American Journal of Surgical Pathology最新文献

{"title":"High-Grade Early-Onset Prostate Cancer: Assessment of TMPRSS2::ERG-Negative Tumors Suggests Low Frequency of Germline Alterations and a Pathogenic Role for HOXB13.","authors":"Daisy Maharjan, Stephanie Siegmund, Květoslava Michalova, Igor Odintsov, Jason L Hornick, Varsha Nair, Muhammad T Idrees, Katrina Collins, Jennifer B Gordetsky, Adeboye O Osunkoya, Liang Cheng, Hiroshi Miyamoto, Ankur R Sangoi, Douglas J Wu, Costantino Ricci, Veronica Mollica, Maria R Raspollini, Felix Contreras, Mariela P P Bernal, Isabel M Fernandez, Adriana Rodriguez, Anandi Lobo, Sambit K Mohanty, Shivani Sharma, Mustafa Goksel, Andres M Acosta","doi":"10.1097/PAS.0000000000002459","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002459","url":null,"abstract":"<p><p>Early onset prostate cancer (EOPC; defined herein as prostate cancer [PCa] affecting men ≤ 55 years-old) tends to show low histologic grade, likely representing early detection of indolent tumors that would otherwise be diagnosed later in life. A small subset of EOPC exhibits Gleason scores consistent with high-risk disease (Grade Groups 4 to 5; high-grade EOPC [HG-EOPC] hereafter). In this study, we assess the clinicopathologic features of HG-EOPC, with genomic analysis of ERG-negative cases. We assessed HG-EOPC using immunohistochemistry for ERG (as a surrogate marker of TMPRSS2::ERG), PMS2 (as a surrogate marker of MLH1/PMS2 inactivation), and MSH6 (as a surrogate marker of MSH2/MSH6 inactivation). Selected ERG negative cases were assessed using Oncopanel, which interrogates 447 genes, including PCa-relevant genes. Ninety-six samples from 96 individual patients (median age: 52 y; range: 40 to 55 y) were included in the study. Immunohistochemical staining with ERG was performed in 95 cases, 52 (54%) of which showed negative staining. PMS2 was performed in 93 cases, being retained in 92 (98.9%) and lost in 1 (1.1%). MSH6 was performed in 96 cases, being retained in 92 (95.8%), lost in 2 (2.1%), and equivocal in 2 (2.1%). Sequencing of 23 ERG-negative primary tumors showed enrichment for alterations that are typically associated with castration resistance, including loss of 8p (>50%), gains of 8q (>50%), and inactivation of CDK12 (n=4). The cohort also showed a relatively high frequency of pathogenic TP53 (n=7) and SPOP (n=4) variants. Pathogenic BRCA2 variants and mismatch repair deficiency were identified in 1 case each. Interestingly, >50% of the tumors showed HOXB13 amplification. In conclusion, TMPRSS2::ERG fusion-negative HG-EOPC shows a high frequency of genomic alterations typically enriched in castration-resistant neoplasms but variants of potential germline origin (including those in mismatch repair genes) are rare. These results demonstrate that HG-EOPC is driven largely by somatic events.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758944","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":"Psammomatous Calcifications Identified in Targeted Needle Biopsies and Radical Prostatectomy From IDH1 Mutant Prostatic Adenocarcinoma: Case Report and Literature Review.","authors":"Yang Zong, Mark Sharobim, Edward M Lawrence, Rong Hu, Wei Huang, Daniel D Shapiro","doi":"10.1097/PAS.0000000000002461","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002461","url":null,"abstract":"<p><p>IDH1 mutant prostatic adenocarcinoma represents a small fraction of prostate cancer with distinct epigenetic changes, characterized by genome-wide DNA hypermethylation. Recently, prostatic adenocarcinoma with intratumoral psammomatous calcifications was found to frequently harbors IDH1 R132 mutations. However, the association with IDH1 hotspot mutations and psammomatous calcifications in prostate cancer remains controversial. Here we report another rare case of IDH1 R132H mutant prostatic adenocarcinoma, showing intratumoral psammomatous calcifications identified in targeted needle biopsies as well as subsequent radical prostatectomy specimen. This case provides independent evidence for identification of IDH1 mutant prostate cancer by combined histologic features, including intratumoral psammomatous calcifications, anterior tumor location, and high Gleason score. In addition, to our knowledge, this is the first case of multifocal prostate cancer reported in the literature, with the co-existence of spatially disparate and genetically distinct tumor foci harboring IDH1 R132H mutation or TMPRSS2-ERG gene fusion in the same prostate.