2025 Proffered Presentations
S039: PITUITARY LOCALIZATION AND HISTOLOGIC CHARACTERISTIC MAPPING IN MRI-NEGATIVE CUSHING'S DISEASE: DR. EDWARD OLDFIELD'S DECADE-LONG LEGACY STUDY
Richard J Chung, BA1; Xue Feng, PhD2; Georgios A Maragkos, MD1; Kristine Ravina, MD3; Jonathan Yun, MD1; Kathryn N Kearns, MD1; John A Jane Jr., MD3; Michael P Catalino, MD, MSc1; 1Department of Neurosurgery, University of Virginia; 2Department of Biomedical Engineering, University of Virginia; 3Department of Neurosurgery, Carilion Clinic, Virginia Tech School of Medicine
Introduction: In cases of clinical Cushing’s disease with ambiguous or negative MRIs, surgical resection of the abnormal pituitary tissue oversecreting ACTH can be challenging. Surgeons rely on visual inspection and palpation of the pituitary tissue, including histologic pituitary mapping that has historically localized corticotrophs to the anteromedian anterior lobe. Corticotroph hyperplasia has also been implicated in Cushing’s disease pathogenesis. Proopiomelanocortin (POMC) cells are distinct ACTH-immunoreactive cell populations related to the ACTH-secreting corticotrophs that form “clustered small cell islands” without follicular cell association, also found outside of the typical corticotroph morphologic distribution. We hypothesize that these cells may be involved in the pathogenesis of MRI-negative Cushing’s disease, leading to more frequent disease recurrence given their diffuse cellular distribution. Furthermore, pituitary mapping of the most common POMC cells and corticotroph hyperplasia locations leading to Cushing’s disease can be useful in guiding surgical resection involving ambiguous or negative imaging. Dr. Edward Oldfield’s surgical pituitary records represent a valuable resource given the meticulous data record and detailed resection drawings. Herein, we developed a heatmap to demonstrate these significantly different anatomic landmarks within MRI-negative patients.
Methods: This retrospective study evaluated 157 patients with Cushing’s disease and pathology-confirmed corticotroph adenoma seen at our institution from December 2007 to March 2017 who underwent transsphenoidal resection by a single surgeon. Two cohorts of MRI-positive and MRI-negative Cushing’s disease patients were established and analyzed. Every patient had postoperative sketches by the late Dr. Oldfield who mapped the anatomical location of abnormal pituitary tissue confirmed by positive ACTH immunohistochemistry. We developed a Python algorithm for image acquisition and processing.
Results: Of 157 patients that met our inclusion criteria, 140 (age 38.2 ± 13.7, 27 male, 113 female) had MRI-positive and 17 (age 40.14 ± 11.5, 3 male, 14 female) had MRI-negative Cushing’s disease. The MRI-positive cohort consisted of 110 microadenomas (78.6%) and 30 macroadenomas (21.4%) with an average tumor diameter of 7.4 ± 3.7mm and volume of 397.2 ± 963.8mm3. No significant differences in invasion, Knosp grading, pre-op UFC, or post-op Q6H nadir cortisol values were observed between the two groups. Postoperatively, 124 (89.2%) MRI-positive and 13 (76.5%) MRI-negative patients achieved remission, and 35 (25.2%) and 2 (12.5%), respectively, received adjuvant gamma knife therapy. In the MRI-positive cohort, heatmap generation demonstrated lower intensity in the pars intermedia upon axial view and a more uniform distribution sagittally. Image processing showed significantly different regions of interest on sagittal view with MRI-positive patients highlighting the posterior portion of the anterior lobe and MRI-negative patients displaying clusters circumferentially near the dura.
Conclusion: Dr. Edward Oldfield’s surgical sketches demonstrated a propensity of MRI-positive corticotrophs in the posterior aspect of the anterior lobe near the pars-intermedia interface, while MRI-negative tumors arise peripherally in proximity to the dura. Despite the advent of radiological imaging, these surgical depictions currently provide the best anatomic landmarks for unseen or inconclusive corticotrophs for surgeons performing exploratory TSR for Cushing’s disease.
