American Journal of Surgical Pathology最新文献

{"title":"Biallelic ARID1A Alterations : A Promising Novel Biomarker for Risk Stratification and Management in Pediatric Malignant Hepatocellular Tumors.","authors":"Kalyani R Patel, Martin Urbicain, Stephen F Sarabia, Cintia R Perez, Angela M Major, Kevin E Fisher, Angshumoy Roy, Frederic Askin, Andras Heczey, Andres F Espinoza, Sanjeev A Vasudevan, Pavel Sumazin, Dolores H Lopez-Terrada","doi":"10.1097/PAS.0000000000002578","DOIUrl":"10.1097/PAS.0000000000002578","url":null,"abstract":"<p><p>Somatic mutations and copy number alterations of the adenine-thymine (AT)-rich interactive domain-containing protein 1A ( ARID1A ), a tumor suppressor gene, are associated with poor prognosis in many cancers, including adult hepatocellular carcinomas (HCC). In this study, ARID1A protein expression, clinicopathologic features, and outcomes were investigated in 59 pediatric malignant hepatocellular tumors (2004 to 2022) relative to ARID1A mutation and copy number status. Additional studies were performed on the impact of the loss of ARID1A protein expression on genomic instability, immune-cell infiltration, and PD-L1 protein expression. Twenty-three of the 59 (38.9%) children with malignant hepatocellular tumors (age: 0.4 to 13.8 y, M:F=2:1) harbored ARID1A alterations (mutations and/or copy number alterations). Nine tumors (15.2%) with biallelic alterations ( ARID1A -/-) showed higher metastasis at presentation ( P =0.01), were frequently CHIC high-risk ( P =0.05), had aggressive histology (HCN-NOS and HCC) ( P =0.002), and were negative for ARID1A immunohistochemistry (IHC) (100%). ARID1A loss by IHC was 100% sensitive and 98% specific, with 90% positive and 100% negative predictive value for ARID1A -/- tumors. ARID1A-negative tumors showed higher chromosomal instability ( P =0.04), immune infiltrates ( P =0.005), and PD-L1 expression by IHC ( P =0.05). Patients with both ARID1A-negative and ARID1A-negative/PD-L1-positive tumors showed the lowest disease-specific survival in the intermediate and high CHIC-risk and all PRETEXT subgroups ( P =ns ) . The association of biallelic ARID1A alterations with high-risk features and poor outcomes identifies ARID1A as a potential new biomarker in the risk stratification of children with malignant hepatocellular tumors. ARID1A IHC is a reliable tool to identify these aggressive tumors. Associated PD-L1 expression may offer new therapeutic options via checkpoint inhibitors.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1106-1119"},"PeriodicalIF":4.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148256996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HOXB13 Is a Sensitive and Specific Diagnostic Marker for Myxopapillary Ependymoma.","authors":"Meng Zhang, Huanli Duan, Wanting Wang, Lihong Zhao, Min Gao, Leiming Wang, Lianghong Teng","doi":"10.1097/PAS.0000000000002581","DOIUrl":"10.1097/PAS.0000000000002581","url":null,"abstract":"<p><p>Myxopapillary ependymoma (MPE) is a rare spinal tumor that remains undercharacterized in systematic investigations. Accurate distinction from histologic mimics in the conus-cauda-filum terminale region is challenging. This study aimed to describe the clinicopathologic features and outcomes of a large single-center MPE cohort, evaluate the diagnostic utility of HOXB13 immunohistochemistry (IHC), and explore the molecular profiles of atypical cases through methylation clustering. HOXB13 IHC was performed on 45 MPEs, 44 spinal ependymomas (SEs), and 35 other nonependymal spinal tumors. Fourteen atypical cases (MPEs with weak HOXB13 or high-level involvement, and HOXB13-positive SEs) were analyzed by DNA methylation microarray with t-SNE and random forest clustering. HOXB13 expression was semiquantitatively graded (0 to 2). Strong positivity was seen in 97.8% (44/45) of MPEs, but only 4.5% (2/44) of SEs and 11.4% (4/35) of nonependymal tumors. Sensitivity and specificity for MPE diagnosis were 97.8% and 92.4%. Methylation clustering showed strong HOXB13 expression aligned with the MPE methylation class (EPN_MPE). Notably, 3 typical MPEs were misclustered due to fresh hemorrhage, stromal sclerosis, or dural components, whereas 2 HOXB13-strong lumbar SEs fell into the EPN_MPE class. MPE patients had 100% 10-year overall survival and 75% progression-free survival (PFS), but PFS was significantly shorter than that of SE patients ( P < 0.01). HOXB13 is a highly specific and sensitive IHC marker for MPE. Histologic artifacts can interfere with methylation-based classification, emphasizing the need for tissue quality assessment and microdissection when indicated. HOXB13 IHC is a simple, reliable diagnostic tool that improves accuracy when added to routine IHC panels.