Human pathology最新文献

{"title":"Cyclin D1-negative mantle cell lymphoma","authors":"Chi Young Ok,&nbsp;L. Jeffrey Medeiros","doi":"10.1016/j.humpath.2024.105698","DOIUrl":"10.1016/j.humpath.2024.105698","url":null,"abstract":"<div><div>Cyclin D1-negative mantle cell lymphoma (MCL) is regarded as a B-cell neoplasm that has morphologic and immunophenotypic findings indistinguishable from typical MCL. These neoplasms lack cyclin D1 overexpression by immunohistochemistry and t(11;14)(q13;q32)/<em>IGH::CCND1</em>. Since cyclin D1-negative MCL was first recognized by gene expression profiling in 2003, there has been diagnostic confusion regarding this entity, mostly attributable to a lack of diagnostic tools to recognize these neoplasms in most clinical laboratories. Accumulated data show that most cyclin D1-negative MCL cases harbor <em>CCND2</em> or <em>CCND3</em> translocation with a variety of gene partners. In this review, the concept of cyclin D1-negative MCL is discussed in chronological order to further our understanding of this entity. We then discuss currently available diagnostic approaches and we conclude with future directions. We also suggest that the more specific terms <em>CCND2</em>-rearranged MCL or <em>CCND3</em>-rearranged MCL be used for neoplasms in which the rearranged gene is known, and that we reserve the term cyclin D1-negative MCL for neoplasms in which the rearranged gene in unknown.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"156 ","pages":"Article 105698"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686808","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":"Epstein-Barr virus-associated B-cell lymphoproliferative disorders and lymphomas: Diagnostic overlaps and defining features","authors":"Ashley K. Volaric ,&nbsp;Yuri Fedoriw","doi":"10.1016/j.humpath.2024.105697","DOIUrl":"10.1016/j.humpath.2024.105697","url":null,"abstract":"<div><div>This review explores four Epstein-Barr virus (EBV)-associated B-cell lymphoproliferative disorders (LPD) and lymphomas with significant diagnostic overlap: EBV(+) mucocutaneous ulcer (EBVMCU), EBV(+) polymorphic LPD, EBV(+) classic Hodgkin lymphoma (CHL), and EBV(+) diffuse large B-cell lymphoma (DLBCL). Each entity is compared for both overlapping and defining features of clinical presentation, morphology, immunohistochemical profile and EBV expression pattern and latency. Our aims for this review are to provide useful guidance to the practicing pathologist in the diagnosis of these EBV-associated entities.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"156 ","pages":"Article 105697"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686811","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":"Lymphomas in 3D and 4D spaces","authors":"Martin-Leo Hansmann ,&nbsp;Sonja Scharf ,&nbsp;Patrick Wurzel ,&nbsp;Sylvia Hartmann","doi":"10.1016/j.humpath.2024.105699","DOIUrl":"10.1016/j.humpath.2024.105699","url":null,"abstract":"<div><div>The cellular compartments in the lymph node form dynamic networks, enabling coordinated innate and adaptive immunological responses. This compartmentalization of the lymph node into subcompartments, such as the T and B zones, has been proven to be beneficial. The study of lymph node microarchitecture has yielded new insights into a range of fields, including anatomy, pathology and biological processes. This review focuses on three-dimensional (3D) and four-dimensional (4D) investigations of human lymph nodes, with a particular emphasis on comparisons with data obtained from mice. It will discuss the findings of 3D/4D investigations of human lymph nodes. The investigation of the immune system in 3D space and time offers numerous advantages over the analysis of thin tissue sections. It provides data that is not visible in two-dimensional (2D) representations. A comparison of volumes, surfaces, cell speeds, cell contact numbers, contact duration times, morphologies and other variables can be made in the context of immune responses and lymphomas. The evaluation of data, the application of statistics and the use of machine learning have all been demonstrated to be valuable. In conditions of reactivity and neoplasia, T cells are the fastest-moving cells. In contrast, B cells show slower movement and higher turning angles in reactive lymphoid tissue and lymphomas. Even slower than B cells are reticulum cells, like follicular dendritic reticulum cells (FDC) of the B zones and macrophages. Fast T cells are especially found in Hodgkin lymphomas and mantle cell lymphomas. Contact times between T and B cells differ between different lymphoma types and may prove useful in defining lymphomas. 4D technologies, which evaluate living tissue slices, are suitable for use in testing checkpoint blockers (such as nivolumab) and other therapeutic drugs or cells. Following incubation with nivolumab, the duration of contacts between CD4-positive T cells and CD30-positive Hodgkin-Reed-Sternberg cells was documented. The preliminary data indicate that 3D and 4D experiments in hematopathology may facilitate new insights into diagnostics, biology, and clinical applications, including the development of new lymphoma classifications.