A family of Gardner's syndrome with report of an autopsy case

A family with Gardner's syndrome including one autopsy case is reported. A 22 year-old man had multiple polyposis of the colon and the small intestine, epidermal cysts, soft part tumor of the abdominal skin and osteomas in the calvarium and rib, and died of a carcinoma in the transverse colon and embolism of the brain. Histologically, all polyps were diagnosed as adenomatous polyp. The greater their diameter, the higher the tendency of atypism was observed. However, the polyps around the cancer were few, small, and with low atypism, and we could not obtain evidence showing direct transformation of adenomatous polyps into carcinoma. His two elder brothers had multiple polyposis of the colon, epidermal cysts and osteomas in the calvarium or mandibular bone, but are still alive.     

Lipomatosis coli,a mimicker of familial polyposis

Multiple intestinal lipomas (lipomatous polyposis) are quite rare, and they can be quite challenging to diagnose because this condition may be clinically confused with familial adenomatous polyposis with a suggestive family history. Herein, we present a case of lipomatous polyposis that was presented with abdominal pain and, in colonoscopy, had more than 100 polyps. The patient was admitted for surgery with diagnosis of familial polyposis. Resected colon specimen had multiple polyps ranging from 0.1 to 1.5 cm. Microscopically, the polyps were composed of mature adipose tissue with normal overlying mucosa. There were also increased fat cells in the submucosa of the colon adjacent to the polyps. Lipomatous polyposis rarely occurs and can be confused with familial polyposis. Polypectomy is a simple and cost-effective procedure to help in diagnosis and prevent a major surgery.     

Familial polyposis coli: heterogeneous polyp expression in 2 kindreds.

We describe 2 extended kindreds supposedly manifesting familial multiple adenomatous polyposis coli (FPC), but which show marked heterogeneity in the phenotypic expression of colorectal adenomatous polyps. In one family, 2 individuals had diffuse polyposis at very early ages (7 and 10 years), while 6 others (aged 23 to 72 years) had solitary polyps only. Of the patients with solitary polyps, 2 had associated colonic malignancies (ages 26 and 35), while another had a prophylactic colectomy performed at age 46. In the second family, 5 of the 11 patients with evidence of polyps showed the classical presentation of FPC, while the remainder showed marked phenotypic variation. The marked variability in frequency and location of colon polyps points to the need to reassess our traditional criteria for diagnosis of FPC. The high risk of early onset colon cancer in patients from these families who have the most minimal manifestation, namely isolated polyps, recommends more careful scrutiny of supposedly unaffected members of all FPC kindreds.     

Oral and maxillofacial considerations in Gardner's Syndrome

Gardner's Syndrome is a variant of familial adenomatosis polyposis (FAP) with a triad consisting of polyps of the colon, multiple osteomas and surface tumors of soft and hard tissue. The intestinal polyps have a %100 risk of undergoing malignant transformation, therefore early identification of this disease is very important. There are several symptoms of Gardner's syndrome in the oral and maxillofacial surgery, which can be discovered during routine dental examination. We report a case of a 25-year old male patient with Gardner's syndrome who has not any intestinal polyps but osteomas in the mandible and jaw deformalities.     

Familial adenomatous polyposis with extracolonic manifestations--case report

The familial adenomatous polyposis syndrome is an autosomal dominant inherited disease characterized by progressive development of multiple adenomatous polyps throughout the colon and rectum. Due to the malignant potential of adenomatous polyps, colorectal cancer develops in 100% of cases, approximately 10-15 years after the onset of symptoms. Extracolonic manifestations of the disease including adenomatous polyps of the stomach, duodenum, small intestine and periampullatory region are rare. The etiology of the disease is germline mutation at the site of tumor suppressor gene located on chromosomes 5q21-22. A case is described of a 48-year-old man hospitalized at the Department of Abdominal Surgery, Sveti Duh General Hospital in Zagreb for the treatment of familial adenomatous polyposis syndrome. For some time the patient reported occasional abdominal pain, frequent stools and diarrhea with blood, anemia and body weight loss. Laboratory, radiology and endoscopy examinations verified multiple adenomatous polyps of the colon and rectum, also with polyps of the stomach, duodenum and jejunum. Histopathology confirmed the polyps to show moderately poorly differentiated cylindric epithelium and moderate to severe dysplasia. Radical surgery was required, so proctocolectomy with Brook ileostomy was performed. The postoperative recovery and wound healing were normal. The patient was discharged twelve days of the surgery for home care. Oncologic treatment was suggested. Verified extracolonic manifestations of the disease require periodical endoscopic follow up and possible treatment.     

Inverted hyperplastic polyposis of the colon.

