Introduction Evaluation of intraoperative squash smear and frozen section (FS) in central nervous system (CNS) neoplasms is consistently practiced for rapid assessment and has several advantages to its credence. It is an invaluable tool to ensure adequacy of tissue obtained to establish the diagnosis. Moreover, it aids in guiding the surgeon for critical decisions regarding the extent of resection. Although molecular markers have been integrated with morphology in the revised 2016 World Health Organization classification of brain tumors, precise morphological assessment still remains the foundation for the diagnosis and rapid intraoperative assessment of morphological details is equally critical and rewarding. Objective This study aims to audit the diagnostic disparity between intraoperative diagnoses based on a combination of squash cytology and FS in cases of CNS lesions with gold standard, final diagnosis based on examination of formalin fixed paraffin embedded hematoxylin, and eosin-stained tissue sections. Materials and Methods All intraoperative squash cytology and FS reported for CNS lesions from January 2017 to December 2020 were reviewed. The cases were categorized into three groups—group 1: when diagnosis of intraoperative diagnosis based on a combination of squash cytology and FS was same as the final histopathological diagnosis (concordant), group 2: partially concordant, and group 3: discordant cases. Statistical Analysis Descriptive statistics was used to classify the data and diagnostic accuracy was calculated. Results Complete concordance was present in 69.96% (191/273) cases, 20.1% (55/273) cases showed partial concordance, and 9.89% (27/273) cases were discordant with histopathological diagnosis. Out of the 27 discordant cases, misclassification of tumor type was the most common category (11 cases, 40%), followed by grading mismatch (7 cases, 25.9%), and misdiagnosis of tumor versus nontumor conditions (9 cases, 33.3%). Conclusion Our study shows that combination of intraoperative squash cytology and FS shows a high percentage of accuracy in arriving at intraoperative diagnosis in cases of intracranial lesions. Regular audits of discordant cases should be conducted by surgeons and pathologists as part of a quality assurance measure to sensitize themselves with the potential pitfalls, minimizing misinterpretation and helping in providing a more conclusive opinion to the operating surgeons.
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