EDITORS J. Thomas Stocker MD Professor of Pathology, Pediatrics and Emerging Infectious Disease Department of Pathology Uniformed Services University of the Health Sciences Bethesda, Maryland Louis P. Dehner MD Professor Division of Anatomic and Molecular Pathology Department of Pathology and Immunology Washington University in St. Louis Attending Surgical Pathologist Lauren V. Ackerman Laboratory of Surgical Pathology Barnes-Jewish and St. Louis Childrens Hospitals at the Washington University Medical Center St. Louis, Missouri Aliya N. Husain MD Professor Department of Pathology University of Chicago Chicago, Illinois P.viii Contributors Hikmat A. Al-Ahmadie MD Assistant Attending, Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York Kevin E. Bove MD Professor, Department of Pathology and Laboratory Medicine, University of Cincinnati, College of Medicine Staff Pathologist, Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio David S. Brink MD Associate Professor, Departments of Pathology and Pediatrics, St. Louis University School of Medicine Associate Pathologist, Department of Pathology, SSM Cardinal Glennon Children's Medical Center, St. Louis, Missouri John J. Buchino MD Emeritus Professor, Department of Pathology, Department of Pediatrics, University of Louisville Emeritus Chief, Department of Pathology, Kosair Children's Hospital, Louisville, Kentucky J. Douglas Cameron MD Professor of Ophthalmology, Departments of Ophthalmology and Pathology, Mayo Clinic, Rochester, Minnesota Ellen Chung Assistant Professor, Department of Radiology and Radiological Sciences and Department of Pediatrics, Uniformed Services University of the Heath Sciences Integrated Chief, Diagnostic Radiology Service, Department of Radiology, Walter Reed National Military Medical Center, Bethesda, Maryland Kim A. Collins MD Professor, Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina Richard M. Conran MD, PhD, JD Professor of Pathology and Emerging Infectious Diseases, Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland Tracey S. Corey Clinical Professor, Division of Forensic Pathology, University of Louisville School of Medicine Chief Medical Examiner, Kentucky Medical Examiner Program, Commonwealth of Kentucky, Louisville, Kentucky Robert F. Debski MD Assistant Professor, Department of Pathology, Department of Pediatrics, University of Louisville Chief, Department of Pathology, Kosair Children's Hospital, Louisville, Kentucky Louis P. Dehner MD Professor, Division of Anatomic and Molecular Pathology, Department of Pathology and Immunology, Washington University in St. Louis Attending Surgical Pathologist, Lauren V Ackerman Laboratory of Surgical Pathology, Barnes-Jewish and St. Louis Children's Hospitals at the Washington University Medical Center, St. Louis, Missouri Christopher Dunham MD Clinical Fellow, Department of Pathology and Immunology, Washington University Clinical Fellow, Department of Pathology and Immunology, Barnes-Jewish Hospital, St. Louis, Missouri Michael K. Fritsch MD, PhD Associate Professor, Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin Dorothy K. Grange MD Professor of Pediatrics, Department of Pediatrics, Division of Genetics and Genomic Medicine, Washington University School of Medicine Professor of Pediatrics, Department of Pediatrics, St. Louis Children's Hospital, St. Louis, Missouri John Hart MD John Hart MD Professor, Department of Pathology, University of Chicago, Chicago, Illinois Anjum Hassan MD Assistant Professor, Division of Anatomic and Molecular Pathology, Washington University School of Medicine Assistant Director FISH Laboratory, Department of Pathology, Washington University Medical Center, Barnes Jewish Hospital, St. Louis, Missouri P.ix M. John Hicks MD, DDS, MS, PhD Professor of Pathology, Department of Pathology and Immunology, Baylor College of Medicine Attending Pathologist, Department of Pathology, Texas Children's Hospital, Houston, Texas D. Ashley Hill MD Associate Professor, Department of Pathology and Pediatrics, The George Washington University Chief, Department of Pathology, Children's National Medical Center, Washington, DC Aliya N. Husain MD Professor, Department of Pathology, University of Chicago, Chicago, Illinois Jason A. Jarzembowski MD, PhD Assistant Professor, Department of Pathology, Medical College of Wisconsin Program Director, Perinatal Pathology, Department of Pathology, Children's Hospital of Wisconsin, Milwaukee, Wisconsin Raj P. Kapur MD, PhD Professor, Department of Pathology, University of Washington Staff Pathologist, Department of Laboratories, Seattle Children's Hospital, Seattle, Washington DC Jochen K. M. Lennerz MD, PhD Division of Anatomic and Molecular Pathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri Haresh Mani MD Assistant Professor, Department of Pathology, Northwestern University's Feinberg School of Medicine Pathologist-in-Chief, Children's Memorial Hospital, Chicago, Illinois Thomas L. McCurley MD Associate Professor, Department of Pathology, Vanderbilt University Director, Department of Immunopathology Laboratory, Nashville, Tennessee Deborah E. McFadden MD Clinical Professor, Department of Pathology and Laboratory Medicine, University of British Columbia Head and Medical Director, Department of Pathology and Laboratory Medicine, BC Children's Hospital and BC Women's Hospital and Health Centre, Vancouver, British Columbia Gary W. Mierau PhD Electron Microscopist, Department of Pathology and Laboratory Medicine, The Children's Hospital, Aurora, Colorado Lili Miles MD Associate Professor, Department of Pathology and Laboratory Medicine, University of Cincinnati, College of Medicine Staff Pathologist, Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio Jeffrey Mueller MD Assistant Professor, Department of Pathology, University of Chicago, Chicago, Illinois Rish K. Pai MD, PhD Associate Staff, Department of Anatomic Pathology, Cleveland Clinic Foundation, Cleveland, Ohio Kathleen Patterson MD Associate Professor, Department of Pathology, University of Washington Associate Pathologist, Department of Pathology, Seattle Children's Hospital, Seattle, Washington DC Elizabeth J. Perlman MD Pathologist-in-chief, Children's Memorial Hospital Professor of Pathology, Northewestern University's Feinberg School of Medicine, Chicago, Illinois Arie Perry MD Professor of Pathology and Neurological Surgery, Director of Neuropathology and Vice Chair of Pathology, Department of Pathology, Division of Neuropathology, University of California, San Francisco (UCSF), San Francisco, California Theodore J. Pysher MD Professor of Pathology, Department of Pathology, University of Utah School of Medicine Division Chief of Pediatric Pathology and Director of Laboratories, Primary Children's Medical Center, Salt Lake City, Utah Vijaya B. Reddy MD Professor, Department of Pathology, Rush Medical College Senior Attending, Department of Pathology, Rush University Medical Center, Chicago, Illinois Raymond W. Redline MD Professor, Pathology and Reproductive Biology, Case Western Reserve University School of Medicine, Cleveland, OH Co-director, Pediatric Pathology, Pathology, University Hospitals Case Medical Center, Cleveland, OH Andrea M. Sheehan MD Assistant Professor, Department of Pathology and Immunology, Department of Pediatrics, Section of Hematology and Oncology, Baylor College of Medicine Director of Hematology and Flow Cytometry, Department of Hematopathology, Department of Pathology, Texas Children's Hospital, Houston, Texas P.x Hiroyuki Shimada MD, PhD Professor, Department of Pathology, University of Southern California Keck School of Medicine Pathologist, Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, California Joseph R. Siebert PhD Professor of Pathology, Adjunct Professor of Pediatrics, Departments of Pathology, Pediatrics, University of Washington Director of Autopsy Services, Department of Laboratories, Seattle Children's Hospital, Seattle, Washington J. Thomas Stocker MD Professor of Pathology, Pediatrics and Emerging Infectious Disease, Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland Mariko Suchi MD, PhD Assistant Professor, Department of Pathology, Medical College of Wisconsin Department of Pathology and Laboratory Medicine, Children's Hospital of Wisconsin, Milwaukee, Wisconsin Jerome B. Taxy MD Professor, Department of Pathology, University of Chicago, Chicago, Illinois Carole A. Vogler MD Professor and Chair, Department of Pathology, Saint Louis University School of Medicine Pathologist, Department of Pediatric Pathology, SSM Cardinal Glennon Children's Medical Center, St. Louis, Missouri Christopher R. Weber MD, PhD Instructor, Department of Pathology, The University of Chicago, Chicago, Illinois Rebecca Wilcox MD Assistant Professor, School of Medicine, The University of Vermont Assistant Professor, Department of Pathology, Fletcher Allen Hospital, Burlington, Vermont Mary M. Zutter MD Professor of Pathology and Cancer Biology, Department of Pathology, Vanderbilt University Director of Hematopathology, Scientific Director, HTAP Shared Resource, Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee Dedication To my children and grandchildren—Louis, Jr., Carl, Christopher, Elizabeth, Rebecca, Rachael, Jennifer, and Charlie. Louis P. Dehner To my mother, Khadija Omar, who has inspired me throughout my life and in memory of my father, Zahid Omar, who saw only the beginnings of his children's lives. Aliya N. Husain To my wife, Pat, the Center of my life, at 44 years together and counting: to our children; Rick, his wife Cathy and sons Jack and Joseph; David, his wife Carol and daughter Sydney; and Meg. How full they make our lives! J. Thomas Stocker Preface There is no other way to put it, a book, especially one that is now in its third edition, has long since become an enduring burden. Almost 10 years have elapsed since the last edition and no decade passes without advances being made and old “truths” being dismissed as folly. We have attempted to capture within the front and back covers of this book a reasonable approximation of the latest truths as they relate to our understanding of those unique disorders of maldevelopmental, infectious, and neoplastic nature that are found predominantly in children and in the period of 9 months preceding childhood. The codex of pediatric pathology is still largely based upon morphologic features that are apparent in their gross manifestations as in the case of congenital heart disease and skeletal dysplasias or on visualizing microscopic features. Immunohistochemistry has become as routine today as the trichrome and Gomori methenamine-silver stains. However, we have now moved into the era of application of molecular diagnostic methodologies that have admitted us into an unseen world in a sense. The pace of discoveries has created a world where yesterday becomes a part of the deep past as we catapult through today. In the microcosm of pediatric pathology, the current endeavor is our attempt to capture what is reasonably stable as the