Background: Pleural effusion is a common clinical condition resulting from a wide range of benign and malignant diseases. Cytological examination of pleural fluid remains the initial diagnostic approach because it is minimally invasive, economical, and provides rapid results. However, conventional smear cytology often suffers from low cellularity, overlapping cells, poor architectural preservation, and difficulty in distinguishing reactive mesothelial cells from malignant cells. Cell block preparation has emerged as an important adjunctive technique that enhances diagnostic accuracy by preserving tissue architecture and allowing additional ancillary investigations.

Objective: To evaluate the contribution of cell block preparation in improving the cytological diagnosis of pleural effusions and compare its diagnostic performance with conventional smear cytology.

Materials and Methods: A prospective observational study was conducted on 150 pleural fluid samples received over 18 months. Each sample was processed simultaneously by conventional smear cytology and the cell block technique. Cytomorphological findings, diagnostic yield, sensitivity, specificity, and detection rates of malignant lesions were compared. Histopathological findings and clinical follow-up served as reference standards.

Results: Conventional smear cytology identified malignant cells in 38 cases (25.3%), whereas cell block examination diagnosed malignancy in 49 cases (32.7%). Combined evaluation improved overall diagnostic sensitivity from 74.5% to 94.1%. Cell block sections demonstrated superior architectural preservation, increased cellularity, improved identification of glandular differentiation, and facilitated immunohistochemistry.

Conclusion: Cell block preparation significantly improves the diagnostic accuracy of pleural fluid cytology. The combined use of conventional smear and cell block should be considered a routine diagnostic protocol, particularly when malignancy is clinically suspected.