THE GOLDEN AGE OF SURGERY
The dramatic technical advances in surgery from 1850 to 1900 greatly contributed to the definition of modern surgical pathology (Figure 14). At midcentury, surgical patients had a 50% chance of dying due to pain, bleeding, shock, infections, or other postoperative complications (1,49). Surgeons were very limited in what they could do for their patients. If a malignant growth was found, it was typically inoperable and the patients died soon afterwards.
Controlling pain through anesthesia was first discovered in nearby Augusta, Georgia. Crawford Long successfully applied ether during a surgical procedure in 1842, but did not publish his findings until 1849 (50,51). At the Massachusetts General Hospital, William Morton employed inhaled ether on October 16th, 1846. This well-documented event is regarded as the public demonstration of inhalational anesthesia (49,52,53).
The control of bleeding through improved hemostasis is the second major technical advance in surgery. This occurred through an increased understanding of physiology and surgical instrumentation.
The third, and perhaps most important, advancement in surgery was the control of infection. Discovery of the bacterial causation of disease led to the applications of antisepsis and asepsis. In Vienna, Ignaz Semmelweis made the observation that handwashing in chlorinated lime solutions could reduce the incidence of postpartum infections (54–56). Although he was ridiculed by his colleagues, this simple task forms one of most important principles of modern infection control (1,49,57). His cause was also championed by Oliver Wendall Holmes in the U.S.(1,49). Another originator of antisepsis was Joseph Lister who used carbolic acid soaks and sprays and markedly decreased postoperative infections (49,55,58,59). Louis Pasteur is credited with the germ theory of disease and many other observations on microbiologic fermentation and putrefaction. Following Pasteur's observations, Robert Koch isolated anthrax bacteria in 1880 and bacillus tuberculosis in 1882. Through these and many other discoveries, “the nature of infection, contagion, and wound suppuration became intelligible”(1).
Along with the applications of antisepsis / and (later) asepsis, there were many radical changes in operating room design in the late 19th century and early 20th century (60). Until the 1880's, surgeons were clad in street clothes, did not wear facemasks or gloves, and operated in dimly lit “operating theaters.” With many onlookers, surgery was more of a gladiatorial event than a veritable therapeutic procedure. To improve postoperative survival, some adventuresome surgeons applied scientific principles learned from microbiology and other disciplines.
By the mid 1880's antisepsis and the beginnings of asepsis were formally accepted into surgical practice (1,49,58). At Johns Hopkins Hospital, William Halsted implemented many aspects of modern aseptic surgical practice (i.e., sterlized gowns, masks, drapes, handwashing) to prevent infections (61). Undoubtedly other “new technologies” of the latter 19th century, such as the introduction of electricity, indoor plumbing, refrigeration, etc, contributed to the practice of modern surgery.
THE NEAR DEATH OF SURGICAL PATHOLOGY
At the highest levels of European political and medical society, surgical pathology was nearly given a death sentence following a particular misdiagnosis of malignancy. In Germany the newly appointed 55-year-old Emperor Frederick III developed a throat lesion in the Spring of 1887 (62–64). The eminent British otolaryngologist Morell MacKenzie came to Berlin and biopsied the laryngeal lesion. This was one of the first uses of the biopsy technique, since microscopic evaluation of tissue from living patients had been largely unheard of. In this case the pathologist was Virchov who had semiretired from active practice of pathology and was more involved with various administrative, social, political, and anthropologic concerns (64). Following at least three sets of laryngeal biopsies, Virchov interpreted these hyperplastic verrucous lesions as benign (pachydermia laryngis and pachydermia verrucosa) (62,64). The Emperor's condition deteriorated and the laryngeal lesions recurred. An expectorated sputum specimen was sent to Wilhelm Waldeyer who ultimately diagnosed it as carcinoma. Within a few months, the Emperor died from the complications of advanced laryngeal carcinoma (62–64).
