Pathology of the Human Placenta, 4th Edition
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vi Preface
is presented more logically, and tables are presented more usefully. The text was
written with WordPerfect 6.1. A complete set of diskettes with the references can be
made 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 many of its people has been
gracious and patient; and my colleagues at the university, 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 appreciative. There are some colleagues, however,
whose inspiration has helped more than others: Marjorie Grafe and Rebecca
Baergen, the dysmorphologists Kenneth L. Jones and his wife Marilyn, and ultra-
sonographers/radiologists George R. Leopold, Dolores Pre tori us, and Nancy
Budorick, who 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 during the past three decades, I have gath-
ered a large amount of material to digest. Most of all, however, I am grateful to Dr.
Geoffrey Altshuler, Oklahoma City, for many stimulating discussions and for his will-
ingness to read and correct much of this manuscript. He undertook this with endless
patience and friendship.
P.K. gratefully acknowledges the scientific cooperation of many former and present
coworkers. These comprise Mario Castellucci, Ayse Demir, Hans-Georg Frank,
Hitoshi Funayama, Gabriele Gaus, Berthold Huppertz, Mahmed Kadirov, Sonja
Kertschanska, Gaby Kohnen, Georg Kosanke, Azizbek Nanaev, Frank Reister, and
the late Gertfried Schweikhart. Many of my data are based on their material, their
findings, and their ideas. Also, many colleagues and friends from other laboratories
have contributed by discussion and by offering technical help. In this respect I am
particularly grateful to Ramazan Demir, Gernot Desoye, Jean-Michel Foidart, John
Kingdom, Hubert Korr, Rudolf Leiser, Hobe Schroder, Tullia Todros, and the late
Elizabeth Ramsey. In many cases it is virtually impossible to differentiate between
their ideas and my own.
These chapters do not only require scientific inspiration but also much artistic, tech-
nical, and secretarial work. The artistic help of Wolfgang Graulich and the photo-
graphic assistance of Gaby Bock as well as that of Helga Kriegel are gratefully
acknowledged. The histological and electron microscopic pictures are based on mate-
rial processed by Marianne von Bentheim, Michaela Nicolau, Lian Shen, Barbara
Ihnow, and Uta Zahn. Perfect secretarial assistance was provided by Jutta Ruppert.
The collaboration of all these coworkers and friends was the basis for my contri-
bution. Last not least, I am very much indebted to my wife for her support and
understanding.
Kurt Benirschke
San Diego, California
Peter Kaufmann
Aachen, Germany
2000
References
Baldwin, V.I: Pathology of Multiple Pregnancy. Springer-Verlag, New York, 1994.
Ballantyne, I w.: The Diseases and Deformities of the Foetus, Vol. I. Oliver & Boyd, Edinburgh,
1892.
Becker, V. and Rockelein, G.: Pathologie der weiblichen Genitalorgane I. Pathologie der
Plazenta und des Abortes. Springer-Verlag, Heidelberg, 1989.
Preface Vll
Benirschke, K. and Driscoll, S.G.: The Pathology of the Human Placenta. Springer-Verlag, New
York,1967.
Fox, H.: Pathology of the Placenta. 2nd Ed. Saunders, Philadelphia, 1997.
Gall, S.A.: Multiple Pregnancy and Delivery. Mosby, St. Louis, Missouri, 1996.
Joshi, Y.Y.: Handbook of Placental Pathology. Igaku-Shoin, New York, 1994.
Kaplan, CG.: Color Atlas of Gross Placental Pathology. Igaku-Shoin, New York, 1994.
Lavery, J.P., ed.: The Human Placenta. Clinical Perspectives. Aspen, Rockville, Maryland, 1987.
Lewis S.H. and Perrin, Y.D.K., eds.: Pathology of the Placenta. Churchill Livingstone, New York,
1999.
Naeye, R.L.: Disorders of the Placenta, Fetus, and Neonate. Mosby Year Book, St. Louis, 1992.
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. 2nd Ed. Springer-Verlag, Heidel-
berg, 1995.
