Cytopathologic Diagnosis of Lymphomas in Serous Effusions, Cerebrospinal and Vitreous Fluid

BACKGROUND: Haematolymphoid lesions in serous effusion, cerebrospinal, and vitreous fluid are encountered regularly. In the paediatric clinical setting, haematolymphoid lesions are the most common cause of malignant serous effusions. Cytologists and cytopathologists should be prepared to evaluate such samples as part of routine diagnostic practice. This article provides a comprehensive overview of the cytomorphological features and diagnostic considerations of lymphomas involving serous fluids, cerebrospinal, and vitreous fluids. SUMMARY: B-cell non-Hodgkin lymphomas are most often encountered in fluid cytology specimens. A practical method for triaging lymphocyte-predominant effusions involves assessing lymphoid cell size, specifically distinguishing between small-to-medium and large lymphoid cells. A significant differential diagnosis of small-medium lymphoid cells in fluid specimens is reactive lymphocytosis while that for large cells is metastatic malignant, and atypical or malignant mesothelial cells. KEY POINTS: Cytologic evaluation of fluids containing lymphocytes provides valuable information regarding the nature of these lesions. Accurate cytologic diagnosis, with clinicopathologic correlation and judicious use of ancillary testing where possible, is essential for identifying the underlying cause of effusion, guiding therapy, monitoring disease progression or relapse, and informing prognosis. To optimize diagnostic outcomes, proper collection, transport, and preparation of fluid specimens is required. Collaboration with haematopathologists and use of standardized cytologic reporting systems further contribute to diagnostic accuracy and consistency. Emerging technologies, including molecular profiling, liquid biopsy, single-cell multi-omics and artificial intelligence, offer promising avenues for advancing the diagnosis and prognostication of haematolymphoid malignancies in fluid-based samples. Further research will determine their clinical utility.