M. Takata et al., Hereditary non-polyposis colorectal cancer associated with disseminated superficial porokeratosis. Microsatellite instability in skin tumours, BR J DERM, 143(4), 2000, pp. 851-855
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.