Jakob Erdheim (1874-1937) was a Viennese pathologist who identified and defined a category of pituitary tumors known as craniopharyngiomas. He named these lesions "hypophyseal duct tumors" (Hypophysenganggeschwülste), a term denoting their presumed origin from cell remnants of the hypophyseal duct, the embryological structure through which Rathke's pouch migrates to form part of the pituitary gland. He described the two histological varieties of these lesions as the adamantinomatous and the squamous-papillary types. He also classified the different topographies of craniopharyngiomas along the hypothalamus-pituitary axis. Finally, he provided the first substantial evidence for the functional role of the hypothalamus in the regulation of metabolism and sexual functions. Erdheim's monograph on hypophyseal duct tumors elicited interest in the clinical effects and diagnosis of pituitary tumors. It certainly contributed to the development of pituitary surgery and neuroendocrinology. Erdheim's work was greatly influenced by the philosophy and methods of research introduced to the Medical School of Vienna by the prominent pathologist Carl Rokitansky. Routine practice of autopsies in all patients dying at the Vienna Municipal Hospital (Allgemeines Krankenhaus), as well as the preservation of rare pathological specimens in a huge collection stored at the Pathological-Anatomical Museum, represented decisive policies for Erdheim's definition of a new category of epithelial hypophyseal growths. Because of the generalized use of the term craniopharyngioma, which replaced Erdheim's original denomination, his seminal work on hypophyseal duct tumors is only referenced in passing in most articles and monographs on this tumor. This article is intended to pay tribute to Erdheim's fundamental breakthroughs, his discovery of craniopharyngiomas and their functional damage to the hypothalamus. On these fundamental achievements, Jakob Erdheim should be recognized as the true father of craniopharyngiomas.
A heterogeneous group of epithelial cystic tumors developed at the infundibulum and the third ventricle disconcerted pathologists at the dawn of the twentieth century. Very little was known at that time about the physiological role played by the pituitary gland, and there was almost complete ignorance regarding the function of the hypothalamus. Acromegaly, or enlargement of acral body parts, described in 1886 by Pierre Marie, was the only disease linked to primary hypertrophies of the pituitary gland, known as "pituitary strumas". A growing number of young patients manifesting an unexplained combination of physical and mental symptoms, including absent or delayed sexual maturation, progressive obesity, abnormal somnolence, and dementia-like changes in behavior were reported to present large solid-cystic tumors which characteristically expanded within the infundibulum and third ventricle, above an anatomically intact pituitary gland. Between 1899 and 1904, five seminal autopsy studies from different countries thoroughly described the anatomical relationships and histological features of this newly recognized type of infundibular tumors. These cases were instrumental in fostering the systematic investigation of similar lesions by the Austrian pathologist Jakob Erdheim (1874-1937), who in 1904 was able to classify these infundibulo-tuberal cysts under the common category of hypophyseal duct tumors. The pioneering American neurosurgeon Harvey Cushing (1869-1939) unsuccessfully attempted to surgically remove one of these cysts, for the first time in history, in 1902. The term "craniopharyngioma", chosen by Cushing in 1929 to designate these lesions, would eventually prevail over Erdheim's more accurate denomination, which linked their origin to squamous cell remnants derived from the embryological structures that give rise to the pituitary gland. This paper presents a comprehensive, renewed account of the five clinical-pathological reports which laid the groundwork for the proper clinical diagnosis, topographic conceptualization and pathological categorization of craniopharyngiomas.
The major classes of psychotropic drugs were introduced in an extraordinary decade of discovery between the late 1940s and late 1950s. In the present climate of pessimism about the absence of new drug development, it may be instructive to look back at the research methods used during that era. The study that identified the first antidepressant is a case in point. It was conducted by Roland Kuhn, a Swiss psychiatrist working in a remote psychiatric hospital. Kuhn, like the other pioneering researchers of his day, was given access to new drug entities, and the method he used to discover their clinical effects was open-minded, exploratory, comprehensive, clinical observation. The paper that reported the results of his study has not been available in English, but because of its historical significance and because Kuhn's achievement stands in such contrast to the present impasse in drug development, the authors thought that it might be informative to read about his discovery in his own words. Accordingly, one of the authors (M.R.) translated the paper into English, and they now present excerpts of that translation with the intent of encouraging reevaluation of contemporary approaches to drug discovery. By today's clinical research standards, Kuhn's method of unfettered, exploratory, clinical observation was substandard, haphazard, even messy. Yet it produced a major breakthrough-the discovery that a drug can alleviate depression-that has had a lasting impact on the treatment of depression and on the development of antidepressant drugs. Kuhn's experience might usefully inform our strategies of drug development.
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