Pancreatic Cytopathology: The Solid Neoplasms

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1 Pancreatic Cytopathology: The Solid Neoplasms Syed Z. Ali, M.D. Professor of Pathology and Radiology Director of Cytopathology The Johns Hopkins Hospital Baltimore, Maryland Pancreatic Cytopathology: Past, Present And Future Fine Needle Aspiration of the Pancreas 60-80% of FNA diagnoses are MALIGNANT % are ACA Pancreatic Cytopathology: Past, Present And Future Pancreatic Cancer New Cases: 43,920 Deaths: 37,390 (85%) 4 th leading cause of cancer-related death in both sexes 4% live 5 years after the diagnosis 80-85% present with advanced unresectable disease *NCI 2012 SEER Cancer Statistics Review 1

2 Pancreatic Cytopathology The Fear Factor 3 rd most common site where normal cells are misinterpreted as neoplastic/malignant ~ 10% of Whipple surgeries performed for presumed malignancy (clinical and/or FNA findings) reveal benign disease on histopathology ~ 25% of these have autoimmune pancreatitis (AIP) or lymphoplasmacytic sclerosing pancreatitis (LSP) Cytopathology Of The Pancreas - A Multi Disciplinary Approach Surgeon Radiologist Clinical Findings Imaging Chemistry Cytomorphology Gastroenterologist Cytopathologist 2

3 Solid Neoplasms Of The Pancreas [Exocrine Pancreas] Ductal Carcinoma Variants Acinar Cell Carcinoma Pancreatoblastoma Solid Pseudopapillary Neoplasm Ductal Adenocarcinoma 3

4 Adenocarcinoma Cytologic Grading Well - Moderate - Poor - Flat Sheets More crowded 3-D Tissue fragments Pleomorphism (Focal) Hypochromatic Micronucleoli More single cells Pleomorphism (Extensive) Hyperchromatic Macronucleoli Why do we grade? Fine-tune our diagnosis and differential diagnoses Optimize cancer therapy (if PD, neoadjuvant therapy is often considered) Prognostication (indicator of poor outcome in resectable disease) Grading should preferably be two tiered (not five) 4

5 Immunoperoxidase Profile CK 7 +, CK 20 - CEA +, CA MUC1 +, MUC4 + MUC2- (Cf IPMN And Mucinous Cystic Neo) Chromogranin+ (Focal, Scattered Cells) DPC4 (SMAD4)- (Loss/Inactivation-55%) Other Markers Mesothelin Fascin 5

6 Ductal Carcinoma - Variants Mucinous Non-cystic Adenocarcinoma (Colloid) Signet-ring Cell Carcinoma Medullary Carcinoma Adenosquamous Carcinoma Undifferentiated Carcinoma With Osteoclast-like Giant Cells Anaplastic (Undifferentiated) Carcinoma Mucinous Non-cystic Adenocarcinoma (Colloid) Majority arise in association with intestinal-type IPMN Overall prognosis better than conventional tubular ductal ACA (not stage-adjusted) 6

7 Signet-ring Cell Carcinoma Highly aggressive and rare cancer Rule out metastasis to the pancreas (gastric, breast lobular) Medullary Carcinoma Associated with microsatellite instability, colonic adenocarcinoma Usually no KRAS mutations, 20% have inactivation of DNA mismatch repair system Adenosquamous Cell Carcinoma 7

8 Poorer Prognosis - median overall survival 10 mo The proportion of squamous differentiation is often not associated with median overall survival (< 30% versus > or = 30%) Undifferentiated Carcinoma with Osteoclast-like Giant Cells Often a component of an in-situ or invasive ACA Poor prognosis (< one year) 8

9 Anaplastic (undifferentiated) Carcinoma Extremely bad prognosis Rule out metastasis to the pancreas (melanoma) Acinar Cell Carcinoma 9

10 Trypsin (100%), lipase (80%), chymotrypsin (40%), and amylase (30%) Focal neuroendocrine marker immunoexpression (upto 43%) Alterations in the KRAS oncogene and in the SMAD4 (DPC4) and p53 tumor suppressor genes are usually not seen Overall median survival 19 months (age, size and stage) 10

11 Solid-Pseudopapillary Neoplasm 11

12 Beta-Catenin CD99 Endocrine Pancreas Pancreatic Neuroendocrine Tumor (PanNet) High-grade NE Carcinoma Small cell type Large cell type Pancreatic Neuroendocrine Tumor (PanNet) 12

13 NE markers +, CK7 -, PAX 8 + Size (>0.5cm are malignant) Grading with Ki-67 % (G1 0-2%, G2 3-20%, G3->20% or NE Carcinoma) 13

14 14

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