Advertisement

Gastrointestinal Tract

  • Bruce R. Pawel
Chapter
Part of the Molecular Pathology Library book series (MPLB)

Abstract

Polyps and tumors of the pediatric gastrointestinal tract may have unique associations with developmental and syndromic disorders, the early recognition of which may be critical in clinical management. Recently modern molecular genetic techniques have been brought to bear on these entities, revolutionizing our ability to make more precise diagnoses, offering the opportunity for novel treatments. This chapter focuses on the main pathologic and molecular genetic features associated with pediatric gastrointestinal polyps and masses. Major entities covered in this chapter include gastrointestinal stromal tumor (GIST), juvenile polyposis, familial adenomatous polyposis (FAP), Peutz-Jeghers syndrome, Cronkhite-Canada syndrome, and PTEN hamartoma tumor syndrome. Each section includes discussion of the clinical presentation, pathology, and molecular genetic features of each entity.

Keywords

Polyposis Gastrointestinal stromal tumor (GIST) Familial adenomatous polyposis (FAP) Juvenile polyposis Peutz-Jeghers syndrome Cowden syndrome PTEN hamartoma syndrome Bannayan-Riley-Ruvalcaba syndrome Gardner’s syndrome 

References

  1. 1.
    Goldblum JR. Gastrointestinal stromal tumors: a review of characteristic morphologic, immunohistochemical, and molecular genetic features. Am J Clin Pathol. 2002;117(Suppl 1):S49–61.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Fletcher CD, Berman JJ, Corless C, Gorstein F, Lasota J, Longley BJ, et al. Diagnosis of gastrointestinal stromal tumors: a consensus approach. Hum Pathol. 2002;33(5):459–65.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Sandberg AA, Bridge JA. Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors. Gastrointestinal stromal tumors. Cancer Genet Cytogenet. 2002;135(1):1–22.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Pappo AS, Janeway K, Laquaglia M, Kim SY. Special considerations in pediatric gastrointestinal tumors. J Surg Oncol. 2011;104(8):928–32.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Zhang L, Smyrk TC, Young WF Jr, Stratakis CA, Carney JA. Gastric stromal tumors in carney triad are different clinically, pathologically, and behaviorally from sporadic gastric gastrointestinal stromal tumors: findings in 104 cases. Am J Surg Pathol. 2010;34(1):53–64.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Rink L, Godwin AK. Clinical and molecular characteristics of gastrointestinal stromal tumors in the pediatric and young adult population. Curr Oncol Rep. 2009;11(4):314–21.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Agaram NP, Laquaglia MP, Ustun B, Guo T, Wong GC, Socci ND, et al. Molecular characterization of pediatric gastrointestinal stromal tumors. Clin Cancer Res. 2008;14(10):3204–15.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Miettinen M, Lasota J, Sobin LH. Gastrointestinal stromal tumors of the stomach in children and young adults: a clinicopathologic, immunohistochemical, and molecular genetic study of 44 cases with long-term follow-up and review of the literature. Am J Surg Pathol. 2005;29(10):1373–81.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Pappo AS, Janeway KA. Pediatric gastrointestinal stromal tumors. Hematol Oncol Clin North Am. 2009;23(1):15–34, vii.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Miettinen M, Lasota J. Histopathology of gastrointestinal stromal tumor. J Surg Oncol. 2011;104(8):865–73.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Boikos SA, Stratakis CA. The genetic landscape of gastrointestinal stromal tumor lacking KIT and PDGFRA mutations. Endocrine. 2014;47(2):401–8.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Miettinen M, Sobin LH, Sarlomo-Rikala M. Immunohistochemical spectrum of GISTs at different sites and their differential diagnosis with a reference to CD117 (KIT). Mod Pathol. 2000;13(10):1134–42.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Kelly L, Bryan K, Kim SY, Janeway KA, Killian JK, Schildhaus HU, et al. Post-transcriptional dysregulation by miRNAs is implicated in the pathogenesis of gastrointestinal stromal tumor [GIST]. PLoS One. 2013;8(5):e64102.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Smithey BE, Pappo AS, Hill DA. C-kit expression in pediatric solid tumors: a comparative immunohistochemical study. Am J Surg Pathol. 