MODERN PATHOLOGY现代病理学
MODERN PATHOLOGY(英文缩写 MODERN PATHOL),ISSN 0893-3952,eISSN 1530-0285,中文译名:现代病理学 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-09-28 至 2026-09-28，按本站收录文献的发表日期统计。
期刊介绍
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2021 | 8.209 | Q1 |
| 2022 | 7.500 | Q1 |
| 2023 | 7.100 | Q1 |
| 2024 | 5.500 | Q1 |
| 2025 | 6.600 | Q1 |
MODERN PATHOLOGY 最新收录文献
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1. Immunohistochemistry Resolves Indeterminate MTAP Deletion Calls from Exome Sequencing: A Pan-Cancer Concordance Study.
PMID:期刊:日期:2026-09-23The deletion of the methylthioadenosine phosphorylase (MTAP) gene is a frequent genomic event across various malignancies, often associated with the loss of the adjacent CDKN2A locus. MTAP deficiency has recently emerged as a promising biomarker for novel targeted therapeutic strategies including inhibitors of the PRMT5-MAT2A axis. Although next-generation sequencing (NGS) allows detection of MTAP copy number alterations, interpretation may be challenging in samples with low tumor purity or borderline copy number scores. In this study, we analyzed MTAP copy number status in a cohort of 2,409 tumors profiled by whole-exome sequencing within the EXOMA2 study (NCT06550687) using the FACETS and TITAN algorithms. Tumors were categorized as wild-type, homozygous deletion, or probable heterozygous deleted. A subset of these cases with available tissue underwent orthogonal validation by immunohistochemistry (IHC) using three MTAP antibody clones (MTAP-RBT, 2G4, and 1813), with selected cases further analyzed by fluorescence in situ hybridization (FISH) and RNA sequencing. Our results show high concordance between IHC and genomic classification in tumors with either wild-type, or homozygous deletion MTAP status. Importantly, IHC enabled reclassification of a substantial proportion of tumors initially classified as heterozygous by NGS; loss of protein expression in these cases correlated with homozygous genomic deletion confirmed by FISH. Moreover, heterozygous NGS calls were not associated with low tumor cellularity. These findings demonstrate that MTAP immunohistochemistry represents a robust and accessible approach for assessing MTAP status and for resolving ambiguous NGS results, an issue not solely driven by low tumor cellularity. Incorporating protein-level assessment analyses with FISH confirmation improve the identification of MTAP-deficient tumors and facilitate more accurate, rapid, and cost-effective patient selection for emerging targeted therapies.
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2. Immunoglobulin Light Chain mRNA In Situ Hybridization Refines Classification Across the NLPHL-cHL Spectrum.
PMID:期刊:日期:2026-09-23Nodular 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.
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3. OTP, CD44, Ki-67 Immunohistochemistry to Predict Prognosis in Preoperative Lung Neuroendocrine Tumor Biopsy Specimens.
PMID:期刊:日期:2026-09-21Previously OTP, CD44 and Ki-67 have been identified as prognostic biomarkers in lung carcinoids (lung neuroendocrine tumors or LNETs). We aimed to assess whether risk profiles can be established using these biomarkers on preoperative LNET biopsies . Patients with LNETs (TNM 8 stage I-III, 2003-2021) who underwent curative resection were selected from Dutch pathology registry (PALGA). Immunohistochemistry for OTP, CD44 and Ki-67 (biomarkers) was performed on matched resection and biopsy (Bx) specimens. Three pathologists revised all cases per the WHO 2021 classification (WHO). OTP and CD44 were assessed by H-score, Ki-67 proliferation index (PI) by eyeball hot-spot scoring. Bx cases diagnosed as carcinoid not otherwise specified (NOS) were considered low risk for relapse and atypical carcinoid (AC) as high risk. Immunostained cases were classified as low risk (OTP≥50, CD44≥30, Ki-67<5%) or high risk (others). Ninety-eight patients were eligible. Nineteen relapse events occurred after a median follow-up of 83 months. The biomarkers correctly identified high risk in 89% (n=17/19) of relapses, outperforming the WHO classification, which assigned 11% (n=2/19) of relapses as AC. Negative predictive value of biomarkers was 0.96 compared to 0.82 for WHO. The biomarkers showed greater prognostic stratification in relapse-free survival analysis and higher inter-observer agreement (biomarkers: κ=0.673; WHO: κ=0.276, both p<0.001). Biomarker expression was more stable between biopsy and resection specimen, improving concordance compared to WHO (biomarkers: κ=0.584, p<0.001; WHO: κ=0.169, p=0.037). In conclusion, an OTP, CD44, and Ki-67 biomarker panel enables reliable identification of low risk LNETs on Bx, outperforming WHO classification for prognostic stratification and biopsy-resection concordance. By accurately identifying tumors with a molecular low risk profile on preoperative biopsies, this panel may help to guide treatment choice for patients considered for sublobar resection.
