Background: Endoscopic pituitary surgery might yield better endocrine outcomes compared to microscopic resection. We conducted a prospective, randomized, single-blinded study to compare the endocrine outcome and quality of life (QoL) of patients with newly diagnosed pituitary adenoma who underwent either endoscopic or microscopic transsphenoidal surgery (NCT03515603). Methods: Due to slow recruitment, this study had to be stopped prematurely. Out of 170 transsphenoidal pituitary surgeries performed during the study period, 36 patients were enrolled in this study. The primary endpoint was based on the development of a new hypopituitarism. Secondary endpoints included the extent of resection, complications, and QoL. Results: Endoscopic surgery was performed in 47.2% (n = 17). A new hypopituitarism was found in 8.3% (n = 3). All these cases underwent microscopic resection. Arginine vasopressin deficiency was found in 2.7% (n = 1) after microscopic resection. Gross total resection was achieved in 94.4% (n = 34). No surgical complications or new neurological deficits were observed. QoL improved significantly after the surgery, as measured by EQ-VAS (p = 0.003). According to EQ-5D3L, QoL improved or remained unchanged in almost all patients. No significant difference was found in QoL between the endoscopic and microscopic groups. Conclusion: The endoscopic technique appears to offer benefits in the treatment of pituitary adenomas, particularly in terms of achieving a favorable endocrine outcome.

Background/Objectives: Pituitary tumors account for over 90% of all sellar region masses. However, a spectrum of rare neoplastic, inflammatory, infectious, and vascular lesions—benign and malignant—can arise in the intra- and parasellar compartments and clinically and radiologically mimic PitNETs. We report a cohort of 47 such rare and cystic midline intracranial lesions, emphasizing their distinctive morphological, clinical, and imaging features and the personalized treatment strategies applied. Methods: In this retrospective single-center study, we reviewed all patients treated for suspected PitNETs via transsphenoidal approach between 2015 and 2024. Of 529 surgical cases, we excluded confirmed PitNETs, meningiomas, and classical intradural craniopharyngiomas. Collected data encompassed patient demographics, tumor characteristics, presenting symptoms, extent of resection or medical therapy, endocrine outcomes, and follow-up information. Results: Among all 529 patients who underwent surgical treatment for sellar lesions from 2015 to 2024, 47 cases (8.9%) were identified as rare or cystic masses. Forty-six underwent transsphenoidal resection; one patient with hypophysitis received corticosteroid therapy alone. Presenting symptoms included headache (n = 16), dizziness (n = 5), oculomotor disturbances (n = 2), and visual impairment (n = 17). Endocrine dysfunction was found in 30 patients, 27 of whom required hydrocortisone replacement. Histopathological diagnoses were led by colloid cysts (n = 14) and Rathke’s cleft cysts (n = 11). The remaining 22 cases comprised plasmacytoma, germinoma, lymphoma, pituicytoma, inverted papilloma, metastatic carcinoma, chordoma, nasopharyngeal carcinoma, chloroma, and other rare entities. Preoperative imaging diagnosis proved incorrect in 38% (18/47) of cases, with several lesions initially misidentified as PitNETs. Conclusions: Nearly 9% of presumed PitNETs were rare, often benign or inflammatory lesions requiring distinct management. Most could be safely resected and demonstrated excellent long-term outcomes. Yet, despite advanced imaging techniques, accurate preoperative differentiation remains challenging, with over one-third misdiagnosed. Clinical red flags—such as early hormone deficits, rapid progression or atypical imaging findings—should prompt early interdisciplinary evaluation and, when indicated, image-guided biopsy to avoid unnecessary surgery and ensure tailored therapy.