Neurosurg Focus 18 (4):E7, 2005

Percival Bailey and the classification of brain tumors

SHERISE FERGUSON, M.A., AND MACIEJ S. LESNIAK, M.D. Division of , The Pritzker School of Medicine, Chicago,

Throughout his illustrious career, Percival Bailey made numerous contributions to the fields of , neu- roanatomy, , neuropathology, and, of course, neurosurgery. His expertise, his curiosity about the nervous system, and his desire to examine it from all angles were unique. With the exception of , Dr. Bailey made some of the greatest contributions in the area of neuro-oncology at the turn of the last century. In this essay the authors summarize the key episodes of Bailey’s life and discuss his impact on the classification and treatment of human brain tumors.

KEY WORDS • Percival Bailey • • • • tumor classification • neurosurgical history

Percival Bailey was born in 1892 in the southernmost routine dissection of the pituitary, Bailey unintention- part of Illinois, a rural area known as “Little Egypt.” He ally damaged the infundibular artery. At the time, Bailey spoke warmly of his memories of childhood and growing thought his mistake was an incredible blunder. Neverthe- up in this small town in his autobiography, Up from Little less, the next morning he found a large pool of urine on Egypt.8 Bailey’s early education took place in a one-room the floor next to the dog. To his surprise, he realized that schoolhouse and then at Southern Illinois Normal Univer- he had produced polyuria without exposing the pituitary sity. He originally intended to become a school teacher, gland. Bailey discussed his finding with a visiting neu- but with the death of his mother when he was 19 years old, rologist from Brussels, Dr. Frederic Bremer. In further his interest shifted to medicine.23 In 1912 Bailey trans- collaboration, the two found that without touching the pi- ferred to the University of Chicago, and while taking a tuitary, puncture of the hypothalamic infundibulum pro- neuroanatomy course he became instantly enamored with voked adiposogenital dystrophy and diabetes insipidus, the nervous system. In keeping with his newfound pas- and they attributed this result to disturbance of hypothala- sion, after earning his undergraduate degree Bailey went mic innervations of the pituitary.9,28 This was a ground- on to complete his doctoral dissertation on the develop- breaking finding and a major contribution to the rising ment of the choroid plexus.28 Indeed, his first publications field of neuroendocrinology. were on this very topic.6,7 By teaching gross anatomy, Bai- The partnership of Cushing and Bailey produced many ley was able to earn a medical education from Northwest- breakthroughs in the field of neurosurgery. Specifically, ern University in Evanston, Illinois. After graduating in their book A Classification of the Tumors of the Glioma 1918, he began a 9-month internship at Mercy Hospital in Group on a Histogenetic Basis with a Correlated Study of Chicago.23 Prognosis,15 which was published in 1926, formed the At the end of his internship, Bailey was positive that basis of modern-day neuro-oncology. Prior to the collabo- he wished to develop the field of neuroscience to a greater ration of these two pioneers, virtually all tumors of the extent. Apparently, he was not particularly concerned brain were called . In 1867, Virchow was the first whether his activities were in neurology, psychiatry, or to put forward the idea that these tumors arose from in- neurosurgery. He wrote two letters, one to Adolf Meyer, a terstitial brain tissue. Then, in 1875, Golgi showed that prominent psychiatrist at Johns Hopkins, and the other to some brain tumors contain distinctive star-shaped neu- Harvey Cushing in Boston, who was already recognized roglial cells of the brain, and he distinguished soft and as a brilliant neurological surgeon. As fate would have it, hard forms.5 Dr. Cushing replied first, and so Bailey arrived at the Peter During this era, it was also known that some tumors Bent Brigham Hospital in 1919.28 It was under the tutelage could be either aggressive or benign. Nevertheless, the of Cushing that Bailey flourished as a neurological sur- classification of brain tumors was in its infancy. Some, geon and made some of his most impressive contributions such as Cushing himself, considered the classification of to the scientific community. glial tumors to be in a state of disarray. Bailey and Cush- Interestingly, Bailey’s first contribution was entirely ing believed that the existing classifications of gliomas accidental. Some of Cushing’s earlier research was dedi- were both inadequate and confusing. They also believed cated to the study of hypophysectomy in dogs, and as his that the only way order could be attained was through the student, Bailey was assigned to these studies. During a meticulous examination of a large series of tumor speci-

