Real-world application of the WHO Reporting System for Lymph Node Cytopathology in the Context of the 5th Edition of the WHO Classification of Hematolymphoid Neoplasms

Background: Cytology is central to the initial work-up of lymphadenopathy in the era of minimally invasive procedures, but some inherent limitations such as loss of tissue architecture require ancillary testing in some cases. Summary: The WHO Reporting System for Lymph Node, Spleen, and Thymus Cytopathology (2024) standardizes category-based reporting and management, while the 5th edition of the WHO Classification of Hematolymphoid Tumors (WHO-HAEM5) defines diagnostic entities and criteria. Key Messages: We review the real-world application of the WHO Reporting System across the five diagnostic categories, highlight cytomorphologic patterns that map to WHO-HAEM5 entities, and provide an overview for triaging material to flow cytometry, immunohistochemistry, as well as molecular and genetic testing. We posit that properly selected and validated ancillary studies enable WHO-concordant diagnoses from cytology and reduce repeat procedures.