Virchows Archiv最新文献

{"title":"Correction to: Succinate dehydrogenase defcient renal cell carcinoma frequently expresses GATA3 and L1CAM.","authors":"Ankur R Sangoi, Sean R Williamson, Murat Oktay, Anthony J Gill, Kiril Trpkov, Farshid Siadat, Fiona MacLean, Laurence A Galea, Dilek Ertoy Baydar, Caglar Cakir, Yasemin Yuyucu Karabulut, Deniz Baycelebi, Ganime Coban, Banu Sarsik, Busra Yaprak Bayrak, Levente Kuthi, Boglarka Posfai, Aysha Mobeen, Sambit K Mohanty, Xulang Zhang, Mohammed A Alghamdi, Liang Cheng, Michelle S Hirsch, Mahmut Akgul","doi":"10.1007/s00428-025-04194-3","DOIUrl":"https://doi.org/10.1007/s00428-025-04194-3","url":null,"abstract":"","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144709001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZC3H7A/B::BCOR fusion fibromyxoid sarcoma of soft tissue: an emerging aggressive sarcoma overlapping with malignant ossifying fibromyxoid tumors.","authors":"Bharat Rekhi, Altan Kavuncuoglu, Nasir Ud Din, Sameer Rastogi, Ali Abdelsatir, Robert Stoehr, Abbas Agaimy, Kemal Kosemehmetoglu","doi":"10.1007/s00428-025-04177-4","DOIUrl":"https://doi.org/10.1007/s00428-025-04177-4","url":null,"abstract":"<p><p>BCOR-rearranged sarcomas constitute ultra-rare tumors. Among these, ZC3H7A/B::BCOR sarcomas are less common and are primarily reported as a subset of high-grade endometrial stromal sarcomas, as well as in the spectrum of malignant ossifying fibromyxoid tumors (OFMTs). Herein, we present the clinicopathological, immunohistochemical, and molecular profiles of seven soft tissue tumors exhibiting ZC3H7A/B::BCOR fusions. The patient's age ranged from 13 to 65 years (median = 38). Locations were neck (2) and one case each in the paraspinal region, scalp, gluteal region, chest wall, and thigh. Histologically, the tumors were composed of round to polygonal or spindle-shaped cells with a variable amount of fibromyxoid stroma, lacking bone shell or ossification, leading to a range of initial differential diagnoses. Immunohistochemically, the tumor cells were positive for S100 (5/6), cyclin D1 (2/3), SATB2 (2/3), BCOR (2/4), and TLE1 (1/3) while negative for MUC4 (0/6), keratin (0/5), EMA (0/4), desmin (0/6), CD34 (0/6), SMA (0/5), SOX10 (0/5), and melanoma cocktail (0/2). Targeted RNA sequencing revealed ZC3H7B::BCOR fusions in six tumors (four with ZC3H7Bex10::BCORex6 and one each ZC3H7Bex12::BCORex7 and ZC3H7Bex12::BCORex6). One tumor revealed a ZC3H7Aex10::BCORex6 fusion. All seven tumors were resected, mostly with clear margins (5/7), including two patients who received adjuvant therapy. Three of four patients with available follow-up (mean = 45 months) died of disease, while one patient was alive with multiple bone metastases. This series comprises seven additional ZC3H7A/B::BCOR soft tissue sarcomas associated with aggressive clinical outcomes. Whether this aggressive sarcoma represents a molecular subtype of malignant OFMT or a genetic variant of BCOR-rearranged sarcomas remains to be further verified.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunohistochemistry scoring for human epidermal growth factor receptor 2 can be used to predict pathological response to cisplatin-based neoadjuvant chemotherapy in a subset of immunohistochemically subtyped muscle-invasive bladder cancer.","authors":"Manduwa Saka, Yuki Teramoto, Hironori Haga","doi":"10.1007/s00428-025-04196-1","DOIUrl":"https://doi.org/10.1007/s00428-025-04196-1","url":null,"abstract":"<p><p>Patients with muscle-invasive bladder cancer (MIBC) are often treated with platinum-based neoadjuvant chemotherapy (NAC). NAC-treated patients have higher odds of pathological downstaging than untreated patients on subsequent cystectomy and, consequently, improved survival. However, not all patients achieve pathological downstaging. Notably, luminal MIBC shows a superior pathological response to cisplatin-based NAC compared with non-luminal MIBC. This study aimed to examine the relationship between human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) status and the molecular subtypes of MIBC and to evaluate its role in the prediction of response to platinum-based neoadjuvant chemotherapy. We performed IHC for GATA binding protein 