ModPath Chat

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.