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Café-au-lait spots and early onset colorectal neoplasia: a variant of HNPCC?

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Abstract

Background: Café-au-lait spots (CALS) are classically found in neurocutaneous syndromes such as neurofibromatosis, but have not been associated with hereditary colorectal cancer. However, review of hereditary colorectal cancer case reports reveals occasional description of CALS on physical exam. Methods: We describe the colonic and extracolonic phenotype in a family with CALS and early onset colorectal neoplasia (adenomas and/or cancer) and review 23 additional families reported in the literature. Results: Among the 24 families, 32/59 (54.2%) individuals had colorectal adenomas diagnosed at a mean age of 15.7 ± 1.1 (SE) years (range 5–38 years). The majority (24/32, 75.0%) of persons at first colorectal examination had oligopolyposis (< 100 polyps) versus polyposis (≥ 100 polyps). Forty-two of 59 (71.2%) individuals were affected with colorectal cancer, diagnosed at a mean age of 31.9 ± 2.7 years (range 5–70 years). A brain tumor was found in 28/59 (47.5%) affected individuals (4 families with 2 or more cases) with an overall mean age of diagnosis of 16.5 ± 1.2. Lymphoma and/or leukemia was found in 8/24 (33.3%) families (one family with 3 cases). Two families had mutation of the mismatch repair gene, hPMS2 (1 with homozygous germline mutation), while two carried homozygous germline mutations of another mismatch repair gene, hMLH1. Conclusions: Café-au-lait spots with early onset colorectal neoplasia may identify families with a variant of HNPCC characterized by oligopolyposis, glioblastoma at young age, and lymphoma. This variant may be caused by homozygous mutation of the mismatch repair genes, such as hPMS2 or hMLH1.

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References

  1. Jones KL. Smith's Recognizable Patterns of Human Malformation, 5th edition. Philadelphia: W.B. Saunders Company, 1997.

    Google Scholar 

  2. Hamilton SR, Liu B, Parson RE et al. The molecular basis of Turcot's syndrome. New England Journal of Medicine 1995; 332: 839-47.

    Google Scholar 

  3. Watson P, Lynch HT. Extracolonic cancer in hereditary nonpolyposis colorectal cancer. Cancer 1993; 71: 677-85.

    Google Scholar 

  4. Vasen HFA, Offerhaus GJA, Den Hartog Jager FCA et al. The tumour spectrum in hereditary non-polyposis colorectal cancer: a study of 24 kindreds in the Netherlands. Int J Cancer 1990; 46: 31-4.

    Google Scholar 

  5. Schmutte, C; Fishel, R. Genomic instability: first step to carcinogenesis. Anticancer Research 1999; 19: 4665-96.

    Google Scholar 

  6. Modrich, P. Mismatch repair, genetic stability and tumour avoidance. Philos Trans R Soc Lond B Biol Sci 1995; 347: 89-95.

    Google Scholar 

  7. Leach FS, Nicolaides NC, Papadopoulos N et al. Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell 1993; 75: 1215-25.

    Google Scholar 

  8. Bronner CE, Baker SM, Morrison PT et al. Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary nonpolyposis colorectal cancer. Nature 1994; 368: 258-61.

    Google Scholar 

  9. Papadopoulos N, Nicolaides NC, Wei YF et al. Mutation of a mutL homolog in hereditary colon cancer. Science 1994; 263: 1625-9.

    Google Scholar 

  10. Akiyama Y, Sato H, Yamada T et al. Germ-line mutation of the hMSH6/GTPB gene in an atypical hereditary nonpolyposis colorectal cancer kindred. Cancer Research 1997; 57: 3920-3.

    Google Scholar 

  11. Nicolaides NC, Papadopoulos BL, Liu B et al. Mutation of two PMS homologues in hereditary nonpolyposis colorectal cancer. Nature 1994; 371: 75-80.

    Google Scholar 

  12. Shalon L, Markowitz J, Bialer M et al. Ovarian neoplasm and endometrioid carcinoma in a patient with Turcot syndrome. Journal of Pediatric Gastroenterology and Nutrition 1997; 25: 224-7.

    Google Scholar 

  13. Wang Q, Lasset C, Desseigne F et al. Neurofibromatosis and early onset of cancers in hMLH1-deficient children. Cancer Research 1999; 59: 294-7.

    Google Scholar 

  14. Ricciardone MD, Ozcelik T, Cevher B et al. Human MLH1 deficiency predisposes to hematological malignancy and neurofibromatosis type 1. Cancer Research 1999; 59: 290-3.

    Google Scholar 

  15. Pratt CB, Parham DM, Rao BN et al. Multiple colorectal carcinomas, polyposis coli, and neurofibromatosis. Journal of the National Cancer Institute 1988; 80: 1170-2.

    Google Scholar 

  16. Kaplan J, Cushing B, Chang C et al. Familial T-cell lymphoblastic lymphoma: association with Von Recklinghausen neurofibromatosis and Gardner syndrome. American Journal of Hematology 1982; 12: 247-50.

