HNPCC (Lynch Syndrome): Differential Diagnosis, Molecular ...

The history of what is known as HNPCC dates to an observation of Aldred Warthin, pathologist at the University of Michigan School of Medicine [7]. He became deeply moved when his seamstress, in 1895, told him that she would likely die of cancer of the colon, stomach, or her female organs, because of the enormous proclivity to these cancers in her family (unfortunately, just as she had told Warthin, she died at a young age of metastatic endometrial carcinoma). Warthin listened intently, developed her pedigree, and along with other similar cancer prone families published his work in 1913 [8]. Warthin updated the family in 1925 [9]. The seamstress's family has since been known as Family G.

Lynch et al. [10] described the natural history and genetics of two large Midwestern kindreds (Families N and M) in 1966. The clinical genetic features in these families were similar to those of Family G [10]. Dr. A. James French, Warthin's successor as chairman of pathology at the University of Michigan, heard about Lynch's research on Families N and M, [10] and recalled that Warthin, his predecessor, had discovered a similar family (Family G) in 1895. Lynch was then invited by French to take custody of all the detailed documents and pathology specimens which the meticulous Warthin had investigated, catalogued, and published over a span of more than 30 years [8, 9]. Family G was then updated and published in 1971 [11]. This material is discussed in a more detailed review of the history of HNPCC [12]. Through the use of conversion technology, [13] an MSH2 mutation was identified in Family G in the year 2000.