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Unauthenticated | Downloaded 09/25/21 10:40 AM UTC S. Ferguson and M. S. Lesniak mens and medical records in cases that had been observed He and Cushing had specimens of 31 of these intriguing over a period of years, from the onset of symptoms to the tumors, each of which they scrutinized in detail in an at- death of the patient.1 With this in mind, they set out to un- tempt to determine its natural history. At that time, Bailey derstand the basis of the structural variability shown by and Cushing formulated a theory on the origin of the gliomas and to determine whether these histological dif- . As recounted in Kunschner,27 they pos- ferences carried clinical implications. Furthermore, they tulated that this tumor was derived from embryonic undif- aimed to refute the ubiquitous notion that microscopic ex- ferentiated cells in the ependymal lining of the fourth ven- amination of a specimen removed at operation could not tricle. Moreover, they described the characteristic gross serve to predict the clinical course of the disease.14 Fortu- and microscopic structure of this tumor; its reddish-gray nately, Cushing had an extensive collection of brain tumor color, extremely cellular nature, numerous mitotic figures, specimens amassed from his surgical experiences and and the formation of pseudorosettes, as detailed later by Bailey was more than happy to take on such an assign- Bailey.5 Additionally, Bailey observed the tendency of this ment. It seemed to be the ideal opportunity to apply his tumor to spread to the leptomeninges, which proved val- knowledge of neuropathology and neuroanatomy to neu- uable in terms of treatment considerations. Bailey and rosurgery. Cushing contributed not only to the description of this This auspicious work began in 1922 when Bailey first neoplasm but also to its treatment. At the time, the grim began to classify the gliomas, working intermittently for prognosis for patients with was well the next 3 years. Bailey began by going through the spec- documented. This fact encouraged Cushing to introduce imens as they came into the laboratory and arranging them radiotherapy in the postoperative care of patients with in groups according to length of the patient’s survival.1 medulloblastomas. In 1928 and 1930, Bailey went further, Additionally, new methods such as impregnation allowed publishing articles about the effects of radiotherapy on for the demonstration of both neuronal and interstitial as- medulloblastomas. Interestingly enough, he was the first pects of the nervous system.32 All in all, Bailey exhaus- to explain the complications associated with this therapy, tively examined and classified the pathological material including brain edema.2,18 This work paved the way for and records of a total of 414 cases of glioma in Cushing’s the use of craniospinal radiation treatment in medullo- series and performed histological tissue studies in 254 of blastomas. these.24 Based on the predominant cellular configuration, Bailey and Cushing spent almost 10 years working Bailey classified these tumors into 13 categories. together, both as clinicians and as researchers. In this time, This histological categorization was the first ever and they wrote a second monograph titled Tumors Arising formed the basis for all subsequent classification. The re- from Blood-Vessels of the Brain; Angiomatous Malfor- sults of the glioma studies were first reported by Cushing mations and ,26 in 1928. Although in the Cameron Prize Lectures given at the University of this book did not receive the recognition accorded to their Edinburgh in October of 1925.24 In 1926, the completed earlier work on tumors of the glioma group, it was ahead monograph by Bailey and Cushing, A Classification of of its time in its depiction of the microscopic structure of the Tumors of the Glioma Group on a Histogenetic Basis hemangioblastomas.22,25,27 In fact, it was Bailey and Cush- with a Correlated Study of Prognosis, was published.14 ing who introduced the term . Another This book completely revolutionized the understanding of noteworthy accomplishment of this pair was their estab- neuro-oncology, and for first time the neurosurgical com- lishment of the microscopic structure of pituitary adeno- munity was presented with an orderly classification of gli- mas. In 1928, they were the first to describe the condition omas based on the tumor’s natural history and clinical known as fugitive acromegaly, in which patients may ex- course. This was, of course, an achievement of immense hibit physical stigmata of acromegaly without biochemi- practical value and earned Bailey and Cushing worldwide cal evidence of the disease.16,22 recognition. After a decade with Cushing, Bailey was ready to ven- In 1927, Bailey3 simplified the glioma classification to ture out on his own, and in 1928 he was selected to head 10 groups, and this new system correlated the tumor type the neurosurgery section at the University of Chicago. with survival (Fig. 1). He also went on to publish a prac- Bailey, delighted with this opportunity, left Cushing’s lab- tical histological atlas of gliomas.4 Cumulatively, the work oratory in Boston with his newly refined neurosurgical ex- of Bailey and Cushing not only changed antiquated think- pertise. After Bailey accepted the associate professorship ing by showing that the microscopic structure of a tumor in 1929, he immediately endeavored to launch an Institute is important for prognosis, but also completely revamped of the Neurosciences. He intended to recruit into his new the understanding of these tumors. In fact, the histopath- department men with backgrounds in all aspects of the ological basis of brain tumors in relation to patient survi- neurosciences, including neurochemistry and neurophysi- val and outcome still influences present-day neurosurgical ology.20 He also started the Neurology Club at the Univer- thought. sity of Chicago, with the goal of encouraging a conducive The collaboration of Bailey and Cushing did not end atmosphere for the growth of inquisitive neuroscientific with their classification system. In 1925, Bailey and Cush- minds.22 In addition to administrative, clinical, and re- ing published a significant paper on medulloblastomas search responsibilities, Bailey was an exceptional teacher. titled Medulloblastoma Cerebelli: a Common Type of During his period at the University of Chicago, Bailey Midcerebellar Glioma of Childhood.15 During their en- trained William H. Sweet, who later became the head of deavor to classify gliomas, Bailey had isolated a peculiar neurosurgery at Harvard. Bailey also trained , a tumor that occurred primarily in the cerebellum of chil- rising neuropathologist, who later became the head of dren, for which he suggested the name medulloblastoma. neurosurgery at and codiscover-

