Hyperplastic Polyposis Syndrome: Phenotypic Presentations and the Role of MBD4 and MYH
2006; Elsevier BV; Volume: 131; Issue: 1 Linguagem: Inglês
10.1053/j.gastro.2006.03.046
ISSN1528-0012
AutoresElizabeth Chow, Lara Lipton, Elly Lynch, Rebecca D’Souza, C. Aragona, L Hodgkin, Gregor J. Brown, Ingrid Winship, Melissa Barker, Daniel D. Buchanan, Shannon Cowie, Steve Nasioulas, Desirée du Sart, Joanne Young, Barbara Leggett, Jeremy R. Jass, Finlay Macrae,
Tópico(s)Colorectal Cancer Treatments and Studies
ResumoBackground & Aims: Hyperplastic polyposis syndrome (HPS) is defined phenotypically with multiple, large and/or proximal hyperplastic polyps. There is no known germ-line predisposition. We aimed to characterize the clinicopathologic features of 38 patients with HPS and explore the role of germ-line mutations in the base excision repair genes MBD4 and MYH. Methods: Utilizing clinical databases of The Royal Melbourne Hospital Bowel Cancer Surveillance Service and the Familial Cancer Clinic, 38 patients with HPS were recruited. The patients were analyzed for age at first diagnosis, features of hyperplastic polyposis, family histories of polyposis and colorectal cancer (CRC), coexisting adenomas, serrated adenomas, incidence of CRC, and microsatellite instability in the tumours. Mutation analysis of MBD4 and MYH were performed. Results: Serrated adenomas were common (26%), and 19 (50%) of the 38 patients had a first-degree relative with CRC. Family history of HPS was uncommon, with only 2 cases found. Ten patients developed CRC, and 3 required surgery for polyposis. No pathogenic mutations in MBD4 were detected in the 27 patients tested, but 6 single nucleotide polymorphisms of uncertain functional significance were identified. Pathogenic biallelic MYH mutations were detected in 1 patient. Conclusions: Mutations in MBD4 are unlikely to be implicated in HPS; MYH mutations should be studied, especially when adenomas occur in the same patient. The clinical, histopathologic, and molecular findings of this study should contribute to our understanding of HPS and its relationship to the serrated neoplasia pathway. Background & Aims: Hyperplastic polyposis syndrome (HPS) is defined phenotypically with multiple, large and/or proximal hyperplastic polyps. There is no known germ-line predisposition. We aimed to characterize the clinicopathologic features of 38 patients with HPS and explore the role of germ-line mutations in the base excision repair genes MBD4 and MYH. Methods: Utilizing clinical databases of The Royal Melbourne Hospital Bowel Cancer Surveillance Service and the Familial Cancer Clinic, 38 patients with HPS were recruited. The patients were analyzed for age at first diagnosis, features of hyperplastic polyposis, family histories of polyposis and colorectal cancer (CRC), coexisting adenomas, serrated adenomas, incidence of CRC, and microsatellite instability in the tumours. Mutation analysis of MBD4 and MYH were performed. Results: Serrated adenomas were common (26%), and 19 (50%) of the 38 patients had a first-degree relative with CRC. Family history of HPS was uncommon, with only 2 cases found. Ten patients developed CRC, and 3 required surgery for polyposis. No pathogenic mutations in MBD4 were detected in the 27 patients tested, but 6 single nucleotide polymorphisms of uncertain functional significance were identified. Pathogenic biallelic MYH mutations were detected in 1 patient. Conclusions: Mutations in MBD4 are unlikely to be implicated in HPS; MYH mutations should be studied, especially when adenomas occur in the same patient. The clinical, histopathologic, and molecular findings of this study should contribute to