Pancreatobiliary Frozen Section Nightmares Aatur D. Singhi, MD PhD Assistant Professor University of Pittsburgh Medical Center Department of Pathology singhiad@upmc.edu Objectives Briefly give an overview or perspective of pancreatic cancer. Review the appropriate margins to be taken for frozen section from pancreatobiliary specimens. Examine the histopathology of pancreatobiliary margins on frozen section. Discuss some of the difficulties ( gray areas ) in assessing pancreatobiliary margins. 4th Leading cause of cancer deaths in the United States. 1st Mortality rate among all major cancers. LAST 40 YEARS Pancreatic Breast Leukemia Cancer 5-Year 5-Year Survival Survival Rate Rate Rate Trend Trend 90.2 % 75.1 % 58.1 % 34.4 % 2 % 6% 1973 Of Breast the 10 Clinical cancer most survival trials lethal have cancers, rates helped have pancreatic turn increased the cancer odds significantly. in remains 2013 Breakthroughs the only favor one in early with of those a detection single-digit with leukemia. deserve survival much rate. credit. Adapted from http://www.pancan.org 1
4th Leading cause of cancer deaths in the United States. 1st Mortality rate among all major cancers. 94% 74% 55% 0 Die within 5 years of being diagnosed. Die within the first year of diagnosis. Increase in new pancreatic cancer cases projected over the next 2 decades. Early detection methods and successful treatment options have been discovered. Adapted from http://www.pancan.org 20% Surgically resectable and considered the only chance for a cure. Adapted from http://www.pancan.org 2
Vascular groove Uncinate process Adapted from http://pathology.jhu.edu/pc/professionals/index.php Vascular groove Uncinate process Adapted from http://pathology.jhu.edu/pc/professionals/index.php 3
Bile Duct Margin Pancreatic Neck Margin Adapted from http://pathology.jhu.edu/pc/professionals/index.php Pancreatic Neck Margin Adapted from http://pathology.jhu.edu/pc/professionals/index.php Bile Duct Margin Bbb Pancreatic Neck Margin Adapted from http://pathology.jhu.edu/pc/professionals/index.php 4
Bile Duct Margin Pancreatic Neck Margin Proximal Duodenal Margin Adapted from http://pathology.jhu.edu/pc/professionals/index.php Adapted from http://pathology.jhu.edu/pc/professionals/index.php Adapted from http://pathology.jhu.edu/pc/professionals/index.php 5
Adapted from http://pathology.jhu.edu/pc/professionals/index.php Adapted from http://pathology.jhu.edu/pc/professionals/index.php Adapted from http://pathology.jhu.edu/pc/professionals/index.php 6
Adapted from http://pathology.jhu.edu/pc/professionals/index.php Adapted from http://pathology.jhu.edu/pc/professionals/index.php Adapted from http://pathology.jhu.edu/pc/professionals/index.php 7
Adapted from http://pathology.jhu.edu/pc/professionals/index.php Pancreatic Neck Margins - Artifacts FFPE Pancreatic Neck Margins - Artifacts 8
Pancreatic Neck Margins - Artifacts Tissue folding Tissue folding Over staining (hematoxylin) Pancreatic Neck Margins - Artifacts Tissue folding Over staining (hematoxylin) Over staining (eosin) Pancreatic Neck Margins - Artifacts 9
Pancreatic Neck Margins - Artifacts Tissue folding Over staining (hematoxylin) Over staining (eosin) Cauterization Tissue folding Over staining (hematoxylin) Over staining (eosin) Cauterization Drying Pancreatic Neck Margins - Artifacts Tissue folding Over staining (hematoxylin) Over staining (eosin) Cauterization Drying Thick sections Pancreatic Neck Margins - Artifacts 10
Pancreatic Neck Margins - Artifacts Tissue folding Over staining (hematoxylin) Over staining (eosin) Cauterization Drying Thick sections Air bubbles Normal Pancreas Pancreatic Neck Margins Normal Pancreas Pancreatic Neck Margins Chronic Pancreatitis Normal Pancreas Chronic Pancreatitis Variable lobules 11
Pancreatic Neck Margins Chronic Pancreatitis Normal Pancreas Chronic Pancreatitis Variable lobules Interlobular fibrosis Pancreatic Neck Margins Chronic Pancreatitis Normal Pancreas Chronic Pancreatitis Variable lobules Interlobular fibrosis (absence of glands) Pancreatic Neck Margins Chronic Pancreatitis Normal Pancreas Chronic Pancreatitis Variable lobules Interlobular fibrosis (absence of glands) Acinar loss 12
