Improving Diagnostic Accuracy: Evaluation of Papanicolaou Staining With Rapid Hematoxylin–Eosin Staining Technique in Intraoperative Touch Imprint Cytology in Central Nervous System Neoplasms: A Prospective Cohort Study

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Abstract
Background: Intraoperative cytological consultation (IOC) is a practical, rapid, and reliable method for evaluating central nervous system (CNS) tumors, enhancing the neurosurgical oncological approach. While some studies have used Papanicolaou (Pap) staining for diagnosis, its exact contribution in comparison to the rapid hematoxylin and eosin (HE) staining technique and its cytological staining characteristics remains to be fully clarified. Method: During 12 months, this prospective study examined and contrasted the final histopathological section diagnoses of 161 specimens collected from 146 consecutive patients who received intraoperative touch‐imprint cytology (TIC) and squash smear preparation (SP) techniques, using both HE and Pap staining methods. Results: The diagnostic accuracy of TIC, relative to the final integrated histopathological diagnosis, was 85.1%. Although data for frozen sections were not separately quantified, TIC remains a rapid, reliable, and practical method for intraoperative evaluation. The evaluation of CNS lesions is best achieved by histopathology, which is considered the gold standard. The most common neoplasms were glioblastoma IDH‐wild type, metastatic cancers, pituitary neuroendocrine tumor (adenoma), and meningiomas. Kappa statistics between Pap and HE staining demonstrated very good overall agreement (kappa 0.9–1, p < 0.01) across all assessed cytological features, with the highest concordance observed for nuclear details, artifacts, mitotic background, necrosis, and cytoplasmic details. Although the Wilcoxon rank‐sum test indicated small but statistically significant differences in the median scores for nuclear details and artifacts, these differences reflect minor quantitative variations and do not affect the very good overall agreement between the two staining methods. Conclusion: Intracranial TIC and SP specimens stained with both HE and Pap demonstrated excellent diagnostic performance, characterized by high sensitivity and specificity. The combined use of Pap staining alongside HE provides a reliable and effective alternative to traditional cytological staining methods.

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