lastly, we highlight investigational biomarkers—including gene signatures, epigenomic alterations, and microbiome influences—that are shaping the future landscape. Together, these advances reflect a shift toward precision oncology in melanoma, with the integration of biomarker-driven strategies offering the potential to personalize treatment and improve patient outcomes.

Dermatopathology doi: 10.3390/dermatopathology12030030

Authors: Carolyne Simard-Bisson Sébastien Larochelle Véronique J. Moulin Bernard Fruteau de Laclos

Stratum Corneum (SC) formation in the human epidermis requires lipid processing. Lipoxygenases (LOXs) such as 12R-Lipoxygenase (12R-LOX) and Epidermis-type lipoxygenase 3 (eLOX-3) contribute to this process. Mutations in their genes cause Autosomal Recessive Congenital Ichthyosis (ARCI) in patients. On the other hand, 12S-lipoxygenase (12S-LOX) is expressed in the human epidermis, but its role still remains to be clarified. The involvement of eLOX-3, 12R, and 12S-LOX in conditions or processes such as skin photodamage, wound healing, psoriasis, and atopic dermatitis is suggested but still remains unclear. In order to eventually gain a better understanding of the role of these LOXs in such processes, models of Tissue-Engineered Skins (TESs) with an impaired expression for the native form of either eLOX-3, 12R-LOX, or 12S-LOX were produced using CRISPR-Cas9(D10A) technology. All three models showed impaired keratinocyte differentiation and changes in the prevalence or the size of lipid droplets within the most superficial layers, thus reproducing features observed in ARCI and supporting a role for 12S-LOX in SC formation. Since eLOX-3 and 12R-LOX depleted TES’s reproduced features observed in ARCI, such models can be considered as reliable tools for the functional studies of these LOXs in the human epidermis.

Dermatopathology doi: 10.3390/dermatopathology12030029

Authors: Sandra Jerkovic Gulin Ivana Ilic Dario Gulin Georgios Kravvas Romana Ceovic

Introduction: Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma, often exhibiting loss of pan-T-cell markers such as CD2, CD3, CD5, and CD7. While these immunophenotypic alterations assist in diagnosis, their prognostic relevance in early-stage MF remains uncertain. This study aimed to determine whether immunohistochemical loss of T-cell markers CD2, CD3, CD5, and CD7 in patients with early-stage mycosis fungoides is associated with overall survival and progression-free survival. Methods: This retrospective included 83 patients with stage IA–IIA MF diagnosed between 2003 and 2012 at a single institution. Immunohistochemical staining of archived biopsy specimens was performed for CD2, CD3, CD5, and CD7. Loss of marker expression was defined as absence in ≥30% of lymphocytes. Clinical and histopathological data were correlated with survival and progression outcomes using Kaplan–Meier curves and log-rank tests. Results: Loss of at least one T-cell marker was identified in 66% of patients, most commonly CD7 (72%), followed by CD5 (11%) and CD2 (11%). No cases showed loss of CD3 expression. CD7 loss was significantly associated with shorter progression-free survival (p < 0.05), but not with overall survival. No significant associations were found between CD2 or CD5 loss and either survival or disease progression. Conclusions: CD7 loss was the only immunohistochemical abnormality significantly associated with earlier disease progression in early-stage MF, suggesting a potential prognostic role. In contrast, loss of CD2 and CD5 did not affect survival or progression, and CD3 was preserved in all cases. These findings highlight the value of incorporating CD7 status into prognostic assessment, although larger studies are needed to confirm its utility.

Dermatopathology doi: 10.3390/dermatopathology12030028

Authors: Lamia Alakrash Renad AlKanaan Rema Aldihan Alanoud Alsuhibani Salman Almalki

Dermatofibroma is a common mesenchymal skin lesion that typically presents as a firm, slow-growing nodule. Generally, such lesions are asymptomatic; however, they can also cause discomfort in some cases. Ulceration is an uncommon feature of dermatofibroma, and diagnosis in such cases is often difficult. We report a case of a 67-year-old female with multiple comorbidities, including pancreatic cancer undergoing neoadjuvant chemotherapy, who was admitted for acute pulmonary embolism. The patient presented with an incidental medial thigh lesion. The lesion was asymptomatic, ulcerated, and oozing pus one month before presentation. Clinical examination revealed a 3 × 2 cm deep ulcer with a punched-out edge, a dry yellow-white base, and a firm violaceous border. Histopathology confirmed dermatofibroma with epidermal hyperplasia, dermal spindle cell proliferation, histiocytes, and collagen trapping. Immunohistochemistry was positive for CD68, CD10, and Factor XIII. Due to the deteriorating condition of the patient, no intervention was provided to her, and she succumbed to her primary illness. This case is unique due to its atypical ulcerative presentation in a patient with complex systemic illness and emphasizes distinguishing between benign lesions and malignant mimics, especially in cases which have ambiguous clinical presentation.

Dermatopathology doi: 10.3390/dermatopathology12030027

Authors: Muhammad N. Mahmood

I have reviewed the insightful comments on my review article titled “Direct Immunofluorescence of Skin and Oral Mucosa: Guidelines for Selecting the Optimum Biopsy Site” [...]

Dermatopathology doi: 10.3390/dermatopathology12030026

Authors: Şebnem Demiral Yunus Özcan Mehmet Gamsızkan

Compilation written by Muhammad N [...]

Dermatopathology doi: 10.3390/dermatopathology12030025

Authors: Nessr Abu Rached Stefanie Bruckmüller Martin Doerler Hanna Telkemeyer Lennart Ocker Yannik Haven Daniel Myszkowski Markus Stücker Eggert Stockfleth Falk G. Bechara

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory disease with a complex immune response. Given the considerable heterogeneity of the clinical phenotype of HS, this study aimed to analyse the immunohistochemical pattern of interstitial inflammation. Methods: Immunohistochemical analysis was performed on skin samples from 49 patients with HS. The immunohistochemical markers CD3, CD4 and CD8 for T-cells, CD20 for B-cells, CD138 for plasma cells and CD30, CD56, Bcl-2 and Bcl-6 were stained on lesional skin. Results: The analysis of immune cell dominance in patients with HS revealed that 33.3% of the cohort exhibited B-cell dominance, defined as a ratio of the sum of CD20+ and CD138+ cells to CD3+ cells greater than 1, while the majority (66.7%) demonstrated T-cell dominance, defined as a ratio of CD3+ cells to the sum of CD20+ and CD138+ cells greater than 1. B-cell-dominant HS is associated with a significantly elevated probability of mammary involvement (13.3% vs. 0%; p = 0.041). T-cell-dominant HS patients tended to demonstrate a higher mean tobacco consumption, but not significantly (20 vs. 5 tobacco pack-years; p = 0.06). CD4-dominant HS patients exhibited a significantly greater involvement of the mons pubis (62.5% vs. 28.6%, p = 0.023) compared to CD8-dominant patients, who demonstrated a significantly higher number of abscesses (p = 0.027). Conclusions: For the first time, we describe the clinical and immunohistochemical characteristics of T-cell- and B-cell-dominant HS. Although HS seems to be more dominated by T-cells, a B-cell dominance was found in 33% of cases.

