Avri Giammanco, Andrey Bychkov, Simon Schallenberg, Tsvetan Tsvetkov, Junya Fukuoka, Alexey Pryalukhin, Fabian Mairinger, Alexander Seper, Wolfgang Hulla, Sebastian Klein, Alexander Quaas, Reinhard Büttner, Yuri Tolkach
Lymph node metastasis (LNM) detection can be automated using artificial intelligence-based diagnostic tools. Only limited studies have addressed this task for colorectal cancer. The aim of this study was to develop of a clinical-grade digital pathology tool for LNM detection in colorectal cancer (CRC) using the original fast-track framework. The training cohort included 432 slides from one department. A segmentation algorithm detecting 8 relevant tissue classes was trained. The test cohorts consisted of materials from five pathology departments digitized by four different scanning systems...
April 16, 2024: Modern Pathology
Aarti E Sharma, Mark Dickson, Samuel Singer, Meera R Hameed, Narasimhan P Agaram
BACKGROUND: GLI1 (12q13.3) amplification is identified in a subset of mesenchymal neoplasms with a distinct nested round cell/epithelioid phenotype. MDM2 and CDK4 genes are situated along the oncogenic 12q13-15 segment, amplification of which defines well-differentiated (WDLPS)/dedifferentiated liposarcoma (DDLPS). The 12q amplicon can occasionally include GLI1 - a gene in close proximity to CDK4. We hereby describe the first cohort of GLI1/MDM2/CDK4 co-amplified WD/DDLPS. MATERIALS AND METHODS: The departmental database was queried retrospectively for all cases of WD/DDLPS having undergone next generation (IMPACT) sequencing with confirmed MDM2, CDK4, and GLI1 co-amplification...
April 13, 2024: Modern Pathology
Brooke Liang, Jingwei Zhao, Yongjun Kim, Keegan Q Barry-Holson, David B Bingham, Gregory W Charville, Teresa M Darragh, Ann K Folkins, Brooke E Howitt, Christina S Kong, Teri A Longacre, Austin J McHenry, Angus M S Toland, Xiaoming Zhang, Koeun Lim, Michelle J Khan, Dongkyun Kang, Eric J Yang
Demand for anal cancer screening is expected to rise following the recent publication of the ANCHOR trial, which showed that treatment of HSIL significantly reduces the rate of progression to anal cancer. While screening for HPV-associated squamous lesions in the cervix is well-established and effective, this is less true for other sites in the lower anogenital tract. Current anal cancer screening and prevention rely on high-resolution anoscopy (HRA) with biopsies. This procedure has a steep learning curve for providers and may cause patient discomfort...
April 12, 2024: Modern Pathology
João Lobo, Sofia Canete-Portillo, Maria Del Carmen Rodriguez Pena, Jesse K McKenney, Manju Aron, Felipe Massicano, Brandon M Wilk, Manavalan Gajapathy, Donna M Brown, Dilek E Baydar, Andres Matoso, Nathalie Rioux-Leclerq, Chin-Chen Pan, Maria S Tretiakova, Kiril Trpkov, Sean R Williamson, Soroush Rais-Bahrami, Alexander C Mackinnon, Shuko Harada, Elizabeth A Worthey, Cristina Magi-Galluzzi
Juxtaglomerular cell tumor (JGCT) is a rare neoplasm, part of the family of mesenchymal tumors of the kidney. Although the pathophysiological and clinical correlates of JGCT are well-known, as these tumors are an important cause of early-onset arterial hypertension refractory to medical treatment, their molecular background is unknown, with only few small studies investigating their karyotype. Herein we describe a multi-institutional cohort of JGCTs diagnosed by experienced genitourinary pathologists, evaluating clinical presentation and outcome, morphologic diversity and, importantly, the molecular features...
April 11, 2024: Modern Pathology
Yurimi Lee, Boram Lee, Yoon-La Choi, Dong-Wook Kang, Joungho Han
The heterogeneous relationship between protein expression, amplification, and mutations in human epidermal growth factor receptor 2 (HER2) in non-small cell lung cancer (NSCLC) and the optimal methods for detecting these alterations remain unclear. We aimed to elucidate the clinicopathological and molecular characteristics of HER2-altered NSCLC and investigate practical approaches for identifying patients who might benefit from HER2-targeted therapies. Using next-generation sequencing (NGS) data from 1,680 individuals, we searched for patients with HER2-altered NSCLCs, including amplifications and mutations...
