Skip to main content
SpringerLink
Log in

Pathology: Premalignant and Malignant Diseases and Molecular Genetics

  • Chapter
  • First Online:
Current and Emerging Therapies in Pancreatic Cancer

  • 1026 Accesses

Abstract

The pathology chapter covers the surgical pathology and cytology of normal pancreas, as well as premalignant and malignant pancreatic processes. Brief radiological and macroscopic findings are presented, to correlate with the detailed microscopic findings. Several illustrative gross photos, microphotographs, and tables are included. Most common hereditary syndromes and their associated risks for pancreatic cancer are listed. Molecular genetics of the following entities are discussed and compared: pancreatic intraductal neoplasia (PanIN), pancreatic ductal adenocarcinoma, intraductal papillary mucinous neoplasm (IPMN), and pancreatic neuroendocrine neoplasms. A helpful table summarizing cystic fluid analysis features of various cystic pancreatic lesions is included. The most current pathologic grading and staging criteria are listed, including Baltimore consensus on grading of dysplasia in PanIN, IPMN, and mucinous cystic neoplasm (MCN) and AJCC eighth edition of pancreatic tumor staging.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30.

    Article  PubMed  Google Scholar 

  2. Matrisian LM, Berlin JD. The past, present, and future of pancreatic cancer clinical trials. Am Soc Clin Oncol Educ Book. 2016;35:e205–15.

    Article  PubMed  Google Scholar 

  3. Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74(11):2913–21.

    Article  CAS  PubMed  Google Scholar 

  4. Bosman FCF, Hruban R, Theise N. World health organization classification of tumours of the digestive system. 4th ed. Lyon: International Agency for Research on Cancer (IARC) Press; 2010. p. 279–337.

    Google Scholar 

  5. Adsay NV, Andea A, Basturk O, Kilinc N, Nassar H, Cheng JD. Secondary tumors of the pancreas: an analysis of a surgical and autopsy database and review of the literature. Virchows Arch. 2004;444(6):527–35.

    Article  PubMed  Google Scholar 

  6. Nakamura E, Shimizu M, Itoh T, Manabe T. Secondary tumors of the pancreas: clinicopathological study of 103 autopsy cases of Japanese patients. Pathol Int. 2001;51(9):686–90.

    Article  CAS  PubMed  Google Scholar 

  7. Andea A, Sarkar F, Adsay VN. Clinicopathological correlates of pancreatic intraepithelial neoplasia: a comparative analysis of 82 cases with and 152 cases without pancreatic ductal adenocarcinoma. Mod Pathol. 2003;16(10):996–1006.

    Article  PubMed  Google Scholar 

  8. Brune K, Abe T, Canto M, O'Malley L, Klein AP, Maitra A, Volkan Adsay N, Fishman EK, Cameron JL, Yeo CJ, et al. Multifocal neoplastic precursor lesions associated with lobular atrophy of the pancreas in patients having a strong family history of pancreatic cancer. Am J Surg Pathol. 2006;30(9):1067–76.

    PubMed  PubMed Central  Google Scholar 

  9. Basturk O, Hong SM, Wood LD, Adsay NV, Albores-Saavedra J, Biankin AV, Brosens LA, Fukushima N, Goggins M, Hruban RH, et al. A revised classification system and recommendations from the Baltimore consensus meeting for neoplastic precursor lesions in the pancreas. Am J Surg Pathol. 2015;39(12):1730–41.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Allen PJ, D'Angelica M, Gonen M, Jaques DP, Coit DG, Jarnagin WR, DeMatteo R, Fong Y, Blumgart LH, Brennan MF. A selective approach to the resection of cystic lesions of the pancreas: results from 539 consecutive patients. Ann Surg. 2006;244(4):572–82.

    PubMed  PubMed Central  Google Scholar 

  11. Brat DJ, Lillemoe KD, Yeo CJ, Warfield PB, Hruban RH. Progression of pancreatic intraductal neoplasias to infiltrating adenocarcinoma of the pancreas. Am J Surg Pathol. 1998;22(2):163–9.

    Article  CAS  PubMed  Google Scholar 

  12. McCarthy DM, Brat DJ, Wilentz RE, Yeo CJ, Cameron JL, Kern SE, Hruban RH. Pancreatic intraepithelial neoplasia and infiltrating adenocarcinoma: analysis of progression and recurrence by DPC4 immunohistochemical labeling. Hum Pathol. 2001;32(6):638–42.

    Article  CAS  PubMed  Google Scholar 

  13. Matthaei H, Schulick RD, Hruban RH, Maitra A. Cystic precursors to invasive pancreatic cancer. Nat Rev Gastroenterol Hepatol. 2011;8(3):141–50.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Lemoine NR, Jain S, Hughes CM, Staddon SL, Maillet B, Hall PA, Kloppel G. Ki-ras oncogene activation in preinvasive pancreatic cancer. Gastroenterology. 1992;102(1):230–6.

