Modern Pathology最新文献

{"title":"FGFR2/3-Altered Intrahepatic Cholangiocarcinoma: A Distinct Clinicopathologic and Molecular Subtype Associated with Improved Disease-Specific Survival.","authors":"Wen-Yu Hsiao, Kartik Angara, Haider A Mejbel","doi":"10.1016/j.modpat.2026.101094","DOIUrl":"https://doi.org/10.1016/j.modpat.2026.101094","url":null,"abstract":"<p><p>Intrahepatic cholangiocarcinoma (iCCA) is an aggressive neoplasm with a poor prognosis. Fibroblast Growth Factor Receptor (FGFR) has emerged as a therapeutic target; however, the clinicopathologic, molecular, and prognostic features of FGFR-altered iCCAs remain incompletely defined. Thus, a 5-year retrospective study of genomically profiled iCCAs using dual whole-exome and whole-transcriptome sequencing, stratified by FGFR2/3 alteration status, to examine their clinicopathologic characteristics, biomarker expression, molecular profile, and prognostic significance on overall (OS), metastasis-free (MFS), progression-free (PFS), and disease-specific survival (DSS) was performed. Ninety iCCAs (25 [27.8%] FGFR2/3-altered and 65 [72.2%] FGFR2/3-wild-type) were identified. FGFR2/3-altered iCCAs encompassed FGFR2 fusions (BICC1, AHCYL1, CREB5, NOL4, NRAP, PAH, POC1B, SH3GLB1, BAIAP2L1, FKBP15, LRRFIP2, and TNS3), FGFR3::TACC3 fusion, and FGFR2 mutations (C382R and Y375C). FGFR2/3-altered iCCA patients were significantly younger (median = 61.0 vs. 68.0 years; p = 0.014), with larger (median = 9.6 vs. 6.4 cm; p = 0.002), well-differentiated (24.0% vs. 1.5%; p < 0.001), non-mucin-producing (84.0% vs. 3.1%; p < 0.001), and small duct tumors (100% vs. 32.3%; p < 0.001), harboring higher BAP1 (36.0% vs. 12.3%; p = 0.016), lower TP53 mutations (4.0% vs. 26.2%; p = 0.019), and ARID1A/KRAS wild-type (0.0% and 0.0% vs. 20% and 13.8%; p = 0.016 and 0.058). FGFR2/3-wild-type iCCAs were TP53/KRAS-enriched and harbored rare fusions (ST7::MET, NRG1::RBPMS, and RAB3GAP2::BRAF). FGFR2/3-altered iCCA patients had significantly higher 1-, 2-, and 3-year DSS (95.8%, 79.1%, and 79.1% vs. 68.4%, 48.2%, and 43.8%; univariate analysis: HR 0.29; 95% CI 0.09-0.95; p = 0.041) but not on multivariate analysis (HR 2.52; 95% CI 0.14-45.07; p = 0.530). In small duct iCCAs, FGFR2/3-altered iCCAs maintained significantly higher DSS versus their wild-type counterparts (95.8%, 79.1%, and 79.1% vs. 60.5%, 32.3%, and 32.3%; HR 0.24; 95% CI 0.06-0.90; p = 0.022), indicating improved survival is attributed to factors beyond small duct subtype. Independent prognostic factors included tumor multifocality (lower MFS), CEA > 2.5 ng/mL (lower PFS), TP53 mutation (lower OS), KRAS mutation (lower OS and DSS), radiotherapy (higher OS), and surgical resection (higher OS, MFS, and DSS). FGFR2/3-altered iCCAs represent a distinct subtype associated with improved DSS, driven by inherent clinicopathologic and co-molecular characteristics rather than FGFR2/3 alteration status alone. Genomic profiling expands the molecular landscape of iCCAs, refines prognostication, and informs patient selection for targeted therapy.</p>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":" ","pages":"101094"},"PeriodicalIF":6.6,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112018","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":"Germline-Somatic Interplay Shapes Molecular Divergence in Peripheral Nerve Sheath Tumors.","authors":"Yurimi Lee, Ji-Young Song, Sungbin An, Jae-Min Choi, Minjung Sung, Kyeong-Tae Lee, Sung Wook Seo, Mi-Sook Lee, So Young Lim, Yoon-La Choi","doi":"10.1016/j.modpat.2026.101091","DOIUrl":"https://doi.org/10.1016/j.modpat.2026.101091","url":null,"abstract":"<p><p>Peripheral nerve sheath tumors (PNSTs) arising in neurofibromatosis type 1 (NF1) show marked histological and clinical heterogeneity, ranging from benign to malignant PNSTs. Although germline NF1 variants underlie tumor predisposition, the mechanisms driving phenotypic and clinical heterogeneity remain incompletely defined. We performed integrated germline and somatic analyses of 208 samples (74 blood samples and 134 tumors) from a primary cohort of 74 patients with NF1. Using a custom NF-focused sequencing panel, we investigated NF1 variant types, co-occurring oncogenic alterations, and affected domains to assess genotype-phenotype associations. Germline analysis identified 55 pathogenic NF1 variants, including eight unreported variants, with recurrent NF1 microdeletions involving SUZ12 in high-grade and premalignant tumors. Among tumors