~ATHOLOGY of the HUMAN PLACENTA

Third Edition

~THOLOGY of the HUMAN PLACENTA Third Edition

Kurt Benirschke

Peter Kaufmann

With 642 Illustrations

Springer Science+Business Media, LLC

Kurt Benirschke, MD Professor of Pathology and Reproductive Medicine University of California, San Diego University Medical Center San Diego, California 92103-8321, USA

Professor Dr. med. Peter Kaufmann Institut fUr Anatomie der Medizinischen FakuWit Rheinisch-Westfiilische Technische Hochschule Aachen 52057 Aachen, Germany

Library of Congress Cataloging-in-Publication Data Benirschke, Kurt.

Pathology of the human placenta I Kurt Benirschke, Peter Kaufmann. -3rd ed.

p. cm. Includes bibliographical references and index. ISBN 978-1-4757-4198-8 ISBN 978-1-4757-4196-4 (eBook) DOI 10.1007/978-1-4757-4196-4 1. Placenta-Diseases. 1. Kaufmann, Peter, 1942- . II. Title. [DNLM: 1. Placenta-pathology. WQ 212 B467p 1995]

RG591.B38 1995 618.3'4-dc20 DNLMIDLC for Library of Congress

Printed on acid-free paper.

© 1995, 1990, 1967 Springer Science+Business Media New York Originally published by Springer-Verlag New York, Inc. in 1967 Softcover reprint of the hardcover 3rd edition 1967

94-25783

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Preface

Most obstetricians and pediatricians would agree that examination of the placenta often helps to explain abnormal neonatal outcome. As early as in 1892 Ballantyne wrote that:

A diseased foetus without its placenta is an imperfect specimen, and a description of a foetal malady, unless accompanied by a notice of the placental condition, is incomplete. Deductions drawn from such a case cannot be considered as conclusive, for in the missing placenta or cord may have existed the cause of the disease and death. During intrauterine life the foetus, the membranes, the cord and the placenta form an organic whole, and disease of any part must react upon and affect the others.

Similar thoughts were succinctly detailed in Price's 1950 discussion of his concept of "prenatal biases" as they affected twins. His contribution admonished us that placental study is a sine qua non for a more perfect understanding of fetal develop­ment. Despite this understanding of our past, there is still great resistance to performing the task of placental examination routinely. For many pathologists, therefore, the placenta has remained a mysterious organ.

In 1967 Shirley G. Driscoll and I (K.B.) wrote the chapter on placental pathology for the German Handbook of Pathology, the Henke-Lubarsch. Because there seemed to be a need for wider dissemination of the text, it was reprinted by Springer-Verlag New York; it soon became unavailable. Since then several books on placental pathology have been written in French, English, and German (Fox, 1978; Perrin, 1984; Philippe, 1986; Baldwin & Lavery, 1987; Becker & R6ckelein, 1989; Naeye, 1992; Vogel, 1992; Baldwin, 1994), and much more interest has been accorded this so readily available but poorly studied organ. A journal (Placenta) has appeared. Regular "Trophoblast Conferences" have been held in Rochester, N.Y.; and European and international meetings have been organized. Much other new information has been obtained, and the enigma of placental nonrejection has been tackled by numerous investigators. In addition, the availability of the placenta for biochemical study has stimulated many cell biologists and molecular biologists to use this organ as a convenient source of human tissue. Genetic information is currently being gathered.

The decision to rewrite the original text to create the second edition was made in 1989 because of the large amount of newly created knowledge, the fact that the placenta had become a focal point of litigation in regard to cerebral palsy and fetal death, and because the anatomic pathologist performing surgical pathological diagnosis still had problems when faced with the task of having to undertake a decisive examination of this organ. Moreover, I (K.B.) had continued to collect material and had the good fortune to be associated with many inquiring minds. Pathologist Marjorie Grafe, dysmorphologists Drs. Kenneth L. Jones and his wife

v

vi

Marilyn Jones, and ultrasonographers/radiologists Drs. George R. Leopold, Dolores Pretorius, and David K. Edwards continue to challenge me and require that I provide explanations for perinatal deaths and abnormalities. Having examined all placentas of all deliveries in the institutions with which I was affiliated for over two decades, I had gathered a large amount of new material. Professor Peter Kaufmann agreed to write about the normal anatomical and histological aspects of placental structure and development.

