Highly Esteemed and Much-Valued Professor [Rokitansky]!

The pathological anatomy considers you its most devoted supporter; your tireless enthusiasm erected an establishment of which our empire can be proud... Europe mentions your name with respect! I had the honor of belonging to the group of your students and you gave me permission to use your celebrated name at the beginning of my first scientific experiment.

Joseph Engel, 1839 [3]

Introduction

Revolutionary progress in medicine was taking place in Vienna at the turn of the nineteenth century. The Second Vienna Medical school modernized the awful state of existing rural European medicine by instituting a scientific, academic medical practice at a large modern hospital, the Allgemeines Krankenhaus (Vienna General hospital) [1]. The pathologist Carl von Rokitansky (1804–1878), a central figure of this school, led this process through his systematic investigation into the causes of disease in thousands of autopsies performed every year on all deceased patients within the Allgemeines Krankenhaus. Furthermore, he was actively involved in the transcendent project of cataloging and preserving all rare pathological specimens which could shed light on the causes of still unknown or poorly defined afflictions [2].

Rokitansky was professor and mentor to numerous distinguished figures of medicine who contributed to spreading the new field of scientific pathology throughout Europe. Among them, Joseph Engel (1816–1899) stands out as one of the most brilliant, yet rather unknown, pathologists of his generation. Soon after finishing his medical degree, Joseph Engel joined Rokitansky’s autopsy house (Leichenhaus) and embarked on his first scientific project, the review of the pituitary and infundibulum tumors collected in the pathological museum. This material enabled him to write a pioneering dissertation entitled “Über den Hirnanhang und den Trichter” (About the Pituitary Gland and the Infundibulum) [3]. This study was instrumental for Jakob Erdheim to categorize hypophyseal duct tumors, currently known as craniopharyngiomas (CPs), in 1904 [4]. Actually, one very old CP specimen included in Engel’s dissertation remains preserved at the Narrenturm, the current site of the anatomical pathological museum of Vienna. This study analyzes Engel’s seminal work and the scientific impact that this CP specimen—very probably the oldest preserved whole CP specimen in the world—made on our understanding of the pituitary gland and its pathologies.

Joseph Engel (1816–1899): a life devoted to pathological anatomy

Joseph Engel (29 January 1816–3 April 1899) was a Viennese physician who devoted his career to teaching and researching anatomical and pathological sciences (Fig. 1A). He has been posthumously recognized as the most brilliant of Rokitansky’s disciples, the first professor in Vienna to teach microscopy, the technology that would revolutionize pathology in the nineteenth century. Regrettably, Engel’s unflinching integrity as a scientist clashed with the authoritarian medical community of Vienna, whose overt hostility towards him hindered his academic career [5, 6]. As a result, Engel fell into contempt and his numerous scientific contributions were forgotten. Among them, his pioneering dissertation on tumors of the pituitary gland and infundibulum, “Über den Hirnanhang und den Trichter,” written in 1839 under the direction of Carl von Rokitansky, represents a truly commendable study in the history of neuroendocrinology as it refuted the erroneous view that pituitary growths were the cause of epilepsy (Fig. 1B1, B2) [3].

Fig. 1
figure 1

A: portrait of a young Joseph Engel (1816–1899) about the time he wrote his seminal dissertation on tumors of the pituitary gland and the infundibulum (“Über den Hirnanhang und den Trichter,” 1839). B1: Cover page of Engel’s dissertation. B2: First page of Engel’s dissertation dedicated in honor to Carl von Rokitansky, his gracious tutor, Doctor of Medicine, Master of Obstetrics, Associate Professor of Pathological Anatomy at the University of Vienna, Member of the Medical School, Full Member of the Imperial-Royal Society of Physicians in Vienna, etc. C: The Josephinum or Josefinische Akademie, the medical-surgical military academy where Josef Engel taught topographic and pathological anatomy from 1854 until 1874 (photograph by the authors)

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After receiving his medical doctorate, Engel began his work as an unpaid intern at Rokitansky’s pathological-anatomical institute, performing numerous pathological studies on the rich material obtained from autopsies and giving successful lectures on anatomy and pathology [6]. He was also the first pathologist in Vienna to give courses on microscopy, and he wrote a detailed manuscript on his microscopic technique [7, 8]. His growing reputation brought about the outbreak of hostilities between him and his colleagues, including Rokitansky. When his courses were halted, Engel was forced to move to Zurich, where he accepted the position of associate professor of topographical anatomy in 1844. Although Engel was much appreciated for his lectures and became full professor in 1846, he remained dissatisfied with his low income and accepted a position as full professor of pathological anatomy at the University of Prague, in 1849 [9].

