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Prognostic criteria in nonfunctioning pancreatic endocrine tumours

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Abstract

To identify prognostic subgroups among nonfunctioning (nonsyndromic) pancreatic endocrine tumours, a series of 61 tumours were analysed systematically for macroscopic, histopathological and immunohistochemical variables potentially predictive of malignancy. High-grade nuclear atypia, elevated mitotic rate and multifocal necrosis allowed us to separate 5 poorly differentiated carcinomas from 56 well differentiated tumours. Among the latter, 29 well-differentiated carcinomas showing gross local invasion or metastases were identified. Vascular or perineural microinvasion, Ki67 proliferative index >2%, mitotic rate ≥2, size ≥4 cm, capsular penetration, nuclear atypia, lack of progesterone receptors and presence of calcitonin were among the variables correlated with malignancy. The first two were the most sensitive and specific. Their presence or absence was used in the 27 tumours lacking evidence of malignancy at the time of surgery to separate 11 cases with increased risk of malignancy (in 2 of which metastases developed during follow-up) from 16 cases with limited risk. The resulting four prognostic groups of nonfunctioning pancreatic endocrine tumours (limited- and increased-risk tumours, well-differentiated carcinomas and poorly differentiated carcinomas) showed distinct survival curves, which were significantly affected by vascular microinvasion, Ki67 proliferative index and metastases.

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References

  1. Abbona GC, Papotti M, Gasparri G, Bussolati G (1995) Proliferative activity in parathyroid tumors as detected by Ki67 immunostaining. Hum Pathol 26:135–138

    Google Scholar 

  2. Bonato M, Cerati M, Pagani A, Papotti M, Bosi F, Bussolati G, Capella C (1992) Differential diagnostic patterns of lung neuroendocrine tumors. A clinico-pathologic and immunohistochemical study of 122 cases. Virchows Arch [A] 420:201–211

    Google Scholar 

  3. Bordi C, Pilato FP, D'Adda T (1988) Comparative study of seven neuroendocrine markers in pancreatic endocrine tumors. Virchows Arch [A] 413:387–398

    Google Scholar 

  4. Broder LE, Carter SK (1973) Pancreatic islet cell carcinoma. Clinical features of 52 patients. Ann Intern Med 79:101–107

    Google Scholar 

  5. Broughan TA, Leslie JD, Soto JM, Herman RE (1986) Pancreatic islet cell tumors. Surgery 99:671–678

    Google Scholar 

  6. Capella C, Riva C, Rindi G, Sessa F, Usellini L, Chiaravalli AM, Carnevali L, Solcia E (1991) Histopathology, hormone products and clinico-pathologic profile of endocrine tumors of the upper small intestine: a study of 44 cases. Endocr Pathol 2:92–110

    Google Scholar 

  7. Capella C, Heitz PU, Höfler H, Solcia E, Klöppel G (1995) Revised classification of neuroendocrine tumors of the lung, pancreas and gut. Virchows Arch 425:547–560

    Google Scholar 

  8. Chejfec G, Falkmer S, Askensten U, Grimelius L, Gould VE (1988) Neuroendocrine tumors of the gastrointestinal tract. Pathol Res Pract 183:143–154

    Google Scholar 

  9. Costes V, Marthy-Anè C, Picot MC, Sure I, Rojol JL, Mary H, Baldet P (1995) Typical and atypical bronchopulmonary carcinoid tumors: a clinicopathologic and Ki67 labelling study. Hum Pathol 26:740–745

    Google Scholar 

  10. Donow C, Baisch H, Heitz PU, Klöppel G (1991) Nuclear DNA content in 27 pancreatic endocrine tumours: correlation with malignancy, survival and expression of glycoprotein hormone alpha chain. Virchows Arch [A] 419:463–468

    Google Scholar 

  11. Frantz VK (1940) Tumors of islet cells with hyperinsulinism: benign, malignant and questionable. Ann Surg 112:116–176

    Google Scholar 

  12. Goldblum JR, Shannon R, Kaldijian EP, Thiny M, Davenport R, Thompson N, Lloyd RV (1993) Immunohistochemical assessment of proliferative activity in adrenocortical neoplasms. Mod Pathol 6:663–668

    Google Scholar 

  13. Grimelius L, Hultquist GT, Stenkvist B (1975) Cytological differentiation of asymptomatic pancreatic islet cell tumours in autopsy material. Virchows Arch [A] 365:275–288

