Prognostic Impact of Ki-67 Index and Tumor Size on Structural Outcomes in Nonfunctioning Pituitary Neuroendocrine Tumors

Introduction: Nonfunctioning pituitary neuroendocrine tumors (NF-PitNETs) represent the most common subtype of pituitary neoplasms. Although generally slow-growing, a subset demonstrates invasive or recurrent behavior. Potential predictors of aggressiveness include adrenocorticotropic hormone (ACTH) immunopositivity, plurihormonal or null-cell phenotype, K i -67 index ≥3%, and tumor size ≥40 mm. Evidence regarding their prognostic value remains inconsistent. This study aimed to evaluate the association between these variables and structural persistence following surgery in a large Latin American cohort. Methods: A retrospective review of medical records from 2010–2020 identified patients with surgically treated pituitary tumors. Inclusion criteria were MRI-confirmed NF-PitNET, complete clinical, radiological, and pathological records, and at least 12 months of follow-up. Eighty-one patients met criteria. Demographic data, presenting symptoms, imaging features, surgical approach, histopathological subtype, and postoperative outcomes were collected. Immunohistochemistry classified tumors by cell lineage and K i -67 index, with ≥3% considered high. Structural persistence was defined as residual tumor on follow-up MRI. Statistical analyses included univariate description and Fisher’s exact test for associations with structural outcomes. Results: Of 140 pituitary tumors reviewed, 81 (58%) were NF-PitNETs. The mean age was 51 years, with 53% female patients. Most tumors were macroadenomas (74%), with 13% classified as giant adenomas. Transsphenoidal surgery was performed in 80%, and 20% underwent a transcranial approach. The most frequent presenting symptoms were visual field disturbances (70%) and headache (66%). Histopathology revealed gonadotroph lineage as the most prevalent (56%), followed by null-cell (24%) and corticotroph (19%). K i -67 indices were available for 67 patients; 78% demonstrated K i -67 ≥3%. Structural persistence was observed in 73% of the entire cohort, and 31% required reoperation. Statistical analysis showed significant associations between K i -67 ≥3% and structural persistence ( p = 0.028) and between tumor size ≥40 mm and structural persistence ( p = 0.030). Patients with K i -67 ≥3% had a 100% incidence of persistence, compared with 72% in those with K i -67