A 36-year-old woman was referred for the evaluation and treatment of a periampullary mass found on esophagogastroduodenoscopy (EGD) performed at a local clinic with the chief complaint of postprandial epigastric pain (Fig. 1). A physical examination revealed café-au-lait spots and multiple cutaneous neurofibromas over the trunk, and she had a familial history of similar cutaneous lesions in the first-degree relatives (father, sister, and daughter). She met the diagnostic criteria of NF1.6 Laboratory analysis showed no abnormal findings, including the levels of serum CEA and CA 19-9. Abdominal CT and MRI revealed a 1.4 cm well-marginated lesion in the periampullary duodenum showing peripheral enhancement in the arterial phase and homogeneous enhancement in the delayed phase as well as another 1.6×1.3 cm mass in the duodenojejunal junction with intense homogeneous enhancement (Fig. 2). Several round lymph nodes, 1.2 cm in size, at the maximum were found around the celiac axis and mesenteric root. An endoscopic biopsy performed at the local clinic revealed a well-differentiated NET. The patient underwent a pylorous-preserving pancreatoduodenectomy for the purpose of a wide regional resection and lymph node dissection. Intraoperatively, several firm and enlarged lymph nodes were found and dissected widely. The surgical specimen (Fig. 3) contained an approximately 1.5 cm-sized luminal protruding ampullary mass and another 1.6 cm sized palpable submucosal mass at the proximal jejunum. Microscopically, the jejunal submucosal mass was GIST and its mitotic figures were not observed (Fig. 4A). Immunohistochemical staining was positive for c-Kit, CD34 and synaptophysin, and CD56. The S100 stain was negative. A histopathological examination of the periampullary mass revealed a well-differentiated neuroendocrine carcinoma (Fig. 4B) without lymphovascular or perineural invasion. All the resection margins were free of invasion, but nine out of 17 lymph nodes harvested from the celiac axis and root of the superior mesenteric artery and vein were positive for invasion. The patient's postoperative recovery was uneventful and she was discharged 18 days after surgery. Three months after surgery, PET-CT revealed a focal hypermetabolic lesion at the upper central abdomen around the greater omentum. This suggested a postoperative change in the greater omentum, but the possibility of early recurrence could not be excluded. Therefore, adjuvant chemotherapy, consisting of etoposide and cisplatin over a period of 9 weeks (3 cycles), was initiated. She remains well and has been in continuous remission since her surgery in June, 2010.

A 55-year-old man with known NF1 was admitted to the authors' institute for a duodenal mass that was detected incidentally by EGD performed for a health-care survey. Abdomen CT and MRI revealed an approximately 2 cm sized, well-defined enhancing mass, in the medial wall of the duodenal 2nd portion. No lymphadenopathy or local infiltrations were found. The results of the routine laboratory tests were all within the normal limits. EGD showed a protruding mass with superficial erosion at the site of the suprapapillar area. A biopsy of the mass was done and the reported histopathology was chronic duodenitis. A pancreatoduodenectomy was performed under the suspicion of a malignant tumor depending on its configuration. Intraoperatively, several small nodules were palpated in the duodenal 4th portion and jejunum, in addition to the known periampullary mass. The surgical specimen showed a 3×3 cm-sized hard mass over the ampula of Vater (Fig. 5A) as well as multiple nodules in the submucosal layer of the duodenum and proximal jejunum (Fig. 5B). Histopathological analysis showed that the ampullary mass was a well-differentiated neuroendocrine carcinoma invading the pancreas that was positive for lymph node invasion (Fig. 5D). Among the 11 lymph nodes harvested, four nodes placed at the head of the pancreas were positive. In addition, multiple submucosal masses located at the duodenum and jejunum were found to be GIST with a low risk (Fig. 5C). All resection margins were negative for tumor cell invasion. Postoperatively, the patient recovered without complications, and was discharged at postoperative day 19. After surgery, the patient has had an ordinary quality of life and a regular follow-up using an abdominal CT scan has not shown any recurrence of the tumor for 10 years after surgery.

An 80-year-old woman visited the authors' hospital for an evaluation of a dilatation of the bile ducts detected by abdomen ultrasonography performed at a local clinic. Her first symptoms were general weakness and weight loss of 3 kg over a one-month period. A physical examination revealed multiple neurofibromas over the face, upper extremities, and trunk (Fig. 6D); her son had similar skin lesions. She was referred to the department of dermatology under the diagnosis of neurofibromatosis and underwent a skin biopsy, which confirmed NF1. Laboratory examinations showed that all the data were within the normal range, including the serum bilirubin level. Abdominal CT scans were obtained to exclude any neoplasm or lithiasis of the biliary tract. A 1.5 cm weakly enhanced mass was found at the ampulla of Vater and marked dilatation of the bile duct and pancreatic duct were observed (Fig. 6A). In addition, another 1.7 cm-sized mass was found between the pancreatic head and posterior to the duodenal 2nd portion (Fig. 6B). EGD showed a prominent papilla of Vater with ulceration (Fig. 6C). A biopsy was performed and histopathologic analysis revealed a NET, grade 1. Initially, a pancreatoduodenectomy was planned, but the patient preferred a less invasive procedure to a radical operation because of concerns of surgical complications. Transduodenal ampullectomy and separate tumorectomy of the retroduodenal area were performed. A histopathology evaluation revealed the ampullary mass to be well-differentiated NET, grade 1, without neurovascular or lymphatic invasion. Tumor-free margins were identified. The retroduodenal mass was identified as GIST with very low risk. The patient's postoperative course was uneventful and she was discharged after 14 days. Thirty-two months after surgery, there has been no evidence of tumor recurrence.