AIMS: To describe and evaluate two apparently unique cases of inverted hyperplastic (metaplastic) polyposis of the colon. METHODS: The cases were analysed by standard histopathological, histochemical, and immunohistochemical techniques and the findings compared with those of regular hyperplastic polyps of the colorectum. RESULTS: Both patients were middle-aged men with concurrent adenocarcinoma of the proximal large intestine. The inverted polyps numbered 18 and 12, measured between 0.4 and 2.5 cm in diameter, and all were present in the proximal ascending colon. The polyps had characteristic macroscopic features: they were positioned on the apex of mucosal folds and demonstrated surface pitting and mucus hypersecretion. Histologically, inversion and misplacement of hyperplastic epithelium was related to lymphoglandular complexes. The polyps showed all the histochemical and immunohistochemical features of regular hyperplastic polyps. CONCLUSIONS: Inverted hyperplastic polyps are an unusual but distinctive polyp of the proximal colon, may be multiple, and share the phenotypic changes of regular hyperplastic polyps. The pathogenesis of epithelial inversion probably relates to misplacement of epithelium through anatomical defects in the muscularis mucosae due to mechanical forces. The polyps may mimic both adenomas and carcinomas. The neoplastic potential of inverted hyperplastic polyposis is likely to be very low: one polyp only showed adenomatous change.     

Morphogenesis of polyps in diffuse polyposis of the colon

Sixty operative specimens of the colon or its fragments removed for diffuse juvenile polyposis (the diagnosis was clinical) were evaluated morphologically. A structural study of the polyps ranging in size from the smallest to large lobular formations elicited a significant role of inflammation in polyp morphogenesis. Large polyps often show fragments of typical adenomatous structure. These adenomatous sites mark a higher risk of malignant transformation which develops in polyps of mixed structure in diffuse juvenile colon polyposis. Structurally, there are more reasons for referring juvenile polyps to adenomas than to hamartomas.     

Multiple juvenile polyposis: A study of the pathogenesis of juvenile polyps and their relationship to colonic adenomas

Soligary juvenile polyps are common lesions whose pathogenesis is poorly understood. Multiple juvenile polyposis is characterized by large numbers of these lesions either confined to the colon or throughout the gastrointestinal tract. A study of two cases of multiple juvenile polyposis provided fresh insight into the pathogenesis of juvenile polyps and their relationship to colonic adenomas. Mucosal ulceration in very early lesions, together with glandular epithelial calcification, suggested that impaired cell renewal resulting from disturbed regenerative kinetics may predispose to surface epithelial erosion, setting in motion a cycle of ulceration, inflammation, and granulation tissue formation. We postulate that a dyskinetic continuum may link juvenile, “metaplastic,” and adenomatous polyps. The finding in our second case of multiple adenomatous lesions, including a villoglandular polyp, emphasizes the neoplastic potential of juvenile polyposis.     

Two cases of 5q deletions in patients with familial adenomatous polyposis: possible link with Caroli''s disease.

Two cases are reported of patients with deletions of chromosome 5q. Both have familial adenomatous polyposis (FAP) and mild mental retardation. In both, macroscopic polyposis was confined to the proximal colon in adult life (in their thirties) although microscopic adenomatosis was shown in the more distal colon with occasional single polyps. Both subjects had dermoid cysts, and congenital hypertrophy of the retinal pigment epithelium (CHRPE) was seen in case 2. Case 1 has gastroduodenal polyps and desmoid tumours; case 2 has a marfanoid habitus with an abnormal pectus, wasted calf muscles and clawing of the toes, and Caroli's syndrome. His deletion is cytogenetically more extensive than that in case 1. The paucity of adenomas in the left side of the colon suggests that FAP cannot always confidently be excluded by sigmoidoscopy alone. The expression of the disease in the colon in these cases could be milder than in the more usual autosomal dominant cases where nonsense mutations resulting from single base changes of small deletions rather than deletion of the whole gene are the usual finding.     

Colorectal carcinomas arising in the hyperplastic polyposis syndrome progress through the chromosomal instability pathway

The hyperplastic polyposis syndrome is characterized by the presence within the colon of multiple large hyperplastic polyps. We describe a case of hyperplastic polyposis syndrome associated with two synchronous carcinomas, one of which arises within a pre-existing hyperplastic lesion. Comparative genomic hybridization was used to determine genetic changes in both carcinomas and several associated hyperplastic lesions. Microsatellite analysis at five loci was performed on carcinomas and representative hyperplastic polyps, and p53 status was analyzed by immunohistochemistry. Both carcinomas showed multiple genetic aberrations, including high level gains of 8q and 13q, and loss of 5q. These changes were not seen in the hyperplastic polyps. Microsatellite instability was not seen in the carcinomas, four separate hyperplastic polyps, the hyperplastic polyp with mild adenomatous change associated with the carcinoma, or a separate serrated adenoma. Allelic imbalance in the cancers at D5S346 and D17S938 suggested allelic loss of both p53 and APC, as well as at the loci D13S263, D13S174, D13S159, and D18S49. An early invasive carcinoma in one hyperplastic polyp stained for p53 protein, but the associated hyperplastic polyp was negative. In this case, neoplastic progression followed the typical genetic pathway of common colorectal carcinoma and occurred synchronously with mutation of p53.     

