1/56. Identification of a novel PTEN mutation (L139X) in a patient with Cowden disease and sjogren's syndrome.Cowden disease is an autosomal dominant disorder associated with an increased risk of breast, thyroid, and skin cancer in which germline mutations in a candidate tumour suppressor gene (PTEN) have been identified previously. sjogren's syndrome is a chronic inflammatory and autoimmune disorder of exocrine glands for which the genetic basis is unknown. This report describes a novel PTEN mutation (L139X) in a patient with Cowden disease and sjogren's syndrome. This observation raises the possibility of a link between mutations in the PTEN gene and sjogren's syndrome.- - - - - - - - - - ranking = 1keywords = breast (Clic here for more details about this article) |
2/56. Dysplastic gangliocytoma (Lhermitte-Duclos disease) associated with Cowden disease: report of a case and review of the literature for the genetic relationship between the two diseases.We report a case of dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease, LDD). The patient also had cutaneous and mucosal hamartomas, adenomatous goiter, bilateral breast tumors, and gastrointestinal polyposis, indicating the diagnosis of Cowden disease (CD), the familial hamartoma syndrome. This was a rare sporadic case without any family history of CD, though CD is considered to be an autosomal dominant hereditary disease. Based on a thorough review of the previously reported cases, it is reasonable to consider that CD is inherited in autosomal dominant fashion through a CD gene (PTEN) containing a germline mutation, and that the occurrence of LDD is predicted on an additional somatic hit on the remaining normal CD allele or another unknown gene.- - - - - - - - - - ranking = 1keywords = breast (Clic here for more details about this article) |
3/56. Transcatheter embolization of arteriovenous malformations in Cowden disease.A patient with Cowden disease and multiple arteriovenous malformations (AVMs) that resulted in high output heart failure is described. Cowden disease is a familial syndrome characterized by endodermal, mesodermal and ectodermal dysplasia causing benign and malignant tumors of the skin, breast, gastrointestinal tract, and thyroid gland. Our patient had gastrointestinal polyposis, a right renal tumor, a left lung tumor, an adenomatous goiter, and typical dermatologic findings such as facial papules, acral keratosis, gingival papillomatosis and hemangiomas. AVMs were observed in the pelvis, cervical vertebra, liver, and right supraclavicular area. Transcatheter embolization was performed 7 times for the pelvic AVMs, but the effect decreased with repetition and the patient died of heart failure 2 years after the first embolization. The serum levels of tissue plasminogen activator (t-PA), platelet-derived growth factor (PDGF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and transforming growth factor beta1 were high, suggesting that these angiogenic molecules may play a role in the pathogenesis of AVMs in Cowden disease.- - - - - - - - - - ranking = 1keywords = breast (Clic here for more details about this article) |
4/56. Pulmonary abnormalities in Cowden's disease.Cowden's disease is an inheritable multiple neoplastic syndrome represented by benign and malignant lesions of skin, digestive tract, mucosae, breast and thyroid. The syndrome, first described by Lloyd and Dennis in 1963, includes benign lung lesions, described in the literature only as hamartomas. The unusual condition of our case consists of multiple and bilateral lipomatous lesions of the lung and of adipose colonic polyps, diagnosed respectively by video assisted mini-thoracotomy and by endoscopic biopsies.- - - - - - - - - - ranking = 1keywords = breast (Clic here for more details about this article) |
5/56. Male breast cancer in Cowden syndrome patients with germline PTEN mutations.Cowden syndrome (CS) (OMIM 158350) is a multiple hamartoma syndrome associated with germline mutations in the PTEN tumour suppressor gene. While CS is characterised most commonly by non-cancerous lesions (mucocutaneous trichilemmomas, acral and palmoplantar keratoses, and papillomatous papules), it is also associated with an increased susceptibility to breast cancer (in females) and thyroid cancer, as well as non-cancerous conditions of the breast and thyroid. Here we report two cases of male breast cancer occurring in patients with classical CS phenotypes and germline PTEN mutations. The first subject was diagnosed with CS indicated primarily by mucocutaneous papillomatosis, facial trichilemmomas, and macrocephaly with frontal bossing at the age of 31 years. He developed breast cancer at 41 years and subsequently died of the disease. A PTEN mutation, c.802delG, was identified in this subject, yet none of his family members showed evidence of a CS phenotype, suggesting that this PTEN mutation may be a de novo occurrence. The second subject had a CS phenotype including multiple trichilemmomas and thyroid adenoma, developed male breast cancer at 43 years, and died of the disease at 57 years. He was a carrier of a PTEN mutation c.347-351delACAAT that cosegregated with the CS phenotype in affected family members. These two cases of male breast cancer associated with germline PTEN mutations and the CS phenotype suggest that CS may be associated with an increased risk of early onset male as well as female breast cancer.- - - - - - - - - - ranking = 11keywords = breast (Clic here for more details about this article) |
