1/35. Germline CDKN2A mutation implicated in predisposition to multiple myeloma.Germline mutations of the CDKN2A (p16(INK4A)) tumor suppressor gene predispose patients to melanoma and pancreatic carcinoma. In contrast, mutations of the murine CDKN2A gene predispose BALB/c mice to pristane-induced plasmacytoma. We describe here a family in which a germline mutation of CDKN2A is present in 4 individuals who developed melanoma as well as in a fifth family member who is suffering from multiple myeloma. To determine whether the CDKN2A mutation predisposed the myeloma patient to her disease, we carried out loss of heterozygosity studies on sorted bone marrow from this individual and observed loss of the wild type CDKN2A allele in the malignant plasma cells. We suggest that germline mutations of CDKN2A may predispose individuals to a wider variety of malignancy than has been hitherto reported, but that the expression of these cancers may depend heavily on the genetic background of the patient. (blood. 2000;95:1869-1871)- - - - - - - - - - ranking = 1keywords = carcinoma (Clic here for more details about this article) |
2/35. Novel germline mutation (300-305delAGTTGA) in the human MSH2 gene in hereditary non-polyposis colorectal cancer (HNPCC).Hereditary non-polyposis colorectal cancer (HNPCC) is a common hereditary syndrome characterized by the high incidence and early onset of colorectal cancer. The majority of the HNPCC families carry germline mutations in either the MSH2 or the MLH1 mismatch repair gene. A 46 year-old female patient whose family history fulfilled the Amsterdam criteria for HNPCC was diagnosed with undifferentiated adenocarcinoma of the transverse colon. Recognizing the Lynch 2 syndrome (the existance of multiple HNPCC related cancers in a pedigree), we used polymerase chain reaction followed by direct sequencing to screen the coding regions of both the MSH2 and the MLH1 genes for germline mutations in dna from the patient. We detected a novel germline mutation (300-305delAGTTGA) in exon 2 of human MSH2. We noted microsatellite instability in four microsatellite loci. immunohistochemistry showed a lack of expression of the MSH2 gene product in the tumor, suggesting that the mutation is a disease-causing mutation. copyright Wiley-Liss, Inc.- - - - - - - - - - ranking = 1.0924954904keywords = carcinoma, adenocarcinoma (Clic here for more details about this article) |
3/35. Molecular pathologic analysis enhances the diagnosis and management of muir-torre syndrome and gives insight into its underlying molecular pathogenesis.The muir-torre syndrome (MTS) is an autosomal dominantly inherited disorder, characterized by visceral malignancies and sebaceous skin lesions. In a subset of MTS families the disease is due to an underlying dna mismatch-repair defect. We have identified a MTS family whose spectrum of reported neoplasia included adenocarcinomas of numerous gastrointestinal sites, carcinomas of the endometrium, ovary and breast, papillary transitional cell carcinoma of the ureter, a range of cutaneous tumors, as well as keratoacanthomas. All tumors were tested for microsatellite instability and immunohistochemically stained for expression of MLH1 and MSH2 proteins. All tumors were found to be microsatellite unstable and lacking in MSH2 protein expression. The subsequent mutation detection focused on hMSH2, and a germline mutation was identified (CAA-->TAA, Gln-->STOP, codon 337). This mutation was subsequently found in a family member with a single skin lesion only. We propose that the combination of immunohistologic and microsatellite instability analysis can be exploited to screen individuals with characteristic skin lesions even before development of visceral tumors and to direct the subsequent germline mutation search. The profile of microsatellite instability and the genes rendered dysfunctional differed between tumor samples, suggesting that the molecular pathogenesis varied between lesions, despite a common germline mutation.- - - - - - - - - - ranking = 3.0924954904keywords = carcinoma, adenocarcinoma (Clic here for more details about this article) |
4/35. No BRCA1 germline mutation in a family with uterine papillary serous carcinoma: a case report.The purpose of the study was to examine BRCA1 germline mutation and its relationship to BRCA1 expression in two patients, a mother and a daughter, both diagnosed with uterine papillary serous carcinoma (UPSC). dna was screened for BRCA1 and BRCA2 germline mutations common in the Jewish population (185delAG, 5382insC, and 6174delT) by PCR-based assay and with a protein truncation test (PTT) to detect mutation in exon 11 of BRCA1 and exons 10 and 11 of BRCA2. BRCA1 expression in fixed tumor tissues was assessed by immunocytochemistry (IHC). No germline mutation in either BRCAI or BRCA2 gene was found in the two patients. Both samples showed reduced levels of BRCAI expression. Taken together, these results suggest that undetected or unscreened for germline mutation may be associated with occurrence of this rare tumor type in two members of the same family. Alternatively, an epigenetic mechanism such as BRCA1 promoter hypermethylation may be responsible for reduced expression of BRCA1 in the absence of dna mutations.- - - - - - - - - - ranking = 5keywords = carcinoma (Clic here for more details about this article) |
5/35. Multiple fibroadenomas harbouring carcinoma in situ in a woman with a family history of breast/ovarian cancer.A 46 year old woman with a family history of breast and ovarian cancer presented with multiple fibroadenomas in both breasts. From three fibroadenomas removed from the left breast carcinoma in situ (CIS) had developed. One fibroadenoma gave rise to ductal CIS, whereas the other two harboured lobular CIS. This is the first report of three fibroadenomas simultaneously giving rise to CIS. In addition, synchronous fibroadenomas harbouring different types of CIS from one fibroadenoma to the other have never been described. Direct sequencing revealed a mutation (5075G-->A) in the BRCA1 gene, but retention of BRCA1 immunohistochemical staining and no loss of heterozygosity at the BRCA1 locus by polymerase chain reaction made a pathogenic mutation in BRCA1 unlikely. Furthermore, in this family no cosegregation of breast cancer with this BRCA1 mutation was seen. Indeed, this mutation is now regarded as a polymorphism. This case stresses the need for histological evaluation of all breast masses in women with a strong positive family history for breast and/or ovarian cancer.- - - - - - - - - - ranking = 5keywords = carcinoma (Clic here for more details about this article) |
