Skip to main content
Annals of Surgery logoLink to Annals of Surgery
. 1975 Oct;182(4):371–385. doi: 10.1097/00000658-197510000-00003

Ectopic apudocarcinomas and associated endocrine hyperplasias of the foregut.

S R Friesen, J E McGuigan
PMCID: PMC1343995  PMID: 241302

Abstract

Foregut endocrine polypeptide-secreting APUD cells (Amine-Precursor-Uptake and Decarboxylation), in their embryologic migration from neural crest to foregut may become "arrested" in the mesoderm or in other ectopic locations. They may become hyperplastic, adenomatous or malignant. Eight illustrative patients are reported. One patient had "pancreatic hyperparathyroidism" with hypercalcemic crises, pancreatic apudocarcinoma, normal parathyroids, biologically active parathormone, but inert immunochemically to the usual parathyroid antisera. Two had gastrin-secreting malignancies in the mesoderm. Remission after excision, but eventual recurrence of the syndrome due to islet cell hyperplasia required total gastrectomy. One patient had a gastric corpus apudocarcinoma found prospectively with hypergastrinemia which required excision of the tumor. One patient had acromegaly with hypergastrinemia and antral gastrinosis treated by pituitary irradiation, One patient had the antral or intermediary type of the Zollinger-Ellison syndrome with moderate hypergastrinemia, duodenal ulcer and antral gastrinosis, treated by vagotomy and antrectomy. One patient had hyperparathyroidism with antral gastrinosis, treated by parathyroidectomy. One patient had malignant Zollinger-Ellison syndrome and developed associated thyroid parafollicular cell hyperplasia and parathyroid chief cell hyperplasia, treated by total gastrectomy and multiple endocrine excisions. These investigative observations demonstrate ectopic loci and associated hyperplasias which support the concept of migration and bizarre potentiality of polypeptide-secreting cells of the foregut.

