Modern Pathology最新文献

{"title":"GLI1-Altered Mesenchymal Tumor—Multiomic Characterization of a Case Series and Patient-Level Meta-analysis of One Hundred Sixty-Seven Cases for Risk Stratification","authors":"Maximus C.F. Yeung ,&nbsp;Anthony P.Y. Liu ,&nbsp;Sio-In Wong ,&nbsp;Herbert H. Loong ,&nbsp;Tony W.H. Shek","doi":"10.1016/j.modpat.2024.100635","DOIUrl":"10.1016/j.modpat.2024.100635","url":null,"abstract":"<div><div><em>GLI1</em>-altered mesenchymal tumors have recently emerged as a distinctive group of neoplasms characterized by <em>GLI1</em> fusions or amplifications. Although there is clearly metastatic potential, the clinicopathologic features predicting for metastasis are currently unknown. Herein, we present 6 cases of <em>GLI1</em>-altered mesenchymal tumors with multiomics analysis. The median patient age was 50 years (range, 3-68 years). They arose from the extremities and trunk (2/6), head and neck region (2/6), and gastrointestinal tract (2/6). Histologically, they featured uniform round to ovoid cells with nested architecture and a rich vascular network. One case displayed abundant multinucleated giant cells. All stained positive for GLI1 (5/5) and CD56 (6/6). Molecularly, they featured <em>GLI1</em> fusion (5/6) and amplification (1/6). Fusion partners included <em>ACTB</em> (3/5), <em>TXNIP</em> (1/5), and novel <em>TUBA1B</em> (1/5). Multiomics analysis revealed they possessed distinct expression and epigenomic profiles. All the 6 cases had follow-up information, with 5 of them having no evidence of disease at a median follow-up of 30 months (range, 17.3-102 months), and 1 case being died of disease with regional neck lymph node and bilateral lung metastasis at 81.5 months of follow-up. By incorporating cases reported in the literature, we analyzed clinicopathologic features of a total of 167 cases predictive of malignant behavior. We found that size ≥6 cm and mitotic count ≥5 per 10 high-power fields are predictive of metastasis. Cases with both high-risk features had significantly poorer survival. This study expands the literature database of <em>GLI1</em>-altered mesenchymal tumors and identifies features that can be used for risk stratification.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 1","pages":"Article 100635"},"PeriodicalIF":7.1,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504278","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":"Clear Cell Stromal Tumor of the Lung: Clinicopathologic, Immunohistochemical, and Molecular Characterization of Eight Cases","authors":"Igor Odintsov ,&nbsp;Alexandra Isaacson ,&nbsp;Karen J. Fritchie ,&nbsp;Yin P. Hung ,&nbsp;Pooria Khoshnoodi ,&nbsp;Lynette M. Sholl ,&nbsp;Christopher D.M. Fletcher ,&nbsp;William J. Anderson","doi":"10.1016/j.modpat.2024.100632","DOIUrl":"10.1016/j.modpat.2024.100632","url":null,"abstract":"<div><div>Clear cell stromal tumor is a recently described mesenchymal neoplasm of the lung, characterized by spindle cells with variably clear-to-pale eosinophilic cytoplasm and prominent vascularity, as well as a recurrent <em>YAP1::TFE3</em> gene fusion in most cases. Diagnosis can be challenging given its rarity and the lack of supportive immunohistochemical (IHC) markers aside from TFE3. To date, less than 20 cases have been reported, and data on clinical behavior are also limited. Although most appear to be benign, aggressive behavior has been reported rarely. In this study, we present the largest multiinstitutional series of clear cell stromal tumor to date, comprising a total of 8 cases and including 6 previously unpublished cases. We investigate its clinicopathologic and genomic features, while also assessing the diagnostic use of IHC for YAP1 C-terminus. Five patients were men and 3 were women. The median age was 59 years (range: 35-84 years). In all cases, a <em>TFE3</em> rearrangement was demonstrated by either fluorescence in situ hybridization or DNA/RNA sequencing. In 7 tumors, the <em>YAP1</em>::<em>TFE3</em> fusion was identified by sequencing. We demonstrate that the combination of YAP1 C-terminus loss and TFE3 overexpression using IHC reliably predicts an underlying <em>YAP1::TFE3</em> fusion in these neoplasms and may be more sensitive than <em>TFE3</em> fluorescence in situ hybridization. Although the median follow-up time for our study was short (18 months, available in 7 cases), all cases pursued a benign clinical course, with no recurrences or metastases. Our study provides further characterization of this novel entity, supporting its wider recognition.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 1","pages":"Article 100632"},"PeriodicalIF":7.1,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470034","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":"Rapid on-site histology of lung and pleural biopsies using higher harmonic generation microscopy and artificial intelligence analysis.","authors":"Laura M G van Huizen, Max Blokker, Johannes M A Daniels, Teodora Radonic, Jan H von der Thüsen, Mitko Veta, Jouke T Annema, Marie Louise Groot","doi":"10.1016/j.modpat.2024.100633","DOIUrl":"https://doi.org/10.1016/j.modpat.2024.100633","url":null,"abstract":"<p><p>Lung cancer is both one of the most prevalent and lethal cancers. To improve health outcomes while reducing the healthcare burden, it becomes crucial to move towards early detection and cost-effective workflows. Currently there is no method for on-site rapid histological feedback on biopsies taken in diagnostic endoscopic or surgical procedures. Higher harmonic generation (HHG) microscopy is a laser-based technique that provides images of unprocessed tissue. Here, we report the feasibility of a HHG portable microscope in the clinical workflow in terms of acquisition time, image quality and diagnostic accuracy in suspected pulmonary and pleural malignancy. 109 biopsies of 47 patients were imaged and a biopsy overview image was provided within a median of 6 minutes after excision. The assessment by pathologists and an artificial intelligence (AI) algorithm showed that image quality was sufficient for a malignancy or non-malignancy diagnosis in 97% of the biopsies, and 87% of the HHG images were correctly scored by the pathologists. HHG is therefore an excellent candidate to provide rapid pathology outcome on biopsy samples enabling immediate diagnosis and (local) treatment.</p>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":" ","pages":"100633"},"PeriodicalIF":7.1,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470036","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":"Digital and Computational Pathology Applications in Bladder Cancer: Novel Tools Addressing Clinically Pressing Needs","authors":"João Lobo ,&nbsp;Bassel Zein-Sabatto ,&nbsp;Priti Lal ,&nbsp;George J. Netto","doi":"10.1016/j.modpat.2024.100631","DOIUrl":"10.1016/j.modpat.2024.100631","url":null,"abstract":"<div><div>Bladder cancer (BC) remains a major disease burden in terms of incidence, morbidity, mortality, and economic cost. Deciphering the intrinsic molecular subtypes and identification of key drivers of BC has yielded successful novel therapeutic strategies. Advances in computational and digital pathology are reshaping the field of anatomical pathology. This review offers an update on the most relevant computational algorithms in digital pathology that have been proposed to enhance BC management. These tools promise to enhance diagnostics, staging, and grading accuracy and streamline efficiency while advancing practice consistency. Computational applications that enable intrinsic molecular classification, predict response to neoadjuvant therapy, and identify targets of therapy are also reviewed.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 1","pages":"Article 100631"},"PeriodicalIF":7.1,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470035","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":"Spatial Profiling of Ovarian Clear Cell Carcinoma Reveals Immune-Hot Features","authors":"Ya-Ting Tai ,&nbsp;Wei-Chou Lin ,&nbsp;Jieru Ye ,&nbsp;Denis T.-H. Chen ,&nbsp;Ko-Chen Chen ,&nbsp;Duncan Y.-T. Wang ,&nbsp;Tuan Z. Tan ,&nbsp;Lin-Hung Wei ,&nbsp;Ruby Y.-J. Huang","doi":"10.1016/j.modpat.2024.100630","DOIUrl":"10.1016/j.modpat.2024.100630","url":null,"abstract":"<div><div>Ovarian clear cell carcinoma (OCCC) has a high incidence in Asia, with a frequent occurrence at an early stage, but without sufficient data on molecular stratification for high-risk patients. Recently, immune-hot features have been proposed as indicators of poor prognosis in early stage OCCC. Specific patterns of intratumoral heterogeneity associated with immune-hot features must be defined. NanoString Digital Spatial Profiling technology (Cold spring biotech corp.) was used to decipher the spatial distribution of the 18-plex protein panel. Regions of interest (ROIs) were collected based on the reference hematoxylin and eosin–stained morphology. Areas of illumination (AOIs) were defined according to the ROI segmentation using the fluorescence signals of the visualization markers pan-cytokeratin (PanCK), CD45, or DNA. Unsupervised hierarchical clustering of 595 AOIs from 407 ROIs showed that the PanCK segments expressed different combinations of immune markers, suggestive