Do mast cells play a pathogenetic role in neurofibromatosis type 1 and ulcerative colitis?

Concurrent association of neurofibromatosis type I and ulcerative colitis has been reported in one clinical case (Tavakkoli et al., 2009). Although this association may represent a casual finding, a common pathophysiology is postulated. Mast cells have been implicated in the pathogenesis of both neurofibromatosis type 1 and ulcerative colitis (He, 2004; Yoshida et al., 2010). Mast cells are typically present in neurofibromas microenvironment where they appear to contribute to tumor initiation, progression and angiogenesis (Staser et al., 2010, 2013). Moreover, interaction of mast cells with nerves throughout the gastrointestinal tract has been correlated with progression and maintenance of ulcerative colitis (Stoyanova and Gulubova, 2002). We describe a 14 year-old male with history of neurofibromatosis type 1 and new onset of ulcerative colitis diagnosed on clinical and histological findings. On gross examination the entire colonic mucosa appeared edematous showing a peculiar granular pattern, with focal erythema, shallow ulcers and multiple sessile polyps. Hematoxylin and eosin stained tissue biopsies from the colonic mucosa showed chronic inflammatory bowel disease, severe activity, consistent with chronic ulcerative colitis. Immunohistochemistry stain of the intestinal lesions revealed high expression of Neuron Specific Enolase (NSE) and S100 highlighting the presence of a Schwann cell component. In addition, c-kit/CD117 positive stain indicated a marked increase of mast cells in the lamina propria. This pattern of cellularity in the lamina propria showing increased mast cells and augmented Schwann cell component was absent in the colonic mucosa of a normal control or a patient with ulcerative colitis alone. Our observation supports the evidence of a pathogenetic role of the mast cell in ulcerative colitis associated with neurofibromatosis type 1. Further investigations are warranted to confirm the significance of this correlation as it may impact therapeutic approaches of these pathologies.