Full text

PDF
371

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ackerman N. B., Winer N. The differentiation of primary hyperparathyroidism from the hypercalcemia of malignancy. Ann Surg. 1975 Feb;181(2):226–231. doi: 10.1097/00000658-197502000-00018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arnaud C. D. Editorial: Parathyroid hormone: coming of age in clinical medicine. Am J Med. 1973 Nov;55(5):577–581. doi: 10.1016/0002-9343(73)90178-2. [DOI] [PubMed] [Google Scholar]
  3. CROCKER D. W., VEITH F. J. MESODERMAL TUMORS ASSOCIATED WITH HYPOGLYCEMIA: REVIEW OF LITERATURE AND REPORT OF A CASE. Ann Surg. 1965 Mar;161:418–427. doi: 10.1097/00000658-196503000-00016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Creutzfeldt W., Arnold R., Creutzfeldt C., Feurle G., Ketterer H. Gastrin and G-cells in the antral mucosa of patients with pernicious anaemia, acromegaly and hyperparathyroidism and in a Zollinger-Ellison tumour of the pancreas. Eur J Clin Invest. 1971 Sep;1(6):461–479. doi: 10.1111/j.1365-2362.1971.tb00558.x. [DOI] [PubMed] [Google Scholar]
  5. Creutzfeldt W., Arnold R., Creutzfeldt C., Track N. S. Pathomorphologic, biochemical, and diagnostic aspects of gastrinomas (Zollinger-Ellison syndrome). Hum Pathol. 1975 Jan;6(1):47–76. doi: 10.1016/s0046-8177(75)80109-2. [DOI] [PubMed] [Google Scholar]
  6. DeWys W. D., Stoll R., Au W. Y., Salisnjak M. M. Effects of streptozotocin on an islet cell carcinoma with hypercalcemia. Am J Med. 1973 Nov;55(5):671–676. doi: 10.1016/0002-9343(73)90190-3. [DOI] [PubMed] [Google Scholar]
  7. Dent R. I., James J. H., Want C. A., Deftos L. J., Talamo R., Fischer J. E. Hyperparathyroidism: gastric acid secretion and gastrin. Ann Surg. 1972 Sep;176(3):360–369. doi: 10.1097/00000658-197209000-00012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fox P. S., Hofmann J. W., Decosse J. J., Wilson S. D. The influence of total gastrectomy on survival in malignant Zollinger-Ellison tumors. Ann Surg. 1974 Oct;180(4):558–566. doi: 10.1097/00000658-197410000-00020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Friesen S. R., Bolinger R. E., Pearse A. G., McGuigan J. E. Serum gastrin levels in malignant Zollinger-Ellison Syndrome after total gastrectomy and hypophysectomy. Ann Surg. 1970 Sep;172(3):504–521. doi: 10.1097/00000658-197009000-00014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Friesen S. R., Hermreck A. S., Mantz F. A., Jr Glucagon, gastrin, and carcinoid tumors of the duodenum, pancreas, and stomach: polypeptide "apudomas" of the foregut. Am J Surg. 1974 Jan;127(1):90–101. doi: 10.1016/0002-9610(74)90017-8. [DOI] [PubMed] [Google Scholar]
  11. Friesen S. R., Schimke R. N., Pearse A. G. Genetic aspects of the Z-E syndrome: prospective studies in two kindred; antral gastrin cell hyperplasia. Ann Surg. 1972 Sep;176(3):370–383. doi: 10.1097/00000658-197209000-00013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. GOLDBERG M. F., TASHJIAN A. H., Jr, ORDER S. E., DAMMIN G. J. RENAL ADENOCARCINOMA CONTAINING A PARATHYROID HORMONE-LIKE SUBSTANCE AND ASSOCIATED WITH MARKED HYPERCALCEMIA. Am J Med. 1964 May;36:805–814. doi: 10.1016/0002-9343(64)90188-3. [DOI] [PubMed] [Google Scholar]
  13. GOODRICK W. I., DOCKERTY M. B. Zollinger Ellison syndromeassociated gastric tumor showing islet-cell features. Minn Med. 1963 Jul;46:634–639. [PubMed] [Google Scholar]
  14. Ganguli P. C., Cullen D. R., Irvine W. J. Radioimmunoassay of plasmagastrin in pernicious anaemia, achlorhydria without pernicious anaemia, hypochlorhydria, and in controls. Lancet. 1971 Jan 23;1(7691):155–158. doi: 10.1016/s0140-6736(71)91932-5. [DOI] [PubMed] [Google Scholar]
  15. Ganguli P. C., Polak J. M., Pearse A. G., Elder J. B., Hegarty M. Antral-gastrin-cell hyperplasia in peptic-ulcer disease. Lancet. 1974 Apr 6;1(7858):583–586. doi: 10.1016/s0140-6736(74)92647-6. [DOI] [PubMed] [Google Scholar]
  16. Harrison T. S., Child C. G., Fry W. J., Floyd J. C., Jr, Fajans S. S. Current surgical management of functioning islet cell tumors of the pancreas. Ann Surg. 1973 Oct;178(4):485–495. doi: 10.1097/00000658-197310000-00011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jones B. S., O'Hagan J. J., Phear D. N., Sheville E. A case of the Zollinger-Ellison syndrome associated with hyperplasia of salivary and Brunner's glands. Gut. 1970 Oct;11(10):837–839. doi: 10.1136/gut.11.10.837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Larsson L. I., Ljungberg O., Sundler F., Håkanson R., Svensson S. O., Rehfeld J., Stadil R., Holst J. Antor-pyloric gastrinoma associated with pancreatic nesidioblastosis and proliferation of islets. Virchows Arch A Pathol Pathol Anat. 1973;360(4):305–314. doi: 10.1007/BF00548351. [DOI] [PubMed] [Google Scholar]
  19. Lukert B. P. Calcium and cancer. Hypercalcemia in malignancy simulating hyperparathyroidism. J Kans Med Soc. 1966 Jun;67(6):305–308. [PubMed] [Google Scholar]
  20. MARKOWITZ A. M., SLANETZ C. A., Jr, FRANTZ V. K. Functioning islet cell tumors of the pancreas. 25-year follow up. Ann Surg. 1961 Dec;154:877–884. [PMC free article] [PubMed] [Google Scholar]
  21. MILLER D. R., BOLINGER R. E., JANIGAN D., CROCKETT J. E., FRIESEN S. R. Hypoglycemia due to nonpancreatic mesodermal tumors: report of two cases. Ann Surg. 1959 Oct;150:684–696. doi: 10.1097/00000658-195910000-00012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. McGuigan J. E., Greider M. H. Correlative immuncchemical and light microscopic studies of the gastrin cell of the antral mucosa. Gastroenterology. 1971 Feb;60(2):223–236. [PubMed] [Google Scholar]