our understanding of HPS and its relationship to the serrated neoplasia pathway. Hyperplastic polyposis syndrome (HPS) is a rare syndrome best characterized by multiple, large, and/or proximal hyperplastic polyps (HPs) and, occasionally, smaller numbers of serrated adenomas (SAs), adenomas, and admixed hyperplastic/adenomatous polyps (ADMPs). Recent studies suggest a link between HPS and colorectal cancer (CRC) with variable levels of microsatellite instability (MSI), possibly arising through a serrated neoplasia pathway. Reported case series of HPS remain few, with the largest series published so far describing 28 patients, 20 of whom had more than 20 HPs.1Renaut A.J. Douglas P.R. Newstead G.L. Hyperplastic polyposis of the colon and rectum.Colorectal Dis. 2002; 4: 213-215Crossref PubMed Scopus (38) Google Scholar We have studied a cohort of 38 patients with either multiple (more than 20), large (>1 cm), or proximally located HPs. The patients’ clinical and pathologic features are described, with particular attention to inheritance and association with CRC. Molecular genetic studies have been performed to explore the role of 2 candidate genes in this syndrome: MBD4 and MYH. Genomic integrity is challenged by endogenous and exogenous DNA damaging agents, and a variety of repair mechanisms exist to counteract these mutagenic and carcinogenic effects. MBD4 plays an important role in maintenance of genomic integrity by impacting on 3 processes: base excision repair, DNA mismatch repair, and cell-cycle response to DNA damage. MYH-associated polyposis (MAP) is a recently characterized autosomal recessive syndrome comprising multiple colorectal adenomas, HPs, and CRC. It is the first human cancer predisposition disorder to be linked to defects in the base excision repair (BER) pathway. Its role in HPS has not been previously explored. Utilizing clinical databases of The Royal Melbourne Hospital Bowel Cancer Surveillance Service and the Familial Cancer Clinic, patients satisfying the diagnostic criteria of HPS according to the World Health Organization (WHO) International Classification were recruited2Burt R.W. Jass J.R. Hyperplastic polyposis.in: Hamilton S.R. Aaltonen L.A. World Health Organisation classification of tumours. Pathology & genetics. Tumours of the digestive system. IARC Press, Lyon2000Google Scholar (Table 1). The Familial Cancer Clinic (FCC) database incorporates patients referred to the FCC because of suspicion of genetic predisposition to polyposis and/or CRC. The clinic and hospital has a statewide reputation for managing polyposis, acting as a common but not exclusive referral resource for a state population of 5 million people.Table 1Diagnostic Criteria of HPS According to the WHO International Classification(1) At least 5 histologically diagnosed hyperplastic polyps proximal to the sigmoid colon, of which 2 are greater than 10 mm in diameter, or(2) Any number of hyperplastic polyps occurring proximal to the sigmoid colon in an individual who has a first-degree relative with hyperplastic polyposis, or(3) greater than 30 hyperplastic polyps but distributed throughout the colonaMore than 20 hyperplastic polyps used in other publications.7a More than 20 hyperplastic polyps used in other publications.7Rashid A. Houlihan P.S. Booker S. Petersen G.M. Giardello F.M. Hamilton S.R. Phenotypic and molecular characteristics of hyperplastic polyposis.Gastroenterology. 