Atlas of Hepatocellular Carcinoma Pathology

194 Pages·2022·67.023 MB·English

by  Haeryoung Kim, Wei-Qiang Leow, Regina Lo, Paulo Giovanni L. Mendoza, Anthony Wing-Hung Chan

Haeryoung Kim · Wei-Qiang Leow ·
Regina Lo · Paulo Giovanni L. Mendoza ·
Anthony Wing-Hung Chan
Atlas of Hepatocellular
Carcinoma Pathology
123
Atlas of Hepatocellular Carcinoma Pathology
Haeryoung Kim • Wei-Qiang Leow • Regina Lo
Paulo Giovanni L. Mendoza
Anthony Wing-Hung Chan
Atlas of Hepatocellular
Carcinoma Pathology
Haeryoung Kim Wei-Qiang Leow
Department of Pathology Department of Anatomical Pathology
Seoul National University Hospital Singapore General Hospital
Seoul National University College of Medicine Singapore
Seoul Singapore
Korea (Republic of)
Paulo Giovanni L. Mendoza
Regina Lo Pathology and Laboratory Department
Department of Pathology and State Key Cardinal Santos Medical Center
Laboratory of Liver Research (HKU) San Juan
The University of Hong Kong Philippines
Hong Kong
China
Anthony Wing-Hung Chan
Department of Anatomical and Cellular Pathology
The Chinese University of Hong Kong
Shatin
Hong Kong
ISBN 978-981-16-8499-9 ISBN 978-981-16-8500-2 (eBook)
https://doi.org/10.1007/978-981-16-8500-2
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My mentor, Young Nyun Park, for guiding me into this beautiful world of liver pathology.
My parents, CK and BH, for their love and support.
HAERYOUNG KIM
My wife, Audrey, for being the bedrock of my life.
My children: Sean, Jeanne, Ean, and Leanne, for giving me the impetus to work hard.
My mentors, Swan, Tony, and Puay Hoon, for showing me what excellence is.
WEI-QIANG LEOW
All mentors at different stages of my life who enlightened and encouraged me with a kind heart.
REGINA LO
My wife, Angela, for being my inspiration and companion in this journey.
My folks: Dolly, Victor; My siblings: Carlo and Dessa for being the constant strength that binds.
My mentors, Neil, Isabel and Tony, for the dedication to share what they do best.
To our patients who continue to drive us to be excellent and persevering.
PAULO GIOVANNI L. MENDOZA
My wife, Joanna, and my aunt, PC, for their unreserved love, support, and encouragement.
My mentors, Alastair, Fernand, and KF, for shepherding me into the amazing world of pathology.
ANTHONY WING-HUNG CHAN
Preface
This fledging group, based in different parts of Asia such as Hong Kong, Philippines, Singapore,
and South Korea, shares a common love and passion for liver pathology. Having been schooled
by some of the world’s most eminent hepatopathologists: Professors Alastair Burt, Irene Ng,
Young Nyun Park, Neil Theise, and Swan Thung, the group members grew in knowledge and
confidence through robust discussion, sharing of the current literature and evidence. It wasn’t
long before when a name for this group was contemplated, and inspired by the impact of suc-
cessful liver pathology study groups such as the Gnomes (International Liver Pathology Group)
and Elves (International Liver Pathology Study Group); the name “smurfs” emerged.
The steady cultivation of this academic kinship resulted in endeavors for the smurfs to
meet in-person, with soirees in the springtime of the 2019 United States and Canadian
Academy of Pathology (USCAP) Annual Meeting and 2019 Hong Kong International
Academy of Pathology (HKIAP) Fall Scientific Meeting. It was in the midst of the COVID-
19 pandemic that the proposal to compile an Atlas of Hepatocellular Carcinoma (HCC)
Pathology originated from our doyen Dr. Anthony Wing-Hung Chan. This proposal was met
with enthusiasm and it is this critical moment that represents the smurfs’ first step into such a
formal academic pursuit.
The incidence of liver cancer is growing worldwide and it is the 3rd leading cause of cancer-
associated deaths globally. Hepatocellular carcinoma (HCC) is the most common form of liver
cancer and accounts for up to 85% of primary liver cancers. Of note, about three quarters of
liver cancer patients are Asian, resulting in a wealth of cases in the backyards of the smurfs,
whose practices include university hospitals, academic medical centers as well as private labo-
ratories. Furthermore, the spotlight on the various subtypes of HCCs in the 2019 Digestive
System Tumours of the 5th edition WHO Classification of Tumours, makes it timely for prac-
ticing pathologists to take a deeper dive into the various histomorphologies and nuances of
HCCs, in order to render an updated modern diagnosis.
Against this backdrop, the Atlas of HCC Pathology is a visual smorgasbord with over 550
high-quality photos and concise synopses. It also strives to be holistic by encompassing not
only chapters of the various HCC subtypes, but also chapters that illustrate the value of gross
morphology, tackle the challenging aspects of precursor lesions, and clarify the controversial
combined hepatocellular-cholangiocarcinoma entity. In this era of rapid locoregional and sys-
temic therapy advances, the Atlas also covers post-treatment changes. To equip pathologists
with the knowledge to yield the armamentarium of ancillary histochemical and immunohisto-
chemical stains, a comprehensive chapter illustrating the use of stains is included. And lastly,
in line with the spirit of the smurfs’ sharing and discussion of challenging cases, a chapter that
highlights the dilemmas and differential diagnoses of HCC concludes the Atlas’s offerings.
The authors hope that the Atlas of HCC Pathology will be a useful reference not only for
vii
viii Preface
pathologists and pathologists-in-training striving to refine their diagnoses of liver cancer but
also for the established field of liver cancer researchers who work tirelessly to uncover the
secrets of this enigmatic cancer.
Seoul, Republic of Korea Haeryoung Kim
Singapore, Singapore Wei-Qiang Leow
Hong Kong, China Regina Lo
San Juan, Philippines Paulo Giovanni L. Mendoza
Shatin, Hong Kong Anthony Wing-Hung Chan
Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
