The Utility of Intraoperative Cytological Smear and Frozen Section in the Surgical Management of Patients with Cushing’s Disease due to Pituitary Microadenomas

Cushing’s disease (CD) is most commonly caused by a microadenoma, which at surgical exploration may not provide adequate tissue for pathologic diagnosis using standard techniques. We wished to determine the accuracy of intraoperative pathologic examination and whether the addition of intraoperative cytology increased the diagnostic yield. We reviewed the pathology reports from 403 operations on 341 patients with CD microadenomas from a single institution. The concordance rates of intraoperative diagnoses (cytology and frozen) with the final (paraffin section) pathological diagnosis were calculated. The overall pathologic confirmation of an adenoma (by either cytology, frozen, or paraffin section) was compared with the result from a historical cohort (using only standard frozen section analysis but not intraoperative cytology) and the pooled result from a meta-analysis of previously published data. The concordance rate between frozen section diagnosis and paraffin section histology was 390/403 (96.8%). The concordance rate between cytological smear and paraffin section histology was 213/246 (86.6%). In 54 cases (13.4%) with ultimate remission, pathologic confirmation was obtained only on intraoperative pathology (frozen section or cytology). Overall, pathologic confirmation was obtained in 326 operations (80.9%) by at least one pathological modality. The overall pathological confirmation of an adenoma was greater after the introduction of intraoperative cytology when compared with the historical control (67.1%, p = 0.015), and compared with the pooled rate of published data from the meta-analysis (72.1%, p < 0.001). Our findings suggest that addition of intraoperative cytological analyses during surgery for CD is an additional useful diagnostic tool for both neurosurgeons and pathologists.