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Rajal B. Shah Ming Zhou Prostate Biopsy Interpretation An Illustrated Guide Second Edition 123 Prostate Biopsy Interpretation Rajal B. Shah • Ming Zhou Prostate Biopsy Interpretation An Illustrated Guide Second Edition Rajal B. Shah Ming Zhou Robert J Tomsich Pathology and Laboratory Tufts Medical Center Medicine Institute Boston, MA Cleveland Clinic USA Cleveland, OH USA ISBN 978-3-030-13600-0 ISBN 978-3-030-13601-7 (eBook) https://doi.org/10.1007/978-3-030-13601-7 © Springer Nature Switzerland AG 2019 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland To my wife, Ami Shah, and sons, Ansh and Alay, for their unconditional love and support and for constantly reminding me that there is life beyond work. To my parents, Bipin Shah and Sharmishtha Shah, for their genes, sacrifice, and motivation. Rajal B. Shah To my wife, Lan Zhou, and daughters, Grace and Rebecca, for their unwavering support. Ming Zhou Preface Since the publication of the first edition of this book, there have been many significant devel- opments in prostate cancer diagnosis and treatment. We have witnessed a paradigm shift in the objectives of prostate cancer management, from diagnosing and treating all cancers to clini- cally significant ones. Recent publication of the World Health Organization (WHO) genitouri- nary bluebook brought forth numerous significant changes in the diagnosis, classification, grading, staging, and reporting of prostate cancer that every pathologist needs to know and integrate in his/her practice. New diagnostic tools, including magnetic resonance imaging (MRI), genomic testing and artificial intelligence (AI), are rapidly reshaping the landscape of prostate cancer diagnosis and management. Pathologists need to understand how these novel diagnostic modalities may dramatically change their practice of prostate biopsy diagnosis. This book retains the core contents of its successful first edition and covers all the practical issues related to prostate biopsy diagnosis in day-to-day practice. Pertinent new information is incorporated in all chapters. In particular, how novel diagnostic tools such as MRI and genomic tests may affect prostate biopsy practice is discussed. An entirely new chapter on pattern-based approaches to prostate biopsy interpretation has been added. This book is not meant to be an all-encompassing, definitive bibliography of pathology of prostate cancer. The primary goal of this book is to provide practicing surgical pathologists as well as trainees a quick and handy reference for all the practical issues relevant to day-to-day interpretation of prostate biopsy. This second edition keeps the format of the original book. It uses abundant algorithms, flow charts, and tables to simulate a pathologist’s thought process during evaluation of prostate biopsies. Readers will learn the most effective way to evaluate a prostate biopsy and how to formulate a diagnostic approach upon encountering a specific clini- cal problem. Cleveland, OH, USA Rajal B. Shah Boston, MA, USA Ming Zhou vii Acknowledgments We wish to express our profound appreciation to many of our colleagues who have generously provided material presented in this book. We also wish to express our gratitude to the trainees and practicing pathologists with whom we have worked for their valuable feedback, which has motivated us to further improve this book for the second edition. Our thanks are also extended to Springer, the publisher of this book, who saw the value of updating this practical atlas as a handy reference for busy practicing pathologists. Our sincere thanks also go to Ms. Diane Lamsback, who has worked tirelessly and meticulously through- out this project to keep us on track to produce a book that we are very proud of. ix Contents 1 Anatomy and Normal Histology of the Prostate Pertinent to Biopsy Interpretation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.1 Anatomy of Normal Prostate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.2 Anatomy and Disease Preference of Three Zones of the Prostate . . . . . . . . . . . . 2 1.3 Histology of Normal Prostate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1.4 Immunophenotype of Prostate Glandular Cells . . . . . . . . . . . . . . . . . . . . . . . . . . 5 1.5 Histology of Three Zones of Normal Prostate Glands, Other Intraprostatic Structures, and Their Mimics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 1.6 Histologic Variations of Normal Prostate Tissue . . . . . . . . . . . . . . . . . . . . . . . . . 8 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 2 Needle Biopsy Sampling Techniques and Role of Multiparametric-Magnetic Resonance Imaging Modality in Prostate Cancer Diagnosis and Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 2.1 Comparisons of Three Biopsy Techniques Utilized for Prostate Cancer Detection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 2.2 Comparisons of Transrectal and Transperineal Biopsy Approach . . . . . . . . . . . . 