1/123. Hereditary desmoid disease in a family with a germline Alu I repeat mutation of the APC gene.Two families with autosomal dominantly inherited desmoid tumors have recently been shown to have germline mutations at the 3' end of the APC gene. We subsequently identified an amish family with autosomal dominantly inherited desmoid tumors. Genetic analysis performed on one family member, a 47-year-old man with multiple desmoid tumors and no colon polyps, revealed a protein truncating mutation in the middle of the APC gene. The truncating mutation is the result of a 337-bp insertion of an Alu I sequence into codon 1526 of the APC gene. The presence of a poly(A) tail at the 3' end of the insertion suggests that the Alu I sequence was inserted by a retrotranspositional event. Germline insertions of Alu I sequences have occasionally been reported to cause other genetic diseases including type I neurofibromatosis, hereditary site-specific breast cancer (BRCA2), and hemophilia b. However, this is the first report of a germline mutation of the APC gene resulting from an Alu I insertion.- - - - - - - - - - ranking = 1keywords = cancer (Clic here for more details about this article) |
2/123. Coexisting carcinoid tumors in familial adenomatous polyposis-associated upper intestinal adenomas.Upper gastrointestinal polyps and extraintestinal tumors are well recognized in association with familial adenomatous polyposis (FAP). Although carcinoid tumors have been reported in association with sporadic colonic neoplasms and ulcerative colitis, to date, carcinoids have not been reported in association with FAP. We report a patient with FAP who has recurrent carcinoid tumors located at the bases of duodenal adenomas. The genetic basis of carcinoid neoplasms is still uncertain. This report may represent the clinical effect of the APC gene mutation on the enterochromaffin cell line manifesting as recurrent carcinoid tumors in physical association with intestinal adenomas. Future genetic analysis and epidemiological studies may be of value in determining whether a true association exists.- - - - - - - - - - ranking = 0.013320357344803keywords = neoplasm (Clic here for more details about this article) |
3/123. Failure to diagnose hereditary colorectal cancer and its medicolegal implications: a hereditary nonpolyposis colorectal cancer case.PURPOSE: We describe a patient who had precancerous colonic symptoms and a positive family history of multiple occurrences of early-onset colorectal cancer in her first-degree and second-degree relatives consistent with hereditary nonpolyposis colorectal cancer. Hereditary nonpolyposis colorectal cancer diagnosis had not been made before her diagnosis of carcinoma of the cecum with liver metastasis. She died at age 20, leading to litigation. Controversies about standards of care, their malpractice implications, and pertinent legal issues are discussed. methods: review of the medical and family history was made by the expert witness (HTL) with appropriate documentation of the chronology of symptoms, as derived from depositions. These documents revealed that the patient's mother had repeatedly discussed with the caregivers her concern about the family history of colon cancer and the need for appropriate surveillance. RESULTS: The patient's colonic symptoms progressed for a period of three years. Flexible sigmoidoscopy was performed by a nonphysician. The physician who ordered the procedure considered this appropriate because isolated polyps were reported in the patient's father and paternal uncle, which apparently led him to believe that the diagnosis was familial adenomatous polyposis. During litigation procedures, a pedigree was constructed and found to be consistent with hereditary nonpolyposis colorectal cancer. The case was settled in favor of the plaintiff before trial. CONCLUSION: It is essential to understand the natural history of hereditary nonpolyposis colorectal cancer, inclusive of the need for surveillance colonoscopy in patients at increased risk by virtue of their position in their family pedigree.- - - - - - - - - - ranking = 15keywords = cancer (Clic here for more details about this article) |