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"156 ","pages":"Article 105699"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lymphoplasmacytic lymphoma and Waldenström macroglobulinemia, a decade after the discovery of MYD88L265P","authors":"Lianqun Qiu,&nbsp;Pei Lin","doi":"10.1016/j.humpath.2024.105708","DOIUrl":"10.1016/j.humpath.2024.105708","url":null,"abstract":"<div><div>There has been remarkable progress over the past 80 years since Jan Waldenstrom first described patients with a hyperviscosity syndrome related to IgM paraprotein in 1944. The definition of Waldenstrom macroglobulinemia (WM) has evolved from a clinical syndrome to a distinct clinicopathologic entity with characteristic morphology, immunophenotype and molecular features. The landmark discovery of <em>MYD88</em> mutation among most WM cases in 2012 marked the dawning of an era of molecular genomic exploration that led to a paradigm shift in clinical practice. In the current World Health Organization (WHO) classification of hematologic neoplasms, WM is included in the category of lymphoplasmacytic lymphoma (LPL) of which WM represents over 90% of cases. LPL/WM is also better defined, resolving ambiguity in many cases that would have been classified as “low-grade B-cell lymphoma with plasmacytic differentiation” a decade before. Nevertheless, challenges still face pathologists because criteria for distinguishing LPL/WM from other types of low-grade B-cell lymphoma, particularly marginal zone lymphoma (MZL), remain imperfect. In this review, we highlight the current understanding of LPL and WM brought to light by new discoveries, which in turn are increasingly translated to improved diagnosis and personalized therapy. Key concepts in the diagnosis and their clinical implications are emphasized. Controversies and challenges are also discussed.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"156 ","pages":"Article 105708"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864111","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":"Aberrant expression in lymphoma, a diagnostic pitfall","authors":"Joo Y. Song ,&nbsp;Zenggang Pan","doi":"10.1016/j.humpath.2024.105706","DOIUrl":"10.1016/j.humpath.2024.105706","url":null,"abstract":"<div><div>One of the major difficulties in practical hematopathology is to accurately assign cell lineage and thus ensure proper classification of lymphomas. The lineage-specific markers of lymphoma are detected by immunohistochemistry or flow cytometry immunophenotypic methods. However, aberrant gain or loss of these markers is occasionally encountered during daily practice, which often creates diagnostic challenges. In addition, lymphoma may aberrantly express non-hematopoietic markers, and vice versa. This review article provides an overview of aberrant gain of expression of lineage-associated antigens in mature lymphoid neoplasms, including recommendations to avoid diagnostic pitfalls and ultimately to reach accurate diagnoses.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"156 ","pages":"Article 105706"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824298","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":"Marginal zone lymphoma of extranodal sites: A review with an emphasis on diagnostic pitfalls and differential diagnosis with reactive conditions","authors":"Roman Segura-Rivera ,&nbsp;Sergio Pina-Oviedo","doi":"10.1016/j.humpath.2024.105683","DOIUrl":"10.1016/j.humpath.2024.105683","url":null,"abstract":"<div><div>Marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) represents 8% of all B-cell lymphomas and it is the most common small B-cell lymphoma arising at extranodal sites. The gold-standard test to establish a diagnosis of MALT lymphoma remains histopathologic analysis with the aid of immunohistochemistry (IHC) and/or flow cytometry immunophenotypic analysis. MALT lymphoma represents a progression from a persistent chronic inflammatory process, and therefore distinguishing MALT lymphoma from chronic inflammation by histopathology may be challenging in some cases. Despite recent trends to consider <em>IGH</em> rearrangement/clonality as a confirmatory diagnostic test of MALT lymphoma, this method is far from ideal for this purpose since a positive or a negative result does not necessarily confirm or exclude that a process is lymphoma or reactive. This test must be correlated with the morphologic findings. Moreover, MALT lymphoma may arise in association with underlying autoimmune conditions where clonal lymphoid populations are not uncommonly detected. Therefore, we believe that an integrated approach including detailed morphologic review in combination with IHC and/or flow cytometry is best to establish a diagnosis of MALT lymphoma in most cases. We present helpful morphologic tips to avoid potential diagnostic pitfalls at some of the most common extranodal sites, including the stomach, ocular adnexa/conjunctiva, salivary gland, lung, thymus, breast, thyroid, small and large intestine and the dura. The differential diagnosis of MALT lymphoma with IgG4-related disease is also discussed.