Pathology of liver diseases PDF
Preview Pathology of liver diseases
Pathology of Liver Diseases Pathology of Liver Diseases Gary C. Kanel, M.D. Clinical Professor of Pathology Keck Medical Center of USC Department of Pathology and Laboratory Medicine Los Angeles, CA, USA This edition first published 2017 © 2017 John Wiley & Sons Ltd. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by law. Advice on how to obtain permission to reuse material from this title is available at http://www.wiley.com/go/permissions. The right of Gary C. Kanel to be identified as the author of this work has been asserted in accordance with law. 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Identifiers: LCCN 2017001716 (print) | LCCN 2017002257 (ebook) | ISBN 9781118895030 (cloth) | ISBN 9781118895023 (pdf) | ISBN 9781118895009 (epub) Subjects: | MESH: Liver Diseases—pathology Classification: LCC RC845 (print) | LCC RC845 (ebook) | NLM WI 700 | DDC 616.3/62—dc23 LC record available at https://lccn.loc.gov/2017001716 Cover images: Courtesy of the author. Set in 10/12pt Warnock Pro by Aptara Inc., New Delhi, India 10 9 8 7 6 5 4 3 2 1 v Contents Preface vi About the companion website viii Chapter 1 Normal Liver 1 Chapter 2 Viral Hepatitis 24 Chapter 3 Fatty Liver Diseases 50 Chapter 4 Diseases of the Biliary Tract 72 Chapter 5 Non-Viral Infectious Diseases 95 Chapter 6 Granulomatous Hepatitis 123 Chapter 7 Autoimmune Hepatitis 131 Chapter 8 Vascular Disorders 143 Chapter 9 Genetic and Metabolic Hepatic Diseases 162 Chapter 10 Developmental Hepatobiliary Disorders and Cystic Diseases 198 Chapter 11 Drug- and Toxin-Induced Liver Diseases 215 Chapter 12 Liver Transplantation 231 Chapter 13 Hepatic Tumors, Benign 266 Chapter 14 Hepatic Tumors, Malignant 289 Chapter 15 Miscellaneous Hepatic Disorders 337 Index 354 vi Preface With all of the advancements in hepatology, also remain the gold standard in the staging including invasive and non-invasive imaging, and grading of chronic liver diseases to deter- laboratory tests targeting specific diseases, mine the appropriate individual therapies. For molecular biology, and genomics, one might all of these reasons, useful reference material, as think that liver biopsy material in patients with presented in this book Pathology of Liver Dis- suspected acute or chronic liver diseases or eases, is most helpful to the pathologist and the hepatic tumors may not be as necessary in arriv- patients’ attending physicians in arriving at the ing at a specific diagnosis as it was in the past; diagnosis or best possibilities that fit each indi- however, what still persists is an inconsistency vidual patient. oftentimes in the way patients clinically present Pathology of Liver Diseases uses both book with laboratory tests and what in fact the biopsy and online material in the presentation of shows. This therefore leads to the continued the whole range of liver diseases seen in both importance of liver biopsy interpretation. the community hospitals as well as academic The settings where liver biopsies are espe- medical centers. The book in fifteen chapters cially crucial tools in patient care are numer- emphasizes not only the pathology seen in ous, are discussed in more detail in Chapter 1, biopsy and surgically resected or transplanted and include assessing patients who present and autopsy material, but also the most per- with clinical signs of acute or chronic liver dis- tinent clinical and laboratory findings includ- ease but with normal liver tests, patients with ing epidemiology and the various etiologic abnormal liver tests inconsistent with the sus- and pathophysiologic concepts, imaging when pected diagnosis (e.g., clinical diagnosis of acute appropriate, and the differential diagnostic viral hepatitis with an unexpectedly high alka- possibilities with references. line phosphatase value), and patients in acute Furthermore, what significantly adds to the liver failure and those with transaminitis of overall usefulness of the book is the online no known cause. Biopsies are often warranted material. An online Library Images that contains in the evaluation of various space-occupying over 850 images of the various liver diseases is lesions when imaging, cultures or fine needle offered that significantly adds to the over 540 aspirates are not conclusive. Biopsies are often images already in the book. Additional online critical in specifically evaluating liver trans- Tables to those already in the book are added so plant patients where the clinical presentation that the reader can have a more detailed refer- and liver test abnormalities can hint at any of a ence to the grading and staging systems of fatty whole range of possibilities including acute or liver diseases, viral and autoimmune hepatitis, chronic rejection, biliary strictures, infections, and liver transplant rejection. In addition 140 or recurrent disease, all of which necessitate Case Examples from patients seen at the Keck different treatment approaches. Lastly biopsies Medical Center of USC as well as from consult Preface vii case material are presented in PowerPoint for- the operating table of the step-by-step process mat that demonstrate the various ways many of in liver transplantation. these disease entities present clinically and the The amount of information targeting the pathology seen, including both classic and com- numerous fields of medicine has exponentially mon examples such as alcoholic hepatitis as well increased over recent years. The addition of this as cases infrequently seen such as progressive book and online material will not only be most familiar intrahepatic cholestasis. Finally, cour- valuable in enabling the viewer to have access to tesy of Dr. Rick Selby, Professor of Surgery and the wealth of material in diagnostics but also in Chief of Hepatobiliary, Pancreatic Surgery and gaining a better overall understanding of these Abdominal Organ Transplantation at the Keck hepatic and hepatobiliary disorders. Medical Center of USC, the PowerPoint pres- entation Liver Transplantation – Surgical Pro- Gary C. Kanel, cedure is also included with photographs from Los Angeles, 2017 viii About the companion website This book is accompanied by a companion website: www.wiley.com/go/kanel/liverpathology The website includes the following to supplement each chapter: ● A complete Reference List ● 140 Case Examples, which include over 420 images that demonstrate the various ways many of these disease entities clinically present. ● A Library that contains over 860 images of the various liver diseases, which adds to over 540 images that are in the book itself. There are also: ● Additional Tables that address in detail the grading and staging of various liver diseases such as viral hepatitis and fatty liver diseases. ● A PowerPoint presentation entitled “Liver Transplantation – Surgical Procedure”, which includes photographs from the operating table of the step-by-step process in liver transplantation. To access the website, you will need to enter the password, which is the first word of the first para- graph in Chapter 15. 1 1 Normal Liver The liver is a unique organ that has numerous first seen as a hollow midline outgrowth stalk structural and physiological functions. It is most (hepatic diverticulum) of the endodermal epi- important when discussing liver pathology that thelium at the distal aspect of the foregut. By one understands first the normal liver histology the fourth week, the diverticulum enlarges from before one can best understand the basic patho- proliferation of the endodermal cell strands physiologic concepts of the numerous liver dis- (hepatoblasts) and projects cranially into the eases. The pathologist plays a fundamental role mesoderm of the septum transversum, eventu- in assessing the various morphologic features ally giving rise to the liver hepatic parenchyma seen in liver tissue, whether by fine needle aspi- and intrahepatic ducts. The cephalic end ulti- rates, needle or wedge biopsies, partial hepatec- mately develops into the right and left hepatic tomies, liver explants, or autopsy material. The lobes, while the stalk between the diverticulum pathologist also has not only routine but also and foregut narrows and forms the extrahepatic numerous special histochemical and immuno- biliary system and gallbladder. histologic stains as well. Yet correlating the his- Solid cords are initially formed by proliferat- tologic findings with the most pertinent clinical ing endodermal cells. These eventually anasto- and laboratory data enables the pathologist to mose to form vesicles and cribriform tubules better arrive at a diagnosis and the most perti- with centrally located lumenal structures (bil- nent differential possibilities. iary canaliculi). The cords eventually merge and This introductory chapter addresses all aspects develop small channels and capillaries that sub- of the normal liver, reviewing the embryologic divide the cords to eventually form the hepatic development, gross and microscopic features, sinusoids. The individual hepatoblasts are pro- the pertinent intracytoplasmic components and genitor cells that develop into mature hepato- how their function varies with their location cytes, with those immediately adjacent to the within the hepatic lobule, and the importance of portal mesenchyme becoming the ductal plates. stem cell function within the liver. Additionally The rapid growth rate of the hepatic cords ena- the various useful stains and laboratory values bles the development of sheets of cells (mura- will also be presented, as well as a brief outline lium multiplex) that persist until birth, after of how best to organize pathologic readings and which the cell sheets narrow to two cells (mura- signouts of liver biopsy specimens. lium duplex) and eventually evolve within the first year of life into a one cell thick trabecular cord (muralium simplex). The perisinusoidal Embryology cells and Kupffer cells appear by three months gestation. The hepatic primordium anlage initially appears The mesoderm from the septum transversum at the end of the third week of gestation and is initially surrounds the liver and is directly in Pathology of Liver Diseases, First Edition. Gary C. Kanel. © 2017 John Wiley & Sons, Ltd. Published 2017 by John Wiley & Sons, Ltd. Companion website: www.wiley.com/go/kanel/liverpathology 2 1 Normal Liver contact with the lesser curvature of the stom- Additionally with time the left lobe diminishes in ach, duodenum, and ventral body wall. The size, and the caudate and quadrate lobes develop mesoderm eventually forms the lesser omen- as subdivisions of the right lobe. tum, the falciform, coronary, and triangular lig- The vascular network, originally derived from aments, with a portion developing into the liver the development of the vitelline and umbilical (Glisson) capsule. The mesoderm on the liver veins, occurs at the same time as proliferation surface is also in continuity with the perito- of the hepatoblasts, with the sinusoids forming neum, and the portion that makes contact with from anastomosis of the hepatic cords and ves- the future diaphragm remains uncovered (bare sels. By the fifth week of gestation most of the area). The developing hepatic artery and vagus major vessels are present and include the right nerve branches follow the mesoderm along and and left umbilical veins, the transverse portal adjacent to the portal vein. sinus, and the ductus venosus, which shunts The mesoderm is the main focus in the devel- blood from the umbilical vein into the inferior opment of hematopoiesis, which begins at about vena cava. The portal vein initially develops 6 weeks and becomes most active during the from the vitelline vein and then subdivides into fifth month of gestation. This process regresses the right and left branches. The hepatic and with increase in bone marrow activity. The portal vein branches divide the parenchyma erythroid precursors are most prominent during into the individual lobules and acini. At birth, fetal development within the hepatic sinusoids a sphincter mechanism closes the ductus veno- while the myeloid and megakaryocytic precur- sus, resulting in cessation of blood flow through sors reside mostly within the portal structures the umbilical vein, with the liver now receiving (Figure 1.1). This hematopoiesis is responsible blood from the left branch of the portal vein. for the enlarged size of the liver (up to 10% body The biliary apparatus develops from mem- weight by the tenth week of gestation, with the branous infoldings between the junctional com- right and left lobes taking up an equal volume), plexes located between individual hepatoblasts but this size significantly regresses at birth (5% and initially appears as intercellular spaces with of body weight) at which time only rare small no distinct wall. The biliary canaliculi are first clusters of normoblasts can be seen. By 4 weeks seen at 6 weeks of gestation, with synthesis of of age hematopoietic activity has usually ceased. bile occurring by the ninth week and secretion of bile by the twelfth week. The ductal plate, which is initially two layers thick, is formed from the periportal hepatoblasts. A lumen develops by the third month (see Figure 1.1) with event- ual formation of double-layered tubular (ductu- lar) structures. The true interlobular bile ducts occur immediately after birth from remodeling of these ductular elements. This biliary network receives its blood supply from a complex of arte- rioles and capillaries formed from the peribiliary plexus. The extrahepatic biliary tree develops from the stalk of the original hepatic outgrowth. Individual cell functions become apparent at different stages of the embryologic develop- Figure 1.1 Embryonic development. A developing ment. α-Fetoprotein, found in high amounts at bile ductule is seen at the border of the portal tract and parenchyma. The portal tract and sinusoids birth, initially is seen within the hepatocytes by contain hematopoietic precursors (extramedullary one month gestation and continues throughout hematopoiesis). fetal development, with high serum levels at Gross Anatomy 3 birth. Fatty change (steatosis), glycogen and gly- liver is larger compared with adjacent thoracic cogen synthesis become most apparent by two and abdominal viscera and constitutes about to three months gestation, with the glycogen 5–6% of the body weight. eventually diminishing due to rapid glycogenol- Anatomically, the liver has four lobes: right, ysis. Hemosiderin is usually seen early on but left, caudate, and quadrate. The right lobe gradually decreases, with some often occurring accounts for one-half to two-thirds of the total in the periportal hepatocytes at birth. liver volume and is divided from the left lobe by the falciform ligament on gross inspection; however, functionally the right and left lobes Gross Anatomy are of about equal size and are divided by a line extending from the inferior vena cava superiorly The adult liver weighs from 1200 to 1800 g, to the middle of the gallbladder fossa inferiorly. dependent on the overall body size, takes up A total of eight functional segments are present, the majority of the right upper abdominal cavity each having its own vascular supply and biliary beneath the rib cage, and extends from the right drainage: the right posterolateral (VI and VII), lateral aspect of the abdomen 15–20 cm trans- right anterolateral (V and VIII), left anterior (IV), versely toward the xiphoid process. Although left posterior (II and III), and the caudate lobe (I), the weight of the adult liver constitutes about the latter being a watershed area of both the right 1.8–3.1% of the total body weight, at birth the and left lobes blood supply (Figure 1.2). Right posterolateral Right anterolateral Left anterior Left posterior Middle hepatic vein Right hepatic vein Left hepatic vein II VII VIII I IV III Umbilical vein (remnant) VI V Inferior vena cava Hepatic artery Portal vein Hepatic duct Figure 1.2 Schematic anatomical vascular arrangements of the liver. The liver is divided into eight functional anatomical segments, each having its own vascular supply and biliary drainage: the right posterolateral (VI and VII), right anterolateral (V and VIII), left anterior (IV), left posterior (II and III), and the caudate lobe (I). Source: Wanless IR. Physioanatomic considerations. In: Schiff’s Diseases of the Liver, 11th edn. Oxford: Wiley Blackwell, 2012. Reproduced with permission of John Wiley & Sons.
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