2002;26(4):486–92.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Gill AJ, Chou A, Vilain R, Clarkson A, Lui M, Jin R, et al. Immunohistochemistry for SDHB divides gastrointestinal stromal tumors (GISTs) into 2 distinct types. Am J Surg Pathol. 2010;34(5):636–44.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Guller U, Tarantino I, Cerny T, Schmied BM, Warschkow R. Population-based SEER trend analysis of overall and cancer-specific survival in 5138 patients with gastrointestinal stromal tumor. BMC Cancer. 2015;15:557.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Reichardt P, Demetri GD, Gelderblom H, Rutkowski P, Im SA, Gupta S, et al. Correlation of KIT and PDGFRA mutational status with clinical benefit in patients with gastrointestinal stromal tumor treated with sunitinib in a worldwide treatment-use trial. BMC Cancer. 2016;16:22.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Antonescu CR, DeMatteo RP. CCR 20th anniversary commentary: a genetic mechanism of imatinib resistance in gastrointestinal stromal tumor-where are we a decade later? Clin Cancer Res. 2015;21(15):3363–5.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Janeway KA, Liegl B, Harlow A, Le C, Perez-Atayde A, Kozakewich H, et al. Pediatric KIT wild-type and platelet-derived growth factor receptor alpha-wild-type gastrointestinal stromal tumors share KIT activation but not mechanisms of genetic progression with adult gastrointestinal stromal tumors. Cancer Res. 2007;67(19):9084–8.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Oudijk L, Gaal J, Korpershoek E, van Nederveen FH, Kelly L, Schiavon G, et al. SDHA mutations in adult and pediatric wild-type gastrointestinal stromal tumors. Mod Pathol. 2013;26(3):456–63.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Lasota J, Wang Z, Kim SY, Helman L, Miettinen M. Expression of the receptor for type i insulin-like growth factor (IGF1R) in gastrointestinal stromal tumors: an immunohistochemical study of 1078 cases with diagnostic and therapeutic implications. Am J Surg Pathol. 2013;37(1):114–9.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Corredor J, Wambach J, Barnard J. Gastrointestinal polyps in children: advances in molecular genetics, diagnosis, and management. J Pediatr. 2001;138(5):621–8.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Gupta SK, Fitzgerald JF, Croffie JM, Chong SK, Pfefferkorn MC, Davis MM, et al. Experience with juvenile polyps in North American children: the need for pancolonoscopy. Am J Gastroenterol. 2001;96(6):1695–7.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Gammon A, Jasperson K, Kohlmann W, Burt RW. Hamartomatous polyposis syndromes. Best Pract Res Clin Gastroenterol. 2009;23(2):219–31.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Ma C, Giardiello FM, Montgomery EA. Upper tract juvenile polyps in juvenile polyposis patients: dysplasia and malignancy are associated with foveolar, intestinal, and pyloric differentiation. Am J Surg Pathol. 2014;38(12):1618–26.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Grotsky HW, Rickert RR, Smith WD, Newsome JF. Familial juvenile polyposis coli. A clinical and pathologic study of a large kindred. Gastroenterology. 1982;82(3):494–501.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Pashankar D, Murphy JJ, Ostry A, Schreiber RA. Life-threatening gastrointestinal hemorrhage due to juvenile polyposis. Am J Gastroenterol. 2000;95(2):543–5.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Desai DC, Murday V, Phillips RK, Neale KF, Milla P, Hodgson SV. A survey of phenotypic features in juvenile polyposis. J Med Genet. 1998;35(6):476–81.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Inoue S, Matsumoto T, Iida M, Hoshika K, Shimizu M, Hisamoto N, et al. Juvenile polyposis occurring in hereditary hemorrhagic telangiectasia. Am J Med Sci. 1999;317(1):59–62.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Woodford-Richens K, Bevan S, Churchman M, Dowling B, Jones D, Norbury CG, et al. Analysis of genetic and phenotypic heterogeneity in juvenile polyposis. Gut. 2000;46(5):656–60.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Coburn MC, Pricolo VE, DeLuca FG, Bland KI. Malignant potential in intestinal juvenile polyposis syndromes. Ann Surg Oncol. 1995;2(5):386–91.CrossRefPubMedGoogle Scholar
  32. 32.