In Prague, Joseph Engel was engaged in very productive anatomical research, but his relationships with colleagues continued to be uneasy, and he wished to return to his hometown. In 1854, Engel accepted a position as professor of topographic and pathological anatomy at the Josefinische Akademie or “Josephinum” (Fig. 1C), the newly founded military medical-surgical academy in Vienna. Nevertheless, despite enjoying a prestigious reputation, his liberal attitude towards medical education clashed again with the military bureaucratic procedures at the Josephinum [5, 9]. The intrigues of the numerous enemies of the Josephinum in Viennese medical circles eventually succeeded in dismantling this institution in 1874, a tragedy for Engel’s career. His ideology opposing the hierarchical, authoritarian system in Austrian Medicine made it impossible for him to continue his academic and scientific work in Vienna. Engel was not offered any other position as professor of pathology and was forced to retire prematurely at the age of 58, a sad event which led to his isolation and loneliness [6, 9]. Although his talents and ethics significantly surpassed many of his contemporaries, he was professionally ostracized during the final stage of his life. He died on 3 April 1899 at the age of 83.

Abnormal pituitary gland growths during Engel’s time: an enigma waiting to be solved

At the beginning of the nineteenth century, almost nothing was known about the pathological nature and clinical meaning of tumors developing in the pituitary gland and/or the infundibulum. In the acclaimed work, “De Humani Corporis Fabrica” written by Andreas Vesalius in 1543, the infundibulum was conceptualized as the hollow structure at the base of the third ventricle allowing for the excretion of the pituita, the cold, humid secretion allegedly produced by the brain according to the classic Galen’s humor theory [10]. Abnormal growths developed from the pituitary gland and/or the infundibulum were found at postmortem examinations and reported in several pioneering works on gross anatomical pathology, such as the masterpiece “De Sedibus et Causis Morborum per Anatomen Indagatis” (1761) by the Italian anatomist Giovanni Battista Morgagni (1682–1771), the father of anatomical pathology [11]. However, no significant insight into the nature of these lesions or their clinical effects was provided in works like this.

The first attempt to link pathological changes of the pituitary gland with a neurological disease was made by the German anatomist and physiologist Joseph Wenzel (1768–1808), in his work Beobachtungen über den Hirnanhang fallsüchtiger Personen (Observations on the hypophysis cerebri of epileptic persons, Mainz 1810) [12]. In this monograph, Wenzel analyzed the anatomical alterations found in the brains of epileptic patients autopsied at Mainz, where in 1802 he founded the first medical society for the scientific study of epilepsy [13]. He observed gross morphological alterations in the pituitary gland of 20 epileptic patients involving its size, color, consistency, or fluid content. Although rather unspecific, Wenzel assumed these findings as a sign of pituitary gland “inflammation” and the plausible cause of epilepsy [12]. Such a premature conclusion was received with strong criticism; Engel in particular devoted a significant part of his dissertation to refute Wenzel’s hypothesis.

Before Engel’s dissertation, the only study providing a comprehensive description of pituitary tumors and their clinical effects was the article Observations sur les maladies de l’appendice sus-sphénoidal, written in 1823 by the French physiologist Pierre-Francoise-Oliver Rayer (1793–1867) [14]. In his work, Rayer analyzed the pituitary tumor cases published in old pathological reports in order to summarize the clinical symptoms they caused and to establish the differentiation between pituitary gland hypertrophies and scirrhous tumors of the gland with a hard consistency. Despite its historical importance, Rayer’s work was not mentioned in Engel’s dissertation. Therefore, he probably did not know the pathological nature and effects of growths developing at the pituitary gland and infundibulum when he wrote his dissertation.

