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A Note from History: Microscopic Contributions of Pioneer Pathologists

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A Note from History: Microscopic Contributions of Pioneer Pathologists Available online at www.annclinlabsci.org Annals of Clinical & Laboratory Science, vol. 41, no. 2, 2011 201 A Note from History: Microscopic Contributions of Pioneer Pathologists Steven I. Hajdu Keywords: history of pathology, history of medicine, history of science, history of microscopy The microscope, such an integral part of with the microscope, physicians in the 17th and pathology today, was only reluctantly accepted 18th centuries were occupied with correlating by physicians at the time of its invention clinical and autopsy findings by naked eye in 1590. After the Dutch Zacharias Janssen examinations [5]. Although the term pathology invented the compound microscope by was introduced by the French physician Fernel combining convex lenses in a tube, Holland and (1497-1558) in 1554 [6], there were only Italy became centers for the production and use sporadic suggestions of using the microscope of the new instrument. The name “microscope” for pathologic studies [7,8]. Two of the greatest was first suggested in 1625 by Faber a botanist. autopsy pathologists, the Swiss Boneti (1620- Early users of the microscope in Italy included: 1689) and the Italian Morgagni (1682-1771) Galileo, an astronomer and physicist, Stelluti, never used a microscope. Later on, astute a naturalist, Fontana, an astronomer, Faber, a pathologists such as the French Bichat (1771- botanists, Spallanzani, a biologist, Kirche, a 1802), the English Baillie (1761-1823) and the Jesuit priest, and two physicians, Borelli and Austrian Rokitansky (1804-1878), continued Malpighi [1]. to make their pathologic observations the traditional way, purely by gross examination By the time the classical period of microscopy of diseased organs and tissues [9]. Because began in the 1660s with publications by Hooke good fixative, paraffin embedding , microtome (1635-1703), Leeuwenhoek (1632-1723), and eosin stain were not available prior to the Swammerdam (1637-1680) and de Graff (1641- 1860s, pioneer microscopic pathologists most 1673), it was apparent that the microscope often obtained their specimens for microscopic had opened a new avenue of discovery [2]. examination by scrapping and teasing out the Most of the early microscopists were botanists, cut-surface of tissues or by preparing smears zoologists, naturalists and amateur scientists. from fluids and aspirates. They made and published random microscopic observations without pursuing any specific line Gabriel Andral (1797-1876) of Paris was the of study, such as Hooke’s discovery in 1665 first gross pathologist turned microscopic of the vegetable cell in cork [3]. This seminal pathologist. Midway in his career as a observation had no follow-up until 1838, pathologist, he focused his attention on when Schwann (1810-1882) recognized and microscopic alterations of the blood. In 1843, he published that animals, humans and plants published the first concise treaty on pathological alike consist of cells [4]. hematology and created a new field in medicine – hematology [10]. In his book, Andral referred While early scientists continued their work to an increased number of globules (white blood cells) in the blood as leukocytosis and observed that excess increase of globules was Address correspondence and reprint requests to Steven I. Hajdu, M.D., 1759 Drumcliff Court, Westlake Village, California 91361- associated with high fever and rapid heartbeat. 1636; tel 805 496 0691; fax 805 496 0620; e-mail [email protected] He noted that anemia was due to a decrease 0091-7370/11/0200-201. © 2011 by the Association of Clinical Scientists, Inc. 202 Annals of Clinical & Laboratory Science, vol. 41, no. 2, 2011 of red globules (red blood cells) in the blood that was named years later as the source of and that anemia could vary from mild to severe chordoma. He identified the paramesonephric depletion of these elements. He also described duct (Mullerian duct) and deduced that lead poisoning, septicemia and polycythemia. vestigial rests of this duct may form tumors thus Another of Andral’s innovations was measuring identifying the source of mixed mesodermal the proportions of blood constituents, such as (Mullerian) tumors of the female pelvic organs. fibrin, globules (cells) and water, in health and He described the histology of radial (Muller) disease. He knew that fibrin could precipitate fibers of the retina and outlined the topography and form solid a structure (thrombus). His of the anterior and posterior spinal nerve roots. examination of blood from patients and from In his book, On the Finer Structure and Form the deceased led him to conclude that there of Morbid Tumors, published in 1838, the existed primary blood diseases [10]. same year his pupil Schwann announced his cell theory, Muller presented the microscopic Shortly after his appointment in 1833 as features of many benign and malignant professor and chairman of pathology at the tumors supporting the cell theory as a basis for University of Berlin, Johannes Muller (1801- comprehension of the nature of cancer [11]. 