3 (GATA3), cytokeratin (CK) 5/6, p16, and synaptophysin to classify MIBC on transurethral resection of bladder tumor/biopsy specimens into molecular subtypes. We then examined the association between HER2 IHC status and the subtypes and its utility in predicting subsequent pathological responses. Out of 49 patients, HER2 IHC positivity (scores 2 + , 3 +) was predominantly observed in the genomically unstable (GU) immunohistochemical molecular subtype (GATA3 + , CK5/6-, p16 +), a surrogate of the luminal unstable transcriptomic subtype. Additionally, all but one patient with HER2-positive GU tumors (n = 8) had absent invasive tumor on subsequent cystectomy following cisplatin-based NAC. Conversely, all patients with HER2-negative (score 0, 1 +) GU tumors had residual invasive tumors. Finally, favourable outcome trends in recurrence-free and cancer-specific survival were observed with HER2 IHC positivity in this subtype. Overall, combining immunohistochemical molecular subtyping with HER2 IHC status may help predict responses to cisplatin-based NAC, guiding MIBC management decisions.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histopathologic and molecular evidence of malignant potential in morules associated with gastrointestinal neoplasia.","authors":"Diana Agostini-Vulaj, Zoltan N Oltavi, Xiaoyan Liao","doi":"10.1007/s00428-025-04181-8","DOIUrl":"https://doi.org/10.1007/s00428-025-04181-8","url":null,"abstract":"<p><p>Gastrointestinal (GI) adenomas with distinct solid cell clusters showing squamous or neuroendocrine differentiation are interchangeably termed as \"squamoid morule (SM)\" or \"microcarcinoid (MC).\" Though considered benign, their biogenesis and malignant potential remain contentious. We reviewed 39 cases of GI neoplasms with morules to characterize their histomorphology, immunoprofile, and molecular features. The cohort included 19 women and 20 men with a median age of 65 years. Eight cases were in the upper GI tract, while 31 were colorectal. Among eight (31%) colorectal morules associated with invasion, seven maintained a bland cytomorphology and one longitudinally progressed to an undifferentiated carcinoma component across 5 years. Morphologically, 23 were arbitrarily classified as SM and 16 as MC. SM were larger (p = 0.037) and showed more single cell necrosis (p = 0.003) than MC. Immunohistochemically, both colorectal SM and MC demonstrated high frequency of expression in nuclear β-catenin (91%), CD10 (87%), CK5 (96%), INSM1 (85%), CDX2 (83%), and SATB2 (100%). SM-like morules were more likely to express p63, while the MC-like morules were more likely to express synaptophysin (p = 0.026). Ki67 was generally low (< 1%) except in two invasive cases (> 10%). Molecular analysis showed KRAS as the most common mutated gene in five of seven (71%) tested cases, followed by PIK3CA (43%) and APC (29%). The morules harbored similar or more pathogenic mutations compared to the background neoplasm. In conclusion, SM and MC in the GI tract represent a spectrum of basal stem cells with Wnt/β-catenin activation and multilineage differentiation plasticity, which can progress to malignancy in rare cases.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indolent pediatric lymphomas/lymphoproliferative disorders: a report of the 2024 EA4HP/SH lymphoma workshop.","authors":"Leonie Frauenfeld, Maurilio Ponzoni, Gorana Gasljevic, Ioannis Anagnostopoulos, Michiel Van den Brand, James R Cook, Camille Laurent, Birgitta Sander, Stefan Dirnhofer, Leticia Quintanilla-Martinez, Olga Balague","doi":"10.1007/s00428-025-04184-5","DOIUrl":"https://doi.org/10.1007/s00428-025-04184-5","url":null,"abstract":"<p><p>The boundaries between indolent neoplastic and reactive lymphoproliferations were discussed during the 2024 European Association for Haematopathology/Society for Hematopathology workshop in Dubrovnik, Croatia. Session 4 focused on the revision of indolent pediatric lymphoid neoplasms/lymphoproliferations. Forty-one cases were submitted, representing good examples of indolent pediatric lymphomas/lymphoproliferations and their diagnostic challenges. The morphologic spectrum of pediatric-type follicular lymphoma (PTFL) was discussed, especially