{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T14:51:15Z","timestamp":1786546275836,"version":"build-2736575974"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2019,5,17]],"date-time":"2019-05-17T00:00:00Z","timestamp":1558051200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Transl Gastroenterol","Clinical and Translational Gastroenterology"],"abstract":"<jats:sec>\n                    <jats:title>INTRODUCTION:<\/jats:title>\n                    <jats:p>Hamartomatous polyposis syndromes (HPS) are rare autosomal-dominant inherited disorders associated with gastrointestinal (GI) tract and other cancers. HPS include Peutz-Jeghers syndrome (PJS), juvenile polyposis syndrome (JPS), and phosphatase and tensin homolog hamartomatous tumor syndromes (PHTS). Diagnosis, management, and outcome prediction of HPS pose a clinical challenge. To characterize genotype, phenotype, histology and outcomes of individuals with HPS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>A retrospective cohort study (2004\u20132017) of consecutive patients that were clinically diagnosed with HPS that visited a specialized GI oncology clinic. Demographic, clinicopathological, and genetic data were obtained from medical records.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Fifty-two individuals from 34 families were included. Common clinical manifestations were GI bleeding (40% JPS, 23% PJS, and 25% PHTS) and bowel obstruction (46.15% PJS and 11.4% JPS). Twenty patients (38.4%) underwent surgery, 5 of whom required multiple procedures. Higher polyp burden was associated with the need for surgery (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.007). Polyp histology varied widely with 69.2% of patients exhibiting histology different from the syndrome hallmark. GI cancer history was positive in 65%, 40%, and 50% of JPS, PJS, and PHTS families, respectively. Five (9.6%) patients developed cancers (one patient each had small bowel-1, colon-1, and thyroid-1, one patient had both small bowel adenocarcinoma and breast cancer, and one had both breast cancer and liposarcoma). Twenty (38.4%) patients tested positive for\n                      <jats:italic toggle=\"yes\">STK11, PTEN<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">SMAD4<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">BMPR1A<\/jats:italic>\n                      , or\n                      <jats:italic toggle=\"yes\">AKT1<\/jats:italic>\n                      mutations: Sanger sequencing and multi-gene next generation sequencing panels detected mutations in 40.9% and 100% of tested cases, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION:<\/jats:title>\n                    <jats:p>HPS patients present versatile phenotypes with overlapping clinical and histological characteristics. Polyp burden is associated with the need for surgery. Next-generation sequencing increases mutation detection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.14309\/ctg.0000000000000035","type":"journal-article","created":{"date-parts":[[2019,5,20]],"date-time":"2019-05-20T07:33:29Z","timestamp":1558337609000},"page":"e00035","source":"Crossref","is-referenced-by-count":22,"title":["Clinical and Histologic Overlap and Distinction Among Various Hamartomatous Polyposis Syndromes"],"prefix":"10.14309","volume":"10","author":[{"given":"Ophir","family":"Gilad","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Tel Aviv Medical Center, Tel-Aviv, Israel;"},{"name":"Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Rosner","sequence":"additional","affiliation":[{"name":"Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel;"},{"name":"Department of Gastroenterology, Tel Aviv Medical Center, Affiliated to Sackler Medical School, Tel-Aviv University, Tel-Aviv, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Fliss-Isakov","sequence":"additional","affiliation":[{"name":"Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel;"},{"name":"Department of Gastroenterology, Tel Aviv Medical Center, Affiliated to Sackler Medical School, Tel-Aviv University, Tel-Aviv, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sivan","family":"Aharon-Kaspi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Tel Aviv Medical Center, Affiliated to Sackler Medical School, Tel-Aviv University, Tel-Aviv, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana","family":"Strul","sequence":"additional","affiliation":[{"name":"Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel;"},{"name":"Department of Gastroenterology, Tel Aviv Medical Center, Affiliated to Sackler Medical School, Tel-Aviv University, Tel-Aviv, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Gluck","sequence":"additional","affiliation":[{"name":"Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel;"},{"name":"Department