Endocrine tumors of the duodenum and upper jejunum. A study of 33 cases with clinico-pathological characteristics and hormone content.

Thirty duodenal and three upper-jejunal endocrine tumors are reported. Clinical manifestations included: a) the Zollinger-Ellison syndrome (10 cases); b) peptic ulcer disease in which hypergastrinemia was not documented (3 cases); c) cholestasis or cholelithiasis (4 cases); d) abdominal pain (4 cases); e) gastro-intestinal bleeding (1 case); f) celiac sprue (1 case). Ten further tumors were discovered incidentally, at autopsy or in pathological specimens after gastrectomy or duodenopan-createctomy. Histological pattern was trabecular in 19 cases, insular in 2 and mixed in ten cases. Two cases were typical ganglioneuromatous paragangliomas. All tumors were examined immunohistochemically. Twelve tumors contained gastrin, four somatostatin, six both of these peptides, one serotonin, two both gastrin and serotonin, and two tumors contained gastrin, serotonin and somatostatin. Ganglioneuromatous paragangliomas combined somatostatin and/or pancreatic polypeptide containing endocrine cells with protein-S100-positive Schwann cells. In four tumors no peptide or amine was demonstrated. Gastrin cell tumors (63.6% of our cases), both functionally active (gastrinomas) and clinically silent, predominated in the proximal duodenum, while somatostatin cell tumors (15.1%) and paragangliomas were mostly found in the periampullary region. Two tumors were classified as malignant on the basis of lymph node metastases, and both were jejunal gastrinomas associated with Zollinger-Ellison syndrome. Two somatostatin cell tumors had manifestations of von Recklinghausen's disease.

Duodenal somatostatinoma with psammoma bodies: an immunohistochemical and ultrastructural study.

We report a case of malignant somatostatinoma of the ampulla of Vater in a 38-year-old woman with diabetes and cholelithiasis. Immunohistochemistry showed that tumor cells contained only somatostatin and electron microscopy revealed D-type granules in their cytoplasm. Psammoma bodies were numerous and appeared to originate in the cytoplasm of somatostatin producing cells. A review of the literature reveals that somatostatinomas with psammoma bodies are found only in the duodenum and do not produce significant amounts of peptides other than somatostatin.

Ampullary somatostatinoma: psammomatous variant of gastrointestinal carcinoid tumor--an immunohistochemical and ultrastructural study. Report of a case and review of the literature.

A 28-year-old man presented with epigastric pain and obstructive jaundice associated with a histologically and immunologically unusual variant of carcinoid tumor involving the ampulla of Vater. The tumor contained abundant psammoma bodies and exhibited immunoreactivity only for somatostatin. Immunoperoxidase studies for insulin, glucagon, vasoactive intestinal peptide, calcitonin, serotonin, and ACTH had negative results. In contrast to most somatostatinomas of pancreatic origin, clinically this ampullary somatostatinoma was not accompanied by features of the somatostatinoma syndrome. A literature review of the clinical and hormonal features in reported cases of gastrointestinal and pancreatic somatostatinomas is presented.

Pancreatic somatostatinoma: abundance of somatostatin-28(1-12)-like immunoreactivity in tumor and plasma.