foundation of morphologic pediatric pathology. In the yesterdays, we may have speculated about the pathogenesis or puzzled over the morphologic findings, but today, we have the ability to test those speculations and begin the process of diagnostic discovery and investigation. As we have all experienced, this process is oftentimes one door leading to another. An attempt has been made in this edition to not only lay out the foundation of pediatric pathology but also convey the idea that another door awaits to be opened. It is to our younger colleagues in pediatric pathology that we address this latter challenge. For the majority of the chapters, about 200 of the most important references are in the printed book; the rest are available as eReferences as indicated in the text. Similarly, some additional photomicrographs are available as eFigures. We have gathered a distinguished group of contributors to this tome whose collective efforts are every bit as worthy as the three names that appear on the front cover. It is very difficult to find individuals as knowledgeable as they are who choose to devote their precious time to the arduous task of writing a chapter that conforms to the goals of this volume as discussed in the preceding paragraph. These authors met and exceeded those aspirations. Some authors questioned whether the third edition would ever become a reality with legitimate cause since we all recognize the prolonged gestation of this enterprise. One of us (LPD) had to be coaxed and even harangued into the yoke but here we are through the monumental efforts of another one of us (ANH). We are grateful to our authors who are also our colleagues, both past and present. Your patience and perseverance are appreciated well beyond this acknowledgment. J. Thomas Stocker MD Louis P. Dehner MD Aliya N. Husain MD Preface to the First Edition Several years ago, the editors of this volume were lamenting the fact that a third edition of Kissane's Pathology of Infancy and Childhood was unlikely because John Kissane had committed himself to another formidable publishing enterprise. Our British colleagues in pediatric pathology have authored two fine references (Keeling's Fetal and Neonatal Pathology and Berry's Paediatric Pathology), but it was our opinion that a comprehensive volume on all major aspects of the pathologic anatomy of chlldhood disorders ranging from chromosomal syndromes and neoplasms to forensic pathology was needed. At this juncture in our deliberations, we were confronted with the daunting nature of the potential task at hand given the required range of expertise necessary to cover all of these areas. Our attention turned to the reservoir of such abilities that exists in an organization of which we are privileged to be members, the Society for Pediatric Pathology, formerly known as the Pediatric Pathology Club. Many of the contributors to this volume are friends and colleagues whom we met through the Society for Pediatric Pathology. It was Albert Einstein who acknowledged the fact that we all stand on the shoulders of giants, and certainly pediatric pathology has evolved to its present state through the seminal contributions of the “first” generation of North American pediatric pathologists. Some of these include Maude Abbott, Dorothy Andersen, James B. Arey, J. Bruce Beckwith, Jay Bernstein, William A. Blanc, Robert P. Bolande, John Craig, John R. Esterly, Sidney Farber, George Fetterman, Enid Gilbert-Barness, M. Daria Haust, John M. Kissane, Benjamin H. Landing, A. James McAdams, Harry B. Neustein, William A. Newton, Ella Oppenheimer, Eugene V. Perrin, Edith Potter, Harvey S. Rosenberg, Marie Valdes-Dapena, Gordon Vawter, and F.W. Wigglesworth, to mention only a few. Virtually all of us in the second and now third generation of pediatric pathologists can call one of these extraordinary individuals our mentor. Because we the editors are also the co-authors of several chapters in this textbook, we appreciate firsthand the many hours that our contributors have invested in the completion of their manuscripts. The time, experience, and patience necessary to compile information into the concise prose required by a textbook of this type are greatly appreciated. This textbook belongs to all of these authors collectively, despite the connotations of the cover and title page. We also thank our colleagues and friends at our respective institutions for their understanding and support during the prolonged gestation and difficult delivery of this textbook. At the Armed Forces Institute of Pathology, these include Robert McMeekin, MD, Robert F. Karnei, MD, Vernon Armbrustmacher, MD, Nancy Roberts, Luther Duckett, Lisa Penalver, and Venetia Valiga. At the University of Minnesota, Ellis S. Benson, MD, Dale Snover, MD, and Diane Perez, and at the Washington University Medical Center, Emil Unanue, MD, Mark R. Wick, MD; Eleanor Grob, and Patricia Dixon are recognized for their special support. J. Thomas Stocker MD Louis P. Dehner MD Acknowledgments Dr. Stocker would like to acknowledge the authors of prior editions who are no longer with us: Drs. Laurence E. Becker and Patricia A. O'Shea. Dr. Dehner would like to acknowledge Jeannie Doerr, Margaret Chesney, and Walter Clermont whose tireless efforts and encouragement brought him back from the lip of the abyss. Dr. Husain would like to acknowledge the strong support and advice given by Drs. Thomas Krausz and Vinay Kumar and the excellent secretarial service provided by Dorothy Peoples and Margaret Rietman.