The consequences of these discrepancies sent shock waves throughout the medical community in Germany and Britain. Although challenged by others, Virchov remained largely unaffected (64). Following the publication of his memoirs, MacKenzie, however, received many personal and professional attacks which led to censorship and expulsion from the Royal College of Physicians (63,65). This reinforced the notion that microscopic examination of tissues from living patients was unreliable and that a knowledge of malignancy can only be obtained from the autopsy (3,66).
DEVELOPMENT OF FROZEN SECTIONS
It has been suggested that surgical pathology began in America (4,5,8,9). Towards the end of the 19th century, the physical, political, and philosophical differences between Europe and America became more apparent. The new intellectual activity, the lack of an interest in formal academia and theory, the adventuresome pioneer spirit, and the willingness to take risks allowed many creative individuals to apply new technology that had not been previously imagined.
In a few years following the opening of the Johns Hopkins School of Medicine, William Welch was the first American pathologist to introduce the frozen section (FS) technique in surgery (9,13,67). Although FS had been used in the early 1880's at the Glasgow Infirmary for examining postmortem tissues, it had not been used during surgery (10). In 1891, using a carbon dioxide freezing microtome, Welch examined breast tissue during a surgical procedure (9,66,68,69). Halsted sent a small piece of breast tissue for analysis and Welch attempted to perform a frozen section. Unfortunately, Welch took so long to perform and interpret the FS that Halsted finished the procedure without knowledge of the results.
It is to Thomas Cullen that we can credit the first published technique for intraoperative FS in 1895 (9,70,71). Having studied in Germany with Johannes Orth, a notable pathologist and student of Virchov (72), Cullen understood the principles of tissue hardening and freezing and performed FS by prefixing tissues in formalin prior to sectioning (9). This new technique enamored Welch so much that the Bulletin of the Johns Hopkins School of Medicine was stopped at press to allow for the first published description of FS technique (9,70,71).
In the ensuing decade others claimed credit for FS technique or modified it; however, none was better publicized than the description from Louis Wilson at the Mayo Clinic (7,9,73,74). Recruited as a “full-time” pathologist at the new Pathology Department in 1905, Wilson was told by William Mayo “I wish you pathologists could tell us if a tissue is cancer or not while the patient in on the table” (73). With a background as a biology teacher and familiar with the use of botanical stains, Wilson described a very simple technique using methylene blue to stain frozen tissue samples (75). This staining method still currently used at the Mayo Clinic would allow for a diagnosis within a few minutes (76,77).
GENERATION OF THE SURGEON-SURGICAL PATHOLOGIST
“The hybrid specialty of Surgical Pathology was born out of necessity and out of wedlock” (78).
Pathologists in academic departments of pathology were more involved with autopsies, research, and were disinterested in clinical or practical applications. It is in departments of surgery or gynecology that physicians applied their surgical and pathological skills to become the first surgical pathologists to utilize microscopic examination of the preoperative biopsy (68). The German gynecologist Carl Ruge made the diagnosis of cervical and uterine cancer by microscopic examination of currettings and published his observations in 1878 and 1880, respectively (4,7,9,66,68). In addition to being an early “surgical pathologist,” Ruge may have been one of the first true international consultants because gynecologists from other countries sent biopsy materials for his interpretation (66).
In the U.S. Cullen became the head of Gynecologic Pathology at Johns Hopkins Hospital (67). His long and illustrious career is noted for authoring several great monographs, including several devoted to cervical and uterine cancer, uterine leiomyomata, and adenomyosis (79–82). Another early surgeon-surgical pathologist was William “Wild-Bill” Clarke at Columbia University who was the Course Director of Surgical Pathology in the Department of Surgery (78,83). His nickname suggested that he was quite a character, but his legacy is most evident in his students Allen O. Whipple and Arthur Purdy Stout, who were really part of the second generation of surgeon-surgical pathologists (78,83).
