Human pathology最新文献

{"title":"Paneth cell-like differentiation in urothelial carcinoma: A hitherto unreported phenomena?","authors":"Carol N Rizkalla, Lisa Friedman, Vivek Charu, 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":" ","pages":"105701"},"PeriodicalIF":2.7,"publicationDate":"2024-11-28","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":"High-grade B-cell lymphomas: Double hit and non-double hit.","authors":"Lianqun Qiu, L Jeffrey Medeiros, Shaoying Li","doi":"10.1016/j.humpath.2024.105700","DOIUrl":"10.1016/j.humpath.2024.105700","url":null,"abstract":"<p><p>The classification of high-grade B-cell lymphoma (HGBL) has continuously evolved over past decades. These neoplasms, as currently defined, represent about 2% of all non-Hodgkin lymphomas and patients with these neoplasms are often refractory or relapsed following standard therapy. The 5th edition of the World Health Organization classification of hematologic neoplasms (WHO-HAEM5) has refined the classification of HGBL and recognizes two types: (1) Diffuse large B-cell lymphoma (DLBCL)/HGBL with MYC and BCL2 rearrangements, with or without BCL6 rearrangements; and (2) HGBL, not otherwise specified (HGBL-NOS). WHO-HAEM5 excluded DLBCL/HGBL with concurrent MYC and BCL6 rearrangements from this category and reclassified them into DLBCL or HGBL-NOS categories respectively based on morphology. The International Consensus Classification (ICC) takes a slightly different approach. In addition to recognizing the two WHO-HAEM5 categories, they recognize HGBL with concurrent MYC and BCL6 rearrangements as a provisional entity. In this review, we provide an update of HGBL and its subgroups, focusing on their clinicopathologic features, diagnosis, molecular genetic features, and pathogenesis. Our diagnostic approach and caveats for differential diagnosis are also discussed with an emphasis on the differential diagnosis with B lymphoblastic leukemia/lymphoma.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105700"},"PeriodicalIF":2.7,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739486","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, Sonja Scharf, Patrick Wurzel, Sylvia Hartmann","doi":"10.1016/j.humpath.2024.105699","DOIUrl":"10.1016/j.humpath.2024.105699","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105699"},"PeriodicalIF":2.7,"publicationDate":"2024-11-26","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathologic findings in a cohort of metastases to the stomach","authors":"Trevor Toussieng ,&nbsp;Brent K. Larson ,&nbsp;Miguel Burch ,&nbsp;Alexandra Gangi ,&nbsp;Jun Gong ,&nbsp;Maha Guindi ,&nbsp;Michael Kozak ,&nbsp;Keith Lai ,&nbsp;Danielle A. Hutchings ,&nbsp;Kevin M. Waters","doi":"10.1016/j.humpath.2024.105694","DOIUrl":"10.1016/j.humpath.2024.105694","url":null,"abstract":"<div><h3>Aims</h3><div>Metastatic tumors to the stomach can mimic primary gastric adenocarcinoma or be subtle and difficult to identify. The current study aimed to characterize the clinicopathology of metastases to the stomach to aid in diagnosis.</div></div><div><h3>Methods and results</h3><div>Forty-three metastatic tumors and 30 primary gastric adenocarcinoma cases were reviewed. Metastases originated from numerous primaries with the most common being mammary (n = 17) or melanoma (n = 9). The gastric metastasis represented the initial diagnosis for 9 (21%) cases without previous history of malignancy. The median age at diagnosis was similar (metastatic 66 years; primary 67.5 years; <em>P</em> = 0.42). The most common indication for procedure was abdominal pain (23%; <em>P</em> = 0.95) in metastases and melena (43%; <em>P</em> &lt; 0.01) in primaries. Procedural findings suggestive of metastasis over primary adenocarcinoma were multiple lesions (23% versus 0%; <em>P</em> = 0.01), non-mass forming mucosal changes (30% versus 0%; <em>P</em> &lt; 0.01), submucosal nodularity (14% versus 0%; <em>P</em> = 0.09), and absence of ulceration (9% versus 53%; <em>P</em> &lt; 0.01). Histologic findings less commonly seen in metastasis were mucosal layer involvement (86% versus 100%; <em>P</em> = 0.09), ulceration (40% versus 70%; <em>P</em> = 0.02), surface epithelial involvement/colonization by tumor (12% versus 60%; <em>P</em> &lt; 0.01), intestinal metaplasia (9% versus 53%; <em>P</em> &lt; 0.01), background dysplasia (0% versus 30%; <em>P</em> &lt; 0.01), and <em>Helicobacter pylori</em> infection (0% versus 20%; <em>P</em> &lt; 0.01). Lymphovascular invasion had similar prevalence (metastatic 23%; primary 20%; <em>P</em> = 0.70).