This third edition has been written because of the many new findings and the ever-growing need to have documentation for legal purposes; moreover, organiza­tion of the second edition left some aspects uncovered. Many changes have been made in the book. Not only was the text updated, a better index was created, the order of chapters is presented more logically, new chapters have been added, and others were combined. Much new information has been incorporated to bring the text to the current state of knowledge.

Now that many more pathologists are required to examine placentas, the need to make some introductory chapters was apparent. To make it easier for the novice of placental morphology, we have added new chapters that serve as guides to normal histology (Chapter 4) and to the principal histopathological aspects of the placenta (Chapter 15).

The text was written with WordPerfect 6.0. A complete set of diskettes con­taining the references is available from the authors, if desired.

I (K.B.) am indebted to many people, foremost to my wife for her understanding and patience with me and this task; the publisher with its many people has been gracious and patient; my colleagues at the university, secretaries, computer consultants, and other persons who have all helped gather data, are gratefully acknowledged. Many students and colleagues have graciously read most chapters, and they have made many helpful suggestions and corrections, for which I am grateful. Most of all, however, I am grateful to Dr. Geoffrey Altshuler, Oklahoma City, for many stimulating discussions and for his willingness to read and cor­rect much of this manuscript. He undertook this task with endless patience and friendship.

I (P.K.) gratefully acknowledge the scientific cooperation of many former and present coworkers: Mario Castellucci, Caterina Crescimanno, Hans-Georg Frank, Berthold Huppertz, Sonya Kertschanska, Gaby Kohnen, Georg Kosanke, Vladimir Mironov, Azizbek Nanaev, Iris Scheffen, and the late Gertfried Schweikhart. Many of my data are based on their material, their findings, and their ideas.

Many colleagues and friends from other laboratories have contributed by discus­sion and by offering technical help. In this respect I am particularly grateful to Graham Burton, Anthony Carter, Ramazan Demir, Gernot Desoye, Gottfried Dohr, Jean-Michel Foidart, Renate Graf, Michaele Hartmann, John Kingdom, Hubert Korr, Rudolf Leiser, Lena Macara, Hobe Schroder, Tullia Todros, Carla Verkeste, and the late Elizabeth Ramsey. In many cases it is virtually impossible to differentiate between their and my ideas.

These chapters have required not only scientific inspiration but also much artistic, technical, and secretarial work. The artistic help of Wolfgang Graulich and the photographic assistance of Gaby Bock and Ute Kaufmann are gratefully acknowl­edged. The histological and electron microscopic pictures are based on material processed by Marianne von Bentheim, Christine Eherer, Michaela Nicolau, Linda Philippens, Barbara Witte, and Uta Zahn. Perfect secretarial assistance was provided by Jutta Jacobs and Michael Kaufmann.

Preface

Preface vii

The collaboration of these coworkers and friends was the basis for my contri­bution. Last but not least, I am very much indebted to my wife for her support and understanding.

1994

References

KURT BENIRSCHKE

La Jolla, California

PETER KAUFMANN

Aachen, Germany

Baldwin, V.J.: Pathology of Multiple Pregnancy. Springer-Verlag, New York, 1994. Ballantyne, J.W.: The Diseases and Deformities of the Foetus. Vol. 1. Oliver & Boyd,

Edinburgh, 1892. Becker, V., and Rockelein G.: Pathologie der weiblichen Genitalorgane. I. Pathologie der

Plazenta und des Abortes. Springer-Verlag, Heidelberg, 1989. Benirschke, K., and Driscoll, S.G.: The Pathology of the Human Placenta. Springer-Verlag,

New York, 1967. Benirschke, K., and Kaufmann, P.: Pathology of the Human Placenta. 2nd ed. Springer­

Verlag, New York, 1990. Fox, H.: Pathology of the Placenta. Saunders, Philadelphia, 1978. Lavery, J.P., ed.: The Human Placenta. Clinical Perspectives. Aspen Publishers, Rockville,

MD,1987. Naeye, R.L.: Disorders of the Placenta, Fetus, and Neonate. Mosby Year Book, St. Louis,

1992. Perrin, V.D.K., ed.: Pathology of the Placenta. Churchill Livingstone, New York, 1984. Philippe, E.: Pathologie Foeto-Placentaire. Masson, Paris, 1986. Price, B.: Primary biases in twin studies: review of prenatal and natal differences-producing

factors in monozygotic pairs. Am. J. Hum. Genet. 2:293-352, 1950. Vogel, M.: Atlas der morphologischen Plazentadiagnostik. Springer-Verlag, Heidelberg,

1992.