13 2.3 Multiparametric-Magnetic Resonance Imaging (mp-MRI) for Prostate Cancer Diagnosis and Management . . . . . . . . . . . . . . . . . . . . . . . . . 13 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 3 Diagnosis of Limited Cancer in Prostate Biopsy . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 3.1 General Approach to Prostate Needle Biopsy Evaluation . . . . . . . . . . . . . . . . . . 19 3.2 Histological Features Considered Specific for and Diagnostic of Cancer . . . . . . 20 3.3 Major and Minor Diagnostic Features of Prostate Cancer in Biopsy . . . . . . . . . 21 3.4 Benign Conditions That Cause Architectural and Cytological Atypia . . . . . . . . 27 3.5 Quantitative Threshold for Diagnosing Limited Cancer in Biopsy . . . . . . . . . . . 29 3.6 Histological Features for and against Cancer Diagnosis in Biopsy . . . . . . . . . . . 30 3.7 A Practical Approach to Diagnosis of Limited Cancer in Needle Biopsy . . . . . . 30 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 4 Immunohistochemistry in Prostate Biopsy Evaluation . . . . . . . . . . . . . . . . . . . . . . 33 4.1 Commonly Used Immunohistochemical Markers for Diagnosis of Prostate Cancer in Biopsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 4.2 Basal Cell Markers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 4.3 Alpha-Methylacyl-CoA Racemase (AMACR) . . . . . . . . . . . . . . . . . . . . . . . . . . 37 4.4 ERG Protein . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 4.5 Antibody Cocktails . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 4.6 Differential Diagnosis of Prostate Cancer by Immunohistochemistry . . . . . . . . 41 4.7 Immunohistochemical Markers for Prognosis and Risk Stratification . . . . . . . . 42 4.8 Practical Guideline for Using Immunohistochemistry in Work-Up of Prostate Biopsies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 xi xii Contents 5 Contemporary Approach to Gleason Grading of Prostate Cancer . . . . . . . . . . . . 45 5.1 Significance of Gleason Grading in Prostate Cancer Management . . . . . . . . . . 46 5.2 Prostate Cancer Nomograms and National Comprehensive Cancer Network (NCCN) Risk Categories and Prediction Models . . . . . . . . . . . . . . . . . . . . . . . . 46 5.3 2005/2014 Modifications of Gleason Grading System . . . . . . . . . . . . . . . . . . . . 48 5.4 Contemporary Gleason Pattern 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 5.5 Contemporary Gleason Pattern 2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 5.6 Contemporary Gleason Pattern 3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 5.7 Common Pitfalls of Pattern 3 (Reasons for Over-interpretation of Pattern 3 as Pattern 4) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 5.8 Contemporary Gleason Pattern 4 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 5.9 Recommendations to Improve Reproducibility of “Poorly Formed” Gleason Pattern 4 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 5.10 Common Pitfalls of Pattern 4 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 5.11 Contemporary Gleason Pattern 5 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 5.12 Morphologic Features That Are Associated with High Reproducibility for Gleason Pattern 5 Prostate Cancer . . . . . . . . . . . . . . . 57 5.13 Gleason Grading of Unusual “Variant” Histology Types and Patterns . . . . . . . . 60 5.14 New Grading System: Grade Groups . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 5.15 Important Facts About Grade Groups . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 5.16 Recommendations for Gleason Grading in the Post-therapy Setting . . . . . . . . . 63 5.17 Rationale for Reporting Percentage Pattern 4 in Gleason Score 7 Prostate Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 5.18 Summary of Current Concepts of Gleason Grading of Prostate Cancer . . . . . . . 66 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 6 Histologic Variants of Acinar Adenocarcinoma, Ductal Adenocarcinoma, Neuroendocrine Tumors, and Other Carcinomas . . . . . . . . . . . . . . . . . . . . . . . . . . 69 6.1 The 2016 World Health Organization Classification of Histological Variants of Acinar Adenocarcinoma, Ductal Adenocarcinoma, Neuroendocrine Tumors, and Other Carcinomas . . . . . . . . . . . . . . . . . . . . . . . . . 69 6.2 Histologic Variants of Acinar Prostate Carcinoma Mimicking Benign Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 6.3 Atrophic Adenocarcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 6.4 Pseudohyperplastic Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 6.5 Microcystic Adenocarcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74 6.6 Foamy Gland Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 6.7 Mucinous (Colloid) Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76 6.8 Signet Ring Cell-Like Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78 6.9 Pleomorphic Giant Cell Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 6.10 Sarcomatoid Carcinoma (Carcinosarcoma) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80 6.11 Prostatic Intraepithelial Neoplasia- Like (PIN-Like) Adenocarcinoma . . . . . . . . 81 6.12 Ductal Adenocarcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 6.13 The 2016 World Health Organization(WHO) Pathologic Classification and Clinical Significance of Neuroendocrine (NE) Differentiation in Prostate Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86 6.14 Small-Cell Neuroendocrine (NE) Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 6.15 Utility of Immunohistochemistry in Neuroendocrine Tumors of the Prostate . . 89 6.16 Urothelial Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91 6.17 Squamos and Adenosquamos Cell Carcinoma (SCC) . . . . . . . . . . . . . . . . . . . . . 92 6.18 Basal Cell Carcinoma (BCC) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95 Contents xiii 7 Benign Mimics of Prostate Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97 7.1 Summary of Atypical Morphological Features Commonly Encountered in Various Benign Mimics of Prostate Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . 99 7.2 Seminal Vesicle/Ejaculatory Duct Epithelium . . . . . . . . . . . . . . . . . . . . . . . . . . .100 7.3 Verumontanum Mucosal Gland Hyperplasia (VMGH) . . . . . . . . . . . . . . . . . . . .101 7.4 Cowper’s Glands . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .102 7.5 Mesonephric Remnant Hyperplasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .103 7.6 Mucinous Metaplasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .103 7.7 Classification of Focal Atrophy Lesions of the Prostate . . . . . . . . . . . . . . . . . . .104 7.8 Focal Atrophy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .104 7.9 Partial Atrophy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .105 7.10 Postatrophic Hyperplasia (PAH) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .107 7.11 Adenosis (Atypical Adenomatous Hyperplasia) . . . . . . . . . . . . . . . . . . . . . . . . .108 7.12 Basal Cell Hyperplasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .110 7.13 Postradiation Atypia in Benign Prostate Glands . . . . . . . . . . . . . . . . . . . . . . . . .112 7.14 Nephrogenic Adenoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .114 7.15 Cribriform Proliferations Encountered in the Prostate Gland . . . . . . . . . . . . . . .117 7.16 Central Zone Glands . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .117 7.17 Clear Cell Cribriform Hyperplasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .118 7.18 Nonspecific Granulomatous Prostatitis (NSGP) . . . . . . . . . . . . . . . . . . . . . . . . .119 7.19 Malakoplakia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .121 7.20 Sclerosing Adenosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .122 7.21 Paraganglia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .123 7.22 Xanthoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .124 7.23 Benign Mimics of Prostate Cancer: Take-Home Messages . . . . . . . . . . . . . . . . .124 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .125 8 Intraductal Carcinoma of the Prostate (IDC-P) and Atypical Intraductal Proliferation (AIP) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .127 8.1 Intraductal Carcinoma of the Prostate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .128 8.2 Pathologic Features That Are Associated with IDC-P and Helpful to Differentiate from Cribriform HGPIN . . . . . . . . . . . . . . . . . . . . .131 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .132 9 High-Grade Prostatic Intraepithelial Neoplasia . . . . . . . . . . . . . . . . . . . . . . . . . . .133 9.1 Histological Features of High-Grade Prostatic Intraepithelial Neoplasia (HGPIN) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .133 9.2 Clinical Significance of HGPIN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .138 9.3 Differential Diagnosis of HGPIN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .138 9.4 Reporting of HGPIN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .140 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .140 10 Atypical Glands Suspicious for Cancer (ATYP) . . . . . . . . . . . . . . . . . . . . . . . . . . .143 10.1 Histological Features Resulting in ATYP . . . . . . . . . . . . . . . . . . . . . . . . . . . . .143 10.2 Working Up Cases with ATYP. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .148 10.3 Clinical Significance and Management of ATYP . . . . . . . . . . . . . . . . . . . . . . .149 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .149 11 Spindle Cell Lesions of the Prostate Gland . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .151 11.1 Classification of Spindle Cell Lesions of the Prostate . . . . . . . . . . . . . . . . . . . .151 11.2 Specialized Stromal Tumors of the Prostate Gland . . . . . . . . . . . . . . . . . . . . . .152 11.3 Solitary Fibrous Tumor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .154 11.4 Inflammatory Myofibroblastic Tumor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .155

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