    Bentley E, Chandrasoma P, Radin R, Cohen H. Generalized juvenile polyposis with carcinoma. Am J Gastroenterol. 1989;84(11):1456–9.PubMedGoogle Scholar
  33. 33.
    Wu TT, Rezai B, Rashid A, Luce MC, Cayouette MC, Kim C, et al. Genetic alterations and epithelial dysplasia in juvenile polyposis syndrome and sporadic juvenile polyps. Am J Pathol. 1997;150(3):939–47.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Coffin CM, Pappin AL. Polyps and neoplasms of the gastrointestinal tract in childhood and adolescence. In: Dahms BB, Qualman SJ, editors. Perspectives in pediatric pathology, vol. 20. Basel: Karger; 1997. p. 127–71.Google Scholar
  35. 35.
    Groisman GM, Benkov KJ, Adsay V, Dische MR. Osseous metaplasia in benign colorectal polyps. Arch Pathol Lab Med. 1994;118(1):64–5.PubMedGoogle Scholar
  36. 36.
    Pham BN, Villanueva RP. Ganglioneuromatous proliferation associated with juvenile polyposis coli. Arch Pathol Lab Med. 1989;113(1):91–4.PubMedPubMedCentralGoogle Scholar
  37. 37.
    van Hattem WA, Brosens LA, de Leng WW, Morsink FH, Lens S, Carvalho R, et al. Large genomic deletions of SMAD4, BMPR1A and PTEN in juvenile polyposis. Gut. 2008;57(5):623–7.CrossRefPubMedGoogle Scholar
  38. 38.
    Giardiello FM, Offerhaus JG. Phenotype and cancer risk of various polyposis syndromes. Eur J Cancer. 1995;31A(7–8):1085–7.CrossRefPubMedGoogle Scholar
  39. 39.
    Coffin CM, Dehner LP. What is a juvenile polyp? An analysis based on 21 patients with solitary and multiple polyps. Arch Pathol Lab Med. 1996;120(11):1032–8.PubMedGoogle Scholar
  40. 40.
    Roth S, Sistonen P, Salovaara R, Hemminki A, Loukola A, Johansson M, et al. SMAD genes in juvenile polyposis. Genes Chromosomes Cancer. 1999;26(1):54–61.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Howe JR, Bair JL, Sayed MG, Anderson ME, Mitros FA, Petersen GM, et al. Germline mutations of the gene encoding bone morphogenetic protein receptor 1A in juvenile polyposis. Nat Genet. 2001;28(2):184–7.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Friedl W, Uhlhaas S, Schulmann K, Stolte M, Loff S, Back W, et al. Juvenile polyposis: massive gastric polyposis is more common in MADH4 mutation carriers than in BMPR1A mutation carriers. Hum Genet. 2002;111(1):108–11.CrossRefPubMedGoogle Scholar
  43. 43.
    Aytac E, Sulu B, Heald B, O’Malley M, LaGuardia L, Remzi FH, et al. Genotype-defined cancer risk in juvenile polyposis syndrome. Br J Surg. 2015;102(1):114–8.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Langeveld D, van Hattem WA, de Leng WW, Morsink FH, Ten Kate FJ, Giardiello FM, et al. SMAD4 immunohistochemistry reflects genetic status in juvenile polyposis syndrome. Clin Cancer Res. 2010;16(16):4126–34.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Sweet K, Willis J, Zhou XP, Gallione C, Sawada T, Alhopuro P, et al. Molecular classification of patients with unexplained hamartomatous and hyperplastic polyposis. JAMA. 2005;294(19):2465–73.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Howe JR, Haidle JL, Lal G, Bair J, Song C, Pechman B, et al. ENG mutations in MADH4/BMPR1A mutation negative patients with juvenile polyposis. Clin Genet. 2007;71(1):91–2.CrossRefPubMedGoogle Scholar
  47. 47.
    Lucci-Cordisco E, Risio M, Venesio T, Genuardi M. The growing complexity of the intestinal polyposis syndromes. Am J Med Genet A. 2013;161A(11):2777–87.CrossRefPubMedGoogle Scholar
  48. 48.
    Gallione CJ, Repetto GM, Legius E, Rustgi AK, Schelley SL, Tejpar S, et al. A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4). Lancet. 2004;363(9412):852–9.CrossRefPubMedGoogle Scholar
  49. 49.