6/56. Germline mutation of the PTEN gene in a Japanese patient with Cowden's disease.Cowden's disease (CD) is an autosomal dominant disorder which confers a high susceptibility to diverse benign and malignant tumors. The PTEN (phosphatase and tensin homologue deleted in chromosome ten) gene has been identified as a tumor suppressor gene responsible for cancers of the endometrium, ovary, prostate, and glioblastomas. Recently, germline mutations of this gene were also found in patients with CD, and it is now recognized as a gene responsible for this disease. We identified a germline nonsense mutation at codon 130 in exon 5 of PTEN in a 56-year-old Japanese woman with CD. The patient had adenoid facies and mucocutaneous lesions including multiple facial papules, acral keratoses on neck and shoulders, palmoplantar keratoses, multiple oral papillomas, scrotal tongue, mucosal and cutaneous hemangiomas, and a sclerotic fibroma on the arm. She also had benign and malignant polypoid neoplasms throughout the entire digestive tract, including adenocarcinoma of the colon and submucosal lipomas of the rectum, as well as bilateral breast carcinomas, multinodular goiters, an ovarian cyst with a fibroma-like nodule, hepatic hemangiomas, and abdominal hernia. We searched CD cases with the same genotypic PTEN mutation as the present case and compared their phenotypes. Further studies will disclose a better understanding of the role of mutation in the PTEN gene in the course of tumorigenesis of both benign and malignant tumors developed in patients with CD.- - - - - - - - - - ranking = 1keywords = breast (Clic here for more details about this article) |
7/56. Cowden syndrome-diagnostic skin signs.Cowden syndrome is a rare autosomal dominant familial cancer syndrome with a high risk of breast cancer. The most important clinical features include carcinomas of the breast and thyroid, and hamartomatous polyps of the gastrointestinal tract. There are characteristic mucocutaneous features which allow early recognition of the disease and are generally present before internal malignancies develop. We report on a woman in whom the diagnosis of Cowden syndrome was first made after she had been treated for both breast cancer and melanoma.- - - - - - - - - - ranking = 3keywords = breast (Clic here for more details about this article) |
8/56. Activation of a cryptic splice site of PTEN and loss of heterozygosity in benign skin lesions in Cowden disease.Cowden disease is an autosomal dominant syndrome characterized by facial trichilemmomas, acral keratoses, papillomatous papules, mucosal lesions, and an increased risk for breast and nonmedullary thyroid cancer. Here, we describe a novel PTEN splicing site mutation in a family with classical Cowden disease and we studied benign skin lesions typical for Cowden disease for loss of heterozygosity. We found a PTEN IVS2 1G > Alpha 5'-splicing acceptor mutation resulting in activation of a cryptic splice site. Activation of this cryptic splice site is predicted to result in a frameshift with a premature stop codon, thus disrupting the phosphatase core motif of PTEN. loss of heterozygosity analysis of two trichilemmomas, one fibroma, and three acanthomas of the index patient demonstrated loss of heterozygosity at the PTEN locus in four of these lesions. In conclusion, our data demonstrate that a PTEN splicing site mutation causes activation of a cryptic splice site, which results in aberrant transcripts.- - - - - - - - - - ranking = 1keywords = breast (Clic here for more details about this article) |
9/56. Cowden's syndrome: a case report.Cowden's syndrome, a rare genodermatosis of autosomal-dominant inheritance with variable expressivity, is characterized by a combination of ectodermal, mesodermal, and endodermal hamartomas that may involve the skin, mucous membranes, breasts, gastrointestinal tract, and thyroid. A 26-year-old woman who presented for replacement of her teeth, all of which had been extracted because of rapidly progressive periodontitis. She was diagnosed with Cowden's syndrome based on mucocutaneous abnormalities, thyroid involvement, and abnormalities of the skeletal and genitourinary systems. The clinical significance and differential diagnosis of this disease are highlighted.- - - - - - - - - - ranking = 1keywords = breast (Clic here for more details about this article) |
10/56. Cowden's disease: a rare cause of oral papillomatosis.Cowden's disease is a rare autosomal dominant condition with characteristic mucocutaneous papillomatous lesions. These lesions are mucocutaneous markers for increased risk of malignancies in the thyroid, breast and the gastrointestinal tract. We discuss the case of a 50-year-old female patient who presented with oral and cutaneous papillomoas and a past history of breast malignancy. Important management aspects of these patients are considered.- - - - - - - - - - ranking = 2keywords = breast (Clic here for more details about this article) |
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