6/35. Familial cylindromatosis.Familial cylindromatosis: we report a daughter with turban tumor and her mother with cylindromatosis. The dermal eccrine cylindroma arose as small, solitary lesions on the head of the mother when she was 28 years old. The following years other tumors became apparent. She was operated on several times. The first lesions appeared on the frontal part of the scalp of the daughter when she was 23 years old. Other tumors grew on the scalp. Histopathological examination of the excised tumors showed the same lesions in both the mother and the daughter: dermal eccrine cylindromata. family history showed that the daughter's maternal aunt had a few tumors. Dermal eccrine cylindroma should be differentiated from malignant syndromes such as basal naevoid carcinoma or metastases and from neurofibromata. The gene of familial cylindromatosis was localised to chromosome 16q12-q13 and it was proposed that this gene is a tumor supressor gene.- - - - - - - - - - ranking = 1keywords = carcinoma (Clic here for more details about this article) |
7/35. Treatment issues in pediatric gastric adenocarcinoma.Gastric adenocarcinoma is a rare diagnosis in children. Modern treatment includes chemotherapy, radiotherapy, and surgery and has evolved over the past decade. The authors report a case of an 8-year-old girl with gastric adenocarcinoma. The case will be followed by a brief discussion of the presentation, current management guidelines, and prognosis of this rare pediatric entity.- - - - - - - - - - ranking = 6.5549729423998keywords = carcinoma, adenocarcinoma (Clic here for more details about this article) |
8/35. Nevoid basal cell carcinoma syndrome or multiple hereditary infundibulocystic basal cell carcinoma syndrome?We present a case of nevoid basal cell carcinoma syndrome, also known as Gorlin syndrome, or basal cell nevus syndrome, which clinically follows a course more consistent with multiple hereditary infundibulocystic basal cell carcinomas or multiple hereditary trichoepitheliomas. The following article describes the case in detail and gives an overview of other genodermatosis, which were initially considered in the differential and which may be linked pathogenetically.- - - - - - - - - - ranking = 10keywords = carcinoma (Clic here for more details about this article) |
9/35. Detection of 1733insC mutations in an Asian family with birt-hogg-dube syndrome.BACKGROUND: birt-hogg-dube syndrome (BHD) is a rare autosomal dominant genodermatosis characterized by skin tumours, including multiple fibrofolliculomas, trichodiscomas and acrochordons. BHD patients also may suffer from associated renal and colonic carcinomas. The defective gene in BHD has been recently identified and is suspected of being a tumour suppressor gene. Several mutations of the BHD gene have been reported only in Caucasian patients. OBJECTIVES: This study reports the first Asian family that has been demonstrated to carry a BHD mutation. patients/methods: The proband was a 26-year-old Japanese man with multiple asymptomatic, soft skin-coloured papules on his face, neck and trunk, which were clinically thought to be acrochordon. His father was also affected. Histopathologically, the papules revealed a fibrofolliculoma that had a circumscribed proliferation of fibroblasts and collagen fibres surrounding an abnormal hair follicle. RESULTS: Mutational analysis of the BHD gene of the proband and the father detected 1733insC, a cytosine insertion mutation in an eight-cytosine tract (nucleotides 1733-1740) in exon 11. Analysis of fibrofolliculoma in the proband showed heterozygous 1733insC mutation, suggesting the absence of loss of heterozygosity. Interestingly, previous mutational analysis in Caucasian patients revealed that both1733insC and 1733delC mutations were hot spots. CONCLUSIONS: This study is the first to find the same hot-spot 1733insC mutation in Asian kindred. The mutations in this polycytosine tract may have a wide, global distribution despite their arising from a different ethnic background.- - - - - - - - - - ranking = 1keywords = carcinoma (Clic here for more details about this article) |
10/35. carcinosarcoma arising in a patient with multiple cylindromas.Familial cylindromatosis (Brooke-Spiegler syndrome) is a rare autosomal dominant inherited disease characterized by the development of adnexal tumors, mostly cylindromas, but also trichoepitheliomas and spiradenomas. Malignant tumors may occur, usually with the features of a cylindrocarcinoma.The authors describe the case of a 75-year-old woman with the Brooke-Spiegler syndrome who presented with multiple nodules of the scalp, face, and trunk. In 1997 she underwent surgical excision of the entire forehead and scalp with skin grafting. Histologic examination revealed multiple cylindromas, some with areas of spiradenoma and one with an extensive adenomatous component; some trichoepitheliomas were also evident. In 2002, a nodule of the trunk suddenly increased in size and became painful. The lesion was excised and histologic and immunohistochemical evaluation revealed a malignant cutaneous biphasic tumor extending into the subcutis, consisting of a major portion with the features of an adnexal carcinoma and of a minor one of atypical spindle cells. Biphasic malignant skin tumors are rare and only a limited number have been described, none in association with the Brooke-Spiegler syndrome. The authors discuss the morphogenesis of the folliculosebaceous-apocrine unit from which the tumors in this syndrome derive, and the pivotal role of mesenchymal cells in determining the process. Since the Brooke-Spiegler syndrome is characterized by a germline mutation in the CYLD oncosuppressor gene, a biphasic tumor in this setting may represent a true carcinosarcoma.- - - - - - - - - - ranking = 2keywords = carcinoma (Clic here for more details about this article) |
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