ModPath Chat

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.