    Gallione CJ, Richards JA, Letteboer TG, Rushlow D, Prigoda NL, Leedom TP, et al. SMAD4 mutations found in unselected HHT patients. J Med Genet. 2006;43(10):793–7.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    O’Malley M, LaGuardia L, Kalady MF, Parambil J, Heald B, Eng C, et al. The prevalence of hereditary hemorrhagic telangiectasia in juvenile polyposis syndrome. Dis Colon Rectum. 2012;55(8):886–92.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Schwenter F, Ratjen F, Berk T, Gallinger S, Gryfe R, Gradinger AB, et al. Juvenile polyposis syndrome, SMAD4 mutations, and hereditary hemorrhagic telangiectasia. J Pediatr Gastroenterol Nutr. 2012;54(1):120–2.CrossRefPubMedGoogle Scholar
  52. 52.
    Wain KE, Ellingson MS, McDonald J, Gammon A, Roberts M, Pichurin P, et al. Appreciating the broad clinical features of SMAD4 mutation carriers: a multicenter chart review. Genet Med. 2014;16(8):588–93.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Delnatte C, Sanlaville D, Mougenot JF, Vermeesch JR, Houdayer C, Blois MC, et al. Contiguous gene deletion within chromosome arm 10q is associated with juvenile polyposis of infancy, reflecting cooperation between the BMPR1A and PTEN tumor-suppressor genes. Am J Hum Genet. 2006;78(6):1066–74.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Burt RW. Screening and survival in familial adenomatous polyposis. J Clin Gastroenterol. 2016;50(1):3–4.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Fearnhead NS, Britton MP, Bodmer WF. The ABC of APC. Hum Mol Genet. 2001;10(7):721–33.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Winter HS. Intestinal polyps. In: Walker WA, Durie PR, Hamilton JR, Walker-Smith JA, Watkins JB, editors. Pediatric gastrointestinal disease. 3rd ed. Hamilton: B. C. Decker Inc.; 2000. p. 796–809.Google Scholar
  57. 57.
    Goedde TA, Rodriguez-Bigas MA, Herrera L, Petrelli NJ. Gastroduodenal polyps in familial adenomatous polyposis. Surg Oncol. 1992;1(5):357–61.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Attard TM, Yardley JH, Cuffari C. Gastric polyps in pediatrics: an 18-year hospital-based analysis. Am J Gastroenterol. 2002;97(2):298–301.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Giardiello FM, Hamilton SR, Krush AJ, Offerhaus JA, Booker SV, Petersen GM. Nasopharyngeal angiofibroma in patients with familial adenomatous polyposis. Gastroenterology. 1993;105(5):1550–2.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Lotfi AM, Dozois RR, Gordon H, Hruska LS, Weiland LH, Carryer PW, et al. Mesenteric fibromatosis complicating familial adenomatous polyposis: predisposing factors and results of treatment. Int J Color Dis. 1989;4(1):30–6.CrossRefGoogle Scholar
  61. 61.
    de Chadarevian JP, Dunn S, Malatack JJ, Ganguly A, Blecker U, Punnett HH. Chromosome rearrangement with no apparent gene mutation in familial adenomatous polyposis and hepatocellular neoplasia. Pediatr Dev Pathol. 2002;5(1):69–75.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Clark SK, Pack K, Pritchard J, Hodgson SV. Familial adenomatous polyposis presenting with childhood desmoids. Lancet. 1997;349(9050):471–2.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Coffin CM. Gardner fibroma. In: Fletcher CD, editor. WHO classification of tumours of soft tissue and bone. Lyon: IARC; 2013.Google Scholar
  64. 64.
    Eichenberger P, Hammer B, Gloor F, Pelloni S, Bossart R. Gardner’s syndrome with glandular cysts of the fundic mucosa. Endoscopy. 1980;12(2):63–7.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW, et al. ACG clinical guideline: genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015;110(2):223–62.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Alkhouri N, Franciosi JP, Mamula P. Familial adenomatous polyposis in children and adolescents. J Pediatr Gastroenterol Nutr. 2010;51(6):727–32.CrossRefPubMedGoogle Scholar
  67. 67.
