American Journal of Surgical Pathology最新文献

{"title":"Insights From Mutational and Transcriptomic Profiles in Epithelial-myoepithelial Carcinoma.","authors":"Ziyad Alsugair, Françoise Descotes, Anne Champagnac, Jonathan Lopez, Maxime Fieux, Pierre Philouse, Philippe Céruse, Brice Thamphya, Daniel Pissaloux, Franck Tirode, Nazim Benzerdjeb","doi":"10.1097/PAS.0000000000002541","DOIUrl":"10.1097/PAS.0000000000002541","url":null,"abstract":"<p><p>Epithelial-myoepithelial carcinoma (EMC) is a rare malignant tumor of the salivary glands, often characterized by HRAS mutations. The present study aimed to better define the molecular and transcriptomic landscape of EMC and explore its relationship with other head and neck neoplasms, particularly basal cell adenoma (BCA). We retrospectively analyzed 14 EMC cases using histology, immunohistochemistry, and whole-exome capture RNA sequencing. HRAS mutations were identified in 57.0% (8/14) of EMC, predominantly at p.Gly61Arg. Additional mutations identified included PIK3CA , STAT5B , and NOTCH1 , as well as gene fusions such as HMGA2 :: WIF1 and FBXO32 :: PLAG1 . A comparative analysis with 54 RAS -mutated head and neck tumors revealed that HRAS mutations were not exclusive to EMC, as they were also found in benign entities such as BCAs. Transcriptomic profiling found that EMC and BCA shared significant gene expression similarities, clustering closely. Differential expression analysis found upregulation of GATA3 , CHI3L1 , GRIA2 , and MME in EMC, while BCAs had enrichment of Wnt-beta-catenin signaling. In contrast, EMCs had activation of the Ras-Raf-MAPK and PI3K-Akt pathways, supported by upregulation of E2F and G2-M checkpoint targets. Immunohistochemistry confirmed GATA3 positivity in HRAS -mutated EMCs. The frequent RAS mutations and overlapping transcriptomic profiles raise important diagnostic considerations and highlight the need for integrated molecular analyses to differentiate these entities. The EMCs displayed a recurrent HRAS mutation, also observed in other head and neck tumors, and were partially clustered with the cases of BCA, suggesting potential biological similarities.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"716-725"},"PeriodicalIF":4.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13263047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147508808","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":"When to Consider AIH-PBC Overlap Syndrome in the Pathology Report.","authors":"Wei Chen, Honghai Xu, Kara Wegermann, Fengming Chen","doi":"10.1097/PAS.0000000000002547","DOIUrl":"10.1097/PAS.0000000000002547","url":null,"abstract":"<p><p>Autoimmune hepatitis-primary biliary cholangitis (AIH-PBC) overlap syndrome remains a diagnostic challenge due to the absence of standardized criteria and the limitations of current frameworks, such as the Paris Criteria. In this retrospective study, we reviewed 71 liver biopsies flagged for possible overlap and reclassified them based on clinical diagnosis as AIH (n=21), PBC (n=17), or overlap syndrome (n=33), incorporating 74 clinically and pathologically confirmed AIH (n=42) and PBC (n=32) cases as external controls. Only 46% of flagged cases were confirmed as overlap, indicating a 54% overcall rate. Florid duct lesions and bile duct loss were highly specific for a biliary component but were absent in over half of overlap cases, where lymphocytic cholangitis, although less specific, provided additional support when interpreted with serologic data. AMA positivity and alkaline phosphatase elevation were more specific indicators of PBC involvement than elevated IgM. In suspected overlap, hepatic inflammation characterized by confluent necrosis, interface hepatitis (mHAI A≥2), and lobular inflammation (mHAI C≥3), in conjunction with AST or ALT ≥2×upper limit of normal, more reliably distinguished overlap from isolated PBC. Overlap cases showed milder necroinflammatory activity compared with isolated AIH controls, suggesting under-recognition when relying solely on existing AIH scoring systems. We propose a refined diagnostic approach that integrates key histologic findings and serologic markers, supported by semiquantitative assessment using the modified Hepatic Activity Index (mHAI), to improve diagnostic accuracy and reporting consistency for AIH-PBC overlap syndrome.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"814-824"},"PeriodicalIF":4.