of Gastroenterology, Tel Aviv Medical Center, Affiliated to Sackler Medical School, Tel-Aviv University, Tel-Aviv, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Revital","family":"Kariv","sequence":"additional","affiliation":[{"name":"Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel;"},{"name":"Department of Gastroenterology, Tel Aviv Medical Center, Affiliated to Sackler Medical School, Tel-Aviv University, Tel-Aviv, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2019,5,22]]},"reference":[{"issue":"1","key":"R1-20230814","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1897-4287-11-4","article-title":"Hamartomatous polyposis syndromes","volume":"11","author":"Stojcev","year":"2013","journal-title":"Hered Cancer Clin Pract"},{"key":"R2-20230814","first-page":"71","article-title":"Peutz-Jeghers syndrome: Its natural course and management","volume":"136","author":"Utsunomiya","year":"1975","journal-title":"Johns Hopkins Med J"},{"key":"R3-20230814","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1097\/00005176-200408000-00027","article-title":"Complications of childhood Peutz-Jeghers syndrome: Implications for pediatric screening","volume":"39","author":"Hinds","year":"2004","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"R4-20230814","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1186\/1750-1172-9-101","article-title":"Hmartomatous polyposis syndromes: A review","volume":"9","author":"Jelsig","year":"2014","journal-title":"Orphanet J Rare Dis"},{"key":"R5-20230814","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/ajg.2014.435","article-title":"ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes","volume":"110","author":"Syngal","year":"2015","journal-title":"Am J Gastroenterol"},{"key":"R6-20230814","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/34432","article-title":"A serine\/threonine kinase gene defective in Peutz-Jeghers syndrome","volume":"391","author":"Hemminki","year":"1998","journal-title":"Nature"},{"key":"R7-20230814","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1097\/DCR.0b013e31826278b3","article-title":"Juvenile polyposis syndrome: A study of genotype, phenotype, and long-term outcome","volume":"55","author":"Latchford","year":"2012","journal-title":"Dis Colon Rectum"},{"key":"R8-20230814","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1136\/gut.2006.116913","article-title":"Risk of colorectal cancer in juvenile polyposis","volume":"56","author":"Brosens","year":"2007","journal-title":"Gut"},{"key":"R9-20230814","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1126\/science.280.5366.1086","article-title":"Mutations in the SMAD4\/DPC4 gene in juvenile polyposis","volume":"280","author":"Howe","year":"1998","journal-title":"Science"},{"key":"R10-20230814","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1007\/BF02557528","article-title":"Germline SMAD4 or BMPR1A mutations and phenotype of juvenile polyposis","volume":"9","author":"Sayed","year":"2002","journal-title":"Ann Surg Oncol"},{"issue":"9412","key":"R11-20230814","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/S0140-6736(04)15732-2","article-title":"A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4)","volume":"363","author":"Gallione","year":"2004","journal-title":"Lancet"},{"issue":"1","key":"R12-20230814","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1007\/s00439-002-0748-9","article-title":"Juvenile polyposis: Massive gastric polyposis is more common in MADH4 mutation carriers than in BMPR1A mutation carriers","volume":"111","author":"Friedl","year":"2002","journal-title":"Hum Genet"},{"key":"R13-20230814","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s10897-008-9187-7","article-title":"Cowden syndrome: A critical review of the clinical literature","volume":"18","author":"Pilarski","year":"2009","journal-title":"J Genet Couns"},{"key":"R14-20230814","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1089\/thy.2010.0226","article-title":"Thyroid pathology in PTEN-hamartoma tumor syndrome: Characteristic findings of a distinct entity","volume":"21","author":"Laury","year":"2011","journal-title":"Thyroid"},{"key":"R15-20230814","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1136\/jmg.2011.088807","article-title":"Predicting PTEN mutations: An evaluation of Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome clinical features","volume":"48","author":"Pilarski","year":"2011","journal-title":"J Med Genet"},{"key":"R16-20230814","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1093\/hmg\/7.3.507","article-title":"Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation","volume":"7","author":"Marsh","year":"1998","journal-title":"Hum