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726554","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":"Interobserver Reproducibility of Pelvicalyceal Invasion in Renal Cell Carcinoma Nephrectomies Among Genitourinary Pathologists.","authors":"Ankur R Sangoi, Mahmut Akgul, Aysha Mubeen, Robert Humble, Douglas Jian-Xian Wu, Richard Pacheco, Andres Acosta, Mahul Amin, Manju Aron, Fadi Brimo, Emily Chan, Liang Cheng, John Cheville, Katrina Collins, Kristine Cornejo, Jasreman Dhillon, Michelle R Downes, Jonathan I Epstein, Michelle Hirsch, Payal Kapur, Anandi Lobo, Rohit Mehra, Sambit Mohanty, George Netto, Adeboye O Osunkoya, Gladell Paner, Priya Rao, Rola Saleeb, Rajal B Shah, Steven Shen, Steven Smith, Satish Tickoo, Maria Tretiakova, Kiril Trpkov, Sara Wobker, Pheroze Tamboli, Debra Zynger, Sean R Williamson","doi":"10.1097/PAS.0000000000002456","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002456","url":null,"abstract":"<p><p>Pelvicalyceal invasion (PCI) is a relatively novel pT3a staging parameter for renal cell carcinoma (RCC) nephrectomies. While interobserver reproducibility staging studies of sinus/vascular invasion in RCC exist, a similar evaluation for PCI has not been performed. Moreover, in our experience, there is also diagnostic variability in how pathologists interpret PCI. Herein, we explore interobserver reproducibility among genitourinary (GU) pathologists. Twenty hematoxylin and eosin-stained digitized slides from RCCs (all grossly approaching the renal pelvis) were distributed to 31 GU pathologists to classify each as PCI or not PCI based on their respective clinical practices; slides with concomitant sinus/fat/vascular invasion were excluded. Slides were then evaluated for the following 4 morphologic features: tumor abutting renal pelvis, tumor pushing/indenting into the renal pelvis, polypoid configuration of tumor into the renal pelvis, and tumor eroding through renal pelvic urothelium. Interobserver reproducibility was assessed, and the morphologic features were correlated with PCI. Relationships between pathologists' interpretations, morphologic features, and PCI were evaluated using hierarchical clustering. Although the diagnosis of PCI was relatively uniform with a majority agreement (>67%) reached in 16/20 slides, overall interobserver reproducibility was only moderate (kappa=0.601). While all 4 morphologic features were sensitive for PCI, polypoid configuration of the tumor into the renal pelvis and the tumor eroding through the renal pelvic urothelium were most specific (90%, 100%, respectively). Although we show general consensus among genitourinary pathologists on PCI assessment, clarifying the diagnostic guidelines with specific criteria should be included in pathologic staging systems.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740968","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":"Tubulocystic Renal Cell Carcinoma With Pure Morphology and Confirmed \"Wild Type\" FH/2SC Immunophenotype: Clinicopathologic Series of 30 Patients.","authors":"Lara R Harik, Cristina Magi-Galluzzi, Varsha Manusha, Sara Wobker, Ankur R Sangoi, Geetha Jagannathan, Faisal Saeed, Jatin S Gandhi, Priti Lal, Priya Rao, Kathleen O'Toole, Jesse K McKenney","doi":"10.1097/PAS.0000000000002457","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002457","url":null,"abstract":"<p><p>Tubulocystic renal cell carcinoma is a rare neoplasm, first adopted into the WHO classification of kidney tumors in 2016. The diagnostic criteria were refined in the 2022 WHO classification, requiring \"pure morphology\" and exclusion of other renal cell carcinoma subtypes with overlapping features. We identified 31 tubulocystic renal cell carcinomas from 30 patients. Median age was 60 years (30 to 77 y) with male:female ratio of 13.5:1. Race was known for 26 patients, and the majority were African American (n = 16/26,62%), followed by white/Caucasian (10/26, 38%). Eleven patients (37%) had a history of chronic or end-stage renal disease. Median tumor size was 2.3 cm (range: 0.4 to 6.3 cm). All tumors were characterized by cysts and tubules, surrounded by fibrotic stroma. Lining epithelial cells had eosinophilic cytoplasm, ranging from flattened to cuboidal to hobnail in arrangement. By definition, solid epithelial nodules and destructive invasion were absent. In addition, all tumors had a normal pattern of FH and 2SC expression by immunohistochemistry. AJCC stage was pT1 for all 31 tumors: 30 pT1a and 1 pT1b. All patients had no evidence of disease at last follow-up (median: 35 mo; range: 1 to 294 mo). We report a large series of tubulocystic renal cell carcinomas with pure morphology and confirmed normal/\"wild type\" FH/2SC immunophenotype. When these strict definitions are applied, our findings confirm an indolent clinical behavior.