Contents

Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v

1 Placental Types. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Placental Shapes ............................................... 3 Types of Maternofetal Interdigitation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Maternofetal Barrier. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Maternofetal Blood Flow Interrelations. . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Placental Types and Phylogeny . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Human Placenta. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

2 Examination of the Placenta. . . . . . . . . . . . . . . . . . . . . . . . . . . .. 14

Macroscopic Examination ....................................... 14 Storage. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 Selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Photography. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Examination. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Placentas of Multiple Births. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 20

Fixation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 21 Special Procedures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 22

3 Macroscopic Features of the Delivered Placenta. . . . . . . . . . .. 25

4 Microscopic Survey. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 28

Typical Histological Features of the First Trimester Placenta. . . . . . . . .. 28 Typical Histological Features of the Third Trimester Placenta. . . . . . . .. 34 Immunohistochemical Markers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 38

5 Normative Values and Tables. . . . . . . . . . . . . . . . . . . . . . . . . . .. 41

IX

x Contents

6 Early Development of the Human Placenta ............... . 49

Pre lacunar Stage .............................................. . 49 Lacunar Stage ................................................. . 51 Early Villous Stages ............................................ . 53

7 Basic Structure of the Villous Trees ..................... . 57 M. Castellucci and P. Kaufmann

Syncytiotrophoblast ............................................ . 57 Syncytium or Multinucleated Giant Cells? ....................... . 57 Syncytial Plasmalemmas and Microvilli ......................... . 60 Syncytiotrophoblastic Cytoskeleton ............................ . 61 Specialized Regions of the Villous Surface ...................... . 62 Epithelial Plates ............................................. . 62 Syncytial Lamellae Covering Langhans' Cells .................... . 64 Syncytiotrophoblast with Prevailing Rough Endoplasmic

Reticulum ................................................ . 64 Syncytiotrophoblast with Prevailing Smooth Endoplasmic

Reticulum ................................................ . 65 Syncytial Knots, Sprouts, Bridges, and Stromal Trophoblastic

Buds ..................................................... . 66 Transtrophoblastic Channels .................................. . 69 Plasma Protrusions or Blebs ................................... . 70

Villous Cytotrophoblast (Langhans' Cells) ........................ . 71 Langhans' Cells as Precursors of the Syncytiotrophoblast .......... . 71 Langhans' Cell Types ........................................ . 71 Nematosomes ............................................... . 74 Endocrine Activity of the Langhans' Cells ....................... . 74 Functional Aspects of Syncytial Fusion ......................... . 75 Regulation of Cytotrophoblastic Proliferation and Fusion ......... . 78

Trophoblastic Basement Membrane .............................. . 81 Connective Tissue ............................................. . 81

Mesenchymal Cells .......................................... . 81 Reticulum Cells ............................................. . 81 Fibroblasts ................................................. . 82 Myofibroblasts .............................................. . 83 Matrix Components of the Villous Stroma ...................... . 84

Hofbauer Cells ................................................ . 84 First Descriptions ............................................ . 84 Morphology ................................................ . 84 Occurrence and Distribution .................................. . 85 Origin ..................................................... . 86 Immunological Aspects ....................................... . 86

Other Free Connective Tissue Cells .............................. . 92 Development and Structure of Fetal Villous Vessels ................ . 92

Origin of the Hemangioblastic Cells ............................ . 92 Capillary Formation During Early Pregnancy .................... . 92 Basic Structure of the Vessel Walls ............................. . 93

Fibrinoid of the Villous Tree .................................... . 94 Perivillous Fibrinoid ......................................... . 94 Intravillous Fibrinoid ......................................... . 96

Cell Biological Trends .......................................... . 97 Cell Isolation and Culture .................................... . 97 Growth Factors, Growth Factor Receptors, Oncogenes ........... . 97

Contents xi

Proteases .................................................. " 98 Extracellular Matrix .......................................... 98

8 Architecture of Normal Villous Trees .................... 116

Structure of Villous Types. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 116 Stem Villi. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 116 Immature Intermediate Villi. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 119 Mature Intermediate Villi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 122 Terminal Villi ............................................. " 124 Mesenchymal Villi ........................................... 124 Immunohistochemical Characterization of Villous Types .......... 126

