A novel PTEN gene promoter mutation and untypical Cowden syndrome

Cowden syndrome （CS）, an autosomal dominant disorder, is one of a spectrum of clinical disorders that have been linked to germline mutations in the phosphatase and tensin homolog （PTEN） gene. Although 70-80% of patients with CS have an identifiable germline PTEN mutation, the clinical diagnosis presents many challenges because of the phenotypic and genotypic variations. In the present study, we sequenced the exons and the promoter of PTEN gene, mutations and variations in the promoter and exons were identified, and a PTEN protein expression negative region was determined by immunohistochemistry （IHC）. In conclusion, a novel promoter mutation we found in PTEN gene may turn off PTEN protein expression occasionally, leading to the disorder of PTEN and untypical CS manifestations.

Dysplastic Gangliocytoma: A Rare Example of Cerebellar Tumor with An Evident Genetic Profile (Cowden Syndrome)

Objective: To describe the histological and immunohistochemical findings observed when studying a dysplastic cerebellar gangliocytoma observed in a 33-year-old man with a history of Thyroid Cancer. Material and Methods: Radiological images (MRI) and histological and immunohistochemical preparations obtained from the cerebellar tissue were received in our laboratory. Results: A neoplasm constituted by aberrant-looking mature neurons was observed that showed negativity for the immunohistochemical markers of the PTEN protein, expression of the activity of the PTEN gene. Conclusions: Verify the diagnosis of a rare entity, clearly related in scientific publications with Cowden’s Syndrome.

Colorectal cancer risk in hamartomatous polyposis syndromes

Colorectal cancer(CRC) is a major cause of morbidity and mortality around the world, and approximately 5% of them develop in a context of inherited mutations leading to some form of familial colon cancer syndromes. Recognition and characterization of these patients have contributed to elucidate the genetic basis of CRC. Polyposis Syndromes may be categorized by the predominant histological structure found within the polyps. The aim of the present paper is to review the most important clinical features of the Hamartomatous Polyposis Syndromes, a rare group of genetic disorders formed by the peutz-Jeghers syndrome, juvenil polyposis syndrome and PTEN Hamartoma Tumor Syndrome(Bannayan-Riley-Ruvalacaba and Cowden Syndromes). A literature search was performed in order to retrieve the most recent and important papers(articles, reviews, clinical cases and clinical guidelines) regarding the studied subject. We searched for terms such as "hamartomatous polyposis syndromes", "Peutz-Jeghers syndrome", "juvenile polyposis syndrome", "juvenile polyp", and "PTEN hamartoma tumour syndrome"(Cowden syndrome, Bananyan-Riley-Ruvalcaba). The present article reports the wide spectrum of disease severity and extraintestinal manifestations, with a special focus on their potential to develop colorectal and other neoplasia. In the literature, the reported colorectal cancer risk for Juvenile Polyposis, Peutz-Jeghers and PTEN Hamartoma Tumor Syndromes are 39%-68%, 39%-57% and 18%, respectively. A review regarding cancer surveillance recommendations is also presented.

Hamartomatous polyps:Diagnosis,surveillance,and management

Hereditary polyposis syndrome can be divided into three categories:Adenomatous,serrated,and hamartomatous polyps.Hamartomatous polyps,malformations of normal tissue presenting in a disorganized manner,are characterized by an autosomal dominant inheritance pattern.These syndromes exhibit hamartomatous gastrointestinal polyps in conjunction to extra-intestinal manifestations,which require conscientious and diligent monitoring.Peutz-Jeghers syndrome,Cowden syndrome,and juvenile polyposis syndrome are the most common displays of hamartomatous polyposis syndrome(HPS).Diagnosis can be pursued with molecular testing and endoscopic sampling.Early identification of these autosomal dominant pathologies allows to optimize malignancy surveillance,which helps reduce morbidity and mortality in both the affected patient population as well as at-risk family members.Endoscopic surveillance is an important pillar of prognosis and monitoring,with many patients eventually requiring surgical intervention.In this review,we discuss the diagnosis,surveillance,and management of HPS.