4/123. Cribriform-morular variant of papillary carcinoma: a distinctive variant representing the sporadic counterpart of familial adenomatous polyposis-associated thyroid carcinoma?We describe herein four cases of an unusual sporadic thyroid tumor that shares the morphologic features of a distinctive follicular cell neoplasm previously proposed as a feasible indicator of familial adenomatous polyposis. We also review five other similar cases reported in the literature. All of the nine patients were young women, aged 16 to 30 years. Grossly, the neoplasms measured 1.5 to 5.6 cm; they were solid and solitary, except one case, which showed two tumor nodules, one in each lobe. Histologically, the lesions were encapsulated, and they exhibited an intricate blending of cribriform, follicular, papillary, trabecular, and solid patterns of growth, with morular (squamoid) areas. Cribriform structures were prominent, being formed by anastomosing bars and arches of cells in the absence of intervening fibrovascular stroma. Follicular areas were usually devoid of colloid, and the papillae were lined by columnar cells. There were focal areas of trabecular arrangement reminiscent of hyalinizing trabecular adenoma. The tumor cells were cuboidal or tall, with frequent nuclear pseudostratification and abundant eosinophilic-to-oxyphilic cytoplasm. The nuclei were usually hyperchromatic, but nuclear grooves, pale or clear nuclei, and intranuclear cytoplasmic inclusions were variably present. Morules with peculiar nuclear clearing caused by biotin accumulation were scattered in the tumors. Vascular and/or capsular invasion were noted in all of the cases except one, and lymph node metastasis was found in two cases. Immunohistochemical stains showed reactivity for thyroglobulin, epithelial membrane antigen, cytokeratins (including 34betaE12), vimentin, estrogen and progesterone receptors, bcl-2, and Rb proteins. Follow-up in seven cases showed that all of the patients were alive with no evidence of disease at 1 to 13 years after diagnosis. Thus, the behavior of this variant seems to be similar to that of conventional papillary carcinoma Because of the distinctive histologic features, we propose naming this tumor the cribriform-morular variant of papillary carcinoma.- - - - - - - - - - ranking = 0.013320357344803keywords = neoplasm (Clic here for more details about this article) |
5/123. Familial adenomatous polyposis: a case report and histologic mucin study.adenocarcinoma arising at an ileostomy is uncommon, and only 29 cases have been reported in the literature. The case of a 54-year-old man who developed an adenocarcinoma at a Brooke ileostomy is reported. The ileostomy had been fashioned 21 years earlier after proctocolectomy for familial adenomatous polyposis (FAP). A wide local excision of the stoma was performed, and a new Brooke ileostomy was fashioned on the opposite side of the abdomen. Histopathologic examination revealed a well-differentiated adenocarcinoma with early invasion of the submucosa. On hematoxylin and eosin staining, the ileal mucosa adjacent to the tumor showed signs of colonic metaplasia, including loss of villous architecture and a reduced number of paneth cells. Mucin staining using the high iron diamine-alcian blue stain demonstrated a mixture of sulfomucin and sialomucin in the ileal mucosa near the tumor, confirming colonic metaplasia. ileostomy site carcinogenesis can be attributed to both the colonic metaplasia and the inherent nature of FAP or ulcerative colitis (UC), where colonic mucosa is susceptible to adenoma formation or dysplasia. Longstanding ileostomies in patients with FAP or UC should be followed to exclude the development of adenoma, dysplasia, or cancer.- - - - - - - - - - ranking = 1keywords = cancer (Clic here for more details about this article) |
6/123. Gastric adenocarcinoma associated with fundic gland polyps in a patient with attenuated familial adenomatous polyposis.Familial adenomatous polyposis (FAP) is a rare autosomal dominant precancerous condition of the colon caused by mutations in the adenomatous polyposis coli (APC) tumor suppressor gene. FAP is characterized by the appearance of innumerable adenomatous polyps throughout the large bowel. Fundic gland polyps are the most common gastric lesion in FAP. It is generally believed that fundic gland polyps have little or no potential for malignant transformation in the population at large, and only a few case reports describe the development of high grade dysplasia or gastric adenocarcinoma associated with diffuse fundic gland polyposis in patients with FAP. We report the second case of gastric adenocarcinoma intimately associated with fundic gland polyposis in a family with an attenuated form of FAP. The patient had undergone routine screening per current guidelines because of his known mutation in the APC gene. This suggests that malignant transformation of fundic gland polyps in patients with FAP occur more frequently than previously believed. Current screening recommendations may not be sufficient for patients with FAP or its attenuated forms.- - - - - - - - - - ranking = 1keywords = cancer (Clic here for more details about this article) |
7/123. Three submicroscopic deletions at the APC locus and their rapid detection by quantitative-PCR analysis.We describe three unrelated kindreds, affected by familial adenomatous polyposis (FAP), with 5q submicroscopic deletions that encompass the entire adenomatous polyposis coli (APC) gene and the adjacent DP1 gene. In one family the deletion encompasses also the MCC (mutated in colon cancer) gene. Affected members of these families had dysplastic adenomatous polyps and congenital hypertrophy of the retinal pigment epithelium (CHRPE); no individual was affected by mental retardation or facial dysmorphism. The deletions were detected by linkage analysis with several intragenic and closely flanking polymorphic markers and confirmed by a quantitative PCR analysis. This procedure could have an impact on the detection of the molecular defect in FAP patients in whom mutational analysis fails to identify the specific mutation.- - - - - - - - - - ranking = 1keywords = cancer (Clic here for more details about this article) |
8/123. Attenuated familial adenomatous polyposis in a man with an interstitial deletion of chromosome arm 5q.Familial adenomatous polyposis (FAP) is an inherited colon cancer syndrome caused by mutations in the APC gene on chromosome region 5q21. patients typically present with several hundred to several thousand polyps throughout the colon. Benign and malignant extracolonic manifestations are often present. Attenuated FAP (AFAP) is a recognized variant of FAP in which patients present with fewer than 100 polyps and appear to have a delayed onset of the clinical manifestations of FAP. Mutations in specific regions of the APC gene are associated with AFAP. A full deletion of the APC gene region has previously been thought to be associated with typical FAP. We now report on a 39-year-old man with a cytogenetically visible interstitial 5q deletion. Fluorescent in situ hybridization analysis with two cosmid probes specific for the 5' and 3' ends of the gene indicated that the entire APC locus is deleted. The number of polyps (50-60) seen in this patient was consistent with AFAP, as was the absence of multiple congenital hypertrophy of the retinal pigment epithelium (CHRPE). This is the first reported case of AFAP associated with a germline deletion of the entire APC gene.- - - - - - - - - - ranking = 1keywords = cancer (Clic here for more details about this article) |
9/123. ganglioglioma in a patient with Turcot syndrome. Case report.A 33-year-old woman with Turcot syndrome harbored a brain tumor and colon cancer and had a familial history of this syndrome. On histological examination, the brain tumor was found to have large and diffusely scattered ganglion cells within a diffuse background of astrocytic cells in a fibrillary matrix. The tumor was diagnosed as a ganglioglioma. No germline mutation in the adenomatous polyposis coli gene was detected using a protein truncation assay. These findings indicate that this patient had brain tumor-polyposis syndrome Type 1 of Turcot syndrome. This is the first report of a ganglioglioma related to Turcot syndrome.- - - - - - - - - - ranking = 1keywords = cancer (Clic here for more details about this article) |
10/123. genetic testing and counseling for hereditary forms of colorectal cancer.The discovery of genes responsible for inherited forms of colorectal cancer have the potential to improve cancer risk assessment and counseling. Germline mutations (nonsense, frameshift) of APC are associated with familial adenomatous polyposis, an autosomal dominant syndrome, clinically characterized by young onset, hundreds of adenomatous polyps in the colon, and increased risk for extracolonic tumors. Mutations in APC are also associated with forms of attenuated familial adenomatous polyposis. Germline mutations in five mismatch repair related genes (hMSH2, hMLH1, hMSH6, hPMS1, and hPMS2) cause hereditary nonpolyposis colorectal cancer and are associated with increased risk of somatic genetic alterations and high dna microsatellite instability. Hereditary nonpolyposis colorectal cancer is characterized by young onset colorectal cancer, proximal colon location, and increased risk of extracolonic cancers. A missense mutation in APC (I1307K) is associated with some familial colorectal cancer in Ashkenazic jews. For persons at risk for hereditary forms of colorectal cancer, testing algorithms and gene test interpretations depend on identification of the pedigree germline gene mutation. Careful evaluation of the kindred for characteristic aggregation of tumor types among affected individuals and the availability of affected persons for testing are important issues in implementing genetic testing and follow-up management. case reports illustrate the importance of genetic counseling as a component of cancer genetic risk assessment. The genetic counseling process includes exploration of patient risk perception, sources of anxiety related to cancer risk, patient education (specific cancer-related issues, prevention/intervention options), discussion of possible gene test options, test limitations, and consequences of various gene test outcomes.- - - - - - - - - - ranking = 15keywords = cancer (Clic here for more details about this article) |
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