Modern Pathology最新文献

{"title":"Computer-Based Evaluation of α-Synuclein Pathology in Multiple System Atrophy as a Novel Tool to Recognize Disease Subtypes","authors":"Ain Kim ,&nbsp;Koji Yoshida ,&nbsp;Gabor G. Kovacs ,&nbsp;Shelley L. Forrest","doi":"10.1016/j.modpat.2024.100533","DOIUrl":"10.1016/j.modpat.2024.100533","url":null,"abstract":"<div><p>Multiple system atrophy (MSA) is a neurodegenerative disorder with variable disease course and distinct constellations of clinical (cerebellar [MSA-C] or parkinsonism [MSA-P]) and pathological phenotypes, suggestive of distinct α-synuclein (αSyn) strains. Neuropathologically, MSA is characterized by the accumulation of αSyn in oligodendrocytic glial cytoplasmic inclusions (GCI). Using a novel computer-based method, this study quantified the size of GCIs, density of all αSyn pathology, density of only the GCIs, and number of GCIs in MSA cases (n = 20). The putamen and cerebellar white matter were immunostained with the disease-associated 5G4 anti-αSyn antibody. Following digital scanning and image processing, total 5G4-immunoreactive pathology (ie, neuronal, neuritic, and glial) and GCIs were optically dissected for inclusion size and density measurement and then evaluated applying a novel computer-based method using ImageJ. GCI size varied between cases and brain regions (<em>P</em> &lt; .0001), and heterogeneity in the density of all αSyn pathology including the density and number of GCIs were observed between regions and across cases, where MSA-C cases had a significantly higher density of all αSyn pathology in the cerebellar white matter (<em>P</em> = .049). Some region-specific morphologic variables inversely correlated with the age of onset and death, suggestive of an underlying aging-related cellular mechanism. Unsupervised K-means cluster analysis classified MSA cases into 3 distinct groups based on region-specific morphologic variables. In conclusion, we developed a novel computer-based method that is easily accessible, providing a first step to developing artificial intelligence–based evaluation strategies for large scale comparative studies. Our observations on the variability of morphologic variables between brain regions and cases highlight (1) the importance of computer-based approaches to detect features not considered in the routine diagnostic practice, and (2) novel aspects for the identification of previously unrecognized MSA subtypes that do not necessarily reflect the current clinical classification of MSA-C or MSA-P.</p></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0893395224001133/pdfft?md5=64f780089a04acaac62b557523c8fd57&pid=1-s2.0-S0893395224001133-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clonal Dynamics and Relapse Risk Revealed by High-Sensitivity FLT3-Internal Tandem Duplication Detection in Acute Myeloid Leukemia","authors":"","doi":"10.1016/j.modpat.2024.100534","DOIUrl":"10.1016/j.modpat.2024.100534","url":null,"abstract":"<div><p>The ability to detect low-level disease is key to our understanding of clonal heterogeneity in acute myeloid leukemia (AML) and residual disease that elude conventional assays and seed relapse. We developed a high-sensitivity next-generation sequencing (HS-NGS) clinical assay, able to reliably detect low levels (1 × 10⁻⁵) of <em>FLT3</em>-ITD, a frequent, therapeutically targetable and prognostically relevant mutation in AML. By applying this assay to 289 longitudinal samples from 62 patients at initial diagnosis and/or clinical follow-up (mean follow-up of 22 months), we reveal the frequent occurrence of <em>FLT3</em>-ITD subclones at diagnosis and demonstrate a significantly decreased relapse risk when <em>FLT3</em>-ITD is cleared after induction or thereafter. We perform pairwise sequencing of diagnosis and relapse samples from 23 patients to uncover more detailed patterns of <em>FLT3</em>-ITD clonal evolution at relapse than is detectable by less-sensitive assays. Finally, we show that rising ITD level during consecutive biopsies is a harbinger of impending relapse. Our findings corroborate the emerging clinical utility of high-sensitivity <em>FLT3</em>-ITD testing and expands our understanding of clonal dynamics in <em>FLT3</em>-ITD–positive AML.