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1129-1137"},"PeriodicalIF":4.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148434862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypertrophic Lichen Sclerosus: A Form of \"Atypical\" Lichen Sclerosus in the Pathway to HPV-Independent Squamous Cell Carcinoma of the Vulva.","authors":"Susanne K Jeffus, Carli Cox, Sara C Shalin, Brannon Broadfoot, Charles M Quick","doi":"10.1097/PAS.0000000000002574","DOIUrl":"10.1097/PAS.0000000000002574","url":null,"abstract":"<p><p>Hypertrophic lichen sclerosus (HLS) is poorly characterized. A recent study described an atypical form of LS (p53 wild type) with a CK17/D2-40 immunohistochemical profile intermediate between classic LS and differentiated vulvar intraepithelial neoplasia (dVIN). Our study aims to characterize HLS through IHC and molecular profiling to determine if it is a classic or atypical LS lesion. We reviewed HLS diagnosed in 12 biopsies (2014 to 2025) and 5 resections for vulvar squamous cell carcinoma (vSCC) (1998 to 2015) from our institution (mean patient age 59; range: 37 to 97). We defined HLS by nonexophytic acanthosis, hyperkeratosis +/- parakeratosis, granular layer retention, irregular dermal-epidermal junction, lack of severe basal layer atypia, homogenization of the superficial dermis, and +/- lichenoid inflammatory infiltrate. In the 5 resections, CK17 expression was suprabasal in 4 (80%) and superficial in 1 (20%) of HLS adjacent to vSCC. D2-40 intensity was moderate in all 5 (100%). All 5 vSCC were p16-/p53 aberrant with intense D2-40 expression and showed diffuse CK17 in 4 (80%) and suprabasal staining in 1 (20%). All 12 HLS biopsies were p16-; 7 (58%) were p53 wild type and 5 (42%) were aberrant. Seven (58%) showed CK17 suprabasal staining; 5 (42%) were diffuse. D2-40 intensity ranged from absent (1/12; 8%) to faint (3/12; 25%) to moderate (3/12; 25%) to intense (5/12; 42%). Frequently altered genes were SDHA (3/6; 50%) and TP53 (2/6; 33%). HLS shows neither the classic morphology of LS nor dVIN but can be p53 aberrant/mutant. Because of its CK17/D2-40 immunophenotype, it should be considered as atypical LS.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1055-1066"},"PeriodicalIF":4.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148136431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Folate Receptor Alpha Expression Across the Spectrum of Serous Tubal Lesions: An Adjunct Biomarker for Distinguishing Serous Tubal Intraepithelial Carcinoma From Serous Tubal Intraepithelial Lesions.","authors":"Yan Feng, Rujia Fan, Zhigang Yao, Zeng Yuan, Ruijiao Zhao, Yuxin Liu, M Ruhul Quddus, Oluwole Fadare, Jayanthi Lea, Beihua Kong, Wenxin Zheng","doi":"10.1097/PAS.0000000000002612","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002612","url":null,"abstract":"<p><p>Folate receptor alpha (FRα) is highly expressed in tubo-ovarian high-grade serous carcinoma (HGSC), but its expression in serous tubal intraepithelial carcinoma (STIC) and earlier tubal lesions has not been systematically characterized. We evaluated FRα expression across the spectrum of fallopian tube lesions and assessed its potential as an adjunctive diagnostic biomarker. Immunohistochemistry was performed on 408 tubal epithelial samples from 262 patients, including 52 normal fallopian tube samples, 110 secretory cell expansions (SCE), 88 secretory cell outgrowths (SCOUT), 72 serous tubal intraepithelial lesions (STIL), and 56 STICs. An additional 30 HGSCs were included for comparison. FRα expression was assessed using the percentage score ≥2+ (PS2+) system. Associations with germline BRCA status and age were evaluated. FRα expression was detectable in normal fallopian tube epithelium but usually below the high-expression threshold. In contrast, expression was increased in STIC and HGSC, with high PS2+ scores in 73.2% and 76.7% of cases, respectively. Earlier tubal lesions showed predominantly low or negative/very low expression. No significant difference in FRα expression was observed between STIC and HGSC. BRCA-mutated STIC and HGSC showed higher FRα expression than their BRCA nonmutated counterparts, whereas earlier lesions showed no such association. In normal fallopian tube epithelium, FRα expression decreased with age. These findings demonstrate that FRα upregulation is established at the STIC stage and maintained in invasive HGSC. Diffuse high-level expression is uncommon in STIL and earlier lesions, suggesting that FRα may serve as an adjunct biomarker for distinguishing STIC from morphologically overlapping lesions. When interpreted in conjunction with morphology, p53, and Ki-67, FRα may improve diagnostic confidence along the STIL-to-STIC spectrum. The early and sustained upregulation of FRα in STIC also raises interesting questions regarding the timing of FRα-targeted interventions.