Human pathology最新文献

{"title":"Application of Flow Cytometry Immunophenotypic Analysis for the Diagnosis of Mature B-Cell Lymphomas/Leukemias.","authors":"Hong Fang, Sa A Wang, L Jeffrey Medeiros, Wei Wang","doi":"10.1016/j.humpath.2024.105711","DOIUrl":"https://doi.org/10.1016/j.humpath.2024.105711","url":null,"abstract":"<p><p>Flow cytometry immunophenotypic analysis 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. Flow cytometry immunophenotyping (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 prior to morphologic evaluation and 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.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105711"},"PeriodicalIF":2.7,"publicationDate":"2024-12-19","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":"Lymphoplasmacytic lymphoma and Waldenström macroglobulinemia, a decade after the discovery of MYD88^L265P.","authors":"Lianqun Qiu, Pei Lin","doi":"10.1016/j.humpath.2024.105708","DOIUrl":"10.1016/j.humpath.2024.105708","url":null,"abstract":"<p><p>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 MYD88 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.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105708"},"PeriodicalIF":2.7,"publicationDate":"2024-12-17","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, Zenggang Pan","doi":"10.1016/j.humpath.2024.105706","DOIUrl":"10.1016/j.humpath.2024.105706","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105706"},"PeriodicalIF":2.7,"publicationDate":"2024-12-16","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":"Primary mediastinal large B-cell lymphoma from the clinic to genomics: Insights for pathologists.","authors":"Najla Fakhruddin, Iman Abou Dalle, Zaher Chakhachiro","doi":"10.1016/j.humpath.2024.105705","DOIUrl":"10.1016/j.humpath.2024.105705","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105705"},"PeriodicalIF":2.7,"publicationDate":"2024-12-10","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}

{"title":"Burkitt lymphoma.","authors":"Hong Fang, Wei Wang, L Jeffrey Medeiros","doi":"10.1016/j.humpath.2024.105703","DOIUrl":"10.1016/j.humpath.2024.105703","url":null,"abstract":"<p><p>Burkitt lymphoma is a mature aggressive B-cell neoplasm with distinctive clinical and morphologic features, a germinal center B-cell immunophenotype, a high proliferation index and MYC rearrangement with an immunoglobulin gene partner. Initially described in equatorial Africa by a surgeon, Denis Burkitt, African (endemic) Burkitt lymphoma was the first neoplasm shown to be associated with a virus, Epstein-Barr virus (EBV), and the first neoplasm shown to be associated with a chromosomal translocation, IGH::MYC. In this article, we provide a brief historical introduction of Burkitt lymphoma, followed by a review of all aspects of this neoplasm including pathogenesis, clinical presentation, morphology, immunophenotype, cytogenetics and molecular findings. We also provide recent updates of this entity, including advances in our understanding of molecular pathogenesis of Burkitt lymphoma and the recent proposal in the current World Health Organization classification that the traditional epidemiologic variants of Burkitt lymphoma are better replaced by presence or absence of EBV infection. We also discuss the differential diagnosis of Burkitt lymphoma and how this neoplasm can be distinguished from reactive conditions and other aggressive B-cell lymphomas/leukemias. Given its very rapid growth and the unique treatment approach employed to treat these patients, it is important to recognize Burkitt lymphoma to facilitate appropriate therapy.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105703"},"PeriodicalIF":2.