Dermatopathology最新文献

{"title":"Comprehensive Genomic Profiling of Cutaneous Adnexal Carcinomas: A Genomic Landscape Study.","authors":"Maroun Bou Zerdan, Kevin T Jamouss, Alexandre Maalouf, Rita Moukarzel, Tanishq Chhabra, Daniel J Zaccarini, Dean Pavlick, Natalie Danziger, Jeffrey Ross","doi":"10.3390/dermatopathology13020015","DOIUrl":"10.3390/dermatopathology13020015","url":null,"abstract":"<p><p>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; <i>p</i> = 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; <i>p</i> = 0.005) and lowest in DPA (2.1 vs. 5.0 in non-DPA; <i>p</i> = 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%; <i>p</i> < 0.0001) and TP53 alterations (76.4% vs. 43.4%; <i>p</i> = 0.0002), suggesting potential neuroendocrine differentiation. MC tumors showed significantly higher PTCH1 alterations than non-MC tumors (36.4% vs. 1.8%; <i>p</i> = 0.044). MSI-high status was most frequent in SEB tumors compared with all other groups (15.7% vs. 1.2%; <i>p</i> = 0.005), and gLOH > 16% was also more common in SEB than SWT tumors (19.6% vs. 7.2%; <i>p</i> = 0.081). The MMR signature occurred more frequently in SEB than SWT tumors (32.0% vs. 2.1%; <i>p</i> = 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; <i>p</i> = 0.001) and DPA (1.4 mut/Mb; <i>p</i> = 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 stu","PeriodicalId":42885,"journal":{"name":"Dermatopathology","volume":"13 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147784592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PRAME Expression in Melanoacanthomas: Expanding the Spectrum of Positive Melanocytes in Sun-Exposed Skin.","authors":"Francesco Fortarezza, Anna Poputchikova, Federica Pezzuto, Christian Ciolfi, Vincenza Guzzardo, Paolo Del Fiore, Gerardo Cazzato, Franco Bassetto, Mauro Alaibac, Angelo Paolo Dei Tos","doi":"10.3390/dermatopathology13010014","DOIUrl":"10.3390/dermatopathology13010014","url":null,"abstract":"<p><p>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 (<i>p</i> < 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.</p>","PeriodicalId":42885,"journal":{"name":"Dermatopathology","volume":"13 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13024871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147533148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal Melanonychia in Children: Clinical and Histopathologic Features and Management with Literature Update.","authors":"Isabelle Moulonguet, Marie Caucanas, Sophie Goettmann","doi":"10.3390/dermatopathology13010013","DOIUrl":"10.3390/dermatopathology13010013","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":42885,"journal":{"name":"Dermatopathology","volume":"13 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13024796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147533107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genital Disorders in Children: What Does a Biopsy Bring?","authors":"Francoise Plantier, Fiona Lewis","doi":"10.3390/dermatopathology13010012","DOIUrl":"10.3390/dermatopathology13010012","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":42885,"journal":{"name":"Dermatopathology","volume":"13 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13025205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147533130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cutaneous Granular Cell Tumor with Overlying Hypertrichosis in an Adult: A Rare Case Report.","authors":"Yara Alhusaini, Abdulaziz Almufadhi, Naif Alzahrani, Nawaf Alqahtani, Ohoud Aljarbou","doi":"10.3390/dermatopathology13010011","DOIUrl":"10.3390/dermatopathology13010011","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":42885,"journal":{"name":"Dermatopathology","volume":"13 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13026042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147532532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Case of Recurrent Chromoblastomycosis Treated with Multiple Surgical Management Options.","authors":"Madeleine Kelly, Crystal Williams, Robert Miller","doi":"10.3390/dermatopathology13010010","DOIUrl":"10.3390/dermatopathology13010010","url":null,"abstract":"<p><p>Chromoblastomycosis is a chronic mycosis of the skin and subcutaneous tissue typically caused by traumatic inoculation of dematiaceous fungi of the <i>Herpotrichiellaceae</i>. 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.</p>","PeriodicalId":42885,"journal":{"name":"Dermatopathology","volume":"13 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13025967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147532293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defining Histological Patterns in Inherited Ichthyoses: Toward a Diagnostic Algorithm Based on 66 Confirmed Cases.","authors":"Kira Süßmuth, Vinzenz Oji, Jacqueline Bodes, Isabelle Jochum, Florian Muhs, Katalin Komlosi, Ingrid Hausser, Matthias Schmuth, Heiko Traupe, Judith Fischer, Dieter Metze","doi":"10.3390/dermatopathology13010009","DOIUrl":"10.3390/dermatopathology13010009","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objectives: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Limitations: </strong>Although some rare subtypes were underrepresented, this cohort represents the largest and most heterogeneous group of molecularly confirmed ichthyosis cases analyzed histologically to date.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":42885,"journal":{"name":"Dermatopathology","volume":"13 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13024824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147532832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Unusual Invader in a Patient with Long-Standing Rheumatoid Arthritis: A Case of <i>Leishmania major</i> Colonization of Rheumatoid Nodules.","authors":"Monia Di Prete, Viviana Lora, Arianna Lamberti, Alessandra Latini, Carlo Cota","doi":"10.3390/dermatopathology13010008","DOIUrl":"10.3390/dermatopathology13010008","url":null,"abstract":"<p><p>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 <i>Leishmania major.</i> 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.</p>","PeriodicalId":42885,"journal":{"name":"Dermatopathology","volume":"13 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12921997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146259088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Behçet-like Syndromes: A Comprehensive Review.","authors":"Gaia Mancuso, Igor Salvadè, Adam Ogna, Brenno Balestra, Helmut Beltraminelli","doi":"10.3390/dermatopathology13010007","DOIUrl":"10.3390/dermatopathology13010007","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objectives: </strong>To summarize clinical features, treatments, and genetic abnormalities reported in BLS, we reviewed all published cases up to January 2024.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":42885,"journal":{"name":"Dermatopathology","volume":"13 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12821650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146012736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor Infiltrating Lymphocytes in Cutaneous Squamous Cell Carcinoma-A Systematic Review.","authors":"Li Yang Loo, Shi Huan Tay, Choon Chiat Oh","doi":"10.3390/dermatopathology13010006","DOIUrl":"10.3390/dermatopathology13010006","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":42885,"journal":{"name":"Dermatopathology","volume":"13 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12821468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146012714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}