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 pa...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.展开更多
Diffuse intestinal ganglioneuromatosis is a hamartomatous polyposis characterized by a disseminated, intramural or transmural proliferation of neural elements involving the enteric plexuses. It has been associated wit...Diffuse intestinal ganglioneuromatosis is a hamartomatous polyposis characterized by a disseminated, intramural or transmural proliferation of neural elements involving the enteric plexuses. It has been associated with MEN Ⅱ, neurofibromatosis type 1 and hamartomatous polyposis associated with phosphatase and tensin homolog mutation. We report the case of a female patient with a history of a breast and endometrial tumor who presented in a colonoscopy performed for rectal bleeding diffuse ganglioneuromatosis, which oriented the search for other characteristic findings of Cowden syndrome given the personal history of the patient. The presence of an esophagogastric polyposis was also noted. Cowden syndrome is characterized by skin lesions, but it is rarely diagnosed by these lesions, because they are usually overlooked. Intestinal polyposis is not a major diagnostic criterion but it is very useful for early diagnosis. The combination of colonic polyposis and glucogenic acanthosis should orient the diagnosis to Cowden syndrome.展开更多
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. Re...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.展开更多
Cowden's disease, one of the several hamartoma syndromes, is characterized by hyperplastic lesions and hamartomas distributed in the whole body. About thirty percent of patients with Cowden's disease have been...Cowden's disease, one of the several hamartoma syndromes, is characterized by hyperplastic lesions and hamartomas distributed in the whole body. About thirty percent of patients with Cowden's disease have been reported to be complicated by malignant tumors. Based on the criteria of the International Cowden Consortium, this disease is mainly diagnosed as trichilemmoma of the face and oral mucosal papillomatosis. However, Cowden's disease patients themselves often do not recognize trichilemmoma of the face and oral mucosal papillomatosis. We report a case of Cowden's disease in a 33-year-old female patient who was diagnosed based on the characteristic findings at gastrointestinal endoscopy. Clinically, the patient was aware of having bloody stools. Multiple polyps found endoscopically in the esophagus, stomach, ileum, colon and rectum showed histopathologically hamartomatous changes and epithelial hyperplasia. Physical examination revealed oral papillomatosis and facial trichilemmomas. A germline mutation in exon 8 of the phosphatase and tensin homolog deleted on chromosome ten (PTEN) gene was found in this case. It was a point mutation of C to T at codon 1003 (CGA→TGA, arginine→stop codon). The characteristic findings on gastrointestinal endoscopy led us to a diagnosis of Cowden's disease. It has been reported that gastrointestinal polyposis with esophageal polyposis is found in about 85.7% of Japanese patients with Cowden's disease. The characteristic findings on gastrointestinal endoscopy can be a useful diagnostic clue to Cowden's disease.展开更多
AIM: To investigate our clinical experience with the colonic manifestations of phosphatase and tensin homolog on chromosome ten (PTEN) hamartoma tumor syndrome (PHTS) and to perform a systematic literature review rega...AIM: To investigate our clinical experience with the colonic manifestations of phosphatase and tensin homolog on chromosome ten (PTEN) hamartoma tumor syndrome (PHTS) and to perform a systematic literature review regarding the same.展开更多
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 characterize...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.展开更多
Background: Testicular lipomatosis is a very rare and benign disorder of the testicles. It usually presents as multiple bilateral ill-defined hyper-echoic intra-testicular lesions of different sizes but generally with...Background: Testicular lipomatosis is a very rare and benign disorder of the testicles. It usually presents as multiple bilateral ill-defined hyper-echoic intra-testicular lesions of different sizes but generally with maximum 4 mm. Testicular lipomatosis is usually reported in association with Cowden’s syndrome. Aim: We aimed to show that there are cases of testicular lipomatosis occurring in the absence of Cowden’s syndrome. Case Presentation: We present a 28-year-old man with testicular pain, who was finally diagnosed as having isolated testicular lipomatosis without other clinical and biochemical abnormalities using magnetic resonance imaging (MRI) technique. Conclusion: We showed that the testicular lipomatosis may occur and be detected without any evidence of Cowden’s disease.展开更多
