13. Hyperplastic Polyposis Syndrome


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13. Hyperplastic Polyposis Syndrome

  1. 1. Hyperplastic Polyposis Syndrome By Yvonne Chua
  2. 2. Background <ul><li>Hyperplastic Polyposis Syndrome (HPS) is an uncommon condition, characterized by the presence within the colon and rectum of multiple hyperplastic polyps (2) </li></ul><ul><li>In the past, hyperplastic polyps were considered benign (no malignant potential) </li></ul><ul><li>Increasing recognition that hyperplastic (metaplastic) colorectal polyps may indeed by neoplastic lesions because they contain genetic changes also seen in colorectal cancer, including mutations of K-ras and MSI (1) </li></ul>
  3. 3. Characteristics of hereditary forms of CRC <ul><li>Unusual early age of onset </li></ul><ul><li>Occurrence of multiple CRCs </li></ul><ul><li>Combined occurrence of CRC with endometrial cancer (in an individual or family) </li></ul><ul><li>Finding of multiple adenomatous or hamartomatous polyps in the colorectum (6) </li></ul>
  4. 4. Current research studies <ul><li>Liljegren A. et. Al. (3) stated that their results suggested that hyperplastic polyps were associated with a risk of colorectal cancer due to a findings of a higher prevalence of hyperplastic polyps being found in patients with CRC compared with those without CRC. </li></ul><ul><li>Recent studies indicate that patients with HPS have a predisposition to develop right sided MSI high colon carcinomas (3) </li></ul><ul><li>Malignant conversion rate for a right sided hyperplastic polyp is approximately the same as that for a colorectal adenoma (4) </li></ul><ul><li>Higuchi T. and Jass J. R. believes that the increased risk of malignancy in association with multiple hyperplastic polyps may not be the result merely of the increased volume of target tissue, but that multiple polyps serve as a marker of a constitutional disturbance in DNA methylation homeostasis, as indicated by the association between DNA methylation in CRC and a positive family history of cancer. (4) </li></ul><ul><li>Genetic predisposition of DNA methylation may increase the likelihood of methylating a rate limiting gene, such as hMLH1. (4) </li></ul><ul><li>The finding of familial clusters of hyperplastic polyposis points to an underlying genetic predisposition to extensive and early onset of DNA methylation . (8) </li></ul>
  5. 5. Adenoma  Carcinoma <ul><li> APC K-RAS </li></ul><ul><li>Normal Dysplastic Early Intermediate </li></ul><ul><li>Colonic aberrant adenoma adenoma </li></ul><ul><li>Epithelium crypt foci </li></ul><ul><li>DCC </li></ul><ul><li> Other changes p53 </li></ul><ul><li>Metastasis Carcinoma Late adenoma </li></ul>
  6. 6. Possible pathways of neoplastic progression in HPS <ul><li>MSI-H MSI-H </li></ul><ul><li>dysplasia Cancer </li></ul><ul><li>Methylation </li></ul><ul><li>of hMLH1 </li></ul><ul><li>Hyperplastic ? </li></ul><ul><li>polyp </li></ul><ul><li>Normal </li></ul><ul><li>?MMR </li></ul><ul><li>defect </li></ul><ul><li>MSI-L MSI-L </li></ul><ul><li>dysplasia Cancer </li></ul><ul><li>Adenoma MSS </li></ul><ul><li>Cancer </li></ul><ul><li>Hyperplastic polyps may evolve through the mild mutator/suppressor pathway or the high </li></ul><ul><li>mutator pathway. MMR: mismatch repair. MSI-H: Microsatellite instability – high. MSI-L: Microsatellite </li></ul><ul><li>instability – low. MSS: microsatellite stable. (3) </li></ul>
  7. 7. Hyperplastic Polyposis  Serrated Adenomas <ul><li>Serrated High risk of </li></ul><ul><li>Adenoma CRC </li></ul><ul><li> BRAF </li></ul><ul><li> mutation </li></ul><ul><li>Hyperplastic Polyposis </li></ul><ul><li> KRAS </li></ul><ul><li> mutation </li></ul><ul><li>admixed HP/ Risk of </li></ul><ul><li>adenoma CRC </li></ul>
  8. 8. Hyperplasia  Carcinoma <ul><li>Dysregulation of methylation (normally meant to silence the promoter region and inactivation of the gene)  allows cell to escape from cell growth control and apoptosis </li></ul><ul><li>Wynter et. Al.’s findings lend support to the concept of a serrated pathway to CRC in which DNA methylation plays an important role in subjects with HPS, characterized by: </li></ul><ul><li>* CIMP-high status </li></ul><ul><li>* Methylation of hMLH1 </li></ul><ul><li>* Absence of K-ras mutation </li></ul><ul><li>* High-frequency of dysplasia (8) </li></ul>
