title: Clinicopathological features of a kindred with SCG5-GREM1-associated hereditary mixed polyposis syndrome.
abstract: Since first characterized in 1997, patients with hereditary mixed polyposis syndrome (HMPS) have been difficult to identify because of lack of well-established diagnostic criteria. Recently, HMPS was found to be caused by a duplication on chromosome 15 spanning the 3' end of the SCG5 gene and a region upstream of the GREM1 locus. Clinical testing for the duplication is available; however, the clinical characteristics of hereditary mixed polyposis to support testing are ill defined. The clinicopathological findings of 10 HMPS patients with confirmed germline SCG5-GREM1 duplication were reviewed. Mean age at presentation was 33.3 years. Fifty-one colonoscopies yielded 207 polyp specimens, all of which were reexamined. Adenomas (n = 80) and a fairly unique polyp composed of a mixture of hyperplastic polyp and inflammatory polyp-type changes (n = 74) were the most common findings; however, other polyps, including hyperplastic (n = 28), mixed inflammatory polyp/adenoma (n = 8), inflammatory polyp (n = 7), prolapse-type polyp (n = 6), and lymphoid aggregates (n = 4), were encountered. None of the patients developed colorectal malignancy during surveillance, demonstrated extracolonic manifestations, or underwent colectomy on follow-up (mean, 26.2 years). SCG5-GREM1 duplication-associated polyposis is characterized by a few polyps per endoscopy with a mixture of phenotypes, most commonly adenoma and nondysplastic mixed hyperplastic/inflammatory polyps. Nine of 10 patients had at least 1 mixed hyperplastic-inflammatory polyp, which is the characteristic lesion of SCG5-GREM1 duplication-associated HMPS.
authors.affiliation: Department of Anatomic Pathology, Cleveland, OH 44195, USA. Electronic address: plesect@ccf.org.
authors.forename: Thomas
authors.initials: T
authors.lastname: Plesec
authors.affiliation: Department of Pathology, Baptist Memorial Hospital, Jackson, MS 39202, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Brown
authors.affiliation: Department of Anatomic Pathology, Cleveland, OH 44195, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Allen
authors.affiliation: Sanford R Weiss Center for Hereditary Colorectal Cancer Neoplasia and Digestive Disease Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: A Burke
authors.affiliation: Sanford R Weiss Center for Hereditary Colorectal Cancer Neoplasia and Digestive Disease Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: James
authors.initials: J
authors.lastname: Church
authors.affiliation: Sanford R Weiss Center for Hereditary Colorectal Cancer Neoplasia and Digestive Disease Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Kalady
authors.affiliation: Sanford R Weiss Center for Hereditary Colorectal Cancer Neoplasia and Digestive Disease Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: LaGuardia
authors.affiliation: Sanford R Weiss Center for Hereditary Colorectal Cancer Neoplasia and Digestive Disease Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: O'Malley
authors.affiliation: Sanford R Weiss Center for Hereditary Colorectal Cancer Neoplasia and Digestive Disease Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Brandie
authors.initials: B
authors.lastname: Heald
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000208:ethnology / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D001706:Biopsy; D002648:Child; D003111:Colonic Polyps / Q000208:ethnology / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D003113:Colonoscopy; D016208:Databases, Factual; D020440:Gene Duplication; D050939:Gene Fusion; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D007585:Jews / Q000235:genetics; D008875:Middle Aged; D051859:Neuroendocrine Secretory Protein 7B2 / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C486399:GREM1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D051859:Neuroendocrine Secretory Protein 7B2; C497678:SCG5 protein, human
keywords: Colorectal; Hamartomatous polyposis; Hereditary mixed polyposis; Polyposis; SCG5-GREM1