Virchow and cellular pathology
Few would argue that Rudolf Virchow (1821-1902, top image) is the father of modern pathology*, and laid the groundwork for morphologic analysis of disease. His dictum, omnis cellula e cellula–all cells come from cells, published in his 1858 textbook, Cellular Pathology, refuted the then current belief in the spontaneous generation of life, and played a central role in ending the conceptually naive system of humoralism. This pseudoscientific doctrine was based on ancient Greek medicine, and attributed disease to an imbalance of the four humors: blood, phlegm, yellow bile and black bile. Whilst Virchow didn’t always get things right, his contributions to the world in general and pathology in particular cannot be underestimated.
*From the Greek pathos, disease and logos, study
On the one hand, Virchow was an avid anthropologist and disproved the tenets of racism concluding, based on his analysis of the hair and eye color of 6.8 million (!!!!) schoolchildren, that one could differentiated between Jews and Germans–dealing a blow to those who believed in an Aryan race. On the other hand, he thought that Darwin had it wrong…and humans could not have possibly come from apes. Virchow’s political influence led to the 1882 exclusion of natural history (Darwinism) from Prussian schools. He was also wrong about Pasteur*, dismissing his germ theory, and Semmelweis*, who ordered his students to wash their hands between performing autopsies and examining pregnant women, a simple procedure that led to a ten-fold reduction in maternal mortality.
*Pasteur and Semmelweis laid the foundation of medical microbiology.
But one can forgive Virchow for his missteps outside of pathology. He was the first to describe leukemia and the first to analyse hair in criminal investigation. He coined the terms agenesis, amyloid degeneration (now known as amyloidosis), chromatin, ochronosis (now alkaptonuria), osteoid, parenchyma, spina bifida, and zoonoses. He elucidated the mechanism of thromboembolism; recognized that cancers arose from previously normal cells; and described autopsy techniques still in use today. He ordered his students to “think microscopically”…which probably explains why we all had to buy microscopes as med students.
The 20th century could be called the golden age of cellular pathology, standing as we have on the shoulders of Virchow and the other giants who followed. The early part of the century saw the development of special stains that allowed identification of iron, mucin, amyloid, and bacteria. The early pathologists described in great detail, the postmortem findings of all ilk of diseases. Therein lay the problem: autopsy findings are little help to the living. In the first half of the 20th century, pathology had not matured as a clinical discipline. A correct diagnosis made a week after death is a pyrrhic victory*. Beginning in the 1940s, pathologists began to interact more regularly with their surgical colleagues, leading to a new discipline, the seminal event for which was the publication in 1953 of the aptly named textbook, Surgical Pathology†, by Lauren Ackerman, the widely acknowledged father of surgical pathology.
*This is from an old joke: What’s the difference between an internist, a surgeon, a psychiatrist, and a pathologist ?
The internist knows everything and does nothing.
The surgeon knows nothing and does everything.
The psychiatrist knows nothing and does nothing.
The pathologist knows everything, but always a week too late.
†It wasn’t the first book on the subject, but its focus on differential diagnosis made it the “go to” reference.
Today, the bulk of pathology practice is in surgical pathology. As surgical pathologists, we are tasked with determining cell lineage (is it carcinoma, melanoma, lymphoma?), aggressiveness (is it well-, moderately- or poorly differentiated?), staging (how deeply has it invaded? are lymph nodes involved? has it metastasized?). Surgical pathology has been the beneficiary of advances in immunodiagnostics, e.g., HER-2 overexpression in breast cancer cells, a marker of aggressiveness (see bottom image), a veritable cornucopia of monoclonal antibodies that improve the diagnostic yield, and digital pathology, which facilitates distant consultations, teaching and archiving. What’s just over the horizon for surgical pathology, application of techniques from the Human Genome Project is even more exciting.…