</p></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0893395224001145/pdfft?md5=f479eb94370104e6c0d1c3ac5762cc87&pid=1-s2.0-S0893395224001145-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression and Prognostic Significance of LAG-3, TIGIT, VISTA, and IDO1 in Endometrial Serous Carcinoma","authors":"Hao Chen ,&nbsp;Kyle Molberg ,&nbsp;Kelley Carrick ,&nbsp;Shuang Niu ,&nbsp;Glorimar Rivera Colon ,&nbsp;Katja Gwin ,&nbsp;Cheryl Lewis ,&nbsp;Jayanthi Lea ,&nbsp;Vandana Panwar ,&nbsp;Wenxin Zheng ,&nbsp;Diego H. Castrillon ,&nbsp;Elena Lucas","doi":"10.1016/j.modpat.2024.100532","DOIUrl":"10.1016/j.modpat.2024.100532","url":null,"abstract":"<div><p>Endometrial serous carcinoma (ESC) is an uncommon, aggressive type of endometrial cancer. While immune checkpoint blockade has emerged as a promising treatment option for endometrial carcinomas, research on the expression of immune checkpoints that could serve as prospective immunotherapy targets in ESC is limited. We examined the prevalence and prognostic value of lymphocyte-activation gene 3 (LAG-3), T-cell immunoglobulin and ITIM domain (TIGIT), V-domain immunoglobulin (Ig) suppressor of T-cell activation (VISTA), and indoleamine 2,3-dioxygenase 1 in 94 cases of ESC and correlated their expression with CD8+ and FOXP3+ tumor-infiltrating lymphocytes (TILs). We observed a positive correlation among LAG-3, TIGIT, and VISTA expressed on immune cells, and among these markers and CD8+ and FOXP3+ TIL densities. In Kaplan–Meier survival analysis, tumors with high levels of LAG-3 and TIGIT expression had better progression-free survival (PFS) and overall survival (OS) than those with lower levels of expression (LAG-3: PFS, <em>P</em> = .03, OS, <em>P</em> = .04; TIGIT: PFS, <em>P</em> = .01, OS, <em>P</em> = .009). In multivariate analysis, only high TIGIT expression was of independent prognostic value for better OS. VISTA expression in immune or tumor cells, and indoleamine 2,3-dioxygenase 1 expression in tumor cells, did not show a significant association with survival. Our data indicate that LAG-3, TIGIT, and VISTA immune checkpoints have roles in the microenvironment of ESC, and their expression patterns highlight the complex interactions among the different components of this system. High levels of these markers, together with high CD8+ TIL, suggest the potential immunogenicity of a subset of these tumors. Further studies are needed to elucidate the roles of various immune components in the ESC microenvironment and their association with intrinsic tumor properties.</p></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0893395224001121/pdfft?md5=92aaa9f50937db9bb2c5c656ca7b0a42&pid=1-s2.0-S0893395224001121-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep Learning for Histopathological Assessment of Esophageal Adenocarcinoma Precursor Lesions","authors":"Michel Botros ,&nbsp;Onno J. de Boer ,&nbsp;Bryan Cardenas ,&nbsp;Erik J. Bekkers ,&nbsp;Marnix Jansen ,&nbsp;Myrtle J. van der Wel ,&nbsp;Clara I. Sánchez ,&nbsp;Sybren L. Meijer","doi":"10.1016/j.modpat.2024.100531","DOIUrl":"10.1016/j.modpat.2024.100531","url":null,"abstract":"<div><p>Histopathological assessment of esophageal biopsies is a key part in the management of patients with Barrett esophagus (BE) but prone to observer variability and reliable diagnostic methods are needed. Artificial intelligence (AI) is emerging as a powerful tool for aided diagnosis but often relies on abstract test and validation sets while real-world behavior is unknown. In this study, we developed a 2-stage AI system for histopathological assessment of BE-related dysplasia using deep learning to enhance the efficiency and accuracy of the pathology workflow. The AI system was developed and trained on 290 whole-slide images (WSIs) that were annotated at glandular and tissue levels. The system was designed to identify individual glands, grade dysplasia, and assign a WSI-level diagnosis. The proposed method was evaluated by comparing the performance of our AI system with that of a large international and heterogeneous group of 55 gastrointestinal pathologists assessing 55 digitized biopsies spanning the complete spectrum of BE-related dysplasia. The AI system correctly graded 76.4% of the WSIs, surpassing the performance of 53 out of the 55 participating pathologists. Furthermore, the receiver-operating characteristic analysis showed that the system’s ability to predict the absence (nondysplastic BE) versus the presence of any dysplasia was with an area under the curve of 0.94 and a sensitivity of 0.92 at a specificity of 0.94. These findings demonstrate that this AI system has the potential to assist pathologists in assessment of BE-related dysplasia. The system’s outputs could provide a reliable and consistent secondary diagnosis in challenging cases or be used for triaging low-risk nondysplastic biopsies, thereby reducing the workload of pathologists and increasing throughput.