from individuals with germline NF1 variants, biallelic NF1 inactivation occurred in 90/124 tumors (72.6%), most frequently through loss of heterozygosity. In addition, high-grade PNSTs frequently harbored co-alterations in CDKN2A, SUZ12, EED, or TP53. Analysis of the distribution of somatic NF1 variants across functional domains further revealed significant enrichment in the GRD in benign tumors, whereas variants involving the LRD, including the Sec14-PH subdomain, showed a trend toward enrichment in premalignant and malignant tumors. Notably, multi-lesion analysis of spatially and temporally distinct tumors from 30 individuals revealed pronounced intrapatient somatic heterogeneity: despite a shared germline NF1 background, individual tumors typically carried distinct NF1 second-hit events, consistent with lesion-specific molecular divergence rather than a single shared somatic driver across lesions. In contrast, microdissected histologically distinct components within individual tumors shared underlying NF1 alterations and showed sequential acquisition of additional alterations involving CDKN2A and EED, supporting stepwise molecular evolution during malignant progression. Together, these data reveal lesion-specific molecular divergence across distinct tumors and stepwise molecular evolution within individual tumors, underscoring the value of lesion-specific genomic evaluation in NF1-associated PNSTs.</p>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":" ","pages":"101091"},"PeriodicalIF":6.6,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112113","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":"Oncogenic Role of BCL6 Rearrangement: A Focus on Follicular and Marginal Zone Lymphomas","authors":"Lucas Pâris,&nbsp;Catherine Chassagne-Clement,&nbsp;Emmanuel Bachy,&nbsp;Hervé Ghesquières,&nbsp;Claire Mauduit,&nbsp;Daniel Pissaloux,&nbsp;Alexis Trecourt,&nbsp;Camille Laurent,&nbsp;Emmanuel Beillard,&nbsp;Alexandra Traverse-Glehen,&nbsp;Marie Donzel","doi":"10.1016/j.modpat.2026.101055","DOIUrl":"10.1016/j.modpat.2026.101055","url":null,"abstract":"<div><div>The <em>BCL6</em> gene is a transcriptional regulator essential for germinal center B-cell function, modulating their activation, survival, cell cycle, and differentiation into plasma or memory B cells. In indolent B-cell lymphomas, particularly follicular lymphoma and a subset of marginal zone lymphomas, <em>BCL6</em> rearrangements are increasingly recognized as recurrent but heterogeneous events. In follicular lymphoma, their clinicopathological significance differs according to the <em>BCL2</em> status. While <em>BCL6</em> rearrangements have limited impact in conventional <em>BCL2</em>–rearranged follicular lymphoma, <em>BCL2</em>–negative/<em>BCL6</em>–rearranged follicular lymphoma frequently displays atypical morphologic, immunophenotypic, and molecular features, including partial overlap with nodal marginal zone lymphoma. These cases may show reduced expression of germinal center markers, plasmacytic or marginal zone differentiation, and mutational profiles overlapping with marginal zone lymphoma, making their classification challenging.</div><div>Altogether, current data suggest that <em>BCL6</em>–rearranged indolent B-cell lymphomas do not represent a single entity but rather a heterogeneous biological spectrum spanning germinal center and postgerminal center features. Understanding these overlaps is essential for improving diagnostic accuracy and refining the classification of indolent B-cell lymphomas.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"39 10","pages":"Article 101055"},"PeriodicalIF":6.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701727","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":"Immunoglobulin Light Chain mRNA In Situ Hybridization Refines Classification Across the NLPHL-cHL Spectrum.","authors":"Jan Bosch-Schips, Antonio Vogelsberg, Sara Quinones, Andrea Molina-Alvarez, Ricardo Rolim, Edurne Pérez-Béliz, Eyyub Bag, Franziska Otto, Esther Kohler, Christiane Hummel, Claudia Hermann, Jakob Milla, Andrea Brunner-Véber, Christian M Schürch, Karl Sotlar, Andreas Chott, Irina Bonzheim, Dominik Nann, Leticia Quintanilla-Martinez, Falko Fend","doi":"10.1016/j.modpat.2026.101089","DOIUrl":"https://doi.org/10.1016/j.modpat.2026.101089","url":null,"abstract":"<p><p>Nodular lymphocyte-predominant Hodgkin/B-cell lymphoma (NLPHL/BL) and classic Hodgkin lymphoma (cHL) are biologically distinct entities, exhibiting