The 100-Year Anniversary of the Description of the Frozen Section Procedure

In contemporary society, the pathologist is largely unknown or poorly understood. Accordingly, few lay persons, whether healthy or ill, have direct professional interaction with pathologists.¹ If a poll of the lay public were undertaken, many would respond that the pathologist is “not a physician,” “the keeper of the dead,” or “the person who performs the autopsy.” Certainly, the portrayal of the pathologist in printed press, cinema, and television, notably in the popular Crime Scene Investigation (CSI) television series, is frequently a distortion of reality.²

While autopsies represent a small and ever-diminishing part of medical practice, most contemporary pathologists are actively and directly involved in rendering care to the living patient through the various facets of the modern clinical laboratory. One of the most crucial tasks of the pathologist is the performance and interpretation of the frozen section or intraoperative consultation for diagnosis, margin assessment, and procurement of tissue for research purposes. This procedure is critical for the performance of accurate surgery: its outcome may guide the surgeon to continue or abort the surgical procedure.

From a historical perspective, the advances in the late 19th century in surgical technique, anesthesia, hemostasis, and control of infection became the cornerstones of modern surgical practice.³ As a result, physicians in departments of surgery or gynecology applied their surgical craft and studied tissues from living patients. Most pathologists of that time, however, were more devoted to autopsies and research and were largely disinterested in practical clinical applications of pathology.³ Yet there were a few brave pathologists who abandoned the trail of the past and ventured into novel applications of microscopy and histotechnique during their colleagues' surgical procedures.

In 1905, William Mayo told his new chief of pathology at the Mayo Clinic in Rochester, Minn, Louis B. Wilson, MD, “I wish you pathologists could tell us if a tissue is cancer or not while the patient is on the table.”⁴ A biology teacher familiar with the use of botanical stains, Wilson deduced a very simple technique using methylene blue to stain frozen tissue specimens during surgery.⁵ Wilson's technique allowed for a diagnosis within minutes while the patient was still on the operating table. His technique, with modifications, is still in use at the Mayo Clinic.^{6 - 7}

In the December 2, 1905, issue of JAMA, Wilson published his description of a reliable technique for the intraoperative frozen section (Figure).⁵ Although various frozen section techniques had been described by other authors for several decades, it is generally recognized that this landmark article in JAMA provided the first well-publicized, consistent method of rendering a dependable frozen section diagnosis that affected patient care during surgery.^{3 ,8 - 9} The impact of the frozen section on patient care since the beginning of the 20th century cannot be overemphasized. As noted in 1927 by Bloodgood,¹⁰ the rate of inoperable cancer at Johns Hopkins Hospital had decreased from 50% in 1900 to less than 5% by 1920 thanks to intraoperative frozen section. During the 20th century, intraoperative frozen section and preoperative biopsy led to vastly improved patient care and to the emergence of the surgical pathologist as a diagnostic consultant to surgeons and other clinicians.^{3 ,8 - 9 ,11}

December 2005 marks the 100-year anniversary of Wilson's seminal article. In celebration of this anniversary, the December issue of Archives of Pathology & Laboratory Medicine features a series of 12 articles by recognized experts reviewing current intraoperative consultation and frozen section diagnosis in multiple major organ systems; these 12 articles include more than 300 color images.

Even while celebrating Wilson's historic article, it is important to remember that like many other discoveries and innovations in medicine and other fields, this advance had predecessors and competitors and subsequent modifications. The idea that tissues could be hardened for sectioning by freezing was not new when Wilson published his procedure in 1905. Several other reports of the use of a frozen tissue technique came intermittently from Europe and North America during the 19th century. At the Glasgow Western Infirmary in the early 1880s, frozen sections were used for examination of autopsy tissue, but the technique was not used during surgery.¹² In 1889, John Warren, a surgeon from Massachusetts General Hospital, mentioned examination of skin biopsies with the freezing microtome but did not detail the technique. Thomas Cullen of Johns Hopkins Hospital, a student of Johannes Orth in Germany, has been credited with publishing the first technique of cutting frozen tissue sections while the patient was still undergoing surgery in 1895, but his technique used prefixing of the tissues with formalin.^{11 ,13 - 14}

To our knowledge, William Welch of Johns Hopkins School of Medicine was the first American pathologist to use the frozen section technique during surgery and used a carbon dioxide freezing microtome.^{11 ,15 - 16} In 1891, the eminent surgeon William Halsted sent a breast biopsy for intraoperative examination to Welch.^{11 ,17 - 19} Welch attempted to perform a frozen section but by the time Welch could perform and interpret the frozen section, Halsted had finished the surgery. When Welch heard about Cullen's frozen section technique using prefixation with formalin, this led to the first published description of a frozen section technique in the Bulletin of the Johns Hopkins School of Medicine.^{11 ,13 - 14}

Even though there are multiple contenders for the inventor of first frozen section and first intraoperative frozen section, it is the procedure of Wilson at the Mayo Clinic published in December 1905 that was the best publicized and the most widely accepted technique, and the one that has stood the test of time.^{3 - 4 ,11 ,20 - 21} Today, intraoperative frozen section is a routine procedure that benefits patients throughout the world on a daily basis. As medicine embraces new technologies in the 21st century, it is inspiring to recall the efforts of past pioneers whose innovations are now taken so much for granted.