    Article  CAS  PubMed  Google Scholar 

  15. Moskaluk CA, Hruban RH, Kern SE. p16 and K-ras gene mutations in the intraductal precursors of human pancreatic adenocarcinoma. Cancer Res. 1997;57(11):2140–3.

    CAS  PubMed  Google Scholar 

  16. Ahlgren JD. Epidemiology and risk factors in pancreatic cancer. Semin Oncol. 1996;23(2):241–50.

    CAS  PubMed  Google Scholar 

  17. Cuzick J, Babiker AG. Pancreatic cancer, alcohol, diabetes mellitus and gall-bladder disease. Int J Cancer. 1989;43(3):415–21.

    Article  CAS  PubMed  Google Scholar 

  18. Ekbom A, McLaughlin JK, Karlsson BM, Nyren O, Gridley G, Adami HO, Fraumeni JF Jr. Pancreatitis and pancreatic cancer: a population-based study. J Natl Cancer Inst. 1994;86(8):625–7.

    Article  CAS  PubMed  Google Scholar 

  19. Ghadirian P, Simard A, Baillargeon J. Tobacco, alcohol, and coffee and cancer of the pancreas. A population-based, case-control study in Quebec, Canada. Cancer. 1991;67(10):2664–70.

    Article  CAS  PubMed  Google Scholar 

  20. Lowenfels AB, Maisonneuve P, Cavallini G, Ammann RW, Lankisch PG, Andersen JR, Dimagno EP, Andren-Sandberg A, Domellof L. Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group. N Engl J Med. 1993;328(20):1433–7.

    Article  CAS  PubMed  Google Scholar 

  21. Voong KR, Davison J, Pawlik TM, Uy MO, Hsu CC, Winter J, Hruban RH, Laheru D, Rudra S, Swartz MJ, et al. Resected pancreatic adenosquamous carcinoma: clinicopathologic review and evaluation of adjuvant chemotherapy and radiation in 38 patients. Hum Pathol. 2010;41(1):113–22.

    Article  CAS  PubMed  Google Scholar 

  22. Poultsides GA, Reddy S, Cameron JL, Hruban RH, Pawlik TM, Ahuja N, Jain A, Edil BH, Iacobuzio-Donahue CA, Schulick RD, et al. Histopathologic basis for the favorable survival after resection of intraductal papillary mucinous neoplasm-associated invasive adenocarcinoma of the pancreas. Ann Surg. 2010;251(3):470–6.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Hong SM, Park JY, Hruban RH, Goggins M. Molecular signatures of pancreatic cancer. Arch Pathol Lab Med. 2011;135(6):716–27.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Hruban RH, Adsay NV. Molecular classification of neoplasms of the pancreas. Hum Pathol. 2009;40(5):612–23.

    Article  CAS  PubMed  Google Scholar 

  25. Shi C, Hruban RH, Klein AP. Familial pancreatic cancer. Arch Pathol Lab Med. 2009;133(3):365–74.

    PubMed  Google Scholar 

  26. Yeo TP. Demographics, epidemiology, and inheritance of pancreatic ductal adenocarcinoma. Semin Oncol. 2015;42(1):8–18.

    Article  PubMed  Google Scholar 

  27. Bergman W, Watson P, de Jong J, Lynch HT, Fusaro RM. Systemic cancer and the FAMMM syndrome. Br J Cancer. 1990;61(6):932–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Berman DB, Costalas J, Schultz DC, Grana G, Daly M, Godwin AK. A common mutation in BRCA2 that predisposes to a variety of cancers is found in both Jewish Ashkenazi and non-Jewish individuals. Cancer Res. 1996;56(15):3409–14.

    CAS  PubMed  Google Scholar 

  29. Couch FJ, Johnson MR, Rabe K, Boardman L, McWilliams R, de Andrade M, Petersen G. Germ line Fanconi anemia complementation group C mutations and pancreatic cancer. Cancer Res. 2005;65(2):383–6.

    CAS  PubMed  Google Scholar 

  30. Lal G, Liu G, Schmocker B, Kaurah P, Ozcelik H, Narod SA, Redston M, Gallinger S. Inherited predisposition to pancreatic adenocarcinoma: role of family history and germ-line p16, BRCA1, and BRCA2 mutations. Cancer Res. 2000;60(2):409–16.

    CAS  PubMed  Google Scholar 

  31. Liede A, Karlan BY, Narod SA. Cancer risks for male carriers of germline mutations in BRCA1 or BRCA2: a review of the literature. J Clin Oncol. 2004;22(4):735–42.

    Article  CAS  PubMed  Google Scholar 

  32. Mahlamaki EH, Hoglund M, Gorunova L, Karhu R, Dawiskiba S, Andren-Sandberg A, Kallioniemi OP, Johansson B. Comparative genomic hybridization reveals frequent gains of 20q, 8q, 11q, 12p, and 17q, and losses of 18q, 9p, and 15q in pancreatic cancer. Genes Chromosomes Cancer. 1997;20(4):383–91.