preserved versus lost B-cell differentiation and immunoglobulin (IG) transcription. However, cases with overlapping morphologic and immunophenotypic features between NLPHL and lymphocyte-rich cHL (cHL-LR), here designated as NLPHL-OL, remain biologically ambiguous. We applied a novel, highly sensitive dual κ/λ mRNA in situ hybridization assay to assess IG light-chain expression across this spectrum. We analyzed 53 lymph node biopsies, including NLPHL-OL cases (n =15), cHL-LR (n = 11), along with typical NLPHL (n = 13) and cHL of other subtypes (n = 14) as controls. Distribution, intensity, and patterns of κ/λ mRNA expression in neoplastic cells was systematically evaluated and correlated with histology, architecture, immunophenotype, and Epstein-Barr virus (EBV) status. Diffuse, strong cytoplasmic light chain mRNA expression, representing the canonical pattern, was detected in the tumor cells of all NLPHL (13/13) and the majority of NLPHL-OL cases (12/15, 80%). In contrast, faint perinuclear or granular cytoplasmic signals (non-canonical patterns) were detected in 6/11 (55%) cHL-LR and 4/14 (28%) of other cHL subtypes. Canonical κ/λ expression was thus restricted to NLPHL and NLPHL-OL, confirming their classification as NLPHL with aberrant features, whereas cHL was negative or displayed exclusively non-canonical patterns. Non-canonical staining was also seen in 3/15 (20%) NLPHL-OL, including two EBV-positive cases. Rare aberrant light chain profiles in NLPHL and NLPHL-OL cases included single-cell κ/λ coexpression, and distinct LP-cell populations with mutually exclusive κ and λ expression. In summary, κ/λ mRNA ISH refines diagnostic classification across the NLPHL-cHL spectrum, is particularly useful in cases with overlapping features, and reveals canonical, non-canonical, and negative staining patterns that may reflect B-cell program integrity, placing these cases along a biological continuum.</p>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":" ","pages":"101089"},"PeriodicalIF":6.6,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030934","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":"Acute Myeloid Leukemia With KMT2A Amplification: A TP53-Alteration-Enriched Subgroup Associated With Chromoanagenesis and Poor Prognosis.","authors":"Thura Win Htut, Wei-Ying Jen, Ghayas C Issa, Sanam Loghavi, Abhishek Maiti, Alexandre Bazinet, Jayastu Senapati, Eitan Kugler, Calos Bueso-Ramos, Qing Wei, Gokce A Toruner, Musa Yilmaz, Gautam Borthakur, Nicholas J Short, Tapan M Kadia, Farhad Ravandi, Naval G Daver, Courtney D DiNardo, Guilin Tang","doi":"10.1016/j.modpat.2026.101086","DOIUrl":"https://doi.org/10.1016/j.modpat.2026.101086","url":null,"abstract":"<p><p>KMT2A amplification (KMT2A-amp) is a rare but aggressive genomic abnormality in acute myeloid leukemia (AML), with limited characterization in prior studies. We retrospectively analyzed 96 patients with AML harboring KMT2A-amp, including 56 newly diagnosed (ND) and 40 relapsed/refractory (RR) cases, with a median age of 68 years. Approximately half of the cases had therapy-related or secondary AML. All cases demonstrated highly complex karyotypes, with frequent -5/del(5q), -7/del(7q), and -17/del(17p). TP53 alteration was present in 93% of patients, whereas other recurrent AML-associated mutations were uncommon, and no AML-defining gene fusions or mutations were identified. In cases evaluated by optical genome mapping, all showed chromoanagenesis involving chromosome 11q23 region. Clinical outcomes were poor, with a median overall survival of 5.5 months in ND and 2.3 months in RR patients. Intensive chemotherapy did not improve survival compared with lower-intensity therapy, whereas venetoclax-based regimens were associated with improved overall survival (7.1 vs 4.6 months; p = 0.04) and event-free survival (6.7 vs 0.17 months; p < 0.01). We conclude that KMT2A-amp AML represents an extremely high-risk subgroup occurring in the context of TP53-associated genomic instability and chromoanagenesis. Its refractoriness to conventional chemotherapy highlights the urgent need for more effective, targeted therapeutic strategies.