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":"https://doi.org/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":"Genetic alteration analysis of non-pediatric diffuse midline glioma, H3 K27-altered.","authors":"Hanbin Jang, Seyoung Moon, Hyun Jung Kwon, Sejoon Lee, Gheeyoung Choe, Kyu Sang Lee","doi":"10.1016/j.humpath.2024.105709","DOIUrl":"https://doi.org/10.1016/j.humpath.2024.105709","url":null,"abstract":"<p><p>Diffuse midline gliomas with H3 K27-alteration (DMGH3) are lethal and inoperable brain tumors. Although DMGH3s mainly occur in pediatric patients, they have also occurred in adult patients. This study aimed to analyze the clinicopathological significance of targetable genetic alterations in non-pediatric DMGH3. Next-generation sequencing (NGS) was conducted on 18 non-pediatric DMGH3 patients to analyze additional genetic alterations. The median age at diagnosis was 35 years, and the mean follow-up duration was 762 days. Fourteen cases involved the thalamus-hypothalamus (77.8%). Histologic high-grade features (WHO histologic grade ≥3) were observed in 11 (61.1%) patients. H3F3A (H3 K27M) alterations were identified in all 18 patients using immunohistochemistry and NGS. TP53 mutations were found in 11 patients (61.1%), FGFR1 or PIK3CA in 3 (16.7%), ATRX in 6 (33.3%), NF1 in 4 (22.2%), and KRAS or ATM in 1 (5.6%). TP53 mutations were significantly correlated with high-grade histological features and worse overall survival (OS) (P < 0.05). Despite non-pediatric DMGH3 cases exhibiting superior OS compared to pediatric DMGH3 cases, TP53 mutations were associated with poorer OS outcomes. Notably, FGFR1 and PIK3CA mutations, which have been identified as potential targetable genes, were detected. In conclusion, non-pediatric DMGH3s showed predominant tumor localization within the thalamus and improved prognosis compared to those in pediatric cases, with TP53 alterations correlating with high-grade histology and shorter survival. Genetic profiling, particularly identifying targetable mutations like FGFR1 and PIK3CA, could inform personalized treatment strategies and improve patient outcomes.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105709"},"PeriodicalIF":2.7,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864110","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":"Characterization of gastric/gastrointestinal-like immunophenotypes in endometrial endometrioid adenocarcinomas, including endometrioid adenocarcinomas with mucinous differentiation.","authors":"Dena Khaefpanah, Somaye Zare, Farnaz Hasteh, Wangpan J Shi, Omonigho Aisagbonhi, Andres A Roma, Oluwole Fadare","doi":"10.1016/j.humpath.2024.105707","DOIUrl":"10.1016/j.humpath.2024.105707","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105707"},"PeriodicalIF":2.7,"publicationDate":"2024-12-15","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":"BRAF V600E gene mutation is present in primary intraosseous Rosai-Dorfman disease.","authors":"Lokman Cevik, Swati Satturwar, Dan Jones, Joel Mayerson, Steve Oghumu, O Hans Iwenofu","doi":"10.1016/j.humpath.2024.105702","DOIUrl":"10.1016/j.humpath.2024.105702","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105702"},"PeriodicalIF":2.7,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817917","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":"PD-L1 expression and immune infiltration across molecular subtypes of endometrial cancer: An integrative-analysis of molecular classification and immune subtypes.","authors":"Yanhui Zhang, Baohui Ju, Runfen Cheng, Tingting Ding, Jianghua Wu","doi":"10.1016/j.humpath.2024.105704","DOIUrl":"10.1016/j.humpath.2024.105704","url":null,"abstract":"<p><p>The immune subtypes of the tumor microenvironment in endometrial cancer (EC), associated with different molecular classifications, warrant further investigation to guide EC immunotherapy strategies. This study focused on programmed death-ligand 1 (PD-L1) expression (Clone SP263) and immune cell (IC) markers (CD3, CD8, CD68, CD20, CD21) in 110 EC cases. In this cohort, the molecular subtype distribution was: POLE mutation (POLEmut) 7.3% (8/110), mismatch repair-deficient (MMRd) 21.8% (24/110), p53 abnormal (p53abn) 14.5% (16/110), and non-specific molecular profile (NSMP) 56.4% (62/110). NSMP subtypes exhibited the lowest PD-L1+ cell densities and scores. POLEmut and MMRd subtypes showed higher IC densities, while p53abn and NSMP subtypes had lower IC densities and fewer tertiary lymphoid structures (TLS). Integrative analysis of immune subtypes with PD-L1 and CD8⁺ tumor infiltrating lymphocytes (TILs) revealed 62.5% of POLEmut and 45.8% of MMRd cases as TIME type Ⅰ (PD-L1⁺ & CD8^high). Conversely, p53abn and NSMP cases were more heterogeneous, with 37.5% of p53abn cases in TIME type Ⅲ (PD-L1⁺ & CD8^low) and 41.9% of NSMP cases in TIME type Ⅱ (PD-L1^- & CD8^low). Higher CD8⁺ T cell density was a prognostic marker for disease-free survival in EC, including within NSMP (p < 0.05). In summary, the four WHO molecular subtypes of EC exhibit distinct TIME subtypes, complementing molecular classification and providing insights for optimizing EC immunotherapy strategies.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105704"},"PeriodicalIF":2.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812903","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}