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697332","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":"Segmental Atrophy of the Liver: An Increasingly Recognized Pseudotumor With Distinct Clinicopathologic and Imaging Features.","authors":"Lakhdar Khellaf, Aude Trinquet, Olivia Sgarbura, François Quénet, Stéphanie Nougaret","doi":"10.1097/PAS.0000000000002543","DOIUrl":"10.1097/PAS.0000000000002543","url":null,"abstract":"<p><p>Segmental atrophy of the liver (SAL) is a recently described vascular-related pseudotumor. We report a series of 26 SAL cases in cancer patients, highlighting clinical, pathologic, and imaging features, with insights into pathogenesis. Cases were prospectively collected between 2017 and 2023 at the Montpellier Cancer Institute. Lesion staging, vascular lesions, and extralesional changes were systematically assessed, with immunohistochemical analysis. All patients (mean age 68 y; female-to-male ratio 1.7) were under oncologic follow-up; 46% had cardiovascular disease and/or diabetes. The median lesion size was 14 mm. Obliterative thrombosis was identified in 14 of 16 evaluable surgical specimens (88%), involving arteries, veins, or both, with intralesional and/or perilesional distribution. Arteriolar hyperplasia was present in 50% of cases, predominantly in advanced lesions, and showed a nonsignificant trend toward higher prevalence in bevacizumab-treated patients. Sinusoidal obstruction syndrome was observed in 31% of cases. Local contributing factors included prior liver-directed therapy (12% of patients) and concurrent tumor involvement (37% of patients), occasionally suggesting tumor-related vascular compression. We identified SMA-positive stromal cells clustered around small- and medium-sized vessels, supporting a perivascular origin and implicating thrombotic vascular injury in fibroelastotic remodeling. These findings highlight the contribution of both local and systemic factors to vascular injury underlying SAL. Recognition of this pseudotumor is essential to avoid misinterpretation and inappropriate clinical management.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"791-803"},"PeriodicalIF":4.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13263046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147643733","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":"A Critical Examination of the Changes Proposed by the AJCCCCEP for the AJCC 9th Edition Colorectal Cancer Staging System.","authors":"Angela Yang Pan, Hojabr Kakavand, Loretta Sioson, Amy Sheen, Mahsa S Ahadi, Angela Chou, Anthony J Gill","doi":"10.1097/PAS.0000000000002539","DOIUrl":"10.1097/PAS.0000000000002539","url":null,"abstract":"<p><p>The AJCC 8th edition colorectal cancer (CRC) staging system demonstrates non-hierarchical survival outcomes, with stage IIIA survivals consistently approximating stage I and exceeding stage II. The AJCC Colon Cancer Expert Panel (AJCCCCEP) has attempted to address this with its new proposal for the 9th edition, which incorporates tumor deposits (TDs) as an independent parameter and rebalances the relative significances of the T-stages and N-stages. We sought to critically assess these proposals in a large single-centre cohort. Patients undergoing CRC resection at our institution from 2005 to 2024 were staged according to the proposed system. Overall survival (OS) was evaluated using Kaplan-Meier analysis and pairwise comparisons made through log-rank tests ( P  < 0.05). Four thousand two hundred fifty-seven CRC patients were identified (median age 74 y, 51% female; 36% node-positive, 17.5% TD positive). Median duration of follow-up was 8.5 years. The proposed staging produced hierarchical OS separation, and all pairwise comparisons achieved statistical significance except stage I versus IIA ( P =0.5), I versus IIB ( P =0.081), and IIA versus IIB ( P =0.10). Surprisingly, in subgroup analysis, patients with low T-stage (T1/T2) with lymph node metastases or tumor deposits (who comprised a small component of the proposed stage IIB grouping) demonstrated superior survival compared with T1/T2 node and tumor deposit-negative patients ( P =0.014). We conclude that the changes proposed by the AJCCCCEP for the 9th edition are an improvement and achieve hierarchical survival stratification. However, if our findings are confirmed in other independent cohorts, the proposal's application in T1/T2 stage disease may need refinement.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"770-778"},"PeriodicalIF":4.