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4. sWGS Identifies a Copy-Number-High Subset of TP53-mutated Multiple-Classifier Endometrial Carcinomas With Adverse Clinicopathological Features.
PMID:期刊:日期:2026-09-17TP53-mutated "multiple-classifier" endometrial carcinomas represent a diagnostically challenging subgroup within current molecular classification algorithms. Although these tumors are assigned to POLE-mutated or mismatch repair-deficient categories according to current ESGO/FIGO-based algorithms, their biological heterogeneity remains incompletely characterized. Herein, we retrospectively analyzed TP53-mutated multiple-classifier endometrial carcinomas identified through routine molecular profiling at our institution between 2022 and 2025 using an integrated histopathological, immunohistochemical, targeted sequencing, and shallow whole-genome sequencing approach. Copy-number alteration-high (CNA-high) status was defined as ≥5 large-scale genomic alterations, corresponding to copy-number gains or losses ≥3 Mb within a single chromosomal arm excluding whole-arm alterations. Among 33 analyzable TP53-mutated multiple-classifier endometrial carcinomas, sWGS identified 12 CNA-high tumors (36.4%) and 21 CNA-low tumors (63.6%). CNA-high tumors were more frequently non-endometrioid, high-grade, and advanced-stage according to FIGO 2023. They showed higher TP53 variant allele frequencies (VAF) and higher TP53 VAF-to-tumor-cellularity ratios. After a median follow-up of 12.8 months, recurrences (6/33; 18.2%) and disease-related deaths (3/33; 9.1%) were observed in the CNA-high subgroup, whereas no recurrence or disease-related death was observed among CNA-low patients. These findings indicate that TP53-mutated multiple-classifier endometrial carcinomas comprise biologically distinct subsets that are not fully captured by current 4-tier TCGA-based molecular classification and ESGO-based risk stratification. In this cohort, sWGS identified a CNA-high group with adverse clinicopathological features and clinical events suggesting a potentially more aggressive clinical course. Integration of genome-wide copy-number profiling may therefore refine the biological interpretation of TP53 alterations in multiple-classifier endometrial carcinomas and warrants validation in larger multicenter cohorts.
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5. Primary Large B-Cell Lymphomas of Immune-Privileged Sites With IRF4 Rearrangement: Clinicopathological and Molecular Characterization.
PMID:期刊:日期:2026-09-17Primary large B-cell lymphoma of immune-privileged sites (IP-LBCL) is an aggressive B-cell lymphoma arising in the central nervous system, vitreoretina, and testis, whereas the molecular features of IP-LBCL with IRF4 rearrangement (IP-LBCL-IRF4-R) remain poorly characterized. Here, we report seven cases of IP-LBCL-IRF4-R, all showing IRF4 rearrangement confirmed by fluorescence in situ hybridization. The cohort included six males and one female, with a median age of 58 years (range, 34-73 years); all patients were immunocompetent. Tumors involved the central nervous system (n = 4) and testis (n = 3). With a median follow-up of 10 months (range, 3-45 months), all patients were alive. Histologically, all IP-LBCL-IRF4-R cases showed diffuse proliferation of medium-to-large B cells with centroblast-like and/or immunoblast-like morphology. Immunophenotypically, one case was classified as the germinal center B-cell subtype and six as the non-germinal center B-cell subtype. Five cases showed BCL2/C-MYC double expression, and all seven cases were negative for Epstein-Barr virus-encoded small RNA. IRF4 rearrangement was detected in all seven cases by break-apart probes, and an IGH::IRF4 fusion was detected in only one case; three cases harbored BCL6 rearrangements, and no BCL2 or MYC rearrangements were detected. Next-generation sequencing identified recurrent mutations in IRF4 and PIM1 (6/7, 85.7% each), followed by MYD88 (5/7, 71.4%) and BTG1, CD79B, and LRP1B (3/7, 42.9% each). LymphGen 2.0 classified five cases as the MCD subtype and two as Other. Our study highlights IRF4 rearrangement as a rare genetic event in IP-LBCL and provides further insights into the molecular diversity of this entity.