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Fig. 1. Chart showing glioma classification scheme devised according to the cellular constitution of each group of tumors. (Reprinted with permission from Bailey P: Intracranial Tumors, ed 2. Springfield, IL: Thomas, 1948.) er of the Kluver–Bucy syndrome. Unfortunately, Bailey’s Intracranial Tumors of Infancy and Childhood,10 which vision of creating a neuroscience institute did not materi- was the first significant writing on this topic; and The Ori- alize. It seemed that others in positions of power did not gin and Nature of Meningeal Tumors.13 In addition to re- share his zeal, and a disheartened Bailey left the Univer- search and teaching the aforementioned outstanding stu- sity of Chicago in 1939.20 Not only did the university lose dents, Bailey was active in teaching undergraduates, and one of its greatest minds but it also forfeited the chance to he established the university clinics as an exceptional in- be a preeminent neuroscience center in the world. stitution for the treatment of brain tumors. During his time at the University of Chicago, Bailey Bailey’s writings on the subject of brain tumors are so continued to pursue his interest in brain tumors. The first extensive that it is impossible to do them all justice in a tumor type he investigated was the . As short treatise. It must be emphasized, however, that he early as 1924, in his paper titled The Interstitial Tissues of made significant contributions to the study of meningio- the Central Nervous System,17 Bailey proposed that, be- mas. In addition to his article titled The Origin and Nature cause were so closely related, one of Meningeal Tumors,13 which he wrote with Bucy in could expect to find gliomas composed primarily of oligo- 1931, Bailey also dedicated a large portion of his book In- dendroglia. Nevertheless, due to a lack of laboratory tech- tracranial Tumors5 (Fig. 2) to the detailed analysis of the nology, this theory could not be fully investigated. With natural history, diagnosis, and treatment of . the passage of years, the development of new laboratory From a neuropathological perspective, Bailey, with the aid methods, and the help of Bucy, Bailey was finally able to of Bucy, contributed much to our knowledge of the struc- engage in an in-depth study of this matter. With the publi- ture of these tumors, as is evidenced by this passage from cation of their memorable paper Oligodendrogliomas of the aforementioned book: “The ordinary meningeal tumor the Brain12 in 1929, these men were the first to confirm the is more or less a bulbous mass, separated from the nervous existence of tumors that were, in fact, composed of oligo- tissue by a capsule of connective tissue but adherent to the dendroglia and to establish this type of glioma as a defi- dura mater.” Furthermore, the descriptions of the micro- nite entity. Other works of Bailey and his pupil Bucy scopic findings provided by Bailey are still used in the included Astroblastomas of the Brain,11 which was one of teaching of medical students today: “ the cells of these the first works to characterize the intricacies of this tumor; masses are somewhat elongated and wound around each