Mol Genet"},{"key":"R17-20230814","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1186\/gb-2011-12-9-228","article-title":"Unlocking Mendelian disease using exome sequencing","volume":"12","author":"Gilissen","year":"2011","journal-title":"Genome Biol"},{"key":"R18-20230814","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1007\/s10620-013-2875-7","article-title":"Exome sequencing revealed novel germline mutations in Chinese Peutz-Jeghers syndrome patients","volume":"59","author":"Wang","year":"2014","journal-title":"Dig Dis Sci"},{"key":"R19-20230814","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/PAP.0000000000000173","article-title":"The Role of the surgical pathologist in the diagnosis of gastrointestinal polyposis syndromes","volume":"25","author":"Rosty","year":"2018","journal-title":"Adv Anat Pathol"},{"issue":"6","key":"R21-20230814","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1053\/j.gastro.2010.06.061","article-title":"Frequent gastrointestinal polyps and colorectal adenocarcinomas in prospective series of PTEN mutation carriers","volume":"139","author":"Heald","year":"2010","journal-title":"Gastroenterology"},{"key":"R22-20230814","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.ajhg.2012.10.021","article-title":"Germline PIK3CA and AKT1 mutations in Cowden and Cowden-like syndromes","volume":"92","author":"Orloff","year":"2013","journal-title":"Am J Hum Genet"},{"key":"R23-20230814","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1038\/ajg.2010.473","article-title":"High cumulative risk of intussusception in patients with Peutz-Jeghers syndrome: Time to update surveillance guidelines?","volume":"106","author":"van Lier","year":"2011","journal-title":"Am J Gastroenterol"},{"key":"R24-20230814","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1053\/j.gastro.2008.12.007","article-title":"A Pooled analysis of advanced colorectal neoplasia diagnoses following colonoscopic polypectomy","volume":"136","author":"Martinez","year":"2009","journal-title":"Gastroenterology"},{"key":"R25-20230814","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1001\/jama.294.19.2465","article-title":"Molecular classification of patients with unexplained hamartomatous and hyperplastic polyposis","volume":"294","author":"Sweet","year":"2005","journal-title":"JAMA"},{"key":"R26-20230814","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/(SICI)1096-9896(199905)188:1<1::AID-PATH327>3.0.CO;2-J","article-title":"The hamartoma-adenoma-carcinoma sequence","volume":"188","author":"Bosman","year":"1999","journal-title":"J Pathol"},{"key":"R27-20230814","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1136\/gut.2010.223750","article-title":"High cancer risk and increased mortality in patients with Peutz-Jaghers syndrome","volume":"60","author":"van Lier","year":"2011","journal-title":"Gut"},{"key":"R28-20230814","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1136\/jmg.2007.052506","article-title":"High proportion of large genomic deletions and a genotype phenotype update in 80 unrelated families with juvenile polyposis syndrome","volume":"44","author":"Aretz","year":"2007","journal-title":"J Med Genet"},{"key":"R29-20230814","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1038\/sj.bjc.6601030","article-title":"Further observations on LKB1\/STK11 status and cancer risk in Peutz-Jeghers syndrome","volume":"89","author":"Lim","year":"2003","journal-title":"Br J Cancer"},{"key":"R30-20230814","doi-asserted-by":"crossref","first-page":"e18","DOI":"10.1136\/jmg.2005.039875","article-title":"LKB1 exonic and whole gene deletions are a common cause of Peutz-Jeghers syndrome","volume":"43","author":"Volikos","year":"2006","journal-title":"J Med Genet"},{"issue":"Suppl 1","key":"R31-20230814","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s12938-017-0359-2","article-title":"Rational confederation of genes and diseases: NGS interpretation via GeneCards, MalaCards and VarElect","volume":"16","author":"Rappaport","year":"2017","journal-title":"Biomed Eng Online"}],"container-title":["Clinical and Translational Gastroenterology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/01720094-201905000-00010","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T13:54:33Z","timestamp":1786542873000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/01720094-201905000-00010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,17]]},"references-count":30,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2019]]}},"URL":"https:\/\/doi.org\/10.14309\/ctg.0000000000000035","relation":{},"ISSN":["2155-384X"],"issn-type":[{"value":"2155-384X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,17]]}}}