    Google Scholar 

  17. Everson RB, Fraumeni JF. Familial glioblastoma with hepatic focal nodular hyperplasia. Cancer 1976; 38: 310-3.

    Google Scholar 

  18. Itoh H, Ohsato K, Yao T et al. Turcot's syndrome and its mode of inheritance. Gut 1979; 20: 414-9.

    Google Scholar 

  19. Tithecott GA, Filler R, Sherman PM. Turcot's syndrome: a diagnostic consideration in a child with primary adenocarcinoma of the colon. Journal of Pediatric Surgery 1989; 24: 1189-91.

    Google Scholar 

  20. Latrive JP, Chaillet MP, Veyssier P, Vorhauer W. Syndrome de Turcot. Gastroenterol Clin Biol 1987; 7: 7-8.

    Google Scholar 

  21. Goldthorn JF, Powars D, Hays DM. Adenocarcinoma of the colon and rectum in the adolescent. Surgery 1983; 93: 409-13.

    Google Scholar 

  22. Jamjoom ZAB, Sadiq S, Mofti AB et al. Turcot syndrome: report of a case and review of the literature. Int Surg 1989; 74: 45-50.

    Google Scholar 

  23. Baughman FA, List CF, Williams JR et al. The Glioma-Polyposis Syndrome. The New England Journal of Medicine 1969; 24: 1345-6.

    Google Scholar 

  24. Kawanami K, Ohno M, Matsuura K, et al. Turcot's syndrome: report of an autopsy case. Stomach Intestine 1976; 11: 1075-82.

    Google Scholar 

  25. Radin DR, Fortgang KC, Zee CS et al. Turcot syndrome: a case with spinal cord and colonic neoplasms. AJR 1984; 142: 475-6.

    Google Scholar 

  26. Iriate G-BLM, Fernandez VA, Cruz GG, et al. Sindrome de Turcot. Dos nuevos casos en hermanos. An Esp Pediatr 1989; 30:223-224.

    Google Scholar 

  27. Pratt CB, Parham DM, Rao BN. Multiple colorectal carcinomas, polyposis coli, and neurofibromatosis. J Nat'l Cancer Inst 1988; 80: 1170-2.

    Google Scholar 

  28. Pratt CB, Jane JA. Multiple colorectal carcinomas, polyposis coli, and neurofibromatosis, followed by multiple glioblastoma multiforme. J Nat'l Cancer Inst 1991; 83: 880-1.

    Google Scholar 

  29. Vasen HFA, Tops C, van Berge Henegouwen G, et al. Turcot's syndrome. Evidence for a separate genetic entity. Int J Colorectal Dis 1991; 6: 232.

    Google Scholar 

  30. Tops CMJ, Vasen HFA, van Berge Henegouwen G et al. Genetic evidence that Turcot syndrome is not allelic to familial adenomatous polyposis. Am J Med Genet 1992; 43: 888-93.

    Google Scholar 

  31. Andre JM, Picard L, Barrucand D, Kissel P. Les manifestations neurologiques des polyposes digestives hereditairs. Rev Neurol 1973; 129: 325-38.

    Google Scholar 

  32. Munden PM, Sobol WM, Weingeist TA. Ocular findings in Turcot syndrome (glioma-polyposis). Ophthalmology 1991; 98: 111-4.

    Google Scholar 

  33. Kamiya J, Muto T, Morioka K et al. The Turcot syndrome. Report of a case. Stomach Intestine 1982; 17: 913-8.

    Google Scholar 

  34. Castello MA, Operamolla P, Clerico A et al. Nonfamilial intestinal polyposis and brain tumor in a 5-year-old girl. Pediatr Hematol Oncol 1987; 4: 247-60.

    Google Scholar 

  35. Arico M, Parigi GB, Locatelli D et al. Turcot's syndrome with intestinal lymphoma in a child: An unusual case of triple tumor. Med Pediatr Oncol 1990; 18: 252-5.

    Google Scholar 

  36. Korf BR. Diagnostic outcome in children with multiple café au lait spots. Pediatrics 1992; 90: 924-7.

    Google Scholar 

  37. Turcot J, Despres JP, St. Pierre F. Malignant tumors of the central nervous system associated with familial polyposis of the colon: report of two cases. Dis Colon Rectum 1959; 2: 465-8.

    Google Scholar 

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Authors and Affiliations

  1. Department of medicine, The John Hopkins Hereditary Colorectal Cancer Registry, 550 N. Broadway, Suite 108, Baltimore, MD, 21205-2011, USA

    Jill D. Trimbath

  2. Mayo Clinic, Rochester, Minnesota, USA

    Gloria M. Petersen

  3. Ohio State University, Columbus, Ohio, USA

    Steven H. Erdman

  4. Roanoke Community Hospital, Roanoke, Virginia, USA

    Merry Ferre

  5. Salt Lake City, Utah, USA

    Michael C. Luce

  6. Department of Medicine and Oncology Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Francis M. Giardiello

Authors
  1. Jill D. Trimbath
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  2. Gloria M. Petersen
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  4. Merry Ferre
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  5. Michael C. Luce
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  6. Francis M. Giardiello
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Trimbath, J.D., Petersen, G.M., Erdman, S.H. et al. Café-au-lait spots and early onset colorectal neoplasia: a variant of HNPCC?. Familial Cancer 1, 103–108 (2001). https://doi.org/10.1023/A:1013881832014

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