</div></div><div><h3>Conclusions</h3><div>Metastasis to the stomach included a variety of primary sites and was not infrequently the initial diagnosis. Patient demographics were similar to primary adenocarcinoma. Multiple lesions, non-mass forming mucosal changes, and/or submucosal nodularity were more common in metastasis. Histologically, the absence of surface epithelial involvement, ulceration, intestinal metaplasia, background dysplasia, or <em>H. pylori</em> infection can raise suspicion for metastasis.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"154 ","pages":"Article 105694"},"PeriodicalIF":2.7,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695479","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":"Angioimmunoblastic T-cell lymphoma: Current Diagnostic Insights and Advances.","authors":"Nana P Matsumoto, Mina L Xu","doi":"10.1016/j.humpath.2024.105696","DOIUrl":"10.1016/j.humpath.2024.105696","url":null,"abstract":"<p><p>Angioimmunoblastic T-cell lymphoma (AITL), or nodal T-follicular helper cell lymphoma, angioimmunoblastic type, is a rare and aggressive type of T-cell lymphoma characterized by a spectrum of clinical and histopathological features that can present diagnostic challenges. Derived from T-follicular helper cells, the genesis of AITL is thought to be a multistep process involving mutations in epigenetic regulatory genes such as TET2 and DNMT3A, followed by driver mutations in RHOA^G17V and IDH2^R172 which promote clonal expansion as well as a characteristic inflammatory milieu. This review aims to provide a comprehensive overview of AITL, including its clinical presentation, epidemiology, pathogenesis, histomorphology and treatment options. Despite advancements in the understanding of AITL biology and the development of novel treatment strategies, the prognosis for patients with AITL remains poor.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105696"},"PeriodicalIF":2.7,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686805","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, Yuri Fedoriw","doi":"10.1016/j.humpath.2024.105697","DOIUrl":"10.1016/j.humpath.2024.105697","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105697"},"PeriodicalIF":2.7,"publicationDate":"2024-11-19","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":"Cyclin D1-negative mantle cell lymphoma.","authors":"Chi Young Ok, L Jeffrey Medeiros","doi":"10.1016/j.humpath.2024.105698","DOIUrl":"10.1016/j.humpath.2024.105698","url":null,"abstract":"<p><p>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)/IGH::CCND1. 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 CCND2 or CCND3 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 CCND2-rearranged MCL or CCND3-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.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105698"},"PeriodicalIF":2.7,"publicationDate":"2024-11-19","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":"Genetic validation of a TSC2 immunohistochemistry assay in TSC/mTOR-pathway altered renal tumors","authors":"Amir Akbari ,&nbsp;Clarence Rachel Villanueva ,&nbsp;Ondrej Hes ,&nbsp;Sean R. Williamson ,&nbsp;Shivani Kandukuri ,&nbsp;Shivani Sharma ,&nbsp;Aggarwal Aditi ,&nbsp;Kristyna Pivovarcikova ,&nbsp;Pedram Argani ,&nbsp;Sambit K. Mohanty ,&nbsp;Kaushal Asrani ,&nbsp;Tamara L. Lotan","doi":"10.1016/j.humpath.2024.105693","DOIUrl":"10.1016/j.humpath.2024.105693","url":null,"abstract":"<div><div>Pathogenic mutations in the genes associated with tuberous sclerosis complex (TSC)/mTOR pathway are linked to histologically diverse renal cell neoplasms, including eosinophilic solid and cystic renal cell carcinoma (ESC RCC), low grade oncocytic tumor (LOT), eosinophilic vacuolated tumor (EVT), and xanthomatous giant cell renal cell carcinoma (XGC RCC). Here, we validate a TSC2 immunohistochemistry (IHC) assay by comparison to genomic data in these neoplasms. Automated TSC2 IHC was performed