Concurrent appearance of stomach polyposis and hepatocellular carcinoma

An 18 year old woman had been known to have juvenile polyposis since five years with multiple hyperplastic polyps of the stomach and several polyps of the colon. Death occurred from hepatic coma with hepatocellular carcinoma. A lymphangiosis carcinomatosa was observed in some stomach polyps with a circumscribed infiltration into the stroma and into the adjacent glands. Such an unusual combination of diseases readily causes diagnostic confusion.     

Nine novel APC mutations in Italian FAP patients

Familial adenomatous polyposis (FAP) is a common hereditary syndrome characterized by early development of colorectal cancer consequent to extensive adenomatous polyps of the colon. In addition to the colonic manifestations the syndrome presents several extracolonic features including polyps of the upper gastrointestinal tract, congenital hypertrophy of the retinal pigment, jaw cysts, osteomata and desmoid tumors. In this study the entire APC coding region has been analysed for mutation in a panel of one Turcot and 33 unrelated Italian FAP patients using SSCP analysis, PTT and DNA sequencing. We detected APC mutations in 23 of them and identified nine which, to our knowledge were not previously reported. All of these novel mutations are in exon 15, including two nonsense mutations, 6 deletions or insertions leading to premature termination of the protein and one missense mutation (7697G>A). This last mutation occurs in the EB1-binding domain of the APC protein and segregates in four relatives of the patient with three of them presenting 2-3 adenomatous polyps.     

Screening for mutations of the APC gene in 66 Italian familial adenomatous polyposis patients: evidence for phenotypic differences in cases with and without identified mutation

Germline mutations in the APC gene are responsible for familial adenomatous polyposis (FAP), a dominantly inherited syndrome characterized by the development of hundreds to thousands of polyps in the colon and in the rectum of affected individuals and by variable extracolonic manifestations (gastric and duodenal polyps, osteomas, retinal lesions, and desmoid tumors). Through the combined use of single-strand conformation polymorphism (SSCP) analysis and the protein truncation test (PTT), we have screened 66 Italian FAP patients and found 29 different APC mutations in a total of 34 cases. Of the identified mutations, 15 were nonsense, 12 were 1- to 5-bp deletions or insertions and two were complex rearrangements, all leading to the formation of premature stop codons. Only 10 mutations had been already previously described at the germline level, confirming the high heterogeneity of the APC mutational spectrum. The mean age of diagnosis in mutation positive cases and their affected relatives was significantly lower than in cases without identified mutation (30.6 vs 39.1 years, respectively; p = 0.003). In addition, among patients without a family history of polyposis, all mutation-positive cases displayed at least one of the extracolonic manifestations usually associated with FAP, whereas in one-half of the cases without identified mutation, none of these phenotypes was observed. Although a fraction of apparently mutation-negative cases were likely to be due to limitations of the mutation screening strategy, our results suggest, in agreement with previous reports, that allelic and/or genetic heterogeneity might be responsible for the phenotypic variability observed in FAP patients.     

Del(10)(q22.3q24.1) associated with juvenile polyposis

Juvenile polyps are the most frequent gastrointestinal polyps with a malignant potential for which the genetic basis is unknown. Juvenile polyps, with a normal epithelium but hypertrophic lamina propria, are histologically quite distinct from adenomatous polyps which have dysplastic changes in epithelial nuclei. Furthermore, the adenomatous polyposis coli (APC) gene on Chr 5, mutated somatically in adenomatous polyps and mutated in the germline of patients with familial adenomatous polyposis, is not linked to hereditary juvenile polyposis. We provide the first report indicating that a tumor suppressor gene associated with juvenile polyposis may be located at 10q22.3q24.1. Cytogenetic studies of a patient with juvenile polyposis and multiple congenital abnormalities of the head, extremities, and abdomen revealed a de novo interstitial deletion of Chr 10 as the only defect, del(10)(10q22.3q24.1). Am. J. Med. Genet. 70:361–364, 1997. © 1997 Wiley-Liss, Inc.     