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Fig. 2. Reproduction of the inside cover of Bailey’s book. Intra- cranial Tumors was one of the most significant academic accom- plishments of his career. (Reprinted with permission from Bailey Fig. 4. Schematic drawings representing the distribution of P: Intracranial Tumors, ed 2. Springfield, IL: Thomas, 1948.) meningiomas. (Reprinted with permission from Bailey P: Intra- cranial Tumors, ed 2. Springfield, IL: Thomas, 1948.) other to form whorls. The central cells of the whorls un- dergo a hyaline transformation and then become calcified. ularly invade the brain but can at times affect the underly- They cause a gritty noise when the tumor is cut, hence ing bone, and reminds us that alterations in the cranium their name of psammoma (sand-like) bodies.” Bailey also are characteristic of this tumor. These changes are charac- noted that the microscopic structure and distribution of terized by both erosion and formation of bone (Fig. 5). In these tumor cells resembled that of arachnoid granulations his book,5 Bailey’s approach to the discussion of menin- (Figs. 3 and 4). Finally, he taught us that these tumors reg- giomas is through cases he encountered in clinical practice

Fig. 5. Schematic drawings based on two x-ray films of the parasagittal region demonstrating alterations of the cranium due to a meningioma. A: Erosion by parasagittal lacunae. B: Erosion Fig. 3. Drawing showing the location of arachnoid granulations and formation of bony spicules by a meningioma. (Reprinted with over the skull base. (Reprinted with permission from Bailey P: permission from Bailey P: Intracranial Tumors, ed 2. Spring- Intracranial Tumors, ed 2. Springfield, IL: Thomas, 1948.) field, IL: Thomas, 1948.)

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any other type of tumor. He also stressed that this neo- plasm must be carefully distinguished from all other con- ditions that cause focal epilepsy. Bailey taught us how to recognize the external clues of a meningioma, including the presence of visibly dilated, tortuous extracranial blood vessels and a prominent crani- al protuberance (Fig. 6). Regarding meningiomas arising from the tuberculum sellae (Fig. 7 left), Bailey contended that this diagnosis can be suspected when a bitemporal visual defect develops in a middle-aged patient. On the other hand, in meningeal tumors arising along the sphe- noidal bone, unilateral exophthalmos is the most promi- nent symptom. Additionally, the triad of anosmia, optic atrophy, and mental status change should lead one to sus- pect a meningioma of the olfactory groove (Fig. 7 right).5 Fig. 6. Drawings of patients showing characteristic skull Even though it was not his most famous work, Bailey’s changes associated with meningiomas. (Reprinted with permission contribution to our present understanding of meningiomas from Bailey P: Intracranial Tumors, ed 2. Springfield, IL: Thom- was quite significant. as, 1948.) In 1939 Bailey transferred to the University of Illinois and joined the faculty with the title of Distinguished Pro- fessor of Neurology and Neurological Surgery. He con- tinued his clinical practice, taught neuropathology, and intermixed with excerpts from current research articles on expanded his research to include neurophysiology. The the subject, including some of his own, and his insights on change in the direction of his research proved to be very diagnosis and treatment. Bailey describes four syndromes valuable to the neurosurgical community. It was at this that typify meningeal tumors, specifically syndromes of time that Bailey began to use temporal lobectomy for the the central region, the olfactory groove, the sphenoidal treatment of some forms of epilepsy.33 He also collaborat- wing, and the sellar tubercle. Despite the fact that menin- ed with Gerhardt von Bonin, a professor of neurology at giomas in these various locations have some similarities, the University of Illinois, to uncover the corticocortical he thought that the manifestations were different enough connections in the brain and the functions of these con- to warrant individual attention. nections in monkeys. Prior to this work, only Brodmann21 According to Bailey, the parasagittal central region is a and Von Economo and Koskinas31 had published studies very common site of origin for meningiomas, hence the of the cerebral cytoarchitecture. Bailey and von Bonin signs of it are of particular importance. He described a pa- wrote two books, The Neocortex of Macaca Mulatta30 in tient who suffered from epileptic seizures that began in his 1947, and The Isocortex of Man19 in 1951. These manu- foot and subsequently involved his leg and face. Bailey scripts were the first to define with precision the cytoar- explained that such a course of events is very characteris- chitecture of the human cortex. Furthermore, in 1959 tic of meningiomas in this region and is rarely caused by German neurologist Georg Schaltenbrand,29 along with

