Seal Hwangbo, et al. oncogene. However the exon-21 hot spot was not mutated in either the tubular adenoma or adeno- carcinoma. DISCUSSION Neurofibromatosis (NF) is an autosomal dominant disorder affecting all three germinal layers. Therefore, it can involve any organ system. It is not a single entity, but rather a group of heterogeneous, multi-systemic neurocutaneous disorders involving both neuroectodermal and mesenchymal derivatives. NF1 affects the gastro- intestinal tract in up to 25% of patients, and stromal tumors have been reported as the most common lesion in gastrointestinal neurofibro- matosis.2,3 Epithelial tumors, including colonic, pancreatic, and small intestinal adenocarcinomas, have also been reported in NF.4,5 Generally, small bowel tumors represent only 1 - 5% of all gastrointestinal malignancies, which is strikingly considering that the small intestine accounts for 75% of the length and 90% of the mucosal surface area of the gastrointestinal tract. Small intestinal adenocarcinomas are extremely rare, and there is evidence that small bowel adenocarcinomas arise from pre-existing adenomas in the same manner that they do in the large bowel. Although there have been several reported cases of small bowel adenocarcinoma developing in NF,6,7 we could not find a case of two separated ileal adenocarcinomas which developed in the background of tubulo- villous adenoma. This finding lends support to the adenoma-carcinoma theory for small bowel adenocarcinoma in NF. Knowing the relationship between ganglion cells and NF, the presence of ganglion cells is frequently described in previous cases of intestinal neurofibromatosis.8-11 However, Chambonniere M-L8 mentioned ganglioneuro- matosis can be distinguished from neurofibro- matosis described in VRN which is characterized by interfasciculating spindle-cell bundles without associated proliferation of ganglion cells. There are two types of GNM defined by their degree of extension: 1) the pure mucosal form defined as nerve hyperplasia predominating in the intestinal mucosa associated with concomitant hyperplasia of the submucosal Meissner plexus; 2) the trans- Yonsei Med J Vol. 48, No. 6, 2007 mural form defined as transmural nerve hyper- plasia with predominant involvement of the myenteric Auerbach plexus. In our case, the ganglion cells were mainly noted in the mucosa and submucosa. However ganglia in the inter- muscular Auerbach plexus were hyperplastic and prominent. Therefore, we could not determine whether this case was purely mucosal, or transmural under Chambonniere's definition. We assert that an intermediate type should be established that combines the two known forms. In summary, we report for the first time a rare case of two separated ileal adenocarcinomas asso- ciated with tubulovillous adenoma and gang- lioneuromatosis in neurofibromatosis. REFERENCES 1. Korf BR. Malignancy in neurofibromatosis type 1. Oncologist 2000;5:477-85. 2. Joo M, Lee HK, Kim H, Kim MK, Chi JG. Multiple small intestinal stromal tumors associated with neurofibromatosis-1. Yonsei Med J 2004;45:564-7. 3. Hochberg FH, Dasilva AB, Galdabini J, Richardson EP Jr. Gastrointestinal involvement in von Recklinghausen's neurofibromatosis. Neurology 1974;24:1144-51. 4. Jones TJ, Marshall TL. Neurofibromatosis and small bowel adenocarcinoma: an unrecognized association. Gut 1987;28:1173-6. 5. Nelson AM. Small bowel adenocarcinoma associated with neurofibromatosis. Am J Gastroenterol 1982;77: 149-51. 6. Perzin KH, Bridge MF. Adenomas of the small intestine: a clinicopathologic review of 51 cases and a study of their relationship to carcinoma. Cancer 1981;48:799-819. 7. Sellner F. Investigations on the significance of the adenoma-carcinoma sequence in the small bowel. Cancer 1990;66:702-15. 8. Chambonniere ML, Porcheron J, Scoazec JY, Audigier JC, Mosnier JF. Intestinal ganglioneuromatosis diag- nosed in adult patients. Gastroenterol Clin Biol 2003;27: 219-24. 9. Shekitka KM, Sobin LH. Ganglioneuromas of the gastrointestinal tract. Relation to Von Recklinghausen disease and other multiple tumor syndromes. Am J Surg Pathol 1994;18:250-7. 10. Snover DC, Weigent CE, Sumner HW. Diffuse mucosal ganglioneuromatosis of the colon associated with adenocarcinoma. Am J Clin Pathol 1981;75:225-9. 11. Shousha S, Smith PA. Colonic ganglioneuroma. Report of a case in a patient with neurofibromatosis, multiple colonic adenomas and adenocarcinoma. Virchows Arch A Pathol Anat Histol 1981;392:105-9.