American Journal of Surgical Pathology最新文献

{"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":"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":"1281-1293"},"PeriodicalIF":4.2,"publicationDate":"2026-11-01","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":"Lipid-Rich Urothelial Carcinoma: A Contemporary Clinicopathologic Study of 40 Patients With Transcriptional Tumor Profiling.","authors":"Huili Li, Swati Bhardwaj, Mingxiao Feng, Meghan McNamara, Anuj Gupta, David McConkey, Adeboye O Osunkoya, Ciera Mangone, Ezra G Baraban, Andres Matoso","doi":"10.1097/PAS.0000000000002595","DOIUrl":"10.1097/PAS.0000000000002595","url":null,"abstract":"<p><p>Lipid-rich urothelial carcinoma (LR-UC) is a rare subtype, with ∼65 cases reported in the literature. Here, we report the largest case series of bladder LR-UC, including 40 patients. Clinical follow-up was available for 29 patients. Twenty-seven patients had at least 2-years follow-up, 15 of whom were alive (55.6%) at 2 years. Twenty-six patients had at least 5-years follow-up, 12 of whom were alive (46%) at 5 years. Definitive resection was associated with improved overall survival (OS) ( P =0.0188). Neoadjuvant treatment showed a trend towards improved OS compared with resection alone. Patients with a higher percentage of LR-UC (>10%) showed a trend of decreased OS. Positive MDM2 immunostain in both LR-UC and adjacent UC was observed in 6 of 8 tumors, with MDM2 gene amplification confirmed by FISH in one case and MDM2 RNA-ISH overexpression in one additional case. RNA-seq was performed on 9 paired microdissected LR-UC and adjacent UC samples. Principal component analysis demonstrated LR-UC clustered with its paired UC more than with the LR component of other patients. PRSS3P2 was the only component detected to be higher in LR-UC than in UC. GSEA analysis demonstrated that 59.1% of positively enriched genes were metabolism-related, and 57.6% of negatively enriched genes were immune/inflammation-related. In summary, we report the largest LR-UC series to date, highlighting its aggressive clinical behavior, and suggesting a possible benefit of definitive surgical resection and neoadjuvant therapy. MDM2 expression in UC with lipoblast-like cells may pose a diagnostic pitfall and transcriptomic profiling confirm the UC origin lipoblast-like cells.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1269-1280"},"PeriodicalIF":4.2,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757770","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":"Immunohistochemical and Molecular Features Distinguishing Metaplastic Breast Carcinoma With Squamous Differentiation From Cutaneous Squamous Cell Carcinoma.","authors":"Cooper D Rutland, Leandra G Kingsley, Sabrina Zdravkovic, Poonam Vohra, Yunn-Yi Chen, Gregor Krings, Gregory R Bean","doi":"10.1097/PAS.0000000000002601","DOIUrl":"10.1097/PAS.0000000000002601","url":null,"abstract":"<p><p>Metaplastic breast carcinoma (MBC) with squamous differentiation can often be diagnosed by routine histopathologic evaluation, but cutaneous squamous cell carcinoma (cSCC) may enter the differential diagnosis in selected pure squamous carcinomas involving the breast/chest, particularly in limited samples or cases lacking definitive epidermal connection, ductal carcinoma in situ, or complete clinical information. Determining the site of origin is clinically important because management strategies for breast and cutaneous carcinomas differ substantially. We sought to identify immunohistochemical and genetic features that could distinguish MBC with squamous differentiation from cSCC arising in breast/chest skin in cases of uncertain origin. To this end, we comprehensively characterized 15 MBC with pure to mixed squamous differentiation and 18 invasive/in situ cSCC arising in breast/chest skin. Comparisons between these cohorts and 48 SCC of other anatomic sites identified significant immunohistochemical differences, with CK7, SOX10, and TRPS1 expression more frequent in MBC than cSCC ( P =0.0005, 0.0227, and 0.0290, respectively). HER2 overexpression was identified only in breast and esophageal carcinomas. Next-generation sequencing of the breast/chest tumors demonstrated more frequent PIK3CA/PIK3R1 alterations in MBC than cSCC ( P =0.0040), whereas NOTCH1 mutations were exclusive to cSCC ( P =0.0407). cSCC showed higher tumor mutational burden and percentage of ultraviolet-associated mutations than MBC ( P =0.0002 and <0.0001, respectively). These distinguishing features were then applied to 9 additional breast cases of uncertain origin, demonstrating the added value of molecular data in diagnostically challenging cases. Overall, these findings support a stepwise diagnostic approach integrating immunohistochemistry, selected molecular features, and clinicopathologic context to aid in this distinction.