<div style="text-align:justify;"> <span style="font-family:Verdana;"><strong>Objective:</strong> To describe the histological and immunohistochemical findings observed when ...<div style="text-align:justify;"> <span style="font-family:Verdana;"><strong>Objective:</strong> 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. <strong>Material and Methods:</strong> Radiological images (MRI) and histological and immunohistochemical preparations obtained from the cerebellar tissue were received in our laboratory. <strong>Results:</strong> 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. <strong>Conclusions:</strong> Verify the diagnosis of a rare entity, clearly related in scientific publications with Cowden’s Syndrome.</span> </div>展开更多
Cowden syndrome is a rare autosomal dominant disorder that is characterized by multiple hamartomas in a variety of tissues and this is associated with germline mutations in the phosphatase and tensin homologue (PTEN) ...Cowden syndrome is a rare autosomal dominant disorder that is characterized by multiple hamartomas in a variety of tissues and this is associated with germline mutations in the phosphatase and tensin homologue (PTEN) gene, which is the tumor suppressor gene located on chromosome 10q23.3. It is characterized by multiple hamartomatous neoplasms of the skin, oral mucosa, gastrointestinal (GI) tract, bones, central nervous system, eyes, and genitourinary tract. Cowden syndrome does not have increased risk of GI malignancy; however, it has an increased risk of breast, thyroid and endometrial cancer development. Herethe authors report a rare case of Cowden syndrome incidentally diagnosed from multiple gastric polyposis. A 29-year-old woman presented with multiple gastric polyps. The laboratory results were normal except for mild anemia, with a hemoglobin level of 11.9 g/dL. Esophagogastroduodenoscopy revealed multiple gastric, duodenal polyps and esophageal acanthosis. Colonoscopy revealed possible hamartomatous polyps in the rectum. Under the suspicion of Cowden syndrome, sonography of the thyroid and breasts was carried out, which revealed multiple thyroid masses. Subsequent fine-needle aspiration biopsy revealed the presence of clusters of follicular epithelial cells, and due to the possibility of malignancy, the patient underwent total thyroidectomy. The pathology was reported as invasive follicular carcinoma. A gene study by direct sequencing showed the presence of a PTEN mutation (c.633C > A /p.Cys211*).展开更多
A 21-year-old woman with complaints of hematochezia was diagnosed as having Cowden's disease (CD), an autosomal dominant condition characterized by multiple hamartomas, since facial papules and gingival papillomas...A 21-year-old woman with complaints of hematochezia was diagnosed as having Cowden's disease (CD), an autosomal dominant condition characterized by multiple hamartomas, since facial papules and gingival papillomas were identified. On endoscopy, multiple hyperplastic polyps were seen in the rectum and left-side colon. There were also esophageal glycogenic acanthosis and hyperplastic polyposis in the antrum accompanied by Helicobacter pylorirelated gastritis. Although gastric hyperplastic polyposis had by no means regressed with unsuccessful first-line eradication therapy for H pylori, following cure of the infection with salvage therapy consisting of rabeprazole,amoxicillin and metronidazole, the polyposis lesions almost disappeared. Follow-up gastroscopy 2 and 3 years after cessation of the second-line eradication therapy revealed almost complete regression of the polyposis lesions with no evidence of H pylori infection. We recommend eradication treatment for CD patients with gastric hyperplastic polyps and the infection, as the occurrence of gastric carcinoma among hyperplastic polyps has been described.展开更多
10号染色体上磷酸酶和张力蛋白同源物(phosphatase and tensin-homolog deleted on chromosome 10,PTEN)是重要的抑癌基因,其突变可引发PTEN错构瘤肿瘤综合征(PTEN hamartoma tumor syndrome,PHTS),常被称为Cowden综合征,是较为罕见的...10号染色体上磷酸酶和张力蛋白同源物(phosphatase and tensin-homolog deleted on chromosome 10,PTEN)是重要的抑癌基因,其突变可引发PTEN错构瘤肿瘤综合征(PTEN hamartoma tumor syndrome,PHTS),常被称为Cowden综合征,是较为罕见的遗传性肿瘤综合征,其与早发性、多发性乳腺癌高度相关。本文报道3例PTEN基因突变相关单侧多中心乳腺癌及同时性、异时性双侧乳腺癌患者,并总结其临床表现、病理特征、诊治经验及随访情况,旨在为临床医生更好地诊治PTEN基因突变相关乳腺癌及Cowden综合征人群提供借鉴。展开更多
基金supported by National Natural Science Foundation of China (30970623)International Science and Technology Cooperation Projects (2010DFA31840 and 2010DFB33720)Beijing Natural Science Foundation(5112030)
文摘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.