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726555","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":"Protein Kinase C-alpha Gene Fusions in Dendritic Cell Neurofibroma: Distinction From Conventional Neurofibroma.","authors":"Arnaud de la Fouchardiere, Elizabeth C Draper, Daniel Pissaloux, Marshall Lukacs, Franck Tirode, John Hanna","doi":"10.1097/PAS.0000000000002460","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002460","url":null,"abstract":"<p><p>Dendritic cell neurofibroma with pseudorosettes is an uncommon but distinctive variant of neurofibroma. The pseudorosette structures are formed by the circumferential arrangement of small, dark cells around an eosinophilic core at the center of which there is often a single larger and paler cell with slender dendrite-like projections. Dendritic cell neurofibroma often shows a multinodular architecture, which can cause confusion with plexiform neurofibroma. Since plexiform neurofibroma is essentially pathognomonic of Neurofibromatosis type I, such confusion could lead to unnecessary and costly clinical work-up. Since its description in 2001, there has been controversy as to whether dendritic cell neurofibroma represents a true subtype of neurofibroma, whose defining molecular feature is loss-of-function mutation in NF1. Here we show in a series of 9 cases that dendritic cell neurofibroma harbors recurrent gene fusions involving protein kinase c-alpha (PRKCA), including SLC44A1::PRKCA. Identical gene fusions are known to occur in a rare brain tumor known as papillary glioneuronal tumor, although this entity appears to be morphologically and clinically distinct from dendritic cell neurofibroma. Our results distinguish dendritic cell neurofibroma from conventional types of neurofibroma and raise consideration that dendritic cell neurofibroma may be better classified as a unique type of benign neural tumor.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740969","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":"Defining a Histologic Scoring System for Gestational Alloimmune Liver Disease.","authors":"Katie Conover, Samantha Saul, Catherine A Chapin, Estella M Alonso, Anita Gupta, Jenna L Bodmer, Mark Lovell, Hector Melin-Aldana, Sarah A Taylor","doi":"10.1097/PAS.0000000000002454","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002454","url":null,"abstract":"<p><p>Gestational alloimmune liver disease (GALD) is a leading cause of neonatal acute liver failure (ALF) with unique histologic features but no established histologic scoring criteria. This study aimed to develop an accurate histologic scoring system to distinguish GALD from non-GALD neonatal ALF. A preliminary system using 6 histologic features characteristic of GALD was created. Four pathologists from 2 institutions applied this system to GALD (n=11) and non-GALD (n=20) neonatal ALF cases from 2008 to 2020. Four cases of Trisomy 21-associated transient myeloproliferative disorder were analyzed separately, as these patients can present with neonatal ALF and display GALD histologic features but are clinically distinguishable. Area under the receiver operating curve (AUROC) was fitted for stepwise combinations of features to determine the most accurate scoring system. GALD histologic features included extensive parenchymal fibrosis and neotubules, and a paucity of healthy hepatocytes, portal tract involvement, extramedullary hematopoiesis, and inflammation. A revised 3-feature system including parenchymal fibrosis, neotubules, and hepatocyte characterization established highest accuracy with an AUROC of 0.891 (P<0.001). Importantly, there were no significant interinstitutional differences in scores assigned to GALD versus non-GALD cases. A 3-factor score of <2 had 100% sensitivity (95% CI: 74%-100%) to exclude GALD and a score >5 had 95% specificity (95% CI: 76%-100%) to diagnose GALD. This study establishes a highly accurate histologic scoring system to differentiate GALD from non-GALD neonatal ALF. Findings may aid in accurate diagnosis of index cases, reducing recurrence risk in subsequent pregnancies and lowering morbidity and mortality associated with GALD.