    Article  CAS  PubMed  Google Scholar 

  33. Su GH, Hruban RH, Bansal RK, Bova GS, Tang DJ, Shekher MC, Westerman AM, Entius MM, Goggins M, Yeo CJ, et al. Germline and somatic mutations of the STK11/LKB1 Peutz-Jeghers gene in pancreatic and biliary cancers. Am J Pathol. 1999;154(6):1835–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. van der Heijden MS, Yeo CJ, Hruban RH, Kern SE. Fanconi anemia gene mutations in young-onset pancreatic cancer. Cancer Res. 2003;63(10):2585–8.

    PubMed  Google Scholar 

  35. Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Kamiyama H, Jimeno A, et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 2008;321(5897):1801–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Furukawa T, Kloppel G, Volkan Adsay N, Albores-Saavedra J, Fukushima N, Horii A, Hruban RH, Kato Y, Klimstra DS, Longnecker DS, et al. Classification of types of intraductal papillary-mucinous neoplasm of the pancreas: a consensus study. Virchows Arch. 2005;447(5):794–9.

    Article  PubMed  Google Scholar 

  37. Kwak HA, Liu X, Allende DS, Pai RK, Hart J, Xiao SY. Interobserver variability in intraductal papillary mucinous neoplasm subtypes and application of their mucin immunoprofiles. Mod Pathol. 2016;29(9):977–84.

    Article  CAS  PubMed  Google Scholar 

  38. Adsay NV, Conlon KC, Zee SY, Brennan MF, Klimstra DS. Intraductal papillary-mucinous neoplasms of the pancreas: an analysis of in situ and invasive carcinomas in 28 patients. Cancer. 2002;94(1):62–77.

    Article  PubMed  Google Scholar 

  39. Adsay NV, Longnecker DS, Klimstra DS. Pancreatic tumors with cystic dilatation of the ducts: intraductal papillary mucinous neoplasms and intraductal oncocytic papillary neoplasms. Semin Diagn Pathol. 2000;17(1):16–30.

    CAS  PubMed  Google Scholar 

  40. Adsay NV, Merati K, Andea A, Sarkar F, Hruban RH, Wilentz RE, Goggins M, Iocobuzio-Donahue C, Longnecker DS, Klimstra DS. The dichotomy in the preinvasive neoplasia to invasive carcinoma sequence in the pancreas: differential expression of MUC1 and MUC2 supports the existence of two separate pathways of carcinogenesis. Mod Pathol. 2002;15(10):1087–95.

    Article  PubMed  Google Scholar 

  41. Basturk O, Chung SM, Hruban RH, Adsay NV, Askan G, Iacobuzio-Donahue C, Balci S, Zee SY, Memis B, Shia J, et al. Distinct pathways of pathogenesis of intraductal oncocytic papillary neoplasms and intraductal papillary mucinous neoplasms of the pancreas. Virchows Arch. 2016;469(5):523–32.

    Article  CAS  PubMed  Google Scholar 

  42. Reid MD, Stallworth CR, Lewis MM, Akkas G, Memis B, Basturk O, Adsay V. Cytopathologic diagnosis of oncocytic type intraductal papillary mucinous neoplasm: criteria and clinical implications of accurate diagnosis. Cancer Cytopathol. 2016;124(2):122–34.

    Article  CAS  PubMed  Google Scholar 

  43. Marchegiani G, Mino-Kenudson M, Ferrone CR, Warshaw AL, Lillemoe KD, Fernandez-del Castillo C. Oncocytic-type intraductal papillary mucinous neoplasms: a unique malignant pancreatic tumor with good long-term prognosis. J Am Coll Surg. 2015;220(5):839–44.

    Article  PubMed  Google Scholar 

  44. Adsay NV, Merati K, Basturk O, Iacobuzio-Donahue C, Levi E, Cheng JD, Sarkar FH, Hruban RH, Klimstra DS. Pathologically and biologically distinct types of epithelium in intraductal papillary mucinous neoplasms: delineation of an "intestinal" pathway of carcinogenesis in the pancreas. Am J Surg Pathol. 2004;28(7):839–48.

    Article  PubMed  Google Scholar 

  45. Frankel TL, LaFemina J, Bamboat ZM, D'Angelica MI, DeMatteo RP, Fong Y, Kingham TP, Jarnagin WR, Allen PJ. Dysplasia at the surgical margin is associated with recurrence after resection of non-invasive intraductal papillary mucinous neoplasms. HPB (Oxford). 2013;15(10):814–21.

    Article  Google Scholar 

  46. Fujii T, Kato K, Kodera Y, Kanda M, Nagai S, Yamada S, Kanzaki A, Sugimoto H, Nomoto S, Takeda S, et al. Prognostic impact of pancreatic margin status in the intraductal papillary mucinous neoplasms of the pancreas. Surgery. 2010;148(2):285–90.