Dermatopathology doi: 10.3390/dermatopathology12030024

Authors: Gianmarco Saponaro Elisa De Paolis Mattia Todaro Francesca Azzuni Giulio Gasparini Antonio Bosso Giuliano Ascani Angelo Minucci Alessandro Moro

Pilomatricomas are benign tumors originating from hair follicle matrix cells and represent the most common skin tumors in pediatric patients. Pilomatricomas may be associated with genetic syndromes such as myotonic dystrophy, familial adenomatous polyposis (FAP), Turner syndrome, Rubinstein–Taybi syndrome, Kabuki syndrome, and Sotos syndrome. This study reviews the literature on pilomatricomas occurring in syndromic contexts and presents a novel case linked to Apert syndrome. A systematic review was conducted using PubMed and Cochrane databases, focusing on case reports, case series, and reviews describing pilomatricomas associated with syndromes. A total of 1272 articles were initially screened; after removing duplicates and excluding articles without syndromic diagnoses or lacking sufficient data, 81 full-text articles were reviewed. Overall, 96 cases of pilomatricomas associated with genetic syndromes were identified. Reports of patients with Apert syndrome who do not develop pilomatricomas are absent in the literature. Pilomatricomas predominantly affect pediatric patients, with a slight female predominance, and are often the first manifestation of underlying genetic syndromes. Our study highlights previously unreported associations of pilomatricoma with Apert syndrome, providing molecular insights. This study contributes to understanding the clinical and molecular features of pilomatricomas in syndromic contexts and underscores the importance of genetic analysis for accurate diagnosis and management.

Dermatopathology doi: 10.3390/dermatopathology12030023

Authors: Ryoji Tanei Yasuko Hasegawa

Whether the spongiotic reaction caused by the interaction of keratinocytes, T-lymphocytes, inflammatory dendritic epidermal cells (IDECs), and Langerhans cells (LCs) observed in atopic dermatitis (AD) represents a common feature of spongiosis in various skin diseases remains unclear. We analyzed the characteristics of spongiosis in AD compared with those in other eczematous dermatitis and inflammatory skin diseases by using immunohistochemical methods. Infiltration of IDECs (CD11c+ cells and/or CD206+ cells) and T-lymphocytes, accompanied by degenerated keratinocytes and aggregated LCs (CD207+ cells), was frequently observed as a common feature of spongiosis in multiple conditions. However, IDECs expressing IgE were identified exclusively in IgE-mediated AD. Aggregation of IDECs was predominantly observed in the spongiosis of adaptive immune-mediated eczematous disorders, such as AD and allergic contact dermatitis. These IDEC aggregations constituted the major components of the epidermal dendritic cell clusters seen in AD and other eczematous or eczematoid dermatoses, and may serve as a useful distinguishing marker from Pautrier collections seen in cutaneous T-cell lymphoma. These findings suggest that IDECs, in cooperation with other immune cells, may play a pivotal role in spongiosis formation in AD and various skin diseases, although the underlying immunopathological mechanisms differ among these conditions.

Dermatopathology doi: 10.3390/dermatopathology12030022

Authors: Amy Xiao Arivarasan Karunamurthy Oleg Akilov

In this review, we explore the complexities of objectively assessing the response to immunotherapy in mycosis fungoides (MF), a prevalent form of cutaneous T-cell lymphoma. The core challenge lies in distinguishing between reactive and malignant lymphocytes amidst treatment, particularly given the absence of uniform pathological biomarkers for MF. We highlight the vital role of emerging histological technologies, such as multispectral imaging and spatial transcriptomics, in offering a more profound insight into the tumor microenvironment (TME) and its dynamic response to immunomodulatory therapies. Drawing on parallels with melanoma—another immunogenic skin cancer—our review suggests that methodologies and insights from melanoma could be instrumental in refining the approach to MF. We specifically focus on the prognostic implications of various TME cell types, including CD8+ tumor-infiltrating lymphocytes, natural killer (NK) cells, and histiocytes, in predicting therapy responses. The review culminates in a discussion about adapting and evolving treatment response quantification strategies from melanoma research to the distinct context of MF, advocating for the implementation of novel techniques like high-throughput T-cell receptor gene rearrangement analysis. This exploration underscores the urgent need for continued innovation and standardization in evaluating responses to immunotherapies in MF, a field rapidly evolving with new therapeutic strategies.

Dermatopathology doi: 10.3390/dermatopathology12030021

Authors: Ji Fung Yong Claudine Howard-James Stephen Crowther Anne-Marie Tobin Caitriona Hackett

A 29-year-old gentleman of African descent presented to the emergency department with a three month history of a rash affecting the trunk, upper limbs, and thighs. The patient was unsure of any triggers and denied any preceding illness, new medications, illicit drug use, or recent vaccinations. On examination, there was a widespread papulosquamous eruption characterised by scaly, hyperpigmented papules and plaques involving the trunk, upper arms, and upper thighs. A definitive diagnosis was established through a diagnostic skin biopsy of a fresh lesion.

Dermatopathology doi: 10.3390/dermatopathology12030020

Authors: Nessr Abu Rached Natalie Orlinski Eggert Stockfleth Markus Stücker Martin Doerler

Background: We present an interesting case involving a tumour comprising both basal cell tumour cells and sarcomatoid tumour cells. An 86-year-old woman presented with an erythematous lesion on her left cheek. Clinical and dermoscopic findings suggested BCC. Complete excision and histopathological examination revealed a BCC with a separate proliferation of atypical spindle and epithelioid cells. Immunohistochemical staining supported the diagnosis, with basaloid cells positive for CK5/6 and Ber-EP4 and sarcomatoid cells positive for CD10 and vimentin. Results: Histology and immunohistochemistry confirmed a basal cell carcinoma with sarcomatoid differentiation. The close proximity of sarcomatoid cells to the BCC component suggests a potential role of epithelial–mesenchymal interactions in tumour development. Further investigations into the exact origin of this tumour are required. Conclusion: Basal cell carcinoma with sarcomatoid differentiation is rare. This case highlights the importance of thorough histological and immunohistochemical evaluation. Further studies are necessary to better understand the pathogenesis of such collision tumours.

Dermatopathology doi: 10.3390/dermatopathology12030019

Authors: Caterina Damiani Cesare Ariasi Giuseppe La Rosa Francesca Di Lauro Mariachiara Arisi Vincenzo Maione Marina Venturini Simone Soglia

Penile intraepithelial neoplasia (PeIN) is a rare but clinically significant condition that can progress to invasive squamous carcinoma. Early diagnosis is crucial but often challenging due to its heterogeneous clinical and dermoscopic presentation, which can mimic other benign or malignant lesions. In this study, we report two cases of pigmented penile lesions evaluated using non-invasive imaging techniques: reflectance confocal microscopy (RCM) and line-field confocal optical coherence tomography (LC-OCT). Both methods revealed characteristic features such as hyperkeratosis, parakeratosis, acanthosis, nuclear pleomorphism of keratinocytes, and the presence of bright intraepithelial dendritic cells, correlating closely with histopathological findings of high-grade basaloid PeIN. Our findings highlight the valuable role of RCM and LC-OCT in improving the differential diagnosis of genital lesions, potentially reducing the need for invasive diagnostic procedures and ensuring early, appropriate management.

