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 .

Diseases
Validation

Diseases presenting "cancer" symptom

achondroplasia

acute rheumatic fever

adrenal incidentaloma

alpha-thalassemia

benign recurrent intrahepatic cholestasis

cadasil

canavan disease

carcinoma of the gallbladder

cholangiocarcinoma

coats disease

congenital adrenal hyperplasia

congenital diaphragmatic hernia

cowden syndrome

cushing syndrome

cutaneous mastocytosis

dedifferentiated liposarcoma

dystrophic epidermolysis bullosa

epidermolysis bullosa simplex

erdheim-chester disease

erythropoietic protoporphyria

esophageal adenocarcinoma

esophageal carcinoma

esophageal squamous cell carcinoma

familial hypocalciuric hypercalcemia

familial mediterranean fever

gm1 gangliosidosis

heparin-induced thrombocytopenia

hereditary cerebral hemorrhage with amyloidosis

hirschsprung disease

hodgkin lymphoma, classical

inclusion body myositis

junctional epidermolysis bullosa

kabuki syndrome

kallmann syndrome

kindler syndrome

lamellar ichthyosis

liposarcoma

locked-in syndrome

lymphangioleiomyomatosis

monosomy 21

neuralgic amyotrophy

oculocutaneous albinism

oligodontia

oral submucous fibrosis

papillon-lefèvre syndrome

pendred syndrome

pleomorphic liposarcoma

primary effusion lymphoma

proteus syndrome

pyomyositis

pyruvate dehydrogenase deficiency

severe combined immunodeficiency

sneddon syndrome

systemic capillary leak syndrome

triple a syndrome

von hippel-lindau disease

waldenström macroglobulinemia

well-differentiated liposarcoma

werner syndrome

wiskott-aldrich syndrome

wolf-hirschhorn syndrome

x-linked adrenoleukodystrophy

This symptom has already been validated