</p></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S089339522400111X/pdfft?md5=9a67368b849f28fe9d419b84414e9974&pid=1-s2.0-S089339522400111X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-Related Clusters and Favorable Immune Phenotypes in Breast Cancer of the Young Patients","authors":"Lise Martine Ingebriktsen ,&nbsp;Amalie Abrahamsen Svanøe ,&nbsp;Anna Kristine Myrmel Sæle ,&nbsp;Rasmus Olai Collett Humlevik ,&nbsp;Karen Toska ,&nbsp;May Britt Kalvenes ,&nbsp;Turid Aas ,&nbsp;Anette Heie ,&nbsp;Cecilie Askeland ,&nbsp;Gøril Knutsvik ,&nbsp;Ingunn Marie Stefansson ,&nbsp;Lars Andreas Akslen ,&nbsp;Erling Andre Hoivik ,&nbsp;Elisabeth Wik","doi":"10.1016/j.modpat.2024.100529","DOIUrl":"10.1016/j.modpat.2024.100529","url":null,"abstract":"<div><p>Breast cancer (BC) patients aged &lt;40 years at diagnosis experience aggressive disease and poorer survival compared with women diagnosed with BC at 40 to 49 years, but the age-related biology is described to little extent. Here, we explored transcriptional alterations in BC to gain better understanding of age-related tumor biology. We studied a subset of the Bergen in-house cohort (n = 127; age range, 26-49 years) and used the NanoString Breast Cancer 360 expression panel on formalin-fixed paraffin-embedded BC tissue, and publicly available global BC messenger RNA expression data (n = 204, age range, 22-49 years), to explore differentially expressed genes between the young (age &lt;40 years) and older (age 40-49 years) patients. Unsupervised hierarchical clustering was applied to identify gene expression–based patient clusters. We applied established computational approaches to define the PAM50 subtypes, risk of recurrence scores (ROR), and risk groups and to infer the proportions of 22 immune cell types from bulk gene expression profiles of patients aged &lt;50 years at BC diagnosis. Differentially expressed genes and gene sets were investigated using OncoEnrichR and g:Profiler to describe functional profiles and pathway enrichment. We identified 4 age-related patient clusters presenting distinct characteristics of PAM50 subtypes and ROR profiles, which demonstrated independent prognostic value when adjusted for traditional clinicopathologic variables and the known molecular subtypes. Our findings showed better survival than expected in the basal-enriched cluster 2 and in triple-negative and basal-like BC. Deconvolution analyses of immunophenotypes indicated higher levels of M0 and M1 macrophages than M2 macrophages in subsets of young BC. Our approach identifies age-based patient clusters with distinct clinicopathologic profiles, to a large extent overlapping with the PAM50 subtypes, although with independent prognostic values in multivariate survival analyses. The patient clusters provided new insight in the immune cell distribution across tumor subtypes, potentially contributing to survival differences between the clusters and the molecular subtypes and indicating age-related mechanisms improving outcome. Our study confirms the applicability of ROR as a valid prognosticator also in a young BC cohort.</p></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0893395224001091/pdfft?md5=44fb1f8e76290c711a7c8d9ad6c4ddc0&pid=1-s2.0-S0893395224001091-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141174316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breast Cancer With HER2 Immunohistochemical Score 2 and Average HER2 Signals/Cell 6 or More and HER2/CEP17 Ratio Less Than 2 ('ISH Group 3'): A Multiinstitutional Cohort Analysis Emphasizing Outcome and Molecular Subtype","authors":"Rana Ajabnoor ,&nbsp;Gloria Zhang ,&nbsp;Yan Hu ,&nbsp;Yuan Gao ,&nbsp;Brian S. Finkelman ,&nbsp;Bradley M. Turner ,&nbsp;Sha Yi ,&nbsp;Ajay Dhakal ,&nbsp;William Audeh ,&nbsp;Zaibo Li ,&nbsp;Xiaoxian Li ,&nbsp;David G. Hicks ,&nbsp;Huina Zhang","doi":"10.1016/j.modpat.2024.100530","DOIUrl":"10.1016/j.modpat.2024.100530","url":null,"abstract":"<div><p>Breast cancer (BC) with average human epidermal