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688681","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":"Clinicopathologic and Molecular Study of TFEB-altered Renal Cell Carcinomas: Tumors With Frequent PDL1 Expression.","authors":"Mengxin Zhang, Jie Xian, Jiaxiang Tang, Ying Yang, Jue Hu, Xiuyi Pan, Linmao Zheng, Yifan Kang, Mengni Zhang, Xuejiao Yu, Xueqin Chen, Ling Nie, Hao Zeng, Qiao Zhou, Ni Chen","doi":"10.1097/PAS.0000000000002458","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002458","url":null,"abstract":"<p><p>TFEB-altered renal cell carcinoma (RCC) included TFEB-rearranged and TFEB-amplified RCC with unclear clinicopathological features and treatment options. Cases of TFEB-altered RCCs were collected. Fourteen cases showed TFEB rearrangement. Five MALAT1::TFEB fusions and one ACTB::TFEB fusion were verified. 8/14 TFEB-rearranged RCCs showed biphasic \"pseudorosette\" structure. All TFEB-rearranged RCC patients were alive without recurrence or metastasis after 3 to 122 months. Fifteen cases showed TFEB amplification, including 5 high-level amplifications (>10 copies) and ten low-level amplifications (5 to 10 copies), including 3 cases showing concomitant TFEB amplification and rearrangement. TFEB-amplified RCCs were high-grade, showing papillary, solid, nested, or alveolar arrangements of cells. In addition, 8 cases showed 3 to 4 TFEB signals were collected, indicating diverse morphologies. PDL1 membranous staining was observed in 9/10 TFEB-rearranged RCCs, and 11/13 TFEB-amplified RCCs. Copy number variation analysis revealed specific amplification of chromosome 6p21.1, where TFEB, VEGFA6, and CCND3 were located, in one high- and 2 low-level amplification cases. Four cases with 3 to 4 TFEB signals did not show specific amplification of this region. Within the follow-up periods of 3 to 64 months, 8/13 TFEB-amplified RCC cases presented with metastasis, and 3/13 patients died in the 12th and 24th months. The treatment processes in several cases and the detailed therapeutic course of a TFEB-amplified case were documented, highlighting the efficacy of PD-1 inhibitors. Our research supported a cutoff of ≥5 TFEB copies for the diagnosis of TFEB-amplified RCCs, though further studies were needed regarding the threshold. The expression of PDL1 might indicate a potential benefit of PD-1 inhibitors.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697433","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 Utility of TRBC1 Immunohistochemistry in the Evaluation of T-Cell Lymphomas.","authors":"Pranav P Patwardhan, Ahmad Al-Attar, Nidhi Aggarwal, Nathanael G Bailey, Katelynn Davis, Majd Jawad, Sara A Monaghan, Bryan Rea, Erika M Moore","doi":"10.1097/PAS.0000000000002455","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002455","url":null,"abstract":"<p><p>T-cell receptor β chain constant region 1 (TRBC1) is a useful marker for the detection of clonal T-cell populations and has been used in flow cytometry, with limited data on its utility as an immunohistochemical marker. We evaluated TRBC1 by immunohistochemistry (IHC) in 42 CD3-positive, T-cell receptor alpha beta-positive T-cell lymphomas and compared their expression pattern to a control cohort of 35 reactive lymph nodes and tonsils. TRBC1 restriction was evident in 37/42 (88%) lymphomas but indeterminate in 5 cases, most of which were follicular helper T-cell lymphomas, angioimmunoblastic type/nodal T follicular helper cell lymphomas, angioimmunoblastic type (AITL). 34/35 (97%) control cases had ∼50% as much TRBC1 staining as CD3; however, one tonsil, while not TRBC1 restricted, had much less staining than CD3, which was confirmed by TRBC1 flow cytometry. TRBC1 IHC was helpful in demonstrating clonality in most T-cell lymphomas, including all cases lacking flow cytometric studies, and in 2 cases without definite molecular evidence of clonality. In differentiating T-cell lymphoma from reactive lymphoid tissue, it had a sensitivity of 88% and specificity of 97%. Thus, TRBC1 IHC is a useful, rapid, and inexpensive tool in the diagnosis of T-cell lymphomas.