Dermatopathology doi: 10.3390/dermatopathology12020018

Authors: Sarah Miny Gaël Runel Julien Chlasta Christelle Bonod

Background: Diabetics accumulate Advanced Glycation End products (AGEs) such as Nε-(carboxymethyl)lysine (CML) in their skin, which can provoke changes in the skin’s biomechanical properties. The same changes are also observed during aging. Collagen is one of the first targets of glycation, and this leads to the disruption of the dermis, potentially contributing to the skin complications seen in diabetes, like impaired wound healing and the formation of chronic ulcers. We therefore investigated whether it was possible to detect differences in the biomechanical properties of the reticular dermis by comparing C57/BL6 control mice, type 1 and type 2 diabetic mice, and aged mice. Methods: To investigate this, we used an Atomic Force Microscope (a type of local probe microscope used to visualize the surface topography of a sample) to measure the elastic modulus of each skin sample. The elastic modulus is a parameter that describes a tissue’s resistance to elastic deformation when stress is applied. We also determined whether diabetes is associated with the accumulation of AGEs via Western blots. Results: We found that type 2 diabetic mice and aged mice had a stiffer reticular dermis than young control mice. No differences were found in type 1 diabetic mice. The results of the Western blot did not reveal any significant differences in the CML content in different types of mice, although a non-significant increase was found in type 2 diabetic and aged mice. We show that there is a significant positive correlation between the amount of CML in a mouse and the rigidity of its reticular dermis. Conclusions/interpretation: We have demonstrated that increased glycation in mouse skin is correlated with the biomechanical properties of that skin, which explains the wound healing defects diabetic patient’s experience. AFM is therefore a powerful technique that could be used to characterize the mechanical effects of treatments aimed at reducing the level of AGEs in the skin.

Dermatopathology doi: 10.3390/dermatopathology12020017

Authors: Aya Fadel Jayakumar Nithura Zahraa F. Saadoon Lamia Naseer Angelo Lopez-Lacayo Ligia Elena Rojas Solano Chaveli Palau Morales Robert J. Hernandez Hussain Hussain

Psoriasis is a chronic immune-mediated inflammatory skin disorder characterized by keratinocyte hyperproliferation, impaired epidermal barrier function, and immune dysregulation. The Th17/IL-23 axis plays a central role in its pathogenesis, promoting the production of key pro-inflammatory cytokines such as IL-17, IL-23, and TNF-α, which sustain chronic inflammation and epidermal remodeling. Emerging evidence suggests that SARS-CoV-2 may trigger new-onset or exacerbate existing psoriasis, likely through viral protein-induced activation of toll-like receptors (TLR2 and TLR4). This leads to NF-κB activation, cytokine release, and enhanced Th17 responses, disrupting immune homeostasis. Erythrodermic psoriasis (EP), a rare and severe variant, presents with generalized erythema and desquamation, often accompanied by systemic complications, including infection, electrolyte imbalance, and hemodynamic instability. In a murine model of SARS-CoV-2 infection, we found notable cutaneous changes: dermal collagen deposition, hair follicle destruction, and subcutaneous adipose loss. Parallel findings were seen in a rare clinical case (only the third reported case) of EP in a patient with refractory psoriasis, who developed erythroderma after off-label initiation of dupilumab therapy. The patient’s histopathology closely mirrored the changes seen in the SARS-CoV-2 model. Histological evaluations also reveal similarities between psoriasis flare-ups following dupilumab treatment and cutaneous manifestations of COVID-19, suggesting a shared inflammatory pathway, potentially mediated by heightened type 1 and type 17 responses. This overlap raises the possibility of a latent connection between SARS-CoV-2 infection and increased psoriasis severity. Since the introduction of COVID-19 vaccines, sporadic cases of EP have been reported post-vaccination. Although rare, these events imply that vaccine-induced immune modulation may influence psoriasis activity. Our findings highlight a convergence of inflammatory mediators—including IL-1, IL-6, IL-17, TNF-α, TLRs, and NF-κB—across three triggers: SARS-CoV-2, vaccination, and dupilumab. Further mechanistic studies are essential to clarify these relationships and guide management in complex psoriasis cases.

Dermatopathology doi: 10.3390/dermatopathology12020016

Authors: Enric Piqué-Duran Mikel Azcue-Mayorga Belinda Roque-Quintana Odalys García-Vázquez Antonio Ruedas-Martínez

A 71-year-old Caucasian woman presented with lesions on both elbows. A physical examination revealed arcuate plaques with raised erythematous edges and central clearing. Comedones and cysts were evident on the border of the lesions. The dermatoscopic view showed the presence of pores, in addition to granuloma annulare changes. The biopsies showed changes according to granuloma annulare, but the granulomas were closely related to comedones and cysts. Furthermore, the presence of elastophagocytosis via multinucleated Langhans-type giant cells was evident. Verhoeff–van Gieson staining highlighted the transepithelial elimination of elastic fibers in the bottom of some cysts. The presence of comedones or cysts is exceptional in granuloma annulare. Only four similar cases have been reported. Although all previous cases showed lesions in sun-exposed areas over photodamaged skin, only our case showed transepithelial elimination of elastic fibers. Diabetes mellitus (DM) could play a role in the pathogenesis of this variant of actinic granuloma annulare, because most cases are associated with uncontrolled DM and the lesions improve after DM is controlled.

Dermatopathology doi: 10.3390/dermatopathology12020015

Authors: Jason El Jalkh Pia Maria Obeid Dorra Guermazi Aya Soubra Elie Saliba

A 64-year-old patient presented for management of symptomatic skin-colored papules symmetrically distributed over the lateral neck over the past two years, which failed to improve on multiple topical corticosteroids, antifungal creams, and topical calcineurin inhibitor. Histopathologic examination showed a regular epidermis with increased melanophages in the papillary dermis, without vacuolar degeneration of the basement membrane. Verhoeff Van Gieson stain highlighted a band-like zone of attenuated elastic fibers in the papillary dermis, while Von Kossa stain was negative for calcified fibers. PAS staining was negative for fungal organisms and Alcian blue showed no increase in dermal mucin.

Dermatopathology doi: 10.3390/dermatopathology12020014

Authors: Andreea Cătălina Tinca Bianca Andreea Lazar Andreea Raluca Cozac-Szőke Georgian Nicolae Radu Simina Petra Simion Diana Maria Chiorean Irina Bianca Kosovski Adrian Horațiu Sabău Raluca Niculescu Iuliu Gabriel Cocuz Raluca-Diana Hagău Emoke Andrea Szasz Sabin Gligore Turdean Ovidiu Simion Cotoi

Cutaneous metastases from internal organ cancers are diagnosed in approximately 0.2% of skin biopsies. This diagnosis can be the first sign of a previously undiagnosed malignancy with an internal organ origin. We conducted a retrospective study that included all cases of cutaneous metastases diagnosed in our hospital. A total of 25 patients were identified (14 females and 11 males). The average age of the patients included was 62.3. The most common primary cancer site was the lung for male patients, while for female patients it was the breast. In seven of our cases, cutaneous metastases were the first sign of an internal organ cancer. Common sites for cutaneous metastases in our study involved the anterior thoracic wall, the abdomen, and the scalp. Our study aims to highlight the importance of recognizing the histopathology of metastatic tumors and differentiating them from primary skin neoplasms. Immunohistochemistry is a mandatory tool for differential diagnosis in all cases, especially for patients who do not have a history of neoplasia.

