Gastrointestinal manifestations of neurofibromatosis type 1 (Recklinghausen's disease): clinicopathological spectrum with pathogenetic considerations

Int J Clin Exp Pathol. 2012;5(9):852-62. Epub 2012 Oct 20.


Neurofibromatosis type 1 (NF-1, Recklinghausen disease) is the most common hereditary multitumor syndrome with an incidence at birth of approximately 1:3000. However, the significant variation in the expression of the disease not infrequently precludes early diagnosis. As a consequence of non-familiarity with their frequency and wide clinicopathological spectrum, gastrointestinal manifestations of NF-1 are seldom thought of in routine clinical practice and might thus be significantly under-recognized. Their heterogeneous spectrum ranges from localized microscopic proliferative lesions of autonomic nerves and interstitial cells of Cajal and diffuse microscopic ganglio/neuro/fibromatosis to grossly recognizable mass-forming neurofibromas and gastrointestinal stromal tumors (GIST). Furthermore, neuroendocrine neoplasms, particularly of the periampullary duodenum seem to be quite characteristic of this disease. Based on our own experience and the available literature, this review summarizes and discusses the clinicopathological spectrum of gastrointestinal manifestations of NF-1 including putative proliferative precursor lesions with emphasis on the differential diagnostic aspects of these disorders and their molecular pathogenesis. In addition, this review underlines the great value of specific gastrointestinal findings in uncovering undiagnosed or missed NF-1 cases.

Keywords: GIST; Gastrointestinal stromal tumor; NF-1; Neuroendocrine tumor; Neurofibromatosis; Recklinghausen disease.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Biopsy
  • DNA Mutational Analysis
  • Gastrointestinal Neoplasms / genetics
  • Gastrointestinal Neoplasms / pathology*
  • Gastrointestinal Stromal Tumors / genetics
  • Gastrointestinal Stromal Tumors / pathology*
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Neurofibromatosis 1 / genetics
  • Neurofibromatosis 1 / pathology*
  • Phenotype
  • Precancerous Conditions / genetics
  • Precancerous Conditions / pathology*
  • Predictive Value of Tests
  • Prognosis