ORIGIN AND DEVELOPMENT OF AMERICAN SURGICAL PATHOLOGY

Abstract

Although the discipline of pathology had its very beginnings in the earliest development and evolution of what became “modern medicine,” the subset of pathology known as “surgical pathology” had its origins only in the last two centuries. Surgical pathology began as a clinico-pathologic analysis of gross morphologic findings with clinical outcomes, beginning with findings at autopsy. With the advent of microscopy, which enabled a higher level of morphologic classification and disease understanding, along with advances in surgery (anesthesia, antisepsis, and then antibiotics), the need for accurate pathologic classification in the living patient became of paramount importance. This review chronicles the evolution of surgical pathology in the United States in the context of advances in the science and practice of medicine generally and surgery specifically.

INTRODUCTION

Surgical pathology today is a discipline within the field of anatomic pathology, a discipline that also includes the autopsy and cytopathology. The general field of pathology began long before the advent of modern surgery. Modern scientific medicine was born out of the knowledge gained from human dissection and, later, the morphological findings at autopsy in various states of clinical disease (along with advances in physiology and chemistry) that correlated for the first time disease states with postmortem anatomical findings (1). In the early nineteenth century, two central figures in pathology emerged: von Rokitansky of Vienna and his onetime pupil, Rudolf Virchow of Berlin (2–4). This era coincided with introduction of the microscope into diagnostic pathology, which was formerly based only on gross findings. This was accompanied by similar advances in tissue fixation and various embedding and staining methodologies (5). The development of modern surgery had to await advances in aseptic technique, anesthesia, and the antibiotic era to realize its full potential from its beginning in the late nineteenth, early twentieth century.

By the end of the nineteenth century, the tools of surgical pathology had been adequately refined to make a diagnosis from biopsy material, prior to surgery. However, this was seldom done in practice, and surgeons relied on gross impressions of the nature of the lesion exposed during surgery. Therefore, pathology was initially practiced by surgeons and gynecologists during surgery based on gross diagnosis; only much later were surgeons aided by microscopic analysis (6).

Within the last 70 years, surgical pathology has been transformed from a subspecialty practice into a stand-alone discipline within the field of pathology training. Strict morphology as the basis of diagnosis in surgical pathology has been supplemented by advances in molecular genetic pathology and will be further enhanced with artificial intelligence in the future. This review will chronicle a subset of American surgical pathology that began under William Henry Welch at Johns Hopkins Hospital and later others such as Arthur Purdy Stout at Columbia, William Councilman at Harvard, James Ewing at Memorial Hospital, Louis Wilson at the Mayo Clinic, and Lauren Ackerman at Washington University.

MATERIALS AND METHODS

This work represents a compilation of literature review based on an automated Internet search for “History of American Surgical Pathology” as well as the book Guiding the Surgeon's Hand: The History of American Surgical Pathology, which was edited by Juan Rosai.

RESULTS AND DISCUSSION

Johns Hopkins

The story begins at Johns Hopkins with William Henry Welch (1850–1934), who is rightfully regarded by many as the “Father of American Pathology.” Although more known as a bacteriologist than as a surgical pathologist, Dr. Welch laid the foundation for the practice of surgical pathology at Hopkins. With his primary research interests in bacteriology, he discovered the organism that causes gas gangrene, Clostridium welchii (now classified as Clostridium perfringens), that was named in recognition of this fact.

Dr. Welch earned his undergraduate degree from Yale and later an MD at Columbia P&S in 1875. Following graduation, he studied in Europe for three years in the pathology laboratories of Waldeyer and von Recklinghausen. He returned to New York City to establish the first hospital pathology laboratory at Bellevue Hospital where he functioned as a surgical pathologist. In 1884, he became the first physician recruited to Johns Hopkins. He nominated and selected three other giants in medicine at Hopkins: William Osler (Medicine), William Halsted (Surgery), and Howard Kelly (Gynecology). Welch became the first dean at Hopkins in 1893 (7).

In 1891, Welch made history by performing a frozen section on a suspected breast cancer case for Halsted. However, the technique required a fixation step prior to sectioning that would normally take an hour or more to complete. By the time Welch had finished the frozen section, Halsted had already completed the operation. This frozen section technique was later discussed by Thomas Cullen in the Bulletin of the Johns Hopkins Hospital in 1895, but it was never widely used due to poor acceptance by surgeons of the time and the inordinate amount of time required during the operation to come to a diagnosis (8).

The story of surgical pathology at Hopkins would not be complete without mentioning Joseph Colt Bloodgood, MD (1867–1935). He graduated from medical school at the University of Pennsylvania in 1891. Following a short stint at Children's Hospital of Philadelphia, he went to Hopkins in 1892 as assistant resident surgeon. After six months, he was sent to study under Billroth in Vienna, one of the premier surgeons and surgical pathologists in the world at that time. He returned to Hopkins in 1893 where he became Halsted's primary assistant. Halsted appointed him to do a systematic study of surgically excised tumors. Halsted later appointed him chief of the first subspecialty division of the department of surgery—the division of surgical pathology. He became a very skilled surgical pathologist, and other surgeons often referred slides of difficult cases to him (9). Although he was not an original proponent of the value of frozen section, he changed his position by the 1920s and made this statement in a 1927 article in JAMA: “When cancer becomes a microscopic disease, there must be tissue diagnosis in the operating room” (10).

New York Cancer Hospital (Memorial Sloan Kettering Cancer Center)

The cornerstone of the hospital was laid in 1884. Although a number of pathologists preceded him, James Ewing was undoubtedly the most prominent pathologist in the history of the institution and arguably in the entire country in that era. He received his medical degree at the College of Physicians and Surgeons of Columbia University (Columbia P&S) in 1891. After a brief stint as a surgeon in the U.S. Army, he joined Cornell in 1899 as the first full-time professor (clinical pathology). With philanthropic help, he established the Clinical Research Center at Memorial Hospital in 1910. He was later appointed hospital president in 1931. Ewing authored one of the most well-known textbooks of surgical pathology at the time, Neoplastic Diseases, a Textbook on Tumors, in 1919 that had three subsequent editions. A soft tissue/bone tumor he described bears his name even today: “Ewing sarcoma.” He was also a giant in the cancer field generally, founding the American Association for Cancer Research in 1907 and the American Society for the Control of Cancer (now the American Cancer Society) in 1913. His trainees established the James Ewing Society which later became the Society of Surgical Oncology. Ewing's picture appeared on the cover of the January 12, 1931 issue of Time magazine with the caption “Cancer Man Ewing” (11).

The tradition of excellent surgical pathology at Memorial Sloan Kettering Cancer Center continued after Ewing under Fred W. Stewart (1894–1991) who was later joined by Frank Foote (1911–1989). Together, they trained more than one generation of surgical pathologists through their fellowship program in oncologic surgical pathology, and they authored seminal works on breast pathology and numerous other topics. Stewart was the first editor of the journal Cancer which became a great forum for publication of high impact surgical pathology papers, in addition to medical and other aspects of cancer treatment (12).

College of Physicians and Surgeons of Columbia University

At Columbia P&S, like Hopkins and Washington University, surgical pathology began in the department of surgery when, in about 1905, Dr. William C. Clarke, one of the young surgeons in the department, was assigned to organize and direct the laboratory of surgical pathology in the department. In 1928, Dr. Arthur Purdy Stout was appointed head of the laboratory of surgical pathology at Columbia P&S where he was destined to become one of the most famous surgical pathologists in the history of American surgical pathology (13).

Stout completed his medical degree at Columbia P&S in 1912 and underwent surgical training at Roosevelt Hospital in New York City. He served as a surgeon in the U.S. Army during World War I. Within a year of returning to Columbia P&S, he was appointed director of the laboratory of surgical pathology, a position he held until the 1950s. He trained large numbers of surgical pathologists over his career, and his former trainees responded by forming the Arthur Purdy Stout Society of Surgical Pathologists in 1947. This body remains a prestigious organization and recognizes pathologists with special skill and accomplishments in surgical pathology. He is also known for his seminal textbook in surgical pathology, Human Cancer, which was published in 1932 (14).