    Article  PubMed  Google Scholar 

  47. Leng KM, Wang ZD, Zhao JB, Cui YF, Zhong XY. Impact of pancreatic margin status and lymph node metastases on recurrence after resection for invasive and noninvasive intraductal papillary mucinous neoplasms of the pancreas: a meta-analysis. Dig Surg. 2012;29(3):213–25.

    Article  PubMed  Google Scholar 

  48. Nakagohri T, Kinoshita T, Konishi M, Takahashi S, Gotohda N. Surgical outcome of intraductal papillary mucinous neoplasms of the pancreas. Ann Surg Oncol. 2007;14(11):3174–80.

    Article  PubMed  Google Scholar 

  49. Raut CP, Cleary KR, Staerkel GA, Abbruzzese JL, Wolff RA, Lee JH, Vauthey JN, Lee JE, Pisters PW, Evans DB. Intraductal papillary mucinous neoplasms of the pancreas: effect of invasion and pancreatic margin status on recurrence and survival. Ann Surg Oncol. 2006;13(4):582–94.

    Article  PubMed  Google Scholar 

  50. Eguchi H, Ishikawa O, Ohigashi H, Sasaki Y, Yamada T, Nakaizumi A, Uehara H, Takenaka A, Kasugai T, Imaoka S. Role of intraoperative cytology combined with histology in detecting continuous and skip type intraductal cancer existence for intraductal papillary mucinous carcinoma of the pancreas. Cancer. 2006;107(11):2567–75.

    Article  PubMed  Google Scholar 

  51. Yamaguchi H, Shimizu M, Ban S, Koyama I, Hatori T, Fujita I, Yamamoto M, Kawamura S, Kobayashi M, Ishida K, et al. Intraductal tubulopapillary neoplasms of the pancreas distinct from pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms. Am J Surg Pathol. 2009;33(8):1164–72.

    Article  PubMed  Google Scholar 

  52. Date K, Okabayashi T, Shima Y, Iwata J, Sumiyoshi T, Kozuki A, Morita S, Hata Y, Noda Y, Nishioka A, et al. Clinicopathological features and surgical outcomes of intraductal tubulopapillary neoplasm of the pancreas: a systematic review. Langenbeck's Arch Surg. 2016;401(4):439–47.

    Article  Google Scholar 

  53. Rooney SL, Shi J. Intraductal tubulopapillary neoplasm of the pancreas: an update from a pathologist's perspective. Arch Pathol Lab Med. 2016;140(10):1068–73.

    Article  PubMed  Google Scholar 

  54. Schonleben F, Qiu W, Bruckman KC, Ciau NT, Li X, Lauerman MH, Frucht H, Chabot JA, Allendorf JD, Remotti HE, et al. BRAF and KRAS gene mutations in intraductal papillary mucinous neoplasm/carcinoma (IPMN/IPMC) of the pancreas. Cancer Lett. 2007;249(2):242–8.

    Article  PubMed  CAS  Google Scholar 

  55. Uemura K, Hiyama E, Murakami Y, Kanehiro T, Ohge H, Sueda T, Yokoyama T. Comparative analysis of K-ras point mutation, telomerase activity, and p53 overexpression in pancreatic tumours. Oncol Rep. 2003;10(2):277–83.

    CAS  PubMed  Google Scholar 

  56. Abe T, Fukushima N, Brune K, Boehm C, Sato N, Matsubayashi H, Canto M, Petersen GM, Hruban RH, Goggins M. Genome-wide allelotypes of familial pancreatic adenocarcinomas and familial and sporadic intraductal papillary mucinous neoplasms. Clin Cancer Res. 2007;13(20):6019–25.

    Article  CAS  PubMed  Google Scholar 

  57. Fujii H, Inagaki M, Kasai S, Miyokawa N, Tokusashi Y, Gabrielson E, Hruban RH. Genetic progression and heterogeneity in intraductal papillary-mucinous neoplasms of the pancreas. Am J Pathol. 1997;151(5):1447–54.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Wada K. p16 and p53 gene alterations and accumulations in the malignant evolution of intraductal papillary-mucinous tumors of the pancreas. J Hepato-Biliary-Pancreat Surg. 2002;9(1):76–85.

    Article  Google Scholar 

  59. Wu J, Jiao Y, Dal Molin M, Maitra A, de Wilde RF, Wood LD, Eshleman JR, Goggins MG, Wolfgang CL, Canto MI, et al. Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitin-dependent pathways. Proc Natl Acad Sci U S A. 2011;108(52):21188–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Wu J, Matthaei H, Maitra A, Dal Molin M, Wood LD, Eshleman JR, Goggins M, Canto MI, Schulick RD, Edil BH, et al. Recurrent GNAS mutations define an unexpected pathway for pancreatic cyst development. Sci Transl Med. 2011;3(92):92ra66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Schonleben F, Qiu W, Ciau NT, Ho DJ, Li X, Allendorf JD, Remotti HE, Su GH. PIK3CA mutations in intraductal papillary mucinous neoplasm/carcinoma of the pancreas. Clin Cancer Res. 2006;12(12):3851–5.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Kim JY, Hong SM. Recent updates on neuroendocrine tumors from the gastrointestinal and pancreatobiliary tracts. Arch Pathol Lab Med. 2016;140(5):437–48.