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688682","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":"Massive/Mass-forming Ductular Reaction Associated With Vascular Occlusion in Various Underlying Basic Liver Diseases.","authors":"Anne Kristin Fischer, Reinhard Büttner, Hans-Peter Fischer","doi":"10.1097/PAS.0000000000002449","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002449","url":null,"abstract":"<p><p>Massive/mass-forming ductular reaction of the liver (MDR) is occasionally in the differential diagnosis with true bile duct tumors. Our diagnostic histomorphological and immunohistochemical study of 14 cases from a consultant collective of 2970 cases follows the appearance of MDR with regard to various underlying liver diseases and the conditions of pathologic perfusion. We describe MDR measuring up to 7 cm in localized form or affecting up to 70% of the parenchyma in subacute liver necrosis. MDR developed in the context of severe inflammatory liver diseases and liver cirrhosis, as well as in colocalization with true malignant neoplasms such as hepatocellular carcinoma, epithelioid hemangioendothelioma, and hepatic angiosarcoma. In all cases, MDR was associated with intra- or directly perilesional thrombotic or tumorous obliteration of intrahepatic portal or hepatic veins or liver sinusoids. In end-stage liver cirrhosis, it was additionally associated with fibrotic occlusion of the portoseptal vascular bed. Further key diagnostic features of this hypoperfused, extensive parenchymal transformation included a monolayered network of small cytokeratin 7-, cytokeratin 19-, and CD56-positive ductules with fingertip-like endings, low proliferative activity (<3% Ki-67-positive cells), and embedded in a loose stroma. The pre-existing lobular architecture, including portal tracts or cirrhotic remodeling, was preserved. In conclusion, MDR of the liver is a rare, confluent pluriacinar and sometimes pseudo-tumorous transformation of the liver parenchyma that is associated with altered liver perfusion. Clinically and histomorphologically, it can mimic a true biliary neoplasm.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648348","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":"Clinicopathologic and Genomic Features of Gastric-Type Intraductal Papillary Neoplasm of the Bile Duct: Potential Role of STK11 in Malignant Progression.","authors":"Yuki Shimada, Takeo Yamamoto, Koji Shindo, Yoshiyuki Nakanishi, Takashi Matsumoto, Shoko Noguchi, Shinichi Aishima, Masafumi Nakamura, Yoshinao Oda","doi":"10.1097/PAS.0000000000002451","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002451","url":null,"abstract":"<p><p>Gastric-type intraductal papillary neoplasm of the bile duct (G-type IPNB) remains an underexplored subtype of IPNBs, with limited molecular characterization. This study aimed to elucidate the clinicopathologic and genomic features of G-type IPNB to better understand its malignant potential and progression. Eighty-three IPNB cases, including 21 G-type IPNBs, were analyzed. The clinicopathologic features and prognosis of G-type IPNB were compared with those of other subtypes. Targeted sequencing was performed in 15 G-type cases, comprising 5 with high-grade dysplasia (HGD), 6 with invasive carcinoma (INV), and 4 with lymph node metastasis (LNM). The samples displayed varying histologic grades. The G-type frequently exhibited HGD; however, invasive G-type IPNBs showed significantly higher rates of lymph node metastasis compared with the other subtypes (P=0.044). Recurrent mutations were detected in KRAS (60%), STK11 (40%), KMT2C (40%), APC (20%), CTNNB1 (13%), and TP53 (13%). Mutational profiles remained highly concordant across histologic grades, with no significant new mutations accumulating during tumor progression. KRAS mutations were predominantly found in preinvasive lesions, supporting their role in early tumorigenesis. STK11 mutations were exclusive to INV and LNM cases, but not detected in HGD cases. Notably, identical mutations were uniformly carried over from preinvasive lesions to invasive carcinoma and metastatic lymph node lesions. Immunohistochemically, aberrant STK11 expression was specific to the G-type compared with other subtypes (P=0.030). These findings highlight the unique clinicopathologic and molecular features of G-type IPNB, including the association of STK11 mutations with invasive behavior and their potential as indicators of tumor progression.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607194","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}