Dermatopathology doi: 10.3390/dermatopathology12020013

Authors: Aurore D. Zhang Michelle Lazar Emiliya Akhundova Candice E. Brem Eric J. Beltrami Neelam A. Vashi

Melasma is an incredibly common dyschromic disorder, mostly impacting women with skin of color. There are three variants of melasma based on the depth of pathologic involvement: epidermal, mixed, and dermal. While there are many treatments for melasma, there is a paucity of research on melasma treatments and their dermatopathological correlates. A scoping review was conducted of all human trials on melasma with histopathologic analysis, including 37 trials in the final analysis. Most studies were conducted on women with a Fitzpatrick skin type of III or greater. Strong histologic evidence supports the utilization of retinols/retinoids for epidermal melasma and microneedling for dermal melasma. There is a paucity of trials conducted on melasma utilizing histologic correlates, and fewer still that are comprehensive to include analyses on quality of life.

Dermatopathology doi: 10.3390/dermatopathology12020012

Authors: Dina El-Rayes Katlin Wilson Sheilagh Maguiness Daniel Miller Gerardo Cazzato Alessio Giubellino

Congenital melanocytic nevi (CMN) are benign tumors present at birth or arising in the first few months of life. A small subset of these nevi present with mild atypical features and heterogeneous differentiation, including Schwannian differentiation. We present a case of a 3-week-old with a 7 cm red/purple scalp nodule consistent with CMN with mild atypical heterogeneous areas. On histology, there were dermal nests of spindle cells in a fibrillar matrix, with increased vessels and clusters of small round melanocytes interspersed between collagen bundles and around adnexal structures. The lesion also exhibited rare pagetoid ascent of melanocytes as single cells and nests. Overall, these features were consistent with a CMN with nodular proliferative neurocristic cutaneous hamartoma (NCH) with a component of a compound mild atypical melanocytic proliferation. Next generation sequencing (NGS) identified a novel SH2B1::BRAF fusion. This case highlights the diagnostic challenges of heterogeneous differentiation within CMN in young children.

Dermatopathology doi: 10.3390/dermatopathology12020011

Authors: Giorgia Di Marco Gianmarco Diego Bigotto Eleonora Cossar Nathalie Rizzo Stefania Guida Franco Rongioletti

Hydroxyurea (HU), a cornerstone treatment for myeloproliferative disorders, is associated with a wide range of cutaneous side effects, from xerosis and hyperpigmentation to more severe conditions like dermatomyositis-like eruptions (DM-LE) and nonmelanoma skin cancers (NMSC), particularly squamous cell carcinoma (SCC). In this review, we present a unique case of HU-induced DM-LE with histological evidence of keratinocyte dysplasia and p53 overexpression, followed by a systematic analysis of similar cases. Our findings reveal that the clinical presentation of DM-LE, while typically considered benign, shares clinical and histological features with hydroxyurea-associated squamous dysplasia (HUSD), a precancerous condition that may progress to SCC in chronically exposed patients. Key insights include the characteristic histopathological findings of DM-LE, the role of chronic HU therapy and UV-induced damage in promoting p53 overexpression, and the overlap between DM-LE and HUSD. Regular dermatologic monitoring, patient education on photoprotection, and the careful assessment of skin lesions in long-term HU users are essential for the early detection and prevention of malignancies. This review underscores the importance of distinguishing between DM-LE, HUSD, and SCC to optimize management and minimize risks associated with HU therapy.

Dermatopathology doi: 10.3390/dermatopathology12020010

Authors: Amal Makansi Charlotta Enerbäck Maria Madentzoglou Georgios Kravvas Sandra Jerkovic Gulin

Dermatofibromas (DFs) represent prevalent benign fibrohistiocytic tumors, typically manifesting as solitary lesions. In the majority of cases, the clinical presentation and dermoscopic and histopathological features of DFs adhere to a characteristic profile. However, DFs may exhibit atypical clinical presentations and, more commonly, histologic attributes, posing challenges in differential diagnosis. Both DFs and basal cell carcinomas (BCCs) are frequently encountered cutaneous lesions, each characterized by distinct clinical and dermoscopic features and microscopic morphology. The simultaneous occurrence of these two entities within the same lesion is rare. DFs have been documented to form collision tumors in conjunction with a spectrum of benign and malignant lesions, encompassing not only BCC but also balloon cell nevus, squamous cell carcinoma (SCC), and melanoma. Alterations in the epidermis overlaying a DF range from simple hyperplasia to the proliferation of basaloid cells. Accurate diagnosis, leading to the complete excision of the lesion, is contingent upon the recognition of dermoscopic criteria, precluding misinterpretation as a benign lesion. We present two cases of collision tumors comprising DF and BCC. This case report underscores the paramount importance of dermoscopy and adherence to dermoscopic criteria in the assessment of collision lesions and the diagnostic process related to cutaneous malignancies.

Dermatopathology doi: 10.3390/dermatopathology12020009

Authors: Marina Corral-Forteza Noelia Pérez-Muñoz Maria-Teresa Fernández-Figueras

The Wolf isotopic response (WIR) refers to the development of cutaneous lesions in areas of previously healed but unrelated skin disease. While most are observed in healed herpes zoster, WIR has been reported in various other contexts. Affected areas are believed to exhibit immune dysregulation, lymphatic dysfunction, and altered neuromediator activity, increasing susceptibility to inflammatory, neoplastic, and infectious conditions. This phenomenon aligns with the broader concept of the “immunocompromised district”, which also encompasses the Koebner phenomenon and its reverse. Herein, we present the case of a 96-year-old woman who developed multiple cysts and comedones at the site of a resolved herpes zoster. Due to persistent and refractory inflammation, curettage was performed, and histopathological examination revealed angiosarcoma with a pseudolymphomatous reaction interspersed among the cysts. The coexistence of multiple types of WIR is rare but not unprecedented, highlighting the importance of recognizing the diverse pathologic conditions that can arise in such settings. In this review, we explore the historical evolution of terminology used to describe lesions in vulnerable skin areas and related phenomena. We also provide an updated overview of current pathogenic theories and present a comprehensive compilation of postherpetic reactions reported to date.

Dermatopathology doi: 10.3390/dermatopathology12010008

Authors: Biagio Scotti Cosimo Misciali Federico Bardazzi Bianca Maria Piraccini Michelangelo La Placa

Hypertrophic lichen planus (HLP) is a chronic inflammatory skin condition defined by verrucous, pruritic, papules and plaques usually affecting the lower limbs. The diagnosis of HLP is primarily clinical. However, due to its feasible generalized presentation and similarities with other hypertrophic cutaneous disorders, histological evaluation is often necessary. Many dermatological conditions that present with a hypertrophic clinical appearance can arise from a histological lichenoid infiltrate (HCLI). Hence, we provide an overview of the clinical, histopathological, and prognostic features of selected HCLI, including HLP, hypertrophic lichenoid dermatitis, hypertrophic lichen sclerosus (HLS), lichen simplex chronicus (LSC), squamous cell carcinoma (SCC), keratoacanthoma (KA), pseudoepitheliomatous hyperplasia (PEH), viral warts, and lupus erythematosus/lichen planus (LE/LP) overlap. Choosing the appropriate procedure and the anatomical site for an incisional biopsy requires thoughtful consideration to ensure sufficient depth and improve diagnostic accuracy by identifying the histological features specific to each hypertrophic condition.