2000; 119: 323-332Abstract Full Text Full Text PDF PubMed Scopus (200) Google Scholar Open table in a new tab The WHO diagnostic criteria of HPS is somewhat arbitrary, and future knowledge of molecular and genetic mechanisms may lead to improved classification and definition of this syndrome. Although some of our patients fall outside these criteria, all have developed multiple, large, and/or right-sided HPs. Approval for the study was obtained from the Human Research Ethics Committee of the Royal Melbourne Hospital. All participants provided written informed consent for participation in the study. The pedigrees were verified, and sequential colonoscopy and histopathology findings were ascertained. Gender, age, and age at first diagnosis of HPS were documented. Family history of polyposis and CRC were ascertained. All patients have had colonoscopic surveillance to follow the natural progression of their disease. Information regarding the number, size, distribution, gross morphology, and histology of polyps were derived from the colonoscopy and histopathology reports. Polyps were classified as HPs, SAs, ADMPs, or adenomas. The total numbers of each polyp type were estimated as rigorously as possible during colonoscopy or from the surgical specimen if a colectomy was performed. Details of CRC were reported. Testing for MSI in a subset of cancers and polyps was performed. Thirty-eight germ-line DNA samples and cell lines were collected. The MBD4 gene (gene ID:8930) is on chromosome 3q21-q22. The messenger RNA (mRNA) (NM003925) sequence contains 8 exons and codes for a 580 amino acid protein. Genomic DNA (gDNA) was extracted from whole blood using a standard ethanol-salt precipitation method. We amplified the 8 exons of this gene using polymerase chain reaction (PCR) and sequenced PCR products using the ABI 3100 Genetic Analyzer (Applied Biosystems, Foster, CA) (Primers and conditions on application to authors). For MYH mutation testing, DNA was amplified in 2 PCR fragments containing exons 13–14 and 6–9, respectively. The common G382D variant was detected by restricting the PCR product with BglII. The Y165C variant was detected by direct sequencing. Table 2 summarizes the phenotypic characteristics and MBD4 and MYH testing results of our cohort of patients.Table 2Summary of FindingsPhenotypic characteristics of 38 patients with HPS Median age (range)52 (32–79) Female/male21/17 Median (range) age at first diagnosis44 (27–78) Number of patients with proximal HPs37 (97%) Number of patients with HPs >10 mm15 (39.5%) Number of patients with more than 5 coexisting adenomas12 (32%) Number of patients with at least 1 serrated adenoma11 (29%) Number of patients with at least 1 ADMP6 (16%) Number of patients with CRC10 (26%) Median (range) age of diagnosis of CRC45 (31–71) Number of families with family history of hyperplastic polyposis2 Number of patients with first-degree relative with CRC19 (50%) Number of patients receiving major colonic resection for CRC10 Number of patients receiving major colonic resection for polyposis3 MSI testing results for 5 polyps and 4 cancersMSSMBD4 gene testing Completed in 27/38 patients6 single nucleotide polymorphismsMYH gene testing Completed in 38/38 patients1 biallelic mutation carrier Y165C homozygote Open table in a new tab The median and mean ages of our cohort were 52 years and 57 years, respectively, with a range of 32 to 79 years. The median and mean ages at first diagnosis of HPS were 44 years and 49 years, respectively, with a range between 27 and 78 years. There were 21 female and 17 male patients. The mean number of surveillance colonoscopies was 5 with a range of 1 to 15. Thirty-two of 38 patients satisfied the WHO criteria for HPS (Table 1). The remaining 6 patients (patients 3, 4, 11, 35, 36, 38) had large, proximal HPs, or multiple SAs (Table 3). Thirty seven patients (97%) had HPs proximal to the rectosigmoid. Twenty-seven patients (71%) had more than 5 HPs proximal to the rectosigmoid. Most HPs were 10 mm (Max size mm)Site of HP >10 mmAdenomas BxSA/ADMPCRC site1M(34)(10)(24)2 (14)Sigmoid102aPatients who completed MBD4 testing.F65 (41)25 (17)40 (24)0003aPatients who completed MBD4 testing.F(3)(1)(2)2 (15)HF004aPatients who completed MBD4 testing.M(9)(3)(6)1 (12)TC10DC5aPatients who completed MBD4 testing.MMultiple (3)4 (1)Multiple (2)021 SADC6aPatients who completed MBD4 testing.M>30 (24)20 (20)10 (4)1 (10)Caecum007aPatients who completed MBD4 testing.F(Multiple)(Multiple)(1)001 SA: TC, 30 mmSigmoid8aPatients who completed MBD4 testing.FMultiple (31)Multiple (30)(1)0309aPatients who completed MBD4 testing.FMultiple (20)5–10 (5)Multiple (15)00010aPatients who completed MBD4 testing.F>50 (Multiple)(Multiple)(Multiple)15 (20)Pancolonic2011aPatients who completed MBD4 testing.F(14)(2)(12)0111 ADMP TC12aPatients who completed MBD4 testing.MMultiple (80)Multiple (40)Multiple (40)Multiple (20)Pancolonic120TC13aPatients who completed MBD4 testing.MMultiple (23)Multiple (20)(3)2 (10)AC, TC2014aPatients who completed MBD4 testing.F(20)(16)(4)01015aPatients who completed MBD4 testing.FMultiple (12)Multiple (4)(8)00016aPatients who completed MBD4 testing.FMultiple (17)Multiple (13)(4)3 (10)Sigmoid2017aPatients who completed MBD4 testing.M50–100 (multiple)Multiple (3)(Multiple)031 SA: rectum, 15 mmDC18aPatients who completed MBD4 testing.FMultiple (27)Multiple (1)Multiple (>6)040019aPatients who completed MBD4 testing.FMultiple (30)>20 (18)Multiple (12)2 (12)DC, R/S1 1 SA: TC, 7 mm1 ADMP: rectum, 15 mm20aPatients who completed MBD4 testing.MMultiple (54)Multiple (45)Multiple (9)05021aPatients who completed MBD4 testing. HPS II familyF(40)(20)(20)05022 HPS II familyM50–100 (30)Multiple (24)Multiple (6)01023aPatients who completed MBD4 testing. HPS II familyM(21)(19)(2)01024aPatients who completed MBD4 testing.MMultiple (8)Multiple (8)3 (Not retrieved)2 (10)Sigmoid1025aPatients who completed MBD4 testing.FMultiple (43)MultipleMultipleUncertain (15)UncertainMultiple (5)3 ADMPs, 3 rectal SAs26aPatients who completed MBD4 testing.MMultiple >100MultipleMultiple0Many027aPatients who completed MBD4 testing.MMultiple (54)Multiple (46)Multiple (8)1 (12)Sigmoid51 ADMP 2 mm TC28aPatients who completed MBD4 testing. HPS I familyFMultiple (33)Multiple (9)Multiple (24)08 2 ADMPs: caecum, AC1 SA R/S29aPatients who completed MBD4 testing. HPS I familyFMultiple (20)Multiple (10)Multiple (10)1 (10)TC30AC30F10012 (no Bx)90 (35)031 SA rectumSF31F20 (17)10 (7)10 (10)1 (10)TC0032MMultiple >30 (8)>20 (6)Multiple (2)02033M15–20 (15)15 (12)(3)011 SA 10 mm sigmoid34MMultiple (32)Multiple (23)Multiple (9)015 5 SAs in colectomy specimen1 ADMP R/SRectum35F15 (4)15 (4)0001 SA: 10 mm TCAC36M(10)(5)(5)0220Caecum37F>40 (10)>30 (4)(6)1 (10)R/S1038F17 (7)15 (5)(2)101 SA 8 mm R/SBx, biopsy; R/S, rectosigmoid; AC, ascending colon; TC, transverse colon; DC, descending colon; SF, splenic flexure; HF, hepatic flexure; SA, serrated adenoma; ADMP, admixed hyperplastic adenomatous polyp.a Patients who completed MBD4 testing. Open table in a new tab Bx, biopsy; R/S, rectosigmoid; AC, ascending colon; TC, transverse colon; DC, descending colon; SF, splenic flexure; HF, hepatic flexure; SA, serrated adenoma; ADMP, admixed hyperplastic adenomatous polyp. CRC was diagnosed in 10 patients, 4 proximal and 6 distal. All 10 patients had CRC diagnosed at their initial colonoscopy. Median and mean ages at diagnosis of CRC were 45 and 49 years, respectively, with a range of 31 to 71 years. Three of these 10 patients had coexistent HPs >10 mm in size. Three patients had more than 5 adenomas. Six patients had coexisting