of immune mimicry. The following 3 immune-hot clusters were identified: granzyme B–high, immune signal-high , and immune-like cells; the following 2 immune-cold clusters were identified: fibronectin-high and immune checkpoint–high cells. In tumor samples at the International Federation of Gynecology and Obstetrics stage IC1/2 experiencing recurrence, there was an increased occurrence of PanCK+ AOIs with immune signal-high and immune-like cell groups in the papillary morphology surrounded by macrophage lineage tumor-infiltrating immune cells (TIIs). In contrast, for tumor samples at the International Federation of Gynecology and Obstetrics stage IC3/II with recurrence, PanCK+ AOIs were prevalent in the fibronectin-high group, particularly in those with a tubulocystic morphology surrounded by lymphoid lineage non-TIIs. Our study on the spatial profiling of early stage OCCC tumors revealed that the immune mimicry of tumor cells, presence of TIIs, and morphologic patterns were associated with recurrence, which switched during tumor progression.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 1","pages":"Article 100630"},"PeriodicalIF":7.1,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470037","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":"Validation of Metallothionein Immunohistochemistry as a Highly Sensitive Screening Test for Wilson Disease","authors":"Nadarra L. Stokes ,&nbsp;Ameya Patil ,&nbsp;Oyedele Adeyi ,&nbsp;Amarpreet Bhalla ,&nbsp;Ian Brown ,&nbsp;Kathleen Byrnes ,&nbsp;Julien Calderaro ,&nbsp;Diane Chen ,&nbsp;Wei Chen ,&nbsp;Caroline Cooper ,&nbsp;Deepti Dhall ,&nbsp;Wendy Frankel ,&nbsp;Gretchen Galliano Gooch ,&nbsp;Raul S. Gonzalez ,&nbsp;Suntrea Hammer ,&nbsp;Gillian Hale ,&nbsp;Stephen Lagana ,&nbsp;Catriona McKenzie ,&nbsp;Daniela S. Allende ,&nbsp;Roger K. Moreira ,&nbsp;Rondell P. Graham","doi":"10.1016/j.modpat.2024.100628","DOIUrl":"10.1016/j.modpat.2024.100628","url":null,"abstract":"<div><div>Wilson disease (WD) is a rare autosomal recessive condition with protean clinical manifestations that result from biallelic <em>ATP7B</em> mutations. However, nondestructive tissue tests to be applied clinically to tissue specimens are not widely available to effectively assess patients for possible WD. Previously, we showed that metallothionein (MTH) immunohistochemistry (IHC) has a high sensitivity and specificity for WD diagnosis and, thus, represents a potentially powerful diagnostic tool that can be used in routine histologic sections. This study aimed to validate this finding in a large cohort of bona fide patients with WD and to correlate metallothionein expression with other histologic features. We identified 91 cases of WD, which included 28 needle biopsies and 64 explants from 14 centers worldwide. Histologic features were evaluated, and a histopathological pattern was assigned to each case. All cases were evaluated with Masson trichrome and MTH IHC (clone UC1MT, Abcam) using a previously published technique. Liver tissues from chronic cholestatic diseases (n = 42) were used as controls. The median age of the cohort was 28.5 years. Of the 91 total cases, 83 were positive for MTH immunostain. In the controls, all 42 cases were negative for MTH immunostain. The sensitivity and specificity of MTH immunostain for WD were 91.20% and 100%, respectively. MTH IHC is a highly sensitive and specific cost-effective screening tool for WD. It can be used for patients across age groups, varied histologic patterns, and fibrosis stages. This marker could prove to be a valuable tool in the evaluation of patients with possible WD.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 1","pages":"Article 100628"},"PeriodicalIF":7.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391763","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":"Early Genetic Divergence of High-Grade Carcinomas Originating from Low-Grade Serous Ovarian Neoplasms","authors":"M. Herman Chui ,&nbsp;Qianqian Song ,&nbsp;Jiarun Zhu ,&nbsp;Yuchen Jiao ,&nbsp;Brant Wang ,&nbsp;Yeh Wang ,&nbsp;Tian-Li Wang ,&nbsp;Russell Vang ,&nbsp;Ie-Ming Shih","doi":"10.1016/j.modpat.2024.100629","DOIUrl":"10.1016/j.modpat.2024.100629","url":null,"abstract":"<div><div>The current paradigm implicates a fallopian tube precursor as the origin of most ovarian high-grade serous carcinomas (HGSCs). However, a rare subset of HGSCs develop via a distinct pathway from low-grade serous ovarian neoplasms (namely, serous borderline tumors and low-grade serous carcinoma). This alternate pathway for the development of HGSC and other poorly differentiated carcinomas of the ovary is not well