Atypical osteosarcomas in Werner syndrome (adult progeria)

Werner syndrome (WS), adult progeria, is more common in Japan than elsewher e. It predisposes to osteosarcoma (OS) and five other rare tumors. To deter mine if and how OS is atypical in this genetic disorder, we studied the cha racteristics of ten Japanese cases with respect to clinical features, patho logy, and radiographs, and compared them with a hospital series of 36 skele tal OS with the same atypical age-range, 35-57 years. The anatomic sites we re also atypical: seven ankle/foot, two radius and one patella compared wit h only one at the ankle in the hospital series. The osteoblastic cell-type was about equally frequent in both series, but, among others than the three major subtypes, there was only one in WS as compared with 14 (39%) in the hospital series. The types of mutations were sought in five WS cases with O S. One showed no mutation at any of the ten known loci for Japanese, two we re of type 4/4 and two of type 6/6. The mutations 4 and 6 have been found i n 66% of alleles of WS cases in Japan. The increased frequency and unusual age and site distributions of OS in WS may be due to increased susceptibili ty, related to later-life leg ulcers, and weight-bearing on spindly ankles weakened by severe loss of lower limb subcutaneous tissue.