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Pancreatic carcinoma, its variants and precursors: Overview of the current WHO classification


Authors: J. Hrudka
Authors place of work: Ústav patologie, 3. lékařská fakulta Univerzity Karlovy v Praze a Fakultní nemocnice Královské Vinohrady, Praha, Česká republika
Published in the journal: Rozhl. Chir., 2024, roč. 103, č. 6, s. 208-218.
Category: Review
doi: https://doi.org/10.33699/PIS.2024.103.6.208–218

Summary

Pancreatic carcinoma is a relatively common malignant tumor with increasing incidence and mortality. The tumor is usually diagnosed at an advanced stage and generally has a poor prognosis, with only 5% of patients surviving 5 years from the time of diagnosis. The stage of the disease at the time of diagnosis is a crucial factor for the prognosis; 25% of patients with localized tumors survive 3 years from diagnosis, compared to only 1% of those with generalized tumors. Radical surgical removal of the tumor (partial or total pancreatectomy) is a key factor in improving survival. Therefore, the topic is highly relevant to surgeons. Statistics on pancreatic carcinoma mainly focus on ductal adenocarcinoma, which is the most common and least favorable malignant tumor of the pancreas. This review focuses on ductal adenocarcinoma, its variants, and precancerous lesions. The article summarizes information from the latest WHO classification of 2019, which was released 11 years after the previous edition. Compared to the previous version, this new WHO classification introduced rather minor changes in the field of ductal adenocarcinoma. The delineation of rare variants of ductal adenocarcinoma is justified based on genetic and morphological similarities and clinical relevance, as individual subtypes significantly differ in prognosis. The article also includes a description of macroscopic and microscopic precursors of ductal adenocarcinoma and their definitions. Genetic and immunohistochemical differential diagnostic aspects are briefly discussed, as these are more relevant to pathologists than to surgeons.

Keywords:

Dysplasia – Pancreas – Adenocarcinoma – ductal – pancreatic intraepithelial neoplasia