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812901","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":"Characterization of gastric/gastrointestinal-like immunophenotypes in endometrial endometrioid adenocarcinomas, including endometrioid adenocarcinomas with mucinous differentiation","authors":"Dena Khaefpanah,&nbsp;Somaye Zare,&nbsp;Farnaz Hasteh,&nbsp;Wangpan J. Shi,&nbsp;Omonigho Aisagbonhi,&nbsp;Andres A. Roma,&nbsp;Oluwole Fadare","doi":"10.1016/j.humpath.2024.105707","DOIUrl":"10.1016/j.humpath.2024.105707","url":null,"abstract":"<div><div>Endometrial mucinous carcinoma of the gastric [gastrointestinal] type (MCG) is a rare, possibly aggressive subtype of endometrial cancer that should be distinguished from its potential mimics, including endometrioid carcinoma (EEC). Herein, we assess the frequency of gastric and gastrointestinal immunophenotypes in EEC without any discernible gastric/gastrointestinal-type morphology. Immunohistochemical analyses for KRT(CK)7, KRT20, CDX2, ER, SATB2, MUC6, PAX8, and HIK1083 were performed on 81 EEC, inclusive of consecutively archived low grade [with (n = 22) and without (n = 47) mucinous differentiation] and high grade (n = 12) cases. None displayed gastric-type morphology or goblet cells. Expression levels were semi-quantified as H-scores (combining intensity and extent of staining) on a standardized 0–300 scale. Among the gastric/gastrointestinal-type markers, 56%, 62%, 23%, 25%, and 0% of cases expressed MUC6, CDX2, KRT20, SATB2, and HIK1083 respectively. The expression levels for positive cases were generally limited, with average H-scores being 49.5 [range 1–250] for MUC6, 33.7 [1–285] for CDX2, 24.0 [1–270] for CK20, and 30.5 [2–220] for SATB2. Ten (12.35%) cases showed high expression (H ≥ 200) of at least 1 gastric/gastrointestinal-type marker, including 1, 2, 2 and 6 cases that were high positive for KRT20, SATB2, CDX2 and MUC6 respectively. Immunoreactive foci were generally indistinguishable from background at the morphologic level. There was no statistically significant correlation between the expression of any of the gastric/gastrointestinal-type markers and ER, KRT7 or PAX8 expression. In summary, gastric/gastrointestinal-type proteins are not uncommonly expressed at low levels in EEC. As such, positivity for these markers cannot be the sole basis for distinguishing EEC from MCG.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"154 ","pages":"Article 105707"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142835526","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":"Survival outcomes of poorly differentiated colorectal carcinoma variants: Insights from a single teaching institute","authors":"Zhengfan Xu ,&nbsp;Brian K. Theisen ,&nbsp;Qing Chang ,&nbsp;Daniel Schultz ,&nbsp;Beena U. Ahsan","doi":"10.1016/j.humpath.2024.105710","DOIUrl":"10.1016/j.humpath.2024.105710","url":null,"abstract":"<div><div>The morphologic diagnosis of colorectal carcinoma (CRC) is typically straight forward. However, there are certain subtypes of CRC that pose diagnostic challenges for daily practice due to sometimes overlapping morphologic and immunohistochemical features. These subtypes include poorly differentiated adenocarcinoma NOS, in the absence of conventional morphology (PDA-NOS), large cell neuroendocrine carcinoma (LCNEC), medullary carcinoma (MC), undifferentiated carcinoma (UC) and lymphoepithelioma-like carcinoma (LELC). This study aims to see if there is a survival difference between poorly differentiated variants of CRC, as well as other clinicopathological features that may affect prognosis. Additionally, we analyzed interobserver agreement among gastrointestinal pathologists (GP) at our institution in subclassifying poorly differentiated CRC. All consecutive patients with the diagnoses of PDA-NOS, MC, LCNEC, UC and LELC between July 2018 and July 2023 were included. Cox proportional regression test was used for multivariate analysis, while log-rank and Kaplan-Meier tests were used for univariate and survival analyses. Out of the same cohort of patients, 58 samples identified and reviewed by 3 GI-subspecialty-trained pathologists who were asked to assign the cases as PDA-NOS, LCNEC, MC, UC and LELC. Interobserver agreement was analyzed using Fleiss Kappa. Of the total 77 patients, 63 were PDA-NOS, 3 were LCNEC, 6 were MC, 4 were UC and 1 was LELC patients. Multivariate analysis using Cox proportional regression showed that tumor size (p = 0.001, HR = 1.22, 95% CI 1.08–1.38), patient age (p = 0.001, HR 1.73, 95% CI 1.24–2.40), and M stage (p = 0.02, HR 2.22, 95% CI 1.14–4.32) were significantly associated with worse OS. For the 58 cases analyzed, 3 GP agreed on 42 (72%) cases. The most common diagnosis was PDA-NOS and for 33 (57%) agreement was unanimous. There was moderate agreement (k 0.41–0.60) between all 3 GP. Our study evaluated the challenges associated with histological evaluation of colon cancers with poorly differentiated morphologies. Among the diagnoses considered in the study, MC and LCNEC had different prognostic implications compared to PDA-NOS and UC. Additionally, our GP showed moderate interobserver agreement, indicating that some level of variability in diagnosing poorly differentiated CRC subtypes may be inevitable.