    Article  PubMed  Google Scholar 

  63. McCall CM, Shi C, Klein AP, Konukiewitz B, Edil BH, Ellison TA, Wolfgang CL, Schulick RD, Kloppel G, Hruban RH. Serotonin expression in pancreatic neuroendocrine tumors correlates with a trabecular histologic pattern and large duct involvement. Hum Pathol. 2012;43(8):1169–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Basturk O, Yang Z, Tang LH, Hruban RH, Adsay V, McCall CM, Krasinskas AM, Jang KT, Frankel WL, Balci S, et al. The high-grade (WHO G3) pancreatic neuroendocrine tumor category is morphologically and biologically heterogenous and includes both well differentiated and poorly differentiated neoplasms. Am J Surg Pathol. 2015;39(5):683–90.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Tang LH, Basturk O, Sue JJ, Klimstra DS. A practical approach to the classification of WHO Grade 3 (G3) well-differentiated neuroendocrine tumor (WD-NET) and poorly differentiated neuroendocrine carcinoma (PD-NEC) of the pancreas. Am J Surg Pathol. 2016;40(9):1192–202.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Basturk O, Tang L, Hruban RH, Adsay V, Yang Z, Krasinskas AM, Vakiani E, La Rosa S, Jang KT, Frankel WL, et al. Poorly differentiated neuroendocrine carcinomas of the pancreas: a clinicopathologic analysis of 44 cases. Am J Surg Pathol. 2014;38(4):437–47.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Hruban RH, Iacobuzio-Donahue C, Wilentz RE, Goggins M, Kern SE. Molecular pathology of pancreatic cancer. Cancer J. 2001;7(4):251–8.

    CAS  PubMed  Google Scholar 

  68. Moore PS, Orlandini S, Zamboni G, Capelli P, Rigaud G, Falconi M, Bassi C, Lemoine NR, Scarpa A. Pancreatic tumours: molecular pathways implicated in ductal cancer are involved in ampullary but not in exocrine nonductal or endocrine tumorigenesis. Br J Cancer. 2001;84(2):253–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Perren A, Komminoth P, Saremaslani P, Matter C, Feurer S, Lees JA, Heitz PU, Eng C. Mutation and expression analyses reveal differential subcellular compartmentalization of PTEN in endocrine pancreatic tumors compared to normal islet cells. Am J Pathol. 2000;157(4):1097–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Serrano J, Goebel SU, Peghini PL, Lubensky IA, Gibril F, Jensen RT. Alterations in the p16INK4a/CDKN2A tumor suppressor gene in gastrinomas. J Clin Endocrinol Metab. 2000;85(11):4146–56.

    Article  CAS  PubMed  Google Scholar 

  71. Jiao Y, Shi C, Edil BH, de Wilde RF, Klimstra DS, Maitra A, Schulick RD, Tang LH, Wolfgang CL, Choti MA, et al. DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors. Science. 2011;331(6021):1199–203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Shi C, Klimstra DS. Pancreatic neuroendocrine tumors: pathologic and molecular characteristics. Semin Diagn Pathol. 2014;31(6):498–511.

    Article  PubMed  Google Scholar 

  73. Yachida S, Vakiani E, White CM, Zhong Y, Saunders T, Morgan R, de Wilde RF, Maitra A, Hicks J, Demarzo AM, et al. Small cell and large cell neuroendocrine carcinomas of the pancreas are genetically similar and distinct from well-differentiated pancreatic neuroendocrine tumors. Am J Surg Pathol. 2012;36(2):173–84.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Gortz B, Roth J, Krahenmann A, de Krijger RR, Muletta-Feurer S, Rutimann K, Saremaslani P, Speel EJ, Heitz PU, Komminoth P. Mutations and allelic deletions of the MEN1 gene are associated with a subset of sporadic endocrine pancreatic and neuroendocrine tumors and not restricted to foregut neoplasms. Am J Pathol. 1999;154(2):429–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Moore PS, Missiaglia E, Antonello D, Zamo A, Zamboni G, Corleto V, Falconi M, Scarpa A. Role of disease-causing genes in sporadic pancreatic endocrine tumors: MEN1 and VHL. Genes Chromosomes Cancer. 2001;32(2):177–81.

