Pancreatic tumors: A simple diagnostic path. Dept. of Pathology University of Tübingen

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1 Pancreatic tumors: A simple diagnostic path Prof. Dr. Bence Sipos Dept. of Pathology University of Tübingen

2 Solid tumors Cystic lesions

3 Solid Tumors Age Gender Size Endocrine Neoplasms Any Both cm Solid Pseudopapillary Female (>95%) 4-12 cm Neoplasms Acinar Cell Carcinomas Both 5-20 cm

4 Solid Tumors Macroscopy Localization Endocrine Neoplasms Solid any white-yellowish no necrosis Solid Pseudopapillary solid-cystic any Neoplasms solid: grey-brown cystic: necrotic-haemorrhagic well-defined Acinar Cell Carcinomas coarsly nodular with necrotic areas any gross infiltration

5 Solid Tumors Endocrine SPN ACC

6 Endocrine Neoplasms

7 Solid Pseudopapillary Neoplasm

8 Acinar Cell Carcinoma

9 IHC of Solid Tumors Endocrine markers Synaptophysin, Chromogranin-A, (CD56,NSE) Endocrine SPN ACC

10 IHC of Solid Tumors Cytokeratins (Pan-CK) CK8,18 (CAM5.2) Endocrine SPN ACC

11 Endocrine Tumors: distinctive markers Vasoactive peptides: Pancreatic : Ins, Gluc, PP, Somatostatin, Ectopic: Gastrin, VIP

12 Solid Pseudopapillary Neoplasms: Vimentin, nuclear ß-catenin, (CD10, PR, α1- antitrypsin, NSE) essential markers Vimentin ß-Catenin α1-antitrypsin

13 Acinar Cell Carcinomas: essential markers Pancreatic Enzymes: Trypsin (> 95%), Lipase (70%), Amylase (30%), bcl-10 Trypsin

14 Solid tumors : Proliferation Rate Ki67 Endocrine SPN ACC

15 Solid tumors Firm, ill-defined, invasive Solid, minimal stroma Glandular differentiation, Desmoplasia, mucin production Ductal adenocarcinoma Young female Cystic, necrotic, Well-defined Vimentin, nu ß-Catenin, CD10, no/minimal Ck Solid without necrosis Well-defined Synaptophysin, Chromogranin Elderly patient Large tumor with Necrosis Gross invasion Trypsin, Chymotripsin Solid pseudopapillary neoplasm Endocrine neoplasm Acinar cell carcinoma

16 Cystic tumors Age Gender Size Serous Cystadenomas >50 Female 5-15 cm Mucinous Cystic Neoplasms >50 Female >5 cm Intraductal Papillary Mucinous Neoplasms >50 Both Variable

17 Cystic tumors Macroscopy Localization Serous Cystadenomas microcystic sponge-like tail-body oligocystic no connection with ducts Mucinous Cystic Neoplasms unicystic or multicystic tail well circumscribed no connection with ducts Intraductal Papillary Mucinous Neoplasms dilated ducts mostly head papillary formations fibrotic pancreas

18 Serous cystic adenoma Mucinous Cystic Neoplasia

19 Serous Microcystic Adenoma

20 Mucinous Cystic Neoplasm

21 Mucinous Cystic Neoplasm Inhibin-α

22 Intraductal papillary mucinous neoplasm

23 IPMN intestinal type

24 IPMN intestinal type MUC 1 MUC2 MUC5 CDX2

25 IPMN pancreatobiliary type

26 IPMN pancreatobiliary type MUC 1 MUC2 MUC5 CDX2

27 IPMN oncocytic type

28 IPMN gastric type

29 IPMN gastric type

30 IPMN gastric type MUC 1 MUC 2 MUC 5

31 Cystic tumors Microcystic, ill-defined, invasive Glandular differentiation, Desmoplasia, mucin production Microcystic well-differentiated ductal adenocarcinoma yes IPMN at the periphery Connection to ducts central no In tail, woman Uni/multicystic Ovarian-like stroma Mucinous cystic neoplasm Well-defined Sponge-like Central scar Clear cells Inhibin Branch duct (gastric) type Intestinal diff (CDX2, CK20) yes no Serous cystadenoma Intestinal type Pancreatobiliary type

32 Classification of IPMN Type Histology Atypia Similar to MUC1 MUC2 MUC5 Invasive carcinoma Intestinal Villous papillae, columnar cells, oval nuclei with pseudostratification Mild to severe Colonic villous adenoma Colloid (mucinous) carcinoma Pancreato- Branching complex papillae, Severe Intraductal Ductal single layer or papillary adenocarcinoma biliary pseudostratification lesions of moderate amphophilic cytoplasm, enlarged nuclei the extrahepatic bile duct Oncocytic Gastric Thick branching complex papillae with intraepithelial lumina, large cells with abundant eosinophilic cytoplasm, large round nuclei Finger-like papillae or flat areas, eosinophilic or clear cytoplasm, basally located nuclei Severe Mild Oncocytic neoplasms of salivary glands Pyloric glands Oncocytic carcinoma Rarely ductal adenocarcinoma

33 Differential diagnosis of IPMN

34 Differential diagnosis of IPMN Yamaguchi et al 2009

35 Intraductal tubular carcinoma (ITC) M/F 1:1. mean age ~60 Solid/nodular tumors obstructing ducts No mucin production High grade nuclear atypia + CK7, CK19, Muc1, Muc6 - Muc2, Muc5AC, Rarely p53, Smad4; no β-catenin, K- ras, braf alterations Prognosis : 8/10 no recurrence (7-66 m) Yamaguchi et al 2009

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