Human pathology最新文献

{"title":"Intracranial low-grade tumors with ALK rearrangement: diverse tumor types with shared molecular alterations","authors":"Kun Mu ,&nbsp;Yu Zhang ,&nbsp;Yuyu Yang ,&nbsp;Weiqing Wang ,&nbsp;Ranran Ma ,&nbsp;Yanzhao Wang ,&nbsp;Jie Gong","doi":"10.1016/j.humpath.2025.105910","DOIUrl":"10.1016/j.humpath.2025.105910","url":null,"abstract":"<div><div>Although <em>anaplastic lymphoma kinase (ALK)</em> gene fusions are increasingly recognized in newly classified pediatric high-grade gliomas, intracranial low-grade tumors harboring <em>ALK</em> rearrangements remain under characterized in the literature. Herein, we present five cases of low-grade intracranial tumors with <em>ALK</em> rearrangements that were diagnosed at a single institution over a continuous 24-month period. Comprehensive clinicopathological evaluation integrating morphological analysis, immunohistochemical profiling, and molecular characterization of fusion partners was performed. Microscopic examination was performed to assess histologic features. A panel of antibodies were used to evaluate protein expression including ALK, desmin, GFAP, Olig2, S100, NeuN, EMA, and CD34. DNA and RNA sequencing was performed, and potential fusion transcripts were analyzed using seed count and structural chromosomal aberrations. All five tumors harbored structural aberrations involving the <em>ALK</em> locus 2p23, and no additional pathogenic mutations, amplifications, deletions, or fusions were identified in all the cases. Among them, two tumors were inflammatory myofibroblastic tumors (IMT) with <em>SQSTM1</em>::<em>ALK</em>, and <em>NPM1</em>::<em>ALK</em> fusion, respectively. One was a tanycytic supratentorial ependymoma (ST-EPN) with <em>HNRNPA1</em>::<em>ALK</em> fusion, and another was ganglioglioma (GG) with <em>PPP1CB</em>::<em>ALK</em> fusion. Interestingly, one case presented as a low-grade myxoid mesenchymal neoplasm with <em>ATIC</em>::<em>ALK</em> rearrangement that did not fit any existing tumor category. All patients underwent complete tumor resection, and were alive with no signs of recurrence during a follow-up period ranging from 1 to 18 months. In summary, ALK fusions may be shared features of a group of low-grade intracranial tumors including IMT, tanycytic ST-EPN, GG, and ALK-rearranged low-grade myxoid mesenchyma neoplasm. Future studies using larger cohorts are warranted to further characterize their clinical and pathological features.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"164 ","pages":"Article 105910"},"PeriodicalIF":2.6,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144821294","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":"Biological behavior of DCIS with or without microinvasion. Same and different","authors":"Lisa Scheidegger ,&nbsp;Heike Frauchiger-Heuer ,&nbsp;Esther Birindelli ,&nbsp;Bärbel Papassotiropoulos ,&nbsp;Constanze Elfgen ,&nbsp;Hisham Fansa ,&nbsp;Umberto Maccio ,&nbsp;Claudia Linsenmeier ,&nbsp;Tamara Rordorf ,&nbsp;Isabell Witzel ,&nbsp;Zsuzsanna Varga","doi":"10.1016/j.humpath.2025.105902","DOIUrl":"10.1016/j.humpath.2025.105902","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Ductal carcinoma in situ (DCIS) is a non-invasive type of breast cancer, detected mostly due to associated calcifications. Although non-invasive and primarily treated with surgical excision, recurrence as in situ or invasive form occurs in a substantial subset of DCIS patients. Microinvasion, defined as less than or equal to 1 mm invasive focus poses a diagnostic, biological and therapeutic dilemma, as the exact biological behavior of DCIS with or without microinvasion is controversially understood. In this retrospective study based on standardized pathology reports from a single center, we addressed the question if DCIS with or without microinvasive foci represents biologically one disease or two distinct entities.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and methods&lt;/h3&gt;&lt;div&gt;We identified 148 patients with surgically treated DCIS and complete clinico-pathological data and follow-up information, 126 of 148 (85.1 %) pure form, 22 of 148 (14.9 %) with microinvasive foci. Events in follow-up (in-situ, invasive recurrent disease, breast cancer related death) were correlated with the presence of microinvasive foci and with pathological parameters (DCIS size, nuclear grade, the presence of necrosis, margin status, biomarkers, hormone receptors and Ki67 index) and clinical information (therapy modalities). Overall time-to-event-probability (TTE) was assessed with Kaplan Meier curves.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;There was a total of 28 events (18.9 % of cohort). 