Hospitals of Harvard Medical School

William T. Councilman arrived at Harvard Medical School in 1892, succeeding Reginald Fitz, and ushered in a new era of pathology in Boston. He received his medical degree from the University of Maryland in 1878 and subsequently studied in Europe under Chiari, Cohnheim, Weigert, and von Recklinghausen. When he returned to the United States, he worked at the University of Maryland. Recruited by Harvard in 1892, he became the institution's first outside professor and founded the first pathology laboratory at Boston City Hospital (15). He trained Frank Burr Mallory (who succeeded him) and James Homer Wright [appointed chief of pathology at Massachusetts General Hospital (MGH)], both of whom became giants in pathology at Harvard. Benjamin Castleman succeeded Mallory's oldest son, Tracy Mallory, as head of the pathology department at MGH in 1953. For many years, Castleman was the driving force behind the case records (CPC) of MGH that were published weekly in the New England Journal of Medicine. He presided over 2,000 CPCs during his tenure and trained over 200 pathologists, 20 of whom became chairs of academic departments of pathology (16).

Washington University, St. Louis, Missouri

Evarts A. Graham (chair of surgery from 1919–1951) had two younger faculty (Nathan Womack and Eugene Bricker) who, in addition to their surgical duties, were active in gross and microscopic/diagnosis of surgically resected surgical specimens. As surgery schedules grew busier and the complexity of cases increased, the need for a full-time surgical pathologist with special training became increasingly clear. Bricker recognized Lauren V. Ackerman as the perfect candidate for the position. Dr. Ackerman had been recruited in 1940 to the Ellis Fischel State Cancer Hospital in Columbia, Missouri, about a two-hour drive from St. Louis (17).

Dr. Ackerman joined the department of surgery at Washington University in 1948. He had an excellent reputation as an academic pathologist, having co-authored with Juan Del Regado (radiation therapist) the popular textbook Cancer: Diagnosis, Treatment and Prognosis (18).

Ackerman's training program for fellows in surgical pathology quickly became the premier training program in the country. For more than 30 years, he turned out many of the great leaders in academic surgical pathology in the United States and around the world. His textbook, Surgical Pathology, published in 1953, became the definitive textbook on the subject and is now in its eleventh edition (19).

Mayo Clinic

The first chief of pathology, Dr. Louis B. Wilson, was recruited by the Mayo brothers in 1904 to the Mayo Clinic at the suggestion of Dr. Henry Plummer. He had graduated from the University of Minnesota in 1896. At Mayo, he perfected and published the modern version of the frozen section using a CO₂ microtome on unfixed tissue and staining the sections with a single stain, methylene blue. This technique permitted rapid (within minutes) assessment of the tissue removed during surgery and was, therefore, able to guide the scope of the operation depending on the histologic diagnosis (20).

He published this technique in the Journal of the American Medical Association in 1905, but it was not until the 1920s that frozen sections became accepted as standard and worthwhile in surgical patient management (21). Up until then, surgeons generally trusted their gross diagnosis much more than the results of a frozen section in managing patients.

Wilson was joined later by others, most notably Albert C. Broders, who developed the first biomarker of cancer—cancer grading. He devised four grades, I–IV, which corresponded to well, moderately, poorly differentiated, and anaplastic, respectively. He published this system in JAMA in 1920 (22). He was also the first to describe the concept of carcinoma in situ, cancer cells that are limited by the basement membrane from invading the underlying connective tissue (23).

Armed Forces Institute of Pathology (AFIP)

The AFIP was established during the Civil War to catalogue pathology specimens from soldiers. It later evolved into a multispecialty surgical pathology and radiology consultation service for both the military and civilian pathology practices. When it ceased operations in 2011 under the “Base Realignment and Closure Act,” it had cataloged over 3 million specimens that served as the basis for innumerable manuscripts describing new entities in surgical pathology.

The first series of the AFIP tumor fascicle publications began in the 1940s and is now in its fourth series with a total of 130 separate publications to date. These highly focused, well-illustrated tumor atlases have formed the backbone of pathology education for decades (24).

The Molecular Revolution and Artificial Intelligence

Diagnoses based strictly on morphology have been augmented by advancements in molecular pathology with the advent of biomarkers associated with these molecular alterations. The addition of these molecular markers has dramatically changed patterns of clinical care and further highlighted the essential role that pathologists play, not only in patient diagnosis but also in the formulation of a specific algorithm of treatment. For example, “Precision Medicine begins with Pathology” is a tag line developed by a major pharmaceutical company in its video presentation material.

Not that long ago, a histological diagnosis of lung cancer was one of two clinically important types: small-cell and non-small-cell. For advanced cancer of the latter type, only one standard treatment was available (chemotherapy with or without radiation therapy). Further subtyping of non-small-cell carcinoma (e.g., adenocarcinoma, squamous cell carcinoma, etc.) had no clinical relevance. In the modern era, however, the therapeutic options for these same tumors are legion with dozens of branch points based on a number of molecular/genetic markers along with immunostaining to judge the likelihood of response to immune checkpoint inhibitors.

Artificial intelligence (AI) is relatively new to surgical pathology and promises to greatly augment the “finder function” of the pathologist in detecting abnormalities that need evaluation and perhaps obviating the need for pathologist assessment in straightforward pathologic interpretation in benign lesions. This has been made possible by the ability to completely digitize a microscopic slide to make the entire slide searchable over multiple magnifications. Most pathologists welcome this new technology, although others are concerned that machines may one day replace all functions of the pathologist. Only time will tell.

SUMMARY

The history of pathology is rich indeed, from its beginning as the basis for understanding disease to the present and beyond where it is/will be the backbone for defining the roadmap for personalized treatment of the individual cancer patient.

DISCUSSION

Bryan, Columbia: Thank you for a wonderful talk. … It certainly rekindled a lot of interest, which stemmed back to my one-year experience as a pathologist working at Hopkins with the likes of Bill Shelly and Bill Hartman during the golden era. Three quick points: First, I hope you get in touch with Jim Wright in Calgary, Alberta, who's your contemporary soulmate in the history of surgical pathology and has published recently in the Bulletin of the History of Medicine for example. Second, I had the impression from Jim that the actual inventor of the frozen section was Tom Cullen working with Welch. Cullen had come down from Canada to be a resident with Kelly. Kelly didn't immediately have a position for him, so he had him work with Welch. Cullen went on to pioneer gynecologic pathology. A third, short point about Castleman. Ben Castleman as you point out was from Maryland and from Hopkins in the early, heady days of Johns Hopkins. He was vigorously opposed to women in medicine. Hopkins as you know accepted women in medicine as a condition for starting in the medical school, and Osler is supposed to have quipped to the people at Harvard: “You got Castleman … we got women medical students.” Thank you.

Wheeler, Houston: Thank you for those comments and yes about Dr. Cullen. He was an obstetrician/gynecologist. I didn't mention him because the person who gets the credit for the modern technique would be the fellow from Mayo Clinic. Cullen was actually the first one that did it, and his work was published in the Bulletin of the Johns Hopkins Hospital I think in 1895. It was quite a different technique and more primitive, but he later became head of the gynecologic pathology department at Hopkins and was also a surgical pathologist.

Bryan, Columbia: Right, it was a little after 1885 because the hospital of course wasn't open then, but Welch was so excited about it. … Welch heard that his paper was published in the Bulletin of the Johns Hopkins Hospital about one day after it was written, which was a record.

Wheeler, Houston: The Bulletin of the Johns Hopkins Hospital was going to press, and Welch was so taken aback by the article that he stopped the presses and made sure it was added.