Section 3 -

The Career and Influence of Pierre Masson (1880-1959) Sean Moore Department of Pathology, McGill University Montréal, Canada Thomas A. Seemayer Department of Pathology and Microbiology University of Nebraska Medical Center Omaha, NE, USA.

Pierre Masson was one of the towering figures of pathology in the 20th century, in particular in the field of histopathology of human tumors (Fig. 1). He was born in Dijon, in the heart of Burgundy, into a family in which the practice of law was predominant, but he chose to study medicine. Following completion of his first year in the Faculty of Medicine in his home town, he decided to continue his studies in Paris. While preparing for his internship he suffered a serious attack of typhoid fever that interrupted his studies and forced him to return to Dijon to convalesce Fig.1. Pierre Masson Having reestablished contact with the famous biologist Eugène Bataillon, whose lectures had aroused his enthusiasm, Masson became his assistant, a position he occupied for 5 years. It was during this time that Bataillon pursued work that led to the discovery of injury-induced parthenogenesis. Under his direction, Masson was introduced to research, and the rigor it demands. He also acquired a solid grounding in biology and embryology, becoming familiar with a variety of laboratory techniques. In addition he developed an interest in anatomical pathology owing to the collaboration of friendly surgeons who sent him tumors for examination. Enriched by this experience and with a degree in Natural Science, Masson returned to Paris in 1907 to complete his medical studies. Masson completed his studies, while being chief of a laboratory service of the Lariboisière Hospital. This was the time when his career became definitely oriented toward anatomical pathology. His doctoral thesis, which he defended in 1909 and which gained the praise of the examiners, was devoted to "ganglioneuroma of the sympathetic nervous system." He then left Lariboisière and became laboratory chief for the famous surgeon Gosset at the Salpêtrière Hospital and also assistant to Borrel at the Pasteur Institute. Borrel was a microbiologist, histologist, and a brilliant researcher, who, at this time, was particularly interested in the cancer problem. These 2 positions provided Masson with rich material in anatomical pathology and a superb research environment. He published several anatomoclinical studies of various lesions, predominantly tumors. He was fascinated by technical developments, as was Borrel. He introduced saffron as a stain for collagen. He devised the famous trichrome stains with which his name would become associated. These innovative techniques, applied with exacting detail, combined with his talent for observation and his scientific perspicacity, produced remarkable results. His studies on carcinoid tumors provide an example of this. In studying carcinoids of the appendix he was struck by the fact that the neoplastic cells contained abundant granules in the basal region below the nucleus. These secretory granules stained strongly with silver nitrate. The cellular arrangement and polarization of the secretory material suggested to him that these were in reality endocrine tumors. He then sought to identify a cell type in the intestine, which could be the precursor of these tumors. His attention was drawn to the enterochromaffin cells (Kulchitzky cells), and he showed that they had the same features as the cells of carcinoid tumors, including their affinity for silver stains. These findings were revealed in a communication to the Academy of Science entitled "The Endocrine Gland of the Human Intestine" and in a publication entitled "The Endocrine Tumors of the Intestine." The confidence and insight of Masson were well illustrated by the titles given to these 2 publications. It would take almost 40 years to have definitive confirmation of these postulates with the characterization of the carcinoid syndrome. This Parisian period, during which there were some 40 publications, was interrupted in 1914 by the commencement of war. Conscripted as a regimental physician, he was taken prisoner during the German offensive in Belgium. He spent 11 months in an officers' detention camp in Prussia where he occupied his time reading German treatises in anatomical pathology. Then, owing to a prisoner exchanged under the auspices of the Red Cross, he returned to France. He was subsequently assigned to the Bouleuse-en Champagne Centre. This was a military hospital but was also a veritable school of the Medicine and Surgery of war, with a mission of teaching and research. Directed by Claudius Regaud, the center gathered together eminent surgeons, internists, and scientists. The laboratories were entrusted to 2 Pasteur Institute colleagues: Magrou in microbiology and Masson in anatomical pathology. In spite of the difficult conditions, Masson completed 3 research projects, notably on wound healing. With the end of hostilities, France regained Alsace and its capital city of Strasbourg, which had been annexed by Germany following the war of 1870. Pierre Masson was named to the Chair of Anatomical Pathology of Strasbourg, which had been made famous by former celebrated occupants such as von Recklinghausen, Chiari, and Mönckeberg. His nomination could have appeared surprising because Masson was only 38 years old and had not previously occupied any rungs on the ladder of the university hierarchy. It is likely that influential people who were very familiar with his career intervened (Gosset and his Bouleuse colleagues were mentioned), convinced as they were of the great worth of Masson. The Anatomical Pathology Institute at Strasbourg is an imposing building with an interior grass courtyard in which there is a pedestal supporting the bust of von Recklinghausen. When Masson arrived early in 1919 the faculty members, all Germans, had left. Only 2 laboratory technicians from Alsace remained and shortly there would be 75 students to instruct. Masson invited 2 colleagues who were friends, L. Gery and J. F. Martin, to join him. Soon 4 young Alsatians, all talented but novices, also came into the Intitute: Wolff, Wohlhuerter, Oberling and Berger. Charles Oberling, who became famous, was to describe the Institute years later as being at that time "the centre of intense activity where the lights were often not extinguished till late at night. Our chief, still young and full of enthusiasm, was always beside us, turning our attention from too much preoccupation with book learning, and urging us to address ourselves to the microscope to read therein the great book of nature." Masson's numerous tasks, including a considerable teaching load, which he fulfilled very successfully, did not remove him from his research activities. Among other publications, he provided the first description of a particular type of hemangioma, which he named "vegetant intravascular hemangioendothelioma," often referred to as "Masson's angioma." The identification of glomus tumors and their origin is another classical work. While pursuing his research on argentaffin cells, he approached the problem of the histogenesis of pigmented nevi. He showed that the melanoblasts belonged to a different cell line than the epidermal cells. Moreover, he identified nerve elements in the dermal component of nevi. Masson then proposed that melanoblasts were of neuroectodermal origin. Again, this insight was ahead of its time, and several decades were to transpire before the derivation of melanoblasts from the neural creast would be established by embryologic studies. In addition to these and many other publications, Masson wrote a book entitled Human Tumors, Histology, Diagnosis, and Technique, which immediately became the bible for histopathologists. Elegantly written, clear and precise, it was a very personal work that, in addition to giving a detailed description of tumors, considered their classification, origin, and histogenesis within the framework of general biology and embryology. For Masson accurate histologic diagnoses required histologic preparations of high quality; therefore, the book included a detailed chapter on techniques, which in itself was a classic. In a few years, the Institute became a famous center to which visitors and students flocked from all over the world. Thus it was with surprise and consternation that it became known at the end of 1926 that Masson had accepted the chair of Anatomical Pathology at the University of Montréal. The reasons for his decision have long been the subject of discussion, but it appeared that 2 factors had played a part; first the pressing invitation from the University of Montréal, and second, Masson's opposition to the system of concours (competitive examinations), which was about to be adopted in Strasbourg. The contacts between Masson and Québec and French Canadians, although intermittent, had been spread out over a longer period and had been more frequent than was generally perceived. The first encounter went back to 1918 when the war was drawing to a close. On May 18 it was suddenly learned at the Bouleuse Centre that German troops had crossed the river Vesle, less than 15 kilometers away. An emergency evacuation of the hospital became necessary. Regaud commissioned Masson and Magrou to go to Troyes to see if it would be possible to evacuate the Canadian hospital located in a girls' high school. Masson was warmly impressed by the encounter, say "the physicians, all French Canadians, received us with open arms, evacuating their patients and freeing up their hospital for us. Such was my first contact with Canadian physicians." In 1922 Abraham Flexner, author of the famous report on the faculties of medicine in the United States and Canada, invited 6 Strasbourg faculty members, including Masson, to visit several American universities. Masson accepted but asked to include a side trip to the Province of Quebec, and thus he was to visit Montréal for the first time. Berger, whom Masson always considered to be one of the students with whom he had the closest relationship and who had become chief of the Anatomical Pathology laboratory in Paris Radium Institute, had departed for the city of Québec to take up a post as Professor at Laval University. Moreover, at that time, 2 young French Canadians, Edouard Morin of Québec and Louis Charles Simard of Montréal, arrived in Strasbourg for periods of training at the Institute. In Montréal, Professor Latreille, responsible for teaching Anatomical Pathology, was sick and would be retiring soon. Enthusiastic and determined, Simard asked Masson if he would consider a position in Montréal. On his return, where he took charge of the Anatomical Pathology service at the Notre-Dame Hospital, Simard persuaded the authorities of the Faculty of Medicine of the University of Montréal to undertake official overtures to Masson. At the same time, in Strasbourg, The Faculty of Medicine planned to adopt the system of concours for the recruitment of teaching faculty. Masson was convinced that this system would be an impediment to the development of research. The best students would want to concentrate their efforts on preparing for the concours and would, with rare exceptions, be lost to research. In spite of the objections of Masson the system of concours was implemented and there is no doubt that Masson was disappointed. On the other hand the approaches of the University of Montréal continued. In the fall of 1926 Masson answered the call of "my Canadian cousins," as he would term it in his first lecture in Montréal. The links with Strasbourg were not cut off, since he at first accepted a mission of 3 years. As he noted much later, he added a zero to the three to make 30. On January 2, 1927, Pierre Masson, now 46 years of age, arrived in Montréal and embraced a new career with vigor. As well as being the Chairman at the Faculty, he was also Director of the Anatomical Pathology laboratories in 3 teaching hospitals: Notre Dame, l'Hôtel-Dieu, and l'Hôpital Sainte-Justine. Masson integrated his activities in practice, teaching, and research by devoting the mornings to the hospitals and the afternoons to the university, where he pursued his research work and gave his lectures. From the beginning he said that he felt completely at home in the French-Canadian environment. The clarity, elegant language, and vivid imagery of his lectures, accompanied by colored slides and blackboard drawings, which he made himself and modified during his presentation to illustrate the evolution of lesions, fascinated his students. The end of the lectures was greeted with enthusiastic applause, a sign of appreciation that was invariably given. As foreseen by Simard, Masson created a school. Young physicians chose Anatomical Pathology as their specialty: Bernier, Riopelle (who filled the same function at Hôtel-Dieu as Simard at Notre-Dame), Manseau, Martin, Laurin, Gelinas, to list only his first assistants. This team, dispersed in the hospitals in the morning, regrouped in the afternoon at the university. Masson continued his studies on carcinoid tumors, tumors of the melanogenic system, and glomus tumors, but he also tackled new themes. He pursued studies on the histogenesis, structure, and classification of tumors of the nervous system, particularly the peripheral nerves. This remarkable work is considered to be classical. To mention only 2 other works among several, he identified and described the spermatocytic seminoma and characterized as mesotheliomas the adenomatoid tumors of the genital tract. It would be necessary to wait several decades for the mesothelial provenance proposed by Masson to be confirmed by ultrastructural and immunohistochemical studies. Dignified, distinguished, and with great presence, Masson could, at first sight, seem somewhat distant and intimidating. But when one approached him, he was found to be affable and considerate, as noted by the students in the laboratory sessions. Residents recalled the interest and care with which he followed their progress, even that of the beginners, showing and discussing with them interesting cases and taking the time to examine the results of their attempts at techniques. Masson deeply loved his work. He avoided any administrative or honorary position, which would distance him from his microscope. His office was in fact a laboratory office where he continued to practice techniques by himself in chosen cases. Another character trait, less apparent at first sight, was a great sensitivity, which was manifested, among others, by his love of music, which showed through equally in his work, where science blended with the esthetic. Michalany, his student from Brazil, and Oberling described him as a true artist of histologic technique, who looked with wonder at the beauty of colored slides and all that they revealed in the tissues and lesions. The language of Masson was revealing on this subject. When he met del Rio Hortega and examined his microscopic slides, he spoke of "histological splendors." Returning in the evenings to their house, which the Massons had decorated with many paintings by their son Henri-Jaques, provided a period of relaxation. Toward 8 P.M. he withdrew to his study to work, accompanied now by classical music. He answered his correspondence by hand, and being very organized, answered letters within 24 hours. He revised his lectures and continued writing his papers. A perfectionist and very demanding of himself, he revised and reworked his papers time and time again. The work extended into the weekends, especially since Masson had undertaken to write a second edition of his book. Each summer the Massons returned to France. This was the time for them to revisit their elder son, a neuropsychiatrist, their younger son, an artist, and their families. Their daughter had come with them to Montréal, where she was a microbiologist at McGill University. They stayed in the property that they had kept in Burgundy in the little community of Athie. These annual trips, which were interrupted by the war of 1939, were resumed in 1946 and Masson renewed contacts with his friends and colleagues. In particular he went to Lyon on Fridays to see his friend Martin who, during the course of the year, had accumulated interesting and difficult cases to review with him. Feroldi and Guichard, joined by Cabanne, who came from Dijon, participated in these gatherings where anatomical pathology was discussed as well as literature, music, and history. In addition, Masson renewed his periodical visits to the Pasteur Institute in Paris. In Strasbourg it had become evident that Masson was well established in Montreal, and Géry, who until then had been acting director, was appointed Professor and Director of the Institute. The second edition of his book, completely rewritten and expanded, appeared in 1956 under the modified title of Human Tumors: Histology, Diagnosis, and Technique. This was the crowning moment of his career. The treatise remained a very personal work, wherein his studies and experience in the study of tumors during half a century occupied an important place. He also set forth his concept of Anatomical Pathology. For him, it was a scientific discipline, obviously very important but one that should not be separated from the other disciplines such as Physiopathology. On the other hand he strongly opposed the erroneous and widely held view that Anatomical Pathology was a static science since it made use of fixed tissues. Masson underline the fact that one could impart movement to the images that the sections gave, which he compared to photography, in studying lesions at different stages and thus make a sort of cinematographic film of their evolution. "From this, the sequence of stages of the lesion being known, the anatomo-pathologist could, from a single slide, deduce those which preceded and those which would follow." For Masson a spontaneously occurring lesion represented a true experiment of nature, more subtle and more difficult to interpret than a planned experiment, but rich in instruction if one observes it with the necessary patience and sagacity. In his detailed chapter on the subject, Masson again insisted on the importance of good techinique, and not concealing his impatience in this regard, he wrote, "if the histologist is accustomed to being satisfied by the technique of a 'gargotier' (akin to the food produced by the chef of a greasy spoon), so much the worse for him and for those who place their confidence in him." Masson could read English but did not speak it well. Nevertheless, links were established with his English Canadian and American colleagues. F.W. Wiglesworth, Professor of Anatomical Pathology at McGill University, came to Masson's laboratory to learn his techniques and introduce them in his hospital "The Children's." The celebrated neurosurgeon and neuropathologist Wilder Penfield, who had come from New York to found the Neurological Institute of McGill University, was familiar with Masson's work on tumors of the nervous system and established communication with him. When Penfield, a former student of del Rio Hortega, organized a conference of neurologist in his memory, it was Masson whom he asked to give an overview of the work of the Spanish master. In the published text of this allocution Masson mentioned that the talent of del Rio Hortega to invent newer techniques allowed him to see what no one had seen before. "His laborious life can serve as a model for all investigators. His work is one of the most honored in the brilliant Spanish school, one of the most honored in the world of histology." In the United States it was especially with A.P. Stout, the eminent histopathologist of Columbia-Presbyterian in New York, that friendly relationships were established, thanks to George Laidlaw. Laidlaw, a cardiologist, on learning that he had developed multiple bladder papillomas, decided to devote the remainder of his life to the study of tumors. He spent a long time in Masson's laboratory to learn the histologic techniques and the histopathology of tumors before returning to New York to Columbia-Presbyterian. Stout, in his recently published autobiography, writes "I have to thank Laidlaw for introducing me to Pierre Masson, who when passing through New York came to call on Laidlaw and Penfield. I already knew Masson by reputation. Meeting him really opened my eyes to what fine technical methods could accomplish in aiding one with the recognition and interpretation of tumors. The friendship thus begun developed slowly but has progressed through the years and I must ever remain grateful to Laidlaw for bringing us together." A dozen of the 54 publications by Masson during his Montréal period were published in English, generally following invitations. It was Laidlaw, then Stout, helped by Haagensen, who undertook to translate the texts written in French. Sidney Kobernick, a graduate from McGill and Professor of Pathology, Wayne State University in Detroit, and a great admirer of Masson, undertook the English translation of his book Human Tumors, an enormous task (1,214 pages) that stretched over more than a decade. Over the years, Masson received many honors and marks of esteem. Decorated with the Légion d'Honneur, he also became a Member of the French Academy of Medicine. In Canada 4 universities conferred on him an honorary doctorate. In the United States, when the associates and students of Stout undertook the project of dedicating to him a special issue of cancer, it was Masson whom they asked to write a preface. When the Mexican pathologists decided to organize a congress to recognize the formation of the Mexican Association of Pathology, Masson was one of the few invited guests of honor. Masson had always enjoyed excellent health. However, in 1958, an unfortunate fall caused the collapse of some vertebrae, and after long months of suffering, in the course of which he was hospitalized twice, he died in hospital on May 11, 1969, at the age of 79. Masson's legacy is vast and enduring. First there is the exemplary worth of an admirable career and life. Endowed with remarkable talents and qualities, he used them to excel in research and teaching as well as the practice of Anatomical Pathology. He created a school and left numerous students and students of his students especially in Quebec and in France, but also in several other countries. His classical works continued to inspire and stimulate other research endeavors. His outlook and his concept of Anatomical Pathology remain current. Now that immunohistochemistry is taking an increasing role in the study and diagnosis of tumors, his insistence on the requirement for rigorously applied technique remains especially relevant. His memory continues to be honoured. In 1997 he was elected to the Canadian Medical Hall of Fame. At the Congress of the International Academy of Pathology held in Boston in 1998, the History of Pathology Society paid honor to 4 giant figures of Surgical Pathology, a discipline, which at the beginning, was particularly developed in North America. The 4 people honored were Pierre Masson, Arthur Purdy Stout, Fred W. Stewart (Memorial Sloan-Kettering Cancer Center), and Lauren V. Ackerman (Washington University). Masson chose to be buried in the Notre-Dame-des-Neiges Cemetery on Mount Royal from where one can look out over the University of Montréal. The amphitheatre in which he gave his lectures now bears his name. Bibliography Cabanne F. Pierre Masson: Précurseur et rénovateur (1880-1959) Ann Pathol 3:95-97, 1983 Cadotte M. L'heritage scientifique du professeur Pierre Masson. Union Méd du Canada 113:344-345, 1984 Gosset A, Masson P. Les tumeurs endocrines de l'appendice. Presse méd 25:237-240, 1914 Levaditi JC. Pierre Masson (1880-1957) Ann Institut Pasteur 97:277-280, 1959 Masson P. La glande endocrine de l'intestin chez l'homme. CR Acad Sci (Paris) 158:59- 61, 1914 Masson P. Tumeurs-Diagnostics Histologiques. A Maloine et Fils, Paris, 1963 Masson P. Hémangio-endothéliome végétant intravasculaire. Bull Soc Anat (Paris) 93:517-523, 1923 Masson P. Le glomus neuro-myo-artériel des régions tactiles et ses tumeurs. Lyon Chir 24:257-280, 1924 Masson P. Les naevi pigmentaires, tumeurs nerveuses. Ann Anat Pathol (Paris) 3:417- 453, 657-696, 1926 Masson P. Leçon d'overture (Université de Montréal). Union Méd du Canada 56:189- 203, 1927 Masson P. Experimental and spontaneous schwannomas (peripheral gliomas). Am J Pathol 8:367-388, 389-416, 1932 Masson P. Tumeurs encapsulées et bénignes des nerfs. Rev Can Biol 1:209-343, 1942 Masson P, Riopelle JL, Simard L.C. Le mésothéliome bénin de la sphère génitale. Rev Can Biol 1:720-751, 1942 Masson P. L'œuvre scientifique de Pio del Rio Oretga. J de Hôtel Dieu (Montréal) 14:405-416, 1945 Masson P. Étude sur le séminome. Rev Can Biol 5:361-397, 1946 Masson P. Pigment cells in man. Special publications of the New York Academy of Sciences 4:15-51, 1948 Masson P. Neuro-nevi "bleu." Arch de Vecchi 14:1-28, 1950 Masson P. My conception of cellular nevi. Cancer 4:9-38, 1951 Masson P. Tumeurs Humaines. Histologie, Diagnostics et Techniques. 2nd ed. Librairie Maloine, Paris, 1956 Masson P. Human tumors. Histology, diagnosis and technique (translated by S. D. Kobernick). Waybe State University Press, Detroit, 1970 Michalany J. Masson's contribution to pathology and to histological technique. With special reference to the discovery of argentaffine cells. Ann Pathol 3:85-93, 1983 Michalany J. Masson que j'ai connu: mon maître et mon ami. Union Méd du Canada 113:386-389, 1984 Oberling C. Pierre Masson (1880-1959). Ann Anat Pathol 5:427-432, 1960 Rheault MJ. Pierre Masson: His influence on the teaching of Pathology in Canada. Can J Surg 28:456-457, 1985 Rheault MJ. Pierre Masson: pilier de l'enseignement de l'histopathologie au Canada. Ann Chir (Paris) 45:833-836, 1991 Riopelle JL. A la mémoire du Professeur Pierre Masson, vingt ans après. Union Méd du Canada 108:473-476, 1979 Seemayer TA. The life and legacy of Professor Pierre Masson. Am J Surg Pathol 7:179- 183, 1983 Simard LC. In Memoriam Pierre Masson (1880-1959). Union Med du Canada 88:1017- 1023, 1959 Stout, AP. Notes on the education of an "oncological" surgical pathologist: The autobiography of Arthur Purdy Stout. In Rosai J (ed): Guiding the surgeon's hand: The history of American surgical pathology. Armed Forces Institute of Pathology, Washington, DC, pp. 197-274, 1997 Tremblay G, Seemayer T. Pierre Masson (1880-1959): un grand maître de l'histopathologie des tumeurs. Bull Cancer 87:625-629, 2000 Vetter JM. Le renouveau français de l'anatomie pathologique. In Héran J (ed): Histoire de la médecine à Strasbourg, Éditions La Nuée Bleue et Faculté de Médecine Louis Pasteur de Strasbourg, Strasbourg, pp. 503-504, 1997