Human pathology最新文献

{"title":"Non-small cell lung carcinomas with diffuse co-expression of TTF-1 and p40: Clinicopathologic and molecular characterization of a rare phenotype.","authors":"Renqing Wang, Chen Qian, Jun Du, Wei Wang, Yin He, Tingting Chen, Jie Yin, Yuanzi Ye, Yao Fu, Xiangshan Fan","doi":"10.1016/j.humpath.2026.106219","DOIUrl":"10.1016/j.humpath.2026.106219","url":null,"abstract":"<p><p>Non-small cell lung carcinomas showing co-expression of TTF-1 and p40 in sampled tumor tissue are rare, diagnostically challenging, and not formally recognized in the current WHO classification of thoracic tumors. We analyzed 15 pulmonary carcinomas with TTF-1/p40 co-expression to characterize their clinicopathologic features and molecular alterations. The cohort consisted predominantly of male patients and was composed mainly of high-grade, poorly differentiated tumors. All cases demonstrated diffuse nuclear co-expression of TTF-1 and p40 by immunohistochemistry. Whole-exome sequencing, performed in 12 cases, revealed frequent TP53 alterations (9/12), occasional concurrent RB1 alterations, and a rare FGFR3::TACC3 fusion, which was further validated by FISH. Two tumors with prominent lymphoid stroma were positive for Epstein-Barr virus-encoded RNA and lacked TP53 alterations, suggesting additional biological diversity within this phenotype. Follow-up data were available for 13 patients (range, 1-29 months); 4 died of disease and 9 were alive at last follow-up. Two additional patients were lost to follow-up. Collectively, these findings suggest that pulmonary carcinomas showing TTF-1/p40 co-expression in sampled tissue comprise a heterogeneous clinicopathologic and molecular group rather than a currently definable distinct entity. Despite the small sample size and the inclusion of several biopsy-only cases, this study provides a descriptive basis for future investigation of this unusual immunophenotypic pattern.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106219"},"PeriodicalIF":3.0,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148723121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathologic characterization of non-mass enhancement lesions of the breast in MRI-guided biopsy.","authors":"Tristan Jordan, Yuanxin Liang, Lorraine Colón Cartagena, Natalia Buza, Uma Krishnamurti, Haiying Zhan","doi":"10.1016/j.humpath.2026.106220","DOIUrl":"10.1016/j.humpath.2026.106220","url":null,"abstract":"<p><strong>Objective: </strong>Breast MRI is widely used for screening high-risk patients and for assessing the extent of disease in patients with breast cancer. The goal of this study was to determine the pathologic findings associated with MRI-guided core needle biopsies performed for non-mass enhancement (NME) lesions of the breast.</p><p><strong>Methods: </strong>We retrospectively identified 270 MRI-guided core needle biopsies from 225 women performed at our institution between January 1, 2024, and Dec 30, 2025. All included cases demonstrated non-mass enhancement on MRI. Radiologic and pathologic findings were reviewed. Cases were divided into two groups: those with a recent diagnosis of ipsilateral malignancy (n = 74) and those without a recent diagnosis of malignancy (n = 196).</p><p><strong>Results: </strong>Biopsies from patients with a known ipsilateral malignancy demonstrated a higher frequency of invasive carcinoma (20% vs. 7%, p = 0.003) and in situ carcinoma (27% vs. 9%, p = 0.0002) compared with those without ipsilateral malignancy, and a lower frequency of benign findings (46% vs. 77%, p = 0.0001). NME-associated invasive carcinomas were predominantly well-to moderately-differentiated carcinomas (96%) and were ER-positive/HER2-negative (>90%). NME-associated DCIS were 57% high grade, 43% intermediate grade, with 36% showing an ER-negative staining.</p><p><strong>Conclusion: </strong>MRI-guided biopsies for NME lesions demonstrate a significant rate of malignancy, particularly in patients with known ipsilateral breast cancer. Most NME-associated malignancies are well-to moderately-differentiated, hormone receptor-positive/HER2-negative carcinomas, while a subset of high-grade, ER-negative DCIS highlights the heterogeneous nature of these lesions.