April 6, 2024: Modern Pathology
Valentina Angerilli, Alessandro Vanoli, Giulia Celin, Carlotta Ceccon, Jessica Gasparello, Marianna Sabbadin, Giuseppe De Lisi, Michele Paudice, Marco Vincenzo Lenti, Laura Rovedatti, Antonio Di Sabatino, Francesca Bazzocchi, Sara Lonardi, Edoardo Savarino, Claudio Luchini, Paola Parente, Federica Grillo, Luca Mastracci, Matteo Fassan
Patients with autoimmune gastritis (AIG) have a 13-fold risk of developing type-1 neuroendocrine tumors, whereas the risk for gastric adenocarcinoma is still uncertain. Here we describe the clinicopathological and molecular features of a series of gastric carcinomas (GC) arising in the context of AIG. A total of 26 AIG-associated GC specimens were collected from four Italian Institutions. Immunohistochemistry for MUC1, MUC2, MUC5AC, MUC6, CDX2, HER2, PD-L1, CLDN18, Mismatch Repair (MMR) proteins, and p53 and EBER in situ hybridization were performed...
April 6, 2024: Modern Pathology
Hiroaki Ito, Akihiko Yoshizawa, Kazuhiro Terada, Akiyoshi Nakakura, Mariyo Rokutan-Kurata, Tatsuhiko Sugimoto, Kazuya Nishimura, Naoki Nakajima, Shinji Sumiyoshi, Masatsugu Hamaji, Toshi Menju, Hiroshi Date, Satoshi Morita, Ryoma Bise, Hironori Haga
Several studies have developed various artificial intelligence (AI) models for immunohistochemical analysis of programmed death ligand 1 (PD-L1) in patients with non-small cell lung carcinoma; however, none have focused on specific ways by which AI-assisted systems could help pathologists determine the tumor proportion score (TPS). Herein, we developed an AI model to calculate the TPS of the PD-L1 22C3 assay and evaluated whether and how this AI-assisted system could help pathologists determine the TPS and analyze how AI-assisted systems could affect pathologists' assessment accuracy...
April 6, 2024: Modern Pathology
Zhenghui Chen, Ivy H M Wong, Weixing Dai, Claudia T K Lo, Terence T W Wong
Lung adenocarcinoma (LUAD) is the most common primary lung cancer and accounts for 40% of all lung cancer cases. The current gold standard for lung cancer analysis is based on the pathologists' interpretation of hematoxylin and eosin (H&E)-stained tissue slices viewed under a brightfield microscope or digital slide scanner. Computational pathology using deep learning has been proposed to detect lung cancer on histology images. However, the histological staining workflow to acquire the H&E-stained images and the subsequent cancer diagnosis procedures are labor-intensive and time-consuming with tedious sample preparation steps and repetitive manual interpretation, respectively...
April 6, 2024: Modern Pathology
Susan Prendeville, Harpreet Kaur, Shervin Ansari, Shifaa Alqaqa, Tracy L Stockley, Katherine Lajkosz, Theodorus van der Kwast, Carol C Cheung, Shamini Selvarajah
Somatic tumor testing in prostate cancer (PCa) can guide treatment options by identifying clinically actionable variants in DNA damage repair (DDR) genes, including acquired variants not detected by germline testing alone. Guidelines currently recommend performing somatic tumor testing in metastatic PCa, while there is no consensus on the role of testing in regional disease and the optimal testing strategy is involving. This study evaluates the frequency, distribution, and pathologic correlates of somatic DDR mutations in metastatic and localized PCa following the implementation of pathologist-driven reflex testing at diagnosis...
April 6, 2024: Modern Pathology
Xinru Bai, Jingjing Wei, David Starr, Xin Zhang, Xiangchen Wu, Yongzhen Guo, Yixuan Liu, Xiaotian Ma, Yuan Wei, Changzhong Li, Megan L Zilla, Wei Zhang, Xianxu Zeng, Chengquan Zhao
The role of Artificial intelligence (AI) in pathology is one that offers many exciting new possibilities for improving patient care. This study contributes to this development by identifying the viability of AICyte Assistive System for cervical screening, and to investigate the utility of the system in assisting with workflow and diagnostic capability. In this study, a novel scanner was developed using a Ruiqian WSI-2400, trademarked AICyte Assistive system, to create AI-generated gallery of the most diagnostically relevant images, objects of interest (OOI), and provide categorical assessment, according to Bethesda category, for cervical ThinPrep Pap slides...
