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Sclerotic fibroma (SF) is an uncommon yet benign tumor that may occasionally be associated with Cowden's disease that presents as an asymptomatic, well-circumscribed lesion. We present a rare case of a patient with a solitary SF of the palpebral conjunctiva. The patient was an 85-year-old male who presented with a right lower lid nodule that was initially treated as a chalazion. Excision yielded a dense mass that was sent to pathology for evaluation. Histologically, the lesion showed a bland storiform spindle cell proliferation embedded in a sclerotic stroma with prominent clefting. [ABSTRACT FROM AUTHOR]

Cowden's syndrome is an autosomal dominant genodermatosis with variable orofacial and systemic manifestations. Here we present one such classical case of Cowden's syndrome in a 45-year-old female patient with features such as multiple cutaneous papillomatosis, oral fibromas, and fibromas involving multiple organs such as gastrointestinal tract (multiple polyps), thyroid disorders, and breast cancer. [ABSTRACT FROM AUTHOR]

Lhermitte-Duclos disease (LDD) is a rare, non-cancerous entity characterized by enlarged, abnormally developed cerebellar folia containing dysplastic cells. Symptomatic LDD is commonly observed in adults (adult-onset LDD, aLDD) as an isolated condition or associated with Cowden's disease (CD). The present study aimed to investigate the magnetic resonance imaging (MRI) characteristics and the underlying pathological findings in 7 cases of aLDD, with emphasis on the association with CD and the need for active cancer surveillance once the diagnosis of LDD is confirmed. The MRI findings along with the clinical and histopathological data collected from 7 patients with aLDD were retrospectively reviewed. The diagnosis of CD was based on a range of clinical characteristics, according to the International Cowden Consortium Criteria. A thorough review of the published data was conducted and our results indicated that all 7 cases shared similar MRI characteristics, whether the aLDD was sporadic (2 cases) or associated with CD (5 cases), including a highly typical non-enhancing striated MRI appearance of thickened folia, consisting of alternating bands on T1- and T2-weighted images. On gross examination, the involved cerebellar folia were distorted and enlarged, whereas the histopathological examination revealed that the molecular layer was widened and occupied by abnormal ganglion cells. Moreover, a reduction in the number or absence of the Purkinje cells and hypertrophy of the granular cell layer were observed. Our findings were consistent with the diagnosis of LDD. Variable levels of vacuolization of the white matter and the molecular layer were observed in all the cases. Notably, CD34 immunohistochemical analysis revealed the presence of angiogenesis within the lesions. aLDD associated with CD exhibited no pathological or immunohistochemical characteristics that were distinct from those of isolated aLDD. Of the 7 cases of aLDD, 5 presented with symptoms suggestive of CD, which is a syndrome associated with a high risk of multiple benign and malignant neoplasms. In conclusion, aLDD exhibits characteristic MRI and histopathological findings and displays a strong association with CD. Therefore, we recommend that the MRI diagnosis of aLDD triggers active cancer surveillance and preventive care. [ABSTRACT FROM AUTHOR]

Over the past decade mutations discovered in genes such as BRCA1, BRCA2, TP53 and PTEN, have emerged as high-penetrance susceptibility genes and are clinically relevant for determination of breast cancer risk. Genetic counseling and subsequent screening for mutations and gene rearrangement has improved patient outcome through early detection and prophylactic interventions in patients with familial breast cancer syndromes. However, these high-penetrance genes only account for a small fraction of the hereditary linked breast cancers. It is currently believed that low-penetrance susceptibility alleles and/or environmental factors may play an important role in the remaining cases. TGFBR1*6A (*6A) is a common hypomorphic variant of the type I TGF-β receptor gene ( TGFBR1) that has been associated with risk for several forms of cancer, in particular breast cancer. Several epidemiological studies have suggested that patients who carry the *6A allele have an increased risk of breast cancer. Furthermore, functional analysis suggests that this mutation alters TGF-β signaling and promotes tumorigenesis. Although a decade of research has provided basic information in regards to the prevalence of this mutation in several cancer types and populations the molecular underpinning of its functional effects are poorly understood. A better understanding of the molecular mechanism of TGFBR1 signaling in breast cancer may have an impact on breast cancer risk assessment and breast cancer prevention. [ABSTRACT FROM AUTHOR]

Abstract: We report on a paediatric observation of Cowden''s disease in a 6-year-old child. Familial steroid-resistant nephrotic syndrome was associated to papulous and papillomatous lesions of gingiva and oral mucosa, multiple hamartoma of the back and of upper limbs, facial dysmorphism and follicular thyroid cancer. Thyroid cancer evolved favorably after surgical treatment, radioactive iodine and L-thyroxin supplementation. Nephrotic syndrome evolved to chronic renal insufficiency after 11 years. The early diagnosis of Cowden''s disease, or multiple hamartoma syndrome, allows a careful monitoring of the patients who are facing the risk of cancer transformation, which is the principal complication of the condition. [Copyright &y& Elsevier]

Summary We report a 54-year-old woman with Cowden's disease (CD) who was found to carry a novel germline mutation in the PTEN gene. The mutation (c.334C→G) introduced a splice donor site within exon 5 that caused the expression of an aberrant transcript lacking 159 nucleotides corresponding to codons 112–164. Clinically, the patient showed multiple benign hamartomatous lesions of the skin, papillomatosis of the lips and oral mucosa, polyposis coli and bilateral fibrocystic disease of the breast. In addition, she developed different types of malignant neoplasms, including bilateral carcinomas of the breast and malignant melanomas of the skin. Molecular genetic analysis of a benign skin hamartoma and an invasive ductal breast carcinoma revealed loss of heterozygosity (LOH) at microsatellite markers on chromosome 10 in the carcinoma but not in the hamartoma. The breast carcinoma additionally carried a somatic TP53 point mutation (c.466C→G; R156G) that was associated with LOH on 17p and nuclear p53 protein accumulation. Taken together, our findings indicate that benign hamartomas in CD may develop without loss of the second (wild-type) PTEN allele, whereas the pathogenesis of malignant tumours, such as breast carcinomas, appears to require the complete inactivation of Pten as well as further alterations such as the loss of p53-dependent growth control. [ABSTRACT FROM AUTHOR]

Cowden’s disease is an autosomal dominantly inherited syndrome characterized by mucocutaneous lesions and multiple hamartomas. We report here a 12 years-old boy case with craniomegaly, intestinal polyps, epilepsy and multiadenomatous goiter. All the lesions were begnins. The predisposing genetic defect has been assignated to chromosomal 10 (PTEN-gene mutation). A long term follow-up is necessary because of the risk of malignancies. [Copyright &y& Elsevier]

Cowden's disease is so often followed by malignant diseases, such as cancer of the breast and thyroid. and different forms of gynaecological cancer, that surgeons should be made especially aware of those changes in skin and mucous membranes which, if multiple are pathognomic. It remains, however, an underdiagnosed syndrome. We believe a number of other conditions are also associated with Cowden's disease. [ABSTRACT FROM AUTHOR]

Cowden's disease is an autosomal dominant genetic syndrome characterized by multiple hamartomas involving organs derived from all three germinal layers. Incidence of Cowden's disease is estimated at approximately 1:2,00,000. A 24 year female presented with multiple asymptomatic skin lesions over the face, of 18 months duration. Mucosa of oral cavity showed firm verrucous lesions and cobble stone appearance. On skin biopsy Trichilemmoma was diagnosed. Oral mucosal biopsy was diagnosed as fibroepithelial polyp. Correlating with the clinicopathological features, a final diagnosis of Cowden's disease was made. [ABSTRACT FROM AUTHOR]