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106220"},"PeriodicalIF":3.0,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148678538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nonconventional colorectal dysplasia is less prevalent and has a more limited morphologic spectrum in patients without inflammatory bowel disease.","authors":"Timothy Law, Dongliang Wang, Gregory Y Lauwers, Won-Tak Choi","doi":"10.1016/j.humpath.2026.106231","DOIUrl":"https://doi.org/10.1016/j.humpath.2026.106231","url":null,"abstract":"<p><p>Colorectal dysplasia in inflammatory bowel disease (IBD) includes conventional and diverse nonconventional morphologic patterns, the latter of which are often endoscopically invisible or flat and are associated with an increased risk of advanced neoplasia. However, the prevalence and significance of nonconventional dysplasia in patients without IBD remain unclear. We analyzed 669 sporadic colorectal dysplastic lesions from 211 patients without IBD or syndromic polyposis, including 103 patients with colorectal cancer (CRC) (293 dysplastic lesions) and 108 without CRC (376 dysplastic lesions). Sporadic lesions were also compared with 317 dysplastic lesions from 168 patients with IBD. In the sporadic cohort, conventional dysplasia predominated (89%), whereas 11% were nonconventional, most commonly Paneth cell-rich dysplasia (9%). Goblet cell-deficient (1%) and hypermucinous (0.4%) patterns were rare, and no cases of basal crypt dysplasia, crypt cell dysplasia, or serrated dysplasia not otherwise specified were identified. Most sporadic lesions were tubular (93%), low-grade (95%), polypoid (97%), and right-sided (60%). Compared with lesions in the non-CRC group, those in the CRC group were more frequently nonconventional (14% vs. 9%, p = 0.045), larger (mean: 1.0 vs. 0.7 cm, p < 0.001), and more likely to show tubulovillous/villous architecture (10% vs. 5%, p = 0.016), high-grade dysplasia (HGD; 10% vs. 2%, p < 0.001), and invisible gross appearance (2% vs. 0%, p = 0.023). When compared with IBD-associated lesions, sporadic lesions occurred at an older age (mean: 61 vs. 53 years, p < 0.001) and showed significantly lower rates of nonconventional morphology (11% vs. 25%, p < 0.001), HGD (5% vs. 16%, p < 0.001), invisible/flat appearance (3% vs. 24%, p < 0.001), and left-sided location (39% vs. 48%, p = 0.006). In conclusion, although nonconventional dysplasia is not exclusive to IBD, several patterns, including hypermucinous, goblet cell-deficient, and basal crypt dysplasias, are rare or absent in patients without IBD. Although their low prevalence suggests that these patterns are unlikely to be major contributors to CRC risk in patients without IBD, a potential association with an increased risk of concurrent or subsequent CRC cannot be excluded, given the paucity of random colonic biopsies in this population.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106231"},"PeriodicalIF":3.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148684466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SMARCA4-altered malignancies: Cytologic diagnostic challenges and clinicopathologic correlation.","authors":"Behtash G Nezami, Qiuying Shi, Xiaoqi Lin","doi":"10.1016/j.humpath.2026.106229","DOIUrl":"https://doi.org/10.1016/j.humpath.2026.106229","url":null,"abstract":"<p><strong>Background: </strong>SMARCA4-deficient undifferentiated tumors (SMARCA4-dUT) have been included in the latest WHO classification of tumors. This study examined the cytomorphology, management, molecular features and prognosis of malignancies harboring SMARCA4 alterations.</p><p><strong>Methods: </strong>Biopsied cytologic slides were reviewed. Next-generation sequencing (NGS) and clinical data were analyzed.</p><p><strong>Results: </strong>Thirty-four cases with SMARCA4 alterations were identified, including 13 primary and 21 metastatic tumors, sampled primarily from lung (35%), lymph nodes (26%) and liver (15%). Tumor origins were predominantly the lung (61%) and gallbladder (9%). The most common tumor type was adenocarcinoma (70%). Predominant architectures included nested, single-cell, tubular/acinar, and 3D clusters. Cells were most commonly round and columnar, with medium cytoplasm mostly showing vacuoles and granular features. Nuclear grade 2-3 was seen in 93% of cases, with prominent nucleoli and coarse chromatin. SMARCA4 alteration included mutations (32) and loss (2). These tumors are characterized by a high co-mutation burden, including TP53 (62%), KRAS (35%), and STK11 (15%). Prognosis is further modulated by allelic status (biallelic vs. monoallelic vs. subclonal), and mutations in DDR pathway (24%). Most tumors presented as stage IV. 26% received surgical resection. Overall, 74% underwent chemotherapy and 29% radiotherapy. Mean follow-up was 17 months, with 2-year OS of 49.1%. Twenty-three (68%) patients were current or former smokers.</p><p><strong>Conclusion: </strong>SMARCA4-altered malignancies show diverse differentiation and lack consistent cytomorphologic features. Majority of cases were differentiated malignancies and only four cases (12%) were undifferentiated, suggesting SMARCA4 alterations were associated with poor prognosis but were not exclusive drivers of undifferentiated malignancy.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106229"},"PeriodicalIF":3.