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13263040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147643770","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":"NFATC2::NUTM2 Fusion Defines a Novel Primary Pulmonary Epithelial Tumor With a Distinctive Immunophenotype.","authors":"Lanlan Feng, Qiao Liu, Xiaoyan Liu, Shumei Wang, Junting Li, Yu Han, Xiaorong Mu, Yuanyuan Wang, Junfeng Jiang, Chun Wu, Xiujuan Han, Shaojun Zhu, Fuqin Zhang, Jing Tian, Zhuo Wang, Wei Zhang, Li Gong","doi":"10.1097/PAS.0000000000002533","DOIUrl":"10.1097/PAS.0000000000002533","url":null,"abstract":"<p><p>With the application of molecular techniques in pathologic diagnosis, several novel primary pulmonary epithelial tumors have been continuously discovered and classified under the WHO classification of thoracic tumors. Recently, a pulmonary tumor with NFATC2 :: NUTM2B fusion was first documented, but the spectrum of NFATC2::NUTM2 fusion variants and their associated pathologic features remains incompletely characterized. Coincidentally, we also found and described 6 primary pulmonary tumors harboring recurrent NFATC2::NUTM2A/E fusions through integrated genomic analysis. These patients, including 4 females and 2 males, with a median age of 53 years, presented with incidentally detected peripheral lung nodules composed of monotonous epithelioid cells arranged in cords, nests, and trabeculae within a prominent desmoplastic stroma. All tumors exhibited a consistent immunophenotype: CK5/6+/GATA3+/calponin+/EMA+/DOG1 (perinuclear dot-like staining)/p63-. High-throughput chromosome conformation capture (Hi-C) analysis showed the structural variation of NFATC2::NUTM2E in all 6 cases, whereas RNA sequencing detected the fusion transcripts in 5 cases ( NFATC2::NUTM2A , n=2; NFATC2::NUTM2E , n=3). Ultrastructural examination of 1 case suggested epithelial differentiation. All patients remained disease-free after complete resection (median follow-up: 24 mo; range: 9 to 41 mo). These findings define a novel primary pulmonary tumor entity driven by NFATC2::NUTM2 fusions, and characterized by a distinctive immunophenotype, expanding the spectrum of NUTM2 -associated neoplasms. Our study underscores the utility of multiomics approaches for characterizing rare neoplasms and provides a diagnostic framework for this entity.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"695-704"},"PeriodicalIF":4.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147442257","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":"International Society of Urological Pathology Consensus on Cancer Precursor Lesions: Working Group 3 Preneoplastic and Precursor Lesions of the Kidney.","authors":"Sean R Williamson, Sara E Wobker, Rohit Mehra, Khaleel I Al-Obaidy, Guido Martignoni, Sambit Mohanty, Steven C Smith, Puay Hoon Tan, Maria Tretiakova, Payal Kapur, Chin Lee Wu, Mahmut Akgul, Ankur R Sangoi, A Ari Hakimi, Brian Shuch, James Brugarolas, Glen Kristiansen, Liang Cheng, Holger Moch","doi":"10.1097/PAS.0000000000002550","DOIUrl":"10.1097/PAS.0000000000002550","url":null,"abstract":"<p><p>Compared with cancers of other organs, precursor lesions of renal cell neoplasms are rarely discussed. However, there are specific scenarios where cysts or microscopic solid lesions are thought to precede tumor formation. In 2024, the International Society of Urological Pathology (ISUP) held a consensus meeting on precursor lesions of urologic neoplasms in Florence, Italy. This report details the findings of Working Group 3-Precursor Lesions of the Kidney. Papillary adenoma is likely the best-established precursor lesion in the kidney, thought to be an incipient form of papillary renal cell carcinoma (RCC) with shared morphology, immunohistochemistry, and genetics. Likewise, in patients with VHL disease, the kidney often contains multiple small nodules of clear cells and/or cysts lined by one or more layers of clear cells, likely representing early tumor or precursor lesions. Interestingly, a precursor counterpart for clear cell RCC in the sporadic setting is not well established. In other scenarios, cysts are considered potential precursors of neoplasia, such as those in acquired cystic kidney disease (ACKD) and possibly in some hereditary renal tumor syndromes. The consensus panel proposes the following terms \"cyst with epithelial proliferation\" for tufted/hyperplastic/cribriform cyst lining in ACKD without solid tumor, and \"papillary hyperplasia\" for tufting of cyst lining in autosomal dominant polycystic kidney. Terms such as \"tumorlet,\" \"microtumor,\" or \"incipient tumor\" are acceptable for incidental unencapsulated microscopic lesions in hereditary syndrome patients. There is insufficient evidence for the diagnosis of \"tubular dysplasia\" as a precursor to RCC at the present time.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"e32-e47"},"PeriodicalIF":4.