Dermatopathology doi: 10.3390/dermatopathology12010007

Authors: Alberto Soto-Moreno Francisco Vílchez-Márquez María Narváez-Simón Julia Castro-Martín Francisco Manuel Ramos-Pleguezuelos Agustín Soto-Díaz Jesús Tercedor-Sánchez Salvador Arias-Santiago

Kikuchi–Fujimoto disease (KFD) is a rare condition characterized by necrotizing lymphadenitis and fever, often associated with immune dysregulation. Histologically, it features necrotic foci with abundant histiocytes and plasmacytoid dendritic cells but notably lacks neutrophils and eosinophils. Recent evidence reveals a notable prevalence among pediatric patients, who may exhibit distinct features compared to adults. We reported the case of an 11-year-old girl presenting with persistent fever, cervical adenopathy, and a malar rash, leading to a diagnosis of KFD following lymph node biopsy, which revealed non-suppurative necrosis and histiocytic infiltration. Empirical treatment with antivirals and antibiotics was ineffective, but corticosteroid therapy achieved symptom remission. A literature review identified 48 relevant studies involving 386 pediatric cases, with histopathological findings consistent with classical descriptions of KFD. Cutaneous involvement was reported in 11.14% of cases, ranging from maculopapular rashes to lupus-like eruptions. Notable complications included the development of systemic lupus erythematous, Sjögren syndrome, and rare instances of hemophagocytic syndrome or central nervous system involvement. Kikuchi–Fujimoto disease should be considered in the differential diagnosis of pediatric patients presenting with fever and lymphadenopathy, taking into account a higher frequency of cutaneous manifestations in pediatric cases. A skin biopsy may be helpful in diagnosing KFD and provide valuable information regarding the potential risk of developing systemic lupus erythematosus in the future.

Dermatopathology doi: 10.3390/dermatopathology12010006

Authors: Torben Fricke Werner Kempf Michael P. Schön Christina Mitteldorf

Based on histologic and genetic patterns, the current World Health Organization (WHO) classification distinguishes six subtypes of lymphomatoid papulosis (Lyp). The aim of our article was to analyze the frequency of histologic and immunohistochemical features of different Lyp subtypes reported in the literature. We used PubMed advanced search builder to systematically review and evaluate English and German literature of Lyp from 1968 to April 2022. We considered only papers in which histopathologic features were mentioned in detail. We identified 48 publications with a total of 518 cases. The diagnoses were based on the diagnostic criteria at the time of publication. In Lyp A and Lyp B a CD8+ phenotype was more often reported than expected (53% and 52%, respectively). A double positive phenotype (CD4+/CD8+) was found in 28% of Lyp E and a double negative (CD4-/CD8-) in 50% of Lyp with 6p25.3 rearrangement. High rates of folliculo- and syringotropism were reported in both Lyp A and B. Surprisingly, strong epidermotropism occurred in 20/38 (53%) cases reported as Lyp B and in 43/64 (67%) of Lyp D cases. The predominating phenotype in Lyp D was CD8+, while TIA-1/granzymeB/perforin expression was reported in 37/46 (80%), and CD56 was expressed in 13/47 (28%) of the investigated cases. The limitation of the data is due to the retrospective approach with diagnostic criteria changing over time and on a case selection in some publications. However, the data indicate that the Lyp subtypes overlap more than assumed. They also show that a prospective study is needed to obtain valid data on the frequency distribution of certain histopathologic criteria.

Dermatopathology doi: 10.3390/dermatopathology12010005

Authors: Zachary K. Ford Adam J. Kirry Steve Davidson

Hyperalgesic priming is a model of the transition from acute to chronic pain. Whether a similar mechanism exists for “pruritic priming” of itch is unknown. Here, we tested the hypothesis that itchy skin in a commonly used mouse model of dry skin pruritus develops latent sensitization after resolution. Acetone–ether–water (AEW) treatment induced a dry and itchy skin condition in the mouse cheek that elicited site-directed scratching behavior. After cessation of treatment and the complete resolution of AEW-induced scratching, histaminergic and non-histaminergic pruritogens were administered to the cheek to test for altered site-directed scratching and wiping behavior. Each pruritogen was also tested following the resolution of carrageenan-induced nociceptor hypersensitivity to test for cross-modality priming. Peak AEW-induced scratching occurred 24 h after the final day of treatment, and 5 days were required for scratching levels to return to baseline. Likewise, epidermal thickening was the greatest on the final treatment day and completely returned to baseline after 5 days. After the resolution of itchy cheek skin, acute histamine- and non-histamine-evoked scratching and wiping behaviors were unchanged, nor were scratching and wiping behaviors to acute pruritogens altered after the resolution of carrageenan-induced hypersensitivity. The results indicate that persistent itch due to dry skin likely resolves completely, without producing a latent primed response to subsequent pruritic stimuli. We conclude that the mechanisms regulating hyperalgesic priming are likely distinct from pruritic signaling in the dry and itchy skin model.

Dermatopathology doi: 10.3390/dermatopathology12010004

Authors: Fadwa Ahmed Christopher DiMarco

Cutaneous silica granulomas are a form of foreign-body granulomatous reactions. They are characterized histopathologically by sarcoidal granulomas in association with silica crystals. Asteroid bodies, a classical histopathological feature of sarcoidosis, have not previously been reported in association with silica granulomas. Herein, we present the case of an 83-year-old man with an asymptomatic papule on the vertex scalp. Histopathology revealed a dermal granulomatous reaction to silica crystals. Asteroid bodies were observed in the cytoplasm of multinucleated giant cells. In the absence of systemic symptoms or laboratory findings suggestive of sarcoidosis, a final diagnosis of silica granuloma with asteroid bodies was made. While they have been observed in several other granulomatous reactions, the present case represents a novel association of asteroid bodies with silica granulomas.

Dermatopathology doi: 10.3390/dermatopathology12010003

Authors: Sébastien Menzinger Rastine Merat Gürkan Kaya

The diagnosis, interpretation, and classification of melanocytic tumors is a very complex topic in the pathology and dermatopathology field that lacks standardization and is still subject to discordance and debate. Here, we review the definitions of dysplastic nevus and superficial atypical melanocytic proliferations and provide an overview of some areas still subject to debate and some attempts of standardization. Furthermore, we describe an algorithmic classification, and provide some examples of clinico-pathological correlation. This step-by-step algorithm has an educational purpose and may automatize the work of dermatopathologists. We hope that through further molecular studies, this fine-grained scheme will prove to be related to the biological behavior of these atypical melanocytic lesions.