understood. To elucidate the molecular pathogenesis and evolutionary trajectory of histologic transformation of low-grade serous neoplasms, we performed whole exome sequencing on microdissected low-grade and higher-grade components from 7 cases of serous borderline tumor or low-grade serous carcinoma associated with a synchronous or metachronous indeterminate/high-grade carcinoma. In most cases, there were relatively few somatic mutations shared between matched low-grade and higher-grade tumors compared with private mutations specific to each component (ie, phylogenetic trees with short trunks and long branches). Truncal mutations, present across all tumor samples from a given patient, included known drivers of low-grade serous neoplasms: <em>KRAS</em> (G12D, n = 4), <em>BRAF</em> (G469A, n = 1), <em>NF2</em> (n = 1), and <em>USP9X</em> (n = 1). Transformation to HGSC was associated with a <em>TP53</em> mutation with bi-allelic inactivation in 3 cases, all with severe nuclear atypia, and associated with genome-wide copy number alterations and allelic imbalances. <em>TP53</em>-wildtype tumors comprised a morphologic spectrum, which included indeterminate-grade serous carcinomas with moderate nuclear atypia and high mitotic activity, although lacking extensive chromosomal instability (n = 2) and poorly differentiated carcinomas (n = 2, including a high-grade Mullerian carcinoma and an undifferentiated carcinoma with sarcomatoid features). In summary, synchronous and metachronous low-grade serous neoplasms and higher-grade carcinomas are clonally related. Early genetic divergence, most evident in cases with <em>TP53</em> mutations, suggests that high-grade transformation may be a relatively early molecular event.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 1","pages":"Article 100629"},"PeriodicalIF":7.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400755","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":"POU4F3 Is a Sensitive and Specific Marker of Merkel Cell Carcinoma","authors":"Paweł Karpinski ,&nbsp;Javier E. Mendez-Pena ,&nbsp;Cheng-Lin Wu ,&nbsp;Ali Akalin ,&nbsp;Kristine M. Cornejo ,&nbsp;Yin P. Hung ,&nbsp;Mai P. Hoang","doi":"10.1016/j.modpat.2024.100627","DOIUrl":"10.1016/j.modpat.2024.100627","url":null,"abstract":"<div><div>Although of therapeutic importance, a single sensitive and specific immunostain to distinguish Merkel cell carcinoma (MCC) from mimics is not currently available. In addition, single tumor cells are difficult to detect in sentinel lymph node biopsy. Leveraging publicly available data sets of 9264 solid tumors and &gt;600,000 single-cell transcriptomes, we identified <em>POU4F3</em> to be a specific marker of MCC. Analyses of Pan-Cancer RNA bulk sequencing data of 24 tumor types from Tumor Cancer Genomic Atlas data sets as well as non-Tumor Cancer Genomic Atlas small cell lung carcinoma and MCC data sets confirmed <em>POU4F3</em> specificity for MCC. Single-cell RNA-sequencing analyses also confirmed the lack of <em>POU4F3</em> expression in lung small cell carcinoma as well as a variety of normal tissues. Nuclear POU4F3 immunohistochemical expression was noted in 98.7% of 153 MCCs and in only 1.7% of mimics (3 of 180 cases, including 95 small cell carcinomas, of which 55 were from lungs and the remainder from other sites). Three POU4F3-positive non-MCC cases were from lungs (2 cases) and vagina (1 case). All 153 tested MCC cases were negative for ASCL1, a key transcriptional regulator highly expressed in small cell lung carcinoma. NeuroD1 was seen in a subset of MCC cases (20.9%, 32/153). POU4F3 immunostain was performed on 29 sentinel lymph nodes, and strong POU4F3 nuclear expression facilitated the ease of metastasis detection, even single tumor cells. Our study built on prior works shows that POU4F3 is a sensitive and specific clinical marker of MCC.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 1","pages":"Article 100627"},"PeriodicalIF":7.1,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350234","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":"A Comparative Genomic Study of Conventional and Undifferentiated Melanoma","authors":"Grant M. Fischer,&nbsp;Navin R. Mahadevan,&nbsp;Jason L. Hornick,&nbsp;Christopher D.M. Fletcher,&nbsp;Eleanor Russell-Goldman","doi":"10.1016/j.modpat.2024.100626","DOIUrl":"10.1016/j.modpat.2024.100626","url":null,"abstract":"<div><div>Undifferentiated melanoma, defined as melanoma that has lost all usual phenotypic and immunohistochemical characteristics of conventional melanoma, can pose significant diagnostic challenges. Molecular studies have advanced our understanding