Germline PTEN mutation Cowden syndrome: an underappreciated form of hereditary kidney cancer.

[cowden syndrome]

Cowden syndrome is a hereditary cancer syndrome associated with a germline mutation in PTEN . Patients are predisposed to multiple malignancies including renal cell carcinoma .Patients with Cowden syndrome were evaluated as part of a clinical protocol . Those with a history of renal cell carcinoma underwent review of clinical features , tumor characteristics and family history . Renal tumors were evaluated for loss of heterozygosity .Among 24 patients with Cowden syndrome 4 were identified with renal cell carcinoma (16 .7 %). Three patients had solitary tumors , 2 with papillary type I histology and 1 with clear cell histology . The fourth patient had bilateral , synchronous chromophobe tumors . No patients had a prior family history of renal cell carcinoma . All patients with renal cell carcinoma had dermatologic manifestations of Cowden syndrome and had macrocephaly . Loss of heterozygosity at the PTEN mutation was identified in 4 tumors (80 %). No genotype-phenotype association was found , as the same mutation was identified in different renal cell carcinoma histologies .Renal cell carcinoma is an underappreciated feature of Cowden syndrome . As most patients lack a prior family history or a distinctive renal cell carcinoma histology , recognition of the associated nonrenal features should target referral for genetic counseling . PTEN loss of heterozygosity is common in Cowden syndrome renal tumors . Because loss of PTEN can activate mTOR and mTOR inhibitors are Food and Drug Administration approved to treat renal cell carcinoma , these agents have clinical potential in renal cell carcinoma associated with Cowden syndrome .