Engel’s dissertation on the pituitary gland and the infundibulum: an early insight into the field of neuroendocrinology

Joseph Engel’s dissertation, Über den Hirnanhang und den Trichter (About the pituitary gland and infundibulum), published in Vienna in 1839, represents one of the earliest attempts to determine the function of the pituitary gland-infundibulum complex [3]. What motivated Engel’s dissertation was Rokitansky’s encouragement to investigate the extensive collection of brain specimens with pituitary and infundibular growths stored in the Vienna pathological museum (Fig. 2). The major aim of Engel’s dissertation was, however, to transcend the field of anatomy and settle the clinical alterations associated with the dysfunction of this neuroendocrine anatomical complex. The connection of the pituitary gland with the cerebrum through the hollow and vascular infundibulum suggested an important function of this organ. Engel speculated about the existence of an “exchange of products” between adjacent parts of the brain parenchyma communicated through the ventricles. This probably represents the earliest hypothesis on neuroendocrine communication within the central nervous system. Engel reasoned that the accumulation of fluid within a ventricle would lead to increased pressure in the brain and interference with the brain functions mediated by blocking the “physiological” interactions between contiguous brain areas [3]. This obstructing effect on the cerebrospinal fluid circulation through the ventricles caused by cerebral tumors could give rise to the psychological disturbances observed in these patients. Even without a basic understanding of electrical or endocrine communication between nervous cells, Engel’s assumptions were not totally misguided.

Fig. 2
figure 2

A: Marble bust of Carl von Rokitansky (1804–1878), located on the landing of the main staircase at the Josephinum (picture taken by main author). B: The Allgemeines Krankenhaus (Vienna General Hospital) as it was at the end of the eighteenth century (original artistic picture located at the Narrenturm, photograph by the authors). The Narrenturm (Fool’s tower) was built at the back of the main hospital (white arrow) and served as Europe’s oldest hospital for insane patients during the nineteenth century. C: Picture of the Narrenturm as it is today (photograph by M. Rosdolsky). The Narrenturm is currently the home of the Pathological-Anatomical Museum of Vienna. D: Façade of the Pathologische Institut in Vienna, the building where Carl von Rokitansky worked and developed the scientific field of pathology. The inscription in gold letters reads “Indagandis sedibus et causis morborum”, words chosen by Rokitansky to pay hommage to Morgagni’s magnum opus “De Sedibus et Causis Morborum per Anatomen Indagatis” written in 1769, which founded the scientific field of pathological anatomy. In this way, Rokitansky dedicated this building to the “investigation of the seats and causes of diseases” (photograph by the authors)

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Engel’s dissertation is organized into three parts: (1) a review of pituitary gland anatomy and embryology in humans; (2) a systematic research of the pathological alterations in this organ as observed in the collection of hypophyseal/infundibular tumors (stored at the Vienna pathological museum), as well as in earlier reports in the medical literature; (3) a final analysis of possible physiological roles of the pituitary gland and the infundibulum based on the correlation of pathological findings with clinical symptoms, with the aim of dismantling prior and not properly substantiated hypotheses.

A major subject of discussion in Engel’s dissertation was the hypothetical relationship between epilepsy and anatomical alterations in the pituitary gland and infundibulum, as proposed in Joseph Wenzel’s work [12]. Wenzel observed some morphological variations of the pituitary gland, such as a softer or a more reddish organ, among epileptic patients. He erroneously interpreted these findings as the consequence of water and/or blood accumulation transmitted through the duct connecting the third ventricle with the gland. Engel firmly opposed Wenzel’s assumptions by confirming that the lower part of the infundibulum was solid, even in cases with an enlarged infundibulum due to “hydrops ventriculi” (hydrocephalus) [3]. From his own observations, he resolved that no valuable conclusions can be drawn from the variations in color or consistency found in the hypophyseal glands of patients.

In the final section of his dissertation, Joseph Engel provides important clinical information related to the impairment of hypothalamic structures by tumors expanding within the infundibulum. In particular, he highlights the frequent incidence of movement and gait disorders, abnormal somnolence, and, above all, psychological disturbances such as memory loss, often leading to a dementia-like status, and mood disorders like anxiety and depression. Engel attempted to explain these alterations by emphasizing the resemblance of the pituitary gland with the cerebellum, as both structures showed similar connections to the brain through a peduncle formed by gray matter (the infundibulum) or white matter (the cerebellar peduncle), respectively [3, 15]. Although we know today that the biological basis of all these neurological and psychiatric disorders lies in the disruption of specific neural networks between the hypothalamus and the limbic structures [16], Engel nearly foresaw two centuries ago the direct role played by the infundibulo-tuberal region in regulating psychological and behavioral functions, a truly remarkable insight at the time.

