Human pathology最新文献

{"title":"Solid basaloid adenoid cystic carcinoma of the breast: A high-grade triple negative breast carcinoma which rarely responds to neoadjuvant chemotherapy","authors":"Katharine Schulz-Costello ,&nbsp;Fang Fan ,&nbsp;Daniel Schmolze ,&nbsp;Javier A. Arias-Stella III ,&nbsp;Lesley Taylor ,&nbsp;Jennifer Tseng ,&nbsp;Michelle Afkhami ,&nbsp;Jamie G. Rand ,&nbsp;Veronica Jones ,&nbsp;Preeti Farmah ,&nbsp;Min Han","doi":"10.1016/j.humpath.2025.105760","DOIUrl":"10.1016/j.humpath.2025.105760","url":null,"abstract":"<div><div>Solid basaloid adenoid cystic carcinoma of the breast (SB-AdCC) is an exceedingly rare but important entity that warrants clear separation from classic AdCC (C-AdCC) for optimal treatment. This case series retrospectively reviewed the diagnosis and treatment of 20 breast AdCCs. While four breast pathologists reached consensus on the diagnosis of all C-AdCCs, there was considerable disagreement when diagnosing pure SB-AdCCs. The morphology and immunohistochemical profiles of SB-AdCC closely resemble those of basaloid triple-negative breast carcinoma (TNBC). Molecular profiling of SB-AdCC revealed frequent mutations in the Notch pathway and alterations in chromatin modifiers, such as <em>CREBBP</em> and <em>KMT2D</em>. <em>MYB-NFIB</em> fusion was rare and detected in only 2 of 9 (22.2 %) SB-AdCCs. Axillary lymph node metastasis was present in 2 of 10 patients with SB-AdCC at the time of surgery. During a median follow-up of 27 months, one patient with SB-AdCC developed axillary recurrence. Moreover, 6 of 12 (50.0 %) patients with SB-AdCC developed distant metastases. Of the three patients who underwent neoadjuvant chemotherapy for SB-AdCC, one achieved near-complete pathological response, while the remaining two had minimal response. In conclusion, this series underscores the aggressive clinical course of SB-AdCC, similar to conventional TNBC. Pathologically, SB-AdCC also closely mimics conventional TNBC. It is imperative for pathologists to clearly indicate C-AdCC or SB-AdCC or give a percentage of each component to ensure appropriate treatment strategies and avoid both over-treatment and under-treatment.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"157 ","pages":"Article 105760"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729566","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":"Estrogen receptor expression in human tumors: A tissue microarray study evaluating more than 18,000 tumors from 149 different entities","authors":"Florian Viehweger ,&nbsp;Justus Gusinde ,&nbsp;Nicolai Leege ,&nbsp;Lisa-Maria Tinger ,&nbsp;Natalia Gorbokon ,&nbsp;Anne Menz ,&nbsp;Ria Schlichter ,&nbsp;Andrea Hinsch ,&nbsp;David Dum ,&nbsp;Christian Bernreuther ,&nbsp;Sören Weidemann ,&nbsp;Florian Lutz ,&nbsp;Simon Kind ,&nbsp;Viktoria Chirico ,&nbsp;Katharina Möller ,&nbsp;Viktor Reiswich ,&nbsp;Andreas M. Luebke ,&nbsp;Morton Freytag ,&nbsp;Maximilian Lennartz ,&nbsp;Frank Jacobsen ,&nbsp;Sarah Minner","doi":"10.1016/j.humpath.2025.105757","DOIUrl":"10.1016/j.humpath.2025.105757","url":null,"abstract":"<div><div>Estrogen receptor (ER) is a ligand-activated transcription factor with a critical role in development and function of multiple organ systems and a well-established drug target for breast cancer. To comprehensively evaluate ER expression in normal and tumor tissues, a tissue microarray containing 18,560 samples from 149 different tumor types and subtypes and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry (IHC). ER positivity was found in 55 different tumor types including 26 entities with at least one strongly positive tumor. ER positivity strongly predominated in breast neoplasms (81.1%) and in other gynecological tumors (39.4%) while only 0.8% of non-gynecological and non-mammary tumors showed ER positivity. Among these, ER staining – often at lower intensity – especially occurred in neuroendocrine neoplasms (up to 9.1%), salivary gland tumors (up to 8.3%), and in squamous cell carcinomas of different sites of origin (up to 6.7%). In invasive breast carcinoma (NST), reduced ER immunostaining was linked to high pT (p &lt; 0.0001), high grade (p &lt; 0.0001), distant metastasis (p = 0.0012), HER2 positivity (p &lt; 0.0001), PR negativity (p &lt; 0.0001) and shorter overall survival (p = 0.0576). In serous high-grade ovarian cancer, reduced ER staining was linked to nodal metastasis (p = 0.0012). ER staining was unrelated to histopathological features in 145 analyzable endometroid endometrial carcinomas. Within non-mammary, non-gynecological, non-prostate, and non-testicular tumors, ER positivity was more common in tumors from female (1.4% of 2528) than from male patients (0.6% of 3228; p = 0.0003). In summary, our data provide a ranking list of tumor entities according to their prevalence of ER positivity and shows that ER can be strongly expressed in a small number of non-breast and non-gynecological tumors which could potentially represent a diagnostic pitfall in a cancer of unknown primary but also represents a therapeutic opportunity.