title: First report of ovarian dysgerminoma in Cowden syndrome with germline PTEN mutation and PTEN-related 10q loss of tumor heterozygosity.
abstract: We present the first report of ovarian dysgerminoma in Cowden syndrome, presenting in a 7-year-old girl. In her second decade, a hamartomatous soft tissue extremity mass and diffuse gastrointestinal hamartomatous polyposis with pathologic features suggestive of either juvenile, Peutz-Jeghers, or Cowden polyps were identified, along with diffuse esophageal glycogenic acanthosis and skin manifestations. During regular thyroid cancer surveillance under the provisional diagnosis of Cowden syndrome, papillary thyroid carcinoma and benign follicular nodules were diagnosed at age 23. PTEN mutational analysis revealed a novel germline nonsense point mutation of Q219X. Loss of PTEN heterozygosity was also present in the ovarian dysgerminoma. Parental mutation testing and phenotype screening were negative. The correct classification of Cowden syndrome is difficult because of its protean manifestations and overlapping phenotypes with other genetic and noninherited pathologies, particularly regarding various gastrointestinal polyposis syndromes. Despite the challenges, correct classification is critical to patient care because of the associated cancer predispositions and necessary surveillance programs. This is the first report of Cowden syndrome presenting with ovarian dysgerminoma, which implicates PTEN in the molecular pathogenesis of dysgerminoma and adds it to the phenotypic manifestations of Cowden syndrome.
authors.affiliation: Department of Pathology, Wonju College of Medicine, Yonsei University, Wonju, Korea.
authors.forename: Mee-Yon
authors.initials: MY
authors.lastname: Cho
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Charis
authors.initials: C
authors.lastname: Eng
authors.forename: Dae Sung
authors.initials: DS
authors.lastname: Kim
authors.forename: Seong Joon
authors.initials: SJ
authors.lastname: Kang
authors.forename: Minseob
authors.initials: M
authors.lastname: Eom
authors.forename: Sang Yeop
authors.initials: SY
authors.lastname: Yi
authors.forename: Mary P
authors.initials: MP
authors.lastname: Bronner
mesh_terms: D000328:Adult; D002648:Child; D002879:Chromosomes, Human, Pair 10; D004407:Dysgerminoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D018095:Germ-Line Mutation; D006223:Hamartoma Syndrome, Multiple / Q000150:complications / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D010641:Phenotype
chemical_list: D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human