Liver MRI: Correlation with Other Imaging Modalities and Histopathology [2nd ed.] 9783319060040, 331906004X

Table of contents :
Cover......Page 1
Contents......Page 14
Part I: MRI Technique, Contrast, Safety, Anatomy, and Differential......Page 18
Literature......Page 19
Literature......Page 21
Literature......Page 23
Literature......Page 25
5: MR Imaging Technique and Protocol......Page 27
Literature......Page 29
Literature......Page 31
Literature......Page 33
Literature......Page 35
Literature......Page 37
Literature......Page 39
Literature......Page 41
Literature......Page 43
Literature......Page 45
Literature......Page 47
Literature......Page 49
Literature......Page 51
18: T2 Bright Liver Lesions: Differential Diagnosis......Page 53
19: T1 Bright Liver Lesions: Differential Diagnosis......Page 55
20: T2 Bright Central Scar: Differential Diagnosis......Page 57
21: Lesions in Fatty Liver: Differential Diagnosis......Page 59
Part II: Fluid-Filled Liver Lesions......Page 61
Literature......Page 62
Literature......Page 64
Literature......Page 66
Literature......Page 68
Literature......Page 70
Literature......Page 72
Literature......Page 74
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Literature......Page 86
Literature......Page 88
Literature......Page 90
Literature......Page 92
Literature......Page 94
Literature......Page 96
Literature......Page 98
Literature......Page 100
Part III Solid Liver Lesions......Page 102
Part III A: Metastases: colorectal......Page 103
Literature......Page 104
Literature......Page 106
Literature......Page 108
Literature......Page 110
Literature......Page 112
Literature......Page 114
Literature......Page 116
Literature......Page 118
Literature......Page 120
Literature......Page 122
Part III B: Metastases: non-colorectal......Page 124
Literature......Page 125
Literature......Page 127
Literature......Page 129
Literature......Page 131
Literature......Page 133
Literature......Page 135
Literature......Page 137
Literature......Page 139
Literature......Page 141
Literature......Page 143
Literature......Page 145
Part III C: Primary solid liver lesions in cirrhotic liver......Page 147
Literature......Page 148
Literature......Page 150
Literature......Page 152
Literature......Page 154
Literature......Page 156
Literature......Page 158
Literature......Page 160
Literature......Page 162
Literature......Page 164
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Literature......Page 168
Literature......Page 170
Literature......Page 172
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Literature......Page 176
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Literature......Page 184
Literature......Page 186
Literature......Page 188
Literature......Page 190
Literature......Page 192
Literature......Page 194
Literature......Page 196
Literature......Page 198
Part III D: Primary solid liver lesions in non-cirrhotic liver......Page 200
Literature......Page 201
Literature......Page 203
Literature......Page 205
Literature......Page 207
Literature......Page 209
Literature......Page 211
Literature......Page 213
Literature......Page 215
Literature......Page 217
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Literature......Page 255
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Literature......Page 259
Literature......Page 261
Literature......Page 263
Literature......Page 265
Part IV: Diffuse Liver Parenchymal Disorders......Page 267
Literature......Page 268
Literature......Page 270
Literature......Page 272
Literature......Page 274
Literature......Page 276
Literature......Page 278
Literature......Page 280
Literature......Page 282
Literature......Page 284
Literature......Page 286
Literature......Page 288
Literature......Page 290
Literature......Page 292
Part V: Vascular Liver Lesions......Page 294
Literature......Page 295
Literature......Page 297
Literature......Page 299
Literature......Page 301
Literature......Page 303
Literature......Page 305
Literature......Page 307
Part VI: Biliary Tree Abnormalities......Page 309
Literature......Page 310
Literature......Page 312
Literature......Page 314
Literature......Page 316
Literature......Page 318
Literature......Page 320
Literature......Page 322
Literature......Page 324
Literature......Page 326
Literature......Page 328
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Literature......Page 338
Literature......Page 340
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Literature......Page 344
Literature......Page 346
Part VII: Pediatric Liver Lesions......Page 348
Literature......Page 349
Literature......Page 351
Literature......Page 353
Index......Page 355

Citation preview

Shahid M. Hussain Michael F. Sorrell

Liver MRI Correlation with Other Imaging Modalities and Histopathology Second Edition

Liver MRI

   

Shahid M. Hussain • Michael F. Sorrell

Liver MRI Correlation with Other Imaging Modalities and Histopathology Second Edition Forewords by Willis C. Maddrey and Richard C. Semelka

Shahid M. Hussain, M.D. Herbert B. Saichek Professor of Radiology University of Nebraska Medical Center Omaha, NE, USA

Michael F. Sorrell, M.D. Robert L. Grissom Professor of Medicine University of Nebraska Medical Center Omaha, NE, USA

ISBN 978-3-319-06003-3    ISBN 978-3-319-06004-0 (eBook) DOI 10.1007/978-3-319-06004-0 Springer Cham Heidelberg New York Dordrecht London Springer International Publishing Switzerland 2015 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. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher's location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. 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. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com)

To Elizabeth, Emma, and Charlotte SMH

To Shirley MFS

   

   

Foreword I

Liver MRI, now in its second edition, is a comprehensive well-written approach to the state of MRI art as regards the liver. Magnetic resonance imaging techniques and applications have rapidly and extensively evolved since the introduction of the technology in the early 1970s. Hepatologists have benefited greatly from the widespread availability and utilization of MRI which allows precise visualization of the liver and its surroundings in multiple planes and with extremely high resolution. Through MRI, we have relearned (or on occasion learned!) the precise anatomy of the liver and the environment in and around the liver. Through MRI we gain often valuable knowledge about blood flow to and from the liver. Furthermore, complications of cirrhosis have been carefully delineated including assessment of portal hypertension and demonstration of blockages in the portal vein, inferior vena cava, or hepatic veins. By going directly to MRI, clinicians save time, increase accuracy of diagnosis, and avoid ionizing radiation. In many aspects MRI is cost-efficient by decreasing the number of often used less precise imaging studies while adding considerably to the surety of a diagnosis. Advances in the formulation of contrast agents have made the procedure progressively safer and reactions to contrast agents have considerably diminished. Problems encountered earlier with nephrogenic fibrosis caused by gadolinium-based contrast media especially in patients with borderline renal function have largely been solved by new formulations. Even the issue of claustrophobia, which is a problem for many patients, has been minimized by the development of more open MRI. The differential diagnosis of a hepatic nodule is a superb example of the power of MRI in directing the clinician to the correct conclusion. A nodule (or suspected nodule) often initially identified on an ultrasonographic examination is evaluated by proceeding directly to MRI. The accurate diagnosis of hepatic nodules requires differentiation between hemangiomas, hepatic adenomas, focal nodular hyperplasia, regenerative nodules, and of course primary or metastatic tumors. Since many small malignant tumors are candidates for surgical removal, the information gleaned from the MRI provides a road map for designing resectional surgery. In addition MRI has well-recognized roles in the assessment of patients being considered for liver transplantation and in the post-transplantation follow-up. All these conditions are fully described in Liver MRI. The use of MRI in patients with a variety of chronic liver diseases may provide sufficient diagnostic information so that liver biopsy is less often needed. Within this volume many highly specific and rarely encountered disorders of the liver are well described. There are sections of the volume such as changes of the liver during pregnancy that I might never use but am comforted by knowing where I should go should the need arise. The section on hepatic vein thrombosis is of particular interest as is the section on iron in the liver and the changes found with progressive accumulation of iron up to and including the stage of cirrhosis. Liver MRI is a worthy companion to standard textbooks regarding the liver. As a non-radiologist, I approached the book cautiously only to be surprised by its accessibility in explaining the interpretation of hepatic disorders through the use of well-chosen images. The artistic drawings accompanying the radiographs are well done and informative. I found myself reading further and enjoying the learning experience. Armed with information from this volume, the clinician will be better prepared for productive consultations with radiologic colleagues. The volume is encyclopedic in scope yet designed so as to be approachable and understandable. Willis C. Maddrey, M.D. Adelyn and Edmund M. Hoffman Distinguished Chair in Medical Science Arnold N. and Carol S. Ablon Professorship in Biomedical Science Department of Internal Medicine UT Southwestern Dallas, TX, USA

Foreword II

In this second edition of this well-received book on MRI of the liver, Shahid Hussain has evolved all aspects of this work. The text is greatly expanded, including description of up-to-date sequences; many more figures are included; and he has incorporated as a coauthor Michael Sorrell who is a highly regarded hepatologist. In this regard Dr. Hussain has incorporated all elements necessary to generate a new textbook that keeps pace with the evolving nature of healthcare. Not only is it necessary to keep current and expand knowledge into imaging, which he has done, but by incorporating the efforts of a highly regarded clinician, he maintains the focus on what is essential for patients and for their care. In the current environment of superspecialization, this attention to patient-centric care, by involvement of experts with differing areas of expertise, is mandatory to ensure optimal patient management and outcome. It is also imperative, as multiple imaging modalities evolve, to pay attention to correlation of findings from the modality under description (MRI) with the other modalities that are commonly used to investigate an organ system, in this case, CT, ultrasound, and nuclear medicine. This serves therefore to put into context all the varying information that may be generated on a particular patient with particular imaging findings in the liver. As individual radiologists with subspecialization focus on their own area of interest, it becomes mandatory that some reference or source ties all this disparate information together. This is what this book accomplishes. The major focus of this book remains the description of MR imaging as the premier imaging modality to investigate the liver. Dr. Hussain has expanded considerably the content of this book in this regard, especially into diffuse liver diseases. As MRI is also very technology driven, this book provides up-to-date information on these technical advances. MR imaging is complex, due to the variety and depth of information provided and to the technical nature of the modality. Drs. Hussain and Sorrell have been able to render MRI descriptions into readily comprehensible information. This is aided by the correlation with other imaging modalities, to contextualize the findings. This book solidifies Shahid Hussain’s standing as one of the world’s greatest authorities on imaging of diseases of the liver. Michael Sorrell brings to the table international expertise into clinical information on patients with a variety of hepatic disease processes. This book remains a must-read for individuals interested in imaging findings in patients with suspected liver disease, including radiologists, hepatologists, residents, radiology technicians, and medical students. Richard C. Semelka, M.D. Professor and Vice-Chair of Quality and Safety, Director of MRI Services Department of Radiology University of North Carolina at Chapel Hill Chapel Hill, NC, USA

Preface

MR imaging has become the major tool for the diagnosis of liver diseases. The cross-sectional imaging techniques in general and MRI in particular often generate bewildering amount of information to accurately assess various liver abnormalities. This textbook provides the in-depth background information of all aspects of liver MRI and its applications to improve the level of understanding of the experts as well as the students of this field. With the faster imaging sequences, safer contrast media, lack of ionizing radiation, superb intrinsic soft tissue contrast, dynamic contrast-enhanced imaging, diffusion-weighted imaging, Dixon-based imaging (liver fat and iron quantification), MRCP, 4D flow imaging, MR elastography, and the liver-specific contrast agents, liver MRI has become central to the assessment of a wide spectrum of benign and malignant liver disorders. A substantial body of literature has demonstrated the efficacy of liver MRI compared to ultrasound and triple-phase CT. The clinicians and radiologists should collaborate and apply the best possible modality to assess the liver disorders in their clinical setting.

How to Use This Book Part I of the book provides the background information in regard to the MRI technique, contrast media, safety, and differential diagnosis. To diagnose most liver diseases, four sequences are most important to evaluate. These include: (1) a fat-suppressed T2-weighted sequence (or an equivalent sequence), (2) a T1 in-phase gradientecho sequence, (3) arterial-phase dynamic gadolinium-enhanced images, and (4) delayed-phase gadoliniumenhanced images. This book provides computer-generated drawings of these or four similar MRI sequences to highlight and explain the most important diagnostic findings. The direct MRI drawing comparison facilitates the interpretation of the important imaging findings. In addition, background information and up-to-date available literature are provided, with correlation to other imaging modalities (US, CT) and pathology. Liver abnormalities are divided into five major categories. Within each category, subcategories are provided and more specific diagnoses are listed alphabetically. Based on this book, liver MRI can be approached as follows: Step I: Categorize the liver abnormality into one of the five groups: 1. High fluid content liver lesions (high signal on T2 which persists on longer T2) 2. Solid liver lesions (moderately high signal on T2; similar to the spleen or lower) 3. Diffuse liver lesions (expressed by the diffuse or segmental abnormal signal or enhancement) 4. Vascular liver lesions (visible mainly in the arterial phase) 5. Biliary tree abnormalities (visible on T2-weighted and MRCP sequences) Step II: Evaluate the signal intensity on fat-suppressed T2- and T1-weighted sequences as well as gadolinium-enhanced images and attempt a more specific diagnosis. Step III: Compare your working diagnosis to the specific examples within each category systematically and confirm your finding into a more definitive (differential) diagnosis. This approach is consistently applied throughout the book, which shows that most liver lesions can be detected and characterized based on this method. Shahid M. Hussain, M.D. Herbert B. Saichek Professor of Radiology University of Nebraska Medical Center Omaha, NE, USA Michael F. Sorrell, M.D. Robert L. Grissom Professor of Medicine University of Nebraska Medical Center Omaha, NE, USA XI  XI

Part I

MRI Technique, Contrast, Safety, Anatomy, and DifferentialXI

Part I MRI Technique, Contrast, Safety, Anatomy, and Differential

   

Contents

Foreword I . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . IX Foreword II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . X Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . XI Part I  MRI Technique, Contrast, Safety, Anatomy, and Differential   1   2   3   4   5   6   7   8   9 10 11 12 13 14 15 16 17 18 19 20 21

Liver MRI: Comparison of the Two Main Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Gadolinium-Based Contrast Agents: An Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Gadolinium-Based Contrast Agents: Uptake and Excretion Pathways . . . . . . . . . . . . . . . . . . . . . 6 Liver-Specific Contrast Agents: Uptake in the Liver and Lesions . . . . . . . . . . . . . . . . . . . . . . . . . 8 MR Imaging Technique and Protocol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 Liver MRI: Pulse Sequence Diagram of T1- and T2-Weighted Sequences . . . . . . . . . . . . . . . . . . 12 Magnetic Resonance Cholangiopancreatography (MRCP) Technique . . . . . . . . . . . . . . . . . . . . . 14 Liver MRI: Diffusion-Weighted Imaging and Apparent Diffusion Coefficient . . . . . . . . . . . . . . . 16 DWI: Liver Lesion Characterization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 Dixon-Based Sequence: Technique and Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 Liver MRI: Simple Steps to Change a Nondiagnostic into Diagnostic Exam . . . . . . . . . . . . . . . . 22 Liver Segmental and Vascular Anatomy at MR Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 Portal and Hepatic Venous Anatomy with the New Liver Anatomy Concepts . . . . . . . . . . . . . . . 26 Hepatic Arterial Anatomy and Variants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 Biliary Tree Anatomy and Variants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 Liver Lesions: Appearance with the Enhancement Patterns (Drawings) . . . . . . . . . . . . . . . . . . . . 32 Liver Lesions: Appearance with the Enhancement Patterns (MR Images) . . . . . . . . . . . . . . . . . . 34 T2 Bright Liver Lesions: Differential Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36 T1 Bright Liver Lesions: Differential Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 T2 Bright Central Scar: Differential Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 Lesions in Fatty Liver: Differential Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42

Part II  Fluid-Filled Liver Lesions 22 Abscess I: Pyogenic Type with US and CT Correlation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 23 Abscess II: Pyogenic Type with DWI and MinIP Patterns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 24 Biliary Hamartomas (Von Meyenburg Complexes) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 25 Cyst I: Typical Small . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52 26 Cyst II: Typical Large with MR-CT Correlation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 27 Cyst III: Multiple Small Lesions with MR-CT-US Comparison . . . . . . . . . . . . . . . . . . . . . . . . . . 56 28 Cyst IV: Adult Polycystic Liver and Kidney Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58 29 Cystadenocarcinoma: Cystic and Solid Components . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60 30 Hemangioma I: Typical Small . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 31 Hemangioma II: Typical Medium Sized with Pathology Description . . . . . . . . . . . . . . . . . . . . . . 64 32 Hemangioma III: Role of Diffusion-Weighted Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 33 Hemangioma IV: Typical Giant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68 34 Hemangioma V: Typical Giant Type with a Large Central Scar . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 35 Hemangioma VI: Flash-Filling with US and CT Correlation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 36 Hemangioma VII: Multiple Lesions, Comparison with US and CT Findings . . . . . . . . . . . . . . . . 74 37 Hemorrhage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76

XIV Contents

38 39 40 41

Hemorrhage: Within a Solid Tumor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78 Hydatid Disease (Echinococcosis): MRI and CT Findings with the Cyst Anatomy . . . . . . . . . . . 80 Mucinous Metastasis I: Mimicking a Hemangioma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82 Mucinous Metastasis II: Role of DWI, PET, and Liver Segmentation . . . . . . . . . . . . . . . . . . . . . . 84

Part III  Solid Liver Lesions III A:  Metastases: colorectal 42 43 44 45 46 47 48 49 50 51

Colorectal Metastases I: Typical Lesion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90 Colorectal Metastases II: MRI Findings in a Fatty Liver . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92 Colorectal Metastases III: With Liver-Specific Gadolinium-Based Contrast Agent . . . . . . . . . . . 94 Colorectal Metastases IV: Typical Multiple Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96 Colorectal Metastases V: Metastases Versus Cyst . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98 Colorectal Metastases VI: Metastases Versus Hemangiomas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100 Colorectal Metastases VII: Large, Mucinous, Mimicking a Primary Liver Tumor . . . . . . . . . . . . 102 Colorectal Metastases VIII: With Portal Vein and Bile Duct Encasement . . . . . . . . . . . . . . . . . . . 104 Colorectal Metastases IX: Recurrent Disease Versus RFA Defect . . . . . . . . . . . . . . . . . . . . . . . . . 106 Colorectal Metastases X: MR Imaging Findings Post-chemotherapy . . . . . . . . . . . . . . . . . . . . . . 108

III B:  Metastases: non-colorectal 52 53 54 55 56 57 58 59 60 61 62

Breast Carcinoma Liver Metastases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112 Melanoma Liver Metastases I: Focal Type . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114 Melanoma Liver Metastases II: Diffuse Type . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116 Neuroendocrine Tumor I: Typical Liver Metastases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118 Neuroendocrine Tumor II: Pancreatic Tumor Metastases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120 Neuroendocrine Tumor III: Gastrinoma Liver Metastases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122 Neuroendocrine Tumor IV: Carcinoid Tumor Liver Metastases . . . . . . . . . . . . . . . . . . . . . . . . . . 124 Neuroendocrine Tumor V: Peritoneal Spread . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126 Neuroendocrine Tumor VI: Role of Diffusion-Weighted Imaging . . . . . . . . . . . . . . . . . . . . . . . . . 128 Ovarian Tumor Liver Metastases: Mimicking Giant Hemangioma . . . . . . . . . . . . . . . . . . . . . . . . 130 Renal Cell Carcinoma Liver Metastasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132

III C:  Primary solid liver lesions in cirrhotic liver 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82