</p>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":" ","pages":"101086"},"PeriodicalIF":6.6,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148990740","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":"An Immunohistochemistry-based Decision Flowchart to De-escalate Axillary Surgery for Biopsy-Diagnosed Pure Ductal Carcinoma In Situ (DCIS) of the Breast","authors":"Julia A.M. Riggi,&nbsp;Christine Galant,&nbsp;Caroline Bouzin,&nbsp;Aurélie Daumerie,&nbsp;Naïma Benhaddi,&nbsp;Hilde Vernaeve,&nbsp;Nathanael Dubois,&nbsp;Maud Vassilieff,&nbsp;Mirela Roman,&nbsp;Latifa Fellah,&nbsp;Amandine Gerday,&nbsp;Carolien H.M. van Deurzen,&nbsp;Martine Berlière,&nbsp;Mieke R. Van Bockstal","doi":"10.1016/j.modpat.2026.101040","DOIUrl":"10.1016/j.modpat.2026.101040","url":null,"abstract":"<div><div>The treatment of ductal carcinoma in situ (DCIS) of the breast and invasive breast cancer (IBC) is considerably similar, despite their different biology. Axillary surgery is increasingly de-escalated by omitting sentinel lymph node biopsies (SLNBs) for hormone receptor-positive, human epidermal growth factor receptor 2-negative (HER2−) early-stage IBCs, supported by recent clinical trial data. The American Society of Clinical Oncology/National Comprehensive Cancer Network guidelines recommend SLNB for patients with DCIS treated with mastectomy, although some patients treated with lumpectomy still undergo SLNB. We aimed to identify markers to predict the upstaging risk after a biopsy diagnosis of pure DCIS and provide data to justify de-escalation of axillary surgery for patients with DCIS. The following features were retrospectively reviewed for 258 DCIS: nuclear grade, necrosis, histological calcifications, stromal architecture, DCIS architecture, tumor-infiltrating lymphocytes, estrogen receptor (ER), and progesterone receptor. Immunohistochemistry for HER2 was performed. Statistical analyses were performed with upstaging to (micro-)invasive carcinoma as the outcome variable. Clinical and radiological data were included in multivariable logistic regression. Solid architecture (<em>P</em> = .001) and radiological size (&gt;20 mm; <em>P</em> = .025) were independently associated with upstaging risk. Two algorithms were created, based on surgery type, ER/HER2 status, and upstaging risk. High upstaging risk was defined as solid architecture and/or radiological size &gt;20 mm (model 1) or solid architecture and/or absent histological calcifications (model 2). Each model identified a single patient with upstaging to ER+/HER2− IBC, without a positive SLNB. Both models showed that SLNBs may be safely omitted in low-risk ER+/HER2− DCIS, even when treated with mastectomy. However, model 1 identified fewer patients as low risk than model 2: 10 patients (17%) vs 32 patients (55%) within the group of 58 ER+/HER2− DCIS treated with mastectomy. Model 2 seems, therefore, more promising for further validation. Routine implementation of this decision flowchart requires retrospective validation before moving to prospective clinical trials but could substantially de-escalate axillary surgery for future patients with DCIS.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"39 9","pages":"Article 101040"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497767","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":"Recurrent TNC::PDGFD Fusions in Ossifying Plexiform Tumors of the Skin","authors":"Shira Ronen,&nbsp;Alexandra Meurgey,&nbsp;Michael Michal,&nbsp;Daniel Pissaloux,&nbsp;Franck Tirode,&nbsp;Colleen J. Beatty,&nbsp;Nicolas Macagno,&nbsp;Gonzague de Pinieux,&nbsp;David S. Cassarino,&nbsp;Nicolas Ortonne,&nbsp;Laurence Lamant,&nbsp;Eduardo Calonje,&nbsp;Michael Tetzlaff,&nbsp;Philip E. LeBoit,&nbsp;Steven D. Billings,&nbsp;Thibault Kervarrec","doi":"10.1016/j.modpat.2026.101042","DOIUrl":"10.1016/j.modpat.2026.101042","url":null,"abstract":"<div><div><em>PDGFB</em> or, more rarely, <em>PDGFD</em> rearrangements are well-established oncogenic drivers of dermatofibrosarcoma protuberans (DFSP). Recently, a <em>TNC::PDGFD</em> fusion has been identified in a superficial spindle cell tumor distinct from DFSP but similar to the tumor entity described as ossifying plexiform tumors of the skin. Herein, we report 7 additional cases of cutaneous ossifying plexiform tumors harboring a <em>TNC::PDGFD</em> fusion transcript.