Second malignant neoplasms in patients with Cowden syndrome with underlying germline PTEN mutations.

[cowden syndrome]

Patients with Cowden syndrome (CS ) with underlying germline PTEN mutations are at increased risk of breast , thyroid , endometrial , and renal cancers . To our knowledge , risk of subsequent cancers in these patients has not been previously explored or quantified .We conducted a 7 -year multicenter prospective study (2005 to 2012 ) of patients with CS or CS -like disease , all of whom underwent comprehensive PTEN mutational analysis . Second malignant neoplasms (SMNs ) were ascertained by medical records and confirmed by pathology reports . Standardized incidence ratios (SIRs ) for all SMNs combined and for breast , thyroid , endometrial , and renal cancers were calculated .Of the 2 ,912 adult patients included in our analysis , 2 ,024 had an invasive cancer history . Germline pathogenic PTEN mutations (PTEN mutation positive ) were identified in 114 patients (5 .6 %). Of these 114 patients , 46 (40 %) had an SMN . Median age of SMN diagnosis was 50 years (range , 21 to 71 years ). Median interval between primary cancer and SMN was 5 years (range , <1 to 35 years ). Of the 51 PTEN mutation -positive patients who presented with primary breast cancer , 11 (22 %) had a subsequent new primary breast cancer and 10 -year second breast cancer cumulative risk of 29 % (95 % CI , 15 .3 to 43 .7 ). Risk of SMNs compared with that of the general population was significantly elevated for all cancers (SIR , 7 .74 ; 95 % CI , 5 .84 to 10 .07 ), specifically for breast (SIR , 8 .92 ; 95 % CI , 5 .85 to 13 .07 ), thyroid (SIR , 5 .83 ; 95 % CI , 3 .01 to 10 .18 ), and endometrial SMNs (SIR , 14 .08 .07 ; 95 % CI , 7 .10 to 27 .21 ).Patients with CS with germline PTEN mutations are at higher risk for SMNs compared with the general population . Prophylactic mastectomy should be considered on an individual basis given the significant risk of subsequent breast cancer .

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