    Google Scholar 

  14. Heitz PU (1991) Pancreatic endocrine tumors. In: Klöppel G, Heitz PU (eds) Pancreatic pathology. Churchill Livingstone, Edinburgh, pp 206–232

    Google Scholar 

  15. Heitz PU, Kasper M, Polak JM, Klöppel G (1982) Pancreatic endocrine tumors: immunocytochemical analysis of 125 tumors. Hum Pathol 13:263–271

    Google Scholar 

  16. Heitz PU, Kasper M, Klöppel G, Polak JM, Vaitukaitis JL (1983) Glycoprotein-hormone alpha-chain production by pancreatic endocrine tumors: a specific marker for malignancy. Cancer 51:277–282

    Google Scholar 

  17. Höfler H, Ruhri C, Pütz B, Wirnsberger G, Hauser H (1988) Oncogene expression in endocrine pancreatic tumors. Virchows Arch [B] 55:355–361

    Google Scholar 

  18. Hsu SM, Raine L, Fanger H (1980) Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques. J Histochem Cytochem 25:577–580

    Google Scholar 

  19. Kahn R, Rosen SW, Weintraub BD, Fajans SS, Gorden P (1977) Ectopic production of chorionic gonadotropin and its subunits by islet cell tumors. N Engl J Med 297:565–569

    Google Scholar 

  20. Kenny BD, Sloan JM, Hamilton PW, Watt PCH, Johnston CF, Buchanan KD (1989) The role of morphometry in predicting prognosis in pancreatic islet cell tumors. Cancer 64:460–465

    Google Scholar 

  21. Kent RB, Van Heerden JA, Weiland LH (1981) Nonfunctioning islet cell tumors. Ann Surg 193:185–190

    Google Scholar 

  22. Kimura N, Miura W, Noshiro T, Miura Y, Ookuma T, Nagura H (1994) Ki67 is an indicator of progression of neuroendocrine tumors. Endocr Pathol 5:223–228

    Google Scholar 

  23. Kitz K, Knosp E, Koos WT, et al (1991) Proliferation of pituitary adenomas: measurement by Mab Ki-67. Acta Neurochir 53 [Suppl]:60–64

    Google Scholar 

  24. Klöppel G, Heitz PU (1988) Pancreatic endocrine tumors. Pathol Res Pract 183:155–168

    Google Scholar 

  25. Kramer A, Saeger W, Tallen G, Ludecke DK (1994) DNA measurement, proliferation markers and other factors in pituitary adenomas. Endocr Pathol 5:198–211

    Google Scholar 

  26. Landolt AM, Shibata T, Kleihues P (1987) Growth rate of human pituitary adenomas. J Neurosurg 67:803–806

    Google Scholar 

  27. La Rosa S, Sessa F, Bosi F, Fabbri A, Capella C (1995) Prognostic factors in nonfunctioning pancreatic endocrine tumors. Lab Invest 72:54A

    Google Scholar 

  28. Larsson LI (1978) Endocrine pancreatic tumors. Hum Pathol 401–416

  29. Liu T, Zhu Y, Cyi Q, Cui L, Ye S, Zhong S, Jia H (1992) Non-functioning pancreatic endocrine tumors. An immunohistochemical and electron microscopic analysis of 26 cases. Pathol Res Pract 188:191–198

    Google Scholar 

  30. Lopez-Krunger R, Dockerty MB (1947) Tumors of the islets of Langerhans. Surg Gynecol Obstet 85:495–511

    Google Scholar 

  31. McNicol AM, Colgan J, McMeekin W, Teasdale GM (1989) Nucleolar organizer regions in pituitary adenomas. Acta Neuropathol 77:547–549

    Google Scholar 

  32. Nairn ER, Crocker J, McGovern J (1988) Limited value of Ag-NOR enumeration in assessment of thyroid neoplasms. J Clin Pathol 41:1136

    Google Scholar 

  33. Pelosi G, Zamboni G, Doglioni C, Rodella S, Bresaola E, Iacono C, Serio G, Iannucci A, Scarpa A (1992) Immunodetection of proliferating cell nuclear antigen assesses the growth fraction and predicts malignancy in endocrine tumors of the pancreas. Am J Surg Pathol 16:1215–1225