</div><div>Four patients were female. Tumors were located on the nose (n = 2), hand (n = 2), forearm (n = 1), flank (n = 1), and foot (n = 1), with a median size of 6 (range, 4-9) mm. Microscopically, these neoplasms were located in the dermis (n = 6) and subcutaneous tissues (n = 1). All specimens exhibited a lobulated architecture and a biphasic appearance characterized by the association of cellular areas composed of bland spindle cells with central regions of bone formation. Immunohistochemistry showed SATB2 positivity in all tested tumors (n = 4). RNA-sequencing analysis confirmed the presence of the <em>TNC::PDGFD</em> fusion transcript in all cases and revealed a transcriptomic profile that was distinct from other soft tissue tumors, including DFSP. Our findings support that <em>TNC::PDGFD</em> is the oncogenic driver of ossifying plexiform tumor of the skin, a rare tumor distinct from DFSP.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"39 9","pages":"Article 101042"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549390","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":"From Information Extraction to Clinical Reasoning: A Systematic Scoping Review of Large Language Models in Cancer Pathology Reports","authors":"Maryam Seifaddini,&nbsp;Mohammad Beheshti,&nbsp;Steven Richberg,&nbsp;Magda Esebua,&nbsp;Iris Zachary","doi":"10.1016/j.modpat.2026.101043","DOIUrl":"10.1016/j.modpat.2026.101043","url":null,"abstract":"<div><div>Pathology reports anchor cancer diagnosis and staging, yet their narrative structure limits the reliable translation into structured, machine-actionable knowledge, creating a bottleneck between expert interpretation and scalable clinical intelligence. Despite decades of clinical natural language processing research, pathology text remains among the most complex and consequential sources of medical data to operationalize at scale. Large language models (LLMs) offer new approaches for reading, extracting, and interpreting these reports. We synthesized the current LLM applications in cancer pathology using a 4-level capability framework across the pathology-report data lifecycle: level 1, text preparation and quality checks; level 2, information extraction; level 3, guideline-based clinical reasoning, such as TNM staging and registry coding; and level 4, interpretive synthesis, such as explanations, summarization, or decision support. Rather than grouping studies by natural language processing task labels, this framework tracks how LLM applications progress from preprocessing and extraction toward higher-level interpretation and synthesis. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines and searched 4 databases through September 2, 2025, identifying 41 eligible studies. Most studies focused on level 2 tasks, with fewer addressing level 3 and level 4 tasks. Encoder-based models, including domain-specific variants, such as BioBERT, were commonly used for structured extraction tasks, whereas generative models, including GPT, LLaMA, and Mistral-family models, were increasingly evaluated for prompt-based extraction, staging, and summarization. Reported performance was often high for well-defined extraction tasks, but external validation was uncommon, and metrics varied across studies, limiting direct comparison. Overall, the evidence suggests that success at lower capability levels does not consistently translate into higher-level reasoning, especially when reports are inconsistent, required staging inputs are missing, or clinical assumptions must be inferred, which helps explain gaps between benchmark results and practical adoption. Future work should prioritize robust multisite validation, clinically meaningful error analysis, transparent evaluation, and privacy-preserving implementation strategies to support the safe integration of LLMs in oncology.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"39 9","pages":"Article 101043"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549423","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":"Coexistent Endometrial and Fallopian Tube Carcinoma: Molecular and Pathological Features for Risk Stratification","authors":"Kianoosh Keyhanian,&nbsp;C. Blake Gilks,&nbsp;Elizabath Priya Mathew,&nbsp;Tanner Mack,&nbsp;Harman Sekhon,&nbsp;Bryan Lo,&nbsp;Peter Greenstreet,&nbsp;Katherine Grondin,&nbsp;Jessica N. McAlpine,&nbsp;Amy Jamieson","doi":"10.1016/j.modpat.2026.101030","DOIUrl":"10.1016/j.modpat.2026.101030","url":null,"abstract":"<div><div>Patients with coexistent endometrial and ovarian carcinoma (CEOC) have been shown to have an excellent prognosis if their tumors meet the International Federation of Gynecology and Obstetrics (FIGO) 2023 endometrial carcinoma (EC) stage IA3 criteria. In addition, excluding the intermediate-risk and high-risk molecular subtypes (mismatch repair deficiency, p53 abnormal, and no specific molecular profile- estrogen receptor