Joseph Engel (1816-1899), author of a meaningful dissertation on tumors of the pituitary infundibulum: his report on the oldest preserved whole craniopharyngioma specimen.

Joseph Engel (1816-1899) was a Viennese anatomist and pathologist trained under the mentorship of Carl von Rokitansky (1804-1878), the man who laid the foundations of gross anatomical pathology. In 1839, Engel completed his first scientific project: the dissertation entitled "Über den Hirnanhang und den Trichter" (About the pituitary gland and the infundibulum). This work analyzed the pathological and clinical characteristics of the pituitary and infundibulum tumor specimens collected at the Vienna Pathologic-Anatomical Museum. This little-known work represents one of the earliest attempts to determine the function of the pituitary gland-infundibulum complex. Among the 12 pituitary/infundibulum tumors examined in Engel's dissertation, one of the cases (no. 10) was instrumental for the definition of hypophyseal duct tumors, or craniopharyngiomas (CPs). This huge cyst, approximately the size of a goose egg (6 × 6 × 4.5 cm), was found in 1828 during the autopsy of a 33-year-old patient who suffered from severe headache, blindness, apathy, and finally somnolence. The cyst had replaced the hypophysis and extended upwards into the hypothalamic region and downwards into the sphenoid sinus, its inferior pole protruding through the soft palate. In 1904, the Viennese pathologist Jakob Erdheim (1874-1937) re-examined this lesion and conclusively categorized it as a hypophyseal duct tumor after a detailed histological study. The original tumor specimen corresponding to this CP case is still preserved at the Narrenturm, the circular building within the old Allgemeines Krankenhaus (Vienna General Hospital) that today holds the pathological collections of Vienna's Federal Pathologic-Anatomical Museum. To the best of our knowledge, this tumor is very probably the oldest preserved whole CP specimen in the world. This paper presents a comprehensive review of Engel's dissertation, the pioneering pathological work on pituitary and infundibulum tumors which laid the groundwork for the proper clinical, topographic, and pathological categorization of craniopharyngiomas.

Learning from cases: Analysis of two cases of craniopharyngioma from the 19 th to the 21 st centuries.

This manuscript describes the study of two cases of craniopharyngioma, which have been examined repeatedly over three separate centuries. This includes analysis by Josef Engel in 1839, who sought to uncover the physiological role of the pituitary gland; Jacob Erdheim in 1904, who initially described the disease we now call craniopharyngioma, and recent high resolution MRI and micro-CT imaging and attempted DNA analyses of the tumours. The cases highlight how, rightly or wrongly, our interpretation of data is shaped by the technologies, methodologies and prevailing theories of a given time.

Harvey Cushing's craniopharyngioma treatment: Part 2. Surgical strategies and results of his pioneering series.

OBJECTIVE: 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. METHODS: The CP records from Cushing's Brain Tumor Registry were carefully reviewed, as were his CP cases published in medical monographs and scientific reports. RESULTS: 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). CONCLUSIONS: 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.

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

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.

The first sixty-five craniopharyngioma operations in France.

Craniopharyngiomas (CPs) are benign epithelial tumors that develop along the hypothalamus-hypophyseal axis and were first described by Jakob Erdheim in 1904. These tumors have represented a challenge for surgeons since the rise of modern neurosurgery. The study of CPs is linked to the development of this surgical discipline in parallel with neuroendocrinology within the French school of neurology, led by Joseph Babinski. For the present study, all CP cases published in the French scientific literature before the development of modern neuroradiology were gathered, and 65 cases that underwent surgical procedures between 1921 and 1973 were selected. From our analysis of them, useful information has been obtained that can be applied to the management of CPs today. Most tumors were adamantinomatous CPs (62 patients) with an infundibulo-tuberal location (40.6%). The most frequent surgical route employed was subfrontal (69%). Selection of the surgical approach and degree of removal did not appear to have been influenced by the presumed topography of the tumor, and resulted in a poor outcome in 47% of patients. However, the authors were able to recognize the presence of symptoms indicating that the tumor had caused hypothalamic and/or infundibular damage, such as seen in the infundibulo-tuberal syndrome, first described by Claude and Lhermitte in 1917. At present, the optimal surgical approach and degree of removal are still the subject of debate, although the presence of clinical signs pointing to hypothalamic involvement by CPs should always be preoperatively accurately assessed to improve surgical outcomes.

Sir Victor Horsley: pioneer craniopharyngioma surgeon.