文摘Diffuse intestinal ganglioneuromatosis is a hamartomatous polyposis characterized by a disseminated, intramural or transmural proliferation of neural elements involving the enteric plexuses. It has been associated with MEN Ⅱ, neurofibromatosis type 1 and hamartomatous polyposis associated with phosphatase and tensin homolog mutation. We report the case of a female patient with a history of a breast and endometrial tumor who presented in a colonoscopy performed for rectal bleeding diffuse ganglioneuromatosis, which oriented the search for other characteristic findings of Cowden syndrome given the personal history of the patient. The presence of an esophagogastric polyposis was also noted. Cowden syndrome is characterized by skin lesions, but it is rarely diagnosed by these lesions, because they are usually overlooked. Intestinal polyposis is not a major diagnostic criterion but it is very useful for early diagnosis. The combination of colonic polyposis and glucogenic acanthosis should orient the diagnosis to Cowden syndrome.
文摘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.
文摘Cowden's disease, one of the several hamartoma syndromes, is characterized by hyperplastic lesions and hamartomas distributed in the whole body. About thirty percent of patients with Cowden's disease have been reported to be complicated by malignant tumors. Based on the criteria of the International Cowden Consortium, this disease is mainly diagnosed as trichilemmoma of the face and oral mucosal papillomatosis. However, Cowden's disease patients themselves often do not recognize trichilemmoma of the face and oral mucosal papillomatosis. We report a case of Cowden's disease in a 33-year-old female patient who was diagnosed based on the characteristic findings at gastrointestinal endoscopy. Clinically, the patient was aware of having bloody stools. Multiple polyps found endoscopically in the esophagus, stomach, ileum, colon and rectum showed histopathologically hamartomatous changes and epithelial hyperplasia. Physical examination revealed oral papillomatosis and facial trichilemmomas. A germline mutation in exon 8 of the phosphatase and tensin homolog deleted on chromosome ten (PTEN) gene was found in this case. It was a point mutation of C to T at codon 1003 (CGA→TGA, arginine→stop codon). The characteristic findings on gastrointestinal endoscopy led us to a diagnosis of Cowden's disease. It has been reported that gastrointestinal polyposis with esophageal polyposis is found in about 85.7% of Japanese patients with Cowden's disease. The characteristic findings on gastrointestinal endoscopy can be a useful diagnostic clue to Cowden's disease.
文摘AIM: To investigate our clinical experience with the colonic manifestations of phosphatase and tensin homolog on chromosome ten (PTEN) hamartoma tumor syndrome (PHTS) and to perform a systematic literature review regarding the same.
文摘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.
文摘Background: Testicular lipomatosis is a very rare and benign disorder of the testicles. It usually presents as multiple bilateral ill-defined hyper-echoic intra-testicular lesions of different sizes but generally with maximum 4 mm. Testicular lipomatosis is usually reported in association with Cowden’s syndrome. Aim: We aimed to show that there are cases of testicular lipomatosis occurring in the absence of Cowden’s syndrome. Case Presentation: We present a 28-year-old man with testicular pain, who was finally diagnosed as having isolated testicular lipomatosis without other clinical and biochemical abnormalities using magnetic resonance imaging (MRI) technique. Conclusion: We showed that the testicular lipomatosis may occur and be detected without any evidence of Cowden’s disease.