Cirrhosis I: Liver Morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136 Cirrhosis II: Regenerative Nodules and Confluent Fibrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138 Cirrhosis III: Dysplastic Nodules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140 Cirrhosis IV: Cyst in a Cirrhotic Liver . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142 Cirrhosis V: Multiple Cysts in a Cirrhotic Liver . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144 Cirrhosis VI: Hemangioma in a Cirrhotic Liver . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146 Hepatocellular Carcinoma: UNOS/OPTN Reporting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148 HCC in Cirrhosis I: Gadoxetate (Liver-Specific) Versus Nonspecific GBCA . . . . . . . . . . . . . . . . 150 HCC in Cirrhosis II: Stepwise Carcinogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 152 HCC in Cirrhosis III: Nodule-in-Nodule in the Arterial Phase and DWI . . . . . . . . . . . . . . . . . . . . 154 HCC in Cirrhosis IV: Small Classic Lesion with EASL/AASLD Diagnostic Criteria . . . . . . . . . . 156 HCC in Cirrhosis V: With History of Nonalcoholic Steatohepatitis (NASH) . . . . . . . . . . . . . . . . 158 HCC in Cirrhosis VI: Typical Small with Pathologic Correlation . . . . . . . . . . . . . . . . . . . . . . . . . 160 HCC in Cirrhosis VII: Small with and Without a Tumor Capsule . . . . . . . . . . . . . . . . . . . . . . . . . 162 HCC in Cirrhosis VIII: Nodule-in-Nodule on the T2-Weighted Sequence . . . . . . . . . . . . . . . . . . 164 HCC in Cirrhosis IX: Mosaic Pattern with Pathologic Correlation . . . . . . . . . . . . . . . . . . . . . . . . 166 HCC in Cirrhosis X: Typical Large with Mosaic and Capsule . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168 HCC in Cirrhosis XI: Mosaic Pattern with Fatty Infiltration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 170 HCC in Cirrhosis XII: Large Growing Lesion with Portal Invasion . . . . . . . . . . . . . . . . . . . . . . . 172 HCC in Cirrhosis XIII: Segmental Diffuse with Portal Vein Thrombosis . . . . . . . . . . . . . . . . . . . 174

Contents

  83   84   85   86   87   88

XV

HCC in Cirrhosis XIV: With History of Nonalcoholic Fatty Liver Disease (NAFLD) . . . . . . . . 176 HCC in Cirrhosis XV: Multiple Lesions Growing on Follow-Up . . . . . . . . . . . . . . . . . . . . . . . . 178 HCC in Cirrhosis XVI: Multiple T1 Hyperintense Lesions with Subtraction Imaging . . . . . . . . 180 HCC in Cirrhosis XVII: Capsular Retraction and Suspected Diaphragm Invasion . . . . . . . . . . . 182 HCC in Cirrhosis XVIII: Diffuse Within the Entire Liver with Portal Vein Thrombosis . . . . . . . 184 HCC in Cirrhosis XIX: With Intrahepatic Bile Duct Dilatation . . . . . . . . . . . . . . . . . . . . . . . . . . 186

III D:  Primary solid liver lesions in non-cirrhotic liver   89 Focal Nodular Hyperplasia I: Typical with Large Central Scar and Septa . . . . . . . . . . . . . . . . . . 190   90 Focal Nodular Hyperplasia II: Typical with Pathologic Correlation . . . . . . . . . . . . . . . . . . . . . . 192   91 Focal Nodular Hyperplasia III: Mimicking Metastasis; Role of Liver-Specific Contrast Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 194   92 Focal Nodular Hyperplasia IV: Typical with Follow-Up Exam . . . . . . . . . . . . . . . . . . . . . . . . . . 196   93 Focal Nodular Hyperplasia V: Multiple FNH Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 198   94 FNH VI: Findings on the Dynamic Contrast-­Enhanced and Hepatobiliary Phases . . . . . . . . . . . 200   95 Focal Nodular Hyperplasia VII: Gadoxetate Versus Gadobenate . . . . . . . . . . . . . . . . . . . . . . . . . 202   96 Focal Nodular Hyperplasia VIII: Fatty Lesion with Concurrent Fatty Adenoma . . . . . . . . . . . . 204   97 Focal Nodular Hyperplasia IX: Atypical with T2 Dark Central Scar . . . . . . . . . . . . . . . . . . . . . . 206   98 Hepatic Adrenal Rest Tumor (HART): Fat-­Containing with a Left Adrenal Mass . . . . . . . . . . . 208   99 Hepatic Angiomyolipoma: MR-CT Comparison . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 210 100 Hepatic Lipoma I: MR-CT-US Comparison . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 212 101 Hepatic Lipoma II: Findings on Dixon Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 214 102 Hepatocellular Adenoma I: Typical with Pathologic Correlation . . . . . . . . . . . . . . . . . . . . . . . . . 216 103 Hepatocellular Adenoma II: New Genotypes and Phenotypes . . . . . . . . . . . . . . . . . . . . . . . . . . . 218 104 Hepatocellular Adenoma III: Role of Liver-Specific Contrast and HBP . . . . . . . . . . . . . . . . . . . 220 105 Hepatocellular Adenoma IV: Large Exophytic with Pathologic Correlation . . . . . . . . . . . . . . . . 222 106 Hepatocellular Adenoma V: Typical Fat-Containing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224 107 Hepatocellular Adenoma VI: With Large Hemorrhage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 226 108 Hepatocellular Adenoma VII: Multiple in Fatty Liver (Non-OC-Dependent) . . . . . . . . . . . . . . . 228 109 Hepatocellular Adenoma VIII: Multiple in Fatty Liver (OC-Dependent) . . . . . . . . . . . . . . . . . . 230 110 Hepatocellular Adenoma IX: Changes During Pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 232 111 HCC in Non-cirrhotic Liver I: Small with MR-Pathology Correlation . . . . . . . . . . . . . . . . . . . . 234 112 HCC in Non-cirrhotic Liver II: Large with MR-Pathology Correlation . . . . . . . . . . . . . . . . . . . . 236 113 HCC in Non-cirrhotic Liver III: Large Lesion with Inconclusive CT . . . . . . . . . . . . . . . . . . . . . 238 114 HCC in Non-cirrhotic Liver IV: Cholangiocellular or Combined Type . . . . . . . . . . . . . . . . . . . . 240 115 HCC in Non-cirrhotic Liver V: Central Scar and Capsule Rupture . . . . . . . . . . . . . . . . . . . . . . . 242 116 HCC in Non-cirrhotic Liver VI: Capsule with Pathologic Correlation . . . . . . . . . . . . . . . . . . . . 244 117 HCC in Non-cirrhotic Liver VII: Very Large with Pathologic Correlation . . . . . . . . . . . . . . . . . 246 118 HCC in Non-cirrhotic Liver VIII: Vascular Invasion and Satellite Nodules . . . . . . . . . . . . . . . . 248 119 HCC in Non-cirrhotic Liver IX: Adenoma-Like HCC with Pathologic Correlation . . . . . . . . . . 250 120 Intrahepatic Cholangiocarcinoma I: With Pathologic Correlation . . . . . . . . . . . . . . . . . . . . . . . . 252 121 Intrahepatic Cholangiocarcinoma II: With DWI, PET, and DSA Correlation . . . . . . . . . . . . . . . 254 Part IV  Diffuse Liver Parenchymal Disorders 122 123 124 125 126 127 128 129

Autoimmune Hepatitis I: Serial MRI Changes with Laboratory Correlation . . . . . . . . . . . . . . . . 258 Autoimmune Hepatitis II: Overlap Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 260 HIV/HCV Hepatitis Developing into Cirrhosis with Laboratory Correlation . . . . . . . . . . . . . . . 262 Congestive Hepatopathy (Nutmeg Liver) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 264 Dixon-Based Sequence: Assessment of Liver Fat and Iron Deposition . . . . . . . . . . . . . . . . . . . . 266 Focal Fatty Infiltration Mimicking Metastases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 268 Focal Fatty Sparing Mimicking Liver Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 270 Hemosiderosis: Iron Deposition, Acquired Type . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 272

XVI

130 131 132 133 134

Contents

Hemochromatosis: Severe Type . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 274 Liver Iron Concentration: Assessment Based on a T2* Map . . . . . . . . . . . . . . . . . . . . . . . . . . . . 276 Hemochromatosis with Solitary HCC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 278 Hemochromatosis with Multiple HCCs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 280 Thalassemia with Iron Deposition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282

Part V  Vascular Liver Lesions 135 136 137 138 139 140 141

Arterioportal Shunt I: Early Enhancing Lesion in a Cirrhotic Liver . . . . . . . . . . . . . . . . . . . . . . 286 Arterioportal Shunt II: Early Enhancing Lesion in a Non-cirrhotic Liver . . . . . . . . . . . . . . . . . . 288 Budd-Chiari Syndrome I: Abnormal Enhancement and Intrahepatic Collaterals . . . . . . . . . . . . 290 Budd-Chiari Syndrome II: Gradual Deformation of the Liver . . . . . . . . . . . . . . . . . . . . . . . . . . . 292 Budd-Chiari Syndrome III: Nodules Mimicking Malignancy . . . . . . . . . . . . . . . . . . . . . . . . . . . 294 Hereditary Hemorrhagic Telangiectasia (HHT) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 296 Hepatic Epithelioid Hemangioendothelioma (HEHE) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 298

Part VI  Biliary Tree Abnormalities 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160

Bile Leakage: Liver-Specific MR Contrast and Correlation with US, CT, and HIDA . . . . . . . . . 302 Caroli’s Disease I: Intrahepatic with Segmental Changes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 304 Caroli’s Disease II: Involvement of the Liver and Kidneys . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 306 Cholelithiasis (Gallstones) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 308 Choledocholithiasis (Bile Duct Stones) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 310 Gallbladder Carcinoma I Versus Gallbladder Wall Edema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 312 Gallbladder Carcinoma II: Hepatoid Type of Adenocarcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . 314 Hilar Cholangiocarcinoma I: Typical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 316 Hilar Cholangiocarcinoma II: Bismuth-Corlette Classification . . . . . . . . . . . . . . . . . . . . . . . . . . 318 Hilar Cholangiocarcinoma III: Intrahepatic Mass . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 320 Hilar Cholangiocarcinoma IV: Partially Extrahepatic Tumor . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322 Hilar Cholangiocarcinoma V: Metal Stent with Interval Growth . . . . . . . . . . . . . . . . . . . . . . . . . 324 Hilar Cholangiocarcinoma VI: Biliary Dilatation Mimicking Klatskin at CT . . . . . . . . . . . . . . . 326 Primary Sclerosing Cholangitis I: Cholangitis and Segmental Atrophy . . . . . . . . . . . . . . . . . . . . 328 Primary Sclerosing Cholangitis II: With Intrahepatic Cholestasis . . . . . . . . . . . . . . . . . . . . . . . . 330 Primary Sclerosing Cholangitis III: With Intrahepatic Stones . . . . . . . . . . . . . . . . . . . . . . . . . . . 332 Primary Sclerosing Cholangitis IV: With Biliary Cirrhosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 334 Primary Sclerosing Cholangitis V: With Intrahepatic Cholangiocarcinoma . . . . . . . . . . . . . . . . 336 Primary Sclerosing Cholangitis VI: With Hilar Cholangiocarcinoma . . . . . . . . . . . . . . . . . . . . . 338

Part VII  Pediatric Liver Lesions 161 Hepatoblastoma I: With Age-Dependent Differential Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . 342 162 Hepatoblastoma II: With Vascular Invasion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 344 163 Undifferentiated Embryonal Sarcoma of the Liver (UESL): MRI and CT Findings . . . . . . . . . . 346 Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 349

Part I MRI Technique, Contrast, Safety, Anatomy, and Differential Overview

and Dixon-based imaging. In addition, simple and easy steps have been defined to optimize the key sequences to This is an entirely new part of this textbook that describes change a nondiagnostic into a diagnostic liver MRI the liver MRI techniques and approaches that are currently protocol. used in the clinical setting. This is followed by the most The appearance of the most common liver lesions has recent information on the gadolinium-based contrast agents been described on the T1, T2, arterial phase, and delayed (GBCAs), including the chemical structure, the biodistribu- phase images that basically covers the MRI appearance of tion, the excretion pathways, and the safety aspects. Since more than 80 % of the liver lesions. the first edition of the book in 2007, tremendous developNormal and variant anatomy of the biliary tree, portal ment occurred regarding the GBCAs. After the initial publi- vein, hepatic veins, and hepatic artery has been described, cation in 2006, the medical community became familiar including the newest insight and concept regarding the porwith a new disease associated with the GBCAs. This is of tal vein anatomy and the segmental liver anatomy. course nephrogenic systemic fibrosis (NSF). After recoverFinally, the normal liver MRI findings and MRI differening from the initial shock, we have learned a great deal tial diagnosis of common liver lesions have been about this disease and how to best deal with the underlying illustrated. causes of NSF. The professional organizations, the vendors, Of special note are the following chapters in this part of the scientists, and the medical community came together the book: and have adequately dealt with NSF. The most problematic Liver MRI: Comparison of the Two Main Approaches GBCAs were identified and practice guidelines were made (Chap. 1) available to apply in the high-risk patients. Liver-Specific Contrast Agents: Uptake in the Liver and A more positive development in regard to the GBCAs Lesions (Chap. 4) was the introduction of newer agents, including the liver-­ Liver MRI: Simple Steps to Change a Nondiagnostic into Diagnostic Exam (Chap. 11) specific gadoxetate (Primovist/Eovist) and gadobenate, which is off-label for the liver-specific applications and has Portal and Hepatic Venous Anatomy with the New Liver Anatomy Concepts (Chap. 13) also dual elimination (the liver and kidney) similar to gadoxetate. Particularly, the introduction of gadoxetate led to an Hepatic Arterial Anatomy and Variants (Chap. 14) entirely new liver MRI approach. We have provided com- Biliary Tree Anatomy and Variants (Chap. 15) parison between the two main liver MRI approaches, with Liver Lesions: Appearance with the Enhancement Patterns (Drawings) (Chap. 16) examples of uptake of contrast in the normal liver as well as common liver lesions based on the cutting-edge scientific Liver Lesions: Appearance with the Enhancement Patterns (MR Images) (Chap. 17) data and original drawings. The most important liver MRI sequences have been described, including the diffusion-weighted imaging (DWI)

© Springer International Publishing Switzerland 2015 S.M. Hussain, M.F. Sorrell, Liver MRI, DOI 10.1007/978-3-319-06004-0_1

1

2  Part I  MRI Technique, Contrast, Safety, Anatomy, and Differential

1

Liver MRI: Comparison of the Two Main Approaches

 ultiparametric Approach Versus Liver-Specific MRI M Contrast Medium Approach

T1-weighted sequence: Another important breakthrough for multiparametric approach came with the introduction of fast low-angle shot (FLASH) imaging in 1986, which is a gradient-echo sequence that The multiparametric approach is basically a product of research and allowed T1-weighted imaging in seconds, facilitating breath-hold MR development since the introduction of MRI in 1973. The liver-specific imaging of the liver for the first time. The dynamic gadolinium-­ contrast medium (gadoxetate) approach has mainly been popularized enhanced MR imaging, first described by Richard Semelka in the by the vendor, since the approval of gadoxetate in the USA in 2008 1990s using FLASH, continues to be the single most important com(Fig. 1.1). The multiparametric approach relies on a combination of ponent of the modern liver MRI. FLASH sequence permitted the multiple sequences, including the multiphasic dynamic contrast-­ acquisition of the central part of the k-space data in only a few secenhanced sequence that allows the detection as well as characteriza- onds, simultaneously for all slices covering the liver with the consistion of liver lesions. In this approach, the enhancement patterns of the tent T1 contrast, and allowed the assessment of the enhancement of the liver lesions, combined with the T2, T1, and DWI appearance, are liver lesions. This was in the time, when CT was slow and did not important. To accurately assess the enhancement patterns of liver allow dynamic imaging. This technical advantage of MRI, combined lesions, a well-timed arterial phase is essential. In the gadoxetate with the lack of ionizing radiation and a relatively safer MR contrast approach, the 20 min delayed hepatobiliary phase (HBP) plays the medium (gadopentetate) compared to hyperosmolar CT contrast media central role; most of the other sequences are often used to explain the of that time, facilitated the implementation of routine multiphasic findings on the HBP. The time between the injection of contrast and dynamic MRI. Currently, the dynamic imaging based on the fat-­ the 20 min HBP is often filled with the early dynamic phases (12 weeks increases the risk of ­postoperative hepatic insufficiency after extended right hepatectomy. In patients treated with long-duration chemotherapy, FLR >30 % reduces the rate of postoperative hepatic insufficiency and may ­provide enough functional reserve.

Literature 1. Ueda K, Matsui O, Nobata K, Takashima T. Mucinous carcinoma of the liver mimicking cavernous hemangioma on pre- and postcontrast MR imaging ­[letter]. Am J Roentgenol. 1996;166:468–9. 2. Outerwater EK, Tomaszewski JE, Daly JM, Kressel HY. Hepatic colorectal metastases; correlation of MR imaging and pathology. Radiology. 1991;180: 327–32. 3. Lacout A, El Hajjam M, Julie C, et al. Liver metastasis of a mucinous colonic carcinoma mimicking a haemangioma in T2-weighted sequences. J Med Imaging Radiat Oncol. 2008;52:580–2. 4. Yeh CL, Chen YK. Utility of FDG metabolism to differentiate synchronous metastatic liver lesions from synchronous colon cancer: nonmucinous versus mucinous adenocarcinoma. Clin Nucl Med. 2010;35:44–6. 5. Hussain SM, Outwater EK, Siegelman ES. Mucinous versus nonmucinous rectal carcinomas: differentiation with MR imaging. Radiology. 1999;213: ­ 79–85. 6. Gao L, Heath D, Fishman E. Abdominal image segmentation using three-­ dimensional deformable models. Invest Radiol. 1996;33:348–55. 7. Shindoh J, Tzeng CW, Aloia TA, et al. Optimal future liver remnant in patients treated with extensive preoperative chemotherapy for colorectal liver ­metastases. Ann Surg Oncol. 2013;20:2493–500.