Tumors of the hypophysis and infundibulum: Engel’s review of pathological specimens at the Vienna Anatomical-Pathological Museum

A large part of Engel’s dissertation is devoted to a detailed review of earlier pathological observations of pituitary gland and/or infundibulum tumors reported in medical literature. Some authoritative figures of anatomy from the sixteenth to the seventeenth centuries such as Giovanni Battista Morgagni, Thomas Willis, and Alexander Monro supported the view that the pituitary gland functioned as a sort of “lymphatic gland,” and that hydrocephalus developed as the consequence of its congestion [3, 11, 15, 17]. The largest account of anatomical observations of the human hypophysis was, however, provided in a work by Johann Ernst Greding (1718–1775) in 1791 [18]. After examining the hypophyses of 199 patients, including epileptic, intellectually retarded and insane cases, Greding assumed that the consistency of this gland is often harder in patients with these conditions, as observed in 81 autopsies. Based on his thorough exam of museum brain specimens, Engel did not support Greding’s conclusions [3].

The main focus of Engel’s dissertation was his thorough anatomical and pathological analysis of 12 whole brain specimens with abnormal growths and other anatomical alterations of the pituitary gland and infundibulum, all obtained from autopsies performed at the Allgemeines Krankenhaus in the prior decade (1828–1836). Table 1 summarizes the main epidemiological, clinical, and pathological findings in these patients [3]. Most of them suffered from chronic conditions such as neoplasms (3 cases), alcoholism, epilepsy, or syphilis and were admitted to the hospital owing to rapid deterioration of neurological functions, such as severe headache caused by hydrocephalus, in 4 cases, or acute visual deterioration in two. Notably, marked psychiatric disturbances with delirium, demented behavior, or abnormal emotional reactions such as unmotivated irritability and rage attacks were described in more than half the cases (7 cases). In one of them (case 12), these alterations led the patient to commit suicide with a gun shot. All but two patients died in the first days/weeks after admission.

Table 1 Series of pituitary gland pathologies and tumors of the infundibulum investigated by Joseph Engel [3]
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The pathological findings consisted of abnormal growths involving the pituitary gland and/or the infundibulum in 8 patients, whereas a yellowish, gelatin-like fluid accumulated within the pituitary gland, between the anterior and posterior lobes, was observed in the remaining 4 cases. The largest tumors (3 to 8 cm) replacing the whole hypophysis and the infundibulum were considered to show a malignant biological behavior and, accordingly, were diagnosed with the common but inaccurate denomination of “sarcoma,” in use at that time [19,20,21]. According to the gross pathological features described, two of these cases certainly correspond to CPs. The remaining tumors were small, pea-size hard cysts located within the pituitary gland or at the infundibulum, some of them also compatible with CPs (Table 1).

Engel’s case number ten: a giant pituitary cyst protruding into the pharynx

Among the pituitary tumors studied by Joseph Engel, case 10 deserves special attention. The patient, Ecker Johann, a 33-year-old waiter, had been hospitalized after a long-running condition of emaciation and weakness. He also complained of headache and abnormal somnolence and suffered from impaired vision which had deteriorated very quickly into blindness. After an excessively quiet and submissive behavior, the patient remained apathetic during his stay at the hospital. His clinical condition progressively worsened with sustained weight loss. Very interestingly, a soft tumor could be palpated at the roof of his pharynx, just beneath the uvula. The patient died suddenly in January 1828.

At the autopsy, a giant cystic mass, the size of a goose egg, filled with brownish fluid was found at the base of the brain (Fig. 3). It caused a marked enlargement of the cerebral ventricles (hydrocephalus). The tumor had replaced the hypophysis and the infundibulum, structures no longer recognizable, and extended upwards into the brain and downwards into the sphenoid sinus. Its upper portion invaded the hypothalamic region and the third ventricle, whereas its inferior pole was connected to the nasopharynx and protruded through the soft palate. The mass pushed the cerebral pedunculi apart and encroached upon the optic chiasm, transforming it into an atrophied, paper-thin structure. The sphenoid body had been eroded by the tumor.

