INTRODUCTION
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Background to the Updates in the 2017 WHO Grading System
Ambiguity of Grade 3 NEC in the 2010 WHO Grading System
Table 1
WHO Classification: Comparison to WHO 2010 and 2017
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*MiNENs may have non-endocrine component other than adenocarcinoma, e.g., squamous cell carcinoma or acinar cell carcinoma. To qualify as MiNEN, each component must be at least 30%. HPF = high power fields, MANEC = mixed adenoneuroendocrine carcinoma, MiNEN = mixed endocrine non-endocrine neoplasm, NEC = neuroendocrine carcinoma, NEN = neuroendocrine neoplasm, NET = neuroendocrine tumor, WHO = World Health Organization
The 2017 WHO Grading System
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Background to the Updates in the 8th AJCC Staging System
Table 2
Differences between AJCC/UICC TNM Staging System and ENETS TNM Staging System (for Well-Differentiated NET of Pancreas)
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*Confined to pancreas means there is no invasion of adjacent organs or wall of large vessels. Extension of tumor into peripancreatic adipose tissue is NOT basis for staging. AJCC = American Joint Committee on Cancer, ENETS = European Neuroendocrine Tumor Society, UICC = Union for International Cancer Control
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Updates in Strategies for Treatment of Pancreatic NENs
Well-Differentiated Grade 1/2/3 NETs
Poorly Differentiated Grade 3 NEC
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Updates Regarding Pancreatic NENs
Imaging of NENs: NETs versus NECs
![]() | Fig. 2Imaging spectrum of pancreatic NENs according to histologic grade.
A. Low-grade NET is generally small-sized and has well-defined margins on imaging (arrow). B. Higher-grade NET is likely to be larger or more frequently show necrotic change (arrow). C. NEC shows less enhancement than NET, and presents as iso-enhancing or hypoenhancing mass in pancreas. Margin of NEC may be less well demarcated than that of NET (arrow).
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![]() | Fig. 3Grade 1 NET in 42-year-old man.
A. 2.9-cm, arterial enhancing hypervascular mass in tail of pancreas was found on initial contrast-enhanced CT (arrows). B. After seven years, hypervascular mass in tail of pancreas had increased in size (arrow) and there was new hypervascular mass in liver (arrowheads), suggestive of hepatic metastasis. Fluid collection and peripancreatic infiltration were also present because of secondary pancreatitis. C. On 18F-FDG PET/CT, tumors showed negative or weak uptake. D. PET/CT with 68gallium-labeled somatostatin analog revealed 3.3-cm mass with markedly increased uptake (maximum standard uptake value, 40.6) in tail of pancreas (arrow), other foci in body of pancreas, and additional hepatic masses (arrowheads) with increased uptake, suggesting multifocal NET with overexpression of somatostatin receptor. Physiologic uptake was seen in both adrenal glands. E. Patient underwent transarterial embolization for management of hepatic metastases and arteriography showed hypervascular mass in right portion of liver. CT = computed tomography, FDG = fluorodeoxyglucose, PET = positron-emission tomography F. On histologic specimens (× 100) obtained during liver biopsy, tumor appeared to have relatively uniform and round nuclei with abundant cytoplasmic granules on H&E staining, low Ki-67 index (1.5%), and diffuse positivity on synaptophysin and chromogranin staining. These imaging and histologic findings suggested morphologically well-differentiated NET. H&E = hematoxylin and eosin
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![]() | Fig. 4Grade 3 NEC in 41-year-old woman.This patient was referred to our hospital with tentative diagnosis of ductal carcinoma of pancreas.
A. Magnetic resonance cholangiopancreatography showed abrupt tapering of intrapancreatic common bile duct with diffuse upstream dilatation. B. Contrast-enhanced CT showed 2.5-cm, relatively well-defined, low attenuating solid mass in head of pancreas. C. Tumor showed high FDG avidity on FDG-PET. Imaging reports suggested possibility of NEC as well as ductal adenocarcinoma of pancreas, indicating need for biopsy. D. H&E staining (× 40) revealed small, round, blue cells in tumor. Immunohistochemistry specimens (× 40) showed positivity on synaptophysin (E) and Ki-67 (F) staining with Ki-67 proliferation index of 70%. These findings confirmed diagnosis of NEC.
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Diagnostic Challenges
![]() | Fig. 5Atypical imaging findings in patients with pancreatic NENs.
A. Intraductal growth in 42-year-old woman. Axial contrast-enhanced CT scan shows large mass (arrow on left) with intraductal growth causing diffuse dilatation of bile duct upstream (arrows on right). First differential diagnosis was invasive cancer arising from intraductal papillary mucinous neoplasm. However, lesion was confirmed to be grade 3 NEC after surgical resection. B. Cystic change in 48-year-old man. Axial contrast-enhanced CT image shows 5.6-cm cystic lesion with relatively thick wall in tail of pancreas. Preoperative imaging diagnosis was pseudocyst or cystic neoplasm of pancreas. However, surgical specimen confirmed that lesion was grade 1 NET with cystic change. C. Vascular invasion with tumor thrombus in 29-year-old man. Axial contrast-enhanced CT image shows large heterogeneous attenuating mass involving body and tail of pancreas and left para-aortic area (arrowhead). Vascular invasion is apparent and there is tumor thrombus extending into splenoportal confluence (arrow). Biopsy confirmed diagnosis of grade 3 NEC.
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Resectability
![]() | Fig. 6Discrepancy in determining resectability between imaging and surgery.
A. Contrast-enhanced axial CT scan in 48-year-old man with NET in body of pancreas. Scan shows 5-cm mass (arrow) distortion of contour of main portal vein because of circumferential contact between tumor and portal vein of more than 180 degrees (arrowheads). These CT findings may suggest vessel invasion and indicate unresectability. B. Surgical specimen. Exploratory surgery in this patient confirmed that tumor was resectable in that main portal vein was severely compressed by tumor but without apparent vessel invasion. Therefore, distal pancreatectomy and splenectomy were performed. Gross specimen showed well-defined, ovoid soft-tissue mass (M) in body of pancreas but without vessel invasion.
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Future Directions of Imaging for NENs
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CONCLUSION
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