    Article  CAS  PubMed  Google Scholar 

  76. Shan L, Nakamura Y, Nakamura M, Yokoi T, Tsujimoto M, Arima R, Kameya T, Kakudo K. Somatic mutations of multiple endocrine neoplasia type 1 gene in the sporadic endocrine tumors. Lab Investig. 1998;78(4):471–5.

    CAS  PubMed  Google Scholar 

  77. Wang EH, Ebrahimi SA, Wu AY, Kashefi C, Passaro E Jr, Sawicki MP. Mutation of the MENIN gene in sporadic pancreatic endocrine tumors. Cancer Res. 1998;58(19):4417–20.

    CAS  PubMed  Google Scholar 

  78. Zhuang Z, Vortmeyer AO, Pack S, Huang S, Pham TA, Wang C, Park WS, Agarwal SK, Debelenko LV, Kester M, et al. Somatic mutations of the MEN1 tumor suppressor gene in sporadic gastrinomas and insulinomas. Cancer Res. 1997;57(21):4682–6.

    CAS  PubMed  Google Scholar 

  79. D'Adda T, Pizzi S, Azzoni C, Bottarelli L, Crafa P, Pasquali C, Davoli C, Corleto VD, Delle Fave G, Bordi C. Different patterns of 11q allelic losses in digestive endocrine tumors. Hum Pathol. 2002;33(3):322–9.

    Article  PubMed  Google Scholar 

  80. Hessman O, Lindberg D, Einarsson A, Lillhager P, Carling T, Grimelius L, Eriksson B, Akerstrom G, Westin G, Skogseid B. Genetic alterations on 3p, 11q13, and 18q in nonfamilial and MEN 1-associated pancreatic endocrine tumors. Genes Chromosomes Cancer. 1999;26(3):258–64.

    Article  CAS  PubMed  Google Scholar 

  81. Hessman O, Lindberg D, Skogseid B, Carling T, Hellman P, Rastad J, Akerstrom G, Westin G. Mutation of the multiple endocrine neoplasia type 1 gene in nonfamilial, malignant tumors of the endocrine pancreas. Cancer Res. 1998;58(3):377–9.

    CAS  PubMed  Google Scholar 

  82. Asbun HJ, Conlon K, Fernandez-Cruz L, Friess H, Shrikhande SV, Adham M, Bassi C, Bockhorn M, Buchler M, Charnley RM, et al. When to perform a pancreatoduodenectomy in the absence of positive histology? A consensus statement by the International Study Group of Pancreatic Surgery. Surgery. 2014;155(5):887–92.

    Article  PubMed  Google Scholar 

  83. Bockhorn M, Uzunoglu FG, Adham M, Imrie C, Milicevic M, Sandberg AA, Asbun HJ, Bassi C, Buchler M, Charnley RM, et al. Borderline resectable pancreatic cancer: a consensus statement by the International Study Group of Pancreatic Surgery (ISGPS). Surgery. 2014;155(6):977–88.

    Article  PubMed  Google Scholar 

  84. Eltoum IA, Alston EA, Roberson J. Trends in pancreatic pathology practice before and after implementation of endoscopic ultrasound-guided fine-needle aspiration: an example of disruptive innovation effect? Arch Pathol Lab Med. 2012;136(4):447–53.

    Article  PubMed  Google Scholar 

  85. Jhala NC, Jhala D, Eltoum I, Vickers SM, Wilcox CM, Chhieng DC, Eloubeidi MA. Endoscopic ultrasound-guided fine-needle aspiration biopsy: a powerful tool to obtain samples from small lesions. Cancer. 2004;102(4):239–46.

    Article  PubMed  Google Scholar 

  86. Volmar KE, Vollmer RT, Routbort MJ, Creager AJ. Pancreatic and bile duct brushing cytology in 1000 cases: review of findings and comparison of preparation methods. Cancer. 2006;108(4):231–8.

    Article  PubMed  Google Scholar 

  87. Adler DG, Witt B, Chadwick B, Wells J, Taylor LJ, Dimaio C, Schmidt R. Pathologic evaluation of a new endoscopic ultrasound needle designed to obtain core tissue samples: a pilot study. Endosc Ultrasound. 2016;5(3):178–83.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Dwyer J, Pantanowitz L, Ohori NP, Pai RK, Vrbin C, Brand RE, Monaco SE. Endoscopic ultrasound-guided FNA and ProCore biopsy in sampling pancreatic and intra-abdominal masses. Cancer Cytopathol. 2016;124(2):110–21.

    Article  PubMed  Google Scholar 

  89. Kamata K, Kitano M, Yasukawa S, Kudo M, Chiba Y, Ogura T, Higuchi K, Fukutake N, Ashida R, Yamasaki T, et al. Histologic diagnosis of pancreatic masses using 25-gauge endoscopic ultrasound needles with and without a core trap: a multicenter randomized trial. Endoscopy. 2016;48(7):632–8.

    Article  PubMed  Google Scholar 

  90. da Cunha SG, Ko HM, Saieg MA. Geddie WR: "The petals and thorns" of ROSE (rapid on-site evaluation). Cancer Cytopathol. 2013;121(1):4–8.