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"156 ","pages":"Article 105683"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619268","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":"Application of flow cytometry immunophenotypic analysis for the diagnosis of mature B-cell lymphomas/leukemias","authors":"Hong Fang,&nbsp;Sa A. Wang,&nbsp;L. Jeffrey Medeiros,&nbsp;Wei Wang","doi":"10.1016/j.humpath.2024.105711","DOIUrl":"10.1016/j.humpath.2024.105711","url":null,"abstract":"<div><div>Flow cytometry immunophenotyping (FCI) is an important and indispensable tool in the diagnosis of mature B-cell lymphomas/leukemias, particularly for small fine needle aspiration and needle core biopsy specimens which are becoming increasingly popular for diagnostic purposes. FCI has several advantages. Given its multiparametric nature, FCI can analyze the expression of multiple antigens simultaneously on the same cell of interest, qualitatively and quantitively. During the diagnostic process, FCI can provide time sensitive and valuable information for triage of other ancillary studies such as immunohistochemical and molecular studies. In this review, we aim to provide common and practical approaches for using FCI in the diagnostic workup of mature B-cell neoplasms. The immunophenotypic features of common mature B-cell neoplasms as well as diagnostic challenges and pitfalls associated with FCI are also discussed.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"156 ","pages":"Article 105711"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871873","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 the diagnosis and classification of intestinal T-cell lymphomas","authors":"Sanam Loghavi,&nbsp;L. Jeffrey Medeiros","doi":"10.1016/j.humpath.2025.105720","DOIUrl":"10.1016/j.humpath.2025.105720","url":null,"abstract":"<div><div>We provide an overview of recent advances in the diagnosis and classification of intestinal T- and NK-cell lymphomas and lymphoproliferative disorders that primarily involve the gastrointestinal (GI) tract. It should be mentioned that systemic T- and NK-cell lymphomas can present initially in the GI tract but are not the focus of this review. Here, we focus on the clinical and pathologic findings of enteropathy-associated T-cell lymphoma, monomorphic epitheliotropic intestinal T-cell lymphoma, intestinal T-cell lymphoma, not otherwise specified, indolent T-cell lymphoma of the GI tract and indolent NK-cell lymphoproliferative disorder of the GI tract (previously known as NK-cell enteropathy). These diseases are uncommon, and their clinical manifestations and pathologic features can show overlap, but are associated with different outcomes making accurate diagnosis essential. In most cases, the diagnosis of intestinal T- and NK-cell lymphomas and lymphoproliferative disorders requires integrating the clinical context with the morphologic, immunophenotypic, and molecular alterations. In this review, we also emphasize the current understanding of the genetic drivers of these diseases.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"156 ","pages":"Article 105720"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038174","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":"Classic Hodgkin lymphoma: An illustrative review of select diagnostic limitations and immunomorphological challenges","authors":"Siba El Hussein ,&nbsp;Dennis P. O'Malley","doi":"10.1016/j.humpath.2024.105678","DOIUrl":"10.1016/j.humpath.2024.105678","url":null,"abstract":"<div><div>The diagnosis of classic Hodgkin lymphoma (CHL) in clinical practice remains reliant on tissue morphological and immunohistochemical evaluation. In this article, we illustrate specific scenarios that we have encountered in our clinical practice pertaining to diagnostic challenges in CHL. We begin with select presentations of morphologic variants of CHL and then discuss certain immunophenotypic deviations from what is deemed “normal patterns” of antigen expression by HRS cells. Lastly, we discuss mimickers of HRS cells, in lymphomatous and non-lymphomatous conditions.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"156 ","pages":"Article 105678"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567695","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":"Primary mediastinal large B-cell lymphoma from the clinic to genomics: Insights for pathologists","authors":"Najla Fakhruddin ,&nbsp;Iman Abou Dalle ,&nbsp;Zaher Chakhachiro","doi":"10.1016/j.humpath.2024.105705","DOIUrl":"10.1016/j.humpath.2024.105705","url":null,"abstract":"<div><div>Primary mediastinal large B-cell lymphoma (PMBL) is a mature aggressive B-cell lymphoma that arises in the anterior mediastinum, likely originating from thymic B cells. Initially considered a subtype of diffuse large B-cell lymphoma, PMBL has since been established as a distinct clinicopathologic entity due to its unique clinical, morphologic, immunophenotypic and genetic characteristics. PMBL primarily affects young adults, especially women, and manifests as a bulky mediastinal mass that can invade adjacent structures, often causing respiratory symptoms. The genomic landscape of PMBL includes alterations in the JAK-STAT, NF-κB signaling pathways, and immune evasion mechanisms. This review explores the clinical presentation, pathogenesis and genetic landscape of PMBL, highlighting its morphologic and immunophenotypic characteristics and differences from related mediastinal lymphomas such as classic Hodgkin lymphoma and mediastinal grey zone lymphoma. We also discuss the implications of these findings on diagnosis, management and personalized treatment approaches.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"156 ","pages":"Article 105705"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812906","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}