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Macroscopic morphology for estimation of malignant potential in pancreatic neuroendocrine neoplasm

  • Original Article – Clinical Oncology
  • Published:
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Abstract

Purpose

Pancreatic neuroendocrine neoplasm (Pan-NEN) representing approximately 1.3 % of pancreatic malignancy cases in incidence has been a so rare disease that it remains major problem to analyze the malignant potential. The aim of this study was to verify whether the macroscopic morphology of Pan-NEN, a novel pathological classification, contributes to malignant potential.

Methods

From a total of 86 patients with Pan-NEN, 41 surgical sections obtained from the primary site were classified by their morphology into a simple nodular (SN) group and a non-SN group. The non-SN group was further divided into three subtypes: simple nodular with extranodular growth (SNEG), confluent multinodular (CM), and infiltrative (IF). The clinicopathological features of the SN and the non-SN groups were retrospectively compared.

Results

Overall 5-year survival rates with and without surgical resection were 94 and 48 %, respectively. SN and non-SN types were identified in 21 and 20 patients, respectively. The non-SN group comprised 14 SNEG type, 2 CM type, and 4 IF type. Synchronous lymph node metastases (p = 0.009), synchronous liver metastases (p = 0.048), microinvasion to an adjacent organ (p < 0.001), vascular invasion (p = 0.023), and neural invasion (p = 0.019) were more significant in the non-SN group than in the SN group. As judged by WHO 2004 classification and TNM stages (AJCC and ENETS), non-SN type showed malignant trend (p < 0.05). Moreover, overall 5-year survival rates of SN and non-SN groups were 100 and 84.4 %, respectively (p = 0.048).

Conclusions

Non-SN tumors may have higher malignant potential than SN tumors.

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References

  • Birnbaum DJ, Turrini O, Ewald J, Barbier L, Autret A, Hardwigsen J, Brunet C, Moutardier V, Le Treut YP, Delpero JR (2014) Pancreatic neuroendocrine tumor: a multivariate analysis of factors influencing survival. Eur J Surg Oncol 40:1564–1571

    Article  CAS  PubMed  Google Scholar 

  • Cherenfant J, Stocker SJ, Gage MK, Du H, Thurow TA, Odeleye M, Schimpke SW, Kaul KL, Hall CR, Lamzabi I et al (2013) Predicting aggressive behavior in nonfunctioning pancreatic neuroendocrine tumors. Surgery 154:785–791

    Article  PubMed  Google Scholar 

  • Choi GH, Han DH, Kim DH, Choi SB, Kang CM, Kim KS, Choi JS, Park YN, Park JY, Kim do Y et al (2009) Outcome after curative resection for a huge (≥ 10 cm) hepatocellular carcinoma and prognostic significance of gross tumor classification. Am J Surg 198:693–701

    Article  PubMed  Google Scholar 

  • Falconi M, Bartsch DK, Eriksson B, Kloppel G, Lopes JM, O’Connor JM, Salazar R, Taal BG, Vullierme MP, O’Toole D (2012) ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms of the digestive system: well-differentiated pancreatic non-functioning tumors. Neuroendocrinology 95:120–134

    Article  CAS  PubMed  Google Scholar 

  • Fischer L, Kleeff J, Esposito I, Hinz U, Zimmermann A, Friess H, Buchler MW (2008) Clinical outcome and long-term survival in 118 consecutive patients with neuroendocrine tumours of the pancreas. Br J Surg 95:627–635

    Article  CAS  PubMed  Google Scholar 

  • Fischer L, Bergmann F, Schimmack S, Hinz U, Priess S, Muller-Stich BP, Werner J, Hackert T, Buchler MW (2014) Outcome of surgery for pancreatic neuroendocrine neoplasms. Br J Surg 101:1405–1412

    Article  CAS  PubMed  Google Scholar 

  • Han X, Xu X, Jin D, Wang D, Ji Y, Lou W (2014) Clinicopathological characteristics and prognosis-related factors of resectable pancreatic neuroendocrine tumors: a retrospective study of 104 cases in a single Chinese center. Pancreas 43:526–531

    Article  PubMed  PubMed Central  Google Scholar 

  • Hashim YM, Trinkaus KM, Linehan DC, Strasberg SS, Fields RC, Cao D, Hawkins WG (2014) Regional lymphadenectomy is indicated in the surgical treatment of pancreatic neuroendocrine tumors (PNETs). Ann Surg 259:197–203

