ª Springer Science+Business Media New York 2015
Abdominal Imaging
Abdom Imaging (2015) DOI: 10.1007/s00261-015-0458-0
Non-hyperfunctioning pancreatic endocrine tumors: multimodality imaging features with histopathological correlation Peter E. Humphrey,1,2 Francesco Alessandrino,3 Andrew M. Bellizzi,4,5 Koenraad J. Mortele2,3 1
Northwest Imaging, Kalispell Regional Medical Center, Kalispell, MT 59901, USA Division of Abdominal Imaging and Intervention, Department of Radiology, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA 3 Division of Body MRI, Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Ansin 224, Boston, MA 02215, USA 4 Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA 5 Department of Surgical Pathology, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA 2
Abstract Purpose: To evaluate the multimodality imaging features of non-hyperfunctioning pancreatic endocrine tumors (NF-PNET) with histopathological correlation. Methods: Preoperative imaging (CT: n = 23; MRI: n = 14; 111In-octreotide: n = 8) of 28 patients (17 female; mean age 55 years) with resected NF-PNET were evaluated for tumor location, size, morphology, attenuation/ signal intensity, 111In-octreotide uptake, cystic degeneration, and enhancement. Tissue specimens were assessed for the extent of stromal fibrosis, vascular density, presence of a fibrous pseudocapsule, and tumor grading. Correlation between imaging and histopathology was made using the Fisher-Freeman-Halton exact test. Results: NF-PNET arose from the pancreatic head/neck (n = 10), body (n = 7), and tail (n = 11). On CT, NFPNET (mean largest diameter: 4.4 cm) appeared predominantly solid (69.6%), well defined (91.3%), and oval (47.8%) in shape. In the late arterial phase, NF-PNET appeared mainly hypovascular (55.5%). Septations (30.4%) and calcifications (21.7%) were relatively uncommon. On MRI, NF-PNET (mean size: 2.6 cm) appeared most commonly as solid (57.1%), encapsulated (71.4%), oval (64.2%) lesions that were hyperintense on T2-WI (64.3%), and hypo- or isovascular to pancreas (66.7%) during the late arterial phase. Cystic NF-PNET (3.8 cm) were not significantly larger than solid (3.5 cm) NF-PNET Correspondence to: Koenraad J. Mortele; email: kmortele@bidmc. harvard.edu
(CT, p = 0.758; MRI, p = 0.451). 111In-octreotide uptake was demonstrated in 5/8 (62.5%) patients. At histopathology, NF-PNET were predominantly encapsulated (69.2%); stromal fibrosis comprised 75% 50–75% 25–50% 66% fibrosis. The 18 NF-PNET with a fibrous pseudocapsule were evaluated by contrast-enhanced CT (n = 15) and MRI (n = 11). Eight capsules were identified by CT (53.3%) and nine (81.8%) by MRI. All remaining encapsulated NF-PNET were characterized as having well-defined margins. Capsules were incorrectly identified by CT in two cases (13.3%) and MRI in one case (9%). The enhancement features of NF-PNET were compared with tumor grading. No statistically significant
P. E. Humphrey et al.: Non-hyperfunctioning pancreatic endocrine tumors Axial SPECT image (A) from an 111In-octreotide study shows radiopharmaceutical uptake (red arrow) within a solid NF-PNET (white arrow) in the body of the pancreas as seen on axial CT during late arterial phase (B); and similar uptake (C) in a cystic encapsulated NF-PNET in the medial pancreatic tail (red arrow) as seen on T1-weighted MR image with fat saturation in portal venous phase (white arrow) (D).
b Fig. 10.
correlation between the NF-PNET grade and enhancement was shown. No significant correlation between the NF-PNET grade and T-2 weighted signal intensity or fibrosis was shown in our study.
