Pioneers of exfoliative cytology in the 19th century: the predecessors of George Papanicolaou.

The purpose of our study was to summarize the knowledge on exfoliative cytology during the 19th century and to track down Papanicolaou's predecessors. A thorough study of texts, medical books and reports, together with a review of the available literature in PubMed, was undertaken. The study of cytological preparations as a diagnostic procedure can be traced back to the work of the famous French microscopist Alfred François Donné. However, the systematic study and the criteria for the diagnosis of malignant cells should be attributed to Johannes Müller. The increasing interest in the cytological examination of various fluids of the human body can be confirmed by a plethora of studies published during this period. By the end of the 19th century, the invention of new techniques in pathology, such as the introduction of cell block techniques, tissue sections and new staining methods which provided the opportunity to study surgical specimens in three dimensions, led to a decrease in the interest in exfoliative cytology, which was re-discovered by George Papanicolaou almost three decades later.