Neuro-endocrine and pancreatic non-adenocarcinomas. Marc Engelbrecht, AMC, Amsterdam

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1 Neuro-endocrine and pancreatic non-adenocarcinomas Marc Engelbrecht, AMC, Amsterdam

2 Pancreatic Tumors q Epithelial Exocrine q Mesenchymal Ductal Adenocarcinoma (85-95%) Metastasis Lymfoma Acinar Cell Carcinoma Solid Pseudopapillairy Tumor Pancreatoblastoma Endocrine Hyperfunctioning Neuro-endocrine tumor Non-Hyper Functioning Neuro-endocrine tumor

3 >95 % Ductal adenocarcinoma q Neuro-endocrine tumor 1-5% q Metastases 2-5% q Solid-pseudopapillairy tumor 1-2% SEER

4 Classification (P)NET Ø Classic: Foregut Midgut - Hindgut Ø Usual: Pancreas-Lung-Stomach Ø Histology: well-moderate-low differentiation Ø Syndrome: Functional vs Non-Hyper functional Ø Carcinoïd Only midgut tumors

5 Clinical features (P)NET Ø increased incidence 1,5 => 5/ / Yr Ø 90 % NF NET detected on radiology Ø yr Ø usually sporadic Ø 1-2 % association with MEN 1, VHL, NF1, TS

6 Classification PNET Functional PNET 25% Insulinoma Gastrinoma Vipoma Glucagonoma Somatostatinoma Non-Hyper functional PNET 75% Zerbi et al Am J Gastroenterol 2010; 105: Clinicopathological Features of Pancreatic Endocrine Tumor: A prospective Multicenter Study in Italy of 297 Sporadic Cases

7 Prognosis Type Tumor Malignant Post-op surv. Non functioning PNET 90% 50% Insulinoma 10% 100% Gastrinoma 60% 90%

8 Pathology Origin is ductal / acinar system (not Langerhans islets) Hormonal activity not correlated with histology Morphology depends on size

9 Morphology ü Small (3cm) ü Well demarcated ü Solid ü Homogeneous enhancement ü Insulinomas - Gastrinomas ü larger (8 cm) ü Well demarcated ü Cystic degeneration/necrosis ü Circumferential enhancement ü Calcification ü Local invasion ü Vascular invasion ü NF-NET

10 Imaging PNET High resolution dual phase CT Oral water / Upper abdomen 2 mm arterial phase imaging sec. post contrast injection 2 mm portal phase imaging sec. post contrast injection Coronal reconstructions MRI PET-CT Indium 111 SPECT/CT if possible treatment with radioactive somatostatine

11 Non functioning PNET ü Clinically relevant PNET ü MEN1/VHL => multiple tumors ü Pain, loss of weight, mass, seldom jaundice ü 60-80% metastases

12 Imaging CT: Depends on size Enhancement art /portal phase hyper attenuating Heterogeneous/ homogeneous Calcifications Nodal and livermetastasen are also hypervascular!

13 Imaging MRI: Low on T1 High on T2 T2 can be intermediate (collagen) Intense homogeneous / heterogeneous enhancement Nodal and liver metastases T2 hyperintens and enhancing

14 5 Serous microcystic adenoma multiple small cysts < 2cm Lobulated Central scar (30%), central Ca (18%) Hypervascular enhancement DD Cystic neuroendocrine tumor Colonna J. et al Pancreatology 2008;8: Kim, H.J. et al AJR 2008; 190: Curry CA et al AJR 175;:99-103

15 Clinical Findings Insulinoma ü Most prevalent hyperfunctional PNET ü Whipple triad (=Hypoglycemia, dizziness, palpitations) ü 90% benign, single mass, < 2 cm ü 2-10% multiple tumors : MEN I ü Homogenenous ü Anywhere in pancreas

16 Imaging ü Arterial enhancement < 2cm homogeneous enhancement > 2cm heterogeneous (ringlike) enhancement ü ü ü ü Larger lesions cystic degeneration / necrosis Calcification Sometimes atypical late enhancement Metastases to nodes and liver may have same enhancement.

17 7 year-old boy Possible epileptic Angry and irritated, better after food Increased appetite and concentration deficit 9/2/2012 large seizure=> blood glucose extreme low, insuline extreme high

18 Gastrinoma ü 2 de Functional PNET ü Zollinger Ellison syndrome = hypersecretion/ Diarrhea Ø 75% sporadic Ø 25% ~ MEN1 syndrome (= PNET/ Hyperparathyreoid/ Hypophysis tumors) ü 60% malignant ü Delay in dx = average 5.2 yr

19 Classical ü Av. size 4 cm ü 50% not localized pre-op ü 90% Gastrinoma Triangle ü 10% corpus/tail Sporadic Gastrinomas: Ø 50-60% pancreas Ø 35-40% duodenum wall Ø remainder stomach / lymphnodes

20 Adenocarcinoma vs NET ü NET = hypervascular, hyperattenuating ü Calcification (2% adenocarcinoma calcification) ü Carcinoma dilatation PD ü Central Necrosis / Cystic degeneration NET Adenocarcinoma

21 So: Think PNET if: ü Hypervascular (rim) enhancement ü Cystic degeneration ü Calcification ü Small tumor homogeneous ü larger tumor heterogeneous

22 Isolated Metastases Pancreas Rare; 2-5% all pancreatic tumors Autopsy: 1,6 % metastases pancreas Isolated secondary tumor (surgical series) Renalcel carcinoma 33% Lymphoma 14% Gastro-intestinal 13% Remainder (Breast, liver, ovary, prostate) 40% Adsay NV Secondary tumors of the pancreas: an analysis of a surgical and autopsy database and review of the literature Virchows Arch (2004) 444: Ioannis T Konstantinidis et al Metastatic Tumors in the Pancreas in the Modern Era J Am Coll Surg December ; 211(6):

23 Solid-pseudopapillary tumor (SPT) Synonyma: Hammoudi tumor, Frantz tumor, Solid Cystic Papillary Epithelial Tumor (SPEN) Demography: Asymptomatic 85% young female Av.: 30 jaar ü Origin primordial cells without endocrine of exocrine differentiation ü Low malignant potential ü Good prognosis after resection, even with metastases Choi J-Y et al AJR 2006;187W178-W186 Buetow, P Radiology 1996; 199:

24 Solid-Pseudopapillary Tumor Ø Large tumor (Av 9.0 cm) Ø Cystic Solid Ø Pseudo capsule Ø Well defined Ø Bleeding (may be absent) Cantisani V AJR:181: Buetow C 1996 Radiology;199:

25 Remember Capsulated cystic tumor Young female Bleeding Ø SPT until proven otherwise

26 So ü Young woman + Cystic Solid Tumor => Solid Pseudopapillary Tumor ü Cystic solid tumor with arterial enhancement in older pts => Neuro-endocriene Tumor

27 Summary Neuroendocrine tumor ü Hypervascular (rim) enhancement ü Cystic Metastasis ü Renal cell carcinoma Solid pseudopapillary tumor ü young female with large tumor

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