Sir Victor Horsley (1857-1916) is considered to be the pioneer of pituitary surgery. He is known to have performed the first surgical operation on the pituitary gland in 1889, and in 1906 he stated that he had operated on 10 patients with pituitary tumors. He did not publish the details of these procedures nor did he provide evidence of the pathology of the pituitary lesions operated on. Four of the patients underwent surgery at the National Hospital for Neurology and Neurosurgery (Queen Square, London), and the records of those cases were recently retrieved and analyzed by members of the hospital staff. The remaining cases corresponded to private operations whose records were presumably kept in Horsley's personal notebooks, most of which have been lost. In this paper, the authors have investigated the only scientific monograph providing a complete account of the pituitary surgeries that Horsley performed in his private practice, La Patologia Chirurgica dell'Ipofisi (Surgical Pathology of the Hypophysis), written in 1911 by Giovanni Verga, Italian assistant professor of anatomy at the University of Pavia. They have traced the life and work of this little-known physician who contributed to the preservation of Horsley's legacy in pituitary surgery. Within Verga's pituitary treatise, a full transcription of Horsley's notes is provided for 10 pituitary cases, including the patients' clinical symptoms, surgical techniques employed, intraoperative findings, and the outcome of surgery. The descriptions of the topographical and macroscopic features of two of the lesions correspond unmistakably to the features of craniopharyngiomas, one of the squamous-papillary type and one of the adamantinomatous type. The former lesion was found on necropsy after the patient's sudden death following a temporal osteoplastic craniectomy. Surgical removal of the lesion in the latter case, with the assumed nature of an adamantinomatous craniopharyngioma, was successful. According to the evidence provided in Giovanni Verga's monograph, it can be claimed that Sir Victor Horsley was not only the pioneer of pituitary gland surgery but also the pioneer of craniopharyngioma surgery.

[The 2013 Sixto Obrador Award. A triple-axis topographical model for surgical planning of craniopharyngiomas. Part I: historical review of the topographical diagnosis and classification schemes of craniopharyngiomas]. / Premio Sixto Obrador 2013. Modelo topográfico de 3 ejes para el tratamiento quirúrgico de los craneofaringiomas. Parte I: Evolución histórica del diagnóstico topográfico y métodos de clasificación de los craneofaringiomas.

INTRODUCTION AND OBJECTIVES: This study reviews the historical evolution of pathological, neuroradiological and surgical evidence that influenced the topographical concepts and classification schemes of craniopharyngiomas. MATERIAL AND METHODS: An extensive, systematic analysis of the surgical series of craniopharyngiomas reported in the literature was performed (n=145 series, 4,588 tumours) to describe the fundamental anatomical findings guiding the topographical classification schemes used for this tumour throughout history. These findings were compared with topographical relationships reported for well-described operated craniopharyngiomas (n=224 cases) as well as for non-operated cases studied in autopsies (n=201 cases). RESULTS: Two major variables define the topography of a craniopharyngioma: its position relative to the sellar diaphragm and its degree of invasion of the third ventricle floor. Suprasellar lesions displacing the third ventricle floor upwards (pseudointraventricular craniopharyngiomas) are amenable to safe, radical resection and must be differentiated from lesions developing primarily within the third ventricle floor (infundibulo-tuberal or not strictly intraventricular craniopharyngiomas). The latter group typically shows tight, circumferential adhesion to the third ventricle floor and represents approximately 40% of all cases. CONCLUSIONS: A triple-axis topographical model for craniopharyngiomas that includes the degree of hypothalamus invasion is useful in planning surgical approach and degree of resection. The group of infundibulo-tuberal craniopharyngiomas associates the highest risk of hypothalamic injury (50%). The endoscopically-assisted extended transsphenoidal approach provides a proper view to assess the topography of the craniopharyngioma and its degree of adherence to the hypothalamus.

Development of intracranial approaches for craniopharyngiomas: an analysis of the first 160 historical procedures.

OBJECT: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Craniopharyngioma: history.

One of the most challenging parasellar tumors, the craniopharyngioma was first described by Friedrich Albert von Zenker in 1857. Following improved understanding of pituitary gland physiology and development, Jakob Erdheim became the first to accurately describe the histopathological characteristics of a craniopharyngioma. Babinski's described the clinical presentation of these patients, with "sexual infantilism and dystrophic adiposity." The first successful surgical resection of a craniopharyngioma was performed by A. E. Halstead of Chicago of July 21st, 1909. Harvey Cushing embraced the transsphenoidal approach for the majority of his pituitary operations, but favored the transcranial approach for craniopharyngiomas. The introduction of antibiotics, corticosteroids, and microscopy significantly improved surgical outcomes. As technology improved, trans-cranial and transsphenoidal approaches were implemented depending on tumor characteristics. Adjuvant therapy, such as stereotactic radiosurgery, radioisotope brachytherapy, and intracapsular chemotherapy have improved overall tumor control rates and decreased the incidence of complications. Building on over 100 years of surgery for "the most formidable of intracranial tumors," results continue to improve. Regardless, challenges continue to remain requiring surgical insight and innovation.