on formalin-fixed paraffin embedded (FFPE) tissues from 38 genetically-confirmed TSC/mTOR-associated renal tumors (6 ESCs, 16 EVTs, 13 LOTs, 2 XGC and 1 clear cell RCC) and visually scored in a semi-dichotomous fashion compared to internal control tissue. The positive predictive value (PPV) of TSC2 protein loss for underlying pathogenic mutation in <em>TSC2</em> was 92% (11/12), while the negative predictive value (NPV) of intact TSC2 by IHC for lack of underlying pathogenic mutation in <em>TSC2</em> was 81% (21/26). Intact TSC2 by IHC was 95% (21/22) specific for absence of underlying pathogenic <em>TSC2</em> mutation. All the cases lacking <em>TSC2</em> mutation with intact TSC2 protein had an underlying mutation in <em>TSC1</em>, <em>MTOR</em> or <em>PIK3CA</em>. Loss of TSC2 was 77% (10/13) sensitive for underlying <em>TSC2</em> truncation mutations and 33% (1/3) sensitive for underlying <em>TSC2</em> missense mutations. Overall, 73% (8/11) tumors with TSC2 IHC loss and underlying pathogenic alterations in <em>TSC2</em> showed heterogeneous protein loss, with rare interspersed positively staining tumor cells. These data support TSC2 IHC as a potentially useful assay for the diagnostic workup of renal tumors suspected to belong to the TSC/mTOR-associated subgroups.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"154 ","pages":"Article 105693"},"PeriodicalIF":2.7,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686825","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":"Validation of Keratin 17 as a tissue biomarker in the diagnosis of upper tract urothelial carcinoma","authors":"Woodson Smelser ,&nbsp;Nam Kim ,&nbsp;Sholeh Jahanfard ,&nbsp;Mark Sarno ,&nbsp;Sam S. Chang ,&nbsp;Giovanna A. Giannico","doi":"10.1016/j.humpath.2024.105682","DOIUrl":"10.1016/j.humpath.2024.105682","url":null,"abstract":"<div><div>Upper tract urothelial carcinoma (UTUC) has a relatively low incidence but presents significant surveillance and treatment challenges. Therefore, novel biomarkers for the accurate detection of upper tract urothelial tumors are urgently needed. We evaluated the expression of Keratin 17 (KRT17), an oncoprotein implicated in the cell cycle progression of multiple human cancers and previously studied in bladder urothelial carcinoma, by immunohistochemistry in 139 UTUC cases, including noninvasive, invasive papillary urothelial carcinoma and urothelial carcinoma in situ. KRT17 expression pattern (basal/negative vs. nonbasal) and H-score were evaluated. The expression pattern was significantly different in normal (NL) compared to malignant urothelium. Nonbasal KRT17 expression was significantly higher in pTa (p &lt; 0.001) and invasive (pTinv) (p = 0.0023) urothelial carcinoma compared to NL, and in pTinv compared to pTa (p = 0.0391). Sensitivity and specificity for distinguishing benign from malignant tumors were 85% and 82, respectively, with an area under the curve of 0.83 (p &lt; 0.001). The KRT17 H-score was significantly higher in pTa and pTinv compared to NL (p &lt; 0.001 and p = 0.0035, respectively). Sensitivity and specificity for distinguishing benign from malignant carcinoma were 91% and 69%, respectively, with an AUC of 0.81 (p = 0.0010). KRT17 was not associated with tumor site, grade, or stage.</div><div>In summary, K17 is a sensitive and specific marker of neoplastic upper tract urothelium, and its potential use in routine diagnostics should be explored in larger studies.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"154 ","pages":"Article 105682"},"PeriodicalIF":2.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644102","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":"Marginal zone lymphoma of extranodal sites: A review with an emphasis on diagnostic pitfalls and differential diagnosis with reactive conditions.","authors":"Roman Segura-Rivera, Sergio Pina-Oviedo","doi":"10.1016/j.humpath.2024.105683","DOIUrl":"10.1016/j.humpath.2024.105683","url":null,"abstract":"<p><p>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 IGH 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.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105683"},"PeriodicalIF":2.7,"publicationDate":"2024-11-13","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}