  9. 9. Features Diagnosis of hyperplastic polyposis syndrome (HPS) is based on the finding of: <ul><li>at least 30 pan-colorectal hyperplastic polyps (4) </li></ul><ul><li>or </li></ul><ul><li>at least 5 hyperplastic polyps proximal to the sigmoid colon of </li></ul><ul><li>which at least 2 are > 10 mm in diameter (4) </li></ul><ul><li>or </li></ul><ul><li>any number of hyperplastic polyps in a patient who has a first </li></ul><ul><li>degree relative with hyperplastic polyposis (4) </li></ul>
  10. 10. Malignant potential of Hyperplastic polyps <ul><li>Hyperplastic polyps with malignant potential have been distinguished from </li></ul><ul><li>classic hyperplastic polyps on the basis of subtle microscopic features that </li></ul><ul><li>include: </li></ul><ul><li>Increased serration </li></ul><ul><li>Crypt dilatation </li></ul><ul><li>Horizontal crypts </li></ul><ul><li>Hypermucinous epithelium (4) </li></ul><ul><li>Other risk factors of increased malignancy: </li></ul><ul><li>Right sided hyperplastic polyps </li></ul><ul><li>Unusually large </li></ul><ul><li>Multiple </li></ul><ul><li>Include dysplastic subclones (mixed polyp) </li></ul><ul><li>Have features that have been associated with sessile serrated adenomas </li></ul><ul><li>Associated with coexisting adenomas (4) </li></ul>
  11. 11. Diagnostic Approach <ul><li>Record the presence of a right sided hyperplastic polyp with attention drawn to the increased potential of these lesions for future malignancy (4) </li></ul><ul><li>Multiple slices through large hyperplastic polyps should be taken to exclude the presence of dysplasia (4) </li></ul><ul><li>Highlight variant hyperplastic polyps with increased malignant potential in publications of basic and clinical research (4) </li></ul>
  12. 12. Management <ul><li>Worth monitoring if hyperplastic polyps are found in high-risk patients (positive family history of CRC) (5) </li></ul><ul><li>Clinicians should be made aware of the increased malignant potential of right sided hyperplastic polyps or sessile serrated adenomas (4) </li></ul><ul><li>Regular colonoscopy with polypectomy (14) </li></ul><ul><li>Prophylactic colectomy, as would be advocated in familial adenomatous polyposis, is probably not warranted in this condition unless a secondary carcinoma is detected (14) </li></ul><ul><li>Significant risk of cancer (40% associated with adenocarcinoma) (14) </li></ul>
  13. 13. References <ul><li>Hawkins N.J., Ward R.L. Sporadic Colorectal Cancers with Microsatellite Instability and their possible origin in Hyperplastic Polyps and Serrated Adenomas . Journal of the National Cancer Institute 2001;93:1307-1313. </li></ul><ul><li>Hawkins N.J., Gorman P., Tomlinson I.P.M., Bullpitt P., Ward R.L. Colorectal Carcinomas Arising in the Hyperplastic Polyposis Syndrome Progress through the Chromosomal Instability Pathway . American Journal of Pathology 2000;157:385-392. </li></ul><ul><li>Jass J.R. et. Al. Neoplastic progression occurs through mutator pathways in hyperplastic polyposis of the colorectum . Gut Online 2000;47:43-49. </li></ul><ul><li>Higuchi T., Jass J. R. My approach to serrated polyps of the colorectum . J. Clinical Pathology 2004;57:682-686. </li></ul><ul><li>Liljegren A. et. Al. Prevalence and incidence of hyperplastic polyps and adenomas in familial colorectal cancer: correlation between the two types of colon polyps . Gut Online 2003;52:1140-1147. </li></ul><ul><li>Vasen H.F.A. Clinical Diagnosis and Management of Hereditary Colorectal Cancer Syndromes . Journal of Clinical Oncology 2000;18:81-92. </li></ul><ul><li>Iion H. et. Al. DNA microsatellite instability in hyperplastic polyps, serrated adenomas, and mixed polyps: a mild mutator pathway for colorectal cancer? J. Clinical Pathology 1999;52:5-9. </li></ul><ul><li>Wynter C.V.A. et al. Methylation patterns define two types of hyperplastic polyp associated with colorectal cancer . Gut Online 2004;53:573-580. </li></ul><ul><li>Jeevaratnam P. et. Al. Familial Giant Hyperplastic Polyposis predisposing to Colorectal Cancer: A new hereditary bowel cancer syndrome . Journal of Pathology 1996;179:20-25. </li></ul>
  14. 14. <ul><li>Melato M. et. Al. Scarce Information ab.out the Risk of Cancer in Colorectal Hyperplastic Polyps and Polyposis . AJG 2001;96:2267-2268. </li></ul><ul><li>Jass J.R. Serrated Adenoma of the Colorectum: A Lesion with Teeth . American Journal of Pathology 2003;162:705-708. </li></ul><ul><li>Chan T.L. et. Al. BRAF and KRAS Mutations in Colorectal Hyperplastic Polyps and Serrated Adenomas . Cancer Research 2003;63:4878-4881. </li></ul><ul><li>Hardy R.G. et. Al. ABC of Colorectal Cancer: Molecular basis of risk factors. BMJ 2000;321:886-889. </li></ul><ul><li>Postgrad. Med. J. Hyperplastic polyposis coli associated with dysplasia. PMJ Online 2001;77:537-547. </li></ul>