2 Precursor Lesions of Hepatocellular Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
2.1 Dysplastic Foci . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
2.1.1 Large Cell Change . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
2.1.2 Small Cell Change . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
2.1.3 Iron-Free Foci . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
2.2 Dysplastic Nodules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
2.2.1 Low-Grade Dysplastic Nodule. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
2.2.2 High-Grade Dysplastic Nodule . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
2.3 Early Hepatocellular Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
2.4 Hepatocellular Adenoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
2.4.1 β-Catenin-Activated HCA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
3 Gross Morphology of Hepatocellular Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . 27
3.1 Gross Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
4 General Histopathological Features of Hepatocellular Carcinoma . . . . . . . . . . . . 31
4.1 Architectural Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
4.2 Cytological Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
4.3 Differentiation and Grading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
4.4 The Tumour Microenvironment of HCC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
4.5 Other Histopathological Features of HCC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
4.6 Multiplicity: Intrahepatic Metastasis Versus Multicentric Occurrence . . . . . . . . 45
4.7 Prognostic Factors of HCC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
5 Fibrolamellar Hepatocellular Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
5.1 Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
5.2 Synopsis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
6 Steatohepatitic Hepatocellular Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
6.1 Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
6.2 Synopsis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
7 Clear Cell Hepatocellular Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
7.1 Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
7.2 Synopsis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
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8 Macrotrabecular-Massive Hepatocellular Carcinoma . . . . . . . . . . . . . . . . . . . . . . 61
8.1 Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
8.2 Synopsis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
9 Scirrhous Hepatocellular Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
9.1 Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
9.2 Synopsis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
10 Lymphocyte-Rich Hepatocellular Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
10.1 Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
10.2 Synopsis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
11 Other Uncommon Histological Variants of Hepatocellular Carcinoma . . . . . . . . 77
11.1 Chromophobe Hepatocellular Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
11.2 Neutrophil-Rich Hepatocellular Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
11.3 Sarcomatoid Hepatocellular Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78
11.4 Cirrhotomimetic Hepatocellular Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
11.5 Myxoid Hepatocellular Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
12 Hepatocellular Carcinoma with Cytokeratin 19 Expression . . . . . . . . . . . . . . . . . 85
12.1 Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
12.2 Synopsis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
13 Combined Hepatocellular- Cholangiocarcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
13.1 Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
13.2 Synopsis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
14 Post-treatment Changes of Hepatocellular Carcinoma . . . . . . . . . . . . . . . . . . . . . . 97
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .101
15 Ancillary Tests for Hepatocellular Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . .103
15.1 Differentiation Between Hepatocellular Carcinoma and
Benign Hepatic Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .103
15.2 Determination of Hepatocellular Differentiation . . . . . . . . . . . . . . . . . . . . . . . .108
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .142
16 Tumour Staging for Hepatocellular Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . .145
16.1 American Joint Committee on Cancer Tumour-Node-Metastasis Staging . . . .145
16.2 Assessment of Liver Functional Reserve . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .145
16.3 Barcelona Clinic Liver Cancer Staging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .148
16.4 Hong Kong Liver Cancer Staging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .151
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .152
17 Differential Diagnoses of Hepatocellular Carcinoma . . . . . . . . . . . . . . . . . . . . . . .155
17.1 Focal Nodular Hyperplasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .155
17.2 Hepatocellular Adenoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .157
17.3 Angiomyolipoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .160
17.4 Cholangiocarcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .163
Contents xi
17.5 Hepatoblastoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .166
17.6 Neuroendocrine Neoplasm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .169
17.7 Hepatoid Adenocarcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .173
17.8 Metastatic Renal Cell Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .176
17.9 Others . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .178
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .192