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José María Pascual and Ruth Prieto

From the very beginning of his career, Harvey Williams Cushing (1869–1939) harbored a deep interest in a complex group of neoplasms that usually developed at the infundibulum. These were initially known as “interpeduncular” or “suprasellar” cysts. Cushing introduced the term “craniopharyngioma” for these lesions, which he believed represented one of the most baffling problems faced by neurosurgeons. The patient who most influenced Cushing's thinking was a 16-year-old seamstress named “Mary D.,” whom he attended in December 1901, exactly the same month that Alfred Fröhlich published his seminal article describing an adiposogenital syndrome in a young boy with a pituitary cyst. Both Cushing's and Fröhlich's patients showed similar symptoms caused by the same type of tumor. Notably, Cushing and Fröhlich had met one another and became good friends in Liverpool the summer before these events took place. Their fortunate relationship led Cushing to realize that Fröhlich's syndrome represented a state of hypopituitarism and provided a useful method of diagnosing interpeduncular cysts. It is noteworthy that Cushing's very first neurosurgical procedure on a pituitary tumor was performed in the case of Mary D.'s “interpeduncular cyst,” on February 21, 1902. Cushing failed to remove this lesion, which was later found during the patient's autopsy. This case was documented as Pituitary Case Number 3 in Cushing's masterpiece, The Pituitary Body and Its Disorders, published in 1912. This tumor was considered “a teratoma”; however, multiple sources of evidence suggest that this lesion actually corresponded to an adamantinomatous craniopharyngioma. Unfortunately, the pathological specimens of this lesion were misplaced, and this prompted Cushing's decision to retain all specimens and documents of the cases he would operate on throughout his career. Accordingly, Mary D.'s case crystallized the genesis of the Cushing Brain Tumor Registry, one of Cushing's major legacies to neurosurgery. In this paper the authors analyze the case of Mary D. and the great influence it had on Cushing's conceptions of the pituitary gland and its afflictions, and on the history of pituitary surgery.

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Ruth Prieto, José María Pascual, Maria Rosdolsky, Inés Castro-Dufourny, Rodrigo Carrasco, Sewan Strauss and Laura Barrios


Craniopharyngioma (CP) adherence strongly influences the potential for achieving a radical and safe surgical treatment. However, this factor remains poorly addressed in the scientific literature. This study provides a rational, comprehensive description of CP adherence that can be used for the prediction of surgical risks associated with the removal of these challenging lesions.


This study retrospectively analyzes the evidence provided in pathological, neuroradiological, and surgical CP reports concerning 3 components of the CP attachment: 1) the intracranial structures attached to the tumor; 2) the morphology of the adhesion; and 3) the adhesion strength. From a total of 1781 CP reports published between 1857 and 2016, a collection of 500 CPs providing the best information about the type of CP attachment were investigated. This cohort includes autopsy studies (n = 254); surgical studies with a detailed description or pictorial evidence of CP adherence (n = 298); and surgical CP videos (n = 61) showing the technical steps for releasing the attachment. A predictive model of CP adherence in hierarchical severity levels correlated with surgical outcomes was generated by multivariate analysis.


The anatomical location of the CP attachment occurred predominantly at the third ventricle floor (TVF) (54%, n = 268), third ventricle walls (23%, n = 114), and pituitary stalk (19%, n = 94). The optic chiasm was involved in 56% (n = 281). Six morphological patterns of CP attachment were identified: 1) fibrovascular pedicle (5.4%); 2) sessile or patch-like (21%); 3) cap-like (over the CP top, 14%); 4) bowl-like (around the CP bottom, 13.5%); 5) ring-like (encircling central band, 19%); and 6) circumferential (enveloping the entire CP, 27%). Adhesion strength was classified in 4 grades: 1) loose (easily dissectible, 8%); 2) tight (requires sharp dissection, 32%); 3) fusion (no clear cleavage plane, 40%); and 4) replacement (loss of brain tissue integrity, 20%). The types of CP attachment associated with the worst surgical outcomes are the ring-like, bowl-like, and circumferential ones with fusion to the TVF or replacement of this structure (p < 0.001). The CP topography is the variable that best predicts the type of CP attachment (p < 0.001). Ring-like and circumferential attachments were observed for CPs invading the TVF (secondary intraventricular CPs) and CPs developing within the TVF itself (infundibulo-tuberal CPs). Brain invasion and peritumoral gliosis occurred predominantly in the ring-like and circumferential adherence patterns (p < 0.001). A multivariate model including the variables CP topography, tumor consistency, and the presence of hydrocephalus, infundibulo-tuberal syndrome, and/or hypothalamic dysfunction accurately predicts the severity of CP attachment in 87% of cases.


A comprehensive descriptive model of CP adherence in 5 hierarchical levels of increased severity—mild, moderate, serious, severe, and critical—was generated. This model, based on the location, morphology, and strength of the attachment can be used to anticipate the surgical risk of hypothalamic injury and to plan the degree of removal accordingly.

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Ruth Prieto, Inés Castro-Dufourny, Rodrigo Carrasco, Laura Barrios and José María Pascual

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José María Pascual, Ruth Prieto, Inés Castro-Dufourny, Rodrigo Carrasco, Sewan Strauss and Laura Barrios


The development of surgical procedures for the removal of craniopharyngiomas (CPs) was greatly influenced by the enormous topographical and morphological heterogeneity displayed by these lesions. In this study the authors reviewed the intracranial approaches designed to treat CPs during the early historical period (1891–1938) with the aim of finding the CP topographical and pathological features that influence patient outcomes.


The authors conducted a systematic retrospective review of well-described cases of surgically treated CPs in publications from the period 1891–1938. Valuable information regarding the diagnosis of the lesion, type of craniotomy performed, CP topography, and outcome was selected from 418 reports included in medical publications from this period. The type of surgical procedure used, degree of tumor removal, CP position and histological variety, and clinical evidence of postoperative hypothalamic injury were the variables analyzed with the aim of defining their influence on the final patient outcome.


A collection of 160 cases was eligible for analysis. Craniopharyngioma topography was significantly related to the existence of postoperative hypothalamic damage and the degree of tumor removal achieved (p < 0.001). The infundibulo-tuberal, or not strictly intraventricular, topography was associated with the highest rate of hypothalamic injury (84%) and impossibility of tumor removal (51%). This topography also showed the worst prognosis (p = 0.001). Additional variables correlated with patient outcome were the presence of hypothalamic damage, type of surgical approach used, and degree of tumor removal. Patients having a poor outcome, suffering from permanent coma, or dying after surgery presented with symptoms of hypothalamic injury in 40% of cases (p < 0.001). The surgical approach associated with the best outcome was the transsphenoidal (58%), followed by the subfrontal (45%) and the transcallosal (45%). Subtotal resection of the lesion yielded the best postoperative results, with only 17% of patients dying or suffering from a poor outcome, in contrast to the 39% reported for gross-total removal of the lesion (p = 0.001).


Two major variables influenced the results of early surgical experience with CPs for the period from 1891 to 1938: 1) the inaccuracy in defining CP topography with the diagnostic methods available at that time; and 2) the ignorance about the risks associated with the dissection of lesions showing tenacious adherence to the hypothalamus. The degree of functional and morphological disturbance of the hypothalamus caused by a CP remains a fundamental variable helping the surgeon to predict the risks associated with the radical excision of the tumor and patient outcome.