A Case of Cronkhite-Canada syndrome showing resolution with Helicobacter pylori eradication and omeprazole]

We describe a 58-year-old woman who was incidentally found to have gastric and colonic polyposis, hypoalbuminemia, cutaneous hyperpigmentation and onychodystrophy (Cronkhite-Canada syndrome). Histology of polyps from the stomach showed features of juvenile or retention type (hamartomatous) polyps with Helicobacter pylori (H. pylori) infection. The large pedunculated colonic polyps showed hamartomatous polyps with adenomatous component and polypectomy was performed. After the treatment with H. pylori eradication and omeprazole, the gastric polyposis, hypoalbuminemia and anemia regressed, and endoscopic polypectomy of gastric polyps were performed. After the continuous use of omeprazole for 14 months, the patient showed complete resolution of clinical features of Cronkhite-Canada syndrome. The experience of this case suggests that eradication of H. pylori and proton pump inhibitor treatment might be considered in patients with gastric polyposis combined with Cronkhite-Canada syndrome.     

An Anti-adenoma Antibody, Adnab-9, May Reflect the Risk for Neoplastic Progression in Familial Hamartomatous Polyposis Syndromes

Patients with the hamartomatous polyposis Peutz-Jeghers and familial juvenile polyposis syndromes are predisposed to colorectal cancer but lack early genetic alterations found in adenomatous premalignant lesions. We studied hamartomatous polyps for the expression of an early preneoplastic colorectal neoplasia risk marker also found in familial adenomatous polyposis patients. Retrospective, genetic, and hospital archival tissue immunohistochemistry using Adnab-9, a premalignant marker often found in Paneth-like cells (PCs), was performed on sections of polyps from eight patients with Peutz-Jeghers syndrome, eight patients with familial juvenile polyposis, and 36 hyperplastic polyp control sections. Anti-α-defensin 5 (AD5), a universal PC marker, was also used to label a subgroup of sections. Hamartomatous polyposis patients also underwent specific genetic analysis. Eighty-nine percent of Peutz-Jeghers syndrome polyps labeled with Adnab-9 compared with 63% for AD5; 88% of familial juvenile polyposis sections also labeled with Adnab-9. Of the 36 hyperplastic polyp sections, only four (11%) labeled with Adnab-9 and one (3%) with AD5. Adnab-9 labeling of PCs in the epithelial elements of hamartomatous colonic lesions of hereditary hamartomatous syndrome patients reflects the predisposition to colorectal cancer, further justifying early intervention strategies.     

Cronkhite-Canada syndrome with adenomatous and carcinomatous transformation of colonic polyp.

We describe a 70-year-old woman who presented with watery diarrhea and was found to have gastric and colonic polyposis, cutaneous hyperpigmentation, alopecia and onychodystrophy (Cronkhite-Canada syndrome). Histology of a polyp from the stomach showed features of juvenile or retention type (hamartomatous) polyp. One colonic polyp revealed features of tubular adenoma, with moderate dysplasia. Another large pedunculated colonic polyp showed a tubulovillous adenoma with a focus of well-differentiated adenocarcinoma confined to the submucosa of the stalk. Adenomatous and carcinomatous epithelial changes can occur in Cronkhite-Canada syndrome.     

