Neuroendocrine tumor of the ampulla of Vater with distant cystic lymph node metastasis: a case report
Discussion
NETs of the ampulla of Vater are rare and difficult to diagnose [1, 2]. Jaundice (60 %) and abdominal pain (40 %) are the most frequent symptoms. Upper gastrointestinal bleeding is a rare presentation (3 %) [1, 10]. In our case, the patient presented with abdominal pain and melena. On admission, upper gastrointestinal endoscopy revealed a bulging papilla with active bleeding. When we performed gastric endoscopy again 7 days later, we found a 10-mm mass of the ampulla of Vater with a superficial ulcer.
Diagnosis of NETs is established by histological and immunohistochemical analysis of endoscopic biopsy specimens [11]. NETs of the ampulla of Vater usually appear as submucosal masses that are small and spherical with a smooth surface and an intact duodenal mucosa. Consequently, superficial biopsies are negative and deeper biopsies are required for a diagnosis [12, 13]. In our present case, we could get the biopsy specimen from the mass because it had an ulcerated surface. Thus, the correct diagnosis of a NET was established preoperatively. However, we could not diagnose the cyst adjacent to the wall of the jejunum as a lymph node metastasis at the time of resection.
Previous reports have suggested that the biological behavior of ampullary NETs is distinct from that of duodenal NETs and they are more aggressive [14]. Randle and colleagues reported that ampullary NETs were larger, higher grade, and higher stage and had a higher rate of lymph node metastasis than duodenal NETs [15]. The incidence of lymph node metastases in patients with resected ampullary NETs and duodenal NETs was 72.9 and 48.4 %, respectively.
In the case of ampullary NETs, even in tumors smaller than 2 cm, a high percentage have lymph node metastases [14, 16–18]. Nikou et al. reported that lymph node metastases were found in two cases of ampullary NET with tumor sizes of 1.0 and 1.2 cm, respectively [19]. In the present case, the histologic examination revealed metastasis to distant lymph nodes despite the tumor only being 9 mm in diameter and within duodenal mucosal layer. These findings suggest that there is no correlation between tumor size and metastatic potential in ampullary NETs. We consider that an anatomical reason is one of the reasons why NETs at the ampulla of Vater have high incidence of metastasis. Ampullary carcinoma with perisphincteric or duodenal submucosal invasion showed more frequent lymph node metastasis and a greater tumor recurrence rate than tumor limited within the sphincter of Oddi muscle [20]. Moreover, the perisphincteric and duodenal submucosal space is relatively small and closer to the next layering of duodenal proper muscle and the pancreas. Thus, the malignant potential of perisphincteric and/or duodenal submucosal invasion may be greater than that of other gastrointestinal tract tumors. Moreover, previous studies have reported that lymph node metastasis is difficult to detect on preoperative imaging [18, 21]. Although some authors report the existence of lymph node metastasis of NETs is not correlated with patient prognosis, this could be due to metastasis to the liver or some other organ, which is an important prognostic factor for NETs. Therefore, radical resection with lymph node dissection is recommended as a treatment of ampullary NETs regardless of tumor size [1, 14, 18, 22, 23].
We performed a pylorus-preserving pancreaticoduodenectomy with regional lymph node resection and also resected a 52-mm lymphatic metastasis adjacent to the wall of the jejunum. Despite the lymph node involvement, the Ki-67-labeling index was low (2 %) and the patient has had no evidence of recurrence for 4 years after surgery.
Randle et al. indicated that tumor size was correlated with poor prognosis, but the presence of positive lymph nodes was not a predictive outcome in resected ampullary NETs [15]. Untch et al. reported that only tumor size and tumor grade were associated with recurrence [24]. Thus, we can perform radical resection and completely remove the tumor with good clinical outcomes.