Dermatopathology doi: 10.3390/dermatopathology12010002

Authors: Zachary Corey Lydia A. Luu Sabrina Newman Shyam S. Raghavan

We present the case of a 60-year-old immunocompromised man who presented with two pruritic pink–red indurated nodules with overlying scale and focal areas of ulceration on his left dorsal and left medial forearm, which evolved over a 2-month period. The pathology showed numerous fungal hyphae present that were pauci-septate with various branched angles and variable hyphal thickness. Fungal cultures grew Rhizopus species and a universal fungal PCR detected the Rhizopus oryzae complex. Based on the clinicopathologic correlation, the diagnosis of cutaneous mucormycosis was made. Cutaneous mucormycosis is an aggressive fungal infection of the Mucorales family occurring after the inoculation of fungal spores in disrupted skin. It usually presents as a necrotic eschar but can also present as cellulitis that evolves into a necrotic ulcer. A prompt diagnosis is critical for the effective management of cutaneous mucormycosis. The treatment includes an immediate systemic treatment with amphotericin B and a surgical debridement of the necrotic regions. Given the wide range of presenting symptoms, clinical suspicion for this emergent condition must remain high in immunocompromised and diabetic patients.

Dermatopathology doi: 10.3390/dermatopathology12010001

Authors: Joana Sorino Mario Della Mura Anna Colagrande Cecilia Salzillo Giuseppe Ingravallo Gerardo Cazzato

Cutaneous squamomelanocytic tumor (SMT) is a very rare cutaneous malignancy, composed of a dual phenotypic population of both malignant melanocytes and keratinocytes, intimately intermingled together. Herein, we report a new case of a SMT occurring in an 82-year-old man, located on the scalp. Histopathology revealed a mixed population consisting of squamous cell carcinoma and melanoma within the same lesion, also confirmed using immunohistochemical staining for high molecular-weight cytokeratins (HMWCKs) and Melan-A. Moreover, to the best of our knowledge, for the first time, we tested SMT for the preferentially expressed antigen in melanoma (PRAME), which revealed a strong and diffuse positivity in the melanocytic component. These tumors need to be distinguished by more frequent collision tumors and colonization. Furthermore, we provide a comprehensive review of the literature, focusing on clinical and histopathological aspects, biological behavior and still-debated, but fascinating histogenesis of this elusive entity.

Dermatopathology doi: 10.3390/dermatopathology11040041

Authors: Carla Stephan Linglei Ma

The diagnostic utility of immunohistochemistry on paraffin-embedded sections in bullous disorders is useful when frozen tissue is not available. In pemphigus vulgaris and pemphigus foliaceus, an intercellular lace-like staining pattern of IgG4 on lesional tissue by immunohistochemistry has been described, with a comparable sensitivity and specificity to direct immunofluorescence on perilesional tissue. This study aimed to evaluate the staining pattern of IgG4 in non-immunobullous disorders to highlight the potential pitfalls when using this stain. In this study, we conducted a retrospective review of our institution’s database of non-immunobullous disorders where immunohistochemistry of IgG4 was performed to rule out pemphigus. We identified 27 cases where IgG4 immunohistochemistry was performed and observed intercellular IgG4 staining in some cases of Grover disease, bullous impetigo, irritated dermal hypersensitivity reaction, acantholytic actinic keratosis, and graft versus host disease. Our results indicate that the interpretation of IgG4 staining by immunohistochemistry in cutaneous acantholytic disorders should be approached with caution. Confirmation on cryosections with direct immunofluorescence study results is important in these settings.

Dermatopathology doi: 10.3390/dermatopathology11040040

Authors: Sylvie Fraitag

Paediatric dermatology is still an expanding subspeciality, which is well illustrated by the growing number of books and articles that have been published on this subject in recent years [...]

Dermatopathology doi: 10.3390/dermatopathology11040039

Authors: Hisham F. Bahmad John Alexis

PRAME (PReferentially expressed Antigen in MElanoma) is a tumor-associated antigen first identified in tumor-reactive T-cell clones derived from a patient with metastatic melanoma. Immunohistochemistry (IHC) for PRAME is useful for diagnostic purposes to support a suspected diagnosis of melanoma. Anecdotally, PRAME has been observed to stain sebaceous units in glands in background skin. We examined the expression of PRAME in adnexal lesions and common skin cancers to determine whether it is of potential diagnostic utility in supporting the differentiation between sebaceous and non-sebaceous lesions. IRB approval from Mount Sinai Medical Center (MSMC) was obtained. This is a single-center retrospective cohort analysis over a ten-year period (1 January 2012, and 31 December 2023). We used the pathological database of skin lesions, including sebaceous, sweat gland, and follicular lesions, in addition to basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs), from 81 patients who underwent shave/punch biopsies or surgical excisions. We evaluated the IHC staining percentage positivity and intensity for PRAME. Staining intensity was subcategorized into negative, weak, moderate, and strong, whereas expression percentage positivity was subcategorized into 0%, 1–25%, 26–50%, 51–75%, and 76–100%. Most sebaceous versus non-sebaceous lesions exhibited cytoplasmic staining of moderate to strong intensity in >75% of cells. PRAME has a sensitivity and specificity of 100.0% and 86.7%, respectively, to support distinguishing between sebaceous and non-sebaceous adnexal lesions (regardless of whether they are benign or malignant). BCCs and SCCs showed weak to moderate nuclear staining for PRAME in >75% of cells. None of the 13 lesions of hair follicle origin showed any staining. A total of 26 of the 32 lesions of sweat gland origin were negative while 6 (18.75%) showed positive staining. In conclusion, we confirm the potential utility of PRAME for supporting the distinction between sebaceous and non-sebaceous adnexal lesions on one hand, and on the other, distinguishing BCC and SCC that may show nuclear staining from sebaceous carcinoma that shows cytoplasmic staining.

Dermatopathology doi: 10.3390/dermatopathology11040038

Authors: Mokhtar H. Abdelhammed Hanna Siatecka A. Hafeez Diwan Christie J. Finch Angela D. Haskins David J. Hernandez Ya Xu

Malignant proliferating trichilemmal tumors (MPTTs), arising from the external root sheath of hair follicles, are exceptionally rare, with limited documentation of their genetic alterations. We present a case of a 64-year-old African American woman who initially presented with a gradually enlarging nodule on her posterior scalp. An initial biopsy at an outside hospital suggested metastatic adenocarcinoma or squamous cell carcinoma (SCC) of an uncertain origin. A subsequent wide local excision revealed a 2.0 cm tumor demonstrating characteristic trichilemmal keratinization, characterized by an abrupt transition from the nucleated epithelium to a laminated keratinized layer, confirming MPTT. Immunohistochemistry demonstrated diffuse p53 expression, patchy CD 34 expression, focal HER2 membranous expression, and patchy p16 staining (negative HPV ISH). A molecular analysis identified TP53 mutation and amplifications in the ERBB2 (HER2), BRD4, and TYMS. Additional gene mutations of uncertain significance included HSPH1, ATM, PDCD1 (PD-1), BARD1, MSH3, LRP1B, KMT2C (MLL3), GNA11, and RUNX1. Assessments for the homologous recombination deficiency, PD-L1 expression, gene rearrangement, altered splicing, and DNA mismatch repair gene expression were negative. The confirmation of ERBB2 (HER2) amplification in the MPTT through a molecular analysis suggests potential therapeutic avenues involving anti-HER2 monoclonal antibodies. The presence of the TP53 mutation, without the concurrent gene mutations typically observed in SCC, significantly aided in this differential diagnosis.