Fig. 3
figure 3

Pituitary-infundibulum tumor no. 10 described in Engel’s dissertation. A1: Artistic illustration of the patient’s skull base showing the bone destruction at the area of the sella turcica caused by this tumor. Instead of the body of the sphenoid bone, there is a large opening (red arrow). The prominence of the sella and part of the lesser wing of the sphenoid are missing. The destruction also involves the diploe of the basilar bone (m). A2: Engel’s original illustration showing the gross aspect of the tumor as seen from a left and posterior view. The pituitary gland and the infundibulum have been replaced by a huge cyst (t), the size of a goose egg, covered by dura mater (red arrows). There is an opening to the cyst cavity (o). The pons cannot be seen but the cerebellum (c) and the medulla oblongata can be identified behind the lesion. B: The brain specimen of Engel’s pituitary-infundibular tumor no. 10 as currently stored in the Anatomical-Pathological Museum at the Narreturm. The tumor diagnosis written on the jar label was “cholesteatoma ad basin cerebri”, although Jakob Erdheim would later redefine this lesion as a hypophyseal duct tumor (craniopharyngioma) in his 1904 monograph. The museum identification number of the specimen (M. N. 1099) is the same indicated in Erdheim’s monograph to identify the tumor (Erdheim’s case no. 5, page 646 in his monograph, see reference 4). Notice that the torn cyst wall of this craniopharyngioma (CP) is covered by the skull base dura mater (yellow arrows), in an identical way as depicted in the sketch of the lesion in Engel’s dissertation

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This case is illustrated with two artistic drawings showing the whole tumor and the eroded cranial base [3] (Fig. 3A1, A2). This huge cystic lesion apparently originated within the sella, as the upper surface of the lesion was partly covered by dura mater, and subsequently extended towards the third ventricle, destroying the region of the tuber cinereum. No histological examination was available at that time, and the tumor was diagnosed according to its gross features as a softened sarcoma of the pituitary gland. This term, usually employed at Rokitansky’s pathological institute for hypophysial growths invading adjacent structures, implicated the concept of malignant behavior and ominous outcome [19,20,21,22]. A very interesting aspect of this case was the tumor tongue protruding through the nasopharynx, an anatomical anomaly indicating the presence of a patent craniopharyngeal canal. Engels linked this finding with a prior observation in a newborn of a prolapse of the sellar dura mater covering the hypophysis into the oral cavity, reported in 1775 by Joseph Thaddäus Klinkosch (1734–1778), an anatomist from Prague [23]. Nevertheless, Engels could not establish the nature of his pituitary tumor nor its presumed embryological origin.

The true nature of Engel’s pituitary case 10: a hypophyseal duct tumor or craniopharyngioma

In 1904, Jakob Erdheim (1874–1937), a young Austrian pathologist working at the Pathological Institute of Vienna, defined the new category of “hypophyseal duct tumors” (Hypophysenganggeschwülste), which included pituitary gland and infundibulum tumors with a presumed origin from cell remnants of an incompletely involuted hypophyseal duct, the embryological transitory canal connecting the embryo’s oral cavity with Rathke’s pouch (Fig. 4A, B) [4, 24]. Erdheim’s original term was later replaced by the name craniopharyngioma (CP), coined in 1929 by the American neurosurgeon Harvey Cushing (1869–1939) and still in use today [25, 26]. Erdheim identified this new tumor category after performing a thorough histological study of the pituitary tumor collection stored at the Vienna pathological museum, a methodology similar to the gross pathological investigation followed by Engel 65 years earlier [19, 24]. Among these cases, Erdheim could find and examine Engel’s case 10, a lesion he conclusively categorized as a hypophyseal duct tumor (Fig. 4C1, C2). Hence, this case, originally considered a “soft medullary sarcoma of the hypophysis” was re-defined as a hypophyseal duct tumor by Erdheim, his fifth case among the seven specimens with this diagnosis studied in his manuscript [4, 24].