12 of 148 (8.1 %) patients had recurrent DCIS, 16 of 148 (10.8 %) developed invasive breast cancer, 5 of 148 (3.4 %) patients died related to breast cancer in follow-up. DCIS with/without microinvasion did not differ significantly in TTE. There was a non-significant trend for worse 5-year breast cancer related death in DCIS with microinvasion. DCIS with microinvasion developed significantly more often in-situ or invasive recurrences in extensive disease (≥5 cm) (p = 0.040), with nuclear high grade (p = 0.045), with necrosis present (p = 0.045), with narrow resection margins (&gt;1 mm) (p = 0.006), with younger age (≤50 years) in follow-up (p = 0.025) and in the absence of adjuvant radio- and/or endocrine therapy (p = 0.009, p = 0.034). No further factors such as calcification, positive margins, hormone receptor status had an impact on TTE on DCIS with or without microinvasive foci.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Our data shows that biological behavior of DCIS with microinvasive foci per se does not differ from pure DCIS in TTE. However, in-situ or invasive recurrences (total or ipsilateral) occur more often in microinvasive DCIS with extensive disease, with nuclear high grade, present necrosis, with narrow resection margins and in younger age in follow-up. These data warrant for further studies to understand the biology of DCIS with microinvasion and to evaluate specific therapy options different from pure DCIS potentially involving adjuvant modalities.&lt;/div&gt;&lt;","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"164 ","pages":"Article 105902"},"PeriodicalIF":2.6,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811975","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":"Fluorescence in situ hybridization (FISH)-based detection of paracentric inversions leading to RBM10::TFE3 rearrangement.","authors":"Sounak Gupta, Daniel R Sill, Loren P Herrera Hernandez, John C Cheville, Hussam Al-Kateb, Rumeal D Whaley, Patricia T Greipp","doi":"10.1016/j.humpath.2025.105907","DOIUrl":"10.1016/j.humpath.2025.105907","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105907"},"PeriodicalIF":2.6,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816480","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":"PAX5 as a diagnostic tool in unconventional acute leukemia: Establishing immunohistochemical evidence of B-cell lineage","authors":"Ernest F. Hidalgo Cedeno ,&nbsp;Sharon Germans ,&nbsp;Zenggang Pan ,&nbsp;Lourdes Mendez ,&nbsp;Olga K. Weinberg ,&nbsp;Mina L. Xu","doi":"10.1016/j.humpath.2025.105903","DOIUrl":"10.1016/j.humpath.2025.105903","url":null,"abstract":"<div><div>Acute leukemia lineage assignment is critical for clinical management. When CD19 expression is dim by flow cytometry, it becomes challenging to meet criteria for B-lymphoblastic leukemia/lymphoma (B-ALL) or B-lineage in mixed phenotype. While many B-lineage specific markers are available by immunohistochemistry (IHC), they have not been systematically validated. This study highlights the utility of PAX5, BOB.1 and OCT2 in lineage assignment when CD19 is dim, allowing for consideration as additional diagnostic criteria.</div><div>The databases of two academic institutions were searched for cases: acute undifferentiated leukemia (AUL), acute myeloid leukemia (AML) with minimal differentiation, mixed phenotype acute leukemia (MPAL), and all acute leukemias with weak CD19-expression. Cases were stained with PAX5, BOB.1 and OCT2. The IHCs were scored by intensity and percentage of positive blasts.</div><div>A total of 55 cases had weak CD19 expression: 18 B-ALL and 37 acute leukemias with weak CD19-expression (14 MPAL). For negative controls, we selected 21 AML with minimal differentiation, 5 T/myeloid cases, 5 near early T-cell precursor (ETP) T-ALLs and 3 ETP T-ALLs. By PAX5 IHC, 18/18 (100 %) B-ALL cases were positive; all minimal differentiation myeloid and T/myeloid leukemias were negative (0/26), and 36/37 (98 %) acute leukemias with weak CD19 were positive.</div><div>Our multicenter data support PAX5 IHC as a sensitive marker of B-lineage assignment when CD19 is dim to negative, especially in acute leukemias with ambiguous lineage or MPAL. BOB.1 and OCT2 can also be helpful but these demonstrated lower sensitivity. In cases where CD19 is dim, with weak CD79a and/or CD22, PAX5 IHC can “rescue” the lineage assignment.