growth factor receptor 2 (HER2) signals/cell ≥6 and HER2/chromosome enumeration probe 17 (CEP17) ratio &lt;2 (in situ hybridization [ISH] group 3) is very rare, accounting for 0.4% to 3.0% of cases sent for the dual-probe ISH assay. Although such patients are currently eligible for treatment with HER2-targeted therapy, their characteristics and outcomes remain poorly understood. Sixty-two BCs with equivocal HER2 immunohistochemical score (2+) and reflex ISH group 3 results were identified across 4 institutions. Available clinicopathologic characteristics, MammaPrint and BluePrint molecular results, and follow-up information were retrospectively analyzed. Most BCs with HER2 equivocal immunohistochemical and ISH group 3 results were histologic grade 2 or 3 (100%), estrogen receptor (ER) positive (90.3%), with an average HER2 signals/cell of 7.3. Molecular profiles revealed that 80% (16/20) of tumors were luminal subtypes, and HER2 molecular subtype was identified in 10% of tumors (2/20). Twelve (19.4%) out of 62 patients developed local recurrence and/or distant metastasis with a median follow-up of 50 months. One (10%) of 10 patients achieved pathologic complete response after neoadjuvant chemotherapy. Forty-nine (79%) out of 62 patients completed anti-HER2 agents, and exploratory analysis showed no statistically significant difference in disease outcomes between patients who completed anti-HER2 treatment and those who did not. Univariate analysis revealed advanced clinical stage, and ER/progesterone receptor negativity was associated with unfavorable disease outcomes, and exploratory multivariate analysis demonstrated that clinical stage was the most significant factor associated with disease outcomes in the studied population. These findings increase our understanding of this rare, but clinically important HER2 category. Large-scale prospective randomized studies are needed to further evaluate the role of perioperative HER2-targeted therapy in this patient population.</p></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141174435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methylation Analysis to Detect CIN3+ in High-Risk Human Papillomavirus-Positive Self-Samples From the Population-Based Cervical Cancer Screening Program","authors":"Jolien de Waard ,&nbsp;Arkajyoti Bhattacharya ,&nbsp;Martine T. de Boer ,&nbsp;Bettien M. van Hemel ,&nbsp;Martha D. Esajas ,&nbsp;Karin M. Vermeulen ,&nbsp;Geertruida H. de Bock ,&nbsp;Ed Schuuring ,&nbsp;G. Bea A. Wisman","doi":"10.1016/j.modpat.2024.100528","DOIUrl":"10.1016/j.modpat.2024.100528","url":null,"abstract":"<div><p>Since 2017, a self-sampling device has been introduced to the Dutch population-based screening program to enable higher participation rates. However, routine triage cytology cannot be performed on self-sampling material. Methylation is an alternative triage method that can be performed directly on DNA extracted from self-samples. Recently, we tested a set of 15 published cervical intraepithelial neoplasia grade 3 or worse (CIN3+)-specific methylation markers and found a panel of 3 markers with a sensitivity of 82% and a specificity of 74%. In this study, we determined the sensitivity and specificity of 2 commercial assays using quantitative methylation-specific PCR. DNA from the same cohort of high-risk human papillomavirus-positive self-sampled material obtained through the population-based screening program in the North of the Netherlands from women with CIN2 or less (&lt;CIN3, n = 208) and women with CIN3+ (n = 96) was used. The QIAsure methylation test (consisting of 2 methylation markers) showed a sensitivity of 65% and a specificity of 72%, whereas the Gyntect assay (consisting of 6 methylation markers) showed a sensitivity of 59% and a specificity of 91% for CIN3+. When we compared all individual 23 methylation markers, receiver operating characteristic analysis showed an area under the curve of ≥0.7 for 11 of 23 markers (<em>P</em> &lt; .001). By model-based recursive partitioning and robustness analysis, we found a panel with a better sensitivity compared with QIAsure and Gyntect (<em>P</em> &lt; .001). This new panel, consisting of <em>ITGA4</em>, <em>ASCL1</em>, and <em>FAM19A4,</em> has a sensitivity of 84% and a specificity of 70%, similar to our previously identified panel (<em>ANKRD18CP</em>, <em>LHX8</em>, and <em>EPB41L3</em>). Thus, in addition to our previously identified panel, the combination of <em>ITGA4</em>, <em>ASCL1</em>, and <em>FAM19A4</em> showed good diagnostic performance and potentially can replace cytology, thereby avoiding additional doctor visits for many women worldwide and reducing the time for decision making for referral to the gynecologist.