Contents
Preface v
1. Examination of the Placenta 1
Storage ..................................................... 1
Selection ................................................... 2
Photography ................................................ 2
Examination ................................................ 2
Placentas of Multiple Births . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Fixation .................................................... 9
Special Procedures ........................................... 11
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
2. Macroscopic Features of the Delivered Placenta ........... 13
References .................................................. 15
3. Microscopic Survey ......................................... 16
Typical Histological Features of the First Trimester Placenta ....... 16
Typical Histological Features of the Third Trimester Placenta ...... 20
Immunohistochemical Markers ................................ 28
4. Placental Types ............................................. 29
Placental Shapes ............................................. 31
Types of Maternofetal Interdigitation ........................... 31
Maternofetal Barrier ......................................... 33
Maternofetal Blood Flow Interrelations ......................... 35
Placental Types and Phylogeny ................................. 39
Human Placenta ............................................. 39
References .................................................. 39
5. Early Development of the Human Placenta ................ 42
Pre lacunar Stage ............................................ 42
Lacunar Stage ............................................... 44
IX
x Contents
Early Villous Stages ........................................ . 46
References ................................................ . 48
6. Basic Structure of the Villous Trees 50
M. Castellucci and P Kaufmann
Syncytiotrophoblast .......................................... 50
Syncytium or Multinucleated Giant Cells? ..................... 50
Syncytial Plasmalemmas and Microvilli ....................... 53
Syncytiotrophoblastic Cytoskeleton .......................... 55
Specialized Regions of the Villous Surface ..................... 55
Vasculosyncytial Membranes ................................ 55
Syncytial Lamellae Covering Langhans' Cells ...... . . . . . . . . . . . 56
Syncytiotrophoblast with Prevailing Rough
Endoplasmic Reticulum .................................. 57
Syncytiotrophoblast with Prevailing Smooth Endoplasmic
Reticulum ................................................ 58
Syncytial Knots, Sprouts, and Bridges ......................... 59
Transtrophoblastic Channels ................................ 63
Trophoblastic Blebbing ..................................... 64
Villous Cytotrophoblast (Langhans' Cells) ...................... 65
Langhans' Cells as Precursors of the Syncytiotrophoblast ........ 65
Langhans' Cell Types ....................................... 66
Nematosomes ............................................. 69
Endocrine Activity of the Langhans' Cells ..................... 69
Syncytial Fusion and Trophoblast Turnover ...................... 72
Functional Aspects of Syncytial Fusion ....................... 72
Trophoblastic Apoptosis .................................... 73
Quantitation of Trophoblast Turnover ........................ 74
Regulation of Cytotrophoblastic Proliferation and Fusion ....... 76
Trophoblastic Basement Membrane ............................ 78
Connective Tissue ............................................ 78
Mesenchymal Cells (V Cells) ................................ 78
Fibroblasts (VD Cells and VDA Cells) ........................ 79
Myofibroblasts (VDAG Cells and VDAGM Cells) .............. 80
Matrix Components of the Villous Stroma ..................... 81
Hofbauer Cells .............................................. 82
First Descriptions .......................................... 82
Morphology ............................................... 82
Occurrence and Distribution ................................ 84
Origin .................................................... 85
Immunological Aspects ..................................... 85
Other Free Connective Tissue Cells ............................ 89
Development and Structure of Fetal Villous Vessels .............. 89
Origin of the Hemangioblastic Cells .......................... 89
Capillary Formation During Early Pregnancy .................. 89
Growth Factor Control of Early Vasculogenesis ................ 89
Basic Structure of the Vessel Walls ........................... 90
Fibrinoid of the Intervillous Tree ............................... 93
Peri villous Fibrinoid ....................................... 93
Intravillous Fibrinoid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
In Vitro Appproaches to the Study of Villous Components ........ 95
References .................................................. 96
Contents xi
7. Architecture of Normal Villous Trees ...................... 116
Structure of Villous Types ..................................... 116
Stem Villi ................................................. 116
Immature Intermediate Villi ................................. 120
Mature Intermediate Villi ................................... 125
Terminal Villi ............................................. 126
Mesenchymal Villi ......................................... 127
Immunohistochemical Characterization of Villous Types ......... 129
Differentiation and Maturation of Villous Types .................. 130
Development of the Mesenchymal Villi ....................... 131
Development and Fate of Immature Intermediate Villi .......... 131
Development of Stem Villi .................................. 131
Development of the Mature Intermediate Villi ................. 132
Development of the Terminal Villi ............................ 132