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"163 ","pages":"Article 105903"},"PeriodicalIF":2.6,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811997","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":"Genomic aberration detection by fluorescence in situ hybridization.","authors":"Liang Cheng, Darrell D Davidson, Shaobo Zhang","doi":"10.1016/j.humpath.2025.105906","DOIUrl":"10.1016/j.humpath.2025.105906","url":null,"abstract":"<p><p>Fluorescence in situ hybridization (FISH) is a simple, rapid, and reliable method for detecting genomic alterations relevant to a wide range of diseases, particularly neoplastic disorders, using routine surgical and cytological specimens. By employing fluorescent-labeled nucleic acid or nucleotide analog probes to target specific DNA sequences on chromosomes, FISH facilitates accurate diagnosis, tumor classification, biomarker identification, selection of targeted therapies, and monitoring of treatment efficacy. As the technology continues to evolve, the demand for FISH is expected to grow, given its cost-effectiveness in supporting diagnostic and therapeutic decisions. However, to fully leverage the potential of this powerful technique, it is essential to be mindful of its underlying chemistry, potential artifacts, interpretive challenges, and the broader clinical context. This article provides an overview of the fundamental principles of FISH data analysis, addresses technical considerations and implementation challenges, and discusses diagnostic criteria, cutoff values, quality control measures, test validation processes, and interpretation of results - with a focus on its application in daily surgical pathology practice.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105906"},"PeriodicalIF":2.6,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811996","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":"Update in lobular breast lesions: Pathological diagnosis in the molecular era","authors":"Lixia Bai ,&nbsp;Megan L. Troxell","doi":"10.1016/j.humpath.2025.105857","DOIUrl":"10.1016/j.humpath.2025.105857","url":null,"abstract":"<div><div><span><span>Lobular breast carcinoma has been recognized as a distinct entity for over 80 years, and the clinicopathologic features of classic cases are familiar. However, the repertoire of morphologic variants, intersection of contemporary </span>immunophenotyping (E-cadherin, catenins), and genomic studies (</span><em>CDH1</em><span><span><span>, loss of heterozygosity, alterations in other </span>cell adhesion pathway genes), provides opportunity to critically revisit diagnostic challenges and update criteria. Judicious application of well validated E-cadherin </span>immunostaining with careful interpretation to distinguish strong membrane pattern from aberrant staining (discontinuous or weak membrane, granular, cytoplasmic, dot-like) can aid in diagnostic reproducibility; p120 and β-catenin immunohistochemistry provides further confirmation, with similar caveats. Nevertheless, with increasing application of immunohistochemistry, ‘lobular’ cancers with intact E-cadherin expression are increasingly encountered. </span><em>CDH1</em><span>, encoding E-cadherin, harbors pathogenic mutations in 65–70 % of lobular carcinomas, as one facet of biallelic inactivation. As with immunohistochemistry, </span><em>CDH1</em><span> mutations are not universal, such that lobular carcinoma defies classification as a purely molecular entity at present. In addition to solidifying contemporary criteria for lobular carcinoma, there is a need to reset the terminology used for ‘mixed’ or ‘uncertain’ ductal-lobular carcinomas, as prior studies in the literature have been inconsistent in nomenclature and definitions. Recent studies provide insight into invasive lobular carcinoma with tubular elements associated with cadherin switching (P-cadherin upregulation) in tubular areas. Lobular-like invasive mammary carcinoma is another term recently applied to morphologically lobular carcinomas with membranous E-cadherin and p120 expression. These studies further understanding of the biologic spectrum of lobular carcinoma, yet salient morphologic, immunophenotypic, and molecular questions remain.</span></div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"162 ","pages":"Article 105857"},"PeriodicalIF":2.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144496085","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":"Current understanding of phyllodes tumors of the breast: Tumor classification, molecular landscape, and best pathology practice","authors":"Matthew David Charles Packer ,&nbsp;Susan Carole Lester","doi":"10.1016/j.humpath.2025.105863","DOIUrl":"10.1016/j.humpath.2025.105863","url":null,"abstract":"<div><div>Phyllodes tumors of the breast are uncommon biphasic fibroepithelial lesions comprised of neoplastic stromal cells and a nonneoplastic epithelial component. Unlike fibroadenomas, which are the most common benign breast neoplasms, phyllodes tumors can be benign, borderline, or malignant and can rarely metastasize. While the accurate diagnosis and classification of these lesions is therefore critical, both often prove challenging for pathologists. This review will provide an overview of phyllodes tumors including their epidemiology, clinical and radiologic presentations, macroscopic and microscopic features, classification and clinical behavior, immunohistochemical profile, differential diagnosis, and management. The review will conclude with a discussion of some of the evolving tools and technologies that may assist with the evaluation of phyllodes tumors in the future.