Differentiation and Maturation of Villous Types. . . . . . . . . . . . . . . . . . .. 127 Development of Mesenchymal Villi. . . . . . . . . . . . . . . . . . . . . . . . . . . .. 127 Development and Fate of Immature Intermediate Villi. . . . . . . . . . .. 130 Development of Stem Villi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 131 Development of Mature Intermediate Villi ...................... 132 Development of Terminal Villi. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 132

Angioarchitecture of Villi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 132 Vascular Arrangement in Immature Villi ...................... " 132 Large Vessels of Stem Villi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 133 Paravascular Capillary Net of Stem Villi. . . . . . . . . . . . . . . . . . . . . . . .. 133 Arrangement of Vessels in Mature Intermediate and Terminal

Villi. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 135 Sinusoids of Terminal Villi .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 137 Capillary Growth as Related to the Development of Terminal

Villi. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 138 Intervillous Space as Related to the Villous Trees ................ 139

Control of Villous Development. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 142 Oxygen as Regulator of Villous Development. . . . . . . . . . . . . . . . . . .. 142 Hormones as Regulators of Villous Development. . . . . . . . . . . . . . . .. 143

Fetomaternal Flow Interrelations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 144

9 Characterization of Developmental Stages ................ 151

Stages of Development ... . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . .. 151 Nucleated Red Blood Cells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 164

10 Three-Dimensional Aspects of Villous Maldevelopment .... 167

Villous Cross-Sectional Features .... . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 167 Villous Maldevelopment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 170

Normal Mature Placenta. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 170 Synchronous Villous Immaturity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 171 Persisting Villous Immaturity and Rhesus Incompatibility. . . . . . . . .. 171 Terminal Villi Deficiency. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 173 Maternal Diabetes Mellitus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 174 Villous Hypermaturity and Preterm Villous Maturation ........... 175 IUGR Combined with Absent End-Diastolic Umbilical Blood

Flow..................................................... 175 Preeclampsia, Hypertensive Disorders, and Placentas at High

Altitude ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 176 Prolonged Pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 177

Classification of Villous Maldevelopment. . . . . . . . . . . . . . . . . . . . . . . . .. 178

xii

11 Nonvillous Parts of the Placenta .......................... 182

Extravillous Trophoblast ........................................ 182 Nomenclature. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 182 Historical Aspects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 183 Composition of the Extravillous Trophoblast Population . . . . . . . . . .. 184 One Stem Cell Origin for Villous Syncytiotrophoblast and the

Extravillous Trophoblast? ................................... 187 Invasive Properties of the Extravillous Trophoblast. . . . . . . . . . . . . . .. 189 Extravillous Trophoblast and Maternofetal Immune Interactions . . .. 190 Secretory Activities of Extravillous Cytotrophoblast . . . . . . . . . . . . . .. 190 Placental Site Giant Cells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 193 Multinucleated Trophoblastic Giant Cells. . . . . . . . . . . . . . . . . . . . . . .. 193 Syncytiogenesis .............................................. 195

Decidua. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 196 Endometrial Stromal Cells and Decidual Cells. . . . . . . . . . . . . . . . . . .. 196 Functional Relevance of Decidual Cells. . . . . . . . . . . . . . . . . . . . . . . . .. 198 Endometrial Large Granular Lymphocytes. . . . . . . . . . . . . . . . . . . . . .. 199 Macrophages ................................................ 200 G Cells ...................................................... 200 Glandular Residues. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 201 Extracellular Matrix .......................................... 201 Decidual Degeneration. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 201

Fibrinoid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 203 Definition of Fibrinoid ........................................ 203 Types of Fibrinoid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 204 Origin of Fibrinoid. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 205 Interactions Between Matrix-Type and Fibrin-Type Fibrinoid ....... 207 Functional Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 208

Calcification .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 210 Chorionic Plate ................................................ 213

Development .......... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 213 Structure at Term ............................................. 214 Amnion ..................................................... 214 Spongy Layer ................................................ 214

Chorionic Mesoderm. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 215 Extravillous Cytotrophoblast. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 216

Langhan's Fibrinoid Layer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 218 Marginal Zone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 218

Subchorial Closing Ring. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 218 Trabeculae .................................................. 219 Marginal Sinus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 219