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1372-1387"},"PeriodicalIF":4.2,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acquired Cystic Disease-Associated Renal Cell Carcinoma: Recurrent Copy-Number Patterns and Overlap With Papillary Renal Cell Carcinoma.","authors":"Richard R Pacheco, Ankur R Sangoi, Andres M Acosta, Deepika Sirohi, Emily Chan","doi":"10.1097/PAS.0000000000002636","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002636","url":null,"abstract":"<p><p>Acquired cystic disease-associated renal cell carcinoma (ACD-RCC) is a histologically distinctive renal neoplasm arising in patients with end-stage renal disease, in which the molecular underpinnings remain incompletely characterized. In this study, 14 ACD-RCC tumors from 13 patients underwent comprehensive targeted next-generation sequencing with copy-number analysis. All tumors had classic histologic features characterized by solid sieve-like and cystic growth with abundant eosinophilic cytoplasm, predominantly high nucleolar grade (13/14), and variably present calcium oxalate crystals (10/14). By sequence analysis, single-gene alterations were relatively infrequent and heterogenous, with no recurrent alterations within the cohort; though several alterations identified were occasionally recurrent across studies on literature review (eg, KMT2C, SETD2, FANCA, and FAT1). Copy-number analysis identified 3 patterns of chromosomal alterations: gain-predominant (n=7), loss-predominant (n=4), and near-euploid (n=3) subgroups. Gain-predominant tumors harbored recurrent gains of chromosomes 3, 7, 16, 17, and 20, whereas loss-predominant tumors showed recurrent losses of chromosomes 6, 9, 14, 19, and 21. The near-euploid group had relatively fewer chromosomal copy-number alterations. Notably, comparison with publicly available The Cancer Genome Atlas papillary renal cell carcinoma (PRCC, TCGA-KIRP) data demonstrated overlapping gains of chromosomes 7, 16, 17, and 20 with the gain-predominant ACD-RCC. In addition, a paired ACD-RCC and synchronous PRCC from the same patient in our cohort displayed highly similar arm-level copy-number profiles, differing only by an additional gain of chromosome 3q in the ACD-RCC. In summary, ACD-RCC demonstrates recurrent arm-level chromosomal alteration patterns despite heterogenous gene-level findings. The gain-predominant tumors show substantial molecular overlap with PRCC, supporting genomic similarity between these entities despite distinct histomorphology. Together, these findings also suggest that copy-number patterns may represent a useful molecular framework for understanding heterogeneity within ACD-RCC.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149260835","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":"The Largest Cohort Study of Intravenous Leiomyomatosis Reveals HMGA2 and Collagen Gene Alterations as Cooperative Drivers.","authors":"Wei Zheng, Xia Liu, Yiwen Sun, Zijun Wang, Dong Chen, Yan Liu, Juan Du, Xiaoya Zhao, Jianfeng Shang, Yang Zhan, Congrong Liu","doi":"10.1097/PAS.0000000000002637","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002637","url":null,"abstract":"<p><p>Intravenous leiomyomatosis (IVL) is a rare, hormonally responsive smooth muscle neoplasm defined by nondestructive intravascular growth. Despite its distinct clinical behavior, the comprehensive molecular landscape of IVL has not been systematically characterized. We collected the clinicopathologic characteristics of 89 IVLs, 106 conventional uterine leiomyomas (cULMs), and 83 cellular leiomyomas (CLs). Using immunohistochemistry (IHC), we evaluated high mobility group AT-hook 2 (HMGA2) expression in 88 IVLs, 106 cULMs, and 83 CLs. We also assessed fumarate hydratase (FH) and 