Although gastrinomas were previously reported to be located pre dominantly in the pancreas, recent series have shown that the duodenum (especially the first and the second part) is the most common location for both sporadic and MEN- 1 associated gastrinomas (50– 88% and 70– 100% of cases, respectively). In cases of pancreatic gastrinomas, the tumour is usually located (70%) in the pancreatic body/ tail. At surgery, 70– 85% of all gastrinomas are found in the so- called gastrinoma triangle, an anatomical area that is defined, superiorly by the confluence of the cystic and common bile duct; inferiorly by the junction of the second and third portions of the duodenum; and medially, by the junction of the neck and body of the pancreas. Rarely (10%), gastrinomas can be found in other abdominal (stomach, liver, bile duct, ovary) or extra- abdominal (heart, small lung cancer) sites.
At presentation, pancreatic gastrinomas are usually large lesions (mean size 3.8 cm), whereas the duodenal ones, especially those as sociated with MEN- 1, are small (1– 20 mm). The latter are usually multiple, while sporadic gastrinomas are predominantly (80%) solitary tumours.
Gastrinomas may metastasize to the liver, lymph nodes, and rarely to the bones. At presentation, the majority of patients have either localized (36%) or locally advanced disease with only lymph node metastases (29%). The development of metastases is independent of tumour size, as even small (<5 mm) duodenal gastrinomas may have a high malignant potential. However, liver metastases seem to be more common in pancreatic rather than duodenal gastrinomas (22– 35% vs. 0– 10%, respectively).
Gastrinomas share the same histopathological features with the other gastroenteropancreatic neuroendocrine tumours (Figure 1). Additionally, they predominantly express gastrin (Figure 2), and can produce other gastrointestinal peptides as well, such as insulin. However, such additional peptides are either not released in the systemic circulation or they are released in small quantities and thus, they are not usually of any clinical significance. Other neuroendocrine tumours may express gastrin, but they are not con sidered gastrinomas if clinical and biochemical features are lacking.
Fig1. Well- differentiated, grade 1, pancreatic gastrinoma.
Fig2. Gastrin immunostaining in the above patient with pancreatic gastrinoma.
According to the recent (2017) World Health Organization (WHO) for pancreatic neuroendocrine neoplasms, gastrinomas are divided into: (1) well- differentiated neuroendocrine tumours of grade(G) 1, G2, or G3; and (2) poorly differentiated neuroendocrine carcinomas (either small- cell or large- cell type) with high- grade (G3) malignant behaviour. Criteria for categorization of these tumours include general morphologic description, mitotic rate (two or more mitoses/ mm2), proliferation index (as assessed by nuclear Ki67 expression), tumour size, and evidence of invasion of blood vessels/ nerves/ adjacent organs. The majority of gastrinomas are well- differentiated neuroendocrine neoplasms.
In 2010, the European Neuroendocrine Tumour Society suggested the TNM system for staging of pancreatic neuroendocrine tumours, including gastrinomas, which also included a grading system based on mitotic rate and proliferation index. That grading system was updated in 2017, as part of the new WHO classification. The TNM system as well as, the 2017 grading system are summarized in Box 1 and Table 1.
Box1. TNM classification for neuroendocrine tumours of the pancreas
Table1. WHO 2017 Grading for pancreatic neuroendocrine neoplasms
