Correspondence Seung Sam Paik, Department of Pathology, College of Medicine, Hanyang University, 17 Haengdang-Dong, Seongdong-Ku, 133-792 Seoul, Korea. Email: email@example.com
Gastrinoma is one of the most symptomatic pancreatic endocrine tumors and is associated with recurrent gastric or duodenal ulcer and an induction of chronic gastric acid hypersecretion. This tumor is commonly involved within the gastrinoma triangle. Herein we report a peripancreatic lymph node gastrinoma in a 56-year-old man who was suffered from a recurrent duodenal or jejunal ulcer perforation. Octreotide scan detected a peripancreatic or periduodenal mass and the serum gastrin level was set in upper normal range (107.73 pg/mL). Whipple's procedure was performed. The resected specimen showed multiple duodenal ulcers, hypertrophic gastric body mucosa and an enlarged peripancreatic node, measured 1.5 × 1.0 cm in cross diameter. Microscopic examination revealed a single enlarged lymph node replaced by tumor cell nests with pale eosinophilic cytoplasm and ‘salt-and-pepper’ chromatin pattern. On immunohistochemical staining, the tumor cells were diffusely positive for chromogranin, synaptophysin, gastrin and focally positive for CD56. He was finally diagnosed as a primary lymph node gastrinoma. After operation, the patient revisited our hospital due to severe esophageal stricture and he underwent endoscopic esophagoplasty.
Gastrinoma is one of the most symptomatic pancreatic endocrine tumors and is associated with recurrent gastric or duodenal ulcer. Most gastrinomas are commonly located within a specific anatomical triangle, the so-called gastrinoma triangle, which is a region bounded by the cystic duct and common bile duct, second and third portions of the duodenum, and the head and body of the pancreas.1–3 Although the existence of primary lymph node gastrinoma is still controversial, lymph nodes have been considered to be a primary site of gastrinoma.4–7 Herein we present a rare case of peripancreatic lymph node gastrinoma with a recurrent duodenal and jejunal ulcer, hypertrophic gastropathy, and esophageal stricture in a 56-year-old man.
A 56-year-old man presented at our hospital with diarrhea, periumbilical pain and abdominal distension for 1 day. He had a history of primary closure due to a jejunal perforation 2 months ago. On routine physical examination, abdominal tenderness was noted. Laboratory examination revealed increased white blood cell count and slightly decreased sodium level. Abdominal computed tomography demonstrated a diffuse wall thickening of the duodenum and proximal jejunum with a large amount of free air in the retroperitoneal space.
Exploratory laparotomy was performed. A large volume of exudates were discovered in the peritoneal cavity and a severe fibrous adhesion around the duodenum. A perforation site was noted in the posterior aspect of the duodenal second portion. Primary closure, vagotomy and pyloroplasty were performed. An ancillary test for discovering the cause of multiple and recurrent ulcers demonstrated that the serum gastrin level was set in upper normal range (107.73 pg/mL; normal range, 0–108 pg/mL). An octreotide scan identified a focal radioactive uptake lesion in the mid-abdomen, suggesting a neuroendocrine tumor of the duodenal third portion without the evidence of other pancreatic mass (Fig. 1). Whipple's procedure was performed under the impression of a duodenal or pancreatic gastrinoma.
On gross examination, an enlarged peripancreatic lymph node, measuring 1.5 × 1.0 cm in diameter, was noted in the pancreatic head portion. The pancreas was unremarkable and the duodenum revealed multiple small ulcerations and a previous perforation site. The gastric mucosa showed a prominent hypertrophic change in the body portion. Histologically, the enlarged lymph node was nearly replaced by the tumor cells with a small rim of lymph node tissue at the margin. The tumor showed solid sheet or trabecular arrangement. The tumor cells had a moderately pale eosinophilic cytoplasm and ‘salt-and-pepper’ chromatin pattern with inconspicuous nucleoli. The tumor cells showed the diffuse positivity for chromogranin, synaptophysin, gastrin and focal positivity for CD56. The gastric mucosa showed a marked hyperplasia of secretory glandular component with the large increase in the number of parietal cells (Fig. 2). The serum gastrin level was dropped by 41.75 pg/mL after the operation. Follow-up serum gastrin level after 2 years was 17.39 pg/mL.
Three months later the patient revisited our hospital due to dysphagia for 3 days. The endoscopic examination revealed the intraluminal narrowing in the gastroesophageal junction. The mucosal surface was covered by white exudative materials, suggestive of reflux esophagitis with esophageal stricture. Upper gastrointestinal barium study revealed a long segmental benign-appearing distal esophageal stricture accompanied by a proximal luminal dilatation (Fig. 3). Esophageal ballooning dilation and stent insertion were performed.
Since the term “lymph node primary gastrinoma” was introduced by Arnold et al. in 1994, several clinical and pathological studies have supported and questioned the existence of primary lymph node gastrinoma.3,8 Although the incidence is rare, primary lymph node gastrinoma has been accepted by many authors as a well defined pathologic entity.1–8 The acceptance of primary gastrinoma of the lymph nodes is based on clinical post-resection eugastrinemia as well as the histological evidence of entrapped neuroendocrine cells in peripancreatic and duodenal lymh nodes during development.7,9,10
Herrmann et al.7 investigated prospectively 20 autopsy cases and identified a total of 417 lymph nodes within the gastrinoma triangle. Five of the 20 gastrinoma triangle cases showed strong reactive cells to the synatophysin antibody and cells that strongly positive with a gastrin antibody were seen in three cases. None of the axillary and inguinal lymph nodes contained neuroendocrine cells. They concluded that the results supported the hypothesis of neuroendocrine cells being locally trapped during embryologic development and the existence of primary nodal gastrinomas. Perrier et al.10 examined 1026 lymph nodes within the gastrinoma triangle from 106 Whipple resections. This study demonstrated that some cells in the gastrinoma triangle were strongly immunoreactive for neuroendocrine cell specific markers and these markers were all negative for the lymph nodes outside of the gastrinoma triangle. Based on these results, they concluded that primary gastrinoma in the peripancreatic lymph node is originated from these neuroendocrine cells.
Some studies have suggested the main criteria of primary lymph node gastrinoma as followed: (a) normalization of serum gastrin level after excision of lymph node gastrinoma; (b) continuous normalization of serum gastrin level without clinical symptoms during a long postoperative period; (c) no evidence of another primary tumor after explorative operation and exact pathologic examination; (d) no evidence of tumor relapse verified by all imaging techniques.2,11,12 In our case, the serum gastrin level of the patient was dropped rapidly after excision of the gastrinoma and there was no evidence of another primary tumor in the gastrinoma triangle, pancreas, duodenum or others. During the 2 years following the operation, there was no evidence of relapse of tumor on the serologic follow-up and imaging evaluation.
1. The chronic effects of gastric acid hypersecretion on the esophagus can result in important complications. Chronic acid hypersecretion increases the gastroesophageal reflux disease which can lead to not only the development of esophageal stricture but also the premalignant condition such as Barrett esophagus. Hoffmann et al.13 found that the patients with multiple endocrine neoplasia type 1 (MEN1) have the higher incidence of development of advanced esophageal disease in comparison with patients without MEN1. Especially, patients who have Zollinger–Ellison syndrome as a part of MEN1 have an increased risk of gastroesophageal reflux, leading to severe esophageal disease, such as esophageal stricture and Barrett's esophagus. Our case showed severe distal esophageal stricture and he received an esophageal ballooning dilation and a stent insertion, however he did not have multiple endocrine neoplasia type 1.
In conclusion, we report an unusual patient with a primary lymph node gastrinoma, Zollinger–Ellison syndrome and severe esophageal stricture, who suffered from multiple duodenal and jejunal peptic ulcers with a recurrent perforation.