</p></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S089339522400108X/pdfft?md5=7f039bde8c816265f35e7c8861ad19d9&pid=1-s2.0-S089339522400108X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141174599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Insights Into the International Association for the Study of Lung Cancer Grading System for Lung Adenocarcinoma","authors":"Kay See Tan PhD ,&nbsp;Allison Reiner MS ,&nbsp;Katsura Emoto MD, PhD ,&nbsp;Takashi Eguchi MD, PhD ,&nbsp;Yusuke Takahashi MD, PhD ,&nbsp;Rania G. Aly MD, PhD ,&nbsp;Natasha Rekhtman MD, PhD ,&nbsp;Prasad S. Adusumilli MD ,&nbsp;William D. Travis MD","doi":"10.1016/j.modpat.2024.100520","DOIUrl":"10.1016/j.modpat.2024.100520","url":null,"abstract":"<div><p>The new grading system for lung adenocarcinoma proposed by the International Association for the Study of Lung Cancer (IASLC) defines prognostic subgroups on the basis of histologic patterns observed on surgical specimens. This study sought to provide novel insights into the IASLC grading system, with particular focus on recurrence-specific survival (RSS) and lung cancer–specific survival among patients with stage I adenocarcinoma. Under the IASLC grading system, tumors were classified as grade 1 (lepidic predominant with &lt;20% high-grade patterns [micropapillary, solid, and complex glandular]), grade 2 (acinar or papillary predominant with &lt;20% high-grade patterns), or grade 3 (≥20% high-grade patterns). Kaplan-Meier survival estimates, pathologic features, and genomic profiles were investigated for patients whose disease was reclassified into a higher grade under the IASLC grading system on the basis of the hypothesis that they would strongly resemble patients with predominant high-grade tumors. Overall, 423 (29%) of 1443 patients with grade 1 or 2 tumors classified based on the predominant pattern–based grading system had their tumors upgraded to grade 3 based on the IASLC grading system. The RSS curves for patients with upgraded tumors were significantly different from those for patients with grade 1 or 2 tumors (log-rank <em>P</em> &lt; .001) but not from those for patients with predominant high-grade patterns (<em>P</em> = .3). Patients with upgraded tumors had a similar incidence of visceral pleural invasion and spread of tumor through air spaces as patients with predominant high-grade patterns. In multivariable models, the IASLC grading system remained significantly associated with RSS and lung cancer–specific survival after adjustment for aggressive pathologic features such as visceral pleural invasion and spread of tumor through air spaces. The IASLC grading system outperforms the predominant pattern–based grading system and appropriately reclassifies tumors into higher grades with worse prognosis, even after other pathologic features of aggressiveness are considered.</p></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0893395224001005/pdfft?md5=e643269bd407bc284267ffcaa2c77971&pid=1-s2.0-S0893395224001005-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clonal Hematopoiesis and Bone Marrow Infiltration in Patients With Follicular Helper T-Cell Lymphoma of Angioimmunoblastic Type","authors":"Lennart Harland ,&nbsp;Vanessa Borgmann ,&nbsp;Franziska Otto ,&nbsp;Mathis Overkamp ,&nbsp;Irina Bonzheim ,&nbsp;Falko Fend ,&nbsp;Leticia Quintanilla-Martinez ,&nbsp;Dominik Nann","doi":"10.1016/j.modpat.2024.100519","DOIUrl":"10.1016/j.modpat.2024.100519","url":null,"abstract":"<div><p>Follicular helper T-cell (TFH) lymphoma harbors recurrent mutations of <em>RHOA</em>^G17V, <em>IDH2</em>^R172, <em>TET2</em>, and <em>DNMT3A</em>. <em>TET2</em> and <em>DNMT3A</em> mutations are the most frequently affected genes in clonal hematopoiesis (CH). The aim of our study was to investigate the frequency of CH in bone marrow biopsies (BMB) of TFH/angioimmunoblastic T-cell lymphoma (TFH-AITL) patients and its association with myeloid neoplasms. A total of 29 BMB from 22 patients with a diagnosis of TFH–AITL were analyzed by next-generation sequencing (NGS) with a custom panel. Morphologically, 5 BMB revealed that TFH–AITL infiltrates of &gt;5% of bone marrow (BM) cellularity confirmed in 4 cases by NGS-based T-cell clonality. <em>IDH2</em>^R172 was demonstrated only in 1 (3%) of 29, and <em>RHOA</em>^G17V in 2 (7%) of 29 samples. <em>TET2</em> and <em>DNMT3A</em> were identified in 24 (83%) of 29 and 17 (59%) of 29 BMB, respectively. In the parallel lymph node the frequencies of mutations were 27% (<em>IDH2</em>^R172), 64% (<em>RHOA</em>^G17V), 86% (<em>TET2</em>), and 50% (<em>DNMT3A</em>). <em>TET2</em> and/or <em>DNMT3A</em> mutations identical in lymph node and BMB were present in 18 (82%) of 22 patients, regardless of BM infiltration. In 3 cases the CH mutations were detected 13, 41, and 145 months before TFH–AITL diagnosis. Cases with <em>TET2/DNMT3A</em> mutations and BM variant allele frequencies &gt;40% (7/18, 39%) showed lower blood counts. However, only low platelet count was statistically significant (<em>P</em> = .024). Myeloid neoplasms and/or myelodysplastic syndrome-related mutations were identified in 4 cases (4/22; 18%); all with high <em>TET2</em> variant allele frequencies (&gt;40%; <em>P</em> = .0114). In conclusion, CH is present in 82% of TFH–AITL and can be demonstrated up to 145 months before TFH–AITL diagnosis. NGS T-cell clonality analysis is an excellent tool to confirm TFH–AITL BM infiltration. Concurrent myeloid neoplasms were identified in 18% of the cases and were associated with <em>TET2</em> mutations with high allelic burden (&gt;40%). We demonstrated that myeloid neoplasms might occur simultaneously or precede the diagnosis of TFH lymphoma.</p></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0893395224000991/pdfft?md5=8e7e9df4bc35b4e1648ad9940e77c56a&pid=1-s2.0-S0893395224000991-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Moving Forward on Tumor Pathology Research Reporting: A Guide for Pathologists From the World Health Organization Classification of Tumors Living Evidence Gap Map by Tumour Type Group","authors":"Richard Colling ,&nbsp;Iciar Indave ,&nbsp;Javier Del Aguilla ,&nbsp;Ramon Cierco Jimenez ,&nbsp;Fiona Campbell ,&nbsp;Magdalena Chechlinska ,&nbsp;Magdalena Kowalewska ,&nbsp;Stefan Holdenrieder ,&nbsp;Inga Trulson ,&nbsp;Karolina Worf ,&nbsp;Marina Pollán ,&nbsp;Elena Plans-Beriso ,&nbsp;Beatriz Pérez-Gómez ,&nbsp;Oana Craciun ,&nbsp;Ester García-Ovejero ,&nbsp;Irmina Maria Michalek ,&nbsp;Kateryna Maslova ,&nbsp;Grzegorz Rymkiewicz ,&nbsp;Joanna Didkowska ,&nbsp;Puay Hoon Tan ,&nbsp;Ian A. Cree","doi":"10.1016/j.modpat.2024.100515","DOIUrl":"10.1016/j.modpat.2024.100515","url":null,"abstract":"<div><p>Evidence-based medicine (EBM) can be an unfamiliar territory for those working in tumor pathology research, and there is a great deal of uncertainty about how to undertake an EBM approach to planning and reporting histopathology-based studies. In this article, reviewed and endorsed by the Word Health Organization International Agency for Research on Cancer’s International Collaboration for Cancer Classification and Research, we aim to help pathologists and researchers understand the basics of planning an evidence-based tumor pathology research study, as well as our recommendations on how to report the findings from these. We introduce some basic EBM concepts, a framework for research questions, and thoughts on study design and emphasize the concept of reporting standards. There are many study-specific reporting guidelines available, and we provide an overview of these. However, existing reporting guidelines perhaps do not always fit tumor pathology research papers, and hence, here, we collate the key reporting data set together into one generic checklist that we think will simplify the task for pathologists. The article aims to complement our recent hierarchy of evidence for tumor pathology and glossary of evidence (study) types in tumor pathology. Together, these articles should help any researcher get to grips with the basics of EBM for planning and publishing research in tumor pathology, as well as encourage an improved standard of the reports available to us all in the literature.</p></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0893395224000954/pdfft?md5=9d39147cd941fd31d0a90056f6918b97&pid=1-s2.0-S0893395224000954-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141029943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}