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Erschienen in: Journal of Cancer Research and Clinical Oncology 6/2016

17.02.2016 | Original Article – Clinical Oncology

Macroscopic morphology for estimation of malignant potential in pancreatic neuroendocrine neoplasm

verfasst von: Eriko Katsuta, Atsushi Kudo, Takumi Akashi, Yusuke Mitsunori, Satoshi Matsumura, Arihiro Aihara, Daisuke Ban, Takanori Ochiai, Shinji Tanaka, Yoshinobu Eishi, Minoru Tanabe

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 6/2016

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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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Literatur
Zurück zum Zitat 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 40:1564–1571CrossRefPubMed 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 40:1564–1571CrossRefPubMed
Zurück zum Zitat 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 154:785–791CrossRefPubMed 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 154:785–791CrossRefPubMed
Zurück zum Zitat 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 198:693–701CrossRefPubMed 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 198:693–701CrossRefPubMed
Zurück zum Zitat 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 95:120–134CrossRefPubMed 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 95:120–134CrossRefPubMed
Zurück zum Zitat 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 95:627–635CrossRefPubMed 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 95:627–635CrossRefPubMed
Zurück zum Zitat 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 101:1405–1412CrossRefPubMed 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 101:1405–1412CrossRefPubMed
Zurück zum Zitat 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 43:526–531CrossRefPubMedPubMedCentral 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 43:526–531CrossRefPubMedPubMedCentral
Zurück zum Zitat 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 259:197–203CrossRefPubMedPubMedCentral 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 259:197–203CrossRefPubMedPubMedCentral
Zurück zum Zitat 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):534–538CrossRefPubMedPubMedCentral 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):534–538CrossRefPubMedPubMedCentral
Zurück zum Zitat 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 18:673–677CrossRefPubMed 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 18:673–677CrossRefPubMed
Zurück zum Zitat Kazanjian KK, Reber HA, Hines OJ (2006) Resection of pancreatic neuroendocrine tumors: results of 70 cases. Arch Surg 141:765–769CrossRefPubMed Kazanjian KK, Reber HA, Hines OJ (2006) Resection of pancreatic neuroendocrine tumors: results of 70 cases. Arch Surg 141:765–769CrossRefPubMed
Zurück zum Zitat 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 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
Zurück zum Zitat Kloppel G (2011) Classification and pathology of gastroenteropancreatic neuroendocrine neoplasms. Endocr Relat Cancer 18(Suppl1):S1–S16CrossRefPubMed Kloppel G (2011) Classification and pathology of gastroenteropancreatic neuroendocrine neoplasms. Endocr Relat Cancer 18(Suppl1):S1–S16CrossRefPubMed
Zurück zum Zitat 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 456:595–597CrossRefPubMed 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 456:595–597CrossRefPubMed
Zurück zum Zitat 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 33:765–770CrossRefPubMed 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 33:765–770CrossRefPubMed
Zurück zum Zitat 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):30–40CrossRefPubMed 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):30–40CrossRefPubMed
Zurück zum Zitat 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 54:376–379PubMed 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 54:376–379PubMed
Zurück zum Zitat 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 115:3068–3077CrossRefPubMed 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 115:3068–3077CrossRefPubMed
Zurück zum Zitat 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 253:94–100CrossRefPubMed 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 253:94–100CrossRefPubMed
Zurück zum Zitat 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 32:2218–2222CrossRefPubMed 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 32:2218–2222CrossRefPubMed
Zurück zum Zitat Nakao A (2010) The sixth edition of general rules for the study of pancreatic cancer by Japan Pancreas Society. Pancreas 39:696CrossRef Nakao A (2010) The sixth edition of general rules for the study of pancreatic cancer by Japan Pancreas Society. Pancreas 39:696CrossRef
Zurück zum Zitat 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 27:277–283CrossRefPubMed 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 27:277–283CrossRefPubMed
Zurück zum Zitat 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 95:71–73CrossRefPubMed 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 95:71–73CrossRefPubMed
Zurück zum Zitat 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 23:824–833CrossRefPubMed 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 23:824–833CrossRefPubMed
Zurück zum Zitat 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 19:117–123CrossRefPubMed 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 19:117–123CrossRefPubMed
Zurück zum Zitat 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 182:177–182CrossRefPubMed 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 182:177–182CrossRefPubMed
Zurück zum Zitat Stahel RA (1992) Morphology, surface antigens, staging, and prognostic factors of small cell lung cancer. Curr Opin Oncol 4:308–314CrossRefPubMed Stahel RA (1992) Morphology, surface antigens, staging, and prognostic factors of small cell lung cancer. Curr Opin Oncol 4:308–314CrossRefPubMed
Zurück zum Zitat 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 21:418–425CrossRefPubMed 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 21:418–425CrossRefPubMed
Zurück zum Zitat 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 20:1172–1182CrossRefPubMed 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 20:1172–1182CrossRefPubMed
Zurück zum Zitat 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 249:118–123CrossRefPubMed 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 249:118–123CrossRefPubMed
Zurück zum Zitat 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 14:3492–3500CrossRefPubMedPubMedCentral 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 14:3492–3500CrossRefPubMedPubMedCentral
Zurück zum Zitat 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 26:3063–3072CrossRefPubMed 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 26:3063–3072CrossRefPubMed
Metadaten
Titel
Macroscopic morphology for estimation of malignant potential in pancreatic neuroendocrine neoplasm
verfasst von
Eriko Katsuta
Atsushi Kudo
Takumi Akashi
Yusuke Mitsunori
Satoshi Matsumura
Arihiro Aihara
Daisuke Ban
Takanori Ochiai
Shinji Tanaka
Yoshinobu Eishi
Minoru Tanabe
Publikationsdatum
17.02.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 6/2016
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-016-2128-1

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