    Article  Google Scholar 

  91. Jhala NC, Eltoum IA, Eloubeidi MA, Meara R, Chhieng DC, Crowe DR, Jhala D. Providing on-site diagnosis of malignancy on endoscopic-ultrasound-guided fine-needle aspirates: should it be done? Ann Diagn Pathol. 2007;11(3):176–81.

    Article  PubMed  Google Scholar 

  92. Cermak TS, Wang B, DeBrito P, Carroll J, Haddad N, Sidawy MK. Does on-site adequacy evaluation reduce the nondiagnostic rate in endoscopic ultrasound-guided fine-needle aspiration of pancreatic lesions? Cancer Cytopathol. 2012;120(5):319–25.

    Article  PubMed  Google Scholar 

  93. Woolf KM, Liang H, Sletten ZJ, Russell DK, Bonfiglio TA, Zhou Z. False-negative rate of endoscopic ultrasound-guided fine-needle aspiration for pancreatic solid and cystic lesions with matched surgical resections as the gold standard: one institution's experience. Cancer Cytopathol. 2013;121(8):449–58.

    Article  PubMed  Google Scholar 

  94. Gleeson FC, Kipp BR, Caudill JL, Clain JE, Clayton AC, Halling KC, Henry MR, Rajan E, Topazian MD, Wang KK, et al. False positive endoscopic ultrasound fine needle aspiration cytology: incidence and risk factors. Gut. 2010;59(5):586–93.

    Article  PubMed  Google Scholar 

  95. Schwartz DA, Unni KK, Levy MJ, Clain JE, Wiersema MJ. The rate of false-positive results with EUS-guided fine-needle aspiration. Gastrointest Endosc. 2002;56(6):868–72.

    Article  PubMed  Google Scholar 

  96. Siddiqui AA, Kowalski TE, Shahid H, O'Donnell S, Tolin J, Loren DE, Infantolino A, Hong SK, Eloubeidi MA. False-positive EUS-guided FNA cytology for solid pancreatic lesions. Gastrointest Endosc. 2011;74(3):535–40.

    Article  PubMed  Google Scholar 

  97. Pitman MB, Centeno BA, Ali SZ, Genevay M, Stelow E, Mino-Kenudson M, Castillo CF, Schmidt CM, Brugge WR, Layfield LJ. Standardized terminology and nomenclature for pancreatobiliary cytology: the Papanicolaou Society of Cytopathology Guidelines. Cytojournal. 2014;11(Suppl 1):3.

    PubMed  PubMed Central  Google Scholar 

  98. Pitman MB, Centeno BA, Ali SZ, Genevay M, Stelow E, Mino-Kenudson M, Fernandez-del Castillo C, Max Schmidt C, Brugge W, Layfield L. Standardized terminology and nomenclature for pancreatobiliary cytology: the Papanicolaou Society of Cytopathology guidelines. Diagn Cytopathol. 2014;42(4):338–50.

    Article  PubMed  Google Scholar 

  99. Pitman MB, Layfield LJ. Guidelines for pancreaticobiliary cytology from the Papanicolaou Society of Cytopathology: a review. Cancer Cytopathol. 2014;122(6):399–411.

    Article  PubMed  Google Scholar 

  100. Stelow EB, Pambuccian SE, Bardales RH, et al. The cytology of pancreatic foamy gland adenocarcinoma. Am J Clin Pathol. 2004;121(6):893–7.

    Article  PubMed  Google Scholar 

  101. Olson MT, Siddiqui MT, Ali SZ. The differential diagnosis of squamous cells in pancreatic aspirates: from contamination to adenosquamous carcinoma. Acta Cytol. 2013;57(2):139–46.

    Article  CAS  PubMed  Google Scholar 

  102. Chute DJ, Stelow EB. Fine-needle aspiration features of paraduodenal pancreatitis (groove pancreatitis): a report of three cases. Diagn Cytopathol. 2012;40(12):1116–21.

    Article  PubMed  Google Scholar 

  103. Holmes BJ, Hruban RH, Wolfgang CL, Ali SZ. Fine needle aspirate of autoimmune pancreatitis (lymphoplasmacytic sclerosing pancreatitis): cytomorphologic characteristics and clinical correlates. Acta Cytol. 2012;56(3):228–32.

    Article  PubMed  Google Scholar 

  104. Jarboe EA, Layfield LJ. Cytologic features of pancreatic intraepithelial neoplasia and pancreatitis: potential pitfalls in the diagnosis of pancreatic ductal carcinoma. Diagn Cytopathol. 2011;39(8):575–81.

    Article  PubMed  Google Scholar 

  105. Hijioka S, Hara K, Mizuno N, Imaoka H, Bhatia V, Mekky MA, Yoshimura K, Yoshida T, Okuno N, Hieda N, et al. Diagnostic performance and factors influencing the accuracy of EUS-FNA of pancreatic neuroendocrine neoplasms. J Gastroenterol. 2016 Sep;51(9):923–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Hooper K, Mukhtar F, Li S, Eltoum IA. Diagnostic error assessment and associated harm of endoscopic ultrasound-guided fine-needle aspiration of neuroendocrine neoplasms of the pancreas. Cancer Cytopathol. 2013;121(11):653–60.

    Article  PubMed  Google Scholar 

  107. Chen S, Wang X, Lin J. Fine needle aspiration of oncocytic variants of pancreatic neuroendocrine tumor: a report of three misdiagnosed cases. Acta Cytol. 2014;58(2):131–7.

    Article  PubMed  Google Scholar 

  108. Levy GH, Finkelstein A, Harigopal M, Chhieng D, Cai G. Cytoplasmic vacuolization: an under-recognized cytomorphologic feature in endocrine tumors of the pancreas. Diagn Cytopathol. 2013;41(7):623–8.

    Article  PubMed  Google Scholar 

  109. Jin M, Roth R, Gayetsky V, Niederberger N, Lehman A, Wakely PE. Grading pancreatic neuroendocrine neoplasms by Ki-67 staining on cytology cell blocks: manual count and digital image analysis of 58 cases. JASC. 2016;5(5):286–95.

    Google Scholar 

  110. Samad A, Shah AA, Stelow EB, Alsharif M, Cameron SE, Pambuccian SE. Cercariform cells: another cytologic feature distinguishing solid pseudopapillary neoplasms from pancreatic endocrine neoplasms and acinar cell carcinomas in endoscopic ultrasound-guided fine-needle aspirates. Cancer Cytopathol. 2013;121(6):298–310.

    Article  PubMed  Google Scholar 

  111. Zhao P, deBrito P, Ozdemirli M, Sidawy MK. Solid-pseudopapillary neoplasm of the pancreas: awareness of unusual clinical presentations and morphology of the clear cell variant can prevent diagnostic errors. Diagn Cytopathol. 2013;41(10):889–95.

    PubMed  Google Scholar 

  112. Sigel CS, Klimstra DS. Cytomorphologic and immunophenotypical features of acinar cell neoplasms of the pancreas. Cancer Cytopathol. 2013;121(8):459–70.

    Article  PubMed  Google Scholar 

  113. Pitman MB. Revised international consensus guidelines for the management of patients with mucinous cysts. Cancer Cytopathol. 2012;120(6):361–5.

    Article  PubMed  Google Scholar 

  114. Pitman MB. Pancreatic cyst fluid triage: a critical component of the preoperative evaluation of pancreatic cysts. Cancer Cytopathol. 2013;121(2):57–60.

    Article  PubMed  Google Scholar 

  115. Pitman MB, Yaeger KA, Brugge WR, Mino-Kenudson M. Prospective analysis of atypical epithelial cells as a high-risk cytologic feature for malignancy in pancreatic cysts. Cancer Cytopathol. 2013;121(1):29–36.

    Article  PubMed  Google Scholar 

  116. Cizginer S, Turner BG, Bilge AR, Karaca C, Pitman MB, Brugge WR. Cyst fluid carcinoembryonic antigen is an accurate diagnostic marker of pancreatic mucinous cysts. Pancreas. 2011;40(7):1024–8.

    Article  CAS  PubMed  Google Scholar 

  117. Khalid A, Zahid M, Finkelstein SD, LeBlanc JK, Kaushik N, Ahmad N, Brugge WR, Edmundowicz SA, Hawes RH, McGrath KM. Pancreatic cyst fluid DNA analysis in evaluating pancreatic cysts: a report of the PANDA study. Gastrointest Endosc. 2009;69(6):1095–102.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, The Ohio State University Wexner Medical Center, 1645 Neil Ave, 129 Hamilton Hall, Columbus, OH, 43210, USA

    Wei Chen M.D., Ph.D., Ming Jin M.D., Ph.D. & Wendy L. Frankel M.D.

Authors
  1. Wei Chen M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ming Jin M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wendy L. Frankel M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wendy L. Frankel M.D. .

Editor information

Editors and Affiliations

  1. Mayo Clinic Cancer Center, Scottsdale, Arizona, USA

    Tanios Bekaii-Saab

  2. Winship Cancer Institute, Emory University, Atlanta, Georgia, USA

    Bassel El-Rayes

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this chapter

Cite this chapter

Chen, W., Jin, M., Frankel, W.L. (2018). Pathology: Premalignant and Malignant Diseases and Molecular Genetics. In: Bekaii-Saab, T., El-Rayes, B. (eds) Current and Emerging Therapies in Pancreatic Cancer . Springer, Cham. https://doi.org/10.1007/978-3-319-58256-6_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-58256-6_3

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-58255-9

  • Online ISBN: 978-3-319-58256-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation