A case of Cowden's syndrome presenting with gastric carcinomas and gastrointestinal polyposis

Al‐Thihli, Khalid; Palma, Laura; Marcus, Victoria; Cesari, Matthew; Kushner, Yaël B.; An, Barkun; Foulkes, William D.

doi:10.1038/ncpgasthep1359

Cited by 30 publications

(28 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Up to our recent GI series by Heald et al , 8 there were several reports of gastric cancers in PTEN mutation carriers, 14, 15 but no reports about adenomatous polyps in the upper GI tract. In our current study from active GI surveillance, we report that all patients had upper GI polyps and that three patients (30%) had adenomatous polyps, the latter contrasts with only 2 of 39 (5%) research participants found to have upper GI adenomatous polyps when EGD was performed for clinical reasons 8 ( P =0.05).…”

Section: Discussionmentioning

confidence: 94%

“…7 Prior to our recent report, 8 there were scattered reports about the occurrence of GI polyposis 9, 10, 11, 12, 13 but few reports documenting age-specific prevalence of gastric and colon cancers in CS patients. 14, 15, 16, 17 In our prospective series of 127 unrelated individuals with pathogenic PTEN mutations, 69 (54.3%) underwent at least one endoscopy and most had GI polyps comprising multiple histologies. 8 Importantly, nine (13%) mutation carriers in this series had prevalent colorectal cancers, yielding an age- and sex-adjusted standardized incidence ratio of >200.…”

Section: Introductionmentioning

confidence: 96%

See 1 more Smart Citation

Upper and Lower Gastrointestinal Findings in PTEN Mutation–Positive Cowden Syndrome Patients Participating in an Active Surveillance Program

Levi

Baris

Kedar

et al. 2011

Clinical and Translational Gastroenterology

View full text Add to dashboard Cite

OBJECTIVES:Cowden syndrome (CS), associated with germline PTEN mutations, is an autosomal-dominant disorder with increased frequencies of thyroid and breast cancers. Recent reports document the occurrence of gastrointestinal (GI) polyps and increased risk of colon cancer in PTEN mutation carriers. Studies to date, however, have not been based on mutation carriers undergoing active, systematic, routine-interval GI surveillance. Our objective is to document the upper and lower GI findings in CS patients undergoing such an active GI surveillance program.METHODS:In a 5-year period, 3,000 consecutive patients were referred to our high-risk GI cancer clinic for various reasons. Of these 3,000, 10 met full-blown clinical criteria for the diagnosis of CS. Individuals with identified PTEN mutations underwent annual upper and lower endoscopy surveillance programs using dual white light and narrow-band imaging. All biopsies including archived materials were reviewed by a single dedicated GI pathologist.RESULTS:Ten PTEN mutation carriers from different ethnic backgrounds were invited and all participated in the active GI surveillance program. Eight patients had colonic polyps, mostly hyperplastic (eight patients) and hamartomatous (five patients), but also adenomatous (three patients), ganglioneuromatous (three patients), and juvenile polyps (two patients). One patient (10%) had an early-onset rectal cancer (aged 44 years), which was null for PTEN expression on immunohistochemistry. All patients had gastric polyps and nine (90%) had duodenal polyps, mostly hyperplastic and hamartomatous. Additional three patients (30%) had adenomatous duodenal polyps.CONCLUSIONS:PTEN mutation–positive CS patients have a higher frequency of upper GI polyps than previously believed. They appear prone to develop adenomatous upper and lower tract dysplastic polyps and cancer. Thus, the polyps encountered during upper or lower endoscopy in these patients should not be automatically considered innocent hamartomas without malignant potential. Active surveillance programs in specialized centers should be considered in these patients.

show abstract

Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 96%

Upper and Lower Gastrointestinal Findings in PTEN Mutation–Positive Cowden Syndrome Patients Participating in an Active Surveillance Program

Levi

Baris

Kedar

et al. 2011

Clinical and Translational Gastroenterology

View full text Add to dashboard Cite

show abstract

“…One patient had a single hamartomatous polyp in the duodenum whereas three had adenomatous polyps. There are reports of gastric and colon cancers in CS patients (183,230). …”

Section: Lynch Syndrome (Ls)mentioning

confidence: 99%

ACG Clinical Guideline: Genetic Testing and Management of Hereditary Gastrointestinal Cancer Syndromes

Syngal

Brand

Church

et al. 2015

American Journal of Gastroenterology

1,352

1,372

View full text Add to dashboard Cite

This guideline presents recommendations for the management of patients with hereditary gastrointestinal cancer syndromes. The initial assessment is the collection of a family history of cancers and premalignant gastrointestinal conditions and should provide enough information to develop a preliminary determination of the risk of a familial predisposition to cancer. Age at diagnosis and lineage (maternal and/or paternal) should be documented for all diagnoses, especially in first- and second-degree relatives. When indicated, genetic testing for a germline mutation should be done on the most informative candidate(s) identified through the family history evaluation and/or tumor analysis to confirm a diagnosis and allow for predictive testing of at-risk relatives. Genetic testing should be conducted in the context of pre- and post-test genetic counseling to ensure the patient's informed decision making. Patients who meet clinical criteria for a syndrome as well as those with identified pathogenic germline mutations should receive appropriate surveillance measures in order to minimize their overall risk of developing syndrome-specific cancers. This guideline specifically discusses genetic testing and management of Lynch syndrome, familial adenomatous polyposis (FAP), attenuated familial adenomatous polyposis (AFAP), MUTYH-associated polyposis (MAP), Peutz–Jeghers syndrome, juvenile polyposis syndrome, Cowden syndrome, serrated (hyperplastic) polyposis syndrome, hereditary pancreatic cancer, and hereditary gastric cancer.

show abstract

“…14 Gastric cancer has been highlighted in case reports of two individuals with CS. 15, 16 The risk of benign and malignant GI neoplasias has yet to be characterized in a large series of individuals with PTEN mutation positive Cowden syndrome. We, therefore, sought to determine the prevalence and characteristics of the GI phenotype in our series of PTEN mutation positive subjects.…”

Section: Introductionmentioning

confidence: 99%

Frequent Gastrointestinal Polyps and Colorectal Adenocarcinomas in a Prospective Series of PTEN Mutation Carriers

et al. 2010

View full text Add to dashboard Cite

BACKGROUND & AIMS Germline PTEN mutations cause Cowden syndrome (CS), associated with breast and thyroid cancers. Case reports found 35–85% of CS patients had gastrointestinal (GI) hamartomas. The association of benign and malignant GI neoplasias with CS remains debatable. Our goal is to describe the GI phenotype in a prospective series of PTEN mutation carriers. METHODS Patients who met relaxed International Cowden Consortium criteria (N=2548) or with ≥5 GI polyps, ≥1 of which was hyperplastic or hamartomatous (N=397) were prospectively recruited. Germline PTEN mutation/deletion analysis was performed. Of the 2945, 127 patients having clear pathogenic PTEN mutations (123/2548+4/397) were eligible for this study. EGD and colonoscopy were performed and pathology reports reviewed. Fisher’s 2-tailed exact test, unpaired t-tests, and age- and gender-adjusted SIR were calculated. RESULTS Of 127 PTEN mutation carriers, 67 underwent ≥1 endoscopy with 62 (95%) having polyps, making GI polyps the second most common feature, after macrocephaly (74.8%). Of the 65, half had hyperplastic polyps and ¼ each with hamartomatous, ganglioneuromatous or adenomatous polyps. There were one to “innumerable” polyps in the colorectum, ileum, duodenum, stomach and/or esophagus, with 24 subjects having both upper and lower GI polyps. Nine (13%) subjects had colorectal cancer, all under the age of 50. The adjusted SIR was 224.1 (95%CI 109.3–411.3, p<0.0001). Cancers were commonly associated with adenomatous and/or hyperplastic polyps. One had gastric signet ring cell carcinoma. CONCLUSIONS PTEN-associated CS should be considered a mixed polyp syndrome, with hyperplastic polyps most prevalent, and a risk of early-onset colorectal cancer. Routine colonoscopy should be considered in PTEN-associated CS especially in the context of hyperplastic and/or adenomatous polyps.

show abstract

A case of Cowden's syndrome presenting with gastric carcinomas and gastrointestinal polyposis

Abstract: Genetic counseling, thyroidectomy, vitamin B(12) supplementation, continued endoscopic surveillance and genetic testing of at-risk family members.

Cited by 30 publications

References 15 publications

Upper and Lower Gastrointestinal Findings in PTEN Mutation–Positive Cowden Syndrome Patients Participating in an Active Surveillance Program

Upper and Lower Gastrointestinal Findings in PTEN Mutation–Positive Cowden Syndrome Patients Participating in an Active Surveillance Program

ACG Clinical Guideline: Genetic Testing and Management of Hereditary Gastrointestinal Cancer Syndromes

Frequent Gastrointestinal Polyps and Colorectal Adenocarcinomas in a Prospective Series of PTEN Mutation Carriers

Contact Info

Product

Resources

About