Dermatopathology doi: 10.3390/dermatopathology11040037

Authors: Tassilo Dege Arno Rütten Matthias Goebeler Hermann Kneitz

Digital papillary adenocarcinoma (DPAC) is a rare, low-grade sweat gland carcinoma primarily found on the hands, fingers, or toes and predominantly affecting males. Distinguishing DPAC from benign sweat gland tumors can be challenging. We present the case of a 52-year-old patient with a progressive tumor on the finger initially misdiagnosed as a viral wart. Histological examination revealed a cytologically basophilic sweat gland tumor with tubular structures, papillary protrusions, and a characteristic immunohistochemical staining pattern for CK 7 and Actin. HPV-42 positivity and molecular analysis confirmed the diagnosis of DPAC. HPV-42 has been strongly associated with DPAC. Additionally, p16 positivity and BRAFV600E negativity were observed. These findings aid in the differential diagnosis of acral sweat gland tumors and guide clinical management, including with respect to the potential for recurrence and metastasis.

Dermatopathology doi: 10.3390/dermatopathology11040036

Authors: Ty Theriot John David Cattar Lacey Falgout Nicholas Culotta Christopher Haas

Spindle cell lipoma (SCL) is a benign adipocytic tumor usually found in the subcutis of the posterior neck, upper back, and shoulder, predominantly in middle-aged males. This case report describes an atypical presentation of SCL in a 26-year-old male with a history of malignant melanoma. The patient presented with an erythematous plaque with central hyperpigmentation on the right upper arm, an uncommon location and presentation for SCL. Histopathological examination revealed an atypical myxoid spindle cell neoplasm with CD34 positivity and an overlying mildly atypical compound melanocytic nevus. The unusual clinical and histological features, combined with the patient’s melanoma history, complicated the differential diagnosis, which included dermatofibrosarcoma protuberans (DFSP) and solitary fibrous tumors (SFTs). A wide local excision with 2 cm margins was performed, and subsequent pathology confirmed clear margins, supporting the diagnosis of SCL. This case highlights the importance of including SCL in the differential diagnosis of CD34-positive spindle cell tumors, even when clinical and histological presentations are atypical, and underscores the need for thorough histopathological evaluation and a broad differential diagnosis in patients with a history of melanoma.

Dermatopathology doi: 10.3390/dermatopathology11040035

Authors: Emmanouil Karampinis Olga Toli Georgia Pappa Anna Vardiampasi Melpomeni Theofili Efterpi Zafiriou Mattheos Bobos Aimilios Lallas Elizabeth Lazaridou Biswanath Behera Zoe Apalla

The dermoscopic rainbow pattern (RP), also known as polychromatic pattern, is characterized by a multicolored appearance, resulting from the dispersion of polarized light as it penetrates various tissue components. Its separation into different wavelengths occurs according to the physics principles of scattering, absorption, and interference of light, creating the optical effect of RP. Even though the RP is regarded as a highly specific dermoscopic indicator of Kaposi’s sarcoma, in the medical literature, it has also been documented as an atypical dermoscopic finding of other non-Kaposi skin entities. We aim to present two distinct cases—a pigmented basal cell carcinoma (pBCC) and an aneurysmatic dermatofibroma—that exhibited RP in dermoscopy and to conduct a thorough review of skin conditions that display RP, revealing any predisposing factors that could increase the likelihood of its occurrence in certain lesions. We identified 33 case reports and large-scale studies with diverse entities characterized by the presence of RP, including skin cancers (Merkel cell carcinoma, BCC, melanoma, etc.), adnexal tumors, special types of nevi (blue, deep penetrating), vascular lesions (acroangiodermatitis, strawberry angioma, angiokeratoma, aneurismatic dermatofibromas, etc.), granulation tissue, hypertrophic scars and fibrous lesions, skin infections (sporotrichosis and cutaneous leishmaniasis), and inflammatory dermatoses (lichen simplex and stasis dermatitis). According to our results, the majority of the lesions exhibiting the RP were located on the extremities. Identified precipitating factors included the nodular shape, lesion composition and vascularization, skin pigmentation, and lesions’ depth and thickness. These parameters lead to increased scattering and interference of light, producing a spectrum of colors that resemble a rainbow.

Dermatopathology doi: 10.3390/dermatopathology11040034

Authors: Yuji Ohara Issei Kido Kozo Nakai

Akatsuki disease (also known as pomade crust) is characterized by skin lesions resulting from inadequate skin hygiene. It is sometimes influenced by underlying psychological factors. Akatsuki disease sometimes mimics cutaneous horn or skin cancer. However, there are no previous reports of skin cancer accompanied with Akatsuki disease. Herein, we report a 79-year-old woman who was referred to our department with a tumor on her left cheek. Before performing a biopsy, we recommended that her family assist with regular facial cleansing. Two months later, the scales and crusts on her entire face had disappeared and the tumor on the left cheek had reduced. Skin biopsy was performed, and histological examination revealed ulcerative basaloid lobules consisting of cells with a small cytoplasm and large hyperchromatic nuclei. Peripheral palisading and tumor-stroma clefting were observed. A diagnosis of basal cell carcinoma was made.

Dermatopathology doi: 10.3390/dermatopathology11040033

Authors: Erin M. McClure Clay J. Cockerell Stephen Hammond Evelyn S. Marienberg Bobby N. Koneru Jon Ward Jeffrey B. Stricker

Non-melanoma skin cancers (NMSCs), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), are highly prevalent and a significant cause of morbidity. Image-guided superficial radiation therapy (IGSRT) uses integrated high-resolution dermal ultrasound to improve lesion visualization, but it is unknown whether efficacy varies by histology. This large retrospective cohort study was conducted to determine the effect of tumor histology on freedom from recurrence in 20,069 biopsy-proven NMSC lesions treated with IGSRT, including 9928 BCCs (49.5%), 5294 SCCs (26.4%), 4648 SCCIS cases (23.2%), and 199 lesions with ≥2 NMSCs (1.0%). Freedom from recurrence at 2, 4, and 6 years was 99.60%, 99.45%, and 99.45% in BCC; 99.58%, 99.49%, and 99.49% in SCC; and 99.96%, 99.80%, and 99.80% in SCCIS. Freedom from recurrence at 2, 4, and 6 years following IGSRT did not differ significantly comparing BCC vs. non-BCC or SCC vs. non-SCC but were slightly lower among SCCIS vs. non-SCCIS (p = 0.002). There were no significant differences in freedom from recurrence when stratifying lesions by histologic subtype. This study demonstrates that there is no significant effect of histology on freedom from recurrence in IGSRT-treated NMSC except in SCCIS. These findings support IGSRT as a first-line therapeutic option for NMSC regardless of histology.