    Attard TM, Giardiello FM, Argani P, Cuffari C. Fundic gland polyposis with high-grade dysplasia in a child with attenuated familial adenomatous polyposis and familial gastric cancer. J Pediatr Gastroenterol Nutr. 2001;32(2):215–8.CrossRefPubMedGoogle Scholar
  68. 68.
    Novelli M. The pathology of hereditary polyposis syndromes. Histopathology. 2015;66(1):78–87.CrossRefPubMedGoogle Scholar
  69. 69.
    Vasudevan SA, Patel JC, Wesson DE, Plon SE, Finegold MJ, Nuchtern JG. Severe dysplasia in children with familial adenomatous polyposis: rare or simply overlooked? J Pediatr Surg. 2006;41(4):658–61.CrossRefPubMedGoogle Scholar
  70. 70.
    Arnason T, Liang WY, Alfaro E, Kelly P, Chung DC, Odze RD, et al. Morphology and natural history of familial adenomatous polyposis-associated dysplastic fundic gland polyps. Histopathology. 2014;65(3):353–62.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Wood LD, Salaria SN, Cruise MW, Giardiello FM, Montgomery EA. Upper GI tract lesions in familial adenomatous polyposis (FAP): enrichment of pyloric gland adenomas and other gastric and duodenal neoplasms. Am J Surg Pathol. 2014;38(3):389–93.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Foulkes WD. A tale of four syndromes: familial adenomatous polyposis, Gardner syndrome, attenuated APC and Turcot syndrome. QJM. 1995;88(12):853–63.PubMedPubMedCentralGoogle Scholar
  73. 73.
    Macrae F, du Sart D, Nasioulas S. Familial adenomatous polyposis. Best Pract Res Clin Gastroenterol. 2009;23(2):197–207.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Hernegger GS, Moore HG, Guillem JG. Attenuated familial adenomatous polyposis: an evolving and poorly understood entity. Dis Colon Rectum. 2002;45(1):127–34.CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Goss KH, Groden J. Biology of the adenomatous polyposis coli tumor suppressor. J Clin Oncol. 2000;18(9):1967–79.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Brosens LA, Offerhaus GJ, Giardiello FM. Hereditary colorectal cancer: genetics and screening. Surg Clin North Am. 2015;95(5):1067–80.CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    McGarrity TJ, Kulin HE, Zaino RJ. Peutz-Jeghers syndrome. Am J Gastroenterol. 2000;95(3):596–604.CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Buck JL, Harned RK, Lichtenstein JE, Sobin LH. Peutz-Jeghers syndrome. Radiographics. 1992;12(2):365–78.CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Shepherd NA, Bussey HJ, Jass JR. Epithelial misplacement in Peutz-Jeghers polyps. A diagnostic pitfall. Am J Surg Pathol. 1987;11(10):743–9.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Harned RK, Buck JL, Sobin LH. The hamartomatous polyposis syndromes: clinical and radiologic features. AJR Am J Roentgenol. 1995;164(3):565–71.CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Howell J, Pringle K, Kirschner B, Burrington JD. Peutz-Jeghers polyps causing colocolic intussusception in infancy. J Pediatr Surg. 1981;16(1):82–4.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Giardiello FM, Brensinger JD, Tersmette AC, Goodman SN, Petersen GM, Booker SV, et al. Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology. 2000;119(6):1447–53.CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    van Lier MG, Westerman AM, Wagner A, Looman CW, Wilson JH, de Rooij FW, et al. High cancer risk and increased mortality in patients with Peutz-Jeghers syndrome. Gut. 2011;60(2):141–7.CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Matuchansky C, Babin P, Coutrot S, Druart F, Barbier J, Maire P. Peutz-Jeghers syndrome with metastasizing carcinoma arising from a jejunal hamartoma. Gastroenterology. 1979;77(6):1311–5.PubMedPubMedCentralGoogle Scholar
  85. 85.
    Narita T, Eto T, Ito T. Peutz-Jeghers syndrome with adenomas and adenocarcinomas in colonic polyps. Am J Surg Pathol. 1987;11(1):76–81.CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Flageole H, Raptis S, Trudel JL, Lough JO. Progression toward malignancy of hamartomas in a patient with Peutz-Jeghers syndrome: case report and literature review. Can J Surg. 1994;37(3):231–6.PubMedPubMedCentralGoogle Scholar
  87. 87.