41  Mucinous Metastasis II: Role of DWI, PET, and Liver Segmentation  85

Fig. 41.1  Metastasis: mucinous type from a colorectal cancer with CT and FDGPET correlation. (a) Axial T2-weighted SSTSE image (SSTSE): two large, hyperintense, lobulated liver lesions (m) are visible with internal low-signal-intensity septations. Note that the lesions have high fluid content (a hallmark of benign liver lesions such as cysts and hemangiomas), similar to the CSF (arrow). (b) Axial fatsuppressed T1-weighted GRE (T1 fatsat): the two liver lesions (m) are hypointense. (c) Axial arterial phase 3D T1-weighted GRE image (ART): the lesions

show very little but still typical intralesional septal enhancement (arrow) (similar to ovarian mucinous cystadenocarcinomas). (d) Axial delayed phase GRE image (DEL): the septal enhancement slightly increases (arrow). (e–g) Axial diffusionweighted image (DWI) and the ADC map (ADC) show variable restricted diffusion; this illustrates a major limitation of DWI approach for the characterization of liver lesions. (h) Coronal delayed phase (DEL) images show additional liver lesions with similar enhanced appearance

Fig. 41.2  Metastasis: mucinous type from a colorectal cancer with CT and FDGPET correlation. (a) Axial magnified FDG-PET image shows a large metastasis in the dome of the liver, which overall is hypometabolic compared to the surrounding liver; the septation, however, does show significant metabolic activity (arrows). (b–d) Multiple composite FDG-PET, the corresponding CT, and the color-coded fused PET-CT images show multiple liver metastasis located in the right liver,

sparing the left lateral segment. (e, f) The septations within the lesions on these CT images are less obvious compared to MRI, rendering the lesions more difficult to identify as metastasis. (g, h) An example of how a post-processing software can be applied for the automatic liver volume calculation and display; the lesions can be segmented and color coded, facilitating in surgical planning

Part III Solid Liver Lesions Overview

focal nodular hyperplasia and adenomas, and (c) biliary leakage after surgery. We do not routinely apply the liver-­ This is the largest part of the book with four major sub- specific contrast agents to assess hepatocellular carcinomas groups: in cirrhotic liver. 1. Metastases from the colorectal cancer Several new cases have been included that illustrate our 2. Metastases from the non-colorectal malignancies overall liver MRI approach for the solid liver lesions. Also 3. Primary solid liver lesions in cirrhotic liver the role of the liver-specific contrast media is illustrated by 4. Primary solid liver lesions in non-cirrhotic liver providing comparative examples. A number of examples have been provided to illustrate the Of particular mention are the new items: typical and atypical colorectal liver metastases. Solid liver 1. New examples of a rare hepatic adrenal rest tumor lesions are best evaluated as follows: (1) the first step is to (HART) that presented as a fat-containing liver lesion assess the heavily T2-weighted single-shot turbo spin echo and a hepatic lipoma demonstrate the importance of (SSTSE) to exclude any fluid-filled liver lesions such as cysts Dixon-based imaging to detect the presence of fat within or hemangiomas; the metastases are either difficult to detect the lesions. or completely obscured on the SSTSE; the reason is the mag- 2. Colorectal liver metastasis in a severely fatty infiltrated netic transfer contrast (MTC) effect caused by the multiple liver: the appearance of the metastases dramatically refocusing pulses; (2) the second step is to assess the lesions changes on the MR imaging sequences. This can be conon the moderately T2-weighted sequences (fat-­suppressed fusing and could potentially lead to misdiagnosis. respiratory-triggered TSE and/or DWI with low b-value of 3. Role of the liver-specific gadolinium-based contrasts 20); (3) the third step is to assess for any fatty infiltration of agents (GBCAs) as a problem-solving tool is highlighted the lesion and liver on the chemical shift or Dixon images; by several new cases. and (4) the fourth step is to assess the enhancement pattern on 4. New classification of the hepatocellular adenomas has the post-contrast T1-weighted arterial and later phases. After been described. these steps, you should be able to detect and characterize the 5. Reporting of (suspected) hepatocellular carcinomas majority of solid liver lesions. We also include in the overall (HCCs) in a cirrhotic liver based on the OPTN and assessment the diffusion-­weighted images (DWI) and apparUNOS criteria has been provided in two simple tables. ent diffusion coefficient (ADC) as problem-solving sequences, 6. Several new cases of HCC have been included to illusfor instance, in atypical lesions, treated metastases, and recurtrate the role of the liver-specific GBCAs, DWI, and subrent or residual disease after locoregional treatment. traction images. The hepatobiliary phase imaging is also used as problem-­ 7. A new case of a large intrahepatic cholangiocarcinoma solving tool, for instance, for (a) the distinction between the was included to show the specific tumor anatomy and primary and secondary liver lesions, (b) distinction between correlation between DWI and FDG-PET imaging

© Springer International Publishing Switzerland 2015 S.M. Hussain, M.F. Sorrell, Liver MRI, DOI 10.1007/978-3-319-06004-0_3

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Part III A: Metastases: colorectal

90  Part III  Solid Liver Lesions  –  III A:  Metastases: colorectal

42

Colorectal Metastases I: Typical Lesion

Metastases are the most common malignant tumors of the liver in the Western countries. Liver metastases usually appear as solitary or ­multiple lesions. Unlike many other cancers, the presence of distant metastases from colorectal cancer does not preclude curative treatment. About 25 % with colorectal liver metastases have no other distant metastases. Of these 10–25 % are candidates for surgical ­ ­resection. For the 75–90 % of patients with liver metastases who are not amenable to surgery, several new minimal invasive treatments are available such as radiofrequency ablation, stereotactic radiation ­therapy, and systemic chemotherapy.

metastases show an irregular continuous ring-shaped (as opposed to the broken ring or peripheral nodular enhancement of hemangioma) enhancement in the arterial phase. This ring-shaped enhancement ­represents the vascularized growing edge of the lesion. In the portal and delayed phases, the metastases often show washout in the outer parts with progressive enhancement toward the center of the lesions (Figs. 42.1, 42.2, and 42.3). Larger lesions may show heterogeneous, cauliflower-like enhancement.

Differential Diagnosis MR Imaging Findings At MR imaging, most colorectal carcinoma liver metastases have target-­ like appearance. The lesions are predominantly low signal intensity on T1-weighted images and moderately high signal intensity on T2-weighted images with fat suppression. On T2-weighted images, the internal tumor anatomy has a target-like configuration: (a) highest (fluid-like) signal intensity is in the center of the lesion due to coagulative necrosis; (b) lower signal intensity in a relatively broad zone outside the center due to the presence of desmoplastic reaction, which mainly forms the tumor matrix; (c) again slightly higher signal intensity in the most outer zone (growing edge) due to more compact tumor cells with more vessels and less desmoplasia. The growing edge of the colorectal metastases is usually very thin. Some lesions may also be surrounded by edema within the surrounding compressed liver parenchyma. After administration of gadolinium, most colorectal ­

Benign (small) liver lesions such as cysts, biliary ­hamartomas, hemangiomas, and focal nodular hyperplasia are common liver entities, which may coexist with the metastatic lesions and form a common differential diagnostic problem. State-of-the-art MR imaging is highly ­ accurate in distinguishing malignant from benign liver lesions.

Literature 1. Outwater E, Tomaszewski JE, Daly JM, et al. Hepatic colorectal metastases: correlation of MR imaging and pathologic appearance. Radiology. 1991;180: 327–32. 2. Semelka RC, Cance WG, Marcos HB, et al. Liver metastases: comparison of current MR techniques and spiral CT during arterial portography for detection in 20 surgically staged cases. Radiology. 1999;213:86–91. 3. Hussain SM, Semelka RC. Liver masses. Magn Reson Imaging Clin N Am. 2005;13:255–75.

42  Colorectal Metastases I: Typical Lesion  91

Fig. 42.1  Metastasis, colorectal, drawings. T2 fatsat: Metastasis is predominantly hyperintense to the liver with a brighter center; T1 in phase: metastasis is hypoin-

tense to the liver; ART: metastasis shows a typical irregular ring-shaped enhancement; DEL: metastasis shows heterogeneous enhancement

Fig. 42.2  Metastasis, colorectal, MRI findings. (a) Axial fatsat T2-weighted TSE image (T2 fatsat): metastasis is predominantly hyperintense to the liver with a brighter center. (b) Axial in-phase T1-weighted GRE (T1 in phase): metastasis is hypointense to the liver. (c) Axial arterial phase post-Gd 3D T1-weighted GRE image (ART): metastasis shows a typical irregular ring-shaped enhancement. (d) Axial delayed phase image (DEL): metastasis becomes more heterogeneous. (e) Axial T2-weighted SSTSE image with TE of 120 ms (T2 longer TE): metastasis

shows a lower signal in the outer parts indicating the solid nature. (f) Axial opposed-phase T1-weighted GRE image (T1 opposed phase) shows a signal drop in the liver indicating steatosis; metastasis becomes isointense with persistent high perifocal signal due to compressed liver (arrow). (g) Coronal T2-weighted SSTSE (SSTSE) shows two identical metastases with typical tumor anatomy (arrows). (h) Coronal delayed phase image (DEL) clearly shows the less enhanced central parts of the metastases (arrows)

Fig. 42.3  Metastasis, colorectal, tumor anatomy. (a) Photomicrograph (H&E, 100×) from the central part of a metastasis shows the less vascularized coagulative necrosis. (b) Photomicrograph (H&E, 100×) from the outer part shows the desmo-

plasia with viable tumor tissue and the growing edge (arrows). (c) Drawing illustrates the tumor anatomy. (d) A detailed view of the axial SSTSE image shows the metastasis anatomy in vivo

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Colorectal Metastases II: MRI Findings in a Fatty Liver

Hepatic metastases are 18–40 times more common than primary liver tumors. Colorectal cancer is the most common malignancy to show metastasis in the liver. The differential diagnosis may be challenging due to the high prevalence of benign liver lesions. It is undesirable and impractical to biopsy these lesions or recommend lengthy follow-up imaging. In a patient with known underlying colon cancer and a suspected liver lesion, we cannot simply postpone the diagnosis. ­ Misdiagnosis of a benign liver lesion as a metastasis or vice versa will dramatically change a patient’s stage and thus treatment options and survival. MR imaging is currently the best imaging modality to provide noninvasive and accurate diagnosis in most patients. MR imaging diagnosis relies on the specific signal intensity characteristics of the lesions on the T1-weighted, T2-weighted, diffusion-weighted, and dynamic gadolinium-enhanced imaging.

MR Imaging Findings The typical appearance of liver metastases on MRI relies on a normal signal intensity of the background liver. Most frequent appearances include a T1 hypointensity, moderate T2 hyperintensity, and a ­perilesional or irregular ring-shaped enhancement, especially in the arterial phase after injection of gadolinium-based contrast agents. This typical appearance, however, may not apply if the background liver has changed by severe fatty infiltration. MR imaging appearance of liver metastases in a fatty liver can be dramatically different (Figs. 43.1 and 43.2). 1. T2-weighted image without fat suppression such as SSTSE (Fig. 43.1a) may show a target-like lesion with a hypointense ring. The hypointense ring is in fact the normal compressed liver ­parenchyma that has no fatty infiltration; this appears hypointense because the background liver is abnormally bright due to the high signal caused by the fatty infiltration. The central part of the lesion is hyperintense because of the higher fluid content. 2. T1-weighted image with fat suppression (Fig. 43.1b) likely will show a hyperintense rim, which is the non-fatty normal liver; the surrounding liver is darker due to the fat-suppression effect. The lesion is also dark due to the high fluid content. 3. The arterial phase (Fig. 43.1c) may either show a ring ­enhancement (usually lesions >1.5 cm) or enhancement of the

4. 5.

6.

7.

entire lesion (usually lesions 5 lesions), relatively small (a few centimeters in diameter), similar in size with sharp margins to the liver, and predominantly very bright (with almost fluidlike signal intensity) on T2-weighted images. At T1-weighted images, the appearance is often unremarkable (low signal intensity compared to the spleen). On gadolinium-­enhanced images, the lesions show irregular ring-shaped

Literature 1. Capella C, Heitz PU, Hofler H, et al. Revised classification of neuroendocrine tumours of the lung, pancreas and gut. Virchows Arch. 1995;425:547–60. 2. Hemminki K, Li X. Incidence trends and risk factors of carcinoid tumors. A nationwide epidemiologic study from Sweden. Cancer. 2001;92:2204–10. 3. Kloppel G, Anlauf M. Epidemiology, tumor biology and histopathological classification of neuroendocrine tumours of gastrointestinal tract. Clin Gastroenterol. 2005;19:507–17.

55  Neuroendocrine Tumor I: Typical Liver Metastases  119

Fig. 55.1  Metastases, neuroendocrine, multiple, drawings. BBEPI: metastases are very bright to the liver. T1 in phase: metastases are hypointense to the liver. ART:

metastases show an intense irregular ring-shaped and perilesional enhancement. DEL: metastases show washout without any prominent capsular enhancement

Fig. 55.2  Metastasis, neuroendocrine, multiple, MRI findings. (a) Axial BBEPI image (BBEPI): metastases are very bright to the liver. (b) Axial in-phase T1-weighted GRE (T1 in phase): metastases are hypointense to the liver. (c) Axial arterial phase image (ART): metastases show an intense irregular ring-shaped and perilesional enhancement. (d) Axial delayed phase image (DEL): metastases show washout of contrast, without any capsular enhancement. (e) Axial TSE image (T2 fatsat): metastases are very bright to the liver, mimicking nonsolid lesions such as

cysts or hemangiomas. (f) Axial opposed-phase image (T1 opposed phase) shows slight signal drop in the liver indicating subtle steatosis. Note that metastases are surrounded by persistent high perifocal signal due to the compressed liver. (g) Axial SSTSE image (SSTSE) shows the metastases as bright lesions, but much less brighter than fluid (e.g., in the spinal canal). (h) Coronal SSTSE image (SSTSE) with a longer TE shows that the metastases become darker, further indicating their solid nature

Fig. 55.3  Metastases, neuroendocrine, the enhancement pattern. (a) Early arterial phase: faint ring-shaped enhancement of metastases, no enhancement of the liver. (b) Peak arterial phase: metastases show intense ring-shaped and perilesional enhancement; the liver shows 25–30 % of the peak enhancement. (c) Portal

phase: the liver shows peak enhancement; the metastases show less perilesional enhancement. The liver veins are enhanced. (d) Venous phase: the lesions show washout without any capsular enhancement. Tissues show homogeneous enhancement

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Neuroendocrine Tumor II: Pancreatic Tumor Metastases

The tumors arising from the pancreas may comprise up to 45 % of all neuroendocrine tumors and about 40 % may be malignant with liver metastases. Of these, the majority is nonfunctioning tumors. Insulinomas are the most common pancreatic NET. They are usually small and solitary and 90 % are located within the pancreas; only 6–10 % of insulinomas are malignant. Multiple tumors present in 10 % of cases and may be associated with multiple endocrine neoplasia type 1 (MEN-1). In malignant tumors, all patients will have liver metastases.

MR Imaging Findings At MR imaging, neuroendocrine tumor metastases from the pancreas are often small and appear as hyperintense on T2-weighted images and low signal intensity on T1 images. After injection of gadolinium, lesions show intense homogeneous or ring-shaped enhancement with variable perifocal enhancement. In the delayed phase, the lesions show washout and become heterogeneous. At CT, the lesions may be less conspicuous because CT is performed as a single-phase study due to radiation issues. For this reason CT may not be a suitable technique for follow-up of such lesions (Figs. 56.1, 56.2, and 56.3).

Management Hepatic metastasis treatment may include (1) primary tumor resection, (2) resection in combination with ablation, (3) transarterial ­chemo-

embolization, and (4) medical therapies including somatostatin analogs, radiation, and systemic chemotherapy. Surgical resection of neuroendocrine hepatic metastases is a proven treatment of symptoms related to systemic hormone release. Advances in operative techniques and equipment have made hepatic resections safer, especially in ­tertiary, high-volume centers. Although the neuroendocrine tumors are frequently characterized by an indolent course, historic controls with hepatic metastases without resection or ablation have a much reduced 5-year survival, which varies from 20 to 30 %. Recently, several groups have reported improved 5-year survival of 50–70 % with resection of neuroendocrine hepatic metastases.

Literature 1. Capella C, Heitz PU, Hofler H, et al. Revised classification of neuroendocrine tumours of the lung, pancreas and gut. Virchows Arch. 1995;425:547–60. 2. Kloppel G, Anlauf M. Epidemiology, tumor biology and histopathological classification of neuroendocrine tumours of gastrointestinal tract. Clin Gastroenterol. 2005;19:507–17. 3. Touzios JG, Kiely JN, Pitt SC, et al. Neuroendocrine hepatic metastases: does aggressive management improve survival? Ann Surg. 2005;241:776–85.

56  Neuroendocrine Tumor II: Pancreatic Tumor Metastases  121

Fig. 56.1  Metastasis, neuroendocrine pancreatic tumor metastasis, before octreotide treatment, drawings. BBEPI: metastasis is hyperintense to the liver. T1 in phase: metastasis is hypointense to the liver. ART: metastasis shows intense homo-

geneous and perilesional enhancement. DEL: metastasis shows washout with some persistent enhancement

Fig. 56.2  Metastasis, neuroendocrine pancreatic tumor metastasis, before octreotide treatment, MRI findings. (a) Axial BBEPI image (BBEPI): metastasis is hyperintense to the liver. The conspicuity of the lesion is improved due to dark vessels (open arrow). (b) Axial in-phase image (T1 in phase): metastasis is hypointense to the liver. (c) Axial arterial phase image (ART): metastasis shows intense homogeneous and perilesional enhancement and therefore appears larger. (d) Axial delayed phase image (DEL): metastasis shows washout with some persistent

enhancement. (e) Axial TSE image (T2 fatsat): metastasis has similar appearance as some of the in-plane bright vessels (open arrow) and hence lesser conspicuity than on the BBEPI image. (f) Axial opposed-phase image (T1 opposed phase) shows no steatosis. (g) Axial portal phase image (POR): the metastasis (arrow) is difficult to appreciate because of the washout of contrast. (h) Axial CT in portal phase: the metastasis (arrow) appears almost isodense to the liver and is difficult to appreciate

Fig. 56.3  Metastasis, neuroendocrine pancreatic tumor metastasis, a 12-month follow-up after octreotide treatment, MRI findings. (a) Axial BBEPI image (BBEPI): metastasis has decreased in size. (b) Axial in-phase image (T1 in phase): metastasis is difficult to see due to its smaller size. (c) Axial arterial phase image

(ART): metastasis shows less intense enhancement compared to the previous MRI. (d) Axial CT in portal phase: due to decreased size and vascularity, the metastasis is even more difficult to assess than the previous CT. Also it is difficult to distinguish the metastasis (solid arrow) from some of the vessels (open arrow)

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Neuroendocrine Tumor III: Gastrinoma Liver Metastases

Gastrinomas can occur in the pancreas, stomach, duodenum, and ­proximal jejunum. About 90 % of these tumors are located within the “gastrinoma triangle” which is formed by the junction between the neck and body of the pancreas medially, the second and third portions of the duodenum inferiorly, and the junction of the cystic and common bile ducts superiorly. The tumors produce gastrin and can give rise to ulcers, diarrhea, and reflux (Zollinger-Ellison syndrome). Gastrinomas, relative to insulinomas, are more often extrapancreatic and multiple. They also tend to be even smaller and less vascular than insulinomas. These features make them even more difficult to localize than insulinomas. As many as 60 % of gastrinomas are malignant; 25 % of these tumors are associated with MEN-1, which is more common in the setting of multiple and extrapancreatic tumors. At the time of diagnosis, 30 % of pancreatic tumors and 10 % of duodenal tumors have metastasized. Metastases most commonly involve the lymph nodes and liver.

MR Imaging Findings Gastrinoma liver metastases typically appear as multiple liver lesions with somewhat variable signal intensity and size. On the T2-weighted imaging, most lesions have high signal intensity compared to the

n­ ormal liver and comparable signal intensity to the spleen. On the T1-weighted images, the lesions have low signal intensity. After injection of gadolinium, small lesions have almost homogeneous ­ enhancement with varied perifocal enhancement and the larger lesions may have ring-shaped or heterogeneous enhancement in the arterial phase. In the delayed phase, the smaller lesions show complete ­washout, whereas the larger lesions may show persistent or even increased enhancement in the central part of the lesions. MR imaging can also show extrahepatic localization, such as nodal involvement. The involved nodes often have similar appearance to the hepatic metastases (Figs. 57.1, 57.2, and 57.3).