Fig. 7. Left: Drawing showing a meningioma of the tuberculum sellae. Right: Drawing showing a meningioma of the cribriform region with invasion of the nasal cavity. (Reprinted with permission from Bailey P: Intracranial Tumors, ed 2. Springfield, IL: Thomas, 1948.)

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Bailey, produced a stereotactic atlas of the human brain 8. Bailey P: Up from Little Egypt. Chicago: Buckskin Press, that became an instant classic because of the caliber and 1969 accuracy of the photographs of the brain. Despite the fact 9. Bailey P, Bremer F: Experimental diabetes insipidus. Arch In- that his later research was not specifically directed at brain tern Med 28:773–803, 1921 10. Bailey P, Buchanan DN, Bucy PC: Intracranial Tumors of In- tumors, the practical applicability of this work to neuro- fancy and Childhood. Chicago: University of Chicago Press, surgical practice is clear. 1939 When he suffered cataracts later in his life, Bailey was 11. Bailey P, Bucy PC: Astroblastomas of the brain. Acta Psychi- unable to continue to work in the laboratory, with the mi- atr Neurol Scand 5:439–461, 1930 croscope, or in the operating theater.28 His interest in the 12. Bailey P, Bucy PC: Oligodendrogliomas of the brain. J Pathol nervous system did not cease with the end of his neuro- Bacteriol 32:735–751, 1929 surgical career. He had long been interested in the rela- 13. Bailey P, Bucy PC: The origin and nature of meningeal tumors. tionship between the brain and human behavior, so natu- Am J Cancer 1:15–54, 1931 rally his attention turned to psychiatry. This focus was 14. Bailey P, Cushing H: A Classification of the Tumors of the quite fitting, in that it was the only neuroscientific field he Glioma Group on a Histogenetic Basis With a Correlated Study of Prognosis. Philadelphia: Lippincott, 1926 had not yet conquered. In 1951 he was appointed director 15. Bailey P, Cushing H: Medulloblastoma cerebelli: a common of the Illinois State Psychiatric Institute, and he dedicated type of midcerebellar glioma of childhood. Arch Neurol Psy- the remainder of his career to cultivating this field. chiatry 14:192–223, 1925 With the death of Percival Bailey in 1973, the neurosur- 16. Bailey P, Cushing H: The microscopic structure of the adeno- gical community lost an exceptional scientist. In his life- mas in acromegalic dyspituitarism (fugitive acromegaly). Am J time, he covered the full spectrum of neurological science, Pathol 4:545–563, 1928 including neurology, neurosurgery, neuropathology, and 17. Bailey P, Hiller G: The interstitial tissues of the central nervous psychiatry, to name just a few. During his career, Bailey system. J Nerv Ment Dis 59:337–361, 1924 truly revolutionized the study of the nervous system and 18. Bailey P, Sosman MC, van Dessel A: Roentgen therapy of gli- omas of the brain. Am J Roentgenol Rad Ther 19:203–264, was able to make numerous contributions to the diagnosis, 1928 treatment, and study of brain tumors. He is known and 19. Bailey P, von Bonin G: The Isocortex of Man. Urbana, IL: honored in the whole medical and scientific community. University of Illinois Press, 1951 Bailey was president of the American Neurological 20. Blustein BE: Percival Bailey and neurology at the University of Association and the Society of Neurological Surgeons, Chicago, 1928–1939. Bull Hist Med 66:90–113, 1992 and he was awarded an honorary Doctor of Science de- 21. Brodmann K: Vergleichende Lokalisationslehre der Gross- gree by Southern Illinois University, the University of hirnrinde in ihren Prinzipien dargestellt auf Grund des Zel- Chicago, and the University of Paris.22 He also held hon- lenbaues. Leipzig: Barth, 1909 orary memberships in approximately 25 foreign medical 22. Bucy PC: In memoriam. Percival Bailey. Biol Psychiatry 8: and scientific societies. To many, he may seem capricious 343–345, 1974 23. Bucy PC: Percival Bailey: May 9, 1892–August 10, 1973. about which field of medicine or academics he chose to Biogr Mem Natl Acad Sci 58:3–46, 1989 pursue. Bailey’s feelings on the matter can be summed up 24. Canale DJ, Longo LD: Harvey Cushing and pediatric neuro- in this statement: “It may look to some as though I have surgery. Neurosurgery 27:602–611, 1990 never been able to make up my mind. I do not feel that 25. Cushing H, Bailey P: Hemangiomas of the cerebellum and reti- way about it. My interest had always been in the nervous na (Lindau’s disease). Arch Ophthamol 57:447–463, 1928 system and how it works. This problem can be approached 26. Cushing H, Bailey P: Tumors Arising From the Blood-Ves- by many pathways.”8 Throughout the world, Bailey was sels of the Brain; Angiomatous Malformations and Heman- acknowledged as having the most expansive understand- gioblastomas. Springfield, IL: Thomas, 1928 ing of the central nervous system. He truly lived up to the 27. Kunschner LJ: Harvey Cushing and medulloblastoma. Arch Neurol 59:642–645, 2002 title of “Mr. Neurology.” 28. Magoun HW, Clemente CD: Percival Bailey: 1892–1973. Anat References Rec 186:235–237, 1976 29. Schaltenbrand G, Bailey p: Introduction to Stereotaxis, With 1. Bailey OT: Genesis of the Percival Bailey-Cushing classifica- an Atlas of the Human Brain. Stuttgart: Thieme, 1959 tion of gliomas. Pediatr Neurosci 12:261–265, 1985–86 30. von Bonin G, Bailey P: The Neocortex of Macaca Mulatta. 2. Bailey P: Further notes on the cerebellar medulloblastomas. The Urbana, IL: University of Illinois Press, 1947 effects of roentgen radiation. Am J Pathol 6:125–135, 1930 31. von Economo C, Koskinas GN: Die cytoarchitektonik der 3. Bailey P: Further remarks concerning tumors of the glioma hirnrinde des erwachsenen menschen. Berlin: J Springer, group. Bull Johns Hopkins Hosp 40:354–389, 1927 1925 4. Bailey P: Histological atlas of gliomas. Arch Pathol Lab Med 32. Walker AE: Obituary. Percival Bailey. 1892–1973. Surg Neu- 4:871–921, 1927 rol 2:85–86, 1974 5. Bailey P: Intracranial tumors, ed 2. Springfield, IL: Thomas, 33. Wortis J: Editorial: Percival Bailey. Biol Psychiatry 8: 1948 263–264, 1974 6. Bailey P: The morphology and morphogenesis of the choroid plexuses, with special reference to the development of the lat- eral telencephalic plexus in chrysemys marginata. J Comp Manuscript received January 25, 2005. Neurol 26:507, 1916 Accepted in final form March 14, 2005. 7. Bailey P: Morphology of the roofplate of the forebrain and the Address reprint requests to: Maciej S. Lesniak, M.D., 5841 lateral choroid plexuses in the human embryo. J Comp Neurol South Maryland Avenue, MC 3026, Chicago, Illinois 60637. email: 26:79, 1916 [email protected].

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