Bernhard Stamm

Gastrinomas in the duodenums of patients with multiple endocrine neoplasia type 1 and the Zollinger-Ellison syndrome.

In patients with multiple endocrine neoplasia type 1 (MEN-1), gastrinomas are common and thought to occur predominantly in the pancreas. We describe eight patients with MEN-1 and hypergastrinemia (seven with the Zollinger-Ellison syndrome) in whom we searched for neuroendocrine tumors in the pancreas and duodenum. Tumors were found in the proximal duodenum in all eight patients: solitary tumors (diameter, 6 to 20 mm) in three patients and multiple microtumors (diameter, 2 to 6 mm) in the other five. Paraduodenal lymph-node metastases were detected in four patients. Immunocytochemical analysis revealed the presence of gastrin in all the duodenal tumors and in their lymph-node metastases. In contrast, no immunoreactivity for gastrin was present in the endocrine tumors found in the seven pancreatic specimens available for study, except for one tumor with scattered gastrin-positive cells. In four of the six patients whose duodenal gastrinomas were removed, serum gastrin levels returned to normal; in the other two patients gastrin concentrations decreased toward normal. We conclude that in patients with MEN-1 and the Zollinger-Ellison syndrome, gastrinomas occur in the duodenum, but the tumors may be so small that they escape detection.

Surgical pathology of gastrinoma. Site, size, multicentricity, association with multiple endocrine neoplasia type 1, and malignancy

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.

Pancreatic lesions and hormonal profile of pancreatic tumors in multiple endocrine neoplasia type I: an immunocytochemical study of nine patients

Pancreatic specimens of nine patients suffering from multiple endocrine neoplasia type I (MEN I) were investigated with regard to tumor frequency and growth pattern, islet hyperplasia and endocrine cell neoformation, immunocytochemical hormone profile of the tumors, and correlation to clinical symptoms. The majority of the 201 tumors were microadenomas (diameter <0.5 cm), which frequently displayed a trabecular growth pattern. Microadenomatosis was considered the most distinct feature of the MEN I pancreas. Additional larger tumors (diameter> 1.0 cm) were found in five patients. Whereas islet hyperplasia appears not to belong to the spectrum of the pancreatic lesions in MEN I, nesidioblastosis was occasionally observed. Immunocytochemical screening revealed that among hormone‐positive tumors (approximately 80% of the tumors), pancreatic polypeptide tumors (PPomas), glucagonomas, and insulinomas were the most frequent. The high incidence of PPomas in these pancreases probably accounts for the elevated serum PP levels found in many MEN I patients. Somatostatinomas, gastrinomas, vasoactive intestinal polypeptide tumors (VIPomas), and neurotensinomas were rare. Clinically overt hyperinsulinism, observed in two patients and associated with a large insulinoma, was cured by tumor resection. Eight of nine patients presented a Zollinger‐Ellisons syndrome (ZES), but only in two patients were gastrin‐producing tumors found. The source of gastrin in MEN I patients with a ZES, in whom no gastrinoma could be detected, remains unclear.

Duodenal and ampullary carcinoid tumors

Twelve duodenal carcinoid tumours are presented, 4 of them located in the ampulla. Symptoms included the Zollinger-Ellison syndrome (4 patients), the carcinoid syndrome (1 patient), mechanical obstruction (3 patients), bleeding (1 patient) and abdominal pain (1 patient). Two further tumours were detected by chance. Three patients with the Zollinger-Ellison syndrome had additional endocrine tumours characteristic of the MEN I syndrome. In 2 of them the duodenal carcinoids were of very small size and were multiple. They were observed in close proximity to focal areas of endocrine cell hyperplasia. Immunohistochemical investigations showed gastrin and somatostatin to be the predominant polypeptide hormones produced by these tumours. No somatostatinoma syndrome was encountered. In half of our cases additional production of insulin, VIP or even calcitonin in smaller amounts was found. Two of our patients had cutaneous manifestations of von Recklinghausens disease and in both of them the carcinoid was located in the ampulla. One of these patients also had a pheochromocytoma.

Acinar cell cystadenocarcinoma of the pancreas.

An unusual tumor of the pancreas occurred in a 42‐year‐old man who presented with a gradually enlarging abdominal mass and weight loss. The mass was a 2 kg/25 cm diameter encapsulated multicystic tumor closely attached to the body and tail of the pancreas. On light microscopy it showed a predominantly tubular architecture and ultrastructurally numerous zymogen granules could be demonstrated in the tumor cells. It is therefore presumed to be of acinar cell origin. This tumor has features similar to the so‐called acinar cell cystadenocarcinoma described in 1981 by Cantrell et al.1 Sixteen months after resection of the primary tumor a solitary liver metastasis was removed at a second operation.