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6. Disentangling the cellular composition of FLCN-mutated tumors in Birt-Hogg-Dubé Syndrome by spatial transcriptomics.
PMID:期刊:日期:2026-09-17Birt-Hogg-Dubé (BHD) syndrome is a hereditary cancer predisposition syndrome caused by pathogenic variants in the folliculin (FLCN) gene and is associated with an increased risk of multifocal renal tumors. FLCN-mutated tumors (FMTs) often exhibit morphological heterogeneity with mixed morphological features resembling renal oncocytoma (RO) and chromophobe renal cell carcinoma (chRCC), yet the molecular basis underlying the heterogeneous morphologic features and the morphologic-genomic correlations remain poorly defined. In our prior work, we identified mutually exclusive expressions of L1 cell adhesion molecule (L1CAM) and forkhead box I1 tboxI1 (FOXI1) labeling the two morphologically distinct cellular populations in BHD-associated FMTs, leading to the hypothesis that these two tumor compartments may have distinct molecular features and may reflect different nephron epithelial differentiation states. In this follow-up study, we tested this hypothesis using L1CAM and FOXI1 as morphology-guided markers for spatial transcriptomic profiling of the distinct tumor compartments in FMTs with the NanoString GeoMX Digital Spatial Profiler (DSP). Six FMTs from three patients with BHD and three normal kidney tissues were analyzed. L1CAM+ and FOXI1+ area of interest (AOI) were collected from tumor areas with various tumor compositions, including L1CAM+ dominant, FOXI1+ dominant, and mixed tumor areas. Spatial transcriptomic analysis identified distinct gene expression signatures in L1CAM+ and FOXI1+ FMT compartments independent of the local tumor compositions. FOXI1+ tumor cells showed robust enrichment for intercalated cells (IC)-associated gene signatures. In contrast, L1CAM+ tumor cells exhibited a heterogeneous transcriptional profile, with partial overlap across a spectrum of renal tubular epithelial cell types rather than a definitive principal cell-like identity. Despite this compartment-specific differences, both compartments share expression of a panel of tumor signature genes, including glycoprotein nmb (GPNMB) gene, and a core of cancer related biological functions and signaling pathways. Together, these findings refined the prior dichotomous model of BHD-associated renal tumors and support a model in which L1CAM+ and FOXI1+ tumor compartments represent divergent evolutionary or differentiation states with a common FLCN-mutant neoplastic transcriptional program. This spatial transcriptomic profiling provides molecular evidence for the morphological heterogeneity of FMTs and insights on the tumor biology of BHD-associated FMTs.
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7. Clinicopathological and Molecular Insights into ERBB2-altered S100/SOX10-positive Uterine Sarcoma: A Report of 6 Cases.