Discussion Our data confirm that NF-PNETs may vary significantly in appearance by CT and MRI, as previously reported in the literature [15–19]. Moreover, radiopharmaceutical uptake was seen in 62.5% of our NF-PNETs, a percentage lower than reported in the literature, in which radiopharmaceutical uptake is reported positive in 75– 100% of cases [17, 20]. In our series, the majority of NF-PNETs were well defined or encapsulated, predominantly solid, and hypovascular compared to the normal pancreas by CT and MRI. The latter observation is important since NFPNETs are reported as typically hypervascular at contrast-enhanced CT or MRI. However, cases with hypovascularity have been described, with varying prevalence [15, 19, 21, 22]. Interestingly, our study showed no correlation between the pattern of enhancement and vascular density, similar to another study on NF-PNET [19]. Previous studies on both hyperfunctioning and non-hyperfunctioning PNET, however, showed correlation between CT enhancement with tumor vascularity [22–24]. No correlation between the WHO grading and enhancement pattern was demonstrated, consistent with results reported in a study on 45 patients with NF-PNET [19]. Another study on 161 patients with PNET showed, however, correlation between enhancement and histological grade [23]. This may be related to the different study populations: while in our study we analyzed only NF-PNET, Kim et al. comprised patients with NFPNET and hyperfunctioning PNET. In addition, significant correlation was shown between Grade 3 and enhancement, when compared to Grade 1–2, while in our study we only compared Grade 1 with Grade 2 NFPNET as no cases of the rare Grade 3 NF-PNETs were present in our study [23]. In our study, 26.9% of NF-PNETs were predominantly cystic, which is lower than that reported by Buetow et al., who found a cystic appearance in 60% of cases [15]. In our series, however, only three patients had MEN1 syndrome, which showed to have a higher
P. E. Humphrey et al.: Non-hyperfunctioning pancreatic endocrine tumors
prevalence of cystic NF-PNET [25]. Interestingly, cystic NF-PNETs were not significantly larger than solid NFPNETs, in contrary to data reported for PNET [15, 26]. We observed NF-PNETs with an essentially completely cystic, unilocular appearance. A ring-like enhancing pseudocapsule was present in these unilocular examples and the observation of a similar-appearing lesion in the pancreas raises the possibility of a NF-PNET as the diagnosis [25]. Twenty percent of NF-PNET had detectable tumoral calcification on imaging, which is consistent with data reported in literature [15, 21]. Our data also supports the prior observation that NF-PNETs are typically hyperintense on T2-WI and hypointense on unenhanced, fat-saturated T1-WI [18, 19, 21]. However, we found a minority (35.7%) of NF-PNET are iso/hypointense on T2-WI. An abundance of intratumoral fibrosis accounts for the hypointense T2-WI appearance seen in some NF-PNETs. In our study, significant correlation between low signal on T2-WI and the degree of fibrosis was shown. In support, a case of carcinoid tumor with low T2-WI signal intensity and presence of fibrosis at histopathology has been previously reported [27]. No significant correlation between the NFPNET grade and T-2 weighted signal intensity or fibrosis was shown in our study. This study has various shortcomings. Firstly, the patient population with resected NF-PNETs is relatively small. However, all cases presented allowed for radiologic-pathologic correlation. Secondly, patients underwent various examinations with different imaging protocols, as these cases were obtained over a long period of time and studies performed at outside institutions were included. In summary, NF-PNETs have variable imaging appearances but are most commonly oval shaped, solid, and well-defined/encapsulated masses, and hypovascular on late arterial and portal venous phase. Cystic degeneration in a NF-PNET appears independent of tumor size. Low signal intensity on T2-WI correlates with extensive intratumoral fibrosis. Conflict of Interest The authors declare that they have no conflict of interest. Statement of Human and Animal Rights All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent For this type of study formal consent is not required.
