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Dermatopathology, Volume 13, Issue 2 (June 2026) – 13 articles

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13 pages, 368 KB  
Article
Cutaneous Melanoma in Adolescents and Young Adults Versus Older Patients: Clinical and Histopathological Differences in Western Romania
by Bianca Roxana Natarâş, Sorina Maria Tăban, Aura Jurescu, Octavia Cornelia Viţa, Remus Florin Cornea, Ioana Hurmuz, Adelina Vidac, Daciana Grujic, Valentin Tudor Popa and Alis Liliana Carmen Dema
Dermatopathology 2026, 13(2), 27; https://doi.org/10.3390/dermatopathology13020027 - 20 Jun 2026
Viewed by 112
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Section Clinico-Pathological Correlation in Dermatopathology)
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6 pages, 17046 KB  
Clinicopathological Challenge
Flesh-Colored Papules on the Glans Penis
by Phatcharawat Chirasuthat, Supaporn Suwanchote and Tanaporn Borriboon
Dermatopathology 2026, 13(2), 26; https://doi.org/10.3390/dermatopathology13020026 - 10 Jun 2026
Viewed by 321
Abstract
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, [...] Read more.
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. Full article
(This article belongs to the Section Clinico-Pathological Correlation in Dermatopathology)
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9 pages, 9117 KB  
Case Report
Perineuriomatous Melanocytic Nevus: A Case Report of a Rare and Underreported Melanocytic Lesion
by Muhammad N. Mahmood and Eunice Y. Chow
Dermatopathology 2026, 13(2), 25; https://doi.org/10.3390/dermatopathology13020025 - 30 May 2026
Viewed by 345
Abstract
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 [...] Read more.
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. Full article
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22 pages, 12540 KB  
Review
Cutaneous Hematologic Neoplasms in Children: Overview and Update
by Philippe Drabent, Anne Welfringer, Alejandro A. Gru, Thierry J. Molina and Sylvie Fraitag
Dermatopathology 2026, 13(2), 24; https://doi.org/10.3390/dermatopathology13020024 - 29 May 2026
Viewed by 354
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue New Insights in Paediatric Dermatopathology 2025)
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25 pages, 5499 KB  
Review
Inflammatory and Infectious Cutaneous Entities Resembling Cutaneous T-Cell Lymphoma (CTCL): An Integrated Clinicopathological Review
by Jade Nasser Eldin, Elias El Tayar, Ossama Abbas and Jag Bhawan
Dermatopathology 2026, 13(2), 23; https://doi.org/10.3390/dermatopathology13020023 - 27 May 2026
Viewed by 480
Abstract
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 [...] Read more.
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. Full article
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16 pages, 1270 KB  
Review
The Cutaneous Immune Microenvironment in Selected Inflammatory Skin Diseases: Linking Histopathology, Mechanisms, and Targeted Therapy
by Andreea Cătălina Tinca, Andreea Raluca Cozac-Szoke and Ovidiu Simion Cotoi
Dermatopathology 2026, 13(2), 22; https://doi.org/10.3390/dermatopathology13020022 - 10 May 2026
Viewed by 941
Abstract
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 [...] Read more.
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. Full article
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2 pages, 423 KB  
Correction
Correction: Cazzato et al. Skin Mycetoma in an 11-Year-Old African Boy: Case Presentation with Emphasis on Histopathological Features and Differential Diagnosis. Dermatopathology 2021, 8, 509–514
by Gerardo Cazzato, Anna Colagrande, Antonietta Cimmino, Lucia Lospalluti, Aurora Demarco, Caterina Foti, Paolo Romita, Francesca Arezzo, Vera Loizzi, Paola Parente, Leonardo Resta and Giuseppe Ingravallo
Dermatopathology 2026, 13(2), 21; https://doi.org/10.3390/dermatopathology13020021 - 8 May 2026
Viewed by 523
Abstract
The authors would like to make the following corrections to this published paper [...] Full article
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15 pages, 1126 KB  
Article
Beyond Binary Positivity: Spectrum of Nodal Tumor Burden in Sentinel Lymph Node Biopsy for High-Risk Cutaneous Squamous Cell Carcinoma
by Irena Janković, Goran Stevanović, Toma Kovačević, Dimitrije Janković and Dimitrije Pavlović
Dermatopathology 2026, 13(2), 20; https://doi.org/10.3390/dermatopathology13020020 - 30 Apr 2026
Viewed by 564
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Section Clinico-Pathological Correlation in Dermatopathology)
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10 pages, 9656 KB  
Case Report
Pseudolymphomatous Granuloma Annulare Rich in B Lymphocytes
by Angel Fernandez-Flores and José Luis Martínez-Amo
Dermatopathology 2026, 13(2), 19; https://doi.org/10.3390/dermatopathology13020019 - 29 Apr 2026
Viewed by 559
Abstract
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 [...] Read more.
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. Full article
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6 pages, 2953 KB  
Clinicopathological Challenge
Pedunculated Acral Keratotic Papule on an Ischemic Foot
by Janmesh D. Patel, Pooja A. Shet, Sara E. Dahle, Joshua M. Schulman and Marat D. Kazak
Dermatopathology 2026, 13(2), 18; https://doi.org/10.3390/dermatopathology13020018 - 21 Apr 2026
Viewed by 553
Abstract
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 [...] Read more.
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. Full article
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26 pages, 20174 KB  
Article
Desmosomal-Type Acantholysis—A New Histologic Pattern Related to Mutations of Genes for Desmosomal Proteins
by Dieter Metze, Kira Süßmuth, Clemens Metze, Vinzenz Oji and Heiko Traupe
Dermatopathology 2026, 13(2), 17; https://doi.org/10.3390/dermatopathology13020017 - 3 Apr 2026
Viewed by 945
Abstract
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. [...] Read more.
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. Full article
(This article belongs to the Special Issue New Insights in Paediatric Dermatopathology 2025)
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12 pages, 5598 KB  
Article
Bilateral Auricular Blastomycosis-like Pyoderma: A Rare Presentation Histologically Misinterpreted as Squamous Cell Carcinoma
by Nazario Pesce, Giorgia Di Marco, Giorgio Stabile, Antonio Podo Brunetti, Alessandro Russo, Stefania Guida and Rongioletti Franco
Dermatopathology 2026, 13(2), 16; https://doi.org/10.3390/dermatopathology13020016 - 1 Apr 2026
Viewed by 968
Abstract
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 [...] Read more.
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. Full article
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14 pages, 1583 KB  
Article
Comprehensive Genomic Profiling of Cutaneous Adnexal Carcinomas: A Genomic Landscape Study
by Maroun Bou Zerdan, Kevin T. Jamouss, Alexandre Maalouf, Rita Moukarzel, Tanishq Chhabra, Daniel J. Zaccarini, Dean Pavlick, Natalie Danziger and Jeffrey Ross
Dermatopathology 2026, 13(2), 15; https://doi.org/10.3390/dermatopathology13020015 - 30 Mar 2026
Viewed by 1063
Abstract
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 [...] Read more.
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. Full article
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