Zdroje
  1. Kleeff J, Korc M, Apte M, et al. Pancreatic cancer. Nat Rev Dis Primers. 2016;2:16022. doi: 10.1038/nrdp.2016.22.
  2. Dyba T, Randi G, Bray F, et al. The European cancer burden in 2020: Incidence and mortality estimates for 40 countries and 25 major cancers. Eur J Cancer 2021;157:308–347. doi: 10.1016/j. ejca.2021.07.039.
  3. Hu JX, Zhao CF, Chen WB, et al. Pancreatic cancer: A review of epidemiology, trend, and risk factors. World J Gastroenterol. 2021;27(27):4298–4321. doi: 10.3748/wjg. v27.i27.4298.
  4. Klimstra DS, Gill AJ, Washington MK. Tumours of the pancreas: Introduction. In: WHO Classification of Tumours Editorial Board. Digestive system tumours. Lyon (France), International Agency for Research on Cancer 2019. (WHO publications of tumours series, 5th ed.; vol. 1:298–299).
  5. Klöppel G, Basturk O, Klimstra DS, et al. Solid pseudopapillary neoplasm of the pancreas. In: WHO Classification of Tumours Editorial Board. Digestive system tumours. Lyon (France), International Agency for Research on Cancer 2019. (WHO publications of tumours series, 5th ed.; vol. 1:340–342).
  6. Fitzgerald TL, Hickner ZJ, Schmitz M, et al. Changing incidence of pancreatic neoplasms: a 16-year review of statewide tumor registry. Pancreas 2008;37(2):134–138. doi: 10.1097/MPA.0b013e318163a329.
  7. Bailey P, Chang DK, Nones K, et al. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature 2016;531(7592):47–52. doi: 10.1038/nature16965.
  8. Hruban RH, Adsay NV, Esposito I, et al. Pancreatic ductal adenocarcinoma. In: WHO Classification of Tumours Editorial Board. Digestive system tumours. Lyon (France), International Agency for Research on Cancer 2019. (WHO publications of tumours series, 5th ed.; vol. 1:322–332).
  9. Jun SY, Son D, Kim MJ, et al. Heterotopic pancreas of the gastrointestinal tract and associated precursor and cancerous lesions: Systematic pathologic studies of 165 cases. Am J Surg Pathol. 2017;41(6):833–848. doi: 10.1097/PAS.0000000000000850.
  10. Schlitter AM, Jesinghaus M, Jäger C, et al. pT but not pN stage of the 8th TNM classification significantly improves prognostication in pancreatic ductal adenocarcinoma. Eur J Cancer 2017;84:121–129. doi: 10.1016/j.ejca.2017.06.034.
  1. He J, Ahuja N, Makary MA, et al. 2564 resected periampullary adenocarcinomas at a single institution: trends over three decades. HPB (Oxford). 2014;16(1):83–90. doi: 10.1111/hpb.12078.
  2. Dal Molin M, Blackford AL, Siddiqui A, et al. Duodenal involvement is an independent prognostic factor for patients with surgically resected pancreatic ductal adenocarcinoma. Ann Surg Oncol. 2017;24(8):2379– 2386. doi: 10.1245/s10434-017-5864-9.
  3. Kosmahl M, Pauser U, Anlauf M, et al. Pancreatic ductal adenocarcinomas with cystic features: neither rare nor uniform. Mod Pathol. 2005;18(9):1157–1164. doi:10.1038/modpathol.3800446.
  4. AdsayV, Logani S, Sarkar F, et al. Foamy gland pattern of pancreatic ductal adenocarcinoma: a deceptively benign-appearing variant. Am J Surg Pathol. 2000;24(4):493–504. doi: 10.1097/00000478-200004000-00003.
  5. Nagata K, Horinouchi M, Saitou M, et al. Mucin expression profile in pancreatic cancer and the precursor lesions. J Hepatobiliary Pancreat Surg. 2007;14(3):243–254. doi: 10.1007/s00534-006-1169-2.
  6. Schlitter AM, Segler A, Steiger K, et al. Molecular, morphological and survival analysis of 177 resected pancreatic ductal adenocarcinomas (PDACs): Identification of prognostic subtypes. Sci Rep. 2017 Feb 1;7:41064. doi: 10.1038/srep41064.
  7. Senoo J, Mikata R, Kishimoto T, et al. Immunohistochemical analysis of IMP3 and p53 expression in endoscopic ultrasound-guided fine needle aspiration and resected specimens of pancreatic diseases. Pancreatology 2018;18(2):176–183. doi: 10.1016/j.pan.2017.12.010.
  8. Boyd CA, Benarroch-Gampel J, Sheffield KM, et al. 415 patients with adenosquamous carcinoma of the pancreas: a population-based analysis of prognosis and survival. J Surg Res. 2012;174(1):12–19. doi: 10.1016/j.jss.2011.06.015.
  9. Seidel G, Zahurak M, Iacobuzio-Donahue C, et al. Almost all infiltrating colloid carcinomas of the pancreas and periampullary region arise from in situ papillary neoplasms: a study of 39 cases. Am J Surg Pathol. 2002;26(1):56–63. doi: 10.1097/00000478-200201000-00006.
  10. Adsay NV, Merati K, Nassar H, et al. Pathogenesis of colloid (pure mucinous) carcinoma of exocrine organs: Coupling of gel-forming mucin (MUC2) production with altered cell polarity and abnormal cell-stroma interaction may be the key factor in the morphogenesis and indolent behavior of colloid carcinoma in the breast and pancreas. Am J Surg Pathol. 2003;27(5):571–578. doi: 10.1097/00000478-200305000-00002.
  11. Askan G, Deshpande V, Klimstra DS, et al. Expression of markers of hepatocellular differentiation in pancreatic acinar cell neoplasms: A potential diagnostic pitfall. Am J Clin Pathol. 2016;146(2):163–169. doi: 10.1093/ajcp/aqw096.
  12. Wilentz RE, Goggins M, Redston M, et al. Genetic, immunohistochemical, and clinical features of medullary carcinoma of the pancreas: A newly described and characterized entity. Am J Pathol. 2000;156(5):1641–1651. doi: 10.1016/ S0002-9440(10)65035-3.
  13. Yamamoto H, Itoh F, Nakamura H, et al. Genetic and clinical features of human pancreatic ductal adenocarcinomas with widespread microsatellite instability. Cancer Res. 20011;61(7):3139–3144.
  14. Guzińska-Ustymowicz K, Niewiarowska K, Pryczynicz A. Invasive micropapillary carcinoma: a distinct type of adenocarcinomas in the gastrointestinal tract. World J Gastroenterol. 2014;20(16):4597-606. doi: 10.3748/wjg.v20.i16.4597.
  15. Winter JM, Ting AH, Vilardell F, et al. Absence of E-cadherin expression distinguishes noncohesive from cohesive pancreatic cancer. Clin Cancer Res. 2008 Jan 15;14(2):412–418. doi: 10.1158/10780432.CCR-07-0487.
  16. Bazzichetto C, Luchini C, Conciatori F, et al. Morphologic and molecular landscape of pancreatic cancer variants as the basis of new therapeutic strategies for precision oncology. Int J Mol Sci. 2020; 21(22):8841. doi: 10.3390/ijms21228841.
  17. Paal E, Thompson LD, Frommelt RA, et al. A clinicopathologic and immunohistochemical study of 35 anaplastic carcinomas of the pancreas with a review of the literature. Ann Diagn Pathol. 2001;5(3):129–140. doi: 10.1053/ adpa.2001.25404.
  18. Lehrke HD, Graham RP, McWilliams RR, et al. Undifferentiated pancreatic carcinomas display enrichment for frequency and extent of PD-L1 expression by tumor cells. Am J Clin Pathol. 2017 Nov 2;148(5):441-449.  doi:  10.1093/ajcp/aqx092.
  19. Muraki T, Reid MD, Basturk O, et al. Undifferentiated carcinoma with osteoclastic giant cells of the pancreas: clinicopathologic analysis of 38 cases highlights a more protracted clinical course than currently appreciated. Am J Surg Pathol. 2016;40(9):1203–1216. doi: 10.1097/ PAS.0000000000000689.
  20. Luchini C, Cros J, Pea A, et al. PD-1, PD-L1, and CD163 in pancreatic undifferentiated carcinoma with osteoclast-like giant cells: expression patterns and clinical implications. Hum Pathol. 2018;81:157–165. doi: 10.1016/j.humpath.2018.07.006.
  21. Hrudka J, Lawrie K, Waldauf P, et al. Negative prognostic impact of PD-L1 expression in tumor cells of undifferentiated (anaplastic) carcinoma with osteoclast-like giant cells of the pancreas: study of 13 cases comparing ductal pancreatic carcinoma and review of the literature. Virchows Arch. 2020;477(5):687–696. doi: 10.1007/s00428-020-02830-8.
  22. Obayashi M, Shibasaki Y, Koakutsu T, et al. Pancreatic undifferentiated carcinoma with osteoclast-like giant cells curatively resected after pembrolizumab therapy for lung metastases: a case report. BMC Gastroenterol. 2020;20(1):220. doi: 10.1186/s12876-020-01362-4.
  23. Besaw RJ, Terra AR, Malvar GL, et al. Durable response to PD-1 blockade in a patient with metastatic pancreatic undifferentiated carcinoma with osteoclast-like giant cells. J Natl Compr Canc Netw. 2021;19(3):247–252. doi: 10.6004/jnccn.2021.7001.
  24. Kanda M, Matthaei H, Wu J, et al. Presence of somatic mutations in most early-stage pancreatic intraepithelial neoplasia. Gastroenterology 2012;142(4):730–733.e9. doi: 10.1053/j.gastro.2011.12.042.
  25. Hruban RH, Takaori K, Canto M, et al. Clinical importance of precursor lesions in the pancreas. J Hepatobiliary Pancreat Surg. 2007;14(3):255–263. doi: 10.1007/ s00534-006-1170-9.
  26. 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.  doi:  10.1097/01.MP.0000087422.24733.62.
  27. Jamiyan T, Shiraki T, Kurata Y, et al. Clinical impacts of resection margin status and clinicopathologic parameters on pancreatic ductal adenocarcinoma. World J Surg Oncol. 2020;18(1):137. doi: 10.1186/ s12957-020-01900-0.
  28. Ingkakul T, Warshaw AL, Fernández-Del Castillo C. Epidemiology of intraductal papillary mucinous neoplasms of the pancreas: sex differences between 3 geographic regions. Pancreas. 2011;40(5):779–780. doi: 10.1097/MPA.0b013e31821f27fb.
  29. Chang YR, Park JK, Jang JY, et al. Incidental pancreatic cystic neoplasms in an asymptomatic healthy population of 21,745 individuals: Large-scale, single-center cohort study. Medicine (Baltimore) 2016;95(51):e5535. doi: 10.1097/ MD.0000000000005535.
  30. Basturk O, Esposito I, Klöppel G, et al. Pancreatic intraductal papillary mucinous neoplasm. In: WHO Classification of Tumours Editorial Board. Digestive system tumours. Lyon (France), International Agency for Research on Cancer 2019. (WHO publications of tumours series, 5th ed.; vol. 1:310–314).
  31. D’Onofrio M, De Robertis R, Tinazzi Martini P, et al. Oncocytic intraductal papillary mucinous neoplasms of the pancreas: Imaging and histopathological findings. Pancreas. 2016 Oct;45(9):1233–1242. doi: 10.1097/MPA.0000000000000676.
  32. Basturk O, Esposito I, Klöppel G, et al. Pancreatic intraductal oncocytic papillary neoplasm. In: WHO Classification of Tumours Editorial Board. Digestive system tumours. Lyon (France), International Agency for Research on Cancer 2019. (WHO publications of tumours series, 5th ed.; vol. 1:315–316).
  33. Basturk O, Esposito I, Klöppel G, et al. Pancreatic intraductal tubulopapillary neoplasm. In: WHO Classification of Tumours Editorial Board. Digestive system tumours. Lyon (France): International Agency for Research on Cancer 2019. (WHO publications of tumours series, 5th ed.; vol. 1:317–318).
  34. Basturk O, Adsay V, Askan G, et al. Intraductal tubulopapillary neoplasm of the pancreas: A clinicopathologic and immunohistochemical analysis of 33 cases. Am J Surg Pathol. 2017 Mar;41(3):313–325. doi: 10.1097/PAS. 0000000000000782.
  35. Basturk O, Esposito I, Klöppel G, et al. Pancreatic mucinous cystic neoplasm. In: WHO Classification of Tumours Editorial Board. Digestive system tumours. Lyon (France): International Agency for Research on Cancer 2019. (WHO publications of tumours series, 5th ed.; vol. 1:319–321).

MUDr. Jan Hrudka, Ph.D.
Ústav patologie
3. LF UK a FN Královské Vinohrady
Šrobárova 1150/50 Praha 10
e-mail:
jan.hrudka@lf3.cuni.cz

Štítky
Surgery Orthopaedics Trauma surgery
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