SAs. MSI testing was completed in 5 polyps and 4 cancers (polyps from patients 2, 10, 18, 26, 27 were tested, and cancers from patients 4, 5, 7, 12 were tested). All tumors tested were microsatellite stable (MSS). All 10 patients with CRC had colonic resections. Patient 7 had a sigmoid colectomy at the age of 31 years for sigmoid cancer and a right hemicolectomy for a 30-mm SA in the transverse colon 10 years later. Patient 12 had an extended left hemicolectomy for a transverse colon cancer with subsequent right hemicolectomy for a tubulovillous adenoma with severe dysplasia. Three patients (7.9%) had total colectomy and ileorectal anastomosis for management of HPS (patients 10, 25, and 26). Twenty-four patients (63%) had family history of CRC. Nineteen patients (50%) had one or more first-degree relatives with CRC. Family history of HPS was very uncommon in our cohort of patients, with only 2 families found (Figure 1, Figure 2).Figure 2HPS family 2.View Large Image Figure ViewerDownload Hi-res image Download (PPT) In family 1, patients 28 and 29 had a family history of consanguinity (Figure 1). Patient 29 was a 73-year-old female who developed cancer of the ascending colon at the age of 67 years. She also had 40 HPs throughout the colon. Three adenomas were biopsied from the ascending colon. Patient 28 was a 71-year-old female who had 70 HPs throughout the colon, as well as 1 SA in the rectosigmoid, 1 ADMP in the rectum, and 1 ADMP in the caecum. Eight adenomas were removed from the ascending and transverse colons. A 2-cm duodenal adenoma requiring polypectomy was also found. Patient 29’s son has mixed polyposis with 4 adenomas in caecum and descending colon and 1 HP in sigmoid. The presence of the duodenal adenoma in patient 29 led to a suspicion of attenuated familial adenomatous polyposis (AFAP); however, extensive adenomatous polyposis coli (APC) gene testing including deletion studies was negative. In family 2, patient 21 was a 78-year-old lady who had 5 adenomas plus 40 biopsy-proven HPs, 20 of which were located proximal to the rectosigmoid (Figure 2). Five of her siblings were affected: 3 with CRCs while in their 60s, 1 with a severely dysplastic tubular adenoma, and 1 with multiple rectosigmoid polyps and an adenoma at the splenic flexure. Patient 21 had 4 sons, 2 of whom expressed the HPS phenotype. Patient 22 was a 51-year-old male who had an estimated 50–100 HPs, with 30 biopsied. A single adenoma was also found. Patient 23 had 21 HPs, 2 of which were proximal to the sigmoid. Twenty-seven of 38 patients had MBD4 mutation testing completed (Table 3). No pathogenic mutations in MBD4 were detected. Six single nucleotide polymorphisms (SNP) of uncertain functional significance were identified (Table 4). Four of 27 patients were heterozygous for IVS2+27 T→C. Four of 27 patients were heterozygous for exon 3 nucleotide (nt) 993G→A. This SNP causes an amino acid substitution, Ala to Thr, at codon 273. Five of 27 patients were heterozygous at nucleotide 1589 C→T in exon 6 with no amino acid change. Six of 27 patients were heterozygous for IVS6+14C→T. Nine of 27 patients were heterozygous, and 5 of 27 patients were homozygous for 3′-untranslated region (UTR) nt 2302 A→G. Four of 27 patients were heterozygous for 3′-UTR nt 2366 G→C. None of these SNPs were considered to be of clinical significance because they would not cause frame shifts or truncating mutations and were unlikely to cause significant conformational changes in the protein.Table 4MBD4 Testing ResultsSingle nucleotide polymorphismPatient sampleGenotypeIVS2+27 T>TC (rs140692)7, 9, 26, 29TCExon 3 nt 993G>GA, A273T (rs10342)7, 9, 26, 29GAEx 6 nt 1589 C>CT (rs140696)7, 