The hamartomatous polyposis syndromes: a clinical and molecular review

Inherited forms of gastrointestinal cancer have been a major focus of study and advancement over the past decade. Familial adenomatous polyposis and hereditary nonpolyposis colon cancer are the two most common heritable colon cancer syndromes. Inherited polyposis syndromes are characterized by the dominant type of polyp (whether adenomatous or hamartomatous) present and by the polyp's location within the gastrointestinal tract. The hamartomatous polyposis syndromes are characterized by an overgrowth of cells native to the area in which they normally occur. They represent a small but appreciable number of the gastrointestinal inherited cancer predisposition syndromes; it is now known that many of these syndromes carry a substantial risk for developing colon cancer as well as other gastrointestinal and pancreatic cancers. Patients afflicted with these syndromes are also at significant risk for extraintestinal malignancies. Seven inherited hamartomatous polyposis syndromes have been described: familial juvenile polyposis syndrome, Cowden's syndrome, Bannayan-Ruvalcaba-Riley syndrome, Peutz-Jeghers syndrome, basal cell nevus syndrome, neurofibromatosis 1, and multiple endocrine neoplasia syndrome 2B. Hereditary mixed polyposis syndrome is a variant of juvenile polyposis characterized by both hamartomatous and adenomatous polyps. The hamartomatous syndromes occur at approximately 1/10th the frequency of the adenomatous syndromes and account for <1% of colorectal cancer in Northern America. While the diagnosis of these inherited syndromes is primarily clinical, genetic testing is now available for all six syndromes. However, there are a significant number of spontaneous mutations seen in each of the syndromes. The management of these patients necessitates a coordinated multidisciplinary approach. The purpose of this review is to characterize the clinical and pathological features of these syndromes and to review the targets of cancer surveillance. The molecular alterations responsible for the inherited hamartomatous polyposis syndromes will also be discussed.     

Familial juvenile polyposis with adenomatous-carcinomatous change

Abstract A family tree of 118 members with five members found to have juvenile polyposis-adenomatous change and four juvenile polyposis-adenomatous-carcinomatous change is presented. All the patients developed bleeding per rectum between 10 and 17 years of age. Four members died of colonic malignancy between 30 and 55 years of age. Colonoscopy in five living members revealed typical juvenile polyps throughout the whole length of the colon and atypical large lobulated polyps containing adenomatous change in juvenile polyps in the rectosigmoid area. An autosomal dominant mode of transmission was evident on analysis of the pedigree. Gastric hyperplastic polyps were present in three of the five living members.
Familial juvenile polyposis may have the potential to progress into adenoma-carcinoma sequence and is not always a benign disorder. Colonoscopic surveillance should be done to detect adenomatous change if any member of the juvenile polyposis family develops colonic malignancy.     

Solitary juvenile polyp developing adenocarcinoma with submucosal invasion

Solitary juvenile polyps are generally non‐neoplastic hamartomatous polyps. Inflammation is suggested as the cause of proliferation and progression of these polyps, and adenomatous and carcinomatous changes are rare. We report a rare case of a solitary juvenile polyp with malignant transformation that developed in the sigmoid colon of a 12‐year‐old boy. A 3 cm, pedunculated polyp was endoscopically resected, and histologic evaluation revealed the characteristic features of a juvenile polyp. However, mucous‐filled ectatic glandular spaces were lined by mucin‐secreting columnar epithelial cells with atypical change, and an admixture of adenocarcinoma invading the submucosa was confirmed. The histologic features may suggest the involvement of the adenoma–carcinoma sequence in the development of adenocarcinoma in the present case. Although rare, solitary juvenile polyps should develop adenocarcinoma and thorough histologic evaluation of the resected polyps is warranted to identify the adenomatous tissue.     

Molecular and phenotypic markers of hamartomatous polyposis syndromes in the gastrointestinal tract.

Hamartomatous gastrointestinal polyposis syndromes have always been considered as non-neoplastic. Nevertheless, an increased cancer risk both within and outside the gastrointestinal tract may exist in these syndromes. The hamartomatous polyps may sometimes harbor dysplasia, but their neoplastic potential is unknown. The genetic defects causing the hamartomatous syndromes are less well established than, for example, familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC). The genetic studies on the Mendelian inherited syndromes FAP and HNPCC have made a major contribution to the identification of genes involved in colorectal tumorigenesis. The genes involved in colorectal cancer development may also contribute to cancer development in the hamartomatous polyposis syndromes, and are currently under investigation. Furthermore, new insights into the development of various cancers may be obtained by the isolation and characterization of genes involved in Mendelian inherited hamartomatous polyposis syndromes. This report summarizes the available literature on this subject, and describes the pheno- and genotypic features of the hamartomatous syndromes of juvenile polyposis, Peutz-Jeghers syndrome, and Cowden's disease.     

Familial juvenile polyposis coli; increased risk of colorectal cancer.

Six patients from one family and one solitary patient with juvenile polyposis coli are described. The histological changes in colonic polyps formed a spectrum from juvenile polyps, through focal to extensive adenomatous change, to adenocarcinomas. One patient aged 49 years had an adenocarcinoma of the colon and in another, aged 33, with rectal polyps and metastatic cancer this was suspected although the primary tumour was not located. Two additional patients, aged 19 and 41 years, had severe adenomatous dysplasia in a juvenile polyp. Four patients also had gastroduodenal polyps. The present findings clearly contradict the previous view that juvenile polyposis coli is not premalignant and only rarely needs surgical treatment. As other recent reports also describe frequent occurrence of neoplastic changes in juvenile polyps, colectomy, and ileorectostomy at the age of about 20 years is recommended as the treatment of choice for juvenile polyposis coli, as in patients with familial adenomatosis coli. Follow up should ideally include gastroduodenoscopy and inspection of the rectal remnant at regular intervals.     

The adenomatous polyp and the hereditary polyposis syndromes

Adenomatous polyps are the benign precursors of colorectal adenocarcinoma. Colonic adenomas occur commonly in adults in Western countries. There is recent evidence that inheritance may play an important role in the etiology of these adenomatous polyps. Colonic adenomatous polyposis (numerous colonic adenomas) is the central feature of several rare inherited syndromes that give rise to colorectal cancer. There also appears to be a risk of gastrointestinal and other malignancies in the rare inherited syndromes of hamartomatous polyposis.     

Small Bowel Polyposis Syndromes

Intestinal polyposis syndromes are relatively rare. However, it is important for clinicians to recognize the potential risks of these syndromes. Based on histology, these syndromes can be classified mainly into hamartomatous polyposis syndromes and familial adenomatous polyposis (FAP), which affects mainly the large intestine. This review discusses the clinical manifestations and underlying genetics of the most common small intestinal polyposis syndromes: Peutz-Jeghers syndrome (PJS), juvenile polyposis (JP), PTEN hamartoma tumor syndrome (PHTS), and the small intestinal implications of familial adenomatous polyposis (FAP).     

Familiäre adenomatöse Polyposis und andere Polyposissyndrome

The number of adenomas allows the clinical differentiation of familial adenomatous polyposis into the classical (FAP), attenuated (AFAP), and atypical (ATFAP) forms. Mutations in the APC gene are found in 80% of FAP patients, with inheritance being autosomal dominant. Mutations in MUTYH (MUTYH-associated polyposis, or MAP) follow a recessive inheritance and clinically dominate AFAP. MAP is associated with adenomas, but hyperplastic polyps and serrated adenomas can also be prevalent. Extraintestinal manifestations are associated with FAP. The recurrence risk for FAP is 50% and is below 1% for MAP. Hyperplastic polyposis syndromes (HPS) can show a familial occurrence; mutation analysis of the polyp tissue allows preliminary subdivision into cases with mutations of either BRAF or KRAS and cases with no mutation in either of these genes. The genetic predisposition of HPS in the germline is thus far unknown. The genetics of juvenile polyposis has been established; hamartomatous polyposis syndromes (Peutz–Jeghers and Cowden syndromes) show a 50% mutation detection rate. Especially in hamartomatous polyposis syndromes, the risk for extraintestinal cancers needs to be considered.     