Fig. 4
figure 4

A: A young Jakob Erdheim (1874–1937) working in the autopsy room of the Pathological-Anatomical Institute of Vienna around the time he published his monograph on hypophyseal-duct tumors. B: The main façade of Erdheim’s Institute today (photograph by the authors). C1: Artistic illustration showing the macroscopic aspect of the hypophyseal duct tumor (craniopharyngioma) number 5 examined and described in Jakob Erdheim’s monograph (which corresponds to Engel’s case no. 10). Lateral view of this huge cystic pituitary-infundibular tumor (T) occupying the region of the third ventricle and the hypothalamus. Note the layer of dura mater covering the upper portion of the tumor (red arrows) and the large opening in the cyst wall (purple arrow). C2: Illustrative drawing of a histological section of the cyst wall examined by Erdheim. Ramified nests of squamous epithelial cells that consist of prickle or spinous cells (a, b) lying on basal layer of cylindrical epithelium were characteristic of this tumor type (hypophyseal duct tumor or CP). In a few sites, a liquefaction of the stroma and the formation of pseudo-cysts were evident (e) as well as balls of stratified epithelium showing signs of calcification (c) (figures C1 and C2 from Erdheim J (1904) Über Hypophysengangsgeschwülste und Hirncholesteatome. Sitzungsb Kais Akad Wissen Math Naturw Klin 113: 537–726)

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In this huge (6 × 6 × 4.5 cm) pituitary cyst, Erdheim identified the typical flat stratified squamous epithelium of hypophyseal duct tumors (CPs) which was lining its inner surface. The epithelium rested upon a layer of fibrous connective tissue, which included cholesterol crystals. He also observed the characteristic process of liquefaction of the tumor stroma, with formation of microcysts coated by epithelial cells (stellate reticulum) [4] (Fig. 4 C2). Prickle cells were seen within the squamous epithelium as well as concentric arrangements of epithelial cells (whorls) and scattered foci of calcification. The cyst lumen contained a brownish fluid with blood clots. All this evidenced that this lesion originated from squamous epithelium of the hypophyseal duct, as Erdheim affirmed in 1904.

Engel’s pituitary case no. 10: the oldest preserved craniopharyngioma specimen

Engel’s dissertation was made possible thanks to the fabulous collection of pituitary tumor specimens stored at the pathological-anatomical museum of Vienna. Under the leadership of Carl Rokitansky, this collection was fundamental for the progress of pathology as a scientific field [2]. The museum is currently housed in the Narrenturm, also known as Fool’s Tower, a round building erected in 1784 next to the Allgemeines Krankenhaus that served as the first public institution created in Europe for mentally ill patients (Fig. 2B) [24, 27]. In 1971 the Narrenturm was designated as the site for Vienna’s Federal Pathologic-Anatomical Museum and it currently operates both as a museum and a center for pathological and anatomical research (Fig. 2C).

Among the 12 pituitary tumors studied in Engel’s dissertation, six showed gross pathological features compatible with craniopharyngiomas (Table 1). The oldest of these CP specimens is pituitary tumor number 10, autopsied in 1828. Remarkably, this pathological specimen is still stored in its original jar at the Narrenturm (Fig. 3). Recently, we studied the Narrenturm’s collection of pituitary/infundibulum tumors and were able to identify 25 CPs (unpublished data). As mentioned above, Engel’s case 10 is the oldest preserved specimen with this histological diagnosis, according to our research. As this case is the oldest tumor with a proven CP diagnosis in Erdheim’s 1904 seminal study, we can certainly conclude that Engel’s case 10 represents, to our knowledge, the world’s oldest preserved CP gross specimen. This specimen represents a true treasure not only for its historical importance, as its histological study was instrumental for the definition of CPs, but also as a landmark case from the original museum project that promoted pathology as the foundation of scientific medicine by the Second School of Medicine in Vienna. This specimen forms part of a pathologic material linking three generations of pathologists: Engel and Rokitansky, Anton Weichselbaum (1845–1920)—a disciple of Engel and mentor of Erdheim—and Jakob Erdheim, through the period from 1839 to 1937 [2]. The physiological functions of the pituitary gland and the infundibulum were gradually identified and integrated through the research on the clinical effects of pituitary tumors [15, 19, 22, 24]. Thus, the birth of neuroendocrinology owes much to the preservation of pathological specimens like this CP reported in Engel’s dissertation.

Conclusions

Joseph Engel’s dissertation on the pituitary gland and the infundibulum, written in 1839, represents a pioneering study on the history of neuroendocrinology providing one of the earliest insights into the functions of the hypophysis-hypothalamus complex. It includes the report of a giant cystic pituitary tumor whose histological examination by Jakob Erdheim facilitated the categorization of hypophyseal duct tumors (craniopharyngiomas). The original whole tumor specimen is stored at the Narrenturm and very probably represents the oldest preserved craniopharyngioma in the world.