9, 17, 26, 29CTIVS6+14 C>CT (rs140697)7, 9, 17, 18, 26, 29CT3′UTR 2302 A>AG (rs2307285) 3, 10, 11, 12, 13, 15, 1721, 23—HPS family IIAG 2, 5, 628, 29—HPS family IGG3′ UTR 2366 G>GC (rs3138366)7, 9, 26, 29GC Open table in a new tab All 38 patients had complete testing for MYH. One patient (patient 18) was found to be a Y165C homozygote. This was a 54-year-old female with more than 150 polyps. Multiple HPs were noted at 10 colonoscopies. Twenty-seven were biopsy-proven HPs, at least 6 of which were proximally located. She also had 40 adenomas scattered throughout the colon. Her sister died at the age of 36 years from CRC in the setting of multiple adenomas. A brother had 1 HP at the hepatic flexure at age 46 years. Of her 3 daughters, 1 had 5 rectal juvenile polyps at the age of 26 years. These polyps were MSS. Another daughter had rhabdomyosarcoma at age 7 years (Figure 3). HPS was first described in the late 1970s.3Cooke S.A. Polyposis coli. The clinical spectrum in adults.S Afr Med J. 1978; 53: 454-457PubMed Google Scholar, 4Cooper H.S.P.A. Marks G. Adenomatous and carcinomatous changes within hyperplastic colonic epithelium.Dis Colon Rectum. 1979; 22: 152-156Crossref PubMed Scopus (109) Google Scholar, 5Spjut H. Estrada R. The significance of epithelial polyps of the large bowel.Pathol Ann. 1977; 12: 147-170Google Scholar A Medline search revealed to date 31 papers published identifying patients with HPS (Table 5). Among the published data, there was no consensus regarding numbers of polyps needed for the diagnosis of HPS. The cases ranged from 1 HP to those with hundreds of HPs. Eighty-four percent of our cohort of 38 patients developed simultaneous HPs, ADMPs and SAs, and adenomas, similar to other published series (Table 5).6Leggett B.A. Devereaux B. Biden K. Searle J. Young J. Jass J. Hyperplastic polyposis association with colorectal cancer.Am J Surg Pathol. 2001; : 177-184Crossref PubMed Scopus (164) Google Scholar, 7Rashid A. Houlihan P.S. Booker S. Petersen G.M. Giardello F.M. Hamilton S.R. Phenotypic and molecular characteristics of hyperplastic polyposis.Gastroenterology. 2000; 119: 323-332Abstract Full Text Full Text PDF PubMed Scopus (200) Google Scholar, 8Lage P. Cravo M. Sousa R. Chaves P. Salazar M. Fonseca R. Claro I. Suspiro A. Rodrigues P. Raposo H. Fidalgo P. Nobre-Leitao C. Management of Portuguese patients with hyperplastic polyposis and screening of at-risk first degree relatives a contribution for future guidelines based on a clinical study.Am J Gastroenterol. 2004; 99: 1779-1784Crossref PubMed Scopus (76) Google ScholarTable 5Published Series of HPSReferenceCases of HPSHPsAdenomasSAs or MPsCRCMSI status (polyp or cancer)37Goldman H. Ming S. Hickock D.F. Nature and significance of hyperplastic polyps of the human colon.Arch Pathol. 1970; 89: 349-354PubMed Google Scholar130NoYesNo5Spjut H. Estrada R. The significance of epithelial polyps of the large bowel.Pathol Ann. 1977; 12: 147-170Google Scholar9MultipleNoYesYes3Cooke S.A. Polyposis coli. The clinical spectrum in adults.S Afr Med J. 1978; 53: 454-457PubMed Google Scholar130NoNoNo4Cooper H.S.P.A. Marks G. Adenomatous and carcinomatous changes within hyperplastic colonic epithelium.Dis Colon Rectum. 1979; 22: 152-156Crossref PubMed Scopus (109) Google Scholar1MultipleYesNoYes13Williams G.T. Arthur J.F. Bussey H.J. Morson B.C. Metaplastic polyps and polyposis of the colorectum.Histopathology. 1980; 4: 155-170Crossref PubMed Scopus (164) Google Scholar750–156YesNoNo38Sumner H.W. Wasserman N.F. McClain C.J. Giant hyperplastic polyposis of the colon.Dig Dis Sci. 1981; 26: 85-89Crossref PubMed Scopus (55) Google Scholar1HundredsNoYesNo39Cohen S.M. Brown L. Janower M.L. McCready F.J. Multiple metaplastic (hyperplastic) polyposis of the colon.Gastrointest Radiol. 