Angioarchitecture of Villi ..................................... 134
Vascular Arrangement in Immature Villi ...................... 134
Larger Vessels of Stem Villi ................................. 134
Paravascular Capillary Net of Stem Villi ...................... 134
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 ............................................ 140
Intervillous Space as Related to the Villous Trees ................ 140
Control of Villous Development ............................... 143
Oxygen and Oxygen-Controlled Growth Factors as
Regulators of Villous Development ........................ 143
Types of Hypoxia and Its Effects on Villous Development ....... 145
Hormones as Regulators of Villous Development .............. 146
Fetomaternal Flow Interrelations .............................. 147
References .................................................. 148
8. Characterization of the Developmental Stages ............. 155
Stages of Development ....................................... 155
Nucleated Red Blood Cells .................................... 166
References .................................................. 170
9. Nonvillous Parts and Trophoblast Invasion 171
H. G. Frank and P. Kaufmann
Extravillous Trophoblast ...................................... 171
Historical Aspects and Nomenclature ......................... 171
Extravillous Trophoblast Is a Tissue of Its Own ... . . . . . . . . . . . . . . 171
Proliferation Patterns of Extravillous Trophoblast .............. 173
Cytokines and Growth Factors ............................... 173
Extracellular Matrix Receptors (Integrins) .................... 178
Other Cell Adhesion Molecules and Gap Junction Molecules .... 179
Proteinases, Activators, and Inhibitors ........................ 179
Endocrine Activities of Extravillous Cytotrophoblast ........... 181
Nitric Oxide Synthase ...................................... 182
Major Basic Protein . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182
Blood Group Antigens ..................................... 182
xii Contents
MHC Class I Molecules ................................... . 184
Switching the Phenotypes of Extravillous Trophoblast .......... . 185
Oxygen-Mediated Regulation of the Invasive Pathway ......... . 185
One Stem Cell Origin for Villous Syncytiotrophoblast and .
the Extravillous Trophoblast? ............................. . 186
Homogeneity of the Extravillous Trophoblast ................. . 187
Placental Site Giant Cells .................................. . 187
Multinucleated Trophoblastic Giant Cells .................... . 188
Decidua ................................................... . 188
Composition of Decidua ................................... . 188
Endometrial Stromal Cells and Decidual Cells ................ . 189
Endocrine and Paracrine Aspects of Decidua ................. . 190
Functional Considerations of Decidualization ................ . 191
B Cells and T Cells ....................................... . 192
Endometrial Large Granular Lymphocytes
(Endometrial NK Cells) ................................. . 193
Macrophages ............................................. . 194
Glandular Residues ....................................... . 195
Extracellular Matrix 195
Fibrinoid ................................................... . 196
Definition and Historical Remarks .......................... . 196
Types of Fibrinoid ........................................ . 196
Origin of Fibrinoids ....................................... . 198
Interactions Between Matrix-Type and Fibrin-Type Fibrinoid ... . 200
Functions of Fibrinoid .................................... . 200
Trophoblast Invasion as a Result of Deciduo-Trophoblastic
Interactions .............................................. . 202
Calcification ............................................... . 203
Chorionic Plate ............................................. . 208
Development ............................................ . 208
Structure at Term ......................................... . 208
Amnion ................................................. . 209
Spongy Layer ............................................ . 209
Chorionic Mesoderm ...................................... . 209
Extravillous Cytotrophoblast ............................... . 209
Langhans' Fibrinoid Layer ................................. . 210
Marginal Zone ............................................. . 210
Subchorial Closing Ring ................................... . 211
Trabeculae ............................................... . 212
Marginal Sinus ........................................... . 212
Basal Plate ................................................ . 214
Trophoblastic Shell and Development of the Basal Plate ....... . 214
Layers of the Basal Plate at Term .......................... . 214
Uteroplacental Vessels ...................................... . 217
Development of Uteroplacental Vessels ..................... . 217
Number and Position of the Uteroplacental Vessels ............ . 219
Physiological Changes of Uteroplacental Arteries ............. . 220
Molecular Mechanisms of Arterial Trophoblast Invasion ....... . 223
Structure of Uteroplacental Veins ........................... . 223
Intramural Fibrinoid of Uteroplacental Arteries and Veins ...... . 224
Functional Aspects of Uteroplacental Vessels ................. . 224
Septa, Cell Islands, and Cell Columns ......................... . 226
Septa .................................................... . 226
Cell Islands .............................................. . 227
Cell Columns 228
Contents xiii
Pathology of Trophoblast Invasion ............................. 229
Placenta Accreta .......................................... 229
Placenta Increta and Percreta ............................... 232
Placenta in Ectopic (Tubal) Pregnancy ........................ 236
Placenta in Abdominal Pregnancy ............................ 238
