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.
José María Pascual and Ruth Prieto
José María Pascual, Ruth Prieto and Laura Barrios
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.
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.
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).
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.
Ruth Prieto, José María Pascual and Laura Barrios
Harvey Cushing (1869–1939) developed pioneering surgical techniques for craniopharyngioma (CP) removal. This study exhaustively analyzes the pathological variables and surgical strategies that influenced Cushing’s results in his entire series of CP patients.
The CP records from Cushing’s Brain Tumor Registry were carefully reviewed, as were his CP cases published in medical monographs and scientific reports.
One hundred twenty-four tumors with characteristics typical of CP comprise Cushing’s entire series (CP124). Cushing performed 198 surgical procedures in the patients in whom these tumors were treated, with a 23% mortality rate within the first 2 months after surgery. Three periods in Cushing’s CP surgical career can be differentiated: an early period (1901–1917, 39 patients) characterized by his use of the transsphenoidal approach and limited cyst drainage procedures, an intermediate period (1919–1925, 42 patients) in which the subfrontal approach was the standard procedure and maximal removal was attempted, and a late period (1926–1932, 43 patients) characterized by the use of air ventriculography for topographical diagnosis and limited resections via a transventricular approach. Among Cushing’s CP series were 92 cases that were pathologically verified (CP92). In this subcohort, the unilateral subfrontal approach was predominantly used (72% of cases), followed by the transsphenoidal (15%) and frontal transcortical-transventricular (8%) approaches. Drainage of the CP cystic component or partial excision of the solid component was achieved in 61% of the cases, subtotal removal in 23%, and macroscopic total removal in 10%. Satisfactory outcomes were obtained in 55% of the patients in CP92, whereas poor outcomes and/or death related to hypothalamic injury was observed in 28%. Postoperative symptoms related to hypothalamic dysfunction occurred 53% of the time. The subfrontal approach yielded the highest rates of radical removal (p < 0.001) and good outcomes (p = 0.01). Partial removals were associated with the highest rates of poor outcomes, including death (p = 0.009). Cushing’s removal of CPs with a primary infundibulo-tuberal topography or showing third ventricle invasion was associated with the highest rates of hypothalamic injury (p < 0.001) and the worst outcomes (p = 0.009).
Harvey Cushing’s techniques and surgical philosophy varied substantially throughout his career. The experience he gained with this large CP series made him aware of the importance of limiting the extent of tumor removal and leaving untouched the tumor portion strongly adhered to the hypothalamus.
José María Pascual, Ruth Prieto, Rodrigo Carrasco and Laura Barrios
Accurate diagnosis of the topographical relationships of craniopharyngiomas (CPs) involving the third ventricle and/or hypothalamus remains a challenging issue that critically influences the prediction of risks associated with their radical surgical removal. This study evaluates the diagnostic accuracy of MRI to define the precise topographical relationships between intraventricular CPs, the third ventricle, and the hypothalamus.
An extensive retrospective review of well-described CPs reported in the MRI era between 1990 and 2009 yielded 875 lesions largely or wholly involving the third ventricle. Craniopharyngiomas with midsagittal and coronal preoperative and postoperative MRI studies, in addition to detailed descriptions of clinical and surgical findings, were selected from this database (n = 130). The position of the CP and the morphological distortions caused by the tumor on the sella turcica, suprasellar cistern, optic chiasm, pituitary stalk, and third ventricle floor, including the infundibulum, tuber cinereum, and mammillary bodies (MBs), were analyzed on both preoperative and postoperative MRI studies. These changes were correlated with the definitive CP topography and type of third ventricle involvement by the lesion, as confirmed surgically.
The mammillary body angle (MBA) is the angle formed by the intersection of a plane tangential to the base of the MBs and a plane parallel to the floor of the fourth ventricle in midsagittal MRI studies. Measurement of the MBA represented a reliable neuroradiological sign that could be used to discriminate the type of intraventricular involvement by the CP in 83% of cases in this series (n = 109). An acute MBA (< 60°) was indicative of a primary tuberal-intraventricular topography, whereas an obtuse MBA (> 90°) denoted a primary suprasellar CP position, causing either an invagination of the third ventricle (pseudointraventricular lesion) or its invasion (secondarily intraventricular lesion; p < 0.01). A multivariate model including a combination of 5 variables (the MBA, position of the hypothalamus, presence of hydrocephalus, psychiatric symptoms, and patient age) allowed an accurate definition of the CP topography preoperatively in 74%–90% of lesions, depending on the specific type of relationship between the tumor and third ventricle.
The type of mammillary body displacement caused by CPs represents a valuable clue for ascertaining the topographical relationships between these lesions and the third ventricle on preoperative MRI studies. The MBA provides a useful sign to preoperatively differentiate a primary intraventricular CP originating at the infundibulotuberal area from a primary suprasellar CP, which either invaginated or secondarily invaded the third ventricle.
Ruth Prieto and Jose María Pascual
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.
Ruth Prieto, Inés Castro-Dufourny, Rodrigo Carrasco, Laura Barrios and José María Pascual
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.