Basal Plate .................................................... 219 Trophoblastic Shell and Development of the Basal Plate ... . . . . . . .. 219 Layers of the Basal Plate at Term. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 222 Development of Uteroplacental Vessels ......................... 227 Number and Position of Uteroplacental Vessels ................... 227 Structure of Uteroplacental Arteries ............................ 228 Structure of Uteroplacental Veins. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 231 Intraarterial Trophoblast ...................................... 231 Intramural Fibrinoid of Uteroplacental Arteries and Veins. . . . . . . .. 233 Functional Aspects of Uteroplacental Vessels. . . . . . . . . . . . . . . . . . . .. 234

Septa ......................................................... 234 Cell Islands. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 237 Cell Columns ....... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 239

Contents

xiii

Cysts and Breus' Mole .......................................... 239 Pathology of Maternal Floor Infarction . . . . . . . . . . . . . . . . . . . . . . . . . . .. 245

12 Anatomy and Pathology of the Placental Membranes ....... 268

Development ......... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 270 Amnion ....................................................... 273

Amnionic Epithelium: Different Cell Types or Cell Degeneration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 273

Cytological and Functional Aspects of the Amnionic Epithelium .... 274 Amnionic Fluid .............................................. 277 Chromosomal Determinations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 278 Cellular Metaplasia and Glycogen. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 278 Amnionic Mesoderm. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 279 Medley of Themes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 280 Clinical and Research Applications. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 281

Chorion Laeve . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 281 Intermediate (Spongy) Layer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 282 Chorionic Mesoderm. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 282 Trophoblast Layer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 283 Immunological Considerations of the Trophoblast. . . . . . . . . . . . . . . .. 284 Decidua. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 284

Tensile Properties of the Membranes. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 285 Cysts, Tumors, Hemorrhage ..................................... 286 Amniotic Fluid Embolism ....................................... 288 Meconium. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 290 Gastroschisis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 296 Epidermolysis Bullosa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 297 Amnion Nodosum .............................................. 297 Amnionic Bands ............................................... 299 Extramembranous Pregnancy .................................... 305

13 Anatomy and Pathology of the Umbilical Cord and Major Fetal Vessels .................................... 319

Development .................................................. 319 Amnionic Epithelium ........................................... 319 Wharton's Jelly ................................................ 321 Structure of Umbilical Vessels. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 321 Innervation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 323 Contractility of Umbilical Vessels. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 323 Hyrtl Anastomosis, False Knots, and Hoboken Nodes ............... 325 Allantois . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 325 Omphalomesenteric Duct. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 326 Spiral Turns of the Cord. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 330 Length of the Cord ......... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 332

Abnormal Length, Nuchal Cord. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 333 Site of Cord Insertion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 337

Furcate Cord Insertion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 338 Velamentous Cord Insertion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 338

Placental Surface Vessels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 342 Nucleated Red Blood Cells ...................................... 345 Cysts and Edema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 345 Single Umbilical Artery ......................................... 347 Placental Transfusion ........................................... 349

XIV Contents

Knots ......................................................... 350 False Knots. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 351 Strictures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 352 Rupture. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 353 Hematoma .................................................... 353 Varices and Aneurysms ... ,..................................... 355 Thrombosis of the Umbilical Vessels .............................. 357 Thrombosis of the Placental Vascular Tree. . . . . . . . . . . . . . . . . . . . . . . .. 360 Tumors of the Umbilical Cord. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 365

14 Placental Shape Aberrations ............................. 378

Site of Placental Attachment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 378 Volumetric Growth ............................................. 379 Abnormal Shapes ("Errors in Outline") .......... . . . . . . . . . . . . . . . .. 380 Placenta Previa. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 383 Placenta Accreta ........... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 387 Placenta Increta and Percreta .................................... 389 Placenta Membranacea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 390 Placenta in Ectopic Pregnancy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 392 Placenta in Abdominal Pregnancy ................................ 393 Circumvallate Placenta (Extrachorial and

Circummarginate Placentas) ................................... 394

15 Histopathological Approach to Villous Alterations ......... 404

Microscopic Evaluation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 404 Assessment of Villous Maturation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 404 Placental Insufficiency. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 406 Examination of Fetal Stem Vessels .............................. 407 Examination of the Fetal Capillary Bed. . . . . . . . . . . . . . . . . . . . . . . . .. 407 Villous Architecture and Fibrinoid . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 409 Intervillous Space, Infarcts. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 409 Abruptio Placentae ........................................... 410

Major Histopathological Findings. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 410 Syncytiotrophoblast. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 410 Knotting of the Syncytiotrophoblast. . . . . . . . . . . . . . . . . . . . . . . . . . . .. 411 Langhans' Cells .............................................. 412 Vasculosyncytial Membranes ................................... 412 Trophoblastic Basement Membrane ............................. 413 Perivillous Fibrinoid ....... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 413 Intravillous Fibrinoid. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 413 Villous Calcification. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 413 Stem Vessels. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 414 Nucleated Red Blood Cells .................................... 414 Villous Capillarization. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 414 Stromal Architecture and Stromal Fibrosis. . . . . . . . . . . . . . . . . . . . . .. 415 Hofbauer Cells (Macrophages) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 415 Inflammatory Changes ........................................ 416 Villous Edema or Immaturity .................................. 417

16 Erythroblastosis Fetalis and Hydrops Fetalis ............... 421

Erythroblastosis Fetalis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 421 Placental Pathology in Erythroblastosis . . . . . . . . . . . . . . . . . . . . . . . . .. 422

Nonimmune Hydrops . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 427 a-Thalassemia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 428 Fetal Hemorrhage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 430 Fetal Tumors ................................................ 431 Congenital Anomalies and Hydrops Fetalis. . . . . . . . . . . . . . . . . . . . . .. 433 Congenital Heart Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 434 Cardiac Arrhythmias. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 435 Nephrotic Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 435 Parvovirus Anemia ............... . . . . . . . . . . . . . . . . . . . . . . . . . . .. 436 Hydrops of Unknown Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 439

17 Transplacental Hemorrhage, Cell Transfer, Trauma. . . . . .. 449

Transplacental Blood and Cell Transfer. . . . . . . . . . . . . . . . . . . . . . . . . . 449 Trauma..................................................... 449

Placenta in Hemorrhage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 454 Technique for Identification of Fetal Red Blood Cells. . . . . . . . . . . . . . 455 Significant Transplacental Hemorrhage .......................... 458 Fetal Consequences of Massive Hemorrhage Across the Placenta. . . . 459 Other Fetal Blood Elements Passing Through the Placenta ......... 463 Mother to Fetus Transfer of Cells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 464

18 Fetal Storage Disorders ............................... 471

19 Maternal Diseases Complicating Pregnancy: Diabetes, Tumors, Preeclampsia, Lupus Anticoagulant. . . . . . . . . . . .. 476

Maternal Diseases ............ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 476 Hematological Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 483 Endocrine Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 485 Diabetes During Pregnancy ......... . . . . . . . . . . . . . . . . . . . . . . . . . 486 Maternal Neoplasms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 489

Hypertensive Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 493 Preeclampsia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 493 Animal Models. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 493 Placental Pathology of Preeclampsia. . . . . . . . . . . . . . . . . . . . . . . . . . . 494 Decidual Arteriopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 494 Infarcts. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 500 Abruptio Placentae ......................................... 503 Fetal Effects of Abruptio Placentae ........................... 508 Other Placental Changes in Preeclampsia ...................... 508 Etiology of Toxemia, PIH or Preeclampsia . . . . . . . . . . . . . . . . . . . . . 511

Lupus Erythematosus and Lupus Anticoagulant. . . . . . . . . . . . . . . . . . . 512 Lupus Erythematosus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 512 Lupus Anticoagulant. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 515

20 Infectious Diseases ................................... 537

Chorioamnionitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 537 Macroscopic Appearance ........ . . . . . . . . . . . . . . . . . . . . . . . . . . . . 537 Microscopic Appearance. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 538

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General Considerations of Chorioamnionitis . . . . . . . . . . . . . . . . . . . . 551 Specific Microorganisms ..................................... 553

Leprosy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 559 Tuberculosis ................................................. 560 Listeriosis ................................................... 560 Bacterial Vaginosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 564

Mycoplasma hominis and Urea plasma urealyticum . . . . . . . . . . . . . . . 564 Chlamydia trachomatis ...................................... 566

Syphilis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 567 Necrotizing Funisitis .......................................... 568 Other Spirochetal Diseases. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 571 Fungus Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 572 Virus Infections and Villitides .................................. 575