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759893","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 and Molecular Characterization of Clear Cell Adenocarcinoma of the Urinary Tract: A Multi-Institutional Study.","authors":"Manju Aron, Darshan S Chandrashekar, Eman Adulfatah, Lakshmi P Kunju, Bassel Zein-Sabatto, João Lobo, Sofia Canete-Portillo, Roni M Cox, Christopher G Przybycin, Khaleel Al-Obaidy, Muhammad T Idrees, Sara M Falzarano, Angela J Wu, Shuko Harada, George J Netto","doi":"10.1097/PAS.0000000000002527","DOIUrl":"10.1097/PAS.0000000000002527","url":null,"abstract":"<p><p>Clear cell adenocarcinoma of the urinary tract (CCA-UT) is a rare, potentially aggressive tumor with very limited information regarding its clinicopathologic characteristics and molecular alterations. This study aimed to elucidate the clinicopathologic features and molecular landscape of one of the largest cohorts (35 cases) of this tumor, to identify genomic alterations and potential therapeutic targets. Seventy-nine percent of the patients were women, with a median age of 61 years. The urethra was the most common site (18; 51%), and all cases were ≥pT2 (pT2:15; pT3:11; pT4:8). Twenty-nine percent of the patients died of their disease on follow-up. On whole-exome sequencing, pathogenic/oncogenic alterations were identified in 91% (32/35) cases. These alterations, most frequently involved chromatin modifiers (66% cases), including ATRX , KMT2C , ARID1A , and ARID1B . Other frequently mutated genes included ATM , NF1 , and ERBB2 . Ninety-seven percent (34/35) of cases were microsatellite stable, and tumor mutational burden (TMB) was >10 mut/Mb in 9% (3/35) of cases. Five cases were homologous recombinant-deficient on ScarHRD analysis, and 3 cases showed BRCA mutations. Recurrent copy number loss events in Chr 1(p36.33-p35.3) were the most common copy number alterations (80%; n=28 cases). RNA-sequencing data analysis revealed numerous differentially expressed genes and enrichment of the epithelial-to-mesenchymal transition gene signature in individual samples. However, there was no statistical significance in the progression-free survival between cases with epithelial and mesenchymal phenotypes. CCA-UT are aggressive tumors with a heterogeneous molecular profile, underscoring the role of molecular analysis in identifying potential therapeutic options for the treatment of this pernicious tumor.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"589-598"},"PeriodicalIF":4.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147347055","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":"International Society of Urological Pathology (ISUP) Consensus Conference on Precursor Lesions: Working Group 4 Precursor Lesions of Testis Results of a Premeeting Survey.","authors":"Felix Bremmer, Maurizio Colecchia, Katrina Collins, Andres M Acosta, Sounak Gupta, Jennifer B Gordetsky, Fiona Maclean, Ewa Rajpert-De Meyts, Klaus-Peter Dieckmann, Seema Kaushal, John R Srigley, Nabil Adra, Timothy Gilligan, Gedske Daugaard, Leendert H J Looijenga, Glen Kristiansen, Liang Cheng, Satish K Tickoo","doi":"10.1097/PAS.0000000000002523","DOIUrl":"10.1097/PAS.0000000000002523","url":null,"abstract":"<p><p>According to the current WHO classification, noninvasive germ cell neoplasia of the testis comprises germ cell neoplasia in situ (GCNIS), specific forms of intratubular germ cell neoplasia, and gonadoblastoma. Because type II germ cell tumors (GCT, type II) arise from GCNIS, accurate detection of precursor lesions is diagnostically important. In preparation for the 2024 International Society of Urological Pathology (ISUP) Consensus Conference on genitourinary precursor lesions, which took place in Florence, Italy, an anonymous survey was distributed to ISUP members to assess current diagnostic practices regarding testicular precursor lesions. The literature and current WHO classification affirm the significance of precursor lesions in testicular tumours. Working Group 4-Precursor Lesions of the Testis-focused on their practical application by individual pathologists rather than establishing consensus from scientific data. There is strong agreement that GCNIS is the preferred and appropriate term for GCT precursor lesions and that its presence should be reported in cases of invasive GCT. Respondents also agree that \"seminoma with intratubular nonseminoma\" is the appropriate terminology for seminoma with an associated noninvasive nonseminomatous (embryonal carcinoma, yolk sac tumor, trophoblasts, or teratoma) component. Most pathologists prefer to use OCT3/4 as the primary immunohistochemical marker, and a panel was generally not considered necessary. No consensus is reached regarding the requirement for immunohistochemistry to confirm GCT precursor lesions in the testis. Three questions remain open: the value of subtyping intratubular lesions, the immunohistochemical approach to gonadoblastoma, and the criteria distinguishing Sertoli cell nodules from Sertoli cell tumors.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"e21-e31"},"PeriodicalIF":4.