Human pathology最新文献

{"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":"https://doi.org/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":"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, Sophie-Marie Hornburg, Katharina Möller, Florian Viehweger, Ria Schlichter, Anne Menz, Andreas M Luebke, Martina Kluth, Claudia Hube-Magg, Andrea Hinsch, Maximilian Lennartz, Christian Bernreuther, Sören Weidemann, Patrick Lebok, Christoph Fraune, Guido Sauter, David Dum, Andreas H Marx, Ronald Simon, Natalia Gorbokon, Eike Burandt, Sarah Minner, Stefan Steurer, Till Krech, Frank Jacobsen, Till S Clauditz","doi":"10.1016/j.humpath.2024.105695","DOIUrl":"https://doi.org/10.1016/j.humpath.2024.105695","url":null,"abstract":"<p><p>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 >98% specificity in case of positivity for at least 2 of these markers.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105695"},"PeriodicalIF":2.7,"publicationDate":"2024-11-19","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":"","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":"https://doi.org/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":"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":"https://doi.org/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":"Genetic Validation of a TSC2 Immunohistochemistry Assay in TSC/mTOR-pathway Altered Renal Tumors.","authors":"Amir Akbari, Clarence Rachel Villanueva, Ondrej Hes, Sean R Williamson, Shivani Kandukuri, Shivani Sharma, Aggarwal Aditi, Kristyna Pivovarcikova, Pedram Argani, Sambit K Mohanty, Kaushal Asrani, Tamara L Lotan","doi":"10.1016/j.humpath.2024.105693","DOIUrl":"https://doi.org/10.1016/j.humpath.2024.105693","url":null,"abstract":"<p><p>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 TSC2 was 92% (11/12), while the negative predictive value (NPV) of intact TSC2 by IHC for lack of underlying pathogenic mutation in TSC2 was 81% (21/26). Intact TSC2 by IHC was 95% (21/22) specific for absence of underlying pathogenic TSC2 mutation. All the cases lacking TSC2 mutation with intact TSC2 protein had an underlying mutation in TSC1, MTOR or PIK3CA. Loss of TSC2 was 77% (10/13) sensitive for underlying TSC2 truncation mutations and 33% (1/3) sensitive for underlying TSC2 missense mutations. Overall, 73% (8/11) tumors with TSC2 IHC loss and underlying pathogenic alterations in TSC2 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.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"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, Nam Kim, Sholeh Jahanfard, Mark Sarno, Sam S Chang, Giovanna A Giannico","doi":"10.1016/j.humpath.2024.105682","DOIUrl":"https://doi.org/10.1016/j.humpath.2024.105682","url":null,"abstract":"<p><p>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<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 <0.001). The KRT17 H-score was significantly higher in pTa and pTinv compared to NL (p < 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. 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.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105682"},"PeriodicalIF":2.7,"publicationDate":"2024-11-14","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":"","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}

{"title":"Perinephric Myxoid Pseudotumor of Fat: A Series of 13 Cases and Literature Review.","authors":"Qingqing Wu, Ezra Baraban, John M Gross","doi":"10.1016/j.humpath.2024.105681","DOIUrl":"https://doi.org/10.1016/j.humpath.2024.105681","url":null,"abstract":"<p><p>Perinephric myxoid pseudotumor of fat (PMPF) is a recently described and rare retroperitoneal mass-forming lesion whose clinical significance chiefly involves mimicry of a variety of soft tissue tumors. For unknown reasons, it commonly occurs in male patients with underlying non-neoplastic renal diseases and/or type 2 diabetes (DMT2). A total of 55 cases have been reported in the literature. Recently, we have encountered 13 such masses with peculiar histologic features; thus, we sought to investigate our experience and review the clinicopathologic characteristics of the literature. Our series confirms that PMPF frequently occurs in adult male patients (11/13, 85%), with an average age of 66 years, and commonly co-occurs with renal disease, such as DMT2 (2/13, 15%), end-stage renal disease (ESRD) (5/13, 39%), renal cysts (4/13, 31%), concurrent or prior renal neoplasia (2/13; 15%), and myeloma/lymphoma (2/13; 15%). Histologic evaluation shows lipomatous masses commonly showing variable amounts of fat necrosis, myxoid degeneration, lymphoplasmacytic inflammation and lacking atypical hyperchromatic stromal spindle cells. Unusual histologic features include extramedullary hematopoiesis (1/13, 8%), hemosiderin deposition (4/13, 31%), and small wisps of mature smooth muscle (6/13, 46%). All cases tested were negative for MDM2 and did not show an increased ratio of IgG4⁺/IgG⁺ plasma cells. Our study confirms the clinical and pathologic features of PMPF and expands its histologic spectrum, underscoring the importance of this entity as a benign pseudotumor which should be included in the differential diagnosis of other fat-containing retroperitoneal masses, particularly well-differentiated liposarcoma.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105681"},"PeriodicalIF":2.7,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619270","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, Karine Lefort, Sylvain Carras, Laurence de Leval","doi":"10.1016/j.humpath.2024.105679","DOIUrl":"10.1016/j.humpath.2024.105679","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105679"},"PeriodicalIF":2.7,"publicationDate":"2024-11-02","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":"","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, Dennis P O'Malley","doi":"10.1016/j.humpath.2024.105678","DOIUrl":"10.1016/j.humpath.2024.105678","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105678"},"PeriodicalIF":2.7,"publicationDate":"2024-11-02","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}