Dermatopathology doi: 10.3390/dermatopathology11040032

Authors: Enric Piqué-Duran

Background: Tumor collision is a rare event, with an estimated incidence of 0.0017%. Seborrheic keratosis, melanocytic nevi, and basal cell carcinoma (BCC) are by far the most common entities involved in collisions. Most authors consider collision to be an incidental event. I planned a retrospective study comparing BCC/apocrine–sebaceous–follicular unit (ASFu) neoplasm collisions with squamous cell carcinoma (SCC)/ASFu neoplasm collisions. Materials and methods: Files from 2005 to 2017 from Dr. José Molina Orosa Hospital were assessed; in the review, cases of collisions between BCCs or SSCs and ASFu tumors, including cysts, were identified. Results: Out of 3247 BCC cases, 12 biopsies were retrieved. Of 825 biopsies, none belonged to the SCC group. The ASFu tumors that collided with a BCC were as follows: four hidrocystomas, three infundibular cysts, two steatocystomas, two trichilemmomas, one spiradenoma, and one clear-cell hidradenoma (one patient had two cysts associated with a BCC). These cases correspond to seven female patients and five male patients aged between 26 and 91 years old. A quarter of these patients were immunosuppressed. Most ASFu neoplasms were found to be located beneath the BCC (8/12). Discussion: To the best of my knowledge, this report describes three new collisions of BCCs with ASFu neoplasms (infundibular cysts, steatocystomas, and a spiradenoma). My results also suggest that immunosuppression could be a factor that predisposes a patient to these collisions. I review current hypotheses in an effort to explain these collisions and contribute some new theories.

Dermatopathology doi: 10.3390/dermatopathology11040031

Authors: Kassiani Boulogeorgou Christos Topalidis Triantafyllia Koletsa Georgia Karayannopoulou Jean Kanitakis

TRPS1 (Tricho-rhino-phalangeal syndrome 1) is a GATA transcriptional activator gene encoding for a protein used as a sensitive immunohistochemical marker of breast carcinomas. In dermatopathology, TRPS1 is used as a marker of mammary and extramammary Paget’s disease and is also expressed by a variety of primary cutaneous tumors, mostly of adnexal origin. So far, very limited data exist on the expression of TRPS1 in metastatic skin tumors. We studied the immunohistochemical expression of TRPS1 in 72 cutaneous metastatic tumors from the breast (n: 19) and other origins (n: 53) in order to assess its diagnostic usefulness. The intensity of TRPS1 immunostaining was expressed as a histoscore: the product of the percentage of positive cells (scored semi-quantitatively 0–4) and the staining intensity (scored 0–3). In normal skin, nuclear TRPS1 expression was predominantly observed in cells of adnexal structures (pilosebaceous follicles and sweat glands). Eighteen (18/19, 94.7%) metastatic breast carcinomas showed diffuse and strong TRPS1 positivity (histoscore 12). Lower reactivity was found in some other metastases, including from the lung (11/22), the female genital tract (3/4), and the kidney (2/4), whereas most (20/22) metastases from the digestive system and peritoneum, along with a case of metastatic prostate carcinoma, were negative. These results suggest that a high histoscore for TRPS1 is in favor of the mammary origin of metastatic cutaneous carcinoma. Although TRPS1 is not absolutely specific or sensitive to a particular primary, we consider that it can be added to a panel of other markers when investigating the origin of a cutaneous metastasis, namely when this is the first manifestation of the neoplastic disease.

Dermatopathology doi: 10.3390/dermatopathology11040030

Authors: Navinda Donsakul Suthep Jerasutus Ittipon Tubtieng Ravion Assavanatenapa Voraphol Vejjabhinanta

Undifferentiated pleomorphic sarcoma (UPS) is an aggressive soft tissue sarcoma with a poor prognosis. The patients are usually found to have metastasis when the primary tumor is diagnosed. Eccrine syringofibroadenoma (ESFA) is a rare cutaneous adnexal lesion of eccrine duct origin. There are five subtypes, one of which is reactive ESFA, known to occur in reaction to an inflammatory or neoplastic process. In this article, we report a case of the co-existence of both UPS and ESFA in a 70-year-old male patient, presenting with a painless, erythematous, irregular surface nodule with a peripherally extended brownish hyperkeratotic plaque on the right palm. The histologic findings revealed an ill-defined dermal tumor of atypical epithelioid and spindle-shaped cells with large pleomorphic hyperchromatic nuclei and abundant eosinophilic cytoplasm. Some of those cells were multinucleated giant cells in the stroma with vascular proliferation and mixed inflammatory cell infiltrate. The tumor cells, which were only positive for vimentin, supported the diagnosis of undifferentiated pleomorphic sarcoma (UPS). Meanwhile, the overlying epidermis demonstrated hyperkeratosis, papillated epidermal hyperplasia, and proliferation of anastomosing slender cords and strands of cuboid cells within loose fibrovascular stroma. These findings are the characteristics of eccrine syringofibroadenoma (ESFA). We describe here a patient in whom reactive ESFA occurred on and surrounded the UPS tumor.

Dermatopathology doi: 10.3390/dermatopathology11040029

Authors: Hisham F. Bahmad Kalin Stoyanov Teresita Mendez Sally Trinh Kristy Terp Linda Qian John Alexis

Considerable controversy exists within the field of dermatopathology in differentiating keratoacanthoma (KA) from squamous-cell carcinoma (SCC). KAs are rapidly growing, benign squamous tumors that are typically well differentiated. This controversy stems from the diverging perspectives on the management, classification, and diagnosis of each entity. Many believe that KAs are benign neoplasms in which intervention may be unnecessary since they are self-limiting and resolve on their own. On the other hand, SCC needs to be treated, as it carries significant morbidity and mortality risks. Early diagnosis and treatment are vital to prevent serious consequences of SCC. Nevertheless, KAs may resemble SCC grossly and microscopically. Various ancillary tests, including immunohistochemical (IHC) staining, have been proposed to differentiate between these entities, though mixed patterns of expression can limit the diagnostic utility of these techniques. Research into this topic is ongoing, with newer genetic and molecular findings illuminating the previously difficult-to-understand aspects of KA and increasing our understanding of this entity. In this review, KA and SCC will be compared along the lines of histological features, genetic, immune, and molecular markers, differential diagnosis, and management to clarify the similarities, differences, and misconceptions about both entities.

Dermatopathology doi: 10.3390/dermatopathology11040028

Authors: Italo Francesco Aromolo Michela Brena Nicola Adriano Monzani Fabio Caviggioli Emilio Berti Donata Micello Riccardo Cavalli

A 11-year-old Caucasian girl presented to our Dermatology Unit with a 2-month history of an erythematous nodule, localized to the medial portion of her left eyebrow, rapidly growing in the two weeks before presentation. The histopathological examination revealed a dermal multi-nodular epithelial neoplasm composed of clear cells, squamous cells, and glandular cells, characterized by cytologic atypia, high mitotic activity, and an infiltrative deep growth pattern. The immunohistochemical profile of the lesion was as follows: CKAE1/AE3+, EMA+, CK8/18+, CK7+, CK19+, AR negative, p63 focally +, Ki67 25%, rare cells GCDFP15+, p53+.

Dermatopathology doi: 10.3390/dermatopathology11040027

Authors: Samir Kamat Ross O’Hagan Catherine Brahe Curtis L. Hardy Vikas Shrivastava Jane M. Grant-Kels Angela M. Crotty

Dermatologic care within the military faces unique ethical challenges. Service members are stationed across nationally and globally diverse settings, and therefore, dermatologic care rendered ranges from within resource-rich, advanced military medical treatment facilities to austere, resource-limited, deployed field environments. Additionally, military service members are often at unique risk for dermatologic disease, given occupational, environmental, and geographic exposures not commonly faced by their civilian counterparts. This review explores topics in dermatoethics via case analyses of ethical considerations within the scope of dermatologic care for military service members.