1858) began collecting tissue samples from He concluded that malignant tumors consisted surgical procedures and postmortem dissections of the growth of abnormal cells. He attributed for microscopic examination with his assistants. cancer to the formation of new cells in diseased Among his laboratory staff were a number organs, with the potential to spread to other of renowned physicians. Theodor Schwann parts of the body by vascular invasion. Muller (1810-1882) in collaboration with the plant associated cancer with aging and identified physiologist Matthias Schleiden (1804-1881) tumor necrosis (apoptosis) as a sign of regression. established the cell theory in 1838 [4]. Schwann He distinguished microscopically epithelial and also identified the perineural cells which are connective tissue tumors. He divided carcinomas named after him. Jacob Henle (1809-1885), into carcinoma simplex (squamous carcinoma), known for his microscopic classification of carcinoma alveolare (adenocarcinoma), tissues, described the loop of Henle in the carcinoma medullare, carcinoma fasciculatum kidney and introduced the term epithelium in (spindle cell carcinoma), carcinoma reticulare, 1857. Robert Remak (1815-1865) introduced and carcinoma melanodes (pigmented the three layer concept – ectoderm, mesoderm melanoma). As to connective tissue tumors, he and endoderm – and in 1852, was the first described myxoid and fibrous lipomas, fibroma, to point out that growth of tissues was infiltrating fibrous tumor (desmoid tumor), accomplished by division of pre-existing cells. cystosarcoma of the breast, chondroma, Rudolph Kolliker (1817-1905) demonstrated enchondroma, osteoma, chondrosarcoma and the cellular origin of spermatozoa in 1841 and osteosarcoma. Muller’s illustrations are distinct he concluded in 1885 that hereditary characters and the corresponding legends are concise. were transmitted by the cell nucleus. Rudolph He wrote that the examination of numerous Virchow (1821-1902) achieved fame because microscopic preparations of tumors has taught of his innumerable contributions to cellular him that cancers are possessed of certain pathology in the 1840s and 1850s. peculiar microscopic features, which may serve to identify them [11]. Muller’s contributions to Muller equipped his laboratory with the pathology are many but, above all, he should be latest achromatic compound microscopes and remembered as the originator of histopathology expected all his assistants to become skilled and cellular pathology. microscopists. Muller himself carried out numerous embryologic and physiologic studies Julius Vogel (1814-1880), a disciple of before he focused on tumor pathology. He Johannes Muller, published his pioneering book discovered the cellular nature of the notochord Pathological Anatomy of the Human Body in Microscopic Contributions of Pioneer Pathologists 203 1843 in Berlin. Being the first comprehensive tumor of bone). Lebert recognized that there general pathology book containing macroscopic are many different microscopic forms of cancer and microscopic illustrations, it was rapidly and that malignant tumors are distinctly translated from German into English and different microscopically from benign tumors. was published in London and Philadelphia in He described and illustrated enlarged nuclei, 1847 [12]. The book consists of text and 10 macronucleoli, and multiple nuclei as hallmarks plates with over 100 microscopic illustrations. of malignant cells [13]. The legends for figures are comprehensive microscopic descriptions of histologic and He emphasized the importance of examining cytologic details. The bulk of the figures show, every pathologic specimen under the microscope for the first time, microscopic features of specific but warned that microscopic examination was pathologic lesions. Among the illustrations time consuming and every observer his own are cytologic preparations of sputum and teacher. Undoubtedly, Lebert was not only a pleural and pericardial effusions of patients microscopic pathologist par excellence, but he with bronchitis, tracheitis and pneumonia. In also published the first microscopic pathology addition to illustrations of various concretions atlas, which served as the basis on which and crystals there are histologic sections of others, including Rudolph Virchow, built their granulomas, gangrene, hyperplastic lymph concepts about the histology of pathologic nodes, cirrhotic and fatty liver, polypoid and lesions. papillary tumors of the uterus and bladder, and carcinomas
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