Cysts and Breus' Mole ...................................... 240
Maternal Floor Infarction ................................... 242
Decidual Degeneration ..................................... 248
References .................................................. 250
10. Involution of Implantation Site and Retained Placenta ..... 273
Involution of the Placental Site ................................. 273
Subinvolution ................................................ 276
Placental Polyps .............................................. 276
Involution of a Remaining Placenta ............................. 278
References ................................................... 279
11. Anatomy and Pathology of the Placental Membranes...... 281
Overview ................................................... 281
Development ................................................ 282
Amnion .................................................... 284
Amnionic Epithelium: Different Cell Types or
Cell Degeneration ........................................ 285
Cytological and Functional Aspects of the
Amnionic Epithelium ..................................... 286
Amnionic Fluid ............................................ 289
Chromosomal Determinations ............................... 290
Cellular Metaplasia and Glycogen ............................ 291
Amnionic Mesoderm ....................................... 292
A Medley of Themes ....................................... 293
Clinical and Research Applications ........................... 293
Chorion Laeve .............................................. 294
Intermediate (Spongy) Layer ................................ 294
Chorionic Mesoderm ....................................... 294
Trophoblast Layer .......................................... 295
Immunological Considerations Concerning the Trophoblast 296
Decidua .................................................. 296
Tensile Properties of the Membranes ........................... 297
Pathology of the Membranes .................................. 297
Pre term Rupture of the Membranes .......................... 297
Cysts, Tumors, and Hemorrhage .............................. 299
Amnionic Fluid Embolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 301
Meconium ................................................ 304
Gastroschisis .............................................. 310
Epidermolysis Bullosa ...................................... 311
Amnion Nodosum ......................................... 311
Amnionic Bands ........................................... 314
Extramembranous Pregnancy ................................ 320
References .................................................. 322
XIV Contents
12. Anatomy and Pathology of the Umbilical Cord and Major
Fetal Vessels ................................................ 335
Development ................................................ 335
Amnionic Epithelium ......................................... 335
Wharton's Jelly .............................................. 337
Umbilical Vessels ............................................ 338
Structure of Umbilical Vessels ............................... 338
Innervation ............................................... 339
Contractility of Umbilical Vessels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 339
Hyrtl Anastomosis, False Knots, and Hoboken Nodes . . . . . . . . . . 341
Embryonic Remnants. . ... ..... . ........ . . ..... . . ............. 341
Allantois .................................................. 341
Omphalomesenteric Duct ................................... 343
Spiral Turns of the Cord ...................................... 346
Length of the Cord ........................................... 348
Abnormal Length, Nuchal Cord ............................. 349
Site of Cord Insertion ...................................... 352
Furcate Cord Insertion ..................................... 353
Velamentous Cord Insertion ................................. 353
Placental Surface Vessels ...................................... 359
Nucleated Red Blood Cells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 362
Cysts and Edema ............................................ 362
Single Umbilical Artery ....................................... 363
Placental Transfusion ......................................... 366
Knots ...................................................... 367
False Knots .................................................. 368
Strictures ................................................... 369
Rupture .................................................... 371
Hematoma .................................................. 371
Varices and Aneurysms ............................. ,......... 373
Thrombosis of the Umbilical Vessels ............................ 375
Thrombosis of the Placental Vascular Tree ....................... 379
Tumors of the Umbilical Cord ................................. 384
References .................................................. 386
13. Placental Shape Aberrations ................................ 399
Site of Placental Attachment .................................. 399
Volumetric Growth .......................................... 400
Abnormal Shapes ("Errors in Outline") ........................ 401
Placenta Previa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 404
Placenta Membranacea ....................................... 408
Circumvallate Placenta (Extrachorial, Circummarginate
Placentas) ................................................. 410
References .................................................. 415
14. Histopathological Approach to Villous Alterations... . . . . .. 419
Microscopic Evaluation ....................................... 419
Assessment of Villous Maturation ............................ 419
Placental Insufficiency ...................................... 422
Examination of Fetal Stem Vessels . . . . . . . . . . . . . . