Case Reports Hematopathology 2025 Exercise 1: Challenges and Pitfalls in the Diagnosis of Myelodysplastic Syndrome with DDX41 Germline Predisposition

Authors

Jason X. Cheng, MD, PhD

Department of Pathology

University of Chicago

Lucy A. Godley, MD, PhD

Robert H Lurie Comprehensive Cancer Center

Northwestern University

Chicago, Illinois

Primary Audience: Pathologists and Clinical Scientists
Secondary Audience: Residents, Laboratory Technologist/Scientist (Includes all sub-specialty areas), Students, Pathologist Assistants,  Laboratory Directors and Educators

Upon completion of this activity, you will be able to:

•  understand the rationale and importance for including the new entity of myeloid neoplasms (MNs) with germline predisposition in the revised 4th edition WHO Classification of Myeloid Neoplasms and Acute Leukemia and the update on this entity in the 5th edition WHO and the 2022 ICC classifications;
• be familiar with the unique clinicopathologic features of DDX41 germline predisposition syndrome;
• understand the importance of distinguishing between premalignant DDX41 germline predisposition syndrome and neoplastic myelodysplastic syndrome (MDS) with DDX41 germline predisposition;
• recognize the diagnostic challenges and pitfalls in the diagnosis of MDS with deleterious DDX41 germline variants and their consequential impact on clinical management;
• know how to avoid over- and under-diagnosing MDS in patients with deleterious DDX41 germline variants by using the diagnostic algorithm and pearls provided by this article; and
• suggest and/or conduct molecular/genetic tests on appropriate samples for DDX41 and other germline predispositions based on their practical considerations and available information and resources.