2-succinocysteine status by IHC in 82 IVLs. Fluorescence in situ hybridization was performed using the HMGA2 break-apart probe in 84 IVLs and the HMGA2/RAD51B fusion probe in 83 IVLs. We detected MED12 exon 2 hotspot mutations by Sanger sequencing in 79 IVLs. Whole-exome sequencing (WES) was performed in 10 IVLs. We found that IVL predominantly affected reproductive-aged women, most with a history of uterine trauma. HMGA2 expression was upregulated in 87.5% (77/88) of IVLs, with strong immunoreactivity in 40.9% (36/88) of IVLs. Half of IVLs harbored HMGA2 rearrangements, predominantly the HMGA2/RAD51B fusion. WES revealed frequent mutations in collagen (COL) gene family members (70.0%, 7/10), all co-occurring with HMGA2 upregulation. Conversely, MED12 exon 2 mutations (2.5%, 2/79) and FH deficiency (2.4%, 2/82) were rare events in this cohort. We propose that IVL pathogenesis likely involves synergistic interplay between dysregulated HMGA2 and COL gene family alterations within a permissive microenvironment influenced by hormones and uterine trauma. FH deficiency and MED12 exon 2 hotspot mutations appear infrequent in IVL and may not represent primary drivers of disease initiation.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149236673","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":"Genetic Alterations in Sclerosing Angiomatoid Nodular Transformation of the Spleen: Insights into Pathogenesis From Next-Generation Sequencing.","authors":"Shu-Hsien Wang, Jen-Chieh Lee, Po-Min Chiang, Yung-Yeh Su, Jen Lin, L Jeffrey Medeiros, Kung-Chao Chang","doi":"10.1097/PAS.0000000000002638","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002638","url":null,"abstract":"<p><p>Sclerosing angiomatoid nodular transformation (SANT) of the spleen is a rare benign lesion with distinctive morphologic features, but its pathogenesis remains controversial. To clarify its biological nature, we analyzed 24 SANT cases using targeted next-generation sequencing with histologic and immunohistochemical evaluation. Three adjacent normal spleen samples served as controls. Most (95.8%) lesions were solitary and detected incidentally (87.5%), with a mean size of 4.5 cm (range: 2.2 to 8.2 cm). All cases showed characteristic multinodular architecture composed of sclerotic stroma, vascular channels, and inflammatory infiltrates; no cases had clinical evidence of IgG4-related disease. Genetic alterations were identified in 12 of 24 (50%) cases, including mutations and copy number gains involving 14 genes. Recurrent alterations affected JAK1, RPS6KB1, MLH1, FGFR3, EPHA5, and CCND1. The most frequent alteration was a JAK1 p.V658F mutation (n=4), followed by MLH1 (n=2) and EPHA5 (n=2) mutations. Two cases each carried copy number gains of RPS6KB1, FGFR3, and CCND1. All SANT cases exhibited low tumor mutational burden (TMB) (mean: 2.26 mutations per megabase) and low microsatellite instability (mean, 2.51%; range: 0% to 7.4%). No genetic alterations were detected in 3 normal spleen samples. Pathway analysis highlighted cell cycle progression as the predominant altered signaling pathway. Compared with negative cases, SANT cases with genetic alterations had fewer IgG4-positive plasma cells (0% vs. 60%, P=0.012) and a trend toward increased CD31-positive endothelial cells (63% vs. 20%, P=0.135). These findings demonstrate that approximately half of SANT cases harbor somatic genetic alterations, supporting a clonal, neoplastic basis for at least a subset of these lesions.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149219872","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":"Pathology, Clinical Features, and Natural History of Low-Grade B-Cell Lymphomas With Primary Osseous Presentation.","authors":"Shenon Sethi, Irem Isgor, Pallavi K Galera, Efrat Luttwak, Heiko Schöder, Gilles A Salles, Ahmet Dogan","doi":"10.1097/PAS.0000000000002631","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002631","url":null,"abstract":"<p><p>Primary bone lymphomas are rare, and most reported cases represent diffuse large B-cell lymphoma. Low-grade B-cell lymphomas presenting with primary osseous involvement (PB-LGBCLs) are far less common, and their clinicopathologic features and clinical course remain poorly defined. We retrospectively analyzed 32 PB-LGBCLs diagnosed