    Article  PubMed  PubMed Central  Google Scholar 

  • Haynes AB, Deshpande V, Ingkakul T, Vagefi PA, Szymonifka J, Thayer SP, Ferrone CR, Wargo JA, Warshaw AL, Fernández-del Castillo C (2011) Implications of incidentally discovered, nonfunctioning pancreatic endocrine tumors: short-term and long-term patient outcomes. Arch Surg 146(5):534–538

    Article  PubMed  PubMed Central  Google Scholar 

  • Inayoshi J, Ichida T, Sugitani S, Tsuboi Y, Genda T, Honma N, Asakura H (2003) Gross appearance of hepatocellular carcinoma reflects E-cadherin expression and risk of early recurrence after surgical treatment. J Gastroenterol Hepatol 18:673–677

    Article  PubMed  Google Scholar 

  • Kazanjian KK, Reber HA, Hines OJ (2006) Resection of pancreatic neuroendocrine tumors: results of 70 cases. Arch Surg 141:765–769

    Article  PubMed  Google Scholar 

  • Klimstra DS, Arnold R, Caoella C, Hruban RH, Kloppel G, Komminoth P, Solcia E, Rindi G (2009) WHO classification of tumors of the digestive system. IARC, Lyon

    Google Scholar 

  • Kloppel G (2011) Classification and pathology of gastroenteropancreatic neuroendocrine neoplasms. Endocr Relat Cancer 18(Suppl1):S1–S16

    Article  PubMed  Google Scholar 

  • Kloppel G, Rindi G, Perren A, Komminoth P, Klimstra DS (2010) The ENETS and AJCC/UICC TNM classifications of the neuroendocrine tumors of the gastrointestinal tract and the pancreas: a statement. Virchows Arch 456:595–597

    Article  PubMed  Google Scholar 

  • Kudo M, Kitano M, Sakurai T, Nishida N (2015) General rules for the clinical and pathological study of primary liver cancer, nationwide follow-up survey and clinical practice guidelines: the outstanding achievements of the liver cancer study group of Japan. Dig Dis 33:765–770

    Article  PubMed  Google Scholar 

  • La Rosa S, Klersy C, Uccella S, Dainese L, Albarello L, Sonzogni A, Doglioni C, Capella C, Solcia E (2009) Improved histologic and clinicopathologic criteria for prognostic evaluation of pancreatic endocrine tumors. Hum Pathol 40(1):30–40

    Article  PubMed  Google Scholar 

  • Michelassi F, Vannucci L, Montag A, Goldberg R, Chappell R, Dytch H, Bibbo M, Block GE (1988) Importance of tumor morphology for the long term prognosis of rectal adenocarcinoma. Am Surg 54:376–379

    CAS  PubMed  Google Scholar 

  • Montironi R, Cheng L, Lopez-Beltran A, Mazzucchelli R, Scarpelli M, Bartels PH (2009) Decision support systems for morphology-based diagnosis and prognosis of prostate neoplasms: a methodological approach. Cancer 115:3068–3077

    Article  PubMed  Google Scholar 

  • Murakata A, Tanaka S, Mogushi K, Yasen M, Noguchi N, Irie T, Kudo A, Nakamura N, Tanaka H, Arii S (2011) Gene expression signature of the gross morphology in hepatocellular carcinoma. Ann Surg 253:94–100

    Article  PubMed  Google Scholar 

  • Nagano Y, Shimada H, Takeda K, Ueda M, Matsuo K, Tanaka K, Endo I, Kunisaki C, Togo S (2008) Predictive factors of microvascular invasion in patients with hepatocellular carcinoma larger than 5 cm. World J Surg 32:2218–2222

    Article  PubMed  Google Scholar 

  • Nakao A (2010) The sixth edition of general rules for the study of pancreatic cancer by Japan Pancreas Society. Pancreas 39:696

    Article  Google Scholar 

  • Park J, Song C, Hong JH, Park BH, Cho YM, Kim CS, Ahn H (2009) Prognostic significance of non-papillary tumor morphology as a predictor of cancer progression and survival in patients with primary T1G3 bladder cancer. World J Urol 27:277–283