Juvenile and adenomatous gastrointestinal polyposis

Summary This is the fourth report of a case showing an association between juvenile and adenomatous polyposis. Starting at age 14, this patient underwent multiple polypectomies and gastrointestinal resections over a 15-year period. Although initial biopsies were diagnosed as juvenile polyps, later biopsies showed both adenomatous polyps and large polypoid masses with a mixture of juvenile and adenomatous features. Several typical small hyperplastic polyps were also found in the stomach. This case contrasts with the previous three cases in that the gastrointestinal tract is more widely involved and in that there is an unusual marked hyperplasia of argentaffin-and argyrophil-positive cells. The case reported here strengthens the relation between adenomatous polyposis and juvenile polyposis.     

Cronkhite-Canada Syndrome Associated with Colon Carcinoma and Adenomatous Changes in C-C Polyps

A 73-yr-old man with the clinical features of Cronkhite-Canada syndrome developed colonic carcinoma. Radiologic and endoscopic examination revealed numerous polyps involving the stomach and large intestine. Histologic examination of the biopsied polyps revealed polypoidal lesions covered by a single layer of normal columnar mucus-secreting epithelial cells. The stroma of each polyp was composed of well-vascularized edematous lamina propria containing inflammatory cells and glands of variable sizes. Some of the glands were cystically dilated and lined by a single layer of mucin-secreting epithelial cells. These polyps were reminiscent of "juvenile polyps" or retention polyps. Some of these polyps also showed definite adenomatous changes at the surface epithelium. In addition, a large cecal tubulovillous adenoma with foci of well-differentiated adenocarcinoma was noted, indicating that adenomatous and carcinomatous epithelial changes can occur in otherwise nonneoplastic polyposis of the Cronkhite-Canada syndrome as seen in the present case.     

Mixed juvenile,adenomatous and intermediate polyposis coli: Report of a case

Summary The unique occurrence of mixed juvenile, adenomatous, and intermediate colonic polyps in a young girl is described. No familial basis of the condition was obtainable. It is suggested that genetic differentiation between juvenile and adenomatous polyposis is probably not absolute. The place of surgery in the management of the condition is briefly discussed.     

Familial Colon Cancer Syndromes: an Update of a Rapidly Evolving Field

Colorectal cancer (CRC) is a major cause of morbidity and mortality in the world. Up to 30?% of CRCs have evidence of a familial component, and about 5?% are thought to be due to well-characterized inherited mutations. This review will focus on recent developments in the understanding of the individual hereditary CRC syndromes, including Lynch syndrome, familial CRC type X, familial adenomatous polyposis, MutYH-associated polyposis, Peutz-Jeghers syndrome, juvenile polyposis syndrome, PTEN hamartomatous syndrome, and serrated polyposis syndrome. Advances within the area of hereditary colon cancer syndromes paint a picture of a rapidly moving, rapidly maturing, and increasingly collaborative field with many opportunities for ongoing research and development.     

Peutz-Jeghers' syndrome with malignant development in a hamartomatous polyp: report of one case and review of the literature

The malignant potential of hamartomatous polyps in Peutz-Jeghers' (PPJ) syndrome has been debated. Although it is a very rare event, these polyps can become malignant, as demonstrated by this report. One case of colonic adenocarcinoma associated with Peutz-Jeghers' syndrome is described in a 62-year-old woman. The patient had colonic carcinoma which developed in a hamartomatous polyp. The malignant development of this colonic hamartomatous polyp arising in Peutz-Jeghers' syndrome was pathologically confirmed at surgery. This case also shows a sequence of hamartoma-dysplasia-carcinoma in a hamartomatous polyp without adenomatous changes. This suggests that hamartomatous polyps in Peutz-Jeghers' syndrome may develop into adenocarcinoma and may be a precursor of gastrointestinal carcinomas. STK 11 is a tumor suppressor gene regulating the development of hamartomas, and this somatic mutation promotes gastrointestinal cancer at later stages in Peutz-Jeghers' syndrome.     