Literature 1. Kumbasar B, Kamel IR, Tekes A, et al. Imaging of neuroendocrine tumors: accuracy of helical CT versus SRS. Abdom Imaging. 2004;29: 696–702. 2. Noone TC, Hosey J, Firat Z, Semelka RC. Imaging and localization of islet-­cell tumours of pancreas on CT and MRI. Best Pract Res Clin Endocrinol Metab. 2005;19:195–211. 3. Semelka RC, Custodio CM, Balci NC, Woosley JT. Neuroendocrine tumors of the pancreas: spectrum of appearances on MRI. J Magn Reson Imaging. 2000;11:141–8.

57  Neuroendocrine Tumor III: Gastrinoma Liver Metastases  123

Fig. 57.1  Metastasis, gastrinoma, multiple drawings. T2 fatsat: metastases are variable in size and slightly hyperintense to the liver. T1 in phase: metastases are hypointense to the liver. ART: larger lesions show irregular ring-shaped and the

smaller lesions homogeneous enhancement; note also the parenchymal enhancement (*). DEL: metastases show washout

Fig. 57.2  Metastasis, gastrinoma, multiple, MRI findings. (a) Axial TSE image (T2 fatsat): metastases are variable in size and slightly hyperintense to the liver. Note also ascites. (b) Axial in-phase image (T1 in phase): metastases are hypointense to the liver. (c) Axial arterial phase image (ART): larger lesions show irregular ring-­shaped and the smaller lesions homogeneous enhancement; note also the parenchymal enhancement (*). (d) Axial delayed phase image (DEL): metastases

show washout. (e) Axial fat-suppressed GRE image (T1 fatsat): metastases show better delineation to the liver due to improved liver-to-lesion contrast. (f) Axial opposed-phase image (T1 opposed phase) shows no fatty infiltration. (g) Coronal SSTSE image (SSTSE) shows irregular contours of the liver suggesting capsular involvement. (h) Coronal delayed image (DEL) shows multiple metastases with washout and central persistent enhancement

Fig. 57.3  Metastasis, gastrinoma, multiple with a large lymph node, MRI findings. (a) Axial TSE image (T2 fatsat) shows multiple liver metastases (*), a large lymph node (solid arrow), and thickened stomach wall (open arrow). (b) Axial

in-phase image (T1 in phase): metastases are hypointense to the liver. (c and d) Axial arterial and delayed phase images (ART/DEL): metastases show similar fashion

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Neuroendocrine Tumor IV: Carcinoid Tumor Liver Metastases

The term “carcinoid” is used for neuroendocrine tumors (NET) from the extrapancreatic origin. The endocrine tumors of the gastrointestinal tract, which are known as carcinoids, originate from the diffuse neuroendocrine cell system. These cells are scattered throughout the mucosa of the GI tract and express neuroendocrine markers such as chromogranin A. Carcinoid tumors can produce serotonin and can cause flushing, diarrhea, and bronchial obstruction (carcinoid syndrome). There are 14 cell types which produce different hormones. Carcinoid shows a nonrandom distribution in the GI tract: stomach (2–3 %; recent studies, 11–41 %), duodenum and proximal jejunum (22 %), distal jejunum and ileum (23–28 %), appendix (19 %), cecum and ascending colon (9 %), and rectosigmoid (20 %). Carcinoid type of tumors is found in up to 55 % of patients with NET and up to 60 % may be malignant with hepatic metastases.

MR Imaging Findings Carcinoid tumor liver metastases may have variable signal intensity on T1- and T2-weighted images. On T2-weighted images lesions may have low-signal-intensity areas, as well as high-signal-intensity areas. The low-signal-intensity areas correspondingly will have high signal intensity on T1-weighted images. These findings are consistent with the presence of hemorrhage or protein content within the lesions. After injection of gadolinium, the lesions show peripheral ring-shaped

enhancement in the arterial phase and washout in the delayed phase. The lesions may be large in size. The presence of calcifications, which are better appreciated on CT, is a nonspecific finding. Relatively large lesions may have cystic components centrally which may be filled with colloid or protein-rich fluid, appearing high on T1-weighted images. Larger tumors also tend to have solid peripheral components with persistent enhancement (Figs. 58.1, 58.2, and 58.3).

Differential Diagnosis Hemorrhage and other hemorrhagic tumors should be distinguished based on characteristic MR imaging findings.

Literature 1. Capella C, Heitz PU, Hofler H, et al. Revised classification of neuroendocrine tumours of the lung, pancreas and gut. Virchows Arch. 1995;425:547–60. 2. Kloppel G, Anlauf M. Epidemiology, tumor biology and histopathological classification of neuroendocrine tumours of gastrointestinal tract. Clin Gastroenterol. 2005;19:507–17. 3. Touzios JG, Kiely JN, Pitt SC, et al. Neuroendocrine hepatic metastases: does aggressive management improve survival? Ann Surg. 2005;241:776–85. 4. McGill DB, Rakela J, Zinsmeister AR, et al. A 21 year experience with major hemorrhage after percutaneous liver biopsy. Gastroenterology. 1990;99: 1396–400.

58  Neuroendocrine Tumor IV: Carcinoid Tumor Liver Metastases  125

Fig. 58.1  Metastasis, carcinoid with hemorrhage, drawings. T2 fatsat: dark hematoma (*) is located in the center of the metastasis, which is predominantly hyperintense to the liver. T1 in phase: hematoma shows high signal caused by

methemoglobin (*). ART: parts of the metastasis show heterogeneous enhancement. DEL: peripheral parts of the metastasis show more enhancement than the central hemorrhagic part

Fig. 58.2  Metastasis, carcinoid with hemorrhage, MR findings. (a) Axial fatsuppressed T2-weighted TSE image (T2 fatsat): dark hematoma (*) is located in the center of the metastasis, which is predominantly hyperintense to the liver. Artifact caused by the metal wire after sternotomy (open arrow). (b) Axial inphase image (T1 in phase): hematoma shows high signal caused by methemoglobin (*). (c) Axial GRE image in the arterial phase (ART): parts of the metastasis show heterogeneous enhancement. (d) Axial delayed phase (DEL): the hematoma

appears to remain unenhanced. (e) Axial SSTSE image (SSTSE) shows decreased signal in the solid parts of the metastasis. (f) Axial opposed-phase image (T1 opposed phase) shows increased perilesional signal caused by steatotic liver (arrow). (g) Magnified view from an axial fat-suppressed T2-weighted image shows the hemorrhage in the center of the mass that is predominantly dark (*). (h) Magnified view from an axial in-phase T1-weighted image shows the hemorrhage in the center of the mass that is predominantly bright (*)

Fig. 58.3  Metastasis (another patient), carcinoid, protein producing, MRI findings. (a) Axial TSE (T2 fatsat) shows three carcinoid metastases with variable solid component (arrows). (b) Axial fat-suppressed T1-weighted image (T1 fatsat): one of the lesions contains fluid with high signal (*), consistent with high

protein content. (c) Axial arterial phase image (ART) shows enhancement of mainly the solid parts (arrows). (d) Axial delayed phase image (DEL) shows persistent enhancement of the solid parts (arrows)

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Neuroendocrine Tumor V: Peritoneal Spread

Peritoneal carcinomatosis has been described in association with ­neuroendocrine tumors. Overall peritoneal spread from neuroendocrine tumors can occur in 10 %. Carcinoid tumors produce peritoneal spread in 27 % and non-gastrinoma pancreatic tumors in 11 %. Peritoneal spread from gastrinoma is rare. In addition to the nature of the primary tumor, the size of the primary tumor of >5 cm is associated with the presence of peritoneal disease from pancreatic endocrine tumors. In patients with carcinoid tumors, an ileal primary tumor is more often associated with peritoneal spread than carcinoid at other locations. Patients with peritoneal metastases can also have concurrent liver metastases. However, it should be kept in mind that capsular implants may show ingrowths and mimic liver lesions at imaging. Particularly, MR imaging can accurately detect peritoneal nodules, liver capsular nodules, ascites, and presence of soft tissue masses within the mesentery as well as in the greater omentum.

c­ apsular lining show increased enhancement which persists in the later phases. Based on the sequences with high soft tissue contrast and routine gadolinium-enhanced imaging, MR imaging provides more accurate information than other modalities including CT (Figs. 59.1, 59.2, and 59.3). MR imaging can better distinguish ascites from solid components.

Differential Diagnosis Based on the imaging findings, the differential diagnosis includes peritoneal spread from other malignancies such as ovarian, breast, and colorectal. Correlation with clinical history and localization of the primary tumor may facilitate distinction.

Literature MR Imaging Findings At MR imaging, the peritoneal carcinomatosis with capsular spread to the liver presents as high signal intensity on T2-weighted images with increased thickness of the peritoneal lining and irregularity of the liver capsule. Some lesions around the liver may become large and show ingrowths into the liver and may become liver lesions. At T1-weighted images the findings are nonspecific. After injection of gadolinium, in the arterial phase, the nodular component and thickened peritoneal and

1. Vasseur B, Cadiot G, Zins M, et al. Peritoneal carcinomatosis in patients with digestive endocrine tumors. Cancer. 1996;78:1686–92. 2. Lebtahi R, Cadiot G, Sarda L, et al. Clinical impact of somatostatin receptor scintigraphy in the management of patients with neuroendocrine gastroenteropancreatic tumors. J Nucl Med. 1997;38:853–8. 3. Krenning EP, Kwekkeboom DJ, Bakker WH, et al. Somatostatin receptor scintigraphy with [111In-DTPAD-Phe1]- and [123I-Tyr3]-octreotide: the ­ Rotterdam experience with more than 1,000 patients. Eur J Nucl Med. 1993;20:716–31. 4. Berger JF, Laissy JP, Limot O, et al. Differentiation between multiple liver ­hemangiomas and liver metastases of gastrinomas: value of enhanced MRI. J Comput Assist Tomogr. 1996;20:349–55.

59  Neuroendocrine Tumor V: Peritoneal Spread  127

Fig. 59.1 Metastasis, neuroendocrine, peritoneal and capsular involvement, drawings. SSTSE: large (*) and small capsular ingrowths (solid arrow) appear as hyperintense to the liver; peritoneal involvement (open arrow). T1 in phase:

lesions are hypointense to the liver. ART: all lesions show enhancement. DEL: note the difference between the capsular (solid arrows) and the peritoneal enhancement (open arrows)

Fig. 59.2  Metastasis, neuroendocrine, peritoneal and capsular involvement, MRI findings at 3.0T. (a) Axial SSTSE image (SSTSE): capsular thickening (solid arrow) and a large ingrowth (*) are hyperintense to the liver; the peritoneal thickening appears darker (open arrow). (b) Axial in-phase T1-weighted GRE (T1 in phase): similar appearance of the larger (*) and the smaller (arrow) capsular lesions suggests their common origin. (c) Axial arterial phase image (ART): the lesions show intense enhancement. (d) Axial delayed phase image (DEL): the cap-

sular (solid arrows) and peritoneal (open arrows) lesions show increased and persistent enhancement. (e) Axial BBEPI image (T2 fatsat): compared to SSTSE, the conspicuity of the capsular lesions (arrows) is improved. (f) Axial contrastenhanced CT (CT) shows the largest lesion (*) well; the smaller capsular lesions are difficult to recognize. (g) Coronal SSTSE image (SSTSE) shows diffuse and irregular capsular thickening (arrows). (h) Coronal delayed phase image (DEL) shows abnormal capsular enhancement (arrows)

Fig. 59.3  Metastasis, neuroendocrine, peritoneal and capsular involvement, CT and MRI findings at a different anatomic level, drawing. (a) Axial enhanced (single phase) CT shows two capsular lesions (arrows). (b) Axial BBEPI image (MRIBBEPI) shows multiple bright lesions (arrows). (c) Axial arterial phase image

(MRI, arterial phase) shows intense enhancement of the capsular lesions (arrows). (d) Drawing illustrates the capsular (solid arrows), peritoneal (open arrows) spread, and lymph node metastases

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60

Neuroendocrine Tumor VI: Role of Diffusion-Weighted Imaging

Neuroendocrine tumors (NETs) are a heterogeneous group of ­neoplasms composed of carcinoid and pancreatic tumors. Most lesions have an indolent rate of growth and a propensity to produce and secrete a variety of hormones and other vasoactive substances, giving rise to diverse clinical syndromes. Carcinoid tumors have distinct features depending on their site of origin. In the 1960s, Williams et al. classified carcinoid tumors based on embryologic derivation, distinguishing between the foregut (bronchial, stomach, duodenal), midgut (jejunal, ileal, cecal, appendiceal), and hindgut (distal colon and rectal). As a rule, metastatic midgut carcinoid tumors produce serotonin and other vasoactive substances that give rise to the typical carcinoid syndrome. This syndrome manifests primarily as diarrhea and flushing, a vasomotor phenomenon that causes redness and warmth in the face and upper torso. Carcinoid heart disease, characterized by fibrosis of the tricuspid and pulmonic heart valves, can also occur in patients with severe and prolonged elevations of circulating serotonin. In contrast, hindgut carcinoid tumors are rarely, if ever, associated with a hormonal syndrome. Therapeutic options for treatment of metastatic NETs are expanding. Octreotide represents the appropriate first-line treatment for most patients with well-differentiated tumors. IFN-α is another agent that can palliate hormonal symptoms and inhibit tumor growth, albeit with higher rates of toxicity than octreotide. Cytotoxic chemotherapy has long been known to be active in poorly differentiated NETs. Liver-­ directed therapies such as surgical cytoreduction, ablation, and embolization are frequently employed for treatment of patients with liver-predominant metastases. New radioembolization techniques utilizing 90Y microspheres are encouraging due to their reduced toxicity. It is important for radiologists to be familiar with the various ­treatment options of particularly the liver-directed therapies, which can affect the MR imaging appearance of the liver lesions after treatment.

MR Imaging Findings Liver metastases from NETs typically are numerous small lesions with similar size. On the T2-weighted images, the lesions appear much brighter than most of the colorectal liver metastasis due to higher fluid content. The lesions show either ring or heterogeneous arterial enhancement and washout in the delayed phase images. On the DWI, the lesions remain bright due to the T2 shine-through and appear very dark on the apparent diffusion coefficient (ADC) that eliminates the T2 shine-through and better demonstrates the restricted diffusion, which is a measure of hypercellularity (Figs. 60.1 and 60.2). After a liver-directed or systemic treatment, the lesions may increase their T2 signal, decrease the enhancement, and increase the ADC values. The constellation of such findings usually indicates a good treatment response. Quantitative measure of treatment response has been developed based on the volumetric assessment that includes changes in vascularity as well as cellularity and can be expressed based on MRI perfusion and ADC histogram analysis. Typically, a shift of the ADC histogram to the right and an increased range denote a good treatment response.

Literature 1. Williams ED, Sandler M. The classification of carcinoid tumours. Lancet. 1963;1:238–9. 2. Kulke MH, Mayer RJ. Carcinoid tumors. N Engl J Med. 1999;340:858–68. 3. Strosberg JR, Nasir A, Hodul P, et al. Biology and treatment of metastatic gastrointestinal neuroendocrine tumors. Gastrointest Cancer Res. 2008;2:113–25. 4. Strosberg JR, Cheema A, Kvols LK. A review of systemic and liver-directed therapies for metastatic neuroendocrine tumors of the gastroenteropancreatic tract. Cancer Control. 2011;18:127–37. 5. Li Z, Bonekamp S, Halappa VG, et al. Islet cell liver metastases: assessment of volumetric early response with functional MR imaging after transarterial chemoembolization. Radiology. 2012;264:97–109.

60  Neuroendocrine Tumor VI: Role of Diffusion-Weighted Imaging  129

Fig. 60.1  Neuroendocrine tumor liver metastasis before right hemihepatectomy. (a) Axial fat-suppressed T2-weighted TSE image (T2 fatsat): numerous liver lesions appear markedly hyperintense compared to the liver; note small perihepatic ascites. (b) Axial T1-weighted in-phase (T1 in phase): the metastases are hypointense compared to the liver. (c) Axial arterial phase 3D T1-weighted image (ART): the lesions show intense heterogeneous enhancement; note the hypertrophic hepatic artery. (d) Axial delayed phase image (DEL): the lesions show variable washout and become heterogeneous. (e) Axial T2-weighted SSTSE image

(SSTSE): note that the lesions are hyperintense, however still lower than the cerebrospinal fluid, rendering these as solid lesions. (f, g) Axial diffusion-weighted image (DWI b = 0) shows the lesions as hyperintense on this baseline diffusion image; with a b-value of 500 (DWI b = 500), the lesions show restricted diffusion with persistent high signal. (h) Apparent diffusion coefficient (ADC) map shows the lesions as dark confirming the restricted diffusion as a measure of hypercellularity

Fig. 60.2  Neuroendocrine tumor liver metastasis after right hemihepatectomy. (a) Axial fat-suppressed T2-weighted TSE image (T2 fatsat): note the postoperative changes with several hyperintense lesions in the left liver remnant. (b–d) Axial T1-weighted images before (T1 fatsat), arterial (ART), and delayed (DEL) phases show similar enhancement of the lesions with more and slightly larger lesions

compared to preoperative MRI above. (e) Color-coded maximum intensity image (MIP) based on the arterial phase shows innumerable liver lesions. (f–h) Axial diffusion-weighted images with b-values of 0 (baseline) and 500 with the ADC map confirm that the lesions have restricted diffusion, similar to the lesions prior to hemihepatectomy

130  Part III  Solid Liver Lesions  –  III B:  Metastases: non-colorectal

61

Ovarian Tumor Liver Metastases: Mimicking Giant Hemangioma

Ovarian cancer has the highest mortality rate of all gynecologic malignancies, in which about 70 % of patients have peritoneal ­ ­involvement at the time of diagnosis. The tumors have tendency to show direct spread as well as intraperitoneal dissemination. The staging system is surgically based: stage I, disease being limited to one or both ovaries; stage II, extra-ovarian spread within the pelvis; stage III, diffuse peritoneal disease involving the upper abdomen; and stage IV, distant metastases including hepatic lesions. Common sites of intraperitoneal seeding include the omentum, paracolic gutters, liver capsule, and diaphragm. Thickening, nodularity, and enhancement are all signs of peritoneal involvement. Microscopic peritoneal and liver capsular spread remains challenging to detect at imaging. Some ­ ­investigators have shown that MR imaging is superior in visualization of small or equivocal peritoneal implants compared with CT.

MR Imaging Findings At MR imaging, the intrahepatic, liver capsular, and peritoneal carcinomatosis presents as high signal intensity on T2-weighted ­ images. Liver lesions may grow diffusely and replace the entire hepatic parenchyma; capsular lesions may show ingrowths into the liver. High signal of the liver lesions may show similarity with giant hemangiomas in the liver. At T1-weighted images the findings are nonspecific. After injection of gadolinium, the liver lesions show heterogeneous enhancement in the arterial phase which remains heterogeneous in the delayed phase due to washout of the contrast as opposed to giant ­hemangiomas which typically show persistent enhancement in the delayed phase (Figs. 61.1 and 61.2). Thickened peritoneum and ­omentum show high signal intensity on T2-weighted images with

­persistent delayed enhancement (Fig. 61.3). MR imaging facilitates better ­distinction between fluid and non-fluid components.

Differential Diagnosis For the differential diagnostic workup, clinical correlation is recommended to distinguish from other disseminated malignancies such as breast and colorectal.

Management Early ovarian cancer is treated with comprehensive staging laparotomy, whereas advanced but operable disease is treated with primary cytoreductive surgery (debulking) followed by adjuvant chemotherapy. Patients with unresectable disease may benefit from neoadjuvant (preoperative) chemotherapy before debulking.

Literature 1. Woodward PJ, Hosseinzadeh K, Saenger JS. From the archives of the AFIP: radiologic staging of ovarian carcinoma with pathologic correlation. RadioGraphics. 2004;24:225–46. 2. Low RN, Carter WD, Saleh F, et al. Ovarian cancer: comparison of findings with perfluorocarbon-enhanced MR imaging, In-111-CYT-103 immunoscintigraphy, and CT. Radiology. 1995;195:391–400. 3. Low RN, Semelka RC, Worawattanakul S, et al. Extrahepatic abdominal imaging in patients with malignancy: comparison of MR imaging and helical CT, with subsequent surgical correlation. Radiology. 1999;210:625–32.

61  Ovarian Tumor Liver Metastases: Mimicking Giant Hemangioma  131

Fig. 61.1  Metastasis, ovarian carcinoma metastases, drawings. T2 fatsat: a large metastasis and several smaller lesions (left liver) are hyperintense to the liver. T1 in phase: metastases are hypointense to the liver. ART: metastases show intense het-

erogeneous enhancement. DEL: metastasis shows persistent heterogeneous enhancement. Note that the liver capsule along the larger lesion is permeated

Fig. 61.2  Metastasis, ovarian carcinoma metastases, MRI findings. (a) Axial TSE image (T2 fatsat): a large metastasis and several smaller lesions (left liver) are hyperintense to the liver. Note that the larger lesions contain low-signal-intensity linear structures, including vessels (open arrow). (b) Axial in-phase image (T1 in phase): metastases are hypointense to the liver. The larger lesion contains an area of high signal intensity (open arrow), most likely mucin. (c) Axial arterial phase image (ART): metastases show intense heterogeneous enhancement. (d) Axial delayed phase image (DEL): metastasis shows persistent heterogeneous enhance-

ment. Note that the liver capsule along the larger lesion is permeated and appears irregular (arrows). (e) Coronal SSTSE image (SSTSE) shows that the right liver is completely replaced by the tumor with abundant ascites, suggesting pseudomyxoma peritonei. (f) Axial SSTSE image (SSTSE) shows a small dark area with large metastasis, consistent with mucin (open arrow). (g, h) Axial portal (POR) and venous (VEN) phase images show the progressive heterogeneous enhancement of the larger lesion

Fig. 61.3  Metastasis, ovarian carcinoma in the pelvis (primary tumor evaluation in the same patient), MRI findings. (a) Coronal TSE image through the pelvis shows the enlarged liver and the ovarian carcinoma with cystic and solid compo-

nents. (b) Sagittal TSE image: ovarian carcinoma consists of several cystic and solid components (*). (c, d) Axial TSE and gadolinium-enhanced delayed phase images show thickened wall of one of the cysts with enhancement (*)

132  Part III  Solid Liver Lesions  –  III B:  Metastases: non-colorectal

62

Renal Cell Carcinoma Liver Metastasis

Renal cell carcinoma (RCC) is the 7th leading malignant condition among men and the 12th among women, accounting for 2.6% of all cancers. The aim of preoperative imaging in RCC is to adequately assess tumor size, localization, and organ confinement; to identify lymph node and/or visceral metastases; and to reliably predict the presence and extent of any thrombus of the vena cava. In 25 % of the patients, advanced disease, including locally invasive or metastatic renal cell carcinoma is found at presentation. Moreover, a third of the patients who undergo resection of localized disease will have a recurrence. Median survival for patients with metastatic disease is about 13 months. Thus, there is a great need for more effective surgical and medical therapies. Nephrectomy may be warranted, even in the presence of metastatic disease. The detection of visceral metastases appears to be crucial since it has been shown that even patients with metastatic disease might benefit from radical nephrectomy followed by systemic immunotherapy. MR imaging provides more comprehensive locoregional evaluation of the primary lesion(s) including the distinction from concurrent (complicated) renal cysts, vascular invasion, and liver metastases.

delayed phases, the metastases often show washout and may become more heterogeneous (Figs. 62.1 and 62.2).

Differential Diagnosis Other hypervascular liver lesions including primary tumors as well as secondary tumors from other sources such as the pancreas may have very similar appearance and need clinical correlation or US-guided biopsy for confirmation of proper diagnosis (Fig. 62.3).

Management Surgical excision of a solitary metastasis in patients with advanced RCC is recommended in many cases, but this approach has not yet been proven to be effective in prolonging survival.

Literature MR Imaging Findings At MR imaging, renal cell carcinoma liver metastases appear as low signal intensity on T1-weighted images and moderately high signal intensity on T2-weighted images with fat suppression. After administration of gadolinium, renal cell carcinoma liver metastases may show variable enhancement patterns including an intense homogeneous to heterogeneous enhancement in the arterial phase. In the portal and

1. Semelka RC, Shoenut JP, Magro CM, et al. Renal cancer staging: comparison of contrast-enhanced CT and gadolinium-enhanced fat-suppressed spin-echo and gradient-echo MR imaging. JMRI. 1993;3:597–602. 2. Heidenreich A, Ravery V. European Society of Oncological Urology: preoperative imaging in renal cell cancer. World J Urol. 2004;22:307–15. 3. Mickisch GH, Garin A, van Poppel H, et al. Radical nephrectomy plus interferon-­alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomized trial. Lancet. 2001;358:966–70. 4. Figlin RA. Renal cell carcinoma: management of advanced disease. J Urol. 1999;161:381–6.

62  Renal Cell Carcinoma Liver Metastasis  133

Fig. 62.1  Metastasis, renal cell carcinoma metastasis, drawings. T2 fatsat: metastasis is hyperintense to the liver. T1 in phase: metastasis is hypointense to the liver.

ART: metastasis shows intense heterogeneous enhancement. DEL: metastasis shows some washout with persistent heterogeneous enhancement

Fig. 62.2  Metastasis, renal cell carcinoma metastasis, MRI findings. (a) Axial TSE image (T2 fatsat): metastasis is hyperintense to the liver. (b) Axial in-phase image (T1 in phase): metastasis is hypointense to the liver. (c) Axial arterial phase image (ART): metastasis shows heterogeneous enhancement. (d) Axial delayed phase image (DEL): metastasis shows some washout with persistent heterogeneous enhancement. (e) Axial SSTSE image (SSTSE): metastasis is slightly hyper-

intense. (f) Axial opposed-phase image (T1 opposed phase) shows slight signal drop in the liver indicating subtle steatosis. Note that metastases are surrounded by persistent high perifocal signal due to the compressed liver. (g) Coronal SSTSE image (SSTSE) shows the metastasis as a relatively bright lesion. (h) Coronal delayed image (DEL) shows the metastasis with persistent heterogeneous enhancement

Fig. 62.3  Metastasis, pancreatic carcinoma metastasis (another patient), MRI findings. (a) Axial TSE image (T2 fatsat) shows two metastases that are slightly hyperintense to the liver (arrows). (b) Axial in-phase image (T1 in phase): metas-

tases are hypointense to the liver (arrows). (c) Axial arterial phase image (ART): metastases show faint, almost homogeneous, enhancement (arrows). (d) Axial delayed phase image (DEL) shows metastases with washout

Part III C: Primary solid liver lesions in cirrhotic liver

136  Part III  Solid Liver Lesions  –  III C:  Primary solid liver lesions in cirrhotic liver

63

Cirrhosis I: Liver Morphology

Damage to the liver, which often leads to fibrosis and cirrhosis, can be caused by several factors, including toxic agents, metabolic disorders, obesity, alcoholism, and viral infections. Aflatoxin is considered an important cause of cirrhosis in endemic areas, such as Africa and Asia. Metabolic and genetic disorders, including hemochromatosis, can lead to cirrhosis as well. Alcohol may directly damage the liver cells, but it also impairs the uptake as well as the oxidation of fatty acids in the hepatocellular mitochondria. Excess dietary fat and carbohydrates are stored as fatty acids and triglycerides in the hepatocytes. In addition, damaged liver cells lose their ability to efficiently remove triglycerides from the liver. Therefore, obesity, diabetes (type II), and alcoholism can lead to fatty liver. Long-standing steatosis can lead to steatohepatitis, which may progress to fibrosis and eventually to cirrhosis. Viral hepatitis is currently the most important etiologic factor leading to liver fibrosis and cirrhosis in North America.

MR Imaging Findings Cirrhosis induces several intra- and extrahepatic changes including enlargement of the caudate lobe and the left lateral segment of the

liver, atrophy of the right hepatic lobe and the left medial segment, nodularity of the liver surface, coarse liver architecture, ascites, splenomegaly, and the development of collaterals. At MR imaging, cirrhotic liver shows changed morphology which may include irregular contours, atrophy of certain segments (usually segment IV), central atrophy, and hypertrophy of some segments. Cirrhotic livers contain regenerative nodules which may develop into dysplastic nodules and hepatocellular carcinomas over time (Figs. 63.1, 63.2, and 63.3).

Literature 1. Hussain SM, Zondervan PE, et al. Benign versus malignant hepatic nodules: MR imaging findings with pathologic correlation. RadioGraphics. 2002;22: 1023–36. 2. Ito K, Mitchell DG, Gabata T, Hussain SM. Expanded gallbladder fossa: ­simple MR imaging sign of cirrhosis. Radiology. 1999;211:723–6. 3. Ito K, Mitchell DG, Siegelman ES. Cirrhosis: MR imaging features. Magn Reson Imaging Clin N Am. 2002;10:75–92. 4. Nonomura A, Enomoto Y, Takeda M, et al. Clinical and pathological features of non-alcoholic steatohepatitis. Hepatol Res. 2005;33:116–21.

63  Cirrhosis I: Liver Morphology  137

Fig. 63.1  Cirrhosis, morphology of the liver, drawings. T1 fatsat: multiple regenerative nodules cause irregular contours of the liver. SSTSE: hypertrophy of segments I, II, and III with right-sided atrophy; note also irregular contours. T1

opposed phase: segment I and right-sided hypertrophy; note also irregular contours. SSTSE: segments II and III with right-sided hypertrophy

Fig. 63.2  Cirrhosis, morphology of the liver, MRI findings from six different patients. (a) Axial fat-suppressed T1-weighted GRE image (T1 fatsat): multiple bright nodules and septa cause irregular contour of the liver. (b) Axial SSTSE image (SSTSE): segments I, II, and III hypertrophy with right-sided atrophy is present. Note the fine irregularity of the liver contours due to intrahepatic nodules (arrows). (c) Axial opposed-phase image (T1 opposed phase): multiple bright nodules with predominant right-sided and segment I hypertrophy are present. (d)

Axial SSTSE image (SSTSE): prominent left- and right-sided hypertrophy (i.e., segmental regenerative). (e) Axial SSTSE image (SSTSE) shows segment IV atrophy (*). (f) Coronal SSTSE image (SSTSE) shows atrophy of the liver and splenomegaly. (g) Axial SSTSE image (SSTSE) shows absence of the segment IV due to complete atrophy. Note the interposition of the bowel loops with the empty gallbladder fossa (*). (h) Coronal SSTSE image (SSTSE) shows hypertrophy of the right and the left lateral segment of the liver

Fig. 63.3  Cirrhosis, morphology of the liver, drawings. (a) Atrophy of segment IV, with relative hypertrophy of the right liver and segments II and III. (b) Atrophy

of the liver with splenomegaly. (c) Complete disappearance of segment IV with empty gallbladder fossa (*). (d) Hypertrophy of the right and the left liver

138  Part III  Solid Liver Lesions  –  III C:  Primary solid liver lesions in cirrhotic liver

64

Cirrhosis II: Regenerative Nodules and Confluent Fibrosis

Cirrhosis is mainly composed of regenerative nodules (RNs) that are surrounded by fibrous septa. In addition to the nodules, cirrhotic livers may have areas of increased segmental fibrosis which may mimic malignancy particularly on US and CT because these modalities lack the inherent tissue contrast and routine use of dynamic contrast-­ enhanced imaging. Also the RNs may be challenging to distinguish from malignancy on these modalities. MR imaging is highly sensitive and specific for diffuse liver lesions including cirrhosis and related abnormalities.

Pathology RNs result from a localized proliferation of hepatocytes and their ­supporting stroma. RNs include monoacinar RNs, multiacinar RNs, cirrhotic nodules, lobar or segmental hyperplasia, and focal nodular hyperplasia. RN is a well-defined region of parenchyma that has enlarged in response to necrosis, altered circulation, or other stimuli. The diameter varies between less than a millimeter and few centimeters. Macronodular cirrhosis contains nodules >3 mm. Cirrhotic nodules are RNs that are largely or completely surrounded by fibrous septa (Fig. 64.3).

MR Imaging Findings At MR imaging, RNs show variable signal intensity on T1-weighted sequences (low, iso, high). By definition, RNs show low signal ­intensity on T2-weighted sequences and do not show any detectable enhancement in the arterial phase after injection of gadolinium. In the later phase, cirrhotic livers often show septal enhancement with some enhancement of the RNs. Unlike previous reports, MR imaging facilitates distinction between confluent fibrosis and segmental or diffuse hepatocellular carcinoma. Confluent fibrosis typically has slightly increased signal on T2-weighted images but lacks arterial enhancement or washout in the delayed phases. Instead, confluence fibrosis shows persistent enhancement in the delayed phases due to the ­presence of fibrosis (Figs. 64.1 and 64.2).

Literature 1. International Working Party. Terminology of nodular hepatocellular lesions. Hepatology. 1995;22:983–93. 2. Hussain SM, Zondervan PE, et al. Benign versus malignant hepatic nodules: MR imaging findings with pathologic correlation. RadioGraphics. 2002;22: 1023–36. 3. Ohtomo K, Baron RL, Dodd III GD, et al. Confluent hepatic fibrosis in ad­van­ ced cirrhosis: evaluation with MR imaging. Radiology. 1993;189: 871–4.

64  Cirrhosis II: Regenerative Nodules and Confluent Fibrosis  139

Fig. 64.1  Cirrhosis, confluent fibrosis. T2 fatsat: the right liver shows atrophy with slight increased signal (*). T1 in phase: the same part has a decreased signal (*). The spleen contains Gamna-Gandy bodies. ART: the suspected part (*) shows

slightly increased enhancement which may suggest an HCC. DEL: the suspected part of the liver (*) becomes almost isointense due to persistent enhancement, compatible with confluent fibrosis

Fig. 64.2  Cirrhosis, confluent fibrosis, MRI findings. (a) Axial fat-suppressed T2-weighted TSE image (T2 fatsat): the liver shows irregular contours with multiple nodules and atrophy of the right liver with slight increased signal (*). (b) Axial T1-weighted in-phase GRE image (T1 in phase): a part of the right liver has decreased signal (*). The enlarged spleen shows Gamna-Gandy bodies as a sign of portal hypertension. (c) Axial arterial phase image (ART): a part of the right liver shows some increased enhancement (*). (d) Axial delayed phase image (DEL): the

enhanced liver (*) does not lose its contrast (no washout), compatible with confluent fibrosis. (e) Axial T2-weighted BBEPI image (BBEPI): due to lack of refocusing pulses, the (iron containing) Gamna-Gandy bodies appear larger. (f) Axial T1-weighted opposed-­phase image (T1 opposed phase) shows the liver with multiple regenerative nodules. (g) Axial SSTSE (SSTSE) shows the liver with irregular contours. (h) Coronal SSTSE (SSTSE) shows the atrophy of the right liver with enlarged spleen. Note a small stone in the gallbladder (arrow)

Fig. 64.3  Cirrhosis, histopathology based on the material from other patients. (a) Photograph of a part of an explant cirrhotic liver with multiple nodules surrounded with septa. The contours of the liver are very irregular (arrow). (b) Photomicrograph (H&E, 40×) shows multiple regenerative nodules (n) surrounded by septa consis-

tent with cirrhosis. (c) Photomicrograph (H&E, 100×) shows a nodule in more detail surrounded by a septum. (d) Photomicrograph (Sirius Red stain, 100×) shows the nodule in C with better demarcation due to specific staining of the fibrotic septum

140  Part III  Solid Liver Lesions  –  III C:  Primary solid liver lesions in cirrhotic liver

65

Cirrhosis III: Dysplastic Nodules

Cirrhotic livers may contain various types of nodules including ­regenerative nodules, dysplastic nodules, and hepatocellular carcinoma (HCC). These nodules are part of the stepwise carcinogenesis of HCC which is based on increasing cellularity and size of the liver lesion. In 1995, an International Working Party of Gastroenterology proposed a terminology in which dysplastic features of the hepatic nodule are expressed. The currently accepted nomenclature in stepwise carcinogenesis of HCC is regenerative nodule → low-grade dysplastic nodule → high-grade dysplastic nodule → small HCC → large HCC. Dysplastic lesions are composed of hepatocytes which show histological characteristics of abnormal growth caused by presumed or proved genetic alteration. Dysplastic nodules include dysplastic focus and dysplastic nodule. Dysplastic focus is defined as a cluster of hepatocytes less than 1 mm in diameter with dysplasia but without definite histologic criteria of malignancy. Dysplasia indicates the presence of nuclear and cytoplasmic changes, such as minimal to severe nuclear atypia and increased amount of cytoplasmic fat or glycogen, within the cluster of cells that compose the focus. Dysplastic foci are common in cirrhosis.

MR Imaging Findings At MR imaging, the signal intensity and enhancement characteristics of the dysplastic nodules are not well established yet. Due to a gradual stepwise transition from a regenerative nodule into a low-grade ­dysplastic nodule, a high-grade dysplastic nodule, and eventually a

small and a large HCC, the hepatocytes within hepatic nodules undergo numerous changes that might not be reflected in their signal intensity or vascularity. So, current MRI sequences might not be able to ­distinguish regenerative nodules from dysplastic nodules with certainty. A majority of high-grade dysplastic lesions and well-differentiated small HCC may have high signal intensity on T1-weighted images. Other findings associated with dysplastic nodules may be fat accumulation, gradual increase in size, increased signal intensity, and increased enhancement (Figs. 65.1, 65.2, and 65.3).

Management In a cirrhotic liver, any nodule with increased size, changed signal intensity, and increased enhancement warrants clinical correlation with alpha-fetoprotein and follow-up with MR imaging.

Literature 1. International Working Party. Terminology of nodular hepatocellular lesions. Hepatology. 1995;22:983–93. 2. Hussain SM, Zondervan PE, et al. Benign versus malignant hepatic nodules: MR imaging findings with pathologic correlation. RadioGraphics. 2002;22: 1023–36. 3. Van den Bos IC, Hussain SM, Terkivatan T, et al. Step-wise carcinogenesis of hepatocellular carcinoma in the cirrhotic liver: demonstration on serial MR imaging. J Magn Reson Imaging. 2006;24:1071–80.

65  Cirrhosis III: Dysplastic Nodules  141

Fig. 65.1  Dysplastic nodules, cirrhotic liver, drawings. Coronal SSTSE: multiple low-signal-intensity nodules are visible in a cirrhotic liver with ascites. TSE fatsat: all nodules have low signal intensity. ART: the largest nodule (arrow) shows

increased enhancement; other nodules show variable enhancement. DEL: the largest nodule (arrow) and other nodules do not show any tumor capsule

Fig. 65.2  Dysplastic nodules, cirrhotic liver, MRI findings. (a) Coronal SSTSE image (SSTSE): multiple low-signal-intensity nodules are present with a cirrhotic liver with splenomegaly and ascites (*). (b) Axial fat-suppressed TSE image (TSE fatsat): all nodules show low signal intensity. (c) Axial arterial phase image (ART): the largest nodule shows increased enhancement (arrow); other lesions show variable enhancement. (d) Axial delayed phase image (DEL): the largest nodule (arrow) does not show any enhancing tumor capsule. (e) Axial opposed-phase

image (T1 opposed phase): most hepatic nodules are bright. (f) Axial in-phase image (T1 in phase): several nodules lose their signal due to iron accumulation, i.e., siderotic nodules (arrows); note also dark Gamna-Gandy bodies in the spleen. (g) Detailed view of the arterial phase (ART): the largest nodule clearly shows enhancement (arrow). (h) Detailed view of the delayed phase (DEL): the largest nodule does not show a tumor capsule (arrow)

Fig. 65.3  Dysplastic nodules, histopathology, drawings. (a) Photomicrograph (H&E stain, 20×) shows a large nodule surrounded by fibrous septa. (b) A detailed photomicrograph (H&E stain, 100×) shows increased cellularity with variable size

of the nuclei indicating at least dysplastic changes. (c) Situation I shows the presence of several dysplastic (DN) and regenerative (RN) nodules in a cirrhotic liver. (d) Situation II shows the presence of a focus of HCC with the largest DN (arrow)

142  Part III  Solid Liver Lesions  –  III C:  Primary solid liver lesions in cirrhotic liver

66

Cirrhosis IV: Cyst in a Cirrhotic Liver

Hepatic cysts are common lesions (may occur in up to 20 % of the general population). Most hepatic cysts are considered to be developmental in origin. Currently, most hepatic cysts are discovered as incidental findings at cross-sectional imaging. Smaller cysts (120 ms) T2-weighted images. After injection of contrast, cysts do not show any enhancement. On delayed post-gadolinium images (up to 5 min) cysts remain unenhanced. MRI is particularly valuable when lesions are small (Figs. 66.1 and 66.2). The cysts differ from small HCC based on the signal intensity and enhancement. As opposed to cysts, small HCC

may vary from low to moderately high signal intensity on T2-weighted images and often show increased arterial enhancement.

Differential Diagnosis Small cysts in the setting of cirrhosis may mimic small HCC on US and CT. MR imaging can reliably distinguish these entities. Hepatic cysts concurrent with cirrhosis are most likely present before the onset of the underlying parenchymal liver disease which leads to cirrhosis (Fig. 66.3).

Literature 1. Murakami T, Imai A, Nakamura H, et al. Ciliated foregut cyst in cirrhotic liver. J Gastroenterol. 1996;31:446–9. 2. Hussain SM, Semelka RC, Mitchell DG. MR imaging of hepatocellular ­carcinoma. Magn Reson Imaging Clin N Am. 2002;10:31–52. 3. Mortele KJ, Ros PR. Cystic focal liver lesions in the adult: differential CT and MR imaging features. RadioGraphics. 2001;21:895–910. 4. Hussain SM, Semelka RC. Liver masses. Magn Reson Imaging Clin N Am. 2005;13:255–75.

66  Cirrhosis IV: Cyst in a Cirrhotic 66  Cirrhosis Liver: IV: Cyst in a Cirrhotic Liver  143

Fig. 66.1  Cyst in a cirrhotic liver, drawings. T2 fatsat: cyst is very bright (fluidlike) compared to the liver with smooth and sharp margins (solid arrow). Note the slightly undulating contours of the liver and a ghost artifact of the cyst (open

arrow). T1 opposed phase: cyst is hypointense to the liver. ART: cyst shows no enhancement. DEL: cyst remains unenhanced

Fig. 66.2  Cyst (solitary) in a cirrhotic liver, MRI findings. (a) Axial fat-suppressed T2-weighted TSE image (T2 fatsat) shows a small sharply marginated bright cyst (solid arrow) with ghost artifacts (open arrows). (b) Axial opposedphase image (T1 in phase): the cyst has low signal intensity. The liver contours are somewhat undulating. (c) Axial gadolinium-enhanced 3D GRE image in the arterial phase (ART): the cyst shows no enhancement. (d) Axial delayed phase (DEL): the cyst remains unenhanced. (e) Coronal T2-weighted SSTSE image with longer

TE of 120 ms (SSTSE): the cyst (arrow) retains its high signal intensity due to high fluid content (typical sign of nonsolid liver lesions). (f) Coronal delayed phase (DEL): the cyst remains unenhanced. (g) A detailed view of the coronal T2-weighted SSTSE image shows the bright cyst (arrow). (h) A detailed view of the coronal delayed phase (DEL) shows the liver with typical cirrhotic morphology (irregular contours and enhanced septa) and the unenhanced cyst (arrow)

Fig. 66.3  Cyst in a cirrhotic liver, schematic drawings explaining the coincidental cyst and cirrhosis. (a–c) Normal liver with cyst should have been present prior to

the development of fibrosis and cirrhosis. (d) A detailed view of the drawing shows the irregular contours of the cirrhotic liver containing a simple cyst

144  Part III  Solid Liver Lesions  –  III C:  Primary solid liver lesions in cirrhotic liver

67

Cirrhosis V: Multiple Cysts in a Cirrhotic Liver

As cysts are common in the liver, multiple small cysts may concur with cirrhosis. Such lesions may have overlapping features with small HCC at imaging. Proper diagnosis is important to avoid unnecessary follow-up and liver biopsy.

MR Imaging Findings At MR imaging, cysts are typically low in signal intensity on T1-weighted images and high in signal intensity on T2-weighted images and retain signal intensity on longer echo time (e.g., >120 ms) T2-weighted images. After injection of contrast, cysts do not show any enhancement. On delayed post-gadolinium images (up to 5 min) cysts remain unenhanced. MRI is particularly valuable when lesions are small. Flow-sensitive MR imaging sequences can be used to reliably distinguish between small cysts from small intrahepatic vessels (Figs. 67.1 and 67.2). It is critical to perform multiphasic dynamic gadolinium-enhanced imaging in the setting of multiple cysts. Particularly, based on these sequences cysts may reliably be distinguished from small HCC. As opposed to multiple cysts, small HCCs show early arterial enhancement.

Differential Diagnosis Multiple small cysts in the setting of cirrhosis may mimic multiple small HCCs. US may be reliable for cysts that are uncomplicated and located superficially in a cirrhotic liver (Fig. 67.3). At CT, it may be challenging to characterize small lesions in the setting of cirrhosis. If MR imaging shows multiple peribiliary cysts, an underlying congenital biliary disease should be considered within the differential diagnosis of patients with multiple liver cysts and cirrhosis.

Literature 1. Murakami T, Imai A, Nakamura H, et al. Ciliated foregut cyst in cirrhotic liver. J Gastroenterol. 1996;31:446–9. 2. Hussain SM, Semelka RC, Mitchell DG. MR imaging of hepatocellular ­carcinoma. Magn Reson Imaging Clin N Am. 2002;10:31–52. 3. Hussain SM, Semelka RC. Liver masses. Magn Reson Imaging Clin N Am. 2005;13:255–75.

67  Cirrhosis V: Multiple Cysts in a Cirrhotic Liver  145

Fig. 67.1  Cyst (multiple) in a cirrhotic liver, drawings. BBEPI: cysts (arrows) are very bright (fluidlike) compared to the liver with smooth and sharp margins; note the slightly undulating contours of the liver, indicating the presence of ­cirrhosis.

T1 in phase: cysts are hypointense to the liver. ART: cysts show no enhancement. DEL: cysts remain unenhanced

Fig. 67.2  Cysts in a cirrhotic liver, MRI findings. (a) Axial black-blood echo planar imaging (BBEPI) shows three hyperintense small lesions (arrows), which in the setting of cirrhosis may mimic foci of hepatocellular carcinoma. (b) Axial inphase image (T1 in phase): the cysts are hardly visible. (c) Axial gadoliniumenhanced GRE image in the arterial phase (ART): the cysts show no enhancement. (d) Axial delayed phase (DEL): two cysts are visible as unenhanced lesion, whereas the third is not quite recognizable. (e) Axial T2-weighted fat-suppressed TSE (T2-weighted fatsat): small cysts and small vessels are difficult to distinguish

due to high signal. (f) Axial opposed-phase image (T1 opposed phase): the cysts are hardly visible. (g) A detailed view of the black-blood EPI (BBEPI) image shows the portal vein (open arrow) and hepatic vein (curved arrow) with signal void due to flow, whereas the cysts (solid arrows) appear bright. (h) A detailed view of the axial arterial phase (ART) shows enhancement of the portal vein (open arrow) and no enhancement of the hepatic veins (curved arrow) and cysts (solid arrows)

Fig. 67.3  Cysts, ultrasound (US) and schematic drawings. (a) US shows typical appearance of cirrhotic liver with irregular contours, which is surrounded by ascites. (b) US shows typical appearance of a simple hepatic cyst (solid arrow) with increased sound transmission (open arrows). (c) Drawing based on BBEPI shows

multiple cysts within a cirrhotic liver (arrows). (d) A detailed view of the drawing shows that the portal vein (open arrow) and hepatic vein (curved arrow) can be distinguished from the cyst (solid arrow) based on the presence of flow and ­anatomic orientation

146  Part III  Solid Liver Lesions  –  III C:  Primary solid liver lesions in cirrhotic liver

68

Cirrhosis VI: Hemangioma in a Cirrhotic Liver

Hepatocellular carcinoma may occur in up to 22 % of patients with long-standing cirrhosis. Hemangiomas can occur in up to 20 % in the general population. In the setting of cirrhosis, however, the incidence of hemangiomas (about 2 %) is lower than expected. The events leading to cirrhosis may obliterate and change the appearance and vascularity of particularly small hemangiomas. MR imaging is likely to offer some advantages over CT in this c­ hallenging setting. In general, contrast enhancement of the cirrhotic liver at CT is often suboptimal. Because of greater sensitivity to small differences in intrinsic tissue contrast as well as gadolinium enhancement, MR imaging is likely to perform better than CT for detection and characterization of liver lesions especially in the setting of cirrhosis.

MR Imaging Findings At MR imaging, small- and medium-sized hemangiomas have characteristic appearance with moderately high signal intensity on T2-weighted sequences and peripheral nodular enhancement in the arterial phase and persistent enhancement in the delayed phase (Figs. 68.1 and 68.2). This characteristic appearance of hemangioma may however change due to gradual parenchymal changes that lead to cirrhosis (Fig. 68.3). The signal intensity as well as the enhancement pattern may become unreliable even on the state-of-the-art MR ­imaging. Therefore, atypical, small,

and fibrotic or hyalinized h­ emangiomas may be difficult to diagnose. In such cases, clinical correlation with alpha-fetoprotein and follow-up studies are preferred to US-guided biopsy which may be undesirable in the setting of cirrhosis.

Differential Diagnosis Small HCCs can show moderately high signal intensity on T2-weighted images, but the signal intensity is typically much lower than the hemangiomas, and the signal may decrease on heavily T2-weighted sequences due to their solid nature. In addition, HCCs usually do not show any persistent enhancement in the delayed phase.

Literature 1. Brancatelli G, Federle MP, Blachar A, et al. Hemangioma in the cirrhotic liver: diagnosis and natural history. Radiology. 2001;219:69–74. 2. Dodd III GD, Baron RL, Oliver III JH, et al. Spectrum of imaging findings of the liver in end stage cirrhosis. II. Focal abnormalities. Am J Roentgenol. 1999;173:1185–92. 3. De Caralt TM, Ayuso JR, Ayuso C, et al. Distortion of subcapsular hepatic hemangioma by hepatic cirrhosis. Can Assoc Radiol J. 1999;50:137–8. 4. Hussain SM, Semelka RC. Liver masses. Magn Reson Imaging Clin N Am. 2005;13:255–75.

68  Cirrhosis VI: Hemangioma in a Cirrhotic Liver  147

Fig. 68.1  Hemangioma in a cirrhotic liver, drawings. BBEPI: hemangioma is markedly hyperintense to the cirrhotic liver (solid arrow). T1 in phase: hemangioma is hypointense to the cirrhotic liver. ART: hemangioma typically shows a

peripheral nodular enhancement (open arrow). DEL: hemangioma becomes completely enhanced and retains its contrast (solid arrow)

Fig. 68.2  Hemangioma in a cirrhotic liver, MRI findings. (a) Axial T2-weighted black-blood echo planar imaging (BBEPI): hemangioma is hyperintense to the liver (arrow). (b) Axial in-phase image (T1 in phase): hemangioma is hypointense to the cirrhotic liver (irregular contours, multiple regenerative nodules, and ascites). Note the ascites (*) and the interposition of the stomach (S) due to liver atrophy. (c) Axial arterial phase image (ART): hemangioma shows typical peripheral nodular enhancement (open arrow). (d) Axial delayed phase (DEL): hemangioma

is completely enhanced and retains its contrast (arrow). (e) Axial T2-weighted SSTSE image with TE of 120 ms (SSTSE): hemangioma retains its high signal indicating its nonsolid nature. Ascites (*). (f) Axial opposed-phase image (T1 opposed phase): hemangioma is hypointense to the liver. (g) A detailed view of the arterial phase shows more clearly the peripheral nodular enhancement (open arrow). (h) A detailed view of the delayed phase shows the homogeneously enhanced hemangioma (arrow)

Fig. 68.3  Preexisting hemangioma in cirrhotic liver, temporal changes, drawings. (a) The drawing shows almost normal contours and morphology of the liver. (b) The drawing shows signs of fibrosis (enlargement of the right liver, rounded edges). (c) The drawing shows signs of cirrhosis (irregular contours with nodules,

atrophy, and left-sided hypertrophy). (d) The drawing shows signs of advanced cirrhosis such as complete atrophy of the area around the falciform ligament with interposition of the stomach

148  Part III  Solid Liver Lesions  –  III C:  Primary solid liver lesions in cirrhotic liver

69

Hepatocellular Carcinoma: UNOS/OPTN Reporting

In 2011, 16,857 patients were awaiting liver transplantation (LTX), while 5,618 adults actually received a liver. In light of this long-­ standing organ shortage, evaluating patients and determining those most in need of a liver transplant and allocation of resources are important issues that have changed over time. Patients with hepatocellular carcinoma (HCC) may receive priority on the transplant list if they meet certain criteria. The Organ Transplant Procurement Network and United Network for Organ Sharing (OPTN/UNOS) Liver Committee, along with the several professional organizations, sponsored a consensus conference on HCC in November 2008. One of the five working groups was specifically charged with developing more specific imaging criteria for HCC exceptions. A recent report had indicated that there was considerable concern that the limited imaging criteria in the current policy were inadequate and led to inappropriate organ allocation. The purpose of the imaging work group, which included radiologists, transplant surgeons, and hepatologists, was the development of more specific imaging criteria for HCC diagnosis and classification, as well as standardization of the report language required by UNOS to qualify LTX candidates for automatic HCC MELD exception points. The diagnostic imaging criteria driving HCC classification rely on the characteristic appearance of HCC on dynamic multiphasic contrast-­ enhanced CT scans or MR images. The qualitative criteria take into consideration not only their common differential increased arterialization but also the relatively decreased presence of contrast agent in most HCC compared with the surrounding liver during portal vein and/or equilibrium phase imaging. A capsule, often seen at equilibrium/ delayed phase imaging, is also considered in the diagnostic criteria. If there is at least one HCC, treated or untreated, present on an image and the report of the imaging study including that image is to be used for obtaining automatic exception MELD points, the clinician

must use the OPTN classification terminology, spelling out the OPTN class for all treated and untreated lesions that meet the diagnostic criteria for HCC and labeling nondiagnostic studies as OPTN 0 (Figs. 69.1 and 69.2). A structured summary at the end of the clinician’s report is strongly encouraged that lists the total number, location (liver segment), size (largest diameter), and OPTN class of all treated or untreated HCC and that states whether the overall radiologic stage of a patient’s HCC meets the Milan criteria, taking into account all relevant current and prior imaging findings. The Liver Imaging Reporting and Data System (LI-RADS) is currently being developed, which is another attempt to standardize the reporting and data collection of CT and MR imaging for HCC. This method of categorizing liver findings for patients with cirrhosis or other risk factors for developing HCC allows the radiology community to: • Apply consistent terminology • Reduce imaging interpretation variability and errors • Enhance communication with referring clinicians • Facilitate quality assurance and research

Literature 1. Pomfret EA, et al. Report of a national conference on liver allocation in patients with hepatocellular carcinoma in the United States. Liver Transpl. 2010;16: 262–78. 2. Willatt JM, et al. MR imaging of hepatocellular carcinoma in the cirrhotic liver: challenges and controversies. Radiology. 2008;247(2):311–30. 3. Hussain SM, et al. Benign versus malignant hepatic nodules: MR imaging ­findings with pathologic correlation. Radiographics. 2002;22:1023–36. 4. Hussain SM, et al. Cirrhosis and lesion characterization at MR imaging. Radiographics. 2009;29:1637–52. 5. http://www.acr.org/Quality-Safety/Resources/LIRADS

69  Hepatocellular Carcinoma: UNOS/OPTN Reporting  149

Fig. 69.1  UNOS/OPTN HCC classes in cirrhosis. The Organ Procurement and Transplantation Network (OPTN) maintains the only US national patient waiting list. The United Network for Organ Sharing (UNOS) works to advance organ availability and transplantation through education, technology, and policy development.

The classes described here are based on the multiparametric MRI approach (i.e., not based on the liver-specific GBCA approach) and can be used when describing MRI findings in cirrhosis. MELD Model for End-Stage Liver Disease

Fig. 69.2  UNOS/OPTN Class 5 lesion subcategories. Once a liver lesion in a cirrhotic liver fulfills the imaging criteria of HCC (OPTN 5), a number of subcategories can be applied to provide more detail in regard to such HCC. Note that the

subcategory OPTN 5A describes stage T1 HCC and OPTN 5B describes stage T2 HCC. Lesions larger than 5 cm are classified as 5X. In addition, a special category of locally or regionally treated HCC (OPTN 5T) has also been described above

150  Part III  Solid Liver Lesions  –  III C:  Primary solid liver lesions in cirrhotic liver

70

HCC in Cirrhosis I: Gadoxetate (Liver-Specific) Versus Nonspecific GBCA

Based on the literature and their own data, Nakamura et al. identified five patterns of hepatocellular carcinomas (HCCs) on gadoxetate (Eovist/Primovist) liver MRI: 1. Early enhancement in the arterial phase and hypointense in hepatobiliary phase (HBP) 2. Early enhancement in the arterial phase and hyperintense in HBP 3. Early enhancement in the arterial phase and isointense in HBP 4. No enhancement in the arterial phase and hypointense in HBP 5. No enhancement in the arterial phase and hyperintense in HBP Based on these patterns, Nakamura et al. found that the overall ­sensitivity of gadoxetate for HCC was only 69 % (the gold standard was based on the explant livers in all cases). The sensitivity was much lower than most of the prior studies (e.g., Di Martino et al., 85 %). The standard of reference of the prior studies with higher gadoxetate sensitivities for HCC was often not based on explant livers. These patterns illustrate the complexity of the HCC appearance as well as their interpretation on gadoxetate liver MRI. The complexity only increases if we add diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) to the mix of findings. The majority of the literature regarding HCC is based on a combination of multiple sequences and use of nonspecific GBCAs, such as gadobenate, gadopentetate, and gadoteridol. Based on the nonspecific GBCAs, the following combinations are considered diagnostic for HCC: 1. T2 hyperintensity (larger HCC) + arterial enhancement + delayed phase washout 2. T2 isointensity/hypointensity (smaller HCC) + arterial enhancement + delayed phase washout The arterial phase should be accurately timed using a bolus track technique; the delayed phase images in this context are acquired 3–4 min after contrast injection. Additional findings that also suggest the diagnosis of HCC include (1) relatively large dominant nodule in a cirrhotic liver, (2) restricted diffusion, (3) capsular enhancement, (4) presence of fat within a nodule, and (5) a nodule-in-nodule appearance (either on T2 or on contrast-enhanced images). Based on the application of nonspecific GBCA, a recent study by Becker-Weidman et al. found an overall sensitivity and specificity of 97 and 100 %, respectively. For lesions ≥2 cm, MR imaging had a sensitivity and specificity of 100 %, respectively. For lesions 5 cm should be considered for surgical or other types of MR Imaging Findings treatment due to the risk of malignancy. Surgery is controversial, particularly in patients with multiple lesions and lesions located at At MR imaging, fat-containing HCAs are bright on T1-weighted in-­ difficult anatomic locations. In patients with multiple adenomas or phase images and decrease their signal intensity on T1-weighted liver adenomatosis, surgical resection or other local treatment may opposed-phase images due to the presence of small amount of fat. be technically impossible. Interval growth and/or elevated serum Some areas within fatty HCAs may appear dark on fat-suppressed alpha-fetoprotein levels in patients with a known hepatocellular adeT2-weighted images as well as on three-dimensional gadolinium-­ noma suggests malignant transformation. HCAs with hemorrhage enhanced gradient-echo images in the delayed phase because the may be treated with hepatic arterial embolization to control the amount of fat may be sufficient to be affected by the fat-suppression hemorrhage. pulse. On the latter images, this finding may mimic washout (Figs. 105.1 and 105.2). At gross pathology, fat-containing HCAs have yellowish areas. At histology, the lesions resemble liver tissue and are Literature often surrounded by a pseudocapsule which consists of compressed 1. Baum JK, Holtz F, Bookstein JJ, et al. Possible association between benign liver parenchyma (Fig. 105.3).

Management The management of HCAs should be individualized based on their size and mode of presentation. The initial step should be to stop any

hepatoma and oral contraceptives. Lancet. 1973;2:926–9. 2. Terkivatan T, de Wilt JH, de Man RA, et al. Indications and long-term outcome of treatment for benign hepatic tumors: a critical appraisal. Arch Surg. 2001;136:1033–8. 3. Hussain SM et al. Hepatocellular adenoma: findings at ultrasound, computed tomography, MR imaging and pathologic analysis. Eur Radiol. 2006;16: 1873–86.

105  Hepatocellular Adenoma IV: Large Exophytic with Pathologic Correlation  223

Fig. 105.1  Adenoma, drawings. T2 fatsat: adenoma is slightly hypointense to the liver. T1 in phase: adenoma is almost isointense to slightly hyperintense to the liver. ART: adenoma shows a moderately intense homogeneous enhancement of

the entire lesion. DEL: adenoma becomes almost isointense to slightly hypointense

Fig. 105.2  Adenoma with fatty infiltration (a) Axial fat-suppressed T2-weighted TSE image (T2 fatsat): adenoma is isointense to the liver. (b) Axial in-phase T1-weighted GRE (T1 in phase): adenoma is slightly hyperintense to the liver. (c) Axial arterial phase post-Gd 3D T1-weighted GRE image (ART): adenoma shows moderately intense and homogeneous enhancement. (d) Axial delayed phase GRE image (DEL): adenoma becomes slightly hypointense to the liver, likely due to the fatty contents of the lesion. (e) Axial 2D T1-weighted GRE image (T1 fatsat): a

part of the adenoma that is most fatty has a lower signal (arrow). (f) Axial opposedphase 2D T1-weighted GRE image (T1 opposed phase): some parts of the lesion lose their signal more than other parts indicating variable amount of fatty infiltration (arrows). (g) Coronal delayed phase post-Gd 3D GRE image (DEL) with high spatial resolution clearly shows the adenoma as an exophytic lesion (arrow). (h) A detailed view of the previous image (DEL) shows the tumor anatomy better (arrow) with a large intratumoral vessel, most likely with accompanying fibrotic tissue

Fig. 105.3  MR-pathology correlation. (a) Photomicrograph (H&E, 40×) shows a small fatty adenoma surrounded by large vessels (arrows). (b) Photomicrograph (H&E, 200×) from the resected adenoma shown above: note normal-appearing

hepatocytes with fat, large vessels and compressed parenchyma. (c) Photomicrograph (H&E, 400×) shows the findings in more detail. (d) Photograph of the gross specimen: large parts of the tumor contain fat and appear yellowish

224  Part III  Solid Liver Lesions  –  III D:  Primary solid liver lesions in non-cirrhotic liver

106

Hepatocellular Adenoma V: Typical Fat-Containing

Fat-containing hepatocellular adenomas (HCAs) are among a variety of other fat-containing tumors of the liver with characteristic histologic features and variable imaging findings. Other common liver lesions that contain fat include focal fatty infiltration (steatosis), focal nodular hyperplasia (FNH), and hepatocellular carcinoma (HCC). Uncommon fat-containing liver lesions include angiomyolipoma, lipoma, liposarcoma, and teratoma. Identification of fat within a liver lesion can be critical in characterization of the lesion. The imaging characteristics of a lesion such as enhancement pattern combined with the pattern of fatty content and the presence of Kupffer cells are helpful in narrowing the differential diagnosis. Computed tomography or ultrasound may indicate the presence of within hepatic lesion; MR imaging is the most specific imaging technique for demonstration of both microscopic and macroscopic fat based on the chemical shift imaging and fat-suppressed sequences.

between primary and secondary liver lesions. Specific contrast media such as SPIO cannot replace the dynamic gadoliniumenhanced imaging because the enhancement patterns play an essential role in the characterization of liver lesions at MR imaging (Figs. 106.1 and 106.2). At histology, fat-containing liver lesions may show striking similarity (Fig. 106.3).

MR Imaging Findings

Literature

At MR imaging, minimally fat-containing HCAs are near isointense on the T1- and T2-weighted sequences, drop their signal on opposed-­ phase images, show homogeneous enhancement in the arterial phase, and fade to isointensity on the delayed phase images. HCAs show uptake of the superparamagnetic iron oxide (SPIO)based contrast media and reveal the presence of small amount of Kupffer cells. Such contrast media can be used to distinguish

1. Prasad SR, Wang H, Rosas H, et al. Fat-containing lesions of the liver: radiologic-­pathologic correlation. RadioGraphics. 2005;25:321–31. 2. Wang YX, Hussain SM, et al. Superparamagnetic iron oxide contrast media: physicochemical characteristics and applications in MR imaging. Eur Radiol. 2001;11:19–31. 3. Hussain SM et al. Hepatocellular adenoma: findings at ultrasound, computed tomography, MR imaging and pathologic analysis. Eur Radiol. 2006;16: 1873–86.

Differential Diagnosis Focal fatty infiltration is often geographic, shows signal drop on the opposed-phase imaging, and does not show washout on the gadolinium-­ enhanced delayed phase images. FNHs contain fat in approximately 6 % and HCC in about 10 % of cases and have tumor morphology and enhancement patterns distinct from HCA at MR imaging.

106  Hepatocellular Adenoma V: Typical Fat-Containing  225

Fig. 106.1  Adenoma, fat containing, drawings. T2 fat sat: adenoma is isointense with a thin bright pseudocapsule. T1 in phase: adenoma is isointense to the liver. ART: adenoma shows an intense homogeneous enhancement of the entire lesion.

DEL: adenoma becomes slightly hypointense to the liver most likely due to fat suppression and not due to washout of contrast material. Note the enhancement of the pseudocapsule

Fig. 106.2  Adenoma, typical, fat-containing, MRI findings. (a) Axial fat-suppressed T2-weighted TSE image (T2 fat sat): adenoma is isointense and only visible due to mass effect and a bright pseudocapsule. (b) Axial in-phase GRE (T1 in phase): adenoma is isointense to the liver. (c) Axial arterial phase GRE image (ART): adenoma shows homogeneous enhancement. (d) Axial delayed GRE image (DEL): adenoma becomes slightly hypointense due to fat suppression and not due to washout. Note the enhanced pseudocapsule. (e) Axial TSE image after SPIO

(T2 fat sat post-SPIO): adenoma shows drop in signal in the periphery of the lesion, indicating its hepatic origin (arrow). (f) Axial opposed-phase GRE image (T1 opposed phase): adenoma drops its signal due to homogeneous fatty infiltration (arrow). (g) Axial fat-suppressed T2-weighted BBEPI image (BBEPI): adenoma is isointense to the liver (arrow). (h) Axial BBEPI after SPIO (BBEPI post-SPIO): adenoma shows drop in signal particularly in the periphery of the lesion due to the presence of the Kupffer cells (arrow)

Fig. 106.3  Adenoma and other fatty tissues and tumors, histology findings. (a) Photomicrograph (H&E, 200×) of a focal fatty infiltration of the liver visible as a lesion at imaging. (b) Photomicrograph (H&E, 200×) from a fatty adenoma (note

the similarity with the previous image). (c) Photomicrograph (H&E, 100×) of biopsy from a fatty focal nodular hyperplasia (FNH). (d) Photomicrograph (H&E, 200×) of biopsy from a fatty hepatocellular carcinoma (HCC)

226  Part III  Solid Liver Lesions  –  III D:  Primary solid liver lesions in non-cirrhotic liver

107

Hepatocellular Adenoma VI: With Large Hemorrhage

Patients with hepatocellular adenomas (HCAs) can present with a number of ways, including pain (32–70 %), hemorrhage (15–42 %), an incidental finding at imaging (15–21 %), or mass at physical or surgical examination (0–26 %). Some women with HCA may present intrahepatic or intraperitoneal (life-threatening) hemorrhage around the menstrual period, which suggests a common hormonal influence on the vasculature of the endometrium and shedding of the endometrial tissue as well as vessels within HCA and hemorrhage. With increasing use of the cross-sectional imaging modalities, including US, CT, and MR imaging, in the assessment of upper abdomen complaints, it is likely that HCA will be discovered as an incidental finding in more patients in the near future.

MR Imaging Findings At MR imaging, hemorrhage has a characteristic appearance on T1-weighted images with predominantly high signal intensity due to the presence of methemoglobin. A thin rim of low signal intensity indicates the presence of hemosiderin. On T2-weighted images, recent hemorrhage has a high signal with low-signal-intensity areas centrally with lower signal intensity in the periphery mainly caused by the hemosiderin. The underlying HCA may be small and may remain latent till the resolution of the most of the hematoma (Figs. 107.1 and 107.2). At ultrasound, the appearance is nonspecific; however, at CT

the hematomas present with fluid collections with relatively high density (Fig. 107.3a, b).

Management In case of acute hemorrhage with an underlying HCA, usually patients are carefully observed and followed with imaging. Hepatic arterial embolization can be an alternative treatment. Digital subtraction angiography prior to embolization may reveal the underlying HCA with an arterial blush and tortuous abnormal tumor vessels (Fig. 107.3c, d). Embolization may be used to control the ongoing hemorrhage, but the underlying HCA can recur after a successful treatment.

Literature 1. Rooks JB, Ory HW, Ishak KG, et al. Epidemiology of hepatocellular adenoma: the role of oral contraceptive use. JAMA. 1979;242:644–8. 2. Terkivatan T, de Wilt JH, de Man RA, et al. Indications and long-term outcome of treatment for benign hepatic tumors: a critical appraisal. Arch Surg. 2001;136:1033–8. 3. Mathieu D, Bruneton JN, Drouillard J, et al. Hepatic adenomas and focal nodular hyperplasia: dynamic CT study. Radiology. 1986;160:53–8. 4. Hussain SM et al. Hepatocellular adenoma: findings at ultrasound, computed tomography, MR imaging and pathologic analysis. Eur Radiol. 2006;16: 1873–86.

107  Hepatocellular Adenoma VI: With Large Hemorrhage  227

Fig. 107.1  Adenoma, drawings. T2 fatsat: adenoma is isointense with a thin bright pseudocapsule. T1 in phase: adenoma is slightly hyperintense to the liver. ART: adenoma shows a moderately intense homogeneous enhancement of the

entire lesion. DEL: adenoma becomes isointense to the liver with enhancement of the pseudocapsule (compressed liver tissue and vessels)

Fig. 107.2  A 24-year-old female – ruptured adenoma, MRI findings before and after embolization. (a) Axial fat-suppressed T2-weighted TSE image (T2 fatsat): a large hematoma is predominantly bright with a dark rim of hemosiderin and a stalklike structure indicating the origin of the hematoma (arrow). (b) Axial inphase T1-weighted GRE (T1 in phase): hematoma is bright to the liver. (c) Axial arterial phase post-Gd T1-weighted GRE image (ART): adenoma shows homogeneous enhancement around the stalklike structure. (d) Axial delayed phase image

(DEL): adenoma becomes almost isointense to the liver. (e) Axial fat-suppressed T2-weighted image after embolization (T2 fatsat): hematoma has decreased in size (arrow). (f) Axial in-phase image (T1 in phase): hematoma has lost most of its high signal (arrow). (g) Axial arterial phase image (ART): multiple (residual or recurrent) adenomas become apparent with homogeneous enhancement (arrows). (h) Axial delayed phase image (DEL): adenomas become almost isointense to the liver

Fig. 107.3  Ruptured adenoma: US, CT, and DSA. (a) Ultrasound (US) shows a large hematoma. (b) Computed tomography (CT) shows the relatively dense hematoma. (c) Selective digital subtraction angiography (DSA) prior to embolization (4 months after the initial MRI) shows multiple areas with extensive arterial

enhancement (blush) of adenoma with multiple abnormal tortuous tumor arteries surrounding the lesion. (d) DSA after completion of the embolization procedure shows no evidence of adenomas

228  Part III  Solid Liver Lesions  –  III D:  Primary solid liver lesions in non-cirrhotic liver

108

Hepatocellular Adenoma VII: Multiple in Fatty Liver (Non-OC-Dependent)

Multiple HCAs often occur in a fatty liver with altered shape and size. Multiple HCAs may also be found in nonfatty livers. Small lesions may mimic metastases with fatty liver. Multiple lesions may occur with type 1 glycogen storage disease and liver adenomatosis (usually >10 HCA). At gross pathologic sectioning, HCAs are well-demarcated yellow or tan lesions that are seldom encapsulated. The consistency is soft or friable, and areas of necrosis and hemorrhage are frequently present. All tumors are highly vascular.

MR Imaging Findings At MR imaging, very small liver lesions within fatty or nonfatty liver can be characterized with much higher accuracy because of the high intrinsic soft tissue contrast based on the T2 characteristics and chemical shift imaging and the ability to visualize enhancement patterns on the routine gadolinium-enhanced dynamic imaging. On follow-up after stopping oral contraceptives (OC), the lesions may remain unchanged. Large exophytic lesion may be characterized as hepatic lesions by identifying the feeding vessels (Figs. 108.1 and 108.2). At US, HCAs within a fatty liver such lesions will appear hypoechoic due to the increased echogenicity of the background liver and may mimic a wide variety of lesions, including liver metastases. At CT, multiple HCAs may appear hyperdense on the unenhanced as well as enhanced scans because of the low density of the fatty liver.

Pathology Histologically, there is no difference among the adenomas arising as single lesions, multiple lesions (2–6 lesions), and liver adenomatosis (>10 lesions) (Fig. 108.3). The difference between “multiple” and “adenomatosis” is arbitrary. Previously, some reports had suggested that liver adenomatosis occurred in a different population and the change in size of these adenomas did not depend on the OC use. Recent reports as well as our own experience contradict this. Therefore, it is likely that “hepatocellular adenomas” and “liver adenomatosis” are two manifestations of the same underlying disease.

Literature 1. International Working Party. Terminology of nodular hepatocellular lesions. Hepatology. 1995;22:983–93. 2. Anthony PP. Tumours and tumour-like lesions of the liver and biliary tract: aetiology, epidemiology and pathology. In: MacSween RNM, Burt AD, Portmann BC, et al. editors. Pathology of the liver. 4th ed. Churchill Livingstone, Philadelphia; 2002. p. 711–5. 3. Flejou JF, Barge J, Menu Y, et al. Liver adenomatosis. An entity distinct from liver adenoma? Gastroenterology. 1985;89:1132–8. 4. Hussain SM et al. Hepatocellular adenoma: findings at ultrasound, computed tomography, MR imaging and pathologic analysis. Eur Radiol. 2006;16: 1873–86.

108  Hepatocellular Adenoma VII: Multiple in Fatty Liver (Non-OC-Dependent)  229

Fig. 108.1  Multiple adenomas, drawings. T1 in phase: no lesions are visible. Adenomas are isointense to the liver. T1 opposed phase: multiple larger as well as very small adenomas are present in the entire liver that shows strong fatty

infiltration. ART: adenomas show homogeneous enhancement. DEL: adenomas become almost isointense to the liver. Note that none of lesions show tumor capsule

a

b

c

d

e

f

g

h

Fig. 108.2  Multiple adenomas, before and after oral contraceptive (OC): MRI findings. (a) Axial in-phase T1-weighted GRE (T1 in phase): adenomas are isointense to the liver. (b) Axial opposed-phase T1-weighted GRE (T1 opposed phase): multiple larger and smaller adenomas become visible due to strong signal drop in the fatty liver. (c) Axial arterial phase T1-weighted GRE image (ART): adenomas show homogeneous enhancement. (d) Axial delayed phase GRE image (DEL): adenomas become isointense to the liver. (e) Axial in-phase

T1-weighted GRE (T1 in phase): 6-month follow-up after stopping OC. No change is visible. (f) Axial opposed-phase T1-weighted GRE (T1 opposed phase): 6-month follow-up after stopping OC. Adenomas remain unchanged in size, number, and signal intensity. (g) Coronal T2-weighted SSTSE (SSTSE): a large exophytic adenoma is visible originating from segment IVB of the liver (*). (h) Coronal delayed phase (DEL): adenoma (*) clearly receives its vasculature from the liver (arrows)

Fig. 108.3  Pathology and histology of multiple adenomas (from a different patient). (a) Photograph of a resected specimen shows multiple adenomas (arrows) within normal liver. (b) Photomicrograph (H&E, 100×) shows the transition with compressed liver (between the lines indicated by arrows), surrounding

the adenoma. (c) Photomicrograph (H&E, 200×) shows an adenoma with mononuclear cells, surrounded by a compressed liver (arrows). (d) Photomicrograph (H&E, 200×): the pseudocapsule is formed by compressed liver (lines and arrows)

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109

Hepatocellular Adenoma VIII: Multiple in Fatty Liver (OC-Dependent)

The exact pathogenesis of HCA is not known. Based on a detailed pathological analysis of various types of lesions that occur in patients with liver adenomatosis, a number of different types of lesions were observed in the same liver. Based on these observations, the following sequence of events was hypothesized: focus → group of foci → nodule → microadenoma → adenoma. Malignant transformation of HCA into HCC has been described in the literature by several groups. Most authors have reported transformation of an existing HCA into HCC. At this point in time, it is not quite clear if all HCAs eventually can transform into HCCs. Also the exact characteristics of HCAs that eventually may undergo malignant transformation are not well known. Currently, most authors consider increase in size of the lesion at imaging, increased serum alphafetoprotein, and suspicious findings at fine-­needle aspiration biopsy as signs of malignant transformation of HCA. According to some authors, some HCA can undergo changes similar to liver cell dysplasia (LCD). In principle, HCA is not premalignant and may undergo reversible change after withdrawal of OC, whereas LCD is an irreversible, premalignant change and will eventually progress to HCC (HCA-LCD-HCC sequence). After stopping OC, HCAs may show decrease in size.

MR Imaging Findings At MR imaging, multiple HCA within a single liver may vary in signal intensity on T2-weighted images. The liver as well as the lesions may contain variable amount of fat on opposed-phase images. Arterial

phase is perhaps the most sensitive sequence to detect lesions. On the delayed phase images, the lesions should not show any washout or enhanced tumor capsule (Figs. 109.1 and 109.2). MR imaging can display many faces of hepatocellular adenomas: (1) a nonfatty single lesion in a nonfatty liver: the lesion appears very similar to the surrounding liver; (2) multiple HCAs within a fatty liver; (3) fatty HCAs and small HCAs associated with intra- and extrahepatic hematomas; and (4) hepatocellular carcinomas (HCCs) may arise from HCAs or at the same anatomic location after regression of HCA. Note the confluent nodules of HCC contained within a thick fibrous tumor capsule (Fig. 109.3).

Literature 1. Gyorffy EJ, Bredfeldt JE, Black WC. Transformation of hepatic cell adenoma to hepatocellular carcinoma due to oral contraceptive use. Ann Intern Med. 1989;110:489–90. 2. Tao LC. Oral contraceptive-associated liver cell adenoma and hepatocellular carcinoma: cytomorphology and mechanism of malignant transformation. Cancer. 1991;68:341–7. 3. Ferrell LD. Hepatocellular carcinoma arising in a focus of multilobular adenoma: a case report. Am J Surg Pathol. 1993;17:525–9. 4. Foster JH, Berman MM. The malignant transformation of liver cell adenomas. Arch Surg. 1994;129:712–7. 5. Lepreux S, Laurent C, Blanc JF, et al. The identification of small nodules in liver adenomatosis. J Hepatol. 2003;39:77–85.

109  Hepatocellular Adenoma VIII: Multiple in Fatty Liver (OC-Dependent)  231

Fig. 109.1  Multiple adenomas, drawings. T2 fatsat: some adenomas are hyperintense, and others isointense and at least one is slightly hypointense to the liver. T1

in phase: all adenomas are isointense. ART: multiple adenomas show homogeneous enhancement. DEL: all adenomas become isointense to the liver

Fig. 109.2  A 43-year-old female – multiple adenomas, before and after oral contraceptive (OC), MRI findings. (a) Axial fat-suppressed TSE image (T2 fatsat): multiple adenomas (arrows) are slightly hyperintense to the liver. (b) Axial in-phase T1-weighted GRE (T1 in phase): adenomas are isointense to the liver. (c) Axial arterial phase post-Gd T1-weighted GRE image (ART): adenomas show homogeneous intense enhancement. (d) Axial delayed post-Gd T1-weighted GRE image (DEL): adenomas become isointense without any central scar or capsular enhancement.

(e) Axial fatsat T2-weighted TSE after SPIO (SPIO T2 fatsat): adenomas show uptake of iron indicating the presence of Kupffer cells and primary origin of the lesions. (f) Axial opposed-phase T1-weighted image (T1 opposed phase): the liver shows some fatty infiltration rendering some of the lesions hyperintense (arrow). (g) Axial arterial phase post-Gd T1-weighted image 6 months after stopping OC (ART): adenomas show significant decrease in size (arrow). (h) Axial delayed post-Gd T1-weighted GRE image (DEL): adenomas remain homogeneous in delayed phase (arrow)

a

b

Fig. 109.3  Many faces of hepatocellular adenoma (HCA). (a) Single HCA that is very similar to the surrounding liver parenchyma and hence difficult to recognize at imaging. (b) Multiple HCA (adenomatosis) in a fatty liver. (c) Fatty HCA and

c

d

HCA associated with intra- and extrahepatic hemorrhage. (d) Adenoma-like HCC may arise as a complication of HCA or long-term oral contraceptive use

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110

Hepatocellular Adenoma IX: Changes During Pregnancy

Hepatocellular adenoma (HCA) in pregnant women requires special considerations because of the risk of hormone-induced growth and spontaneous rupture, due to increased levels of steroid hormones during pregnancy that may threaten the life of both mother and child. Most experts advocate that women with HCA should not get pregnant or advise surgical resection before pregnancy. Cobey et al. reported a maternal and fetal mortality risk of ruptured HCA during pregnancy of 44 and 38 %, respectively. However, all these cases were published in the 1970s and 1980s. The introduction and widespread use of highly advanced imaging modalities have probably decreased the delay in the diagnosis of HCA. More recent reports therefore propose not to discourage women with HCA from pregnancy. In a recent study by Noels et al., 12 women were monitored with documented HCAs during a total of 17 pregnancies. In four cases HCAs grew during pregnancy, requiring a Caesarean section in one patient and radiofrequency ablation in another case during the first trimester of pregnancy. All remaining pregnancies had an uneventful course with a successful maternal and fetal outcome. A “wait and see” management may be advocated in pregnant women presenting with a hepatocellular adenoma. In women with large tumors or in whom hepatocellular adenoma had complicated previous pregnancies, surgical resection may be recommended. In women with smaller adenomas, it may no longer be necessary to discourage pregnancy. Both ultrasound and MR imaging can be applied to monitor the HCAs during pregnancy. Although ultrasound is less expensive, MR imaging provides more reproducible results in regard to the size of the

lesions as well as any rupture with new hemorrhage, which are crucial in the management of HCAs during pregnancy.

MR Imaging Findings HCAs typically show increase in size during pregnancy with the other findings including the T1, T2, and enhancement remaining similar to the prepregnancy appearance of the lesions. After the pregnancy, the lesions should gradually decrease to the size prior to the pregnancy or smaller (Figs. 110.1 and 110.2). Hemorrhage (after a few days) will appear bright on the non-contrast T1-weighted images.

Literature 1. Hussain SM, et al. Hepatocellular adenoma: findings at state-of-the-art MRI, US, CT and pathologic analysis. Eur Radiol. 2006;16:1873–86. 2. Rooks JB, et al. Epidemiology of hepatocellular adenoma. The role of oral contraceptive use. JAMA. 1979;242:644–8. 3. Santambrogio R, et al. Liver transplantation for spontaneous intrapartum rupture of a hepatic adenoma. Obstet Gynecol. 2009;113:508–10. 4. Cobey FC, Salem RR. A review of liver masses in pregnancy and a proposed algorithm for their diagnosis and management. Am J Surg. 2004;187:181–91. 5. Van der Windt DJ, Kok NF, Hussain SM, et al. Case-orientated approach to the management of hepatocellular adenoma. Br J Surg. 2006;93:1495–502. 6. Noels JE, et al. Management of hepatocellular adenoma during pregnancy. J Hepatol. 2011;54:553–8.

110  Hepatocellular Adenoma IX: Changes During Pregnancy   233

Fig. 110.1  Hepatocellular adenoma (HCA) in a woman at baseline (prior to stopping the oral contraceptives (OCP)), at 6 months after stopping OCP, during pregnancy, and 6 months postpartum; correlation with CT and ultrasound. (a) Axial contrast-enhanced baseline image (CT) shows a large HCA with a large active bleed extending into the liver subcapsular space (red arrow); note the second HCA in the left liver that is near isodense with the liver. (b) Axial fat-suppressed T1-weighted GRE (T1 fatsat) shows the resolved hemorrhage in the right liver; HCA in the left liver is slightly smaller, likely due to OCP cessation. (c) Axial

arterial phase 2D T1-weighted image (ART) shows blush of homogeneous enhancement in the HCA on the left. (d) Axial delayed phase 2D GRE image (DEL): HCA in the left liver fades to isointensity. (e–f) Axial fatsat TSE (TE fatsat) and SSTSE image (SSTSE) shows the HCA isointense with the liver. Note the darker area in the right liver, a sequela of prior hemorrhage (red arrow). (g–h) Axial in-phase and opposed-phase images show mild fatty infiltration of the liver; no fat in the lesion is present. Note (in h) the right is better visible due to the loss of the signal in the background mildly fatty liver (red arrow)

Fig. 110.2  Hepatocellular adenoma (HCA) in a woman showing growth during pregnancy and then getting smaller after birth. (a) Oblique sagittal SSTSE (SSTSE) shows the fetus; patient became pregnant 3 years after stopping with OCP. (b) Ultrasound suggested growth of the HCA in the left liver. (c–d) MR imaging indeed confirmed that there was a significant increase in the size of the lesion as well as the liver; patient was followed with serial MR imaging exams without any

intravenous gadolinium-based contrast injection; the lesions did not show complication of hemorrhage. (e–h) Axial opposed-phase, in-phase, arterial, and diffusion-weighted images (6 months postpartum) show that the HCA in the left liver has significantly decreased in size. The imaging findings clearly demonstrate the hormone-dependent nature of the HCA in this patient

234  Part III  Solid Liver Lesions  –  III D:  Primary solid liver lesions in non-cirrhotic liver

111

HCC in Non-cirrhotic Liver I: Small with MR-Pathology Correlation

Hepatocellular carcinomas (HCCs) usually occur in patients with cirrhosis with an underlying viral hepatitis or alcohol abuse. HCC in cirrhosis typically shows a stepwise carcinogenesis (regenerative nodule-dysplastic nodule-HCC). In Europe and North America, HCC in non-cirrhotic livers may be present in up to 40 % of patients with HCC. HCC in non-cirrhotic is believed to occur according to de novo carcinogenesis: a microscopic focus of HCC gradually develops into full-grown HCC. HCCs in non-cirrhotic livers are likely to be solitary and relatively large dominant encapsulated mass with a central scar. However, mid-sized lesions do occur at imaging. It is important to recognize HCC in non-cirrhotic liver because these lesions are amenable to surgery even with a large size with good clinical outcome.

MR Imaging Findings At MR imaging, HCC in non-cirrhotic livers have often moderately high signal intensity on T2-weighted images and low signal intensity on T1-weighted images and, in this respect, may resemble metastases. The lesions show heterogeneous enhancement in the arterial phase and washout with capsular enhancement in the delayed phase (Figs. 111.1 and 111.2).

Pathology At gross pathology, mid-sized HCC in non-cirrhotic liver appears as a yellowish dominant nodule in a normal liver with smooth edges and normal color. At histology, the nodule may have great similarities to their cirrhotic counterparts and may contain sub-nodules with variable amount of fat and a fibrous tumor capsule (Fig. 111.3).

Literature 1. Okuda K, Nakashima T, Sakamoto K, et al. Hepatocellular carcinoma arising in noncirrhotic and highly cirrhotic livers: a comparative study of histopathology and frequency of hepatitis B markers. Cancer. 1982;49:450–5. 2. Nakayama M, Kamura T, Kimura M, et al. Quantitative MRI of hepatocellular carcinoma in cirrhotic and noncirrhotic livers. Clin Imaging. 1998;22:280–3. 3. Winston CB, Schwartz LH, Fong Y, et al. Hepatocellular carcinoma: MR imaging findings in cirrhotic and noncirrhotic livers. Radiology. 1999;210:75–9. 4. Hussain SM, Semelka RC, Mitchell DG. MR imaging of hepatocellular carcinoma. Magn Reson Imaging Clin N Am. 2002;10:31–52.

111  HCC in Non-cirrhotic Liver I: Small with MR-Pathology Correlation  235

Fig. 111.1  HCC, non-cirrhotic liver, medium-sized, drawings. T2 fatsat: HCC is hyperintense compared to the liver. T1 in phase: HCC is hypointense with a dark tumor capsule. ART: HCC is more enhanced in the peripheral than in the central

part (mosaic pattern). DEL: HCC shows washout with enhancement of the tumor capsule

Fig. 111.2  HCC, non-cirrhotic, medium-sized, MRI findings. (a) Axial fat-suppressed T2-weighted TSE image (T2 fatsat): HCC is hyperintense compared to the liver. (b) Axial in-phase T1-weighted GRE (T1 in phase): HCC is slightly hypointense compared to the liver with a darker tumor capsule. (c) Axial arterial phase postGd 2D T1-weighted GRE image (ART): HCC is more enhanced in the peripheral than in the central part. (d) Axial delayed phase 3D T1-weighted GRE image (DEL): HCC

shows washout with enhancement of the tumor capsule. (e) Axial T2-weighted SSTSE image (SSTSE): HCC is slightly hyperintense compared to the liver (arrow). (f) Coronal SSTSE image (SSTSE): HCC becomes more hypointense due to its solid nature (arrow). (g) Axial arterial phase GRE image (ART): HCC is more enhanced in the peripheral (arrow) than in the central part (*). (h) Axial delayed phase GRE image (DEL): HCC shows washout with enhancement of the tumor capsule (arrows)

Fig. 111.3  HCC, non-cirrhotic liver, medium-sized, direct MR-pathology correlation. (a) Photograph of the resected specimen with the normal liver (non-cirrhotic liver) and a HCC. (b) Photomicrograph (H&E, 40×) from the HCC shows two parts

of the HCC with a thick capsule. (c) Photomicrograph (H&E, 100×) shows HCC surrounded by a thick capsule. (d) Photomicrograph (Sirius Red stain, 100×) more clearly shows the stained fibrous tissue composing the thick tumor capsule

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112

HCC in Non-cirrhotic Liver II: Large with MR-Pathology Correlation

Hepatocellular carcinomas (HCCs) in non-cirrhotic patients are more likely to be solitary than it is in patients with cirrhosis (72 % vs. 27 %). The lesions are significantly larger than in cirrhotic livers and are well-­ circumscribed masses in 57 % of cases (median size 8.8 cm). Central scar is more frequent in HCC in non-cirrhotic than in cirrhotic liver (6 % vs. 50 %). Smaller satellite nodules are present in only 6 % of cases. Venous invasion is substantially more common in patients with cirrhosis (41 %) than in patients without underlying liver disease (15 %) and thus potentially promotes transhepatic hematogenous tumor spread. HCC originating in a non-cirrhotic liver is more likely to involve lymph nodes.

MR Imaging Findings At MR imaging, HCC in non-cirrhotic liver will typically present as a large hyperintense lesion on T2-weighted images. Unencapsulated lesions are likely to show satellite nodules. At opposed-phase T1-weighted images, the lesions may be surrounded by a rim of compressed, nonfatty, liver parenchyma within a fatty liver. Due to neoangiogenic activity, the lesions contain large tumor vessels which can be seen on gadolinium-enhanced images in the arterial phase, particularly after post-processing (Figs. 112.1 and 112.2). MR imaging can provide an exact road map for surgical resection. MR-pathology correlation may provide evidence for the vasoinvasive growth which is most likely the basis for the satellite nodules (Fig. 112.3).

Management For HCC in cirrhotic livers, the size of a lesion is an important variable for both treatment planning and patient outcome. Lesions larger than 5 cm in diameter have been shown to be associated with a poorer prognosis after hepatic resection. For HCC in non-cirrhotic livers this may not be true. In one study, 72 % of patients with HCC in non-cirrhotic livers (median size >8 cm) underwent partial resection. These patients may develop late recurrence, but aggressive surgery is nonetheless justified. Surgical procedures may consist of major hepatectomy (three segments or more). Operative mortality and morbidity are, respectively, 2.9 % and 19.0 %. The 1-, 3-, 5-, and 10-year survivals and the survivals without recurrence were 74 %, 52 %, 40 %, and 26 % and 69 %, 43 %, 33 %, and 19 %, respectively.

Literature 1. Okuda K, Nakashima T, Sakamoto K, et al. Hepatocellular carcinoma arising in noncirrhotic and highly cirrhotic livers: a comparative study of histopathology and frequency of hepatitis B markers. Cancer. 1982;49:450–5. 2. Winston CB, Schwartz LH, Fong Y, et al. Hepatocellular carcinoma: MR imaging findings in cirrhotic and noncirrhotic livers. Radiology. 1999;210:75–9. 3. Bismuth H, Chiche L, Castaing D. Surgical treatment of hepatocellular carcinoma in non-cirrhotic liver: experience in 68 liver resections. World J Surg. 1995;19:35–41. 4. Smalley S, Moertel C, Hilton J, et al. Hepatoma in the noncirrhotic liver. Cancer. 1988;62:1414–24.

112  HCC in Non-cirrhotic Liver II: Large with MR-Pathology Correlation  237

Fig. 112.1  HCC, non-cirrhotic, drawings. T2 fatsat: HCC is hyperintense to the liver; note the satellite nodule in the periphery of the tumor (arrow). T1 in phase: HCC is hypointense to the liver. ART: HCC shows intense heterogeneous enhance-

ment. DEL: HCC shows washout with enhancement of the discontinuous tumor capsule

Fig. 112.2  HCC, non-cirrhotic, large, typical MRI findings. (a) Axial TSE image (T2 fatsat): HCC is hyperintense to the liver with similar satellite nodules (arrow). (b) Axial in-phase image (T1 in phase): HCC is hypointense to the liver. (c) Axial arterial phase image (ART): HCC as well as the satellite nodules (arrow) shows intense heterogeneous enhancement. (d) Axial delayed phase image (DEL): HCC shows washout with enhancement of the tumor capsule that partially surrounds the HCC (arrow). (e) Axial TSE image (T2 fatsat) at a different anatomic level: note

a satellite nodule at the level of the tumor capsule (arrow). (f) Axial opposedphase image (T1 opposed phase): subtle fatty liver has decreased its signal with persistent high signal in the perilesional compressed liver parenchyma (arrow). (g) Pixel-wise color-coded display of the relative enhancement shows the intratumoral arterial vessels. (h) Pixel-wise color-coded display of the area under the curve shows the total amount of contrast of the liver and the HCC, which is much larger

Fig. 112.3  HCC, non-cirrhotic, direct MR-pathology correlation. (a) Coronal SSTSE image shows the liver, HCC, and the resection surface (white dashed line). (b) Photograph of the right-sided hemihepatectomy specimen shows a large HCC that is – inpart – surrounded by a tumor capsule. (c) Photomicrograph (H&E,

100×) shows two adjacent HCC nodules that are separated by a septum. (d) Photomicrograph (H&E, 100×) shows an HCC thrombus within a large peritumoral vessel, which explains – in part – the presence of satellite nodules

238  Part III  Solid Liver Lesions  –  III D:  Primary solid liver lesions in non-cirrhotic liver

113

HCC in Non-cirrhotic Liver III: Large Lesion with Inconclusive CT

The fundamental limitation of CT is its lack of intrinsic soft tissue contrast and its moderate sensitivity for the presence of intravenous contrast. For detection and characterization, CT mainly relies on high in-plane spatial resolution and vascularity of liver lesions. Small liver lesions (