    Avendano-Garcia M, Mercado U, Marin ME. A case of Peutz-Jeghers syndrome associated with duodenal carcinoma and sickle cell anemia. Am J Gastroenterol. 2002;97(3):762–3.CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Estrada R, Spjut HJ. Hamartomatous polyps in Peutz-Jeghers syndrome. A light-, histochemical, and electron-microscopic study. Am J Surg Pathol. 1983;7(8):747–54.CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Shaco-Levy R, Jasperson KW, Martin K, Samadder NJ, Burt RW, Ying J, et al. Morphologic characterization of hamartomatous gastrointestinal polyps in Cowden syndrome, Peutz-Jeghers syndrome, and juvenile polyposis syndrome. Hum Pathol. 2016;49:39–48.CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Bronner MP. Gastrointestinal inherited polyposis syndromes. Mod Pathol. 2003;16(4):359–65.CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Hemminki A. The molecular basis and clinical aspects of Peutz-Jeghers syndrome. Cell Mol Life Sci. 1999;55(5):735–50.CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Aretz S, Stienen D, Uhlhaas S, Loff S, Back W, Pagenstecher C, et al. High proportion of large genomic STK11 deletions in Peutz-Jeghers syndrome. Hum Mutat. 2005;26(6):513–9.CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Slavik T, Montgomery EA. Cronkhite-Canada syndrome six decades on: the many faces of an enigmatic disease. J Clin Pathol. 2014;67(10):891–7.CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Burke AP, Sobin LH. The pathology of Cronkhite-Canada polyps. A comparison to juvenile polyposis. Am J Surg Pathol. 1989;13(11):940–6.CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Kucukaydin M, Patiroglu TE, Okur H, Icer M. Infantile Cronkhite-Canada syndrome? Case report. Eur J Pediatr Surg. 1992;2(5):295–7.CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Scharf GM, Becker JH, Laage NJ. Juvenile gastrointestinal polyposis or the infantile Cronkhite-Canada syndrome. J Pediatr Surg. 1986;21(11):953–4.CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    Bettington M, Brown IS, Kumarasinghe MP, de Boer B, Bettington A, Rosty C. The challenging diagnosis of Cronkhite-Canada syndrome in the upper gastrointestinal tract: a series of 7 cases with clinical follow-up. Am J Surg Pathol. 2014;38(2):215–23.CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Hobert JA, Eng C. PTEN hamartoma tumor syndrome: an overview. Genet Med. 2009;11(10):687–94.CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Parisi MA, Dinulos MB, Leppig KA, Sybert VP, Eng C, Hudgins L. The spectrum and evolution of phenotypic findings in PTEN mutation positive cases of Bannayan-Riley-Ruvalcaba syndrome. J Med Genet. 2001;38(1):52–8.CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Cohen MM Jr. Proteus syndrome review: molecular, clinical, and pathologic features. Clin Genet. 2014;85(2):111–9.CrossRefPubMedPubMedCentralGoogle Scholar
  101. 101.
    Mester J, Charis E. PTEN hamartoma tumor syndrome. Handb Clin Neurol. 2015;132:129–37.CrossRefPubMedPubMedCentralGoogle Scholar
  102. 102.
    Stanich PP, Owens VL, Sweetser S, Khambatta S, Smyrk TC, Richardson RL, et al. Colonic polyposis and neoplasia in Cowden syndrome. Mayo Clin Proc. 2011;86(6):489–92.CrossRefPubMedPubMedCentralGoogle Scholar
  103. 103.
    Pilarski R, Stephens JA, Noss R, Fisher JL, Prior TW. Predicting PTEN mutations: an evaluation of Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome clinical features. J Med Genet. 2011;48(8):505–12.CrossRefPubMedPubMedCentralGoogle Scholar
  104. 104.
    Hobert JA, Embacher R, Mester JL, Frazier TW 2nd, Eng C. Biochemical screening and PTEN mutation analysis in individuals with autism spectrum disorders and macrocephaly. Eur J Hum Genet. 2014;22(2):273–6.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Anatomic Pathology, Department of Pathology and Laboratory MedicineThe Children’s Hospital of Philadelphia and the Perelman School of Medicine, University of PennsylvaniaPhiladelphiaUSA

Personalised recommendations