Pancreatic Neck Margins Chronic Pancreatitis Normal Pancreas Chronic Pancreatitis Variable lobules Interlobular fibrosis (absence of glands) Acinar loss Pancreatic Neck Margins Chronic Pancreatitis Normal Pancreas Chronic Pancreatitis Variable lobules Interlobular fibrosis (absence of glands) Acinar loss Ductal changes Pancreatic Neck Margins Chronic Pancreatitis Normal Pancreas Chronic Pancreatitis Variable lobules Interlobular fibrosis (absence of glands) Acinar loss Ductal changes - Reactive 13
Pancreatic Neck Margins Chronic Pancreatitis Normal Pancreas Chronic Pancreatitis Variable lobules Interlobular fibrosis (absence of glands) Acinar loss Ductal changes - Reactive - Open lumen - Absence of luminal debris Pancreatic Neck Margins Chronic Pancreatitis Normal Pancreas Chronic Pancreatitis Variable lobules Interlobular fibrosis (absence of glands) Acinar loss Ductal changes - Reactive - Open lumen - Absence of luminal debris - Remains within the lobule Pancreatic Neck Margins Chronic Pancreatitis Normal Pancreas Chronic Pancreatitis Variable lobules Interlobular fibrosis (absence of glands) Acinar loss Ductal changes - Reactive - Open lumen - Absence of luminal debris - Remains within the lobule 14
Pancreatic Neck Margins Chronic Pancreatitis Normal Pancreas Chronic Pancreatitis Variable lobules Interlobular fibrosis (absence of glands) Acinar loss Ductal changes - Reactive - Open lumen - Absence of luminal debris - Remains within the lobule - Squamous metaplasia - Intraluminal concretions Pancreatic Neck Margins Normal Pancreas Normal Pancreas Chronic Pancreatitis Variable lobules Interlobular fibrosis (absence of glands) Acinar loss Ductal changes Pancreatic Neck Margins Chronic Pancreatitis Normal Pancreas Chronic Pancreatitis Variable lobules Interlobular fibrosis (absence of glands) Acinar loss Ductal changes Islets of Langerhans - Aggregation 15
Pancreatic Neck Margins Chronic Pancreatitis Normal Pancreas Chronic Pancreatitis Variable lobules Interlobular fibrosis (absence of glands) Acinar loss Ductal changes Islets of Langerhans - Aggregation - Fusion Pancreatic Neck Margins Chronic Pancreatitis Normal Pancreas Chronic Pancreatitis Variable lobules Interlobular fibrosis (absence of glands) Acinar loss Ductal changes Islets of Langerhans - Aggregation - Fusion - Myxoid change Pancreatic Neck Margins Chronic Pancreatitis Normal Pancreas Chronic Pancreatitis Variable lobules Interlobular fibrosis (absence of glands) Acinar loss Ductal changes Islets of Langerhans - Aggregation - Fusion - Myxoid change - Pseudoglandular appearance 16
Pancreatic Neck Margins Chronic Pancreatitis Normal Pancreas Chronic Pancreatitis Variable lobules Interlobular fibrosis (absence of glands) Acinar loss Ductal changes Islets of Langerhans - Aggregation - Fusion - Myxoid change - Pseudoglandular appearance - Persistence of reticular architecture 17
Glands in interlobular septa Glands in interlobular septa FFPE Glands in interlobular septa 18
Glands in interlobular septa Growth near muscular vessels Glands in interlobular septa Growth near muscular vessels Growth near nerves Glands in interlobular septa Growth near muscular vessels Growth near nerves 19
Glands in interlobular septa Growth near muscular vessels Growth near nerves Lymphovascular and perineural invasion Glands in interlobular septa Growth near muscular vessels Growth near nerves Lymphovascular and perineural invasion FFPE Glands in interlobular septa Growth near muscular vessels Growth near nerves Lymphovascular and perineural invasion 20
Glands in interlobular septa Growth near muscular vessels Growth near nerves Lymphovascular and perineural invasion FFPE Glands in interlobular septa Growth near muscular vessels Growth near nerves Perineural invasion Glands in interlobular septa Growth near muscular vessels Growth near nerves Lymphovascular and perineural invasion Luminal necrosis or debris 21
Glands in interlobular septa Growth near muscular vessels Growth near nerves Lymphovascular and perineural invasion Luminal necrosis or debris Incomplete glands Glands in interlobular septa Growth near muscular vessels Growth near nerves Lymphovascular and perineural invasion Luminal necrosis or debris Incomplete glands 4:1 nuclear variability Glands in interlobular septa Growth near muscular vessels Growth near nerves Lymphovascular and perineural invasion Luminal necrosis or debris Incomplete glands 4:1 nuclear variability 22
Glands in interlobular septa Growth near muscular vessels Growth near nerves Lymphovascular and perineural invasion Luminal necrosis or debris Incomplete glands 4:1 nuclear variability Glands in interlobular septa Growth near muscular vessels Growth near nerves Lymphovascular and perineural invasion Luminal necrosis or debris Incomplete glands 4:1 nuclear variability FFPE Normal Bile Duct Bile Duct Margins - Normal 23
Bile Duct Margins - Artifact Tissue folding Over staining (hematoxylin) Over staining (eosin) Cauterization Drying Thick sections Air bubbles Bile Duct Margins - Normal Bile Duct Margins - Normal 24
Bile Duct Margins - Adenocarcinoma Perineural invasion Perineural invasion Bile Duct Margins - Adenocarcinoma Perineural invasion Involvement of periductular soft tissue Bile Duct Margins - Adenocarcinoma 25
Proximal Duodenal Resection Margins - Normal Proximal Duodenal Resection Margins - Adenocarcinoma Lymphovascular invasion Proper appreciation of normal anatomy, histology and non-neoplastic pathology Features supporting a diagnosis of adenocarcinoma - pattern - Glands within interlobular septa - Growth of glands near muscular vessels and nerves - Lymphovascular and perineural invasion - Incomplete glands - Necrotic glandular debris - Nuclear variation, 4:1 26
Challenging Issues The presence of pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasms (IPMN) at the pancreatic neck margin Dysplasia at the bile duct margin Acellular mucin present within the pancreatic parenchymal margin Adenocarcinoma within a lymph node at a margin Lymphovascular or perineural invasion within the peripancreatic soft tissue at the pancreatic neck margin Incidentalomas Pancreatic Intraepithelial Neoplasia (PanIN) Pancreatic Intraepithelial Neoplasia (PanIN) 27
Pancreatic Intraepithelial Neoplasia (PanIN) Pancreatic Intraepithelial Neoplasia (PanIN) Intraductal Papillary Mucinous Neoplasm (IPMN) 28
Intraductal Papillary Mucinous Neoplasm (IPMN) Intraductal Papillary Mucinous Neoplasm (IPMN) Intraductal Papillary Mucinous Neoplasm (IPMN) 29
Intraductal Papillary Mucinous Neoplasm (IPMN) Intraductal Papillary Mucinous Neoplasm (IPMN) Biliary Dysplasia at the Bile Duct Margin 30
Biliary Dysplasia at the Bile Duct Margin Biliary Dysplasia at the Bile Duct Margin Frozen FFPE The Presence of Acellular Mucin 31
The Presence of Acellular Mucin The Presence of Acellular Mucin Colloid Carcinoma The Presence of Acellular Mucin Colloid Carcinoma 32
The Presence of Acellular Mucin Neoadjuvant Chemotherapy FFPE The Presence of Acellular Mucin Neoadjuvant Chemotherapy FFPE Adenocarcinoma within a Lymph Node at a Margin 33
Adenocarcinoma within a Lymph Node at a Margin Intraneural or Perineural Invasion within the Peripancreatic Soft Tissue Intraneural or Perineural Invasion within the Peripancreatic Soft Tissue 34
Intraneural or Perineural Invasion within the Peripancreatic Soft Tissue Frozen FFPE Incidental Lesions Incidental Lesions 35
Objectives Briefly give an overview or perspective of pancreatic cancer. Review the appropriate margins to be taken for frozen section from pancreatobiliary specimens. Examine the histopathology of pancreatobiliary margins on frozen section. Discuss some of the difficulties ( gray areas ) in assessing pancreatobiliary margins. Pancreatobiliary Frozen Section Nightmares Aatur D. Singhi, MD PhD Assistant Professor University of Pittsburgh Medical Center Department of Pathology singhiad@upmc.edu 36