    Google Scholar 

  34. Prinz RA, Badrinath R, Chejfec G, Freark RJ, Grenlee HB (1983) “Nonfunctioning” islet cell carcinoma of the pancreas. Am Surg 49:345–349

    Google Scholar 

  35. Reyes CV, Wang T (1981) Undifferentiated small cell carcinoma of the pancreas: a report of five cases. Cancer 47:2500–2502

    Google Scholar 

  36. Rindi G, Luinetti O, Cornaggia M, Capella C, Solcia E (1993) Three subtypes of gastric argyrophil carcinoid and the gastric neuroendocrine carcinoma: a clinicopathologic study. Gastroenterology 104:994–1006

    CAS  PubMed  Google Scholar 

  37. Rosai J, Carcangiu ML, DeLellis RA (1992) Tumors of the thyroid gland. Rosai J (ed) Atlas of tumor pathology, 3rd series, fasc 5. Armed Forces Institute of Pathology, Washington, DC

    Google Scholar 

  38. Rüschoff J, Willemer S, Brunzel M, Trautmann ME, Frank M, Arnold R, Klöppel G (1993) Nucleolar organizer regions and glycoprotein-hormone alpha-chain reaction as markers of malignancy in endocrine tumors of the pancreas. Histopathology 22:51–57

    Google Scholar 

  39. Ruttman E, Klöppel G, Bommer G, Kiehn M, Heitz PU (1980) Pancreatic glucagonoma with and without syndrome. Immunocytochemical study of 5 tumor cases and review of the literature. Virchows Arch [A] 388:51–67

    Google Scholar 

  40. Soga J, Tazawa K (1971) Pathologic analysis of carcinoids. Histologic revaluation of 62 cases. Cancer 28:990–998

    Google Scholar 

  41. Solcia E, Sessa F, Rindi G, Bonato M, Capella C (1991) Pancreatic endocrine tumors: general concepts; nonfunctioning tumors and tumors with uncommon function. In: Dayal Y (ed) Endocrine pathology of the gut and pancreas. CRC Press, Boca Raton, Fla, pp 105–131

    Google Scholar 

  42. Stamm B, Häcki WH, Klöppel G, Heitz PU (1991) Gastrin producing tumors and Zollinger-Ellison syndrome. In: Dayal Y (ed) Endocrine pathology of the gut and pancreas. CRC Press, Boca Raton, Fla, pp 155–194

    Google Scholar 

  43. Stefaneanu L, Horvath E, Kovacs K (1989) Argyrophil organizer region proteins (AGNORs) in adenohypophysial cells and adenomas of the human pituitary. Mod Pathol 2:192–199

    Google Scholar 

  44. Stefanini P, Carboni M, Patrassi N, Basoli A (1974) Beta-islet cell tumors of the pancreas. Results of a study on 1067 cases. Surgery 75:597–609

    Google Scholar 

  45. Strodel WE, Vinik AI, Lloyd RV, Glaser B, Eckhauser FE, Fiddian-Green RG, Turcotte JG, Thompson NW (1984) Pancreatic polypeptide-producing tumors. Silent lesions of the pancreas? Arch Surg 119:508–514

    Google Scholar 

  46. Van Heerden JA, Hay ID, Goellener JR, Salomao D, Ebersold JR, Bergstrahl EJ, Grant CS (1992) Follicular thyroid cercinoma with capsular invasion alone: a nonthreatening malignancy. Surgery 112:1130–1138

    Google Scholar 

  47. Viale G, Doglioni C, Gambacorta M, Zamboni G, Coggi G, Bordi C (1992) Progesterone receptors immunoreactivity in pancreatic endocrine tumors. Cancer 70:2268–2277

    Google Scholar 

  48. Vollmer RT (1996) Multivariate statistical analysis for pathologists. Am J Clin Pathol 105:115–126

    Google Scholar 

  49. Wilander E, El-Salhy M, Willen R, Grimelius L (1981) Immunohistochemistry and electron microscopy of an argentaffin endocrine tumour of the pancreas. Virchows Arch [A] 292:263–269

    Google Scholar 

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La Rosa, S., Capella, C., Sessa, F. et al. Prognostic criteria in nonfunctioning pancreatic endocrine tumours. Vichows Archiv A Pathol Anat 429, 323–333 (1996). https://doi.org/10.1007/BF00198436

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