Treatment of distal ulcerative colitis with beclomethasone enemas: High therapeutic efficacy without endocrine side effects

Sixteen patients with 18 attacks of distal ulcerative colitis were treated randomly with either 0.5 mg topically administered beclomethasone dipropionate (BDP) or 5 mg betamethasone phosphate (BMT). The effect of the steroid enemas on adrenocortical function was examined by ACTH tests, which were performed before and 20 days after treatment. At completion of the trial, a marked suppression of the adrenocortical function was found in seven of eight patients treated for nine attacks with BMT but not in any patients in the BDP group (P<0.01). The mean posttreatment basal and stimulated plasma cortisol levels in the BMT group were significantly lower as compared with the BDP group. The overall therapeutic response assessed by score systems was comparable in the two treatment groups. It is concluded that, in the topical treatment of ulcerative colitis, BDP is preferable to BMT because it exerts an equal anti-inflammatory action without affecting adrenocortical function.

Mucosal biopsy of vascular ectasia (angiodysplasia) of the large bowel detected during routine colonoscopic examination

Between 1975 and 1983, 9434 colonoscopic examinations were performed at the University Hospital of Zürich. Localized vascular ectasia was detected in 84 patients and there were 48 mucosal biopsies from 46 patients. From the total of 48 biopsies only 24 (50%) showed vascular anomalies. The most frequent lesion encountered was groups of thin‐walled dilated vessels in the lamina propria seen in 21 biopsies from 20 patients. These dilated vessels are not specific but in respect of age (median 69 years), location (predominantly in the caecum and the ascending colon) and frequent multiplicity, they are suggestive of angiodysplasia. Five of the 20 patients suffered from chronic anaemia due to haemorrhages. The three other positive biopsies (from two patients) revealed a tiny haemangioma in the sigmoid colon of a 28‐year‐old woman and a few large, thick‐walled probably malformed vessels in the mucosa of the caecum of a 17‐year‐old boy. Twenty‐four biopsies did not show any histologically significant vascular anomaly. Mucosal biopsy of vascular lesions detected during routine colonoscopic examination will, if positive, most frequently simply confirm the endoscopically diagnosed vascular ectasia and may in rare cases show or alert suspicion to vascular lesions other than angiodysplasia. Definitive morphological diagnosis will however only rarely be achieved by this method of investigation.

Coincidence of fundic glandular hyperplasia and carcinoma of the stomach

Eight patients with stomach cancer are described who had also a striking glandular hyperplasia of the fundic mucosa adjacent and remote from the tumor. Five of the eight patients were young women (30 to 37 years of age). The tumors were poorly differentiated carcinomas and six of the eight patients have died of their disease. None of the patients had clinical evidence of endocrine dysfunction including the Zollinger‐Ellison syndrome. Immunohistochemistry revealed cells with endocrine differentiation in five of eight tumors, and in two tumors gastrin producing cells were found. Five of seven patients showed increased numbers of antral G‐cells. In two patients numerous endocrine (chromogranin‐positive) cells were present in the fundic mucosa, specific products of which could not be identified with the antigens tested. No satisfactory explanation exists for this coincidence and its apparent predominance in young female patients. It may be that endocrine substances are responsible for this fundic hyperplasia and that they may also act as promotors of tumor growth.

Localization of proinsulin and insulin in human insulinoma: Preliminary immunohistochemical results

SummaryWe have carried out an immunohistochemical investigation of 15 human insulinomas applying monoclonal antibodies specifically recognizing proinsulin and insulin. Our results demonstrate that the epitopes unique to proinsulin and insulin can be detected with the respective monoclonal antibodies using the protein A-gold technique after routine formaldehyde fixation and paraffin embedding of the tissues. The immunostaining pattern for proinsulin and insulin in the insulinomas was different from the observed in B cells of pancreatic islets present in the adjacent normal pancreas. Furthermore, the pattern of immunostaining was found to vary from tumor to tumor. These findings strongly suggest the possibility of a disturbed proinsulin to insulin conversion in human insulinomas

Small pedunculated tubular adenoma of the colon with carcinoma restricted to the head, invasion of lymphatics and widespread metastases

The case of a 66 year old woman who died of metastatic adenocarcinoma is reported. The origin of the tumor was found at autopsy to be a focal carcinoma in the head of a small pedunculated tubular adenoma at the recto-sigmoidal junction. Nine similar case reports from the literature are briefly presented.