Practical implications of the World Health Organization Reporting System for Lymph Node, Spleen, and Thymus Cytopathology: Categories and ancillary testing for subtyping of hematolymphoid tumors on FNA biopsy cytopathology using a pattern-based approach.

The objective of the recently published World Health Organization Reporting System for Lymph Node, Spleen, and Thymus Cytopathology (WHO system) is to standardize the diagnostic approach to fine-needle aspiration biopsies of hematolymphoid tissues. By categorizing specimens into five diagnostic groups-inadequate/insufficient/nondiagnostic, benign, atypical, suspicious for malignancy, and malignant-the system provides a structured framework that enhances diagnostic clarity and facilitates communication between cytopathologists and clinicians. Each category is associated with a defined risk of malignancy, supporting informed clinical decision making regarding further diagnostic workup. Accurate categorization requires the integration of cytomorphologic features and clinical context, and final and specific diagnoses often require ancillary techniques such as flow cytometry, immunocytochemistry, in situ hybridization, and molecular diagnostics. To assist cytopathologists, especially those less familiar with hematolymphoid neoplasms, the WHO system incorporates a pattern-based diagnostic approach. Four cytopathologic patterns-mixed lymphoid cell; predominantly small/intermediate cell; predominantly large/pleomorphic/blastic cell; and single, very large, atypical cell-serve as guides to narrow down differential diagnoses. However, interpretation can be challenging because of overlapping features, variable inflammatory backgrounds, and limited sample material. This review provides a brief overview of the WHO system and its application to hematolymphoid proliferations, emphasizing the importance of clinical correlation and the use of relevant ancillary techniques. It then provides in-depth discussion of the pattern-based approach to diagnosing hematolymphoid neoplasms on cytopathology. It highlights the strengths and limitations of cytopathologic evaluation in hematolymphoid neoplasms and provides practical insights for applying the WHO system in routine practice.