7. ERBB2改变型S100/SOX10阳性子宫肉瘤的临床病理与分子学见解：6例报告PMID:期刊:日期:2026-09-17A novel entity of ERBB2/ERBB3-mutated S100/SOX10-positive uterine sarcoma has recently been proposed. However, the detailed clinicopathologic spectrum and molecular features of this emerging entity remain to be further elucidated. Here, we describe 6 cases of ERBB2-altered uterine sarcoma. The patients ranged from 41 to 65 years old (median, 48 years). Most tumors (5/6; 83.3%) were centered in the cervical stroma. An infiltrative, interdigitating border was a consistent finding, with neoplastic cells intimately admixed with entrapped pre-existing smooth muscle fascicles. The tumor exhibits alternating hypercellular and hypocellular areas. Most cases (5/6; 83.3%) showed a predominantly spindled architecture arranged in a fascicular, herringbone, or storiform pattern. The tumor cells typically showed mild-to-moderate cytologic atypia, scant cytoplasm, and a brisk mitotic count (median: 28.5/10 HPFs). Intriguingly, the remaining case (1/6; 16.7%) harbored a concurrent TP53 nonsense mutation and exhibited a predominantly epithelioid architecture with marked cytological atypia. Notably, another distinctive finding was the presence of neoplastic multinucleated giant cells exhibiting a characteristic floret-like nuclear arrangement in all cases. The background stroma exhibited focal myxoid change, hyalinization, and variable inflammatory infiltrates. All cases exhibited strong and diffuse positivity for S100 and SOX10. Next-generation sequencing revealed a highly recurrent molecular signature characterized by universal oncogenic ERBB2 missense mutations (including the canonical V777L variant as well as other activating mutations) and CDKN2A copy number loss, frequently accompanied by inactivating ATRX mutations (66.7%), CDKN2B (66.7%), MTAP (50.0%) copy number loss, ERBB3 mutations (50.0%), and concurrent ERBB2 amplification (33.3%). Of the 6 patients, 1 (harboring a TP53 nonsense mutation) had bone metastasis at diagnosis and was lost to follow-up, 2 progressed at 3.5 and 5 months (one death at 10 months), and 3 remained alive with no evidence of disease at 10-12 months. Our results support this emerging entity as a distinct, aggressive gynecologic mesenchymal neoplasm harboring actionable ERBB2 alterations.
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8. Acute Myeloid Leukemia With KMT2A Amplification: A TP53-Alteration-Enriched Subgroup Associated With Chromoanagenesis and Poor Prognosis.
PMID:期刊:日期:2026-09-17KMT2A 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.
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10. Cross-Platform Concordance in DNA Methylation Based Classification of CNS Tumors.
PMID:期刊:日期:2026-09-07DNA methylation profiling enables precise classification of pediatric central nervous system (CNS) tumors. Oxford Nanopore Technologies (ONT) offers same-day, single-sample methylation readouts, but its concordance with Illumina EPIC arrays in routine diagnostic tasks remains incompletely defined. We profiled 23 pediatric tumors (18 CNS, 5 non-CNS) by EPIC arrays and ONT. Methylation profiles from both platforms were classified with crossNN (brain model or pan-cancer model); ONT data were additionally classified with Rapid-CNS2 and Sturgeon. We compared (i) classifier agreement with integrated histology (w/o NGS) at family/class levels, (ii) pass-rate above platform-specific score cutoffs, (iii) cross-platform concordance of copy-number variation (CNV), and MGMT promoter methylation status. In CNS cases, ONT and EPIC methylation profiles demonstrated strong correlation, except for a single outlier (P2), which was excluded from further analysis. Comparative assessment of the two platforms showed that: (a) Molecular classification of CNS tumors using the crossNN classifier was consistent with histology (w/o NGS) at the family level in all cases. (b) Copy-number profiles showed high concordance between platforms. (c) MGMT promoter methylation status matched in 94% of cases (16/17). When comparing ONT-specific analysis pipelines using the ONT data, the Rapid-CNS2 pipeline yielded the most reliable class level assignments with 94% (16/17) concordance with the histopathological diagnosis, which marginally exceeded the crossNN and sturgeon classifiers. In non-CNS tumors, the pan-cancer model produced low-confidence outputs with poor agreement with histology (w/o NGS) (only 1/5 concordant), indicating limited readiness for these entities. In conclusion, ONT enables same-day, clinically reliable family-level CNS tumor classification with high concordance to arrays, while EPIC retains a modest class-level edge. A key limitation of ONT is its reliance on fresh-frozen DNA and on classifiers originally built around array-derived CpG sites, rather than on models developed natively from ONT data.