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148689065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular subtypes and genetic diagnostics in B-cell acute lymphoblastic leukemia.","authors":"Roberta S Azevedo, L Jeffrey Medeiros, Sanam Loghavi, Nicholas J Short","doi":"10.1016/j.humpath.2026.106216","DOIUrl":"10.1016/j.humpath.2026.106216","url":null,"abstract":"<p><p>The molecular classification of B-cell acute lymphoblastic leukemia (B-ALL) has evolved substantially with the introduction of genome-wide technologies for diagnosis, leading to the recognition of numerous genetic subtypes with distinct biological and prognostic implications. While historically defined chromosomal subgroups remain central to current classification systems, genomic profiling has enabled the identification of additional entities that were previously designated as not otherwise specified (NOS) in older classification schemes. Accurate recognition of these ALL subtypes is important for risk stratification, prognostic assessment, and the expanding use of targeted therapies. However, implementation of comprehensive genomic testing remains challenging because multiple complementary diagnostic techniques are often required for complete assessment and advanced sequencing approaches are not universally available. This review briefly summarizes the morphologic and immunophenotypic features of B-ALL and then focuses on the current molecular classification of B-ALL, highlighting the genetic features of established and newly recognized subtypes, their clinical significance, and the diagnostic approaches used for their identification. Future efforts should focus on integrating genomic classification, secondary genetic alterations, and measurable residual disease (MRD) assessment to further refine risk-adapted and personalized treatment strategies.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106216"},"PeriodicalIF":3.0,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148619760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Introduction to special issue on leukemia.","authors":"Sanam Loghavi, L Jeffrey Medeiros","doi":"10.1016/j.humpath.2026.106212","DOIUrl":"10.1016/j.humpath.2026.106212","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106212"},"PeriodicalIF":3.0,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148420716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mixed phenotype acute leukemia: Lineage assignment, immunophenotypic classification and genetic insights.","authors":"Vasiliki Leventaki, Sa A Wang","doi":"10.1016/j.humpath.2026.106206","DOIUrl":"10.1016/j.humpath.2026.106206","url":null,"abstract":"<p><p>Mixed phenotype acute leukemia (MPAL) is a rare and biologically heterogeneous category characterized by discrete admixed populations of myeloid and lymphoid blasts (bilineal or mixed lineage) or with coexpression of lymphoid and myeloid markers in a single blast population (biphenotypic or mixed phenotype). Despite advances in diagnostic criteria, MPAL remains a significant diagnostic and therapeutic challenge due to its immunophenotypic complexity and genetic diversity. Accurate classification relies heavily on multiparameter flow cytometry immunophenotyping, integrated with cytogenetic and molecular studies. The current World Health Organization classification and International Consensus Classification recognize specific genetic subtypes, including MPAL with t(9; 22)(q34.1; q11.2)/BCR::ABL1 and MPAL with KMT2A rearrangement, reflecting the increasing importance of genomic profiling in disease characterization. Recent genomic studies have revealed additional recurrent alterations involving transcription factors, epigenetic regulators, signaling pathways, and lineage-specifying genes, including ZNF384 rearrangements, BCL11B alterations, mutations involving PHF6, WT1, FLT3, and RUNX1, and mutations affecting chromatin remodeling and cytokine signaling pathways. Importantly, distinct genetic lesions appear to correlate with specific immunophenotypic patterns, suggesting biologically meaningful disease subsets and providing insights into mechanisms of lineage plasticity and leukemogenesis. This review summarizes the current understanding of the immunophenotypic and genetic landscape of MPAL, emphasizing the integration of morphologic, immunophenotypic, cytogenetic, and molecular findings into diagnosis and subclassification.