Cytomegalovirus Infection ................................... 575 Herpes Simplex Virus Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 580 Varicella (Chickenpox) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 584 Epstein-Barr Virus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 584 Smallpox, Vaccinia, Alastrim, Parvovirus B19 .................. 584 Enteroviruses .............................................. 585 Influenza, Mumps, Rabies ................................... 586 Hepatitis .................................................. 586 Rubella (German Measles). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 587 Rubeola (Measles) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 587 Human Immunodeficiency Virus Infection. . . . . . . . . . . . . . . . . . . . . . 588

Toxoplasmosis ............................................... 589 Chagas' Disease ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 593 Babesiosis, Trichomoniasis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 593 Malaria. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 593 Other Parasitic Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 595 Villitis of Unknown Etiology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 596

21 Abortion, Placentas of Trisomies, and Immunological Considerations of Recurrent Reproductive Failure . . . . . . .. 624

Anatomical Findings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 626 Summary of Placental Findings in Chromosomally Defined

Abortions ............................................... 629 Induced Abortion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 633 Incomplete Abortion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 636 Placenta in Chorionic Villus Sampling ........................... 637 Trisomic Placentas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 640

Chemical Markers and Trisomy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 641 Other Findings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 641 Recurrent or Habitual Abortion ................................ 642

22 Molar Pregnancies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 653

Hydatidiform Moles. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 653 Incidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 654 Genetics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 655 Morphology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 659 Other Characteristics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 664 Deportation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 665

Contents xvii

Chorioadenoma Destruens (Invasive Mole) . . . . . . . . . . . . . . . . . . . . . . . 666 Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 668

Ectopic Moles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 670 Partial Hydatidiform Mole . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 670 Mole and Fetus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 673

PHM with Twin Gestation ...... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 675

23 Choriocarcinoma..................................... 686

Choriocarcinoma In Situ and Choriocarcinoma with Pregnancy. . . . . . 692 Trophoblastic Pseudotumors ................................... 695 Ultrastructure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 698 Antigenic Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 698 Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 699 Endocrine Aspects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 700 Ectopic Choriocarcinomas; Tumors in Men. . . . . . . . . . . . . . . . . . . . . . . 700 Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 701 Choriocarcinoma in Animals ........ . . . . . . . . . . . . . . . . . . . . . . . . . . . 702 Choriocarcinoma in Cell Lines and Genetics. . . . . . . . . . . . . . . . . . . . . . 702

24 Benign Tumors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 709

Angiomas ................................................... 709 Other Benign Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 715 Chorangiosis, Chorangiomatosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 715

25 Multiple Pregnancy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 719

Zygosity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 719 Placenta in the Study of Zygosity ............................... 720 Causes and Incidence of Multiple Births ......................... 725 Third Type of Twin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 731 Twinning Incidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 731 Superfetation and Superfecundation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 733 Vascular Anatomy of Twin Placentas. . . . . . . . . . . . . . . . . . . . . . . . . . . . 733 Monoamnionic Monochorionic Twin Placenta .................... 742 Diamnionic Monochorionic Twin Placenta ....................... 752 Diamnionic Dichorionic Twin Placenta .......................... 755 Vanishing Twin Phenomenon. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 757 Fetus Papyraceus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 759 Transfusion Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 767 Acardiac Twins. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 778 Conjoined Twins. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 786 Sacrococcygeal Teratoma, Epignathus . . . . . . . . . . . . . . . . . . . . . . . . . . . 789 Congenital Anomalies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 791 Cytogenetics and "Heterokaryotypic MZ Twins" . . . . . . . . . . . . . . . . . . 792 Chimerism, Mosaicism ........................................ 792

Whole-Body-Chimerism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 794 Triplets and Higher Multiple Births ............................. 794 Twins Associated with Abortion and Ectopic Pregnancy. . . . . . . . . . . . 802 Morbidity and Mortality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 803 Hormones in Twin Pregnancy .................................. 806

xviii Contents

26 Involution of Implantation Site and Retained Placenta .... . 827 Involution of the Placenta Site ................................. . 827 Subinvolution ............................................... . 829 Placental Polyps ............................................. . 830 Involution of a Remaining Placenta ............................ . 832

27 Legal Considerations ................................. . 835 Twinning Problems .......................................... . 838 Inflammation ................................................ . 839 Green Placenta .............................................. . 841 Vascular Abnormalities ....................................... . 842 Umbilical Cord .............................................. . 843 Placental Villous Color ....................................... . 843 Other Types of Pathology ..................................... . 844

28 Glossary ............................................ . 849

Index .............................................. . 853