文摘<div style="text-align:justify;"> <span style="font-family:Verdana;"><strong>Objective:</strong> 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. <strong>Material and Methods:</strong> Radiological images (MRI) and histological and immunohistochemical preparations obtained from the cerebellar tissue were received in our laboratory. <strong>Results:</strong> 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. <strong>Conclusions:</strong> Verify the diagnosis of a rare entity, clearly related in scientific publications with Cowden’s Syndrome.</span> </div>
文摘Cowden syndrome is a rare autosomal dominant disorder that is characterized by multiple hamartomas in a variety of tissues and this is associated with germline mutations in the phosphatase and tensin homologue (PTEN) gene, which is the tumor suppressor gene located on chromosome 10q23.3. It is characterized by multiple hamartomatous neoplasms of the skin, oral mucosa, gastrointestinal (GI) tract, bones, central nervous system, eyes, and genitourinary tract. Cowden syndrome does not have increased risk of GI malignancy; however, it has an increased risk of breast, thyroid and endometrial cancer development. Herethe authors report a rare case of Cowden syndrome incidentally diagnosed from multiple gastric polyposis. A 29-year-old woman presented with multiple gastric polyps. The laboratory results were normal except for mild anemia, with a hemoglobin level of 11.9 g/dL. Esophagogastroduodenoscopy revealed multiple gastric, duodenal polyps and esophageal acanthosis. Colonoscopy revealed possible hamartomatous polyps in the rectum. Under the suspicion of Cowden syndrome, sonography of the thyroid and breasts was carried out, which revealed multiple thyroid masses. Subsequent fine-needle aspiration biopsy revealed the presence of clusters of follicular epithelial cells, and due to the possibility of malignancy, the patient underwent total thyroidectomy. The pathology was reported as invasive follicular carcinoma. A gene study by direct sequencing showed the presence of a PTEN mutation (c.633C > A /p.Cys211*).
文摘A 21-year-old woman with complaints of hematochezia was diagnosed as having Cowden's disease (CD), an autosomal dominant condition characterized by multiple hamartomas, since facial papules and gingival papillomas were identified. On endoscopy, multiple hyperplastic polyps were seen in the rectum and left-side colon. There were also esophageal glycogenic acanthosis and hyperplastic polyposis in the antrum accompanied by Helicobacter pylorirelated gastritis. Although gastric hyperplastic polyposis had by no means regressed with unsuccessful first-line eradication therapy for H pylori, following cure of the infection with salvage therapy consisting of rabeprazole,amoxicillin and metronidazole, the polyposis lesions almost disappeared. Follow-up gastroscopy 2 and 3 years after cessation of the second-line eradication therapy revealed almost complete regression of the polyposis lesions with no evidence of H pylori infection. We recommend eradication treatment for CD patients with gastric hyperplastic polyps and the infection, as the occurrence of gastric carcinoma among hyperplastic polyps has been described.
文摘10号染色体上磷酸酶和张力蛋白同源物(phosphatase and tensin-homolog deleted on chromosome 10,PTEN)是重要的抑癌基因,其突变可引发PTEN错构瘤肿瘤综合征(PTEN hamartoma tumor syndrome,PHTS),常被称为Cowden综合征,是较为罕见的遗传性肿瘤综合征,其与早发性、多发性乳腺癌高度相关。本文报道3例PTEN基因突变相关单侧多中心乳腺癌及同时性、异时性双侧乳腺癌患者,并总结其临床表现、病理特征、诊治经验及随访情况,旨在为临床医生更好地诊治PTEN基因突变相关乳腺癌及Cowden综合征人群提供借鉴。
