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ModPath Chat is the official podcast of Modern Pathology, the journal of the US and Canadian Academy of Pathology (USCAP). ModPath Chat features interviews with authors, opinion leaders and experts on the latest science, technology, and developments in the field of pathology. The monthly podcast series is hosted by Dr. George J. Netto, the Editor-in-Chief of Modern Pathology and the Simon Flexner Professor and Chair, Department of Pathology and Laboratory Medicine at the University of Pennsylvania Perelman School of Medicine in Philadelphia
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This episode is a conversation with Professor Anne Vincent-Salomon from Institut Curie, Paris and
Dr. Maxim De Schepper from University Hospitals Leuven, Belgium. The topic is the European Lobular Breast Cancer
Consortium study aiming to harmonize the pathological diagnosis of ILC by comparing 5 commonly used E-cadherin
antibody clones (NCH-38, EP700Y, Clone 36, NCL-L-E-cad [Clone 36B5], and ECH-6). Based on the study findings,
the guests describe the indication for E-cadherin staining, choice of antibodies, and IHC interpretation to
standardize ILC diagnosis in current pathology practice
Drs. Guido Martignoni and Anna Caliò from the University of Verona in Italy discuss their recent study on primary and metastatic fumarate hydratase (FH)-deficient renal cell carcinomas. Six metastatic tumors were histologically documented with high frequency of involvement of lymph nodes, liver and peritoneal cavity. Metastases were morphologically heterogeneous often differing from corresponding primary. Interestingly, some peritoneal metastases morphologically resembled a benign reactive mesothelial process or primary peritoneal mesothelioma, a pitfall that can be avoided by performing IHC panels that include PAX8 and FH. As for therapeutic predictors, significant PD-L1 labeling was found in 60% of primary renal tumors, whereas none of them carried pathogenetic EGFR mutations.
Dr. Claudio Luchini from the University of Verona and Dr. Gaetano Paolini from Brescia University Hospital in Italy discuss their systematic review article, published in Modern Pathology, on Intraductal oncocytic papillary neoplasm (IOPN) of the pancreas.
Our host discusses with Drs. Shaomin Hu from Cleveland Clinic and Yue Xue MD PhD, from Case Western
Reserve in Cleveland Ohio, their multi-institutional study on gastrointestinal (GI) tract involvement by Langerhans
cell histiocytosis (LCH). The authors highlight new insights from their large study showing that adult patients with
multisystem LCH exhibit similar clinicopathologic features to those of pediatric patients. Adults with single-system
LCH involving the GI tract have an excellent prognosis, whereas multisystem LCH occurring at any age carries an
unfavorable prognosis. High-risk features of GI LCH include pediatric age, GI symptomatology, noncolorectal GI
involvement, multifocal GI disease, nonpolypoid lesions, and infiltrative growth pattern.
Our host discusses with Dr. Anna Laury, from the Department of Pathology, University of Helsinki, Finland, her team's study on the utilization of AI-guided spatial transcriptomic analysis to allow for the biological interpretation of morphologic features detected by AI algorithms when applied to WSI of standard H&E sections.
The authors previously trained an AI model to identify HGSC (high-grade serous carcinoma of the ovary) tumor regions that are highly associated with outcome status but are indistinguishable by conventional morphologic methods. In the here discussed study, Dr. Laury’s team applied spatially resolved transcriptomics to further profile the AI-identified tumor regions in 16 patients (8 per outcome group) and identify molecular features related to disease outcome in patients who underwent primary debulking surgery and platinum-based chemotherapy.
Our host discusses with Drs. Prendeville and Selvarajah, from the departments of Laboratory Medicine and Pathobiology at the University of Toronto, their recent study on Pathologist-Driven somatic testing for DNA Damage Repair (DDR) in prostate carcinoma (PCa).
516 FFPE samples from metastatic and localized high risk PCa cases including needle biopsies, TURP and RP specimens were tested using a custom NGS panel of 83 cancer predisposition genes encompassing 4 Homologous Recombination Repair (HRR) genes [BRCA1/2, ATM, PALB2] and 4 Mismatch Repair (MRR) [MLH1, MSH2, MSH6, PMS2]. 13.9% of patients had at least one AMP/ASCO/CAP tier I or tier II variant, whereas 21.5% patients had a tier III variant. Tier I/II variant(s) were identified in 27% of metastatic biopsy samples and 13% of primary samples.
The presence of a tier I/II variant was not significantly associated with the grade group (GG) or presence of intraductal (IDC-P) /cribriform carcinoma in the primary tumor and therefore may not be reliable to guide patient selection.
Non-small cell lung carcinomas (NSCLCs) commonly present as 2 or more separate tumors. They encompass separate primary lung carcinomas (SPLCs), representing independently arising tumors, or intrapulmonary metastases (IPMs), representing intrapulmonary spread of a single tumor. In this episode, Dr. Natasha Rekhtman, from Memorial Sloan Kettering Cancer Ctr, NY provides an update on the growing applications of genomic testing as a clinically relevant benchmark for determining clonal relationships in multiple NSCLCs. She discusses the limitations of morphology-based distinction of SPLCs vs IPMs and the pivotal insights that have emerged from studying multiple NSCLCs using genomic approaches as a gold standard.
Our host discusses with Drs. Djerroudi and Vincent-Salomon, from the Institut Curie in Paris France, their recent study comparing HER2-negative invasive breast cancer of no special type (IBC-NST), with HER2-negative ILC.
HER2-negative ILC had a higher frequency of HER2-zero cases (59.4% vs 53.7%) and a lower frequency of HER2-low (40.6% vs 46.3%). Clinicopathological features associated with HER2-low status (vs HER2-zero) in ILC were older age, postmenopausal status, non-classic ILC histological types, higher grade, and ER expression. While HER2-low ILC patients had a lower risk of local recurrence (vs HER2-zero) there was no association between HER2 status and either breast cancer specific survival or distant metastasis-free interval. ERBB3 was the unique mutated gene exclusively associated with HER2-low ILCs, albeit mutated at a low frequency (7.1%). The guests highlighted the potential therapeutic significance of their findings that HER2-low ILCs exhibit unique molecular and clinical attributes.
A most exciting conversation with some of the many engaged listeners of our podcast around the globe. Our host is joined by Dr. Zeeshan Ansar from Karachi, Pakistan; Dr. Emilian Olteanu, from Timisoara, Romania; Dr. Sanam Loghavi from Houston, USA and Dr. Sanjay Mukhopadhyay, from Clevland, USA.
In this episode, our host and Dr. Lisa Rooper from Johns Hopkins University, on behalf of her group of esteemed coauthors, discuss their recent study on the molecular characteristics of “Olfactory Carcinoma.” Targeted molecular profiling of 23 cases of the rare sinonasal tumor was performed to help clarify their pathogenesis and classification. The authors found recurrent Wnt pathway and ARID1A alterations, suggesting that sinonasal neuroendocrine and epithelial tumors may be best regarded as a histologic and molecular spectrum.
Integration of molecular analyses in routine diagnostics is the new practice paradigm of surgical pathology practice. The 2024 USCAP Long Course led by Dr. John Hart from the University of Chicago and Daniela Allende of Cleveland Clinic focuses on hepatic neoplasms and medical diseases where there are opportunities for ancillary molecular testing to refine the diagnosis and provide clinically relevant prognostic information. In this episode, the guests offer a preview of the long course sessions encompassing the utility of germline testing to identify liver disease risk alleles and the exciting potential of emerging technologies.
In this meet the expert episode, ModPath CHAT host Dr. George Netto discusses with Dr. Liron Pantanowitz, Chair of Pathology at UPMC and a pioneer leader in the field, his views on the current status and future direction of Digital Pathology. The conversation touches the various aspects of the digital transformation journey in AP, from infrastructure requirement to talent acquisition and training, regulatory hurdles and expectation of financial return on investments.
Flow cytometric analysis of blood & bone marrow for diagnosis of acute myelogenous leukemia (AML) relies heavily on manual intervention in the processing & analysis steps. Attention-based multi-instance learning models (ABMILMs) are deep learning models that make accurate predictions & generate interpretable insights regarding the classification of a sample from individual events.The Drs. Olga Pozdnyakova and Joshua Lewis discuss their newly developed computational pipeline using ABMILMs for the automated diagnosis of AML cases based exclusively on flow cytometric data. The study is the first to illustrate the feasibility of using deep learning-based analysis of flow cytometric data for automated AML diagnosis & molecular characterization.
Modern Pathology is publishing a seminal series of review articles highlighting the recently completed fifth edition of the World Health Organization classification of hematolymphoid tumors (WHO-HEM5). In this episode of ModPath CHAT, Dr. Sanam Loghavi from The MD Anderson Cancer Center in Houston, discusses the major updates in the classification of myeloid neoplasms, providing a comparison with WHO-HEM4R, and offering guidance on how the new classification can be applied to the diagnosis of myeloid neoplasms in routine practice.
Polymorphous adenocarcinoma (PAC) is a common, usually low-grade salivary gland carcinoma. While conventional PACs are most associated with PRKD1 p.E710D hotspot mutations, the cribriform subtype is often associated with gene fusions in PRKD1, PRKD2, or PRKD3. The guest, Dr. Justin Bishop from UT Southwestern Medical Center in Dallas, discusses his team’s recent study characterizing the fusions associated with PAC with NGS. A diverse group of fusion partners, including 13 novel partners, were identified. The most common partners for the PRKD genes were ARID1A and ARID1B.
Endoscopic evidence of disease is a critical predictor of relapse in patients with Crohn’s disease (CD). While histologic disease activity is evolving as a similarly important end point, classical morphologic features of CD may overlap with postoperative inflammatory changes, confounding the evaluation of anastomotic biopsies.In this episode, Dr, John Hart, Professor and Vice Chair of Anatomic Pathology at the University of Chicago discusses his team’s critical recent study in Modern Pathology showing that due to the above extensive morphologic overlap and the lack of specific histologic features of relapse, biopsies from anastomotic sites are of no value in predicting clinical CD progression. On the other hand, CD activity in biopsies obtained away from anastomotic sites should be used for guiding endoscopic sampling and clinical management.
This episode features Dr. Laura Lamps , a leader in the field of gastrointestinal pathology. Dr. Lamps is the Godfrey D. Stobbe Professor and Director of Gastrointestinal Pathology and Assistant Chair for Faculty Development and Program Director of GI Pathology Fellowship at the Department of Pathology, Michigan Medicine, at the University of Michigan. The former President of US and Canadian Academy of Pathology (USCAP) shares with the audience her perspectives as a brilliant leader on the importance of seeking a diverse mentorship and investing in leadership development resources. The informative discussion centers on how to build and empower the next generation of pathologists.
In this episode, Dr. Tamara Lotan from Johns Hopkins University discusses the potential of deep-learning (DL) algorithms trained on H and E-stained whole slide images (WSI) to screen for clinically relevant genomic alterations in prostate cancer (PCA).Dr. Lotan reviews her team’s recent publication in Modern Pathology, where they were able to create DL algorithms to identify PCA with underlying ERG fusions or PTEN deletions. By applying the algorithms to multiple radical prostatectomy and needle biopsy cohorts, the authors demonstrated the ability of DL models to accurately predict ERG/PTEN status from H and E stained WSI.
In this episode, Dr. Arnaud de la Fouchardiere, from the Universite Claude Bernard in Lyon France, discusses his multinational team’s recent study on the clinical and histologic presentation of 51 cutaneous melanocytic neoplasms with a PKC fusion gene.
Most tumors occurred in young adults (median age, 29.5 years) and some presented in newborns. Histologically, 42 tumors were classified as benign, presenting predominantly as biphasic dermal proliferation with nests of small melanocytes surrounded by fibrosis with haphazardly arranged spindled and dendritic melanocytes, resembling those reported as “combined blue nevi.” Six tumors had sheets of atypical melanocytes infiltrating the dermis and were classified as melanomas. Two of the melanomas displayed loss of BAP1 nuclear expression with one patient developing metastatic disease and another dying of their melanoma.
ROS1 alterations are uncommon in gliomas and are primarily described in infants. In this episode, our host discusses with Dr. Xinyan Lu from the Feinberg School of Medicine in Chicago her team’s recent study on characterizing the clinicopathological features and molecular signatures of the full spectrum of ROS1 fusion–positive gliomas across all age groups. A multi-institutional cohort of 32 new and 58 published cases was divided into 3 age groups (19 infants, 40 pediatric patients, and 31 adults). Tumors in infants and adults showed uniformly high-grade morphology; however, tumors in pediatric patients exhibited diverse histologic features. The GOPC::ROS1 fusion was prevalent (61/79, 77%) across all age groups. Adult tumors showed recurrent genomic alterations characteristic of IDH wild-type glioblastoma, including the +7/-10/CDKN2A deletion and amplification of CDK4, MDM2, and PDGFRA. The outcomes were significantly poorer in adult patients.
The authors conclude that ROS1 likely acts as a driver in infant and pediatric gliomas and as a driver or codriver in adult gliomas. Integrated comprehensive clinical testing might be helpful in identifying such patients for possible targeted therapy.
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