Harvey Cushing's craniopharyngioma treatment: Part 1. Identification and clinicopathological characterization of this challenging pituitary tumor

Abstract

Objective: Harvey Cushing (1869-1939) coined the term "craniopharyngioma" (CP) in 1929 to describe a kaleidoscopic group of epithelial tumors involving the hypothalamic-pituitary axis. Throughout his career, he endured a long struggle to accurately diagnose and safely remove these complex lesions, and his resulting surgical series has never before been analyzed in depth. The authors here conduct such an analysis.

Methods: In this study, the authors retrospectively examined the CP patient records available in the Cushing Brain Tumor Registry, as well as those CP cases reported by Cushing in medical monographs and scientific reports.

Results: Cushing's CP series comprises a total of 124 tumors (CP124) compatible with a CP diagnosis. Among this series are 92 cases that could be pathologically verified (CP92). This subcohort showed a bimodal age distribution (41% aged ≤ 19 years old) and a balanced sex distribution. Clinical evolution up to diagnosis was longer than 3 years in half of the patients. Typical symptoms found at diagnosis were severe headache (94%), visual deficits (97%), panhypopituitarism (76%), psychiatric disturbances (47%), and abnormal somnolence (47%). The highest rate of endocrine deficits occurred in patients younger than 19 years of age (p < 0.001), whereas hypothalamic disturbances were observed mainly in adults between 30 and 49 years (p = 0.02). Hydrocephalus was present in 63% of the patients, predominantly involving the younger subgroup (p < 0.001). Preoperative diagnosis was based on clinical signs, funduscopic exams, and skull radiographs, the latter study showing suprasellar calcifications in 64% of cases. The majority of tumors (61%) had developed within the third ventricle (3V) or had invaded it. The adamantinomatous histological variant was the predominant one (73%). Squamous-papillary CPs occurred only in adults older than 40 years of age (p < 0.001). Strong CP adherences to the hypothalamus were demonstrated in 63% of cases. The infundibulo-tuberal and sellar/suprasellar-3V CP topographies were associated with the highest rates of hypothalamic dysfunction before surgery (p < 0.001), surgical hypothalamic injury (p < 0.001), and severe postoperative morbidity and/or mortality (p = 0.009). Both topographies showed the strongest adherences to the hypothalamus and 3V (p < 0.001).

Conclusions: Cushing's CP series comprises severely ill patients with tumors in the late stages of progression, with a high rate of tumors developing primarily within the hypothalamus (infundibulo-tuberal CPs) or invading this structure from the sellar/suprasellar regions. Craniopharyngioma topography was the fundamental variable influencing the clinical manifestations, tumor features, and patient outcomes in this series.

Keywords: 3V = third ventricle; 3VF = 3V floor; BTR = Brain Tumor Registry; CP = craniopharyngioma; CP124 = Cushing’s entire series of 124 CPs; CP92 = Cushing’s subcohort of 92 pathologically verified CPs; DI = diabetes insipidus; Harvey Cushing; IT = infundibulo-tuberal; craniopharyngioma; history of pituitary surgery; hypothalamus; infundibulum; pituitary gland; pituitary tumors; third ventricle.