References 1. Niederle MB, Hackl M, Kaserer K, Niederle B (2010) Gastroenteropancreatic neuroendocrine tumours: the current incidence and staging based on the WHO and European Neuroendocrine Tumour Society classification: an analysis based on prospectively collected parameters. Endocr Relat Cancer 17(4):909–918
2. Halfdanarson TR, Rubin J, Farnell MB, Grant CS, Petersen GM (2008) Pancreatic endocrine neoplasms: epidemiology and prognosis of pancreatic endocrine tumors. Endocr Relat Cancer 15:409– 427 3. Hruban RH, Pitman MB, Klimstra DS (2007) Endocrine neoplasms. In: Hruban RH, Pitman MB, Klimstra DS (eds) Tumors of the pancreas: AFIP atlas of tumor pathology fourth series. Washington DC: American Registry of Pathology, pp 251–304 4. Vortmeyer AO, Huang S, Lubensky I, Zhuang Z (2004) Non-islet origin of pancreatic islet cell tumors. J Clin Endocrinol Metab 89(4):1934–1938 5. Singh S, Dey C, Kennecke H, et al. (2014) Consensus recommendations for the diagnosis and management of pancreatic neuroendocrine tumors: guidelines from a Canadian National Expert Group. Ann Surg Oncol. doi:10.1245/s10434-014-4145-0 6. Metz DC, Jensen RT (2008) Gastrointestinal neuroendocrine tumors: pancreatic endocrine tumors. Gastroenterology 135:1469– 1492 7. Falconi M, Bartsch DK, Eriksson B, et al. (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(2):120–134 8. Taupenot L, Harper KL, O’Connor DT (2003) The chromogranin secretogranin family. N Engl J Med 348:1134–1149 9. Horton KM, Hruban RH, Yeo C, Fishman EK (2006) Multi-detector row CT of pancreatic islet cell tumors. Radiographics 26:453–464 10. Vagefi PA, Razo O, Deshpande V, et al. (2007) Evolving patterns in the detection and outcomes of pancreatic neuroendocrine neoplasms: the Massachusetts General Hospital experience from 1977 to 2005. Arch Surg 142:347–354 11. Jensen RT, Berna MJ, Bingham DB, Norton JA (2008) Inherited pancreatic endocrine tumor syndromes: advances in molecular pathogenesis, diagnosis, management, and controversies. Cancer 113(7 Suppl):1807–1843 12. Anlauf M, Schlenger R, Perren A, et al. (2006) Microadenomatosis of the endocrine pancreas in patients with and without the multiple endocrine neoplasia type 1 syndrome. Am J Surg Pathol 30(5):560– 574 13. Triponez F, Dosseh D, Goudet P, et al. (2008) Epidemiology data on 108 MEN 1 patients from the GTE with isolated nonfunctioning tumors of the pancreas. Ann Surg 243(2):265–272 14. Blansfield JA, Choyke L, Morita SY, et al. (2007) Clinical, genetic and radiographic analysis of 108 patients with von Hippel-Lindau disease (VHL) manifested by pancreatic neuroendocrine neoplasms (PNETs). Surgery 142(6):814–818 15. Buetow PC, Parrino TV, Buck JL, et al. (1995) Islet Cell Tumors of the Pancreas: pathologic-imaging correlation among size, necrosis and cysts, calcification, malignant behavior, and functional status. Am J Roentgenol 165:1175–1179 16. Balci NC, Semelka RC (2001) Radiologic features of cystic, endocrine and other pancreatic neoplasms. Eur J Radiol 38(2):113– 119 17. Lewis RB, Lattin GE Jr, Paal E (2010) Pancreatic endocrine tumors: radiologic-clinicopathologic correlation. Radiographics 30(6):1445–1464 18. Buetow PC, Miller DL, Parrino TV, Buck JL (1997) Islet cell tumors of the pancreas: clinical, radiologic, and pathologic-correlation in diagnosis and localization. Radiographics 17:453–472 19. Manfredi R, Bonatti M, Mantovani W, et al. (2013) Non-hyperfunctioning neuroendocrine tumours of the pancreas: MR imaging appearance and correlation with their biological behaviour. Eur Radiol 23(11):3029–3039 20. De Herder WW, Kwekkeboom DJ, Valkema R, et al. (2005) Neuroendocrine tumors and somatostatin: imaging techniques. J Endocrinol Invest 28(11):132–136 21. Foti G, Boninsegna L, Falconi M, Mucelli RP (2013) Preoperative assessment of nonfunctioning pancreatic endocrine tumours: role of MDCT and MRI. Radiol Med 118(7):1082–1101 22. Rodallec M, Vilgrain V, Couvelard A, et al. (2006) Endocrine pancreatic tumours and helical CT: contrast enhancement is correlated with microvascular density, histoprognostic factors and survival. Pancreatology 6(1–2):77–85
P. E. Humphrey et al.: Non-hyperfunctioning pancreatic endocrine tumors
23. Kim DW, Kim HJ, Kim KW, et al. (2014) Neuroendocrine neoplasms of the pancreas at dynamic enhanced CT: comparison between grade 3 neuroendocrine carcinoma and grade 1/2 neuroendocrine tumour. Eur Radiol. doi:10.1007/s00330014-3532-z 24. Jang KM, Kim SH, Lee SJ, Choi D (2014) The value of gadoxetic acid-enhanced and diffusion-weighted MRI for prediction of grading of pancreatic neuroendocrine tumors. Acta Radiol 55(2):140–148
25. Bordeianou L, Vagefi PA, Sahani D, et al. (2008) Cystic pancreatic endocrine neoplasms: a distinct tumor type? J Am Coll Surg 206(3):1154–1158 26. Gallotti A, Johnston RP, Bonaffini PA, et al. (2013) Incidental neuroendocrine tumors of the pancreas: MDCT findings and features of malignancy. Am J Roentgenol 200(2):355–362 27. Takaji R, Matsumoto S, Mori H, et al. (2008) Carcinoid tumors of the pancreas: dynamic CT and MRI features with pathological correlation. Abdom Imaging 34(6):753–758
Abdominal Imaging
Abdom Imaging (2015) DOI: 10.1007/s00261-015-0458-0
Non-hyperfunctioning pancreatic endocrine tumors: multimodality imaging features with histopathological correlation Peter E. Humphrey,1,2 Francesco Alessandrino,3 Andrew M. Bellizzi,4,5 Koenraad J. Mortele2,3 1
Northwest Imaging, Kalispell Regional Medical Center, Kalispell, MT 59901, USA Division of Abdominal Imaging and Intervention, Department of Radiology, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA 3 Division of Body MRI, Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Ansin 224, Boston, MA 02215, USA 4 Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA 5 Department of Surgical Pathology, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA 2
Abstract Purpose: To evaluate the multimodality imaging features of non-hyperfunctioning pancreatic endocrine tumors (NF-PNET) with histopathological correlation. Methods: Preoperative imaging (CT: n = 23; MRI: n = 14; 111In-octreotide: n = 8) of 28 patients (17 female; mean age 55 years) with resected NF-PNET were evaluated for tumor location, size, morphology, attenuation/ signal intensity, 111In-octreotide uptake, cystic degeneration, and enhancement. Tissue specimens were assessed for the extent of stromal fibrosis, vascular density, presence of a fibrous pseudocapsule, and tumor grading. Correlation between imaging and histopathology was made using the Fisher-Freeman-Halton exact test. Results: NF-PNET arose from the pancreatic head/neck (n = 10), body (n = 7), and tail (n = 11). On CT, NFPNET (mean largest diameter: 4.4 cm) appeared predominantly solid (69.6%), well defined (91.3%), and oval (47.8%) in shape. In the late arterial phase, NF-PNET appeared mainly hypovascular (55.5%). Septations (30.4%) and calcifications (21.7%) were relatively uncommon. On MRI, NF-PNET (mean size: 2.6 cm) appeared most commonly as solid (57.1%), encapsulated (71.4%), oval (64.2%) lesions that were hyperintense on T2-WI (64.3%), and hypo- or isovascular to pancreas (66.7%) during the late arterial phase. Cystic NF-PNET (3.8 cm) were not significantly larger than solid (3.5 cm) NF-PNET Correspondence to: Koenraad J. Mortele; email: kmortele@bidmc. harvard.edu