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"157 ","pages":"Article 105757"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143577909","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":"Systemic ALK-negative anaplastic large cell lymphoma: Insights into morphologic, immunophenotypic, genetic and molecular characteristics","authors":"Wei Xie ,&nbsp;L. Jeffrey Medeiros ,&nbsp;Guang Fan ,&nbsp;Shaoying Li ,&nbsp;Jie Xu","doi":"10.1016/j.humpath.2024.105671","DOIUrl":"10.1016/j.humpath.2024.105671","url":null,"abstract":"<div><div>Anaplastic large cell lymphoma (ALCL) is a mature T-cell neoplasm characterized by large pleomorphic cells, often with horseshoe- or kidney-shaped nuclei and abundant cytoplasm (hallmark cells), and uniformly strong CD30 expression. Based on ALK expression or <em>ALK</em> rearrangement, ALCL is further classified into ALK-positive (ALK+) and ALK-negative types. This review focuses on the clinicopathologic, immunophenotypic, cytogenetic and molecular features of systemic ALK-negative ALCL. These patients are usually older adults who present with advanced stage disease and often a poor prognosis. ALK-negative ALCL is morphologically indistinguishable from the common pattern of ALK+ ALCL, but some cases show non-common morphology, such as “donut cells”, Hodgkin-like features. ALK-negative ALCL is often negative for T-cell antigens (so-called “antigen loss”) and in some cases can have a “null” immunophenotype and be confused with other hematopoietic and non-hematopoietic neoplasms. Recurrent genetic/molecular alterations have been identified in systemic ALK-negative ALCL, including rearrangements of <em>DUSP22</em>, <em>TP63, JAK2, FRK, MYC, ROS1</em> and <em>TYK2</em>; mutations of <em>JAK1, STAT3</em> and <em>MSCE</em>; and aberrant expression of <em>ERBB4</em>. Some of these alterations may have prognostic significance and/or provide potential therapeutic targets. Data support the idea that ALK-negative ALCL with <em>DUSP22</em> rearrangement is a distinctive variant due to its unique morphologic, immunophenotypic and molecular features. Gene expression profiling data have shown that ALK-negative ALCL has distinctive molecular signatures, different from ALK+ ALCL and other T-cell lymphomas. Better understanding of the morphologic, immunophenotypic, genetic and molecular features of ALK-negative ALCL will help establish the correct diagnosis, guide therapeutic strategies and improve patient outcomes.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"156 ","pages":"Article 105671"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464054","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)00037-1","DOIUrl":"10.1016/S0046-8177(25)00037-1","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"156 ","pages":"Article 105750"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571482","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 ,&nbsp;Mina L. Xu","doi":"10.1016/j.humpath.2024.105696","DOIUrl":"10.1016/j.humpath.2024.105696","url":null,"abstract":"<div><div>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 <em>TET2</em> and <em>DNMT3A</em>, followed by driver mutations in <em>RHOA</em>^{<em>G17V</em>} and <em>IDH2</em>^{<em>R172</em>} 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.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"156 ","pages":"Article 105696"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indolent clonal lymphoid disorders","authors":"Jan Delabie,&nbsp;Ali Sakhdari","doi":"10.1016/j.humpath.2025.105715","DOIUrl":"10.1016/j.humpath.2025.105715","url":null,"abstract":"<div><div>Indolent clonal lymphoid disorders are not recognized as lymphomas as they generally need no systemic treatment, and depending on the lesion, need only limited clinical follow-up. These lesions are usually incidentally diagnosed during the work up for other disease. The recognition of indolent clonal lymphoid disorders is important to avoid misdiagnosis as lymphoma and unnecessary treatment. Notwithstanding, some indolent disorders, especially B-cell disorders, may give important morbidity that is not related to disease burden but related to auto-immune disease which may need treatment. Further, some of these lesions may, at various rates, ultimately progress to lymphoma. As such, the indolent clonal lymphoid disorders also give an insight into the earliest stages of clonal lymphoid disease that may increase our understanding of lymphoma, although much needs yet to be elucidated. In this article both B- and T-cell indolent clonal lymphoid disorders are reviewed. Not included in this review are lymphoid lesions that may be mistaken for lymphoma, but are not clonal, such as indolent T-lymphoblastic proliferation or marginal zone hyperplasia with immunoglobulin light chain restriction. Further, an emphasis has been given to clonal lymphoid lesions and therefore indolent plasma cell lesions have not been included. Also excluded is indolent lymphoma that may not need treatment but nonetheless requires more regular follow up. One may rightfully argue that there may be a gray zone between what constitutes an indolent clonal lymphoid disorder and an indolent lymphoma. This discussion is reflected in the different terminology used for some entities between editions of the WHO classification and between the Fifth Edition of the WHO Classification and the International Consensus Classification (ICC). The former has been used as a selection basis for this review, but cross-reference has been made to the ICC nomenclature when that differs as well as to the earlier Revised Fourth Edition of the WHO Classification (WHO-r4). For this reason, indolent T-cell lymphoma of the gastrointestinal tract (ICC: indolent clonal T-cell lymphoproliferative disorder of the gastrointestinal tract) is not included in this review.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"156 ","pages":"Article 105715"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964616","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":"Clinical use of circulating tumor DNA analysis in patients with lymphoma","authors":"Bettina Bisig ,&nbsp;Karine Lefort ,&nbsp;Sylvain Carras ,&nbsp;Laurence de Leval","doi":"10.1016/j.humpath.2024.105679","DOIUrl":"10.1016/j.humpath.2024.105679","url":null,"abstract":"<div><div>The analysis of circulating tumor DNA (ctDNA) in liquid biopsy specimens has an established role for the detection of predictive molecular alterations and acquired resistance mutations in several tumors. The low-invasiveness of this approach allows for repeated sampling and dynamic monitoring of disease evolution. Originating from the entire body tumor bulk, plasma-derived ctDNA reflects intra- and interlesional genetic heterogeneity. In the management of lymphoma patients, ctDNA quantification at various timepoints of the patient’s clinical history is emerging as a complementary tool that may improve risk stratification, assessment of treatment response and early relapse detection during follow-up, most prominently in patients with diffuse large B-cell lymphoma or classic Hodgkin lymphoma. While liquid biopsies have not yet entered standard-of-care treatment protocols in these settings, several trials have provided evidence that at least a subset of lymphoma patients may benefit from the introduction of liquid biopsies into daily clinical care. In parallel, continuous technological developments have enabled highly sensitive ctDNA assessment methods, which span from locus-specific techniques identifying single hotspot mutations, to sequencing panels and genome-wide approaches that explore broader genetic and epigenetic alterations. Here, we provide an overview of current methods and ongoing technical developments for ctDNA evaluation. We also summarize the most important data from a selection of clinical studies that have explored the clinical use of ctDNA in several lymphoma entities.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"156 ","pages":"Article 105679"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567876","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":"High-grade B-cell lymphomas: Double hit and non-double hit","authors":"Lianqun Qiu,&nbsp;L. Jeffrey Medeiros,&nbsp;Shaoying Li","doi":"10.1016/j.humpath.2024.105700","DOIUrl":"10.1016/j.humpath.2024.105700","url":null,"abstract":"<div><div>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 <em>MYC</em> and <em>BCL2</em> rearrangements, with or without <em>BCL6</em> rearrangements; and (2) HGBL, not otherwise specified (HGBL-NOS). WHO-HAEM5 excluded DLBCL/HGBL with concurrent <em>MYC</em> and <em>BCL6</em> 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 <em>MYC</em> and <em>BCL6</em> 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.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"156 ","pages":"Article 105700"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","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":"Burkitt lymphoma","authors":"Hong Fang,&nbsp;Wei Wang,&nbsp;L. Jeffrey Medeiros","doi":"10.1016/j.humpath.2024.105703","DOIUrl":"10.1016/j.humpath.2024.105703","url":null,"abstract":"<div><div>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 <em>MYC</em> 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, <em>IGH::MYC</em>. 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.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"156 ","pages":"Article 105703"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","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":"Bridging clinicopathologic features and genetics in follicular lymphoma: Towards enhanced diagnostic accuracy and subtype differentiation","authors":"Jan Bosch-Schips ,&nbsp;Xenia Parisi ,&nbsp;Fina Climent ,&nbsp;Francisco Vega","doi":"10.1016/j.humpath.2024.105676","DOIUrl":"10.1016/j.humpath.2024.105676","url":null,"abstract":"<div><div>Follicular lymphoma (FL) is a neoplasm that originates from germinal center B cells and typically forms at least a partial follicular pattern. Approximately 85% of FL cases harbor the t(14;18)(q32;q21)/<em>IGH::BCL2</em> which leads to the overexpression of BCL2. These cases are referred to as classic FL in the current World Health Organization classification [1]. These neoplasms often exhibit hallmark epigenetic deregulation due to recurrent mutations in genes such as <em>KMT2D</em>, <em>CREBBP</em>, and <em>EZH2,</em> with <em>KMT2D</em> and <em>CREBBP</em> considered founding events in FL lymphomagenesis. In contrast, about 15% of FL cases are negative for the t(14;18), which could present diagnostic challenges. These cases may lack the typical genetic markers and require careful pathological and molecular analysis for accurate diagnosis.</div><div>This review aims to provide an up-to-date pathology resource on FL, focusing on the pathological and molecular characteristics of these neoplasms. We will detail the diagnostic criteria for FL and emphasize the importance of genetic and mutational analyses in accurately characterizing and distinguishing FL subtypes. Furthermore, we will propose methodologies and best practices for the diagnostic work-up of FL to enhance diagnostic accuracy.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"156 ","pages":"Article 105676"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567497","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}