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"154 ","pages":"Article 105710"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881967","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":"Information for Authors","authors":"","doi":"10.1016/S0046-8177(25)00014-0","DOIUrl":"10.1016/S0046-8177(25)00014-0","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"154 ","pages":"Article 105727"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143093049","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":"Paneth cell-like differentiation in urothelial carcinoma: A hitherto unreported phenomena?","authors":"Carol N. Rizkalla,&nbsp;Lisa Friedman,&nbsp;Vivek Charu,&nbsp;Ankur R. Sangoi","doi":"10.1016/j.humpath.2024.105701","DOIUrl":"10.1016/j.humpath.2024.105701","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"154 ","pages":"Article 105701"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755074","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":"PAX6 is a useful marker for pancreatic origin of neuroendocrine neoplasms: A tissue microarray study evaluating more than 19,000 tumors from 150 different tumor types","authors":"Florian Lutz ,&nbsp;Sophie-Marie Hornburg ,&nbsp;Katharina Möller ,&nbsp;Florian Viehweger ,&nbsp;Ria Schlichter ,&nbsp;Anne Menz ,&nbsp;Andreas M. Luebke ,&nbsp;Martina Kluth ,&nbsp;Claudia Hube-Magg ,&nbsp;Andrea Hinsch ,&nbsp;Maximilian Lennartz ,&nbsp;Christian Bernreuther ,&nbsp;Sören Weidemann ,&nbsp;Patrick Lebok ,&nbsp;Christoph Fraune ,&nbsp;Guido Sauter ,&nbsp;David Dum ,&nbsp;Andreas H. Marx ,&nbsp;Ronald Simon ,&nbsp;Natalia Gorbokon ,&nbsp;Till S. Clauditz","doi":"10.1016/j.humpath.2024.105695","DOIUrl":"10.1016/j.humpath.2024.105695","url":null,"abstract":"<div><div>PAX6 immunohistochemistry (IHC) was proposed as a tool to identify a pancreatic origin of neuroendocrine neoplasms (NENs). To evaluate the diagnostic utility of PAX6 IHC, a tissue microarray containing 19,214 samples from 150 tumor types was analyzed. Data on progesterone receptor (PR) and glutamate decarboxylase 2 (GAD2) expression were available from previous studies. PAX6 staining occurred in 2.6% of 17,224 analyzable tumors and 60 tumor categories showed PAX6 positivity in at least one case. The highest rates of PAX6 positivity occurred in pancreatic (42.9–70.8%) and other NENs (up to 50.0%), testicular tumors (up to 58.3%), basal cell carcinomas of the skin (51.9%), squamous cell carcinomas of different organs (1.5–11.8%), and in gynecological tumors (up to 30%). For detection of pancreatic origin of NENs, sensitivity was highest for PAX6 (68.7%) followed by GAD2 (62.6%) and PR (52.5%) while specificity was highest for GAD2 (95.2%), followed by PR (91.3%), and PAX6 (91.1%). Of the analyzed combinations, the highest sensitivity (53.8%) and specificity (100%) was found for PAX6/GAD2, although combinations of PAX6/PR (49.5%/99.3%), PR/GAD2 (40.7%/98.9%), and PAX6/PR/GAD2 (40.6%/100%) did also result in high specificity. Only 14% of the 118 NENs with negativity for all three antibodies were of pancreatic origin. It is concluded that PAX6 IHC is useful to identify a pancreatic origin in case of NEN metastases of unknown origin. The combination with GAD2 and PR further increase the diagnostic performance of PAX6 and results in a &gt;98% specificity in case of positivity for at least 2 of these markers.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"154 ","pages":"Article 105695"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686831","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}