Diffuse filiform polyposis with unique histology mimicking familial adenomatous polyposis in a patient without inflammatory bowel disease

Filiform polyposis is an uncommon entity that is most often encountered in the colon of patients with a history of inflammatory bowel disease (IBD). Filiform polyposis is characterized by a large number of "wormlike" polyps lined by histologically normal colonic mucosa. These polyps can mimic adenomatous polyps. Only rare cases without a history or evidence of IBD have been reported. Neuromuscular and vascular hamartoma of the small bowel is a rare, focal disorder characterized by disorganized smooth muscle fascicles throughout the submucosa accompanied by fibrosis, nerve fibers, ganglion cells, and vessels. To our knowledge, there is only one report of this lesion in the large bowel (cecum), where it presented as a mass. Here we report the case of a 50-year-old man with no known history or symptoms of IBD presenting with filiform polyposis involving the entire colon, clinically mimicking familial adenomatous polyposis, and showing histologic features similar to neuromuscular and vascular hamartoma of the small bowel.     

Comparative molecular pathology of sporadic hyperplastic polyps and neoplastic lesions from the same individual

AIM: The biology of colorectal hyperplastic polyps is of considerable relevance, because recent evidence suggests that under certain circumstances hyperplastic polyps may be precursors of neoplasms. The aim of this study was to assess and compare the clinical and molecular characteristics of hyperplastic polyps and neoplastic lesions removed from patients without the hyperplastic polyposis syndrome. METHODS: One hundred and twenty six patients were identified through a series of genetic epidemiological studies. Each patient had at least one neoplastic lesion and one hyperplastic polyp; there was a total of 147 hyperplastic polyps. All lesions were evaluated for K-ras mutations, loss of heterozygosity (LOH) of the adenomatous polyposis coli (APC) gene, and microsatellite instability. RESULTS: K-ras mutation was detected in 15 (10%) hyperplastic polyps, all from the rectosigmoid colon. No hyperplastic polyp had APC LOH or microsatellite instability. Patients with adenomas or carcinomas showing K-ras mutations were not more likely to have hyperplastic polyps with K-ras mutations. The average number of adenomas did not differ between those patients with hyperplastic polyps with K-ras mutations and those without K-ras mutations. There was no association between the hyperplastic polyp and the adenoma regarding the colon segments from which the two lesions were removed. CONCLUSIONS: The sporadic hyperplastic polyp is a lesion with limited molecular change and no relation to patients' neoplastic lesions.     

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.     

Coexisting juvenile polyps and tubulovillous adenoma of colon with carcinoma in situ: report of a case

The coexistence of juvenile and adenomatous polyps is confirmed by the present case of a 17-year-old girl who had two juvenile polyps and a tubulovillous adenoma of the colon with carcinoma in situ, a clinically benign lesion. The relation between the juvenile and adenomatous processes and the risk of the development of colonic carcinoma in such cases remain ill defined.     

Association between thyroid cancer of cribriform variant and familial adenomatous polyposis.

A case of a 20 year old Japanese woman who developed thyroid cancer exhibiting unusual cribriform structures while being followed up for familial adenomatous polyposis/Gardner's syndrome is reported. The patient presented with osteomas, pigmented retinal lesions, and adenomas of the duodenum and the papilla of Vater, in addition to numerous adenomatous polyps in the colorectum. On ultrasonography, the thyroid cancer was localised to the right lobe and was identified as an irregular, internal echo tumour with a peripheral hypoechoic zone, measuring 1.8 cm in diameter. Histological examination of the resected tumour showed a concomitance of papillary proliferation and cribriform structures with follicles of varying sizes. These features can be distinguished from sporadic thyroid cancer.     

Familial adenomatous polyposis (FAP): genotype correlation to FAP phenotype with osteomas and sebaceous cysts

Gardner syndrome is characterized by the triad of colorectal adenomas, soft and hard tissue tumors. This disorder was regarded as a separate disease until the identification of the APC gene when it was recognized that mutations in the APC gene were the underlying cause of both Gardner syndrome and familial adenomatous polyposis (FAP). The present study aimed at examining whether a particular APC genotype could be delineated in FAP patients with benign extracolonic manifestations: sebaceous cysts and/or osteomas. A questionnaire was sent to all Danish FAP patients (N = 234) asking for occurrence of sebaceous cysts and palpable osteomas. Medical records later verified positive findings, when possible. The results for each patient were correlated to the position of his or her mutation in the APC gene. Positive participation compliance was 77% (N = 180), and in 105 of these patients the pathogenic APC mutation was known. Palpable osteomas were reported in 17 of the patients in whom a pathogenic mutation had been identified. Osteomas were only identified in patients with mutations between codon 767 and 1513, a gene area also associated with congenital hypertrophy of the retinal-pigmented epithelium (CHRPE) and hepatoblastoma. Sebaceous cysts were reported in 51% of the patients, and their APC mutations were evenly distributed in the gene with no particular hotspot. Osteomas appeared most frequently in patients with sebaceous cysts, odds ratio 6.6, P < 0.001. The study provides molecular evidence that Gardner syndrome is a variant of FAP and essentially obsolete in clinical practice.