Robbins and Cotran PATHOLOGIC BASIS OF DISEASE

1 IIIIII Robbins and Cotran PATHOLOGIC BASIS OF DISEASE Seventh EditionVINAY KUMAR MBBS, MD, FRCPath Alice Hogge and Arthur Baer Professor Chairman, Department of Pathology The University of Chicago, Pritzker School of Medicine Chicago, IllinoisABUL K. ABBAS MBBS Chair, Department of Pathology University of California, San Francisco San Francisco, CaliforniaNELSON FAUSTO MD Chairman, Department of Pathology University of Washington School of Medicine Seattle, WashingtonA-PDF Split DEMO : Purchase from to remove the watermarkWith Illustrations by James A. Perkins, MS, MFAELSEVIER SAUNDERSIVELSEVIER SAUNDERS An Imprint of ElsevierThe Curtis Center 170 S Independence Mall W 300E Philadelphia, Pennsylvania 19106 Robbins AND Cotran PATHOLOGIC BASIS OF DISEASE , 7/E0-7216-0187-1 International Edition ISBN 0-8089-2302-1 Copyright 2005, Elsevier Inc.

2 All rights part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Permissions may be sought directly from Elsevier's Health Sciences Rights Department in Philadelphia, PA, USA: phone: (+1) 215 238 7869, fax: (+1) 215 238 2239, e-mail: You may also complete your request on-line via the Elsevier homepage ( ), by selecting 'Customer Support' and then 'Obtaining Permissions'. NOTICEM edicine is an ever-changing field. Standard safety precautions must be followed, but as new research and clinical experience broaden our knowledge, changes in treatment and drug therapy may become necessary or appropriate. Readers are advised to check the most current product information provided by the manufacturer of each drug to be administered to verify the recommended dose, the method and duration of administration, and contraindications.

3 It is the responsibility of the treating physician, relying on experience and knowledge of the patient, to determine dosages and the best treatment for each individual patient. Neither the publisher nor the authors assume any liability for any injury and/or damage to persons or property arising from this publication. Previous editions copyrighted 1999, 1994, 1989, 1984, 1979, 1974 Library of Congress Cataloging-in-Publication Data Robbins and Cotran PATHOLOGIC BASIS of DISEASE . 7th [edited by] Vinay Kumar, Abul K. Abbas, Nelson Fausto ; with illustrations by James A. Perkins. p. ; cm. Rev. ed. of: Robbins PATHOLOGIC BASIS of DISEASE , 1999. ISBN 0-7216-0187-1 1. Pathology. [DNLM: 1. Pathology. QZ 4 R6354 2004] I. Title: PATHOLOGIC BASIS of DISEASE . II. Kumar, Vinay. III. Abbas, Abul K. IV. Fausto, Nelson. V. Robbins , Stanley L.

4 (Stanley Leonard). VI. Cotran , Ramzi S. Robbins PATHOLOGIC BASIS of DISEASE . 2004 dc22 2004046835 Publishing Director: William Schmitt Managing Editor: Rebecca Gruliow Design Manager: Ellen ZanollePrinted in ChinaLast digit is the print number: 9 8 7 6 5 4 3 2 1 VIN MEMORY OF Dr. Stanley L. Robbins (1915 2003) and Dr. Ramzi S. Cotran (1932 2000) Dear friends, respected colleagues, and dedicated teachers They leave a legacy of excellence that will enrich the lives of generations of future Contributors Charles E. Alpers MD Professor of Pathology, Adjunct Professor of Medicine, University of Washington School of Medicine; Pathologist, University of Washington Medical Center, Seattle, WA The KidneyDouglas C. Anthony MD, PhD Professor and Chair, Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO Peripheral Nerve and Skeletal Muscle; The Central Nervous SystemJon C.

5 Aster MD, PhD Associate Professor of Pathology, Harvard Medical School; Staff Pathologist, Brigham and Women's Hospital, Boston, MA Red Blood Cell and Bleeding Disorders; Diseases of White Blood Cells, Lymph Nodes, Spleen, and ThymusJames M. Crawford MD, PhD Professor and Chair, Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine; Professor and Chair, Shands Hospital at the University of Florida, Gainesville, FL The Gastrointestinal Tract; Liver and Biliary TractChristopher P. Crum MD Professor of Pathology, Harvard Medical School; Director, Women's and Perinatal Pathology, Brigham and Women's Hospital, Boston, MA The Female Genital TractUmberto De Girolami MD Professor of Pathology, Harvard Medical School, Boston; Director of Neuropathology, Brigham and Women's Hospital, Boston, MA Peripheral Nerve and Skeletal Muscle; The Central Nervous SystemJonathan I.

