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SECRETORY GRANULES IN BENIGN AND MALIGNANT GLUCAGONOMAS OF THE PANCREAS

Two cases of glucagonoma, one benign and the other malignant, were presented. Benign glucagonoma in a 29‐year old man with multiple endocrine neoplasia type 1 was composed largely of tumor cells with secretory granules ranging from 139 to 417 nm in diameter identical to A cell granules. There were a few tumor cells which contained no A cell granules but smaller granules of approximately 166 nm diameter similar to those of pancreatic polypeptide‐containing cells. Radioimmunoassay of the tumor extract showed 319 μg/g wet weight of glucagon and 0.72 μg/g wet weight of pancreatic polypeptide. Malignant glucagonoma in a 34 year‐old man was a massive tumor of 7x6x5 cm replacing the tail and body of the pancreas with multiple metastases. The tumor contained 0.2 μg/g wet weight of glucagon and 0.065, ug g wet weight of vasoactive intestinal peptide. The electron microscopic examination revealed that the tumor cells had variable numbers of atypical secretory granules measuring 110 to 200 nm in diameter different from A cell granules. An analysis of plasma glucagon by the gel filtration technique showed the heterogeneity of glucagon molecules indicating the presence of large glucagon. Atypical secretory granules in malignant glucagonoma were considered to represent immature granules containing the precursor or intermediate of glucagon.