Modern Pathology最新文献

{"title":"Clinicopathologic Characteristics and Follow-Up Outcomes of Invasive Breast Carcinoma With Different Positive HER2 Fluorescence In Situ Hybridization Patterns: Experience From a Single Academic Institution","authors":"Zaibo Li,&nbsp;Yan Hu,&nbsp;Dan Jones,&nbsp;Weiqiang Zhao,&nbsp;Gary Tozbikian,&nbsp;Anil V. Parwani","doi":"10.1016/j.modpat.2024.100637","DOIUrl":"10.1016/j.modpat.2024.100637","url":null,"abstract":"<div><div>Human epidermal growth factor receptor 2 (HER2)-positive breast carcinoma (BC) encompasses a spectrum of molecular subtypes, characterized by varying <em>HER2/CEP17</em> ratios and <em>HER2</em> copy numbers, influencing responses to anti-HER2 therapy. This study stratified <em>HER2</em> fluorescence in situ hybridization (FISH)-positive patients into 3 distinct groups—group 1 with high copy number (G1-HC: ratio ≥2, copy number ≥6), group 1 with low copy number (G1-LC: ratio ≥2, copy number ≥4 and &lt;6), and group 3 (G3: ratio &lt;2.0, copy number ≥6.0)—and evaluated their clinicopathologic features, response to anti-HER2 therapy, and outcomes. In a cohort of 2702 continuous primary BCs, G1-HC BCs accounted for 304 cases (11.3%), G1-LC for 37 cases (1.4%), and G3 for 75 cases (2.8%). G1-HC BCs were associated with younger age, higher tumor grade, and estrogen receptor negativity compared with G1-LC BCs. Furthermore, G1-HC BCs exhibited increased progesterone receptor negativity and HER2 immunohistochemistry 3+ compared with G1-LC and G3 BCs. Analysis of the subgroup of HER2 immunohistochemistry 2+-only cases (n = 166) showed similar results. Notably, G1-HC patients exhibited significantly enhanced responses to anti-HER2 neoadjuvant chemotherapy compared with G1-LC and G3 patients. Conversely, G1-LC patients displayed a lower likelihood of disease-free status compared with G1-HC and G3 patients, albeit with no significant differences in overall survival, distant metastasis, or local recurrence among the groups. These findings offer valuable clinicopathologic insights into different <em>HER2</em> FISH positive subgroups, potentially informing future criteria for interpreting <em>HER2</em> FISH results.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 1","pages":"Article 100637"},"PeriodicalIF":7.1,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567507","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":"Evaluation of a Task-Specific Self-Supervised Learning Framework in Digital Pathology Relative to Transfer Learning Approaches and Existing Foundation Models","authors":"Tawsifur Rahman ,&nbsp;Alexander S. Baras ,&nbsp;Rama Chellappa","doi":"10.1016/j.modpat.2024.100636","DOIUrl":"10.1016/j.modpat.2024.100636","url":null,"abstract":"<div><div>An integral stage in typical digital pathology workflows involves deriving specific features from tiles extracted from a tessellated whole-slide image. Notably, various computer vision neural network architectures, particularly the ImageNet pretrained, have been extensively used in this domain. This study critically analyzes multiple strategies for encoding tiles to understand the extent of transfer learning and identify the most effective approach. The study categorizes neural network performance into 3 weight initialization methods: random, ImageNet-based, and self-supervised learning. Additionally, we propose a framework based on task-specific self-supervised learning, which introduces a shallow feature extraction method, employing a spatial-channel attention block to glean distinctive features optimized for histopathology intricacies. Across 2 different downstream classification tasks (patch classification and weakly supervised whole-slide image classification) with diverse classification data sets, including colorectal cancer histology, Patch Camelyon, prostate cancer detection, The Cancer Genome Atlas, and CIFAR-10, our task-specific self-supervised encoding approach consistently outperforms other convolutional neural network–based encoders. The better performances highlight the potential of task-specific attention-based self-supervised training in tailoring feature extraction for histopathology, indicating a shift from using pretrained models originating outside the histopathology domain. Our study supports the idea that task-specific self-supervised learning allows domain-specific feature extraction, encouraging a more focused analysis.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 1","pages":"Article 100636"},"PeriodicalIF":7.1,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504223","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":"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 ,&nbsp;Max Blokker ,&nbsp;Johannes M.A. Daniels ,&nbsp;Teodora Radonic ,&nbsp;Jan H. von der Thüsen ,&nbsp;Mitko Veta ,&nbsp;Jouke T. Annema ,&nbsp;Marie Louise Groot","doi":"10.1016/j.modpat.2024.100633","DOIUrl":"10.1016/j.modpat.2024.100633","url":null,"abstract":"<div><div>Lung cancer is one of the most prevalent and lethal cancers. To improve health outcomes while reducing health care burden, it becomes crucial to move toward early detection and cost-effective workflows. Currently, there is no method for the on-site rapid histologic 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. In this study, we report the feasibility of an HHG portable microscope in the clinical workflow in terms of acquisition time, image quality, and diagnostic accuracy in suspected pulmonary and pleural malignancy. One hundred nine biopsies of 47 patients were imaged and a biopsy overview image was provided within a median acquisition time of 6 minutes after excision. The assessment by pathologists and an artificial intelligence algorithm showed that image quality was sufficient for a malignancy or nonmalignancy 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 a rapid pathology outcome on biopsy samples, enabling immediate diagnosis and (local) treatment.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 1","pages":"Article 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":"OA","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}