at a single tertiary cancer center. Cases were included when the disease presented with bone-only involvement, with or without contiguous soft tissue extension, and without lymph node, spleen, or noncontiguous extranodal disease at initial diagnosis. Staging marrow and low-level peripheral blood involvement were recorded but were not used as exclusion criteria. The cohort included follicular lymphoma (FL; 22/32, 69%), marginal zone lymphoma (MZL; 6/32, 19%), lymphoplasmacytic lymphoma (LPL; 2/32, 6%), and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; 2/32, 6%). Median age was 64 years (range: 39 to 87), and 25/32 patients (78%) had multifocal skeletal disease, most often involving the pelvis and spine. Primary bone FL frequently showed features typical of conventional FL, including germinal center B-cell phenotype, frequent BCL2 rearrangement, and recurrent FL-associated mutations. Non-FL subtypes showed clinicopathologic features and molecular findings compatible with their systemic counterparts. Among 27 patients with more than 6 months of follow-up, disease progression or transformation occurred in 12 patients. Three FLs transformed to diffuse large B-cell lymphoma. No deaths occurred. PB-LGBCLs are rare with FL as the most common subtype and show heterogeneous biology and clinical behavior. Recognition of this presentation is important to avoid misclassification as aggressive lymphoma, nonhematolymphoid bone neoplasm, or reactive condition.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149219829","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":"Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma: Clinicopathologic and Genetic Analysis of a Large Chinese Cohort.","authors":"Keya Li, Ran Wei, Mingzhen Su, Ruohong Shui, Hongfen Lu, Xiaoqiu Li, Xiongzeng Zhu, Xiaoyan Zhou, Baohua Yu","doi":"10.1097/PAS.0000000000002629","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002629","url":null,"abstract":"<p><p>Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare and aggressive T-cell lymphoma with incompletely characterized features. We analyzed 120 Chinese patients (88 males, 32 females; median age 58y), including 43% at stage I. All patients had gastrointestinal (GI) involvement, with 78% confined to the small intestine. The tumor cells were typically monomorphic and medium-sized, expressing CD3 (99%), CD7 (90%), CD8 (94%), CD56 (90%), and TIA-1 (97%). Low expression rates were noted for CD4 (9%) and CD5 (13%). CD20 was aberrantly expressed in 4% cases. TCRαβ expression was more common than TCRγδ (1.1:1). The next-generation sequencing (NGS) results showed that all cases had loss-of-function mutations in SETD2 (100%). Other frequently mutated genes included STAT5B (67%), JAK3 (50%), TP53 (33%), and KRAS (22%). All patients had detectable single nucleotide polymorphisms (SNPs). Copy number variations (CNVs) were detected in TSC2 (11%), CDH1 (5%), STK11 (5%), CDKN2B (5%), and SDHD (5%). In addition, novel fusions involving PML-RPH3A (5%), TP63-PRKAR2A (5%), MAD2L1-CD28 (5%), and DPP6-TP63 (5%), were identified. Among these patients, 89% underwent surgery, 83% received systemic chemotherapy, and 7% received stem cell transplantation (SCT). The median overall survival (OS) of 77 patients was 9 months. Age 58 years or older and Ki-67 >50% were significantly associated with poor prognosis in univariate analysis, while Ki-67 >50% and the presence of B symptoms were independent adverse prognostic factors in multivariate analysis. Our findings expand the molecular spectrum of MEITL and support precision medicine approaches for this therapy-resistant disease.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190363","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":"Whole-Exome and Whole-Genome Sequencing Identifies Driver CTNNB1 Mutations in Ossifying Renal Tumor of Infancy.","authors":"Yifei Wang, Zhou Zhou, Xiaowei Li, Chunfang Yao, Manli Zhao, Hengli Ni","doi":"10.1097/PAS.0000000000002630","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002630","url":null,"abstract":"<p><p>Ossifying renal tumor of infancy (ORTI) is an exceedingly rare pediatric renal neoplasm with an inherently benign clinical course. Although histomorphologically well-described, its underlying molecular pathogenesis remains