UNLABELLED: In the present study we characterized and compared the relative amounts of the different molecular forms of somatostatin-14 like immunoreactivity (S-14 LI) and of somatostatin-28(1-12) like immunoreactivity (S-28(1-12) LI) in extracts of tumor and peripheral plasma of a patient with a pancreatic somatostatinoma. Tissue and plasma were chromatographed on Sephadex G-50 columns equilibrated with 6 M urea. Immunoreactivity in the eluting fractions was assayed with two separate, region specific RIAs using antibodies R149 (S-14 LI) and S309 (S-28(1-12)LI). RIA R149 recognizes the 6-8 and 14 regions of the S-14 sequence and detects S-14, S-28, and prosomatostatin, an approximately 14,000 mol wt precursor for the two peptides. RIA S309 recognizes the 2-11 segment of S-28 and reacts with S-28, S-28(1-12), and higher mol wt S-28(1-12) LI but not S-14. Total tumor S-14 LI was 190 pmol/mg protein and consisted of three peaks of immunoreactivity of apparent 14,000 mol wt (14K S-14 LI), 3,200 mol wt (3.2K corresponding to S-28) and 1,600 mol wt (1.6K corresponding to S-14). The three peaks comprised, respectively, 7%, 57%, and 36% of total S-14 LI. Total tumor S-28(1-12) LI was 594 pmol/mg protein and eluted as four major peaks of immunoreactivity as follows: peak I (mol wt 15,000, 10% of total S-28(1-12) LI); peak II (mol wt 8,000, 20% of S-28(1-12) LI), peak III (corresponding to S-28, 19% of S-28(1-12) LI); peak IV (corresponding to S-28(1-12), approximately 50% of total S-28(1-12) LI). Total plasma concentration of S-14 LI was 714 pM, being made up of the three peaks found in tumor but in the following relative amounts (14K S-14 LI, 22%; 3.2K, 29%; 1.6 K, 49%). Plasma S-28(1-12) LI was 4 times higher (2879 pM) than S-14 LI and contained immunoreactivity corresponding to each of the four peaks found in the tumor. CONCLUSIONS: 1) The tumor and plasma concentrations of S-28(1-12) LI were greater than that of S-14 LI. 2) Both tumor and plasma S-14 LI and S-28 LI were heterogeneous and comprised species corresponding not only to S-14 but also S-28, S-28(1-12), prosomatostatin, and other higher mol wt forms of S-28.(ABSTRACT TRUNCATED AT 400 WORDS)

Psammomatous somatostatinomas of the duodenum.

The presence of psammoma bodies in carcinoid tumors of the gastrointestinal tract is a rare occurrence; it has also been reported to be associated with features of somatostatin production by the tumor cells. The morphologic features of three such tumors arising in the duodenum were studied by a combination of histochemical, immunocytochemical, and ultrastructural techniques in an effort to delineate their secretory profile and further subclassify them. All tumors showed a mixed architectural pattern with prominent areas of glandular differentiation. The psammoma bodies were almost exclusively located within the glandular lumina. In each instance, the majority of tumor cells showed histochemical and immunocytochemical features of somatostatin-containing cells, and one tumor studied ultrastructurally showed numerous large- and small-sized intracytoplasmic secretory granules, both of which contained somatostatin. In contrast to other endocrine tumors of the duodenum that frequently have a multihormonal secretory profile, psammomatous duodenal carcinoids are associated with the exclusive presence of somatostatin within tumor cells. While many more of such examples of this uncommon tumor need to be systematically investigated for their immunocytochemical and ultrastructural characteristics, duodenal somatostatinomas need to be included in the differential diagnosis of psammomatous tumors.

Human somatostatin I: sequence of the cDNA.

RNA has been isolated from a human pancreatic somatostatinoma and used to prepare a cDNA library. After prescreening, clones containing somatostatin I sequences were identified by hybridization with an anglerfish somatostatin I-cloned cDNA probe. From the nucleotide sequence of two of these clones, we have deduced an essentially full-length mRNA sequence, including the preprosomatostatin coding region, 105 nucleotides from the 5' untranslated region and the complete 150-nucleotide 3' untranslated region. The coding region predicts a 116-amino acid precursor protein (Mr, 12.727) that contains somatostatin-14 and -28 at its COOH terminus. The predicted amino acid sequence of human somatostatin-28 is identical to that of somatostatin-28 isolated from the porcine and ovine species. A comparison of the amino acid sequences of human and anglerfish preprosomatostatin I indicated that the COOH-terminal region encoding somatostatin-14 and the adjacent 6 amino acids are highly conserved, whereas the remainder of the molecule, including the signal peptide region, is more divergent. However, many of the amino acid differences found in the pro region of the human and anglerfish proteins are conservative changes. This suggests that the propeptides have a similar secondary structure, which in turn may imply a biological function for this region of the molecule.