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106206"},"PeriodicalIF":3.0,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148328967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic myelomonocytic leukemia revisited: A comprehensive review with emphasis on the oligomonocytic subtype.","authors":"Sanam Loghavi, Guillermo Montalban-Bravo","doi":"10.1016/j.humpath.2026.106207","DOIUrl":"10.1016/j.humpath.2026.106207","url":null,"abstract":"<p><p>Oligomonocytic chronic myelomonocytic leukemia (OM-CMML) is defined by an absolute monocyte count of 0.5-<1.0 × 10⁹/L with relative monocytosis ≥10%. This entity was formally recognized in the 2022 WHO Classification of Haematolymphoid Tumours and the International Consensus Classification, representing a paradigm shift from prior thresholds requiring monocyte counts ≥1.0 × 10⁹/L. This change in criteria captures a clinically and biologically meaningful disease state with independent prognostic significance and an almost 50% five-year cumulative incidence of progression to overt CMML. However, this change has also expanded the diagnostic boundaries of OM-CMML into territory previously classified as myelodysplastic syndromes (MDS). Accurate diagnosis requires integration of bone marrow morphology, flow cytometric monocyte subset partitioning, and genomic profiling. Cases harboring biallelic TET2 inactivation or TET2+SRSF2 co-mutation show the highest bone marrow monocyte burden, frequent classical monocyte (MO1; CD14+/CD16-) elevation, and highest progression risk representing biologically true OM-CMML, whereas SF3B1-mutated and biallelic TP53 mutated cases show MDS-directed biology and warrant reclassification. This review synthesizes current diagnostic frameworks, molecular heterogeneity, risk stratification approaches, and evolving classification proposals, thereby providing a practical guide for pathologists navigating OM-CMML in the modern genomic era.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106207"},"PeriodicalIF":3.0,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148307992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAR-T cell therapy and its complications: Role of the pathologist in diagnosis.","authors":"Iman Sarami, L Jeffrey Medeiros","doi":"10.1016/j.humpath.2026.106199","DOIUrl":"10.1016/j.humpath.2026.106199","url":null,"abstract":"<p><p>CAR-T cell therapy has transformed the treatment of patients with hematologic malignancies but has also introduced a spectrum of post-therapy complications that frequently require histopathologic evaluation. While clinical toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are well characterized, the pathologist's role in interpreting post-CAR-T biopsy specimens remains underdefined and challenging. In this review, we focus on the histopathologic, immunophenotypic, and molecular features of post-CAR-T complications, including cytopenias, immune effector cell-associated syndromes, therapy-related myeloid neoplasms, secondary malignancies, and CAR-derived lymphoproliferations. We emphasize diagnostic pitfalls, differential diagnoses, and practical approaches to distinguishing reactive, inflammatory and neoplastic processes. Our aim in this review is to provide a pathology-centered framework to guide accurate diagnosis, prevent misclassification and support clinical decision-making in the evolving landscape of CAR-T therapy.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106199"},"PeriodicalIF":3.0,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148211192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contemporary approach to diagnosis and classification of acute myeloid leukemia.","authors":"Derek M Loneman, Valentina Nardi, Robert P Hasserjian","doi":"10.1016/j.humpath.2026.106197","DOIUrl":"https://doi.org/10.1016/j.humpath.2026.106197","url":null,"abstract":"<p><p>The term acute myeloid leukemia (AML) refers to a group of myeloid neoplasms characterized by maturation arrest, classically defined as ≥20% myeloblasts or myeloblast equivalents in the peripheral blood or bone marrow. In recent decades, a wealth of genetic information has reshaped our understanding of AML biology and enabled recognition of discrete molecular subgroups. However, questions remain, especially regarding which genetic lesions are class-defining and which are, at most, prognostic. These questions acquired particular salience with the advent of two classification systems, the 2022 International Consensus Classification and the WHO 5th Edition (WHO), replacing the prior WHO revised 4th Edition. While efforts are underway to unite current classification schemes, it is essential for pathologists to understand the rationale behind AML classification in the interest of patient care. Given the growing complexity in this area, this review aims to provide a practical guide for AML diagnosis and contemporary classification while highlighting areas of active inquiry which may inform future classification.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106197"},"PeriodicalIF":2.6,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148175933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}