Craniopharyngioma: historical notes.

For centuries tumors have been described which today with some confidence can be diagnosed as craniopharyngiomas. It was not until 1904 Erdheim described what he called 'hypophysial duct tumors', and which Cushing later gave the name craniopharyngioma. The first operation for this neoplasm took place in 1909. It soon became evident that the outcome of surgery was rather dismal with high mortality and morbidity rates-even after corticosteroid therapy became available around 1950. Radiotherapy was introduced and later refined as radiosurgery. This paper presents a short survey of the accumulation of knowledge of craniopharyngiomas.

Craniopharyngiomas. Historical aspects of their management.

The history of the management of craniopharyngiomas offers a comprehensive review of the exciting progress in neurosurgery, neuroimaging, neuroendocrinology and radiation oncology during the last century. In this historical note, we present the evolution in management of these most challenging of brain tumours, which, despite the substantial knowledge and expertise gained since the first attempt of surgical removal, remains a subject of considerable debate.

The evolution of the endonasal approach for craniopharyngiomas.

Craniopharyngiomas have always been an extremely challenging type of tumor to treat. The transsphenoidal route has been used for resection of these lesions since its introduction. The authors present a historical review of the literature from the introduction of the endonasal route for resection of craniopharyngiomas until the present. Abandoned early due to technological limitations, this approach has been expanded both in its application and in its anatomical boundaries with subsequent progressive improvements in outcomes. This expansion has coincided with advances in visualization devices, imaging guidance techniques, and anatomical understanding. The progression from the use of headlights, to microscopy, to endoscopy and fluoroscopy, and finally to modern intraoperative magnetic resonance-guided techniques, combined with collaboration between otolaryngologists and neurosurgeons, has provided the framework for the development of current techniques for the resection of sellar and suprasellar craniopharyngiomas.

A history of the treatment of craniopharyngiomas.

RATIONALE: Nearly 100 years have passed since the first surgical attempt to remove a craniopharyngioma was undertaken, and the management of patients with these tumors continues to both challenge and frustrate those involved with their treatment. METHODS: By constructing a historical framework from past literature on the treatment of craniopharyngioma, the authors have attempted to document the early and important events in the treatment of these tumors in order to add a historical dimension to their current treatment and to engender a more comprehensive understanding of the modern treatment of craniopharyngioma. CONCLUSION: The application of radiotherapeutic techniques to the management of craniopharyngioma would begin to complement the role of surgery, but debate would soon emerge as to what constituted the most appropriate management for craniopharyngioma in children.

Diabetes insipidus and blindness caused by a suprasellar tumor: Pieter Pauw's observations from the 16th century.

Tumors in the suprasellar region may cause both visual and endocrinologic symptoms. This association, well known to modern physicians, was established during the 19th century. However, we have identified a 16th-century autopsy report, written by the Dutch professor of anatomy Pieter Pauw (1564-1617), which describes an 18-year-old girl who developed marked polyuria and subsequently became totally blind from a cystic tumor compressing the optic chiasm. Based on prevailing theories on the nature of diabetes, Pauw attributed the disease to the kidneys. Undoubtedly, however, his lucid report is the earliest known account of diabetes insipidus caused by an arachnoid cyst, the Rathke cleft cyst, or craniopharyngioma in the region of the pouch of Rathke. The description also gives insights into the role of anatomic dissections in late 16th-century northern Europe.

History of surgery for craniopharyngiomas.

Craniopharyngiomas, although histologically benign, are usually so intimately associated with the hypothalamus that total extirpation of these tumors was generally followed by death from hypotension and gross endocrine deficiencies. During the first half of the present century, those recording their tribulations include the famous names of Grant, Bailey, Bucy, Peet, Kahn, Olivecrona, Norlen, Sjöqvist, Rougerie and Northfield. Matson and Sweet were the first to achieve major reductions in mortality by giving massive doses of cortisone plus meticulous dissection, which took advantage of the reactive glial envelope which surrounds the great majority of these tumors.