Cytologic Diagnosis of Large B-Cell Lymphoma: Diagnostic Approach and Differential Diagnosis

BACKGROUND: Large B-cell lymphoma (LBCL) encompasses a diverse group of aggressive lymphoid neoplasms, the most common of which is diffuse large B-cell lymphoma (DLBCL). A precise diagnosis is critical for determining prognosis and therapeutic strategies, particularly as new molecular subtypes and classification criteria have been introduced in the 5th edition of the World Health Organization (WHO) classification of hematolymphoid tumors (WHO-HAEM5, 2022). Fine needle aspiration cytology is a safe and minimally invasive diagnostic tool for assessing lymphadenopathy and extranodal masses. SUMMARY: LBCLs are typically characterized by single cells with large nuclei, vesicular chromatin pattern, and prominent nucleoli. The diagnosis of LBCL and the distinction distinguishing between LBCL subtypes requires the integration of cytomorphologic features with ancillary techniques, including immunocytochemistry, flow cytometry, fluorescence in situ hybridization, and next-generation sequencing. KEY MESSAGES: This review synthesizes the cytologic features, immunophenotypic profiles, molecular signatures, and clinical implications of LBCL subtypes, highlighting recent advances in cytopathology and classification.