Genetics of the hamartomatous polyposis syndromes: a molecular review

Background and aims  Hamartomatous polyposis syndromes are a heterogeneous group of disorders that are inherited in an autosomal dominant fashion. These syndromes only represent a small number of the inherited gastrointestinal cancer predisposition syndromes. However, many of these syndromes carry a substantial risk for developing colorectal cancer, as well as extra-colonic malignancy. Materials and methods  We searched for articles on inherited hamartomatous polyposis syndromes, including familial juvenile polyposis syndrome, Peutz–Jeghers syndrome, PTEN hamartoma tumor syndrome, multiple endocrine neoplasia syndrome 2B, hereditary mixed polyposis syndrome, Cronkhite–Canada syndrome, basal cell nevus syndrome, and neurofibromatosis 1, in PubMed, Embase, and Elsevier ScienceDirect. In this review, we briefly discuss the diagnosis and clinical features of these disorders and the molecular alterations responsible for these syndromes. Results and conclusion  Given the clinical similarities of these hamartomatous syndromes and the autosomal dominant pattern of inheritance, it is sometimes difficult to differentiate hamartomatous polyps, especially with atypical presentation. The molecular analysis and diagnosis make it possible to identify the subtype of these syndromes. In addition, these tests raise an intriguing possibility that surveillance and early medical intervention will allow for the identification of at-risk patients and the reduction of morbidity and mortality.     

Mixed familial polyposis syndromes

Three cases of polyposis consisting of adenomatous and hamartomatous elements are described. The literature on mixed polyposis syndromes is reviewed.     

Polyposissyndrome des Gastrointestinaltrakts

Hereditary gastrointestinal polyposis syndromes account for around 1% of all colorectal cancers; most of them are associated with a broad spectrum of extracolonic tumors. The initial diagnosis is based on endoscopic findings and polyp histology. Molecular genetic screening is important for the delineation of conditions with a similar phenotype such as autosomal dominant familial adenomatous polyposis (FAP) and autosomal recessive MUTYH-associated polyposis (MAP). Identification of the germline mutation in an affected person is a prerequisite for the exact evaluation of the recurrence risk in relatives and the predictive testing of asymptomatic persons at risk. Beside cases with attenuated adenomatosis or few colorectal adenomas, diagnostic difficulties are common among the hamartomatous polyposes such as the juvenile polyposis syndrome due to their broad clinical overlap and uncertainties in histological assessment. Several poorly defined nonhereditary polyposis syndromes and those with an as yet unknown etiology exist including hyperplastic polyposis syndrome. Early detection and accurate classification are essential since effective methods for surveillance and treatment are available.     

Synchronous primary carcinomas of the ampulla of Vater and ascending colon in a patient with multiple flat adenomas

Multiple primary cancers occurring in the same patients have been reported to represent 1.8–3.9% of all cancers. The majority of all patients reported to have had a combination of simultaneous neoplastic changes in the ampulla of Vater and the colon showed familial adenomatous polyposis (FAP) syndrome. Variants of familial adenomatous polyposis coli are: attenuated adenomatous polyposis coli (AAPC, previously also known as flat adenoma syndrome) and multiple adenoma coli. AAPC is characterized clinically by many, but usually fewer than 100, colonic lesions that are characteristically slightly elevated and plaque-like, with a reddish surface and sometimes central depression. Genetically it represents an extremely rare variant of FAP. Another group of individuals, so-called multiple adenoma patients, have a phenotype similar to AAPC, but most have no demonstrable germ-line adenomatous polyposis coli mutation, as do patients with FAP or AAPC. However, there have been only a few reports that discussed concurrent neoplastic changes in the ampulla of Vater and colon in patients with multiple colonic flat adenomas, but without the florid phenotype of classical FAP. We present rare clinical course of a patient with multiple (more than 60) flat adenomas in the proximal colon and two primary cancers: of the ampulla of Vater and of the ascending colon. This patient and his family history did not show polyposis compatible with FAP or hereditary nonpolyposis colorectal cancer (HNPCC) syndrome.