Pathology of the Pancreas A Practical Approach Fiona Campbell Caroline S. Verbeke Second Edition 123 Pathology of the Pancreas Fiona Campbell • Caroline S. Verbeke Pathology of the Pancreas A Practical Approach Second Edition Fiona Campbell Caroline S. Verbeke Department of Pathology Department of Pathology Royal Liverpool University Hospital Oslo University Hospital Liverpool University of Oslo UK Oslo Norway ISBN 978-3-030-49847-4 ISBN 978-3-030-49848-1 (eBook) https://doi.org/10.1007/978-3-030-49848-1 © Springer Nature Switzerland AG 2021 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland Preface There have been many advances in pancreatic pathology since we wrote the first edition of this book. Emerging endoscopy and tissue sampling proce- dures, such as pancreatoscopy, micro-forceps biopsies, and fine-needle biop- sies, are now being incorporated into routine diagnostic practice, and neoadjuvant therapy has become part of standard treatment. New diagnostic entities have been described, classifications and international guidelines have been updated, and molecular pathology is beginning to play a role in diagnos- tics and patient management. All of these advances have been incorporated into this new edition of the book. The book covers the spectrum of pancreatic pathology from congenital abnormalities and hereditary disorders to inflammatory disease and neopla- sia, and it now also includes an entirely new chapter on pancreas transplant pathology (kindly provided by René Michel). There is also limited informa- tion on the small super-specialized area of pediatric pancreatic pathology, and the cytology chapter has been kindly revised by M. Priyanthi Kumarasinghe and Ian Yusoff. The book incorporates the recent WHO 2019 classification and TNM8, and brief summaries of the main molecular alterations found in the most common pancreatic neoplasms have also been added. This is a practical bench book, intended for trainees in histopathology and consultants, who deal with pancreatic specimens. It aims to provide both practical information for all aspects of the diagnostic process and in-depth, up-to-date knowledge that is required for the pathologist’s participation in the multidisciplinary team meetings and discussions. There are more than 200 new macroscopic and microscopic images, enabling us to illustrate the wide range of appearances that the same tumor or disease entity can exhibit. The numerous illustrations are also used to provide a detailed, practical, step-by-step guide to macroscopic examination and specimen handling, as well as to explain the embryology and anatomy of the pancreas. There are more quick-reference tables, and the potential mimics and diagnostic pitfalls are included in differential diagnoses. There is exten- sive cross-referencing to allow the reader easy access to relevant information. v vi Preface Reporting checklists are provided for the main diagnostic entities with a sum- mary of key data items to include in the pathology report. We do hope that the reader will enjoy reading this new edition of the book and that it will continue to serve as a comprehensive resource in daily diag- nostic practice and multidisciplinary team discussion. Liverpool, UK Fiona Campbell Oslo, Norway Caroline S. Verbeke Acknowledgements We are grateful to Øystein Horgmo, University of Oslo, for his professional help with the photography. We thank Paul Brown, Specialist Medical Illustrator, The Leeds Teaching Hospitals NHS Trust, Leeds, UK for Medical Drawings. We would also like to thank all of our pathology and clinical col- leagues in Liverpool, Oslo, and Stockholm who, knowingly or unknowingly, have contributed to our knowledge and understanding of pancreatic pathology. Permission to use copyrighted illustrations has kindly been granted by • Elsevier (Cancer Treatment Reviews 2015;41:17–26) for Fig. 1.27 • Elsevier (Surgical Pathology 2016;19:523–38) for Figs. 3.19 and 3.34 • Springer Nature (Springer eBook—Operative specimen handling and evaluation of resection margins) for Fig. 3.31 • Blackwell Publishing Limited (Histopathology 2010;56:669–82) for Figs. 20.11 and 20.12 • John Wiley and Sons (American Journal of Transplantation 2003;3:599– 605) for Fig. 22.12 Chapter 22 on Pathology of Pancreas Transplantation is an updated ver- sion of the chapter ‘Pancreas Transplantation’ in: Michel RP, Berry GJ, edi- tors. Pathology of Transplantation A Practical Diagnostic Approach. Switzerland: Springer; 2016. p. 265–98. vii Contents Part I General Principles 1 Embryology, Anatomy, and Histology . . . . . . . . . . . . . . . . . . . . . . 3 1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1.2 Embryology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1.3 Anatomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 1.4 Histology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 2 Pancreatic Specimen Types . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 2.1 Pancreatoduodenectomy Specimens . . . . . . . . . . . . . . . . . . . . 25 2.2 Distal Pancreatectomy Specimens . . . . . . . . . . . . . . . . . . . . . . 26 2.3 Total Pancreatectomy Specimens . . . . . . . . . . . . . . . . . . . . . . . 27 2.4 Duodenum-Preserving Pancreatic Resection Specimens . . . . . 27 2.5 Complex Multivisceral En Bloc Resection Specimens . . . . . . 28 2.6 Central Pancreatectomy Specimens . . . . . . . . . . . . . . . . . . . . . 28 2.7 Enucleation Specimens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 2.8 Specimens Following Frey, Beger, or Puestow Procedures . . . 29 2.9 Laparoscopic and Robot- Assisted Resection Specimens . . . . 30 2.10 Pancreas Allograft . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 3 Specimen Dissection and Sampling . . . . . . . . . . . . . . . . . . . . . . . . 33 3.1 Handling of Fresh Specimens . . . . . . . . . . . . . . . . . . . . . . . . . 33 3.2 Specimen Fixation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 3.3 Macroscopic Examination of Pancreatoduodenectomy Specimens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 3.4 Dissection of Distal Pancreatectomy Specimens . . . . . . . . . . . 55 3.5 Dissection of Total Pancreatectomy Specimens . . . . . . . . . . . 56 3.6 D issection of Multivisceral En Bloc Resection Specimens . . . . . 56 3.7 Dissection of Other Pancreatic Specimen Types . . . . . . . . . . . 56 3.8 Handling of Pancreatic Biopsies . . . . . . . . . . . . . . . . . . . . . . . 59 3.9 Reporting Checklist of Macroscopic Findings . . . . . . . . . . . . 59 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 4 The Pancreatic Multidisciplinary Team . . . . . . . . . . . . . . . . . . . . 61 4.1 Discussion of Postoperative Cases . . . . . . . . . . . . . . . . . . . . . . 61 4.2 Discussion of Pretreatment Cases . . . . . . . . . . . . . . . . . . . . . . 62 ix x Contents 4.3 Other Roles and Responsibilities . . . . . . . . . . . . . . . . . . . . . . . 63 Reference . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 Part II E xocrine Pancreas: Non-Cystic 5 Common Minor Changes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 5.1 Acinar Cell Nodules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 5.2 Acinar Dilatation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 5.3 Acinar to Ductal Metaplasia . . . . . . . . . . . . . . . . . . . . . . . . . . 68 5.4 Duct Epithelial Metaplasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 5.5 Lobulocentric Atrophy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 5.6 Age-Related Alterations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 5.7 Fatty Replacement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 5.8 Changes in Islets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 5.9 Autolytic Change . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76 6 Hereditary Exocrine Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . 77 6.1 Cystic Fibrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77 6.2 Hereditary Hemochromatosis . . . . . . . . . . . . . . . . . . . . . . . . . 78 6.3 Hereditary Pancreatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 6.4 Inherited Pancreatic Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . 82 6.5 Familial Pancreatic Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 6.6 Screening High-Risk Individuals . . . . . . . . . . . . . . . . . . . . . . . 83 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84 7 Inflammatory Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 7.1 Acute Pancreatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 7.2 Chronic Pancreatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93 7.3 Other Inflammatory Diseases of the Pancreas . . . . . . . . . . . . . 128 7.4 Pancreatitis in Children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132 7.5 Reporting Checklist . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134 8 Pancreatic Intraepithelial Neoplasia . . . . . . . . . . . . . . . . . . . . . . . 137 8.1 WHO Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138 8.2 Classification and Microscopy . . . . . . . . . . . . . . . . . . . . . . . . . 138 8.3 Variants of PanIN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139 8.4 Associations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140 8.5 Lobulocentric Atrophy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140 8.6 Differential Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143 Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143 9 Ductal Adenocarcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145 9.1 Definition and Terminology . . . . . . . . . . . . . . . . . . . . . . . . . . . 145 9.2 Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145 9.3 Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146 9.4 Clinical Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147 Contents xi 9.5 Macroscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147 9.6 Microscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150 9.7 Grading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154 9.8 Morphological Patterns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155 9.9 Immunohistochemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159 9.10 Tumor Propagation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161 9.11 Staging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 164 9.12 Differential Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 170 9.13 Treatment and Prognosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179 9.14 Histological Subtypes of Ductal Adenocarcinoma . . . . . . . . . 181 9.15 Carcinoma with Mixed Differentiation . . . . . . . . . . . . . . . . . . 191 9.16 Mixed Acinar-Ductal Carcinoma . . . . . . . . . . . . . . . . . . . . . . . 191 9.17 Ductal Adenocarcinoma Following Neoadjuvant Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191 9.18 Diagnostic Molecular Pathology . . . . . . . . . . . . . . . . . . . . . . . 197 9.19 Reporting Checklist . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 198 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199 10 Acinar Cell Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203 10.1 WHO Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203 10.2 Terminology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203 10.3 Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203 10.4 Clinical Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203 10.5 Macroscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204 10.6 Microscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205 10.7 Histochemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207 10.8 Immunohistochemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207 10.9 Molecular Pathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209 10.10 Variants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209 10.11 Differential Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 210 10.12 Staging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213 10.13 Prognosis and Management . . . . . . . . . . . . . . . . . . . . . . . . . . 213 10.14 Reporting Checklist . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213 Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 214 11 Non-Epithelial Neoplasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215 11.1 Mesenchymal Neoplasms of the Pancreas . . . . . . . . . . . . . . . 216 11.2 Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223 12 Secondary Neoplasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225 12.1 Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225 12.2 Clinical Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225 12.3 Macroscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 226 12.4 Microscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227 12.5 Differential Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 228 12.6 Synchronous Primary and Metastatic Cancer . . . . . . . . . . . . 231 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234