  23. McGuigan J. E., Trudeau W. L. Serum gastrin concentrations in pernicious anemia. N Engl J Med. 1970 Feb 12;282(7):358–361. doi: 10.1056/NEJM197002122820703. [DOI] [PubMed] [Google Scholar]
  24. McGuigan J. E., Trudeau W. L. Serum gastrin levels before and after vagotomy and pyloroplasty or vagotomy and antrectomy. N Engl J Med. 1972 Jan 27;286(4):184–188. doi: 10.1056/NEJM197201272860404. [DOI] [PubMed] [Google Scholar]
  25. O'Neal L. W., Kipnis D. M., Luse S. A., Lacy P. E., Jarett L. Secretion of various endocrine substances by ACTH-secreting tumors--gastrin, melanotropin, norepinephrine, serotonin, parathormone, vasopressin, glucagon. Cancer. 1968 Jun;21(6):1219–1232. doi: 10.1002/1097-0142(196806)21:6<1219::aid-cncr2820210625>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
  26. OBERHELMAN H. A., Jr, NELSEN T. S., JOHNSON A. N., Jr, DRAGSTEDT L. R., 2nd Ulcerogenic tumors of the duodenum. Ann Surg. 1961 Feb;153:214–227. doi: 10.1097/00000658-196115320-00008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Palmieri G. M., Nordquist R. E., Omenn G. S. Immunochemical localization of parathyroid hormone in cancer tissue from patients with ectopic hyperparathyroidism. J Clin Invest. 1974 Jun;53(6):1726–1735. doi: 10.1172/JCI107724. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Pearse A. G., Polak J. M. Endocrine tumours of neural crest origin: neurolophomas, apudomas and the APUD concept. Med Biol. 1974 Feb;52(1):3–18. [PubMed] [Google Scholar]
  29. Pearse A. G., Polak J. M. Neural crest origin of the endocrine polypeptide (APUD) cells of the gastrointestinal tract and pancreas. Gut. 1971 Oct;12(10):783–788. doi: 10.1136/gut.12.10.783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Polak J. M., Bussolati G., Pearse A. G. Cytochemical, immunofluorescence and ultrastructural investigations on the antral G cells in hyperparathyroidism. Virchows Arch B Cell Pathol. 1971;9(3):187–197. doi: 10.1007/BF02894045. [DOI] [PubMed] [Google Scholar]
  31. Polak J. M., Stagg B., Pearse A. G. Two types of Zollinger-Ellison syndrome: immunofluorescent, cytochemical and ultrastructural studies of the antral and pancreatic gastrin cells in different clinical states. Gut. 1972 Jul;13(7):501–512. doi: 10.1136/gut.13.7.501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Powell D., Singer F. R., Murray T. M., Minkin C., Potts J. T., Jr Nonparathyroid humoral hypercalcemia in patients with neoplastic diseases. N Engl J Med. 1973 Jul 26;289(4):176–181. doi: 10.1056/NEJM197307262890403. [DOI] [PubMed] [Google Scholar]
  33. Raisz L. G. Prostaglandins and the hypercalcemia of cancer. N Engl J Med. 1973 Jul 26;289(4):214–215. doi: 10.1056/NEJM197307262890412. [DOI] [PubMed] [Google Scholar]
  34. Riggs B. L., Arnaud C. D., Reynolds J. C., Smith L. H. Immunologic differentiation of primary hyperparathyroidism from hyperparathyroidism due to nonparathyroid cancer. J Clin Invest. 1971 Oct;50(10):2079–2083. doi: 10.1172/JCI106701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Rosen S. W., Weintraub B. D. Ectopic production of the isolated alpha subunit of the glycoprotein hormones. A quantitative marker in certain cases of cancer. N Engl J Med. 1974 Jun 27;290(26):1441–1447. doi: 10.1056/NEJM197406272902601. [DOI] [PubMed] [Google Scholar]
  36. Royston C. M., Brew D. S., Garnham J. R., Stagg B. H., Polak J. The Zollinger-Ellison syndrome due to an infiltrating tumour of the stomach. Gut. 1972 Aug;13(8):638–642. doi: 10.1136/gut.13.8.638. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Schein P. S. Islet cell tumors: current concepts and management. Ann Intern Med. 1973 Aug;79(2):239–257. doi: 10.7326/0003-4819-79-2-239. [DOI] [PubMed] [Google Scholar]
  38. Stefanini P., Carboni M., Patrassi N., Basoli A. Hypoglycemia and insular hyperplasia: review of 148 cases. Ann Surg. 1974 Jul;180(1):130–135. doi: 10.1097/00000658-197407000-00020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Stremple J. F., Watson C. G. Serum calcium, serum gastrin, and gastric acid secretion before and after parathyroidectomy for hyperparathyroidism. Surgery. 1974 Jun;75(6):841–852. [PubMed] [Google Scholar]
  40. Unger R. H., Eisentraut A. M. Entero-insular axis. Arch Intern Med. 1969 Mar;123(3):261–266. [PubMed] [Google Scholar]
  41. Vance J. E., Stoll R. W., Kitabchi A. E., Williams R. H., Wood F. C., Jr Nesidioblastosis in familial endocrine adenomatosis. JAMA. 1969 Mar 3;207(9):1679–1682. [PubMed] [Google Scholar]
  42. WERMER P. Genetic aspects of adenomatosis of endocrine glands. Am J Med. 1954 Mar;16(3):363–371. doi: 10.1016/0002-9343(54)90353-8. [DOI] [PubMed] [Google Scholar]
  43. Weichert R., Reed R., Creech O., Jr Carcinoid-islet cell tumors of the duodenum. Ann Surg. 1967 May;165(5):660–669. doi: 10.1097/00000658-196705000-00002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. ZOLLINGER R. M., ELLISON E. H. Primary peptic ulcerations of the jejunum associated with islet cell tumors of the pancreas. Ann Surg. 1955 Oct;142(4):709-23; discussion, 724-8. [PMC free article] [PubMed] [Google Scholar]
  45. Zollinger R. M. Islet cell tumors of the pancreas and the alimentary tract. Am J Surg. 1975 Feb;129(2):102–110. doi: 10.1016/0002-9610(75)90284-6. [DOI] [PubMed] [Google Scholar]

Articles from Annals of Surgery are provided here courtesy of Lippincott, Williams, and Wilkins

RESOURCES