1981; 6: 333-335Crossref PubMed Scopus (18) Google Scholar1MultipleNoNoNo40Franzin G. Novelli P. Adenocarcinoma occurring in a hyperplastic (metaplastic) polyp of the colon.Endoscopy. 1982; 14: 28-30Crossref PubMed Scopus (70) Google Scholar11NoNoYes41Tulman A.B. Bradford S. Lee E. Brady P.G. Giant hyperplastic polyps associated with vasculitis of the colon.J Fla Med Assoc. 1982; 69: 380-383PubMed Google Scholar115NoNoNo42Yamada N F.S. Ogawa T. Nishikage S. Adachi M. Muto T. Multiple metaplastic polyps of the colon associated with adenomas complicating focal carcinoma, report of a case.Stomach Intestine. 1983; 18: 529-530Google Scholar120YesYesYes43Urbanski S.J. Kossakowska A.E. Marcon N. Bruce W.R. Mixed hyperplastic adenomatous polyps—an underdiagnosed entity. Report of a case of adenocarcinoma arising within a mixed hyperplastic adenomatous polyp.Am J Surg Pathol. 1984; 8: 551-556Crossref PubMed Scopus (164) Google Scholar10YesYesYes44Bengoechea O. Martinez-Penuela J.M. Larrinaga B. Valerdi J. Borda F.J. Hyperplastic polyposis of the colorectum and adenocarcinoma in a 24-year-old man.Am J Surg Pathol. 1987; 11: 323-327Crossref PubMed Scopus (86) Google Scholar128NoYesYes45McCann B.G. A case of metaplastic polyposis of the colon associated with focal adenomatous change and metachronous adenocarcinomas.Histopathology. 1988; 13: 700-702Crossref PubMed Scopus (50) Google Scholar160YesYesYes46Teoh H.H. Delahunt B. Isbister W.H. Dysplastic and malignant areas in hyperplastic polyps of the large intestine.Pathology. 1989; 21: 138-142Crossref PubMed Scopus (59) Google Scholar118YesYesYes47Kusunoki M. Fujita S. Sakanoue Y. Shoji Y. Yanagi H. Yamamura T. Utsunomiya J. Disappearance of hyperplastic polyposis after resection of rectal cancer. Report of two cases.Dis Colon Rectum. 1991; 34: 829-832Crossref PubMed Scopus (20) Google Scholar219–61NoNoYes48Shepherd N.A. Inverted hyperplastic polyposis of the colon.J Clin Pathol. 1993; 46: 56-60Crossref PubMed Scopus (30) Google Scholar212–18YesNoYes49Warner A.S. Glick M.E. Fogt F. Multiple large hyperplastic polyps of the colon coincident with adenocarcinoma.Am J Gastroenterol. 1994; 89: 123-125PubMed Google Scholar116YesNoYes50Lieverse R.J. Kibbelaar R.E. Griffioen G. Lamers C.B. Colonic adenocarcinoma in a patient with multiple hyperplastic polyps.Neth J Med. 1995; 46: 185-188Crossref PubMed Scopus (18) Google Scholar1MultipleYesNoYes51Beusnel C. Le Berre N. Pagenault M. Luherne Y. Bargain A. Ramee M.P. Gosselin M. Bretagne J.F. Giant hyperplastic polyposis with adenomatous tissue.Gastroenterol Clin Biol. 1996; 20: 294-297PubMed Google Scholar1MultipleYesNoNo52Torlakovic E. Snover D.C. Serrated adenomatous polyposis in humans.Gastroenterology. 1996; 110: 748-755Abstract Full Text Full Text PDF PubMed Scopus (332) Google Scholar6>50–100NoYesYes17Jeevaratnam P. Cottier D.S. Browett P.J. Van De Water N.S. Pokos V. Jass J.R. Familial giant hyperplastic polyposis predisposing to colorectal cancer a new hereditary bowel cancer syndrome.J Pathol. 1996; 179: 20-25Crossref PubMed Scopus (151) Google Scholar51 to multipleYesYesYesMSI H: 2 cancers, 1 20 mm HP all in 1 individual53Jorgensen H. Mogensen A.M. Svendsen L.B. Hyperplastic polyposis of the large bowel. Three cases and a review of the literature.Scand J Gastroenterol. 1996; 31: 825-830Crossref PubMed Scopus (38) Google Scholar3Multiple to 68NoNoYes54Orii S. Nakamura S. Sugai T. Habano W. Akasaka I. Nakasima F. Kazama H. Hasimoto Y. Takahasi H. Sugawara M. Sato S. Hyperplastic (metaplastic) polyposis of the colorectum associated with adenomas and an adenocarcinoma.J Clin Gastroenterol. 