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Absent Cyclin D1 Expression in Myeloid Sarcomas Distinguishes From Malignant Histiocytic Neoplasms: When Morphologic Ambiguity is Deceptive.","authors":"Alyssa M Lee, Neha Seth, Wayne Tam, Liuyan Jiang, Jithma P Abeykoon, Dongni Yi, Rebecca L King, Kaaren K Reichard, Ronald S Go, Gaurav Goyal, Diana M Morlote, Karen L Rech, Aishwarya Ravindran","doi":"10.1097/PAS.0000000000002570","DOIUrl":"10.1097/PAS.0000000000002570","url":null,"abstract":"<p><p>Myeloid sarcoma (MS) is a tumor mass involving any extramedullary site composed of myeloid-lineage blasts with myeloid, myelomonocytic, or monocytic differentiation. Distinguishing MS from malignant histiocytic neoplasms (MHNs) is diagnostically challenging due to morphologic and immunophenotypic overlap, particularly for MS with monocytic differentiation, which can mimic MHNs, especially the subtypes of histiocytic sarcoma and interdigitating dendritic cell sarcoma, leading to potential misdiagnosis and inappropriate management. Cyclin D1 overexpression is implicated in MHNs, but its utility in differentiating these entities has not been systematically characterized. We evaluated cyclin D1 immunostaining in 43 MS cases and 30 MHNs. The median age at MS diagnosis was 59 years (range: 0.1 to 90), while the median age at MHN diagnosis was 62 years (range: 9 to 90), with heterogeneous sites of involvement. Cyclin D1 evaluation showed 100% MHNs with strong cyclin D1 positivity in ≥50% tumor cells, compared with 7% MS with weak-to-intermediate positivity in a minor subset of tumor cells. Additional immunohistochemical evaluation showed no difference in PU.1 expression in MHNs (93%) versus MS (84%) but demonstrated a higher proportion of OCT2-positivity in MHNs over MS (52% vs. 23%, P <0.05). Our study demonstrates a high sensitivity (100%) and specificity (93%) in utilizing cyclin D1 to distinguish MHNs (mature phenotype) from MS (immature phenotype) in diagnostic practice. It is particularly valuable in challenging scenarios of MS with the absence of immature/myeloid lineage-defining markers (MPO, CD34, or CD117) and provides a cost-effective tool to resolve this diagnostic pitfall, ensuring an accurate subclassification.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1067-1075"},"PeriodicalIF":4.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Highly Vascularized Scars in Cases of Regressed Testicular Germ Cell Tumors: An Occasional Mimic of Hemangioma and a Diagnostic Pitfall.","authors":"Thomas M Ulbright, Ani Toklu, Andres M Acosta","doi":"10.1097/PAS.0000000000002569","DOIUrl":"10.1097/PAS.0000000000002569","url":null,"abstract":"<p><p>We identified 34 cases of regressed testicular germ cell tumors with highly vascularized scars; in 4 cases, the blood vessels were so prominent that hemangioma rather than germ cell tumor regression was considered, a misinterpretation that could result in clinical mismanagement since patients with regressed germ cell tumors require evaluation for metastases and, at a minimum, surveillance. The patients were 16 to 67 years old (median, 37) and usually presented with masses or metastases. Eleven of 12 cases of partial regression had a seminoma component, and seminoma was found in 5 of 7 different cases with sampled metastases. On microscopic examination, the cases usually showed numerous small blood vessels and a variably prominent lymphoplasmacytic infiltrate within scars, often with the greatest vessel concentration at the scar periphery. In 4 cases, a diffuse pattern of numerous, closely packed, small, round or slit-like vessels in fibrous stroma simulated hemangiomas, but with a lymphocyte-rich background. Quantification of the vessel concentration within the scar in the 30 cases where hemangioma was not mimicked showed an average increase in vessel density of 2.6 (range: 1.2 to 8.0) over non-neoplastic parenchyma. For the 4 \"hemangiomatoid\" cases, this ratio exceeded 6. The testis surrounding the scars showed, in all cases, the atrophic changes common to testes harboring germ cell neoplasia in situ-derived germ cell tumors. We conclude that highly vascularized testicular scars caused by regression of testicular germ cell tumors can occasionally show such a high concentration of blood vessels that they mimic hemangiomas. Seminoma is the most common germ cell tumor type to induce this florid reaction. Recognition of this phenomenon is important for proper clinical management.