Hereditary non-polyposis colorectal cancer associated with disseminated superficial porokeratosis. Microsatellite instability in skin tumours

A 73-year-old man presented with typical lesions of disseminated superficia l porokeratosis (DSP) and multiple seborrhoeic keratoses on his face, trunk and extremities, and later developed a keratoacanthoma on his lip. He belo nged to a cancer-prone pedigree susceptible to colonic, uterine and other i nternal cancers, and had a personal history of early gastric cancer and adv anced adenocarcinoma of the descending colon without adenomatous polyps at age 59 years. Polymerase chain reaction amplification of skin samples for s even separate microsatellite polymorphisms revealed microsatellite instabil ity (MSI) at multiple loci in five of six seborrhoeic keratoses and the ker atoacanthoma, strongly suggesting underlying defects in DNA mismatch repair . Although no germline mutations in two mismatch repair genes hMSH2 and hML H1 were found, our patient was recognized as having hereditary non-polyposi s colorectal cancer (HNPCC) based on the family history and the findings of the microsatellite analysis of skin tumours. This confirmed the usefulness of detection of MSI in prevalent and readily accessible skin lesions, incl uding non-sebaceous non-dysplastic tumours such as seborrhoeic keratosis in the screening of HNPCC families. Although DSP may also be inherited as an autosomal dominant condition, this particular skin disease appeared to be s poradic in our patient and, to our knowledge, no association of DSP or othe r forms of porokeratosis with HNPCC has previously been reported. In contra st to the seborrhoeic keratoses and keratoacanthoma, no MSI was observed in two samples from DSP lesional epidermis examined.