(CT, p = 0.758; MRI, p = 0.451). 111In-octreotide uptake was demonstrated in 5/8 (62.5%) patients. At histopathology, NF-PNET were predominantly encapsulated (69.2%); stromal fibrosis comprised 75% 50–75% 25–50% 66% fibrosis. The 18 NF-PNET with a fibrous pseudocapsule were evaluated by contrast-enhanced CT (n = 15) and MRI (n = 11). Eight capsules were identified by CT (53.3%) and nine (81.8%) by MRI. All remaining encapsulated NF-PNET were characterized as having well-defined margins. Capsules were incorrectly identified by CT in two cases (13.3%) and MRI in one case (9%). The enhancement features of NF-PNET were compared with tumor grading. No statistically significant
P. E. Humphrey et al.: Non-hyperfunctioning pancreatic endocrine tumors Axial SPECT image (A) from an 111In-octreotide study shows radiopharmaceutical uptake (red arrow) within a solid NF-PNET (white arrow) in the body of the pancreas as seen on axial CT during late arterial phase (B); and similar uptake (C) in a cystic encapsulated NF-PNET in the medial pancreatic tail (red arrow) as seen on T1-weighted MR image with fat saturation in portal venous phase (white arrow) (D).
b Fig. 10.
correlation between the NF-PNET grade and enhancement was shown. No significant correlation between the NF-PNET grade and T-2 weighted signal intensity or fibrosis was shown in our study.
Discussion Our data confirm that NF-PNETs may vary significantly in appearance by CT and MRI, as previously reported in the literature [15–19]. Moreover, radiopharmaceutical uptake was seen in 62.5% of our NF-PNETs, a percentage lower than reported in the literature, in which radiopharmaceutical uptake is reported positive in 75– 100% of cases [17, 20]. In our series, the majority of NF-PNETs were well defined or encapsulated, predominantly solid, and hypovascular compared to the normal pancreas by CT and MRI. The latter observation is important since NFPNETs are reported as typically hypervascular at contrast-enhanced CT or MRI. However, cases with hypovascularity have been described, with varying prevalence [15, 19, 21, 22]. Interestingly, our study showed no correlation between the pattern of enhancement and vascular density, similar to another study on NF-PNET [19]. Previous studies on both hyperfunctioning and non-hyperfunctioning PNET, however, showed correlation between CT enhancement with tumor vascularity [22–24]. No correlation between the WHO grading and enhancement pattern was demonstrated, consistent with results reported in a study on 45 patients with NF-PNET [19]. Another study on 161 patients with PNET showed, however, correlation between enhancement and histological grade [23]. This may be related to the different study populations: while in our study we analyzed only NF-PNET, Kim et al. comprised patients with NFPNET and hyperfunctioning PNET. In addition, significant correlation was shown between Grade 3 and enhancement, when compared to Grade 1–2, while in our study we only compared Grade 1 with Grade 2 NFPNET as no cases of the rare Grade 3 NF-PNETs were present in our study [23]. In our study, 26.9% of NF-PNETs were predominantly cystic, which is lower than that reported by Buetow et al., who found a cystic appearance in 60% of cases [15]. In our series, however, only three patients had MEN1 syndrome, which showed to have a higher
P. E. Humphrey et al.: Non-hyperfunctioning pancreatic endocrine tumors