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1120-1128"},"PeriodicalIF":4.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148025640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lessons Learned From 26 Adenomyoepitheliomas of the Breast.","authors":"Lorraine Colón Cartagena, Nichelle Perera, Yuanxin Liang, Haiying Zhan, Uma Krishnamurti","doi":"10.1097/PAS.0000000000002598","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002598","url":null,"abstract":"<p><p>Adenomyoepithelioma (AME) of the breast is a biphasic neoplasm prone to misclassification. To enhance diagnostic awareness, we evaluated 26 AMEs stratified across a spectrum of benign (54%), atypical (27%), special salivary gland-like (12%), and malignant (8%) subtypes. Size and borders stratified the spectrum: benign, atypical, and special subtypes (median: 12 to 18 mm) exhibited lobulated/multilobulated contours, whereas malignant AMEs were larger (median: 27.5 mm) and infiltrative. Cytologic atypia and mitoses were predominant in atypical and malignant subtypes. Overall, 35% of cases were reclassified. Surgical excision corrected 6 core biopsy misinterpretations: 3 benign nodular adenosis-like, 1 unidentified benign AME, 1 benign tubular adenoma-like, and 1 atypical AME mimicking infarcted papilloma. Retrospective review reclassified 3 cases: upgrading 2 benign AMEs to atypical due to cytologic atypia with mitoses, and correcting a metastatic malignant AME misclassified as a papilloma with ductal carcinoma in situ. Aberrant myoepithelium was seen in 19% of cases as loss or heterogeneous p63 and calponin expression. Sequencing of a metastatic malignant AME identified co-occurring AKT1 E17K and GNAS R844C mutations shared between the primary mass and its pulmonary metastasis, confirming clonality. Over a median follow-up of 44 months, the disease-free survival rate was 89%, with one benign local recurrence at 29 months and one malignant pulmonary metastasis at 134 months. Recognizing the histologic spectrum of AMEs allows early detection of these tumors with recurrent or metastatic potential. Given the 35% reclassification rate, excision is recommended for AME-like lesions on core biopsy, particularly those measuring >20 mm.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148862937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRBC1 Immunohistochemistry Utilization in Formalin-fixed Paraffin-embedded Tissue as an Adjunct to T-cell Clonality Testing in the Assessment of Cutaneous Lymphoproliferative Disorders.","authors":"David G Grand, Jeffrey M Cloutier, Sarah R Palmer-DeClara, Jeremiah X Karrs, Shaofeng Yan, Shabnam Momtahen, Soma Jobbagy, Nicole Trepanowski, Joi B Carter, Frederick Lansigan, Robert E LeBlanc","doi":"10.1097/PAS.0000000000002572","DOIUrl":"10.1097/PAS.0000000000002572","url":null,"abstract":"<p><p>T-cell receptor β chain constant region 1 (TRBC1) immunohistochemistry (IHC) has emerged as a novel tool for identifying T-cell clonality in skin biopsies. Its performance in routine formalin-fixed, paraffin-embedded (FFPE) skin specimens across the spectrum of cutaneous T-cell lymphoma (CTCL), however, remains an area of active investigation. We evaluated TRBC1 IHC in 36 cases of cutaneous T-cell lymphoproliferative disorders and 31 polyclonal controls. TRBC1 was assessed relative to CD3 by blinded consensus interpretation followed by semiquantitative estimation of TRBC1-positive cells as a percentage of CD3-positive T-cells. Results were compared with molecular clonality test data, and subtype-specific analyses were performed. Overall concordance of TRBC1 consensus interpretation with clonality testing was 79% (sensitivity 64%, specificity 97%, positive predictive value 96%, negative predictive value 70%). Sensitivity was higher (72%) when analysis was restricted to cases of mycosis fungoides (MF) and controls, but sensitivity decreased (50%) when assessment was restricted to only the intraepithelial T-cells. Sensitivity was also lower (56%) with the assessment of non-MF CTCL. Thresholds of ≤20% or ≥80% and ≤30% or ≥70% TRBC1-positive cells permitted optimal discrimination between monoclonality and polyclonality. As anticipated, lymphoproliferative disorders composed of T-cells that did not express a β chain, including those composed of TCR-ɣ/δ T-cells, lacked TRBC1 expression. Overall, TRBC1 IHC demonstrated modest utility as an adjunctive marker of T-cell clonality in FFPE skin biopsies, with greatest diagnostic value in MF when evaluation is not restricted to intraepithelial lymphocytes.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1007-1014"},"PeriodicalIF":4.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148052085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Outcomes and Prognostication of CRTC1::TRIM11 Fusion Cutaneous Tumors.","authors":"Nithya S Trichy, Jonathan Braat, Lindsay J Holic, Shantel Olivares, Klaus J Busam, Alison Cheah, Jeffrey M Cloutier, Damian Collins, Pranav Dorwal, Arnaud de la Fouchardière, John Gross, Eleni Ieremia, Ivy John, Arivarasan Karunamurthy, Konstantinos Linos, Ata S Moshiri, José A Salinas, Sara Shalin, Campbell Stewart, Khin Thway, Gillian Weston, Pedram Gerami","doi":"10.1097/PAS.0000000000002575","DOIUrl":"10.1097/PAS.0000000000002575","url":null,"abstract":"<p><p>Since the original description of CRTC1::TRIM11 fusion cutaneous tumors (CTCT) in 2018, an increasing number of cases with metastatic behavior have been reported, yet there are limited studies analyzing prognostic parameters. This expanding data set presents an opportunity for reappraisal of clinical behavior. We present a series of 21 cases with detailed morphologic, molecular, clinical outcomes, and therapeutic response data. We utilize this data and a meta-analysis of all the cases in the literature to assess potential prognostic parameters to assist in clinical management. Primary tumors resulting in metastasis were larger ( P =0.038), had higher mitotic counts ( P <0.001), were more frequently ulcerated ( P =0.001), and exclusively harbored TERT promoter mutations ( P =0.005). A functional analysis of mixed data demonstrated a clear clustering pattern in which metastatic cases had larger diameters and were more mitotically active compared with nonmetastatic cases. Inclusion of TERT promoter mutational status further improved the model. There were no metastatic events among cases meeting all the following criteria: size <1.2 cm, <7 mitoses/mm 2 , and absent TERT promoter mutation. Metastatic events frequently involved regional lymph nodes, and all patients with distant metastasis had pulmonary involvement. Considering metastatic events in 23% of cases, sentinel lymph node biopsy and imaging studies may be considered in some cases, while, in cases with smaller size, low mitotic counts, and no evidence of a TERT promoter mutation, excision alone may be adequate. Given poor therapeutic responses in reported metastatic cases, more therapeutic options should be explored.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1015-1028"},"PeriodicalIF":4.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148148157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urothelial Carcinoma in Children and Young Adults is Characterized by Higher Frequency of HRAS Mutations and Lower Prevalence of TERT Promoter and FGFR3 Mutations.","authors":"Liang Cheng, Hui Min Tan, Antonio Lopez-Beltran, Rodolfo Montironi, Adeboye O Osunkoya, Michael Cheng, Ali Amin, Alessia Cimadamore, Shaobo Zhang","doi":"10.1097/PAS.0000000000002566","DOIUrl":"10.1097/PAS.0000000000002566","url":null,"abstract":"<p><p>Urothelial carcinoma in young patients is exceedingly rare, and their molecular oncogenesis is not well understood. In this study, we investigated the frequencies of HRAS, TERT promoter, and FGFR3 mutations in a cohort of 31 urothelial neoplasms occurring in children and young adults, to understand their molecular characteristics and underpinnings. Thirty-one urothelial neoplasms were identified in patients less than 30 years of age. Genomic DNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissue sections. Real-time polymerase chain reaction was used to detect HRAS, TERT promoter, and FGFR3 mutations, and the results were analyzed using high-resolution fluorescence melting curves. The cohort included 2 urothelial papillomas, 1 papillary urothelial neoplasm of low malignant potential (PUNLMP), 23 noninvasive low-grade papillary urothelial carcinomas, and 5 noninvasive high-grade papillary urothelial carcinomas. The patients' mean age was 18 years old, and the male-to-female ratio was 1.4:1. HRAS mutation was detected in 55.2% (16/29) of the premalignant/malignant cases and in 100% (2/2) of the urothelial papillomas, with an overall incidence of 58.1%. TERT promoter mutation was detected in 37.9% (11/29) of PUNLMP and malignant cases, and in none of the benign cases. FGFR3 mutation was not detected in any of the cases. Urothelial carcinomas occurring in children and young adults exhibit a distinct molecular profile compared with those in older patients, characterized by a higher frequency of HRAS mutations and a significantly lower prevalence of TERT promoter and FGFR3 alterations.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"999-1006"},"PeriodicalIF":4.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147947520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}