largely unknown, often posing diagnostic pitfalls when distinguishing it from malignant mimics such as Wilms tumor and cellular congenital mesoblastic nephroma. Here, we systematically evaluated the clinicopathologic, immunohistochemical, and genomic spectrum of 4 pediatric ORTI cases from male infants aged 0.5 to 10 months (median: 2.5 mo), all presenting with gross hematuria. Histologically, all tumors exhibited a characteristic biphasic architecture composed of an osteoid/osteoblast-rich component intermixed with a bland spindle cell component, accompanied by variable calcification, localized blastema-like foci, and a lobulated growth pattern. By immunohistochemistry, all cases (4/4, 100%) demonstrated strong, diffuse nuclear β-catenin accumulation in both components, alongside diffuse nuclear positivity for WT1 and SATB2, and focal cyclin D1 expression. The Ki-67 proliferation index revealed a distinct gradient, being consistently higher in the spindle cell component (5% to 30%) than in the osteoid areas (2% to 15%). All tumors were negative for pan-TRK, ALK, CD34, S100, and PAX8. Next-generation sequencing (NGS) (WGS/WES) identified a recurrent, somatic activating hotspot mutation in exon 3 of CTNNB1 (c.A121G, p.T41A) in 100% of cases (4/4), perfectly correlating with nuclear β-catenin localization. Secondary alterations in Wnt pathway regulators (APC, AXIN1/AXIN2) and BMPR1A were also detected, while FISH confirmed the absence of ETV6::NTRK3 gene rearrangements. All patients achieved long-term disease-free survival following complete surgical resection (follow-up up to 10 y). In summary, ORTI is a distinct, CTNNB1-driven pediatric renal neoplasm defined by recurrent exon 3 hotspot mutations and aberrant nuclear β-catenin expression. Recognition of these pathognomonic molecular and immunophenotypic hallmarks establishes robust diagnostic criteria to definitively distinguish ORTI from its malignant pediatric renal mimics.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190321","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":"Peritumoral Malignant Cellular Foci Performs Better Than Tumor Budding and Poorly Differentiated Cluster in Risk Stratification of Lymph Node Metastasis in pT1 Colorectal Cancer.","authors":"Chaofeng Yuan, Chao Wang, Jiajun Lai, Jiannan Huang, Jiewei Chen, Wenfei Wu, Jingyun Yang, Zeji Yang, Xuemei Liang, Qi Zhang, Keli Zhong, Guiyu Wang, Xiaosheng He","doi":"10.1097/PAS.0000000000002632","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002632","url":null,"abstract":"<p><p>As biomarkers separated by the arbitrary 5-tumor-cell cutoff at the tumor invasive front, tumor budding (TB) and poorly differentiated clusters (PDC) are recognized as high-risk factors for lymph node metastasis (LNM) in pT1 colorectal cancer (CRC). Nonetheless, relevant findings remain inconsistent. Furthermore, the association between the tumor invasive front biomarker and D3 LNM in pT1 CRC remains unknown. To identify a biomarker that captures the full morphologic spectrum and eliminates the need for such cutoffs at the tumor invasive front for predicting LNM, particularly D3 LNM, in pT1 CRC, we defined peritumoral malignant cellular foci (PMCF) as nonglandular foci composed of ≥1 tumor cell at the tumor invasive front. After enrolling 2611 endoscopically or surgically resected pT1 CRC patients from 6 high-volume Chinese institutions, we found that neither TB nor PDC exhibited a consistent independent association with LNM across the training and validation cohorts. In contrast, PMCF emerged as an independent risk factor with superior risk stratification of LNM in both cohorts (P<0.05). The association between PMCF and LNM remained significant in subgroup analyses stratified by age, sex, tumor location, and BMI (P<0.05). Moreover, PMCF correlated with a greater number of metastatic lymph nodes and exhibited a stronger association with D3 LNM than with D1 and D2 LNM (P<0.05). In conclusion, PMCF not only suggests additional radical surgery after endoscopic resection in pT1 CRC, but may also indicate D3 lymph node dissection. PMCF provides an evidence-based rationale to optimize surgical decision-making in pT1 CRC.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178819","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}