prevalence of cystic NF-PNET [25]. Interestingly, cystic NF-PNETs were not significantly larger than solid NFPNETs, in contrary to data reported for PNET [15, 26]. We observed NF-PNETs with an essentially completely cystic, unilocular appearance. A ring-like enhancing pseudocapsule was present in these unilocular examples and the observation of a similar-appearing lesion in the pancreas raises the possibility of a NF-PNET as the diagnosis [25]. Twenty percent of NF-PNET had detectable tumoral calcification on imaging, which is consistent with data reported in literature [15, 21]. Our data also supports the prior observation that NF-PNETs are typically hyperintense on T2-WI and hypointense on unenhanced, fat-saturated T1-WI [18, 19, 21]. However, we found a minority (35.7%) of NF-PNET are iso/hypointense on T2-WI. An abundance of intratumoral fibrosis accounts for the hypointense T2-WI appearance seen in some NF-PNETs. In our study, significant correlation between low signal on T2-WI and the degree of fibrosis was shown. In support, a case of carcinoid tumor with low T2-WI signal intensity and presence of fibrosis at histopathology has been previously reported [27]. No significant correlation between the NFPNET grade and T-2 weighted signal intensity or fibrosis was shown in our study. This study has various shortcomings. Firstly, the patient population with resected NF-PNETs is relatively small. However, all cases presented allowed for radiologic-pathologic correlation. Secondly, patients underwent various examinations with different imaging protocols, as these cases were obtained over a long period of time and studies performed at outside institutions were included. In summary, NF-PNETs have variable imaging appearances but are most commonly oval shaped, solid, and well-defined/encapsulated masses, and hypovascular on late arterial and portal venous phase. Cystic degeneration in a NF-PNET appears independent of tumor size. Low signal intensity on T2-WI correlates with extensive intratumoral fibrosis. Conflict of Interest The authors declare that they have no conflict of interest. Statement of Human and Animal Rights All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent For this type of study formal consent is not required.
References 1. Niederle MB, Hackl M, Kaserer K, Niederle B (2010) Gastroenteropancreatic neuroendocrine tumours: the current incidence and staging based on the WHO and European Neuroendocrine Tumour Society classification: an analysis based on prospectively collected parameters. Endocr Relat Cancer 17(4):909–918
2. Halfdanarson TR, Rubin J, Farnell MB, Grant CS, Petersen GM (2008) Pancreatic endocrine neoplasms: epidemiology and prognosis of pancreatic endocrine tumors. Endocr Relat Cancer 15:409– 427 3. Hruban RH, Pitman MB, Klimstra DS (2007) Endocrine neoplasms. In: Hruban RH, Pitman MB, Klimstra DS (eds) Tumors of the pancreas: AFIP atlas of tumor pathology fourth series. Washington DC: American Registry of Pathology, pp 251–304 4. Vortmeyer AO, Huang S, Lubensky I, Zhuang Z (2004) Non-islet origin of pancreatic islet cell tumors. J Clin Endocrinol Metab 89(4):1934–1938 5. Singh S, Dey C, Kennecke H, et al. (2014) Consensus recommendations for the diagnosis and management of pancreatic neuroendocrine tumors: guidelines from a Canadian National Expert Group. Ann Surg Oncol. doi:10.1245/s10434-014-4145-0 6. Metz DC, Jensen RT (2008) Gastrointestinal neuroendocrine tumors: pancreatic endocrine tumors. Gastroenterology 135:1469– 1492 7. Falconi M, Bartsch DK, Eriksson B, et al. (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(2):120–134 8. Taupenot L, Harper KL, O’Connor DT (2003) The chromogranin secretogranin family. N Engl J Med 348:1134–1149 9. Horton KM, Hruban RH, Yeo