Type III Gastric Neuroendocrine Tumor-a Case Report

1 Department of Gastroenterology, Emergency University Hospital, „Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania 2 3rd Department of Surgery, Emergency University Hospital, „Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania Corresponding author: Lucian NEGREANU, Department of Gastroenterology, Emergency University Hospital, „Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania. E-mail: negreanu_99@yahoo.com Abstract


INTRODUCTION
Neuroendocrine tumors (NETs) are rare, slowly growing neoplasms originating in the neuroendocrine cells. Th ey can occur anywhere in the body, but most commonly occur in the lungs, appendix, small intestine, rectum and pancreas 1 .
Gastrointestinal tract NETs account for 67% of NETs, the small bowel (especially the ileum) being the most frequent primary site, with an incidence of 42% within this group. Also, NETs account for 37% of all small bowel cancers 2 . Th eir clinical behavior can range from benign to malignant 3 . rate being 7 per 2 power fi elds. Out of 7 lymph nodes examined, 4 presented tumoral invasion. According to AJCC edition 8-it is a pT1 N1 stage.
Th e patient had an uneventful postoperative course.

DISCUSSION
Based on morphological characteristics there are four types of neuroendocrine tumors. Th e type I lesions correspond to the majority of gastrointestinal NETs found in the stomach (70-80%) and are associated with autoimmune chronic atrophic gastritis. Diagnosis of type I is made by upper gastrointestinal endoscopy with biopsy that reveals pale, yellowish and transparent blood vessels of the antral mucosa. Th e

CASE PRESENTATION
A 71 year old female presented with intense fatigue, weight loss and several episodes of melena. On physical exam, the abdomen was soft, non-distended, and painful in the epigastric area.
An esophagogastroduodenoscopy was performed using the Sonoscape 550 endoscope and the 4 LED processor, showing a polypoid ulcerated lesion with a large implantation base -approximately 7 cm in diameter, located medio-gastric on the great curvature. Multiple infra-centimetric polyps were spotted in the gastric corpus and the gastric mucosa appeared pale with visible vascularization of the submucosa. Multiple biopsies were taken (Figure 1).
A CT scan for evaluation was performed and showed a voluminous gastric tumor with distant metastasis located in the liver (segments 5 and 7) and also to the lymph nodes.
Th e patient was referred for surgery and underwent a subtotal gastrectomy with a gastro-entero-anastomosis, including a peri-gastric lymph node dissection (Figures 2 and 3).
Th e pathology exam revealed a polypoid mass with an 8 cm diameter, with a histological aspect of a type III neuroendocrine tumor, grade 2 according to the World Health Organization classifi cation, the mitotic   table imaging studies are essential in planning therapy and evaluating treatment response and the possible need for new approaches 14 . CT scan of the abdomen is recommended for type I and II gNETs larger than 2 cm and for all type III lesions. MRI of the abdomen, octreotide scintigraphy and PET-CT may be useful in specifi c cases 15 .
Th e treatment options depend on the type of tumor, its location and whether the patient is experiencing signs and symptoms of excess hormones produced by the tumor.
In general, treatment options might include chemotherapy, targeted drug therapy, peptide receptor radionuclide therapy (PRRT), medications to control excess hormones and radiation therapy, besides surgery 1 . If there is resectable metastatic disease, it should also be treated. For unresectable liver disease, local therapies such as arterial embolization or radio-ablation have a success rate of 50% 16 . For the carcinoid syndrome, symptom control is achieved using somatostatin analogs (octreotide or lanreotide) and low doses interferon alfa for refractory cases 17 .

CONCLUSION
Gastric NETs include 4 diff erent subtypes that have distinct pathogenesis and management, and need to be correctly diagnosed in order to be able to prescribe the correct course of treatment. Although our patient had a voluminous tumor, surgical resection was possible and chemotherapy was started with good evolution.
Compliance with ethics requirements: Th e authors declare no confl ict of interest regarding this article. Th e authors declare that all the procedures and experiments of this study respect the ethical standards in the Helsinki Declaration of 1975, as revised in 2008(5), as well as the national law. Informed consent was obtained from all the patients included in the study. neuroendocrine tumors are visualized as small, reddish polyps and often being multiple, with neuroendocrine cell hyperplasia on the histological examination. Anti-parietal cell and anti-intrinsic factor antibodies may also be present, and the gastric acidity dosage reveals high pH (pH>7) 4,5 .
Type II lesions are caused by gastrinomas. Similarly to type I, they are usually benign with a low risk of malignancy. Often they are associated with Zollinger Ellison syndrome and in most cases, the patient has multiple endocrine neoplasia type I 6 . Gastric biopsy reveals normal or hypertrophic gastric mucosa, associated with hypergastrinemia and hyperchlorhydria 7 . After confi rming the diagnosis, it is important to localize the gastrinoma and to remove it surgically, if possible 8 .
Type III lesions are sporadic lesions with the greatest potential to generate metastasis. Generally, the lesion is unique, larger than 1 cm and with normal gastrin levels. Th e largest type III mass described measures 10/7/7 cm, located adjacent to the gastroesophageal junction, in the gastric wall 9 . Diagnosis is made by upper gastrointestinal endoscopy with biopsy. Rarely, the carcinoid syndrome can be the initial clinical manifestation 10 .
Type IV consists of multiple small lesions, histology revealing hypertrophy and hyperplasia of parietal cells associated with achlorhydria and hypergastrinemia 11 .
Most g-NETs are found on endoscopic examinations and because type I and II commonly present as polypoid lesions, they are often amenable to endoscopic resection 12 . For type III and IV gNETs surgical gastric resection is recommended, due to their behavior that is very similar to gastric adenocarcinomas, with a high incidence of invasion beyond the submucosa and distant metastasis on presentation (50-100%) 13 .
Accurate tumor imaging is essential to planning the approach of management if patients with NETs. Surgical and endoscopic resection represents the only curative treatment methods. When the tumor is unresec-