1997; 25: 369-372Crossref PubMed Scopus (28) Google Scholar1200YesYesYes55Keljo D.J. Weinberg A.G. Winick N. Tomlinson G.A. Rectal cancer in an 11-year-old girl with hyperplastic polyposis.J Pediatr Gastroenterol Nutr. 1999; 28: 327-332Crossref PubMed Scopus (27) Google Scholar1>100Not reportedNoYes14Place R.J. Simmang C.L. Hyperplastic-adenomatous polyposis syndrome.J Am Coll Surg. 1999; 188: 503-507Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar650–100YesNoYes7Rashid A. Houlihan P.S. Booker S. Petersen G.M. Giardello F.M. Hamilton S.R. Phenotypic and molecular characteristics of hyperplastic polyposis.Gastroenterology. 2000; 119: 323-332Abstract Full Text Full Text PDF PubMed Scopus (200) Google Scholar13Multiple to >100YesYesYes MSI H: 4/129 HPsMSI L: 2/129 HPs, 1/6 SAs, 1/3 MPs9Jass J.R. Iino H. Ruszkiewicz A. Painter D. Solomon M.J. Koorey D.J. Cohn D. Furlong K.L. Walsh M.D. Palazzo J. Edmonston T.B. Fishel R. Young J. Leggett B.A. Neoplastic progression occurs through mutator pathways in hyperplastic polyposis of the colorectum.Gut. 2000; 47: 43-49Crossref PubMed Scopus (228) Google Scholar46–50YesYesYes MSI H: 6/11 cancers, 4/13 dysplastic fociMSI L: 2/11 cancers, 3/13 dysplastic foci, 1/13 HPsMSS: 12/13 HPs, 6/13 dysplastic foci, 3/11 cancers12Hawkins N.J. Gorman P. Tomlinson I.P. Bullpitt P. Ward R.L. Colorectal carcinomas arising in the hyperplastic polyposis syndrome progress through the chromosomal instability pathway.Am J Pathol. 2000; 157: 385-392Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar175NoYesYesMSS in cancer, SA, HPs6Leggett B.A. Devereaux B. Biden K. Searle J. Young J. Jass J. Hyperplastic polyposis association with colorectal cancer.Am J Surg Pathol. 2001; : 177-184Crossref PubMed Scopus (164) Google Scholar12>15 to >100YesYesYes MSI H: 1/47 HPs, 2/8 cancersMSI L: 2/47 HPs, 2/8 SAsMSS: 44/47 HPs, 1/1 MP, 6/8 SAs, 2/2 adenomas, 6/8 cancers16Koide N. Saito Y. Fujii T. Kondo H. Saito D. Shimoda T. A case of hyperplastic polyposis of the colon with adenocarcinomas in hyperplastic polyps after long-term follow-up.Endoscopy. 2002; 34: 499-502Crossref PubMed Scopus (31) Google Scholar1MultipleYesNoYes1Renaut A.J. Douglas P.R. Newstead G.L. Hyperplastic polyposis of the colon and rectum.Colorectal Dis. 2002; 4: 213-215Crossref PubMed Scopus (38) Google Scholar28>20YesYesYes18Ferrandez A. Samowitz W. DiSario J.A. Burt R.W. Phenotypic characteristics and risk of cancer development in hyperplastic polyposis case series and literature review.Am J Gastroenterol. 2004; 99: 2012-2018Crossref PubMed Scopus (93) Google Scholar1515–207YesYesYes15Hyman N.H. Anderson P. Blasyk H. Hyperplastic polyposis and the risk of colorectal cancer.Dis Colon Rectum. 2004; 47: 2101-2104Crossref PubMed Scopus (133) Google Scholar13>20YesYesYes8Lage P. Cravo M. Sousa R. Chaves P. Salazar M. Fonseca R. Claro I. Suspiro A. Rodrigues P. Raposo H. Fidalgo P. Nobre-Leitao C. Management of Portuguese patients with hyperplastic polyposis and screening of at-risk first degree relatives a contribution for future guidelines based on a clinical study.Am J Gastroenterol. 2004; 99: 1779-1784Crossref PubMed Scopus (76) Google Scholar1419 to >100YesYesYes Open table in a new tab Considerable evidence supports the concept of a serrated neoplasia pathway of colorectal tumorigenesis. Serrated polyps demonstrate serrated or “sawtoothed” appearance on histology because of infolding of the crypt epithelium. The classification is complex and controversial, covering a spectrum of lesions ranging from HPs to SAs and ADMPs. SAs have the sawtoothed architecture of H
Referência(s)