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147269559","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":"International Society of Urological Pathology (ISUP) Multidisciplinary Consensus on Premalignant and Putative Precursor Lesions of Penile Cancer: Working Group 5 report on Terminology, Grading, and Molecular Testing Practices.","authors":"Santosh Menon, Diego F Sanchez, Alcides Chaux, Giovanna A Giannico, Pedro Oliveira, Andrea Necchi, Sigrid Regauer, Philippe E Speiss, Pheroze Tamboli, Toyonori Tsuzuki, Velazquez Elsa F, Glen Kristiansen, Liang Cheng, Antonio Cubilla","doi":"10.1097/PAS.0000000000002453","DOIUrl":"10.1097/PAS.0000000000002453","url":null,"abstract":"<p><p>The classification and diagnosis of penile intraepithelial neoplasia (PeIN) remains inconsistent among pathologists, despite its recognized role and understanding as a precursor to penile squamous cell carcinoma (PSCC). The International Society of Urological Pathology (ISUP) convened a consensus group of multidisciplinary thought leaders to assess current global practices regarding the usage of terminology, grading, and molecular testing in penile cancer precursor lesions. A preconference survey was distributed to ISUP members in 2024, collecting responses from 112 pathologists, predominantly genitourinary specialists, to evaluate the use of penile cancer precursor lesion classification systems, grading approaches, and diagnostic biomarkers. The results were presented at the ISUP Multidisciplinary Consensus Conference on Cancer Precursor Lesions in September 2024, where further consensus was achieved through electronic voting. The survey revealed that 89.4% of respondents classify PeIN based on HPV association, with 76% supporting further subtyping into basaloid, warty, and differentiated subtypes. Grading of PeIN remains controversial; 51.3% initially favored grading, but 82% finally voted that PeIN should not be graded. p16 immunohistochemistry (IHC) was widely utilized (91.5%) to distinguish HPV-associated from HPV-independent PeIN, whereas p53 IHC and HPV genotyping lacked consensus for routine use. Reporting practices for PeIN margins and their association with lichen sclerosis were widely endorsed, while the value and concordance of subtyping HPV-independent PeIN remains an area for further investigation. This ISUP consensus paper guides PeIN classification, confirming the importance of HPV-related stratification and p16 IHC staining and reporting as standard practice. However, significant variability persists in PeIN grading and molecular testing strategies. These findings highlight the need for further research and standardization to optimize diagnostic accuracy and clinical relevance in PeIN.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"e6-e20"},"PeriodicalIF":4.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144870977","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":"AXIN1 Mutated Hepatocellular Carcinoma.","authors":"Michael Torbenson, Chantal E McCabe, Jessica D Hohenstein, Daniel O'Brien, Zongming E Chen, Tsung-Teh Wu, Sanjay Kakar, Nguyen H Tran, Chen Wang","doi":"10.1097/PAS.0000000000002528","DOIUrl":"10.1097/PAS.0000000000002528","url":null,"abstract":"<p><p>CTNNB1- mutated hepatocellular carcinomas are characterized by a distinctive morphology and activation of the Wnt pathway. AXIN1 also plays a key role in the Wnt pathway, but the morphology of AXIN1-mutated tumors has not been examined. In addition, there are ongoing questions on the ability of AXIN1 mutations to activate the Wnt pathway in hepatocellular carcinoma. AXIN1 mutated tumors (N=18) were studied, along with control groups: CTNNB1 (N=17), APC (6), or \"Other\" genes in the Wnt pathway (5). Wnt pathway activation was studied by immunostains for beta-catenin and glutamine synthetase. Findings were supplemented by gene expression analysis using TCGA data. On histologic examination, the classic morphology associated with beta-catenin mutations was found in all 4 groups: 8/18 AXIN1 (44%), 10/17 CTNNB1 (59%), 4/6 APC (67%), and 1/5 Other (20%). By immunohistochemistry, Wnt pathway activation was found in 11/18 AXIN1 (61%), 15/17 CTTNB1 (88%), 6/6 APC (100%), and 5/5 (100%) of Other. In AXIN1- mutated tumors, the Wnt pathway was weakly activated. Glutamine synthetase stains also highlighted a new \"progressed pattern\" associated with distinct subnodules of staining. Tertiary lymphoid structures were uncommon except for cases with CTTNNB1 mutations plus additional mutations in the Wnt pathway. In summary, the classic morphology associated with CTNNB1 mutations is found in hepatocellular carcinomas with mutations in AXIN1 , APC , and other Wnt genes. AXIN1 mutated tumors have Wnt activation that is detectable but at lower levels than CTNNB1 mutated tumors. As tumors progress, their level of Wnt activation can change.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"642-655"},"PeriodicalIF":4.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147389214","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}