exploring unifying features of cases with and without marginal zone differentiation (MZD) (the first also referred to as pediatric nodal marginal zone lymphoma). Unusual features like relapses/recurrences; extranodal involvement and high proliferation rate in the marginal zone differentiated component were observed in PTFL with or without MZD. Rare follicle center-derived neoplasms occurring in children other than PTFL where discussed, such as primary testicular follicular lymphoma and follicle center lymphoma of the lower female genital tract. Testicular follicular lymphomas were compared to cases known from literature, defining a better picture of their clinicopathological features. The criteria for the diagnosis of atypical lymphoid hyperplasia were reviewed and nodal and extranodal cases are discussed. Plasmacytic proliferations in the pediatric population are exceedingly rare, but do exist in clonal and non-clonal forms. A heterogeneous group of extranodal lymphomas is included, among them extranodal marginal zone lymphomas (MZL) of the stomach with a large cell transformation and an intramuscular MZL with comparable features of a cutaneous MZL/lymphoproliferation with IgG4 expression. In this report, the different spectrum of indolent pediatric lymphomas compared to the adult counterpart will be highlighted, to avoid misdiagnosis and overtreatment.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proficiency test of BRAF immunohistochemistry as a surrogate marker of p.V600E mutation: Assessment of staining and interpretation quality in Taiwan.","authors":"Yun-An Chen, Jyie-Yu Lai, Chih-Yi Hsu, Huang-Chun Lien, Jen-Fan Hang","doi":"10.1007/s00428-025-04192-5","DOIUrl":"https://doi.org/10.1007/s00428-025-04192-5","url":null,"abstract":"<p><p>BRAF immunohistochemistry (IHC) serves as a surrogate for BRAF p.V600E but shows variable performance across tumor types and institutions. This study evaluated BRAF IHC staining quality and interpretation in general pathology laboratories through a nationwide proficiency test (PT) in Taiwan, focusing on the most commonly encountered thyroid neoplasm and colorectal cancer. This PT was organized by the Taiwan Society of Pathology using a tissue microarray, containing six tumor cores with confirmed BRAF mutation status and one positive control. Participating laboratories performed BRAF IHC staining and interpretation independently, with results centrally reviewed for concordance, accuracy, and staining quality. Twenty-six pathology laboratories participated. Two laboratories failed the initial control check. Among the remaining 24, 17 (70.83%) demonstrated optimal staining, while 5 (20.83%) showed over-staining and 2 (8.33%) under-staining. No significant associations were found between staining quality and antibody clones, platforms, dilution folds, or assay types. Interpretation was highly concordant (100% agreement and accuracy) for tissues with 3 + or negative staining. However, discrepancies arose in tissues with 2 + intensity (50% positive, 41.67% negative, 8.33% equivocal) and 1 + intensity (83.33% disagreement with test results). The overall accuracy was 79.2%, with sensitivity at 58.3% and specificity at 100%. Under-calling was frequent in cases with 1 + staining (33 cores across 23 laboratories) and 2 + staining (3 cores across 3 laboratories). Our study highlights the importance of optimizing staining quality and reinforcing education on interpretation criteria. To minimize false-negative results, we recommend molecular confirmation for all cases exhibiting diffusely weak staining.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"YAP1::MAML2, YAP1::NUTM1, and RNF13::PAK2 rearrangements in trichoblastomas and adnexal tumors with panfollicular differentiation: expanding the spectrum of YAP1/PAK-fused skin adnexal tumors.","authors":"Thibault Kervarrec, Nicolas Macagno, Aurelie Houlier, Daniel Pissaloux, Brice Thamphya, Baptiste Louveau, Samia Mourah, Maxence Mancini, Dmitry Kazakov, Kim Harnisch, Franck Tirode, Gerardo Cazzato, Pierre Sohier, Arnaud de la Fouchardière, Maxime Battistella, Eduardo Calonje","doi":"10.1007/s00428-025-04175-6","DOIUrl":"https://doi.org/10.1007/s00428-025-04175-6","url":null,"abstract":"<p><p>In 2019, YAP1::MAML2 and YAP1::NUTM1 rearrangements were demonstrated in the majority of poromas and in porocarcinomas. Recently, our group demonstrated recurrent fusions of PAK (p21 (RAC1) activated kinase) 1/2/3 genes in a subset of poromas and porocarcinomas frequently harboring hair follicle and sebaceous differentiation. To expand the spectrum of YAP1/PAK-fused tumors, we report six adnexal neoplasms with follicular differentiation with in frame YAP1::MAML2, YAP1::NUTM1, or RNF13::PAK2 fusion transcripts. Four cases of trichoblastoma and two neoplasms with panfollicular differentiation were included. Median age was 66 (range 39-76). Two patients were female. Tumors were located on the head (n = 4), chest (n = 1), or leg (n = 1). Microscopically, tumors were located in the dermis (n = 4) and/or subcutaneous tissue (n = 5), and showed macro (n = 6), micronodular (n = 5), and cystic (n = 4) structures. A delicate fibrillar stroma was present in 5 cases. Infundibulocystic structures, cell balls, and sebocytes were observed in 5, 1, and 3 cases, respectively. Immunohistochemistry revealed BerEP4 expression and Merkel cell hyperplasia in 5 and 2 cases, respectively. YAP1 (C-terminal) loss was observed in 5 cases. Accordingly YAP1::MAML2 (n = 2), YAP1::NUTM1 (n = 1), or RNF13::PAK2 (n = 1) inframe fusion transcripts were detected in the four trichoblastomas. YAP1::MAML2 fusions were also detected in the two tumors with panfollicular differentiation. In conclusion, we report six cases of follicular tumors with YAP1::MAML2, YAP1::NUTM1, or RNF13::PAK2 fusions and therefore suggest that in addition to poroid tumors, YAP1 and PAK2 fusions might be the oncogenic driver in a subset of adnexal tumors with prominent follicular differentiation.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intranodal palisaded myofibroblastoma shows a unique epigenetic profile-first molecular study of their epigenetic and copy number variation profile.","authors":"Sandra Leisz, Maximilian Scheer, Uwe Hildebrandt, Merle Wiegers, Christian Strauss, Christian Scheller, Thomas Mentzel, Andreas von Deimling, Anja Harder","doi":"10.1007/s00428-025-04170-x","DOIUrl":"https://doi.org/10.1007/s00428-025-04170-x","url":null,"abstract":"<p><p>Intranodal palisaded myofibroblastomas with amianthoid fibers (IPM) are rare mesenchymal neoplasms showing a myofibroblastic differentiation. Histopathologically, they might be difficult to distinguish from schwannoma or other neoplasia with spindle cell morphology, especially on limited biopsies. CTNNB1 gene variants have been detected in at least 50% of tumors. In this study, we determined the methylation profile including the copy number variation profile in a series of six patients. These analyses enabled genes with the highest gains or losses compared to myoblasts and fibroblasts to be identified. We identified a new methylation cluster that is not included in the Heidelberg Sarcoma Classifier so far. Furthermore, significantly differentially hypo- and hypermethylated genes compared to normal myoblasts and fibroblasts were detected in all samples, e.g., ARID5A, MIB2, TRIM58, and others were > 17-fold hypomethylated, while NEDD4, RUNX1, SLC8A1, and others were > 75-fold hypermethylated. Additionally, when combining positive ß-catenin expression and sequencing results, the aberrant/mutant CTNNB1 gene was shown in three tumors (75% of analyzed cases) in this IPM series. The present data provides additional support/adjunct to establish the rare diagnosis of intranodal palisaded myofibroblastomas with amianthoid fibers by molecular testing in diagnostically challenging cases.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144660316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indirect clinical validation for predictive biomarkers in oncology: International Quality Network for Pathology (IQN Path) Position Paper.","authors":"Emina E Torlakovic, Raed Al Dieri, Tony Badrick, Zongming Eric Chen, Carol C Cheung, Zandra Deans, Andrew Dodson, Francesca Fenizia, Hiroshi Kijima, Joerg Maas, Antonio Martinez, Søren Nielsen, Simon Patton, Etienne Rouleau, Peter Schirmacher, Tanuja Shet, Tracy Stockley, Nicola Normanno","doi":"10.1007/s00428-025-04169-4","DOIUrl":"https://doi.org/10.1007/s00428-025-04169-4","url":null,"abstract":"<p><p>Validation of biomarker assays is mandatory not only for their applications in clinical trials but also for their subsequent transfer to clinical laboratories in routine clinical care. There are two critical components relevant to their transfer to clinical practice: regulatory oversight and methodology transfer. Both aspects are simplified where companion diagnostic (CDx) assays relevant to a given indication are being implemented in clinical laboratories. However, when laboratory developed tests (LDTs) are being used either because CDx is not available or because LDT is preferred, both aspects need special consideration from regulatory agencies as well as clinical laboratories. The key component that links these two aspects is evidence of validation of the new LDTs. For predictive and prognostic biomarkers in oncology, clinical validation is feasible only in clinical trials. This approach is not available or feasible to clinical laboratories that develop LDTs. While clinical laboratories routinely perform technical/analytical validation, depending on the type of biomarker, this may not be sufficient to provide evidence of the LDT's clinical relevance. Laboratories must perform and document their assessment for the need for indirect clinical validation. When indirect clinical validation is required, it must be performed according to existing guidelines for this purpose. This paper provides expert consensus guidance and recommendations on how to assess for the need for indirect clinical validation and how to perform indirect clinical validation where required. This paper also provides a conceptual framework to regulatory agencies for determining requirements for validation of predictive and prognostic biomarkers in oncology.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rare occurrence of penoscrotal basal cell carcinoma: Clinicopathologic findings from a single institution cohort and comprehensive literature review.","authors":"Bethany Batson, Tiarra Price, Dimitrios Korentzelos, Melissa Russell, Arivarasan Karunamurthy, Siobhan I Telfer, Gabriela M Quiroga-Garza","doi":"10.1007/s00428-025-04188-1","DOIUrl":"https://doi.org/10.1007/s00428-025-04188-1","url":null,"abstract":"<p><p>Basal cell carcinoma (BCC) is a frequently diagnosed cancer often associated with increased cumulative sun exposure. BCCs rarely occur on sun-protected areas, such as the external genitalia. Herein, we present the largest single-institution case series and comprehensive literature review of penoscrotal BCC. We performed a retrospective analysis of penoscrotal BCC cases diagnosed between 2000 and 2023 and collected information regarding demographics, risk factors, clinicopathologic features, treatment, and outcome. Available slides were reviewed by an experienced dermatopathologist and a genitourinary pathologist, and risk categories were assigned based on histologic subtype in accordance with the current World Health Organization (WHO) classification guidelines. Twenty cases of scrotal BCC and two cases of penile BCC were diagnosed during the study period. Reported risk factors included other non-melanoma skin cancer involving sun-exposed areas (42.9%) and sun-protected areas (9.5%), tobacco use (42.9%), chronic kidney disease (19%), moderate to severe sun exposure (14%), immunosuppressive/modulatory medication (9.5%), external beam radiation, and psoriasis. The median age at time of diagnosis, time to presentation, and lesion size were 69 years, 0.5 years, and 1.5 cm, respectively. Among the recognized subtypes, nodular BCC occurred most frequently (68.4%) and overall most cases (63%) were categorized as low risk. All nineteen cases with available treatment information had been treated with either Mohs (21%), excision (74%), or both (5%). No metastases were reported, and 75% of patients were alive without recurrence at follow-up. Our case series highlights important insights regarding penoscrotal BCC and increases knowledge and awareness of an unusual presentation of a common entity.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}