C, Fishman EK (2006) Multi-detector row CT of pancreatic islet cell tumors. Radiographics 26:453–464 10. Vagefi PA, Razo O, Deshpande V, et al. (2007) Evolving patterns in the detection and outcomes of pancreatic neuroendocrine neoplasms: the Massachusetts General Hospital experience from 1977 to 2005. Arch Surg 142:347–354 11. Jensen RT, Berna MJ, Bingham DB, Norton JA (2008) Inherited pancreatic endocrine tumor syndromes: advances in molecular pathogenesis, diagnosis, management, and controversies. Cancer 113(7 Suppl):1807–1843 12. Anlauf M, Schlenger R, Perren A, et al. (2006) Microadenomatosis of the endocrine pancreas in patients with and without the multiple endocrine neoplasia type 1 syndrome. Am J Surg Pathol 30(5):560– 574 13. Triponez F, Dosseh D, Goudet P, et al. (2008) Epidemiology data on 108 MEN 1 patients from the GTE with isolated nonfunctioning tumors of the pancreas. Ann Surg 243(2):265–272 14. Blansfield JA, Choyke L, Morita SY, et al. (2007) Clinical, genetic and radiographic analysis of 108 patients with von Hippel-Lindau disease (VHL) manifested by pancreatic neuroendocrine neoplasms (PNETs). Surgery 142(6):814–818 15. Buetow PC, Parrino TV, Buck JL, et al. (1995) Islet Cell Tumors of the Pancreas: pathologic-imaging correlation among size, necrosis and cysts, calcification, malignant behavior, and functional status. Am J Roentgenol 165:1175–1179 16. Balci NC, Semelka RC (2001) Radiologic features of cystic, endocrine and other pancreatic neoplasms. Eur J Radiol 38(2):113– 119 17. Lewis RB, Lattin GE Jr, Paal E (2010) Pancreatic endocrine tumors: radiologic-clinicopathologic correlation. Radiographics 30(6):1445–1464 18. Buetow PC, Miller DL, Parrino TV, Buck JL (1997) Islet cell tumors of the pancreas: clinical, radiologic, and pathologic-correlation in diagnosis and localization. Radiographics 17:453–472 19. Manfredi R, Bonatti M, Mantovani W, et al. (2013) Non-hyperfunctioning neuroendocrine tumours of the pancreas: MR imaging appearance and correlation with their biological behaviour. Eur Radiol 23(11):3029–3039 20. De Herder WW, Kwekkeboom DJ, Valkema R, et al. (2005) Neuroendocrine tumors and somatostatin: imaging techniques. J Endocrinol Invest 28(11):132–136 21. Foti G, Boninsegna L, Falconi M, Mucelli RP (2013) Preoperative assessment of nonfunctioning pancreatic endocrine tumours: role of MDCT and MRI. Radiol Med 118(7):1082–1101 22. Rodallec M, Vilgrain V, Couvelard A, et al. (2006) Endocrine pancreatic tumours and helical CT: contrast enhancement is correlated with microvascular density, histoprognostic factors and survival. Pancreatology 6(1–2):77–85
P. E. Humphrey et al.: Non-hyperfunctioning pancreatic endocrine tumors
23. Kim DW, Kim HJ, Kim KW, et al. (2014) Neuroendocrine neoplasms of the pancreas at dynamic enhanced CT: comparison between grade 3 neuroendocrine carcinoma and grade 1/2 neuroendocrine tumour. Eur Radiol. doi:10.1007/s00330014-3532-z 24. Jang KM, Kim SH, Lee SJ, Choi D (2014) The value of gadoxetic acid-enhanced and diffusion-weighted MRI for prediction of grading of pancreatic neuroendocrine tumors. Acta Radiol 55(2):140–148
25. Bordeianou L, Vagefi PA, Sahani D, et al. (2008) Cystic pancreatic endocrine neoplasms: a distinct tumor type? J Am Coll Surg 206(3):1154–1158 26. Gallotti A, Johnston RP, Bonaffini PA, et al. (2013) Incidental neuroendocrine tumors of the pancreas: MDCT findings and features of malignancy. Am J Roentgenol 200(2):355–362 27. Takaji R, Matsumoto S, Mori H, et al. (2008) Carcinoid tumors of the pancreas: dynamic CT and MRI features with pathological correlation. Abdom Imaging 34(6):753–758