6 Epstein MD Professor of Pathology, Urology, and Oncology; The Rinehard Professor of Urologic Pathology, The Johns Hopkins University School of Medicine, Baltimore; Director of Surgical Pathology, The Johns Hopkins Hospital, Baltimore, MD The Lower Urinary Tract and Male Genital SystemRobert Folberg MD Frances B. Greever Professor and Head, Department of Pathology, University of Illinois at Chicago, Chicago, IL The EyeMatthew P. Frosch MD, PhD Assistant Professor of Pathology, Harvard Medical School Boston; Assistant Pathologist, Kubik Laboratory for Neuropathology, Massachusetts General Hospital, Boston, MA Peripheral Nerve and Skeletal Muscle; The Central Nervous SystemRalph H. Hruban MD Professor of Pathology and Oncology, The Johns Hopkins University School of Medicine; Attending Pathologist, The Johns Hopkins Hospital, Baltimore, MD The PancreasAliya N.

7 Husain MBBS Professor, Department of Pathology, Pritzker School of Medicine, University of Chicago, Chicago, IL The LungAgnes B. Kane MD, PhD Professor and Chair, Department of Pathology and Laboratory Medicine, Brown University Medical School, Providence, RI Environmental and Nutritional PathologySusan C. Lester MD, PhD Assistant Professor of Pathology, Harvard Medical School; Chief, Breast Pathology, Brigham and Women's Hospital, Boston, MA The BreastVIIIMark W. Lingen DDS, PhD Associate Professor, Department of Pathology, University of Chicago, Chicago, IL Head and NeckChen Liu MD, PhD Assistant Professor of Pathology, University of Florida College of Medicine, Gainesville, FL The Gastrointestinal TractAnirban Maitra MBBS Assistant Professor, Department of Pathology, The Johns Hopkins University School of Medicine; Pathologist, The Johns Hopkins Hospital, Baltimore, MD Diseases of Infancy and Childhood; The Endocrine SystemAlexander J.

8 McAdam MD, PhD Assistant Professor of Pathology, Harvard Medical School; Medical Director, Infectious Diseases Diagnostic Laboratory, Children's Hospital Boston, Boston, MA Infectious DiseasesMartin C. Mihm Jr. MD Clinical Professor of Pathology, Harvard Medical School; Pathologist and Associate Dermatologist, Massachusetts General Hospital, Boston, MA The SkinRichard N. Mitchell MD Associate Professor, Department of Pathology, Harvard Medical School; Director, Human Pathology, Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School; Staff Pathologist, Brigham and Women's Hospital, Boston, MA Hemodynamic Disorders, Thromboembolic DISEASE , and ShockGeorge F. Murphy MD Professor of Pathology, Harvard Medical School; Director of Dermatopathology, Brigham and Women's Hospital, Boston, MA The SkinAndrew E.

9 Rosenberg MD Associate Professor of Pathology, Harvard Medical School; Associate Pathologist, James Homer Wright Laboratories, Department of Pathology, Massachusetts General Hospital, Boston, MA Bones, Joints, and Soft Tissue TumorsFrederick J. Schoen MD, PhD Professor of Pathology and Health Sciences and Technology, Harvard Medical School; Director, Cardiac Pathology and Executive Vice Chairman, Department of Pathology, Brigham and Women's Hospital, Boston, MA Blood Vessels; The HeartKlaus Sellheyer MD Assistant Professor of Pathology, Thomas Jefferson University; Attending Dermatopathologist, Jefferson Medical College, Philadelphia, PA The SkinArlene H. Sharpe MD, PhD Professor of Pathology, Harvard Medical School; Chief, Immunology Research Division, Department of Pathology, Brigham and Women's Hospital, Boston, MA Infectious DiseasesRobb E.

10 Wilentz MD Voluntary Faculty, Department of Dermatology, University of Miami School of Medicine; Laboratory Director, Division of Pathology, Skin and Cancer Associates, Miami, FL The PancreasIX Preface We launch the seventh edition of PATHOLOGIC BASIS of DISEASE with mixed emotions, excitement and enthusiasm, as we enter the new millennium, tempered by sadness over the loss of our dear colleagues Drs. Stanley Robbins and Ramzi Cotran . To acknowledge their immeasurable and everlasting contribution to this text, the book is now renamed Robbins and Cotran PATHOLOGIC BASIS of edition, like all previous ones, has been extensively revised, and some areas completely rewritten. Some of the more significant changes are as follows: Chapter 1 has been completely reorganized to include the entire spectrum of cellular responses to injury, from adaptations and sublethal injury to cell death.