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It is interesting to contemplate how differently margin assessment techniques might have evolved had it not been for a few key people. Who knows, perhaps instead of freezing and finely slicing tissue for margin assessment, we would be scanning tumors using some less-accurate imaging technology. Or maybe we would be diving straight into some form of costly and difficult molecular assessment.


In the 19th century, many surgeons examined tumors macroscopically themselves. By today’s standards, this was crude, but it did serve some purpose in trying to determine whether a lesion was malignant. The specimen was often disposed of afterward without much in the way of documentation or a formal diagnosis. The introduction of methods of fixation, the microtome (an instrument that finely cuts tissues to prepare microscopic slides), and microscopy paved the way for surgical pathology. Rudolf Virchow (1821-1902) is generally recognized as the father of microscopic pathology. An innovative polymath, he was known by his colleagues at Berlin’s Charité Hospital as “The Pope” due to his authority and influence. Due in no small part to his contributions, surgical pathology expanded from a purely macroscopic examination performed by surgeons to become the enormously important specialized medical field it continues to be today.1-3


The invention of the frozen section can be traced back to various vague descriptions of assessments of fresh tissue using a microscope in the 1800s, and then more concise descriptions in the early 1900s.

In the Virchow laboratory, Julius Cohnheim pioneered the use of the frozen section examination. Unfortunately, Cohnheim neither shared Virchow’s influence nor went to the trouble of clearly publishing his observations, and thus his contributions went largely unnoticed.

Later (1891), at the recently established Johns Hopkins Hospital and Medical School in Baltimore, William Welch used a carbon dioxide–freezing microtome to examine breast tissue removed by the preeminent surgeon William Halstead. Unfortunately, Welch did not appreciate the potential benefit of interpreting the frozen section slides immediately and so by the time he was ready to communicate the results, Halstead had already finished operating.

Welch’s student Thomas S. Cullen is generally given credit for first publishing the technique for intraoperative frozen section in 1895. Cullen understood the principles of freezing and he sliced sections from intraoperative specimens by pre-fixing tissues in formalin.4,5 Soon, the Mayo Clinic in Rochester, Illinois, led the way in refining the technique and a 1905 paper by Mayo’s Louis B. Wilson provided a comprehensive description of the technique still used today. Though the paper has been criticized for not referencing the previous works of Cullen and others, the descriptions are clear, concise, and introduced many readers to the technique.6-8 William Mayo reportedly encouraged the innovation and apparently often complained, “I wish you pathologists would find a ...

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