    Article  CAS  PubMed  Google Scholar 

  • Salazar R, Wiedenmann B, Rindi G, Ruszniewski P (2012) ENETS (2011) consensus guidelines for the management of patients with digestive neuroendocrine tumors: an update. Neuroendocrinology 95:71–73

    Article  CAS  PubMed  Google Scholar 

  • Scarpa A, Mantovani W, Capelli P, Beghelli S, Boninsegna L, Bettini R, Panzuto F, Pederzoli P, delle Fave G, Falconi M (2010) Pancreatic endocrine tumors: improved TNM staging and histopathological grading permit a clinically efficient prognostic stratification of patients. Mod Pathol 23:824–833

    Article  CAS  PubMed  Google Scholar 

  • Sharpe SM, In H, Winchester DJ, Talamonti MS, Baker MS (2015) Surgical resection provides an overall survival benefit for patients with small pancreatic neuroendocrine tumors. J Gastrointest Surg 19:117–123

    Article  PubMed  Google Scholar 

  • Shimada M, Rikimaru T, Hamatsu T, Yamashita Y, Terashi T, Taguchi K, Tanaka S, Shirabe K, Sugimachi K (2001) The role of macroscopic classification in nodular-type hepatocellular carcinoma. Am J Surg 182:177–182

    Article  CAS  PubMed  Google Scholar 

  • Stahel RA (1992) Morphology, surface antigens, staging, and prognostic factors of small cell lung cancer. Curr Opin Oncol 4:308–314

    Article  CAS  PubMed  Google Scholar 

  • Tsutsumi K, Ohtsuka T, Fujino M, Nakashima H, Aishima S, Ueda J, Takahata S, Nakamura M, Oda Y, Tanaka M (2014) Analysis of risk factors for recurrence after curative resection of well-differentiated pancreatic neuroendocrine tumors based on the new grading classification. J Hepatobiliary Pancreat Sci 21:418–425

    Article  PubMed  Google Scholar 

  • Volante M, Brizzi MP, Faggiano A, La Rosa S, Rapa I, Ferrero A, Mansueto G, Righi L, Garancini S, Capella C et al (2007) Somatostatin receptor type 2A immunohistochemistry in neuroendocrine tumors: a proposal of scoring system correlated with somatostatin receptor scintigraphy. Mod Pathol 20:1172–1182

    Article  CAS  PubMed  Google Scholar 

  • Yang LY, Fang F, Ou DP, Wu W, Zeng ZJ, Wu F (2009) Solitary large hepatocellular carcinoma: a specific subtype of hepatocellular carcinoma with good outcome after hepatic resection. Ann Surg 249:118–123

    Article  PubMed  Google Scholar 

  • Yao JC, Eisner MP, Leary C, Dagohoy C, Phan A, Rashid A, Hassan M, Evans DB (2007) Population-based study of islet cell carcinoma. Ann Surg Oncol 14:3492–3500

    Article  PubMed  PubMed Central  Google Scholar 

  • Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, Abdalla EK, Fleming JB, Vauthey JN, Rashid A et al (2008) One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol 26:3063–3072

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by Grant-in-Aid for Scientific Research (C) Grant Number 15K10046.

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Authors and Affiliations

  1. Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan

    Eriko Katsuta, Atsushi Kudo, Yusuke Mitsunori, Satoshi Matsumura, Arihiro Aihara, Daisuke Ban, Takanori Ochiai & Minoru Tanabe

  2. Department of Human Pathology, Graduate School of Tokyo Medical and Dental University, Tokyo, Japan

    Takumi Akashi & Yoshinobu Eishi

  3. Department of Molecular Oncology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan

    Shinji Tanaka

Authors
  1. Eriko Katsuta
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  2. Atsushi Kudo
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  3. Takumi Akashi
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  4. Yusuke Mitsunori
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  5. Satoshi Matsumura
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  7. Daisuke Ban
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  8. Takanori Ochiai
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  11. Minoru Tanabe
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Correspondence to Atsushi Kudo.

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Katsuta, E., Kudo, A., Akashi, T. et al. Macroscopic morphology for estimation of malignant potential in pancreatic neuroendocrine neoplasm. J Cancer Res Clin Oncol 142, 1299–1306 (2016). https://doi.org/10.1007/s00432-016-2128-1

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  • DOI: https://doi.org/10.1007/s00432-016-2128-1

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