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.

Aloe-emodin suppresses esophageal cancer cell TE1 proliferation by inhibiting AKT and ERK phosphorylation

“…Accumulating evidence indicates that numerous molecular changes are associated with EC tumorigenesis, including epidermal growth factor receptor (EGFR) amplification, phosphoinositide 3-kinase, catalytic subunit alpha (PIK3CA) amplification and mutation (8)(9)(10), and phosphatase and tensin homolog (PTEN) mutation or loss (11,12). Alteration of these molecular events contributes to downstream pathway activation (8)(9)(10)(11)(12).…”

“…Alteration of these molecular events contributes to downstream pathway activation (8)(9)(10)(11)(12). The phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated protein kinase kinase (MEK)/ERK signaling pathways are two important pathways that can be activated by EGFR amplification and PTEN loss, which may ultimately lead to tumorigenesis (13).…”

Diagnóstico de disgerminoma ovariano durante a gestação

“…2,9,11 In the case described here, giant left-side uterine leiomyoma was diagnosed during prenatal tests and neither adnexal tumor nor ovarian neoplasm were considered. Although the 14-week obstetric US showed a corpus luteum cyst in an enlarged left ovary, to a certain extent, this corresponds to what takes place in around 70% to 80% of cases, when the US operator does not routinely measure the diameter 8,11,12 . Furthermore, the fact that the US at 19 weeks and 2 days did not identify structural abnormalities, either in the fetus or the ovary, raises the question of whether or not there was a mass in the ovary at that point, since the US operator reported nothing.…”

“…Furthermore, the fact that the US at 19 weeks and 2 days did not identify structural abnormalities, either in the fetus or the ovary, raises the question of whether or not there was a mass in the ovary at that point, since the US operator reported nothing. The specialist literature indicates that certain neoplasms may undergo geometric growth of up to around 20% of their original size in a very short period of time (1 -2 months) 12,14,26 . When the 31-week US identified a solid mass in the left adnexa, its syndromes have associations with dysgerminoma, as is the case with Cowden's syndrome 12 , ataxia telangiectasia syndrome 13 , Swyer syndrome (pure gonadal dysgenesis associated with the XY 46 karyotype) 14,15 , Apert syndrome (an autosomal dominant disorder) 16 and Down Syndrome 17 .…”

“…The specialist literature indicates that certain neoplasms may undergo geometric growth of up to around 20% of their original size in a very short period of time (1 -2 months) 12,14,26 . When the 31-week US identified a solid mass in the left adnexa, its syndromes have associations with dysgerminoma, as is the case with Cowden's syndrome 12 , ataxia telangiectasia syndrome 13 , Swyer syndrome (pure gonadal dysgenesis associated with the XY 46 karyotype) 14,15 , Apert syndrome (an autosomal dominant disorder) 16 and Down Syndrome 17 . Since the patient described here was pregnant and had no phenotypical signs that would suggest relevant syndromic data, she was not asked about, or assessed for, this possibility.…”