of undifferentiated melanoma by demonstrating that a subset of these tumors harbors known melanoma driver alterations in genes such as <em>BRAF</em>, <em>NRAS</em>, and <em>NF1</em>. However, there is a paucity of data describing genetic alterations that may distinguish undifferentiated melanoma from conventional melanoma. In this study, we directly compared the genomic profiles of undifferentiated melanoma to a cohort of conventional melanomas, including 14 undifferentiated melanoma cases (comprised of 2 primary cases, 2 cutaneous recurrences, and 10 metastases) and a cohort of 127 conventional melanomas including primary, recurrent, and metastatic cases. Targeted sequencing of 447 cancer-associated genes was performed, including identification of mutations and copy number alterations. <em>NRAS</em> was the most frequent melanoma driver in undifferentiated melanoma (8/14 cases, 57%), although notably, only 1 undifferentiated melanoma harbored an <em>NRAS</em> Q61R mutation. Compared with the conventional melanoma cohort, undifferentiated melanoma demonstrated statistically significant enrichment of pathogenic activating <em>RAC1</em> mutations (6/14 total cases, 43%), including P29S (4/6 cases), P29L (1/6 cases), and D11E (1/6 cases). In addition to providing insight into the molecular pathogenesis of undifferentiated melanoma, these findings also suggest that RAS Q61R immunohistochemistry may have limited utility for its diagnosis. The presence of recurrent <em>RAC1</em> mutations in undifferentiated melanoma is also notable as these alterations may contribute to mitogen-activated protein kinase pathway–targeted therapy resistance. Furthermore, the <em>RAC1</em> alterations identified in this cohort have been shown to drive a melanocytic to mesenchymal switch in melanocytes, offering a possible explanation for the undifferentiated phenotype of these melanomas.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"37 12","pages":"Article 100626"},"PeriodicalIF":7.1,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350230","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":"DNA Methylation Profiling of Salivary Gland Tumors Supports and Expands Conventional Classification","authors":"Philipp Jurmeister ,&nbsp;Maximilian Leitheiser ,&nbsp;Alexander Arnold ,&nbsp;Emma Payá Capilla ,&nbsp;Liliana H. Mochmann ,&nbsp;Yauheniya Zhdanovic ,&nbsp;Konstanze Schleich ,&nbsp;Nina Jung ,&nbsp;Edgar Calderon Chimal ,&nbsp;Andreas Jung ,&nbsp;Jörg Kumbrink ,&nbsp;Patrick Harter ,&nbsp;Niklas Prenißl ,&nbsp;Sefer Elezkurtaj ,&nbsp;Luka Brcic ,&nbsp;Nikolaus Deigendesch ,&nbsp;Stephan Frank ,&nbsp;Jürgen Hench ,&nbsp;Sebastian Försch ,&nbsp;Gerben Breimer ,&nbsp;Stephan Ihrler","doi":"10.1016/j.modpat.2024.100625","DOIUrl":"10.1016/j.modpat.2024.100625","url":null,"abstract":"<div><div>Tumors of the major and minor salivary glands histologically encompass a diverse and partly overlapping spectrum of frequent diagnostically challenging neoplasms. Despite recent advances in molecular testing and the identification of tumor-specific mutations or gene fusions, there is an unmet need to identify additional diagnostic biomarkers for entities lacking specific alterations. In this study, we collected a comprehensive cohort of 363 cases encompassing 20 different salivary gland tumor entities and explored the potential of DNA methylation to classify these tumors. We were able to show that most entities show specific epigenetic signatures and present a machine learning algorithm that achieved a mean balanced accuracy of 0.991. Of note, we showed that cribriform adenocarcinoma is epigenetically distinct from classical polymorphous adenocarcinoma, which could support risk stratification of these tumors. Myoepithelioma and pleomorphic adenoma form a uniform epigenetic class, supporting the theory of a single entity with a broad but continuous morphologic spectrum. Furthermore, we identified a histomorphologically heterogeneous but epigenetically distinct class that could represent a novel tumor entity. In conclusion, our study provides a comprehensive resource of the DNA methylation landscape of salivary gland tumors. Our data provide novel insight into disputed entities and show the potential of DNA methylation to identify new tumor classes. Furthermore, in future, our machine learning classifier could support the histopathologic diagnosis of salivary gland tumors.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"37 12","pages":"Article 100625"},"PeriodicalIF":7.1,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350232","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}