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"162 ","pages":"Article 105863"},"PeriodicalIF":2.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527697","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":"Artificial intelligence in breast pathology: Overview and recent updates","authors":"Sneha Datwani,&nbsp;Hikmat Khan,&nbsp;Muhammad Khalid Khan Niazi,&nbsp;Anil V. Parwani,&nbsp;Zaibo Li","doi":"10.1016/j.humpath.2025.105819","DOIUrl":"10.1016/j.humpath.2025.105819","url":null,"abstract":"<div><div>Breast cancer remains a major global health concern where timely and accurate pathologic diagnosis is critical for effective management. The traditional reliance on expert interpretation of histopathology is increasingly challenged by rising workloads, inter-observer variability, and the complexity of current precision pathology. The advent of digital pathology through whole slide imaging (WSI) has enabled the integration of artificial intelligence (AI) into breast pathology practice, offering promising solutions to these challenges.</div><div>This review explores the major advancements of AI in breast pathology, including its applications in diagnosis and classification, histological grading, lymph node metastasis detection, and biomarker quantification (ER, PR, HER2, Ki-67, and others). We also discuss AI's emerging roles in prognosis, treatment response, tumor microenvironment analysis, and the discovery of novel biomarkers. Despite the significant progress, barriers such as data quality, generalizability, model interpretability, regulatory challenges, and integration into clinical workflows remain. Future directions emphasize the development of foundation models, multimodal data integration, explainable AI, real-world clinical validation, and decentralized learning approaches. With careful navigation of these challenges and continued interdisciplinary collaboration, AI is poised to transform breast pathology and advance patient care.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"162 ","pages":"Article 105819"},"PeriodicalIF":2.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179958","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":"Genetic landscapes of breast tumors by next-generation sequencing with focus on less common types and genotype-phenotype correlations","authors":"Raza S. Hoda,&nbsp;Gregor Krings","doi":"10.1016/j.humpath.2025.105826","DOIUrl":"10.1016/j.humpath.2025.105826","url":null,"abstract":"<div><div>Next-generation sequencing (NGS) has transformed our understanding of oncogenic pathways and mutational processes underlying many breast tumors. Although large-scale NGS studies included mostly common invasive breast carcinomas, the genetic landscapes of several less common or rare special histologic types and other breast tumors have now also been elucidated. Many of these lesions harbor highly specific types of mutations or rearrangements/gene fusions, including invasive lobular carcinoma, tall cell carcinoma with reversed polarity, most salivary gland-like neoplasms, fibroepithelial neoplasms, and mesenchymal tumors such as fibromatosis, nodular fasciitis, and dermatofibrosarcoma protuberans. In some cases, surrogate immunohistochemical or RNA <em>in situ</em> hybridization markers evaluable by light microscopy have been shown to correlate with the underlying genetic alterations. Angiosarcomas and other special breast cancer subtypes, such as triple negative apocrine carcinomas, metaplastic carcinomas, and a subset of ER-positive carcinomas (mucinous and micropapillary carcinomas, neuroendocrine neoplasms) have not been associated with specific genetic underpinnings but are enriched for certain genetic features and oncogenic pathways. The identification of characteristic genetic alterations or their molecular surrogates can be useful to establish an accurate diagnosis, and in some cases, may point to potentially actionable therapeutic targets. This review aims to summarize the genetic landscapes of less common benign and malignant breast tumors, with special attention to genotype-phenotype correlations and to the diagnostic utility of genetics and surrogate markers when applicable. <em>BRCA1/2</em>-associated breast carcinomas will also be discussed due to the association of so-called BRCAness with basal-like histology.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"162 ","pages":"Article 105826"},"PeriodicalIF":2.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247660","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":"Inside front cover - Masthead","authors":"","doi":"10.1016/S0046-8177(25)00182-0","DOIUrl":"10.1016/S0046-8177(25)00182-0","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"162 ","pages":"Article 105895"},"PeriodicalIF":2.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144895331","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}