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

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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.

ABBREVIATIONS BTR = Brain Tumor Registry; CP = craniopharyngioma; CP92 = Cushing’s subcohort of 92 pathologically verified CPs; CP124 = Cushing’s entire series of 124 CPs; DI = diabetes insipidus; IT = infundibulo-tuberal; 3V = third ventricle; 3VF = 3V floor.

Article Information

Correspondence José María Pascual: La Princesa University Hospital, Madrid, Spain. jmpasncj@hotmail.com.

INCLUDE WHEN CITING Published online October 5, 2018; DOI: 10.3171/2018.5.JNS18153.

J.M.P. and R.P. contributed equally to this work.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    A: Portrait of Harvey Williams Cushing (1869–1939), artist William James, 19th–20th century, oil on canvas, sight: 75.7 × 50.4 cm, framed: 90.5 × 65.4 × 3.8 cm, Harvard University Portrait Collection, gift of the three daughters of Harvey Williams Cushing to the Medical School, 1948, HNA72. It is hung at Harvard’s Countway Library of Medicine, Boston, Massachusetts. Photograph Imaging Department © President and Fellows of Harvard College. Reprinted with the kind permission of the Harvard Art Museums. B: Drawing of an interpeduncular cyst, sketched by Harvey Cushing at the time of autopsy. It corresponds to the first intracranial tumor (case 1) surgically treated by Cushing, February 1902, at Johns Hopkins Hospital. Although this lesion was considered a “teratoma” by William Welch (1850–1934), head of the Hopkins Pathology Department at the time, multiple sources of evidence indicate that this tumor actually corresponds to a CP. From Cushing: J Nerv Ment Dis 33:704–716, 1906. Public domain. C: Pictures of a patient (case 110) taken on July 26, 1929, and a discharge note showing Cushing’s handwritten word “craniopharyngioma,” its first appearance in his BTR. From Cushing’s BTR. Public domain. Panels B and C courtesy of the Manuscripts and Archives department of the Sterling Memorial Library, Yale University. Figure is available in color online only.

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    Midsagittal tumor sections from autopsy specimens showing the five major tumor topographies evidenced in Cushing’s CP92 series. A: Sellar/suprasellar: tumor occupies both the sellar and suprasellar compartments beneath an intact 3VF. B: Pseudo-intraventricular: this suprasellar tumor causes upward displacement of the 3VF, mimicking an intraventricular position. C: Sellar/suprasellar–secondary intraventricular: a sellar and/or suprasellar lesion that eventually invades the 3V after breaking through the 3VF (case 75). D: Infundibulo-tuberal: tumor develops within the nervous tissue of the 3VF (within the infundibulum and/or tuber cinereum) and predominantly expands within the 3V (case 21). E: Strictly intraventricular: tumor primarily originates within the 3V, above an intact 3VF (case 6). Panels A, B, and E from Cushing: The Pituitary Body and Its Disorders, JB Lippincott, 1912. Public domain. Panel D from Walker: Arch Ophthalmol 45:407–437, 1916. Public domain. Panel C reproduced from Cushing’s BTR. Public domain. Courtesy of the Manuscripts and Archives department of the Sterling Memorial Library, Yale University. F: Bar chart showing the relationship between the tumor topography and the histological variant in CP92. Note the lack of papillary cases among the sellar/suprasellar and secondary intraventricular topographies and the predominance of this histological variant in the group of strictly intraventricular CPs (p < 0.001). S = sellar; SS = suprasellar. Figure is available in color online only.

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    Epidemiological and topographical characterization of Cushing’s CP124 series. A: Histogram of age distribution. Half of the patients are between the ages of 10 and 29 years old. B: Bar graph showing the distribution of CP topographies. Sellar-SS = sellar/suprasellar (15%); SS-Pseudo 3V = suprasellar pseudointraventricular (19%); Secondary 3V = sellar/suprasellar–secondary intraventricular (33%); Infundibulo-Tuberal = not strictly intraventricular (25%); 3V-Strict = strictly intraventricular (5%). C: Bar graph displaying the number of patients treated by Cushing for the time periods indicated. Note that the proportion of verified cases was higher from the 1920s onwards, coinciding with the refinement of diagnostic and histological methods. The low number of cases treated between 1916 and 1920 is due to Cushing’s service during World War I.

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    Clinical and histological characterization of Cushing’s CP series. A: Bar graph displaying the distribution of the main clinical symptoms in CP124. Dark green area within each bar represents the cases within each category presenting with hydrocephalus or symptoms of intracranial hypertension (ICH). Headache (95%), endocrine deficits (76%), and severe visual deficits (Visual [sev]; 68%) were the most common symptoms in this cohort. B: Correlation between age and the presence of hydrocephalus or symptoms of ICH in CP92. Note that 76% of patients under 20 years of age suffered from ICH symptoms (p < 0.001). C: Relationship between age and histological variant in the CP92. Note that all papillary CPs were diagnosed in patients ≥ 20 years of age (p < 0.001). Figure is available in color online only.

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    Harvey Cushing’s methodology for CP diagnosis. Fröhlich’s syndrome phenotype: a 12-year-old boy with incipient feminine-type obesity and failed sexual development (J.A.D., case 64, A1) and a young woman, 19 years old, with amenorrhea and marked obesity (H.B., case 23, A2). Perimetry exam showing bitemporal hemianopia, a visual defect characteristic of the optic chiasm injury caused by CPs (J.C.A., case 9, B). Lateral skull radiograph of J.A.B. (case 92, C), obtained in October 1926, showing dense suprasellar shadows just above the sella turcica, the radiological correlate of tumor calcifications. Picture of tumor specimen removed from D.A. (case 17, D) in June 1913. Note the multilobulated, solid-cystic structure of the lesion, whose hard capsule was tightly adhered to the vessels of the circle of Willis. This patient died shortly after tumor removal because of the severe intraoperative bleeding and permanent hypothalamic injury caused by en bloc resection of the mass. Sketch of the microscopic appearance of a typical CP, created by Louise Eisenhardt (1891–1967), Cushing’s associate neuropathologist, on April 10, 1931 (S.G.W., case 117, E1). Examination of the solid tumor portion via the supravital technique showed epithelial cells arranged in concentric masses or whorls (a) and cholesterin crystals (b). Handwritten description (E2) of histological characteristics of tumor featured in E1, by Louise Eisenhardt. Reproduced from Cushing’s BTR. Public domain. Courtesy of the Manuscripts and Archives department of the Sterling Memorial Library, Yale University.

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