low/negative) has been recently shown to improve risk stratification in CEOC. In contrast, coexistent EC with fallopian tube (FT) involvement is considered pathological T3/FIGO stage III. Our objective was to assess whether the FIGO 2023 IA3 criteria for CEOC can identify a subset of patients with coexistent EC and FT carcinoma at low risk of recurrence and if incorporation of molecular features can aid in prognostic stratification. An institutional database search was carried out at 2 institutions to identify T3a EC with FT involvement. Cases with nodal, pelvic sidewall, vaginal, parametrial, adnexal soft tissue, or peritoneal involvement or treated with neoadjuvant therapy were excluded. A total of 71 patients were identified. Fourteen carcinomas (14/71, 19.7%) recurred; of these, 85.7% (12/14) were endometrioid FIGO grade 3 or nonendometrioid histotypes, and 85.7% (12/14) had intermediate or adverse molecular features. Eight carcinomas (8/71, 11.3%) met the FT-adapted FIGO 2023 IA3 criteria with no recurrences. Further modifying the criteria by excluding tumors with adverse molecular features while expanding the pathology criteria to include ovarian and/or bilateral adnexal involvement identified 11 of 71 patients (15.5%), none of whom experienced a recurrence. By adapting the FIGO 2023 criteria for low-risk CEOC to assess coexistent EC and FT carcinoma, we identified a subset of patients with excellent outcomes, such that treatment de-escalation could be considered. Furthermore, it may be possible to expand this category of low-risk coexistent EC and FT carcinoma, based on refined molecular/pathological features, so more patients with uterus/adnexa-confined carcinoma and indolent disease behavior can be identified.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"39 8","pages":"Article 101030"},"PeriodicalIF":6.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148284055","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":"Multiomics Integration Identifies a Molecular Subtype of Intrahepatic Cholangiocarcinoma With Enhanced Benefit From Adjuvant Therapy","authors":"Zhuo Li,&nbsp;Haiyang Li,&nbsp;Weiqi Rong,&nbsp;Boyang Sun,&nbsp;Bingzhi Wang,&nbsp;Jin Li,&nbsp;Yanling Yuan,&nbsp;Haifeng Zhang,&nbsp;Bingning Wang,&nbsp;Susheng Shi,&nbsp;Fan Wu,&nbsp;Ting Xiao","doi":"10.1016/j.modpat.2026.101017","DOIUrl":"10.1016/j.modpat.2026.101017","url":null,"abstract":"<div><div>Intrahepatic cholangiocarcinoma (iCCA) is a molecularly heterogeneous liver cancer with a poor prognosis. Improved stratification is needed to guide postoperative therapy. In this study, we applied integrative multiomics analysis to classify iCCA and identify biomarkers predictive of adjuvant treatment benefit. Using publicly available datasets (including whole exome sequencing, RNA sequencing, proteomics, and phosphoproteomics from FU-iCCA cohort and a transcriptomic cohort GSE244807), we defined 3 robust molecular subtypes of iCCA. These subtypes exhibited distinct genomic alterations, pathway activation, and immune microenvironments, with significant differences in overall survival (OS). Through protein–protein interaction network analysis and consensus feature selection using 10 clustering algorithms, we prioritized 8 marker genes distinguishing the subtypes. A Cox proportional–hazards model constructed from these markers stratified patients into high- and low-risk groups. High-risk iCCA, characterized by elevated expression of markers such as <em>CLDN18</em>, <em>MUC1</em>, and <em>MUC5AC</em>, had significantly worse OS in the absence of adjuvant therapy. Notably, in an independent validation of 174 patients with iCCA who underwent resection (single-center cohort), high expression of any of these 3 markers were associated with markedly prolonged OS in patients who received adjuvant chemotherapy or chemoembolization, compared with those who did not. In contrast, marker-negative patients showed no clear benefit from adjuvant therapy. In conclusion, our multiomics approach identified a high-risk, mucin-enriched subtype of iCCA. CLDN18, MUC1, and MUC5AC emerge as candidate predictive biomarkers for adjuvant chemotherapy benefit in iCCA, warranting prospective validation to improve personalized postoperative management.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"39 7","pages":"Article 101017"},"PeriodicalIF":6.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005835","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}