April 6, 2024: Modern Pathology
Sol Beccari, Esraa Mohamed, Viva Voong, Stephanie Hilz, Marisa Lafontaine, Anny Shai, Yunita Lim, Jerry Martinez, Benjamin Switzman, Ryon L Yu, Janine M Lupo, Eddie F Chang, Shawn L Hervey-Jumper, Mitchel S Berger, Joseph F Costello, Joanna J Phillips
Biomarker-driven therapeutic clinical trials require implementation of standardized, evidence-based practices for sample collection. In diffuse glioma, phosphatidylinositol 3 (PI3)-kinase/AKT/mTOR (PI3/AKT/mTOR) signaling is an attractive therapeutic target for which window of opportunity clinical trials could facilitate identification of promising new agents. Yet, the relevant preanalytic variables and optimal tumor sampling methods necessary to measure pathway activity are unknown. To address this, we used a murine model for IDH-wildtype glioblastoma (GBM) and human tumor tissue, including IDH-wildtype GBM and IDH-mutant diffuse glioma...
April 6, 2024: Modern Pathology
Jamie Lee, Simon Cheung, Andrew Churg
No abstract text is available yet for this article.
April 5, 2024: Modern Pathology
Kyu-Young Oh, Ji-Hoon Kim, Hye-Jung Yoon
Calcifying odontogenic cyst (COC), once called calcifying cystic odontogenic tumor (CCOT), is classified under the category of odontogenic cysts. However, the proliferative capacity of the lesional epithelium and consistent nuclear β-catenin expression raise questions about its current classification. This study aimed to determine whether COC would be better classified as a neoplasm in the histologic and molecular context. Eleven odontogenic lesions diagnosed as COC or CCOT were included in this study...
April 2, 2024: Modern Pathology
Amir Momeni-Boroujeni, Kerry Mullaney, Sara E DiNapoli, Mario M Leitao, Martee L Hensley, Nora Katabi, Douglas H R Allison, Kay J Park, Cristina R Antonescu, Sarah Chiang
Recurrent gene fusions have been observed in epithelioid and myxoid variants of uterine leiomyosarcoma. PGR::NR4A3 fusions were recently described in a subset of epithelioid leiomyosarcomas exhibiting rhabdoid morphology. In this study, we sought to expand the clinical, morphologic, immunohistochemical, and genetic features of gynecologic leiomyosarcomas harboring NR4A3 rearrangements with PGR and novel fusion partners. We identified 9 gynecologic leiomyosarcomas harboring PGR::NR4A3, CARMN::NR4A3, ACTB::NR4A3, and possible SLCO5A1::NR4A3 fusions by targeted RNA sequencing...
March 18, 2024: Modern Pathology
Rebeca Martínez-Hernández, Ana Serrano-Somavilla, Raul Fernández-Contreras, Cristina Sanchez-Guerrero, Nuria Sánchez de la Blanca, Pablo Sacristán-Gómez, Fernando Sebastian-Valles, Miguel Sampedro-Núñez, Javier Fraga, María Calatayud, Almudena Vicente, Gonzalo García-de-Casasola, Ancor Sanz-García, Marta Araujo-Castro, Ignacio Ruz-Caracuel, Manel Puig-Domingo, Mónica Marazuela
Pituitary neuroendocrine tumors (PitNETs) account for approximately 15% of all intracranial neoplasms. Although they usually appear to be benign, some tumors display worse behavior, displaying rapid growth, invasion, refractoriness to treatment, and recurrence. Increasing evidence supports the role of primary cilia (PC) in regulating cancer development. Here, we showed that PC are significantly increased in PitNETs and are associated with increased tumor invasion and recurrence. Serial electron micrographs of PITNETs demonstrated different ciliation phenotypes (dot-like versus normal-like cilia) that represented PC at different stages of ciliogenesis...
March 18, 2024: Modern Pathology
Ezra G Baraban, Roy Elias, Ming-Tseh Lin, Yasser Ged, Jing Zhu, Aparna Pallavajjala, Nirmish Singla, Tamara L Lotan, Pedram Argani, James R Eshleman, Jonathan I Epstein
Chromophobe renal cell carcinoma (ChRCC) is the third most common subtype of renal cell carcinoma, and typically exhibits indolent behavior, though a rare subset can exhibit high-grade morphological features and are associated with a poor prognosis. Although there is limited data on the molecular characteristics of metastatic and sarcomatoid ChRCC, the molecular features of high-grade non-sarcomatoid ChRCC remain unexplored. Herein, we characterize 22 cases of ChRCC with high-grade, non-sarcomatoid components...
March 14, 2024: Modern Pathology
Jeffrey M Cloutier, Meng Wang, Swapna S Vemula, Sonia Mirza, Jingly Weier, Jamie D Aquino, Timothy H McCalmont, Philip E LeBoit, Boris C Bastian, Iwei Yeh
NRAS activating mutations are prevalent in melanocytic neoplasia, occurring in a subset of common acquired melanocytic nevi and approximately 30% of cutaneous melanomas. In this study, we describe a cohort of seven distinctive melanocytic tumors characterized by activating point mutations in codon 61 of NRAS with amplification of the mutant NRAS allele and shared clinicopathologic features. These tumors occurred predominantly in younger patients, with a median age of 20 years (ranging from 6 to 56). They presented as papules on the helix of the ear (four cases) or extremities (three cases)...
March 9, 2024: Modern Pathology
Bence Bátai, Laura Kiss, Luca Varga, Ákos Nagy, Jacob Househam, Ann-Marie Baker, Tamás László, Anna Udvari, Róbert Horváth, Tibor Nagy, Judit Csomor, József Szakonyi, Tamás Schneider, Trevor A Graham, Donát Alpár, Jude Fitzgibbon, Ágota Szepesi, Csaba Bödör
Primary cutaneous follicle center lymphoma (PCFCL) has an excellent prognosis using local treatment, while nodal follicular lymphoma (nFL) occasionally presenting with cutaneous spread, often requires systemic therapy. Distinction of the two diseases based on histopathology alone might be challenging. Copy number alterations (CNAs) have scarcely been explored on a genome-wide scale in PCFCL, yet they might serve as potential biomarkers during differential diagnosis and risk stratification. Low-coverage whole genome sequencing (lcWGS) is a robust, high-throughput method for genome-wide copy number profiling...
March 7, 2024: Modern Pathology
John K Choi, Wenbin Xiao, Xueyan Chen, Sanam Loghavi, Kojo S Elenitoba-Johnson, Kikkeri N Naresh, L Jeffrey Medeiros, Magdalena Czader
This manuscript represents a review of lymphoblastic leukemia/lymphoma (acute lymphoblastic leukemia/lymphoblastic lymphoma), acute leukemias of ambiguous lineage, mixed-phenotype acute leukemias, myeloid/lymphoid neoplasms with eosinophilia and defining gene rearrangements, histiocytic and dendritic neoplasms and genetic tumor syndromes of the 5th edition of the World Health Organization Classification of Tumors of the Haematopoietic and Lymphoid Tissues (WHO-HEM5). The diagnostic clinicopathologic, cytogenetic and molecular genetic features are discussed...
March 7, 2024: Modern Pathology
Ming Zhao, Hualei Gan, Shan Zhong, Qiuyan Xia, Yanfeng Bai, Jiayun Xu, Xiaodong Teng, Jian Wang
Soft tissue neoplasms harboring fusions between EWSR1 or FUS with genes encoding CREB transcription factors family (ATF1, CREB1, and CREM) are an emerging heterogeneous group of mesenchymal tumors that differ significantly in morphology, immunophenotypes, and behavior. Recently, EWSR1/FUS::CREB fusions have been recognized to define a group of aggressive neoplasms of epithelioid morphology with multiple growth patterns and a striking predilection for mesothelial-lined cavities. These neoplasms presenting as a primary neoplasm of intra-abdominal visceral organs is rare, which could elicit a wide range of differential diagnoses due to their diverse morphologies and immunohistochemical profiles...
March 7, 2024: Modern Pathology
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