At Johns Hopkins, Joseph Bloodgood was one of the most important surgeon-surgical pathologists in the first quarter of the 20th Century (67). Like Halsted and Cullen, Bloodgood studied surgery, histology, and patholgy at various European institutions and was influenced by Theodore Bilroth and Theodore Kocher (84). In 1893 he established the first Department of Surgical Pathology within the Department of Surgery and by 1897 he was one of the first surgeons to routinely use FS during surgery (13,61,66,67,84). He was an innovator, a stimulating teacher, and a strong advocate of surgical pathology (84). Bloodgood was somewhat dubious of FS at first, but later fought very hard to validate it (7,9,67,69,85). He was politically active and influenced major medical organizations, such as the American College of Surgeons to mandate that FS be employed during surgery (7,9,67).
Not every major American pathologist of this era was a supporter of FS (7,9,66). James Ewing at Memorial Hospital was not an advocate of the FS (9). In an editorial in 1925, Ewing wrote “Having made more errors by the frozen section method in breast cases than by gross examination, I have not resorted to frozen sections in this field for many years, but rely almost entirely on gross inspection of the breast tissue. Many of my colleagues report to me the same tendency”(86). Other pathologists of that era, Francis Delafield, T. Mitchell Pruden, Aldred Warthin, W. M. Late Coplin, and many others distrusted the FS (7,9). The debate continued into the 1930's: the performance of FS during surgery was thought to be a fad, folly, or fetish (Figure 15) (9,87). But it was not until the pre-World War II era that surgeons, as well as pathologists, finally realized the major significance and contributions of FS.
THE FAMILY TREE
Nearly every practicing American surgical pathologist today can trace a strong link to at least one of four institutions (Johns Hopkins University, Columbia University, Memorial Sloan Kettering, and Washington University) where the many generations of surgeon-surgical pathologists and then surgical pathologists developed and refined their craft (3,13).
In New York City, Arthur Purdy Stout and Raphael Lattes formed one of the most comprehensive Departments of Surgical Pathology (78,83,88,89). Also in New York City at Memorial Hospital, James Ewing was followed by Fred Stewart and Frank Foote who influenced many aspiring young surgical pathologists (90–92). And finally, in St. Louis, Lauren Ackerman's spirited intensity stimulated many promising young individuals who joined him and have become many of the leaders of modern surgical pathology (93,94).
Surgical pathology essentially began at the turn of the last century from the technical contributions in microscopy, histochemistry, and surgery (9). The clinicopathological correlation began with the autopsy and later was extended to surgery. The use of the microscope enabled surgeons, and then pathologists, to translate morphologic findings present in small biopsy specimens into specific and relevant clinical information (4). The many contributions (and demands) from our surgical colleagues led to the need for precise and accurate pre-and intraoperative diagnoses, and continues to do so today.
The first three generations of surgeons-surgical pathologists were trained in surgery, but had an enormous interest in applications of pathology (13). Not until the mid-20th century did surgical pathologists gain autonomy and fiscal independence from other clinical disciplines. Divisions of Surgical Pathology were initially within Departments of Surgery, but were later incorporated into Departments of Pathology. At some institutions this union did not occur until the early 1960's (R.R. Pascal, personal communication September, 2000) (3,13,78,83).
The practice of modern surgical pathology continues the traditions of the past. That is, the integration of the technical and scientific advances of the day: in the 19th century—light microscopy, histochemical stains, and frozen sections— and in the 20th century—fluorescence microscopy, electron microscopy, and immunochemistry. As for the 21st century, the crystal ball forecasts that molecular techniques could play a very active role in diagnostic pathology. But will these “novelties de jour” supplant light microscopy? Only time will tell, but one can safely assume that a single stain, hematoxylin–which celebrates its 146th birthday in the millennium—will be here for many years to come.
The author would like to dedicate this manuscript to the histotechnologists at Emory University Hospital. Additional acknowledgments are to Robert Santoianni and Donna Martin for their superb assistance with the preparation of the figures.
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Keywords:© 2001 Lippincott Williams & Wilkins, Inc.
History of medicine; History of pathology; Microscopy; Histotechnique; Surgical pathology