Specimens from the pancreas and duodenum of 26 patients with sporadic Zollinger‐Ellison syndrome (ZES) and 18 patients with multiple endocrine neoplasia type 1 (MEN‐1) and hypergastrinemia (17 with ZES) were screened immunocytochemically for gastrinomas. Location, size, multicentricity, and malignancy of the gastrinomas were evaluated. The MEN‐1 patients had gastrinomas in the duodenum (nine of 18), pancreas (one of 18), and periduodenal lymph nodes (two of 18). No gastrinoma was identified in six patients. Most duodenal gastrinomas were multiple (five of nine) and smaller than 0.6 cm (six of nine). Lymph node metastases were present in eight of 12 patients. All 26 patients with sporadic ZES had a solitary gastrinoma; 14 were found in the pancreas and had a diameter greater than 2 cm. Ten patients had a duodenal gastrinoma, two with a diameter less than 0.6 cm. In two patients, only periduodenal “lymph node gastrinomas” were detected. Eighteen of the sporadic gastrinomas were malignant. These results suggest that duodenal location and multicentricity of gastrinomas are associated with the MEN‐1 syndrome, and solitary gastrinomas, either in the pancreas or the duodenum, are predominantly seen in sporadic ZES.

During the three decades since the recognition of the Zollinger-Ellison syndrome (ZES), major progress has been made in the diagnosis and treatment of this disease. However, the many failed operations in patients with ZES, the existence of primary lymph node gastrinomas, and the surgical approach of patients with ZES and multiple endocrine neoplasia type I (MEN-I) have remained controversial issues. In this review, our experience with the pathology of immunocytochemically identified gastrinomas in 44 patients with ZES is presented and related to the relevant literature. (1) Gastrinomas occur frequently in the duodenum (> 40%) and are commonly small (< 1 cm). They can therefore easily be missed at surgical exploration; lymph node metastases from such occult gastrinomas may be mistaken for primary tumors. (2) Most pancreatic gastrinomas reside in the head of the gland and have a diameter of 1 to 3 cm. (3) Gastrinomas associated with MEN-I are predominantly of duodenal origin and frequently multicentric; sporadic gastrinomas are single and more often pancreatic. Because MEN-I associated pancreatic tumors seldom contain gastrin, ZES in MEN-I patients is almost never cured by resection of the pancreatic tumors. (4) The metastatic potential of most small duodenal gastrinomas seems to be restricted to the regional lymph nodes.

Paraffin-embedded tissue from resection specimens of 14 functioning and 13 nonfunctioning pancreatic endocrine tumours (PET) was analysed for nuclear DNA content by image cytometry. Data on follow-up (mean 5.5 years) were available in all patients. DNA histograms with a diploid pattern were found in 13 (48%) tumours, while an aneuploid pattern was seen in the remaining 14 tumours (52%). Six (40%) of the diploid tumours and 9 (60%) of the aneuploid tumours were malignant. Survival was shorter in patients with malignant and aneuploid PET (mean 3.5 years, range 0.5-7) than in those with malignant and diploid PET (mean 5.7 years, range 3-8). Human chorionic gonadotropin-alpha was expressed in 3 of 12 benign PET, with 1 being aneuploid, and 6 of 15 malignant PET, with 4 being aneuploid. We conclude from these results that the ploidy pattern of PET allows no discrimination between benign and malignant tumours but may provide prognostic information on the aggressiveness of malignant PET.