Cowden's disease (CD) is an autosomal dominant disorder which confers a hig
h susceptibility to diverse benign and malignant tumors. The PTEN (phosphat
ase and tensin homologue deleted in chromosome ten) gene has been identifie
d as a tumor suppressor gene responsible for cancers of the endometrium, ov
ary, prostate, and glioblastomas. Recently, germline mutations of this gene
were also found in patients with CD, and it is now recognized as a gene re
sponsible for this disease. We identified a germline nonsense mutation at c
odon 130 in exon 5 of PTEN in a 56-year-old Japanese woman with CD. The pat
ient had adenoid facies and mucocutaneous lesions including multiple facial
papules, acral keratoses on neck and shoulders, palmoplantar keratoses, mu
ltiple oral papillomas, scrotal tongue, mucosal and cutaneous hemangiomas,
and a sclerotic fibroma on the arm. She also had benign and malignant polyp
oid neoplasms throughout the entire digestive tract, including adenocarcino
ma of the colon and submucosal lipomas of the rectum, as well as bilateral
breast carcinomas, multinodular goiters, an ovarian cyst with a fibroma-lik
e nodule, hepatic hemangiomas, and abdominal hernia. We searched CD cases w
ith the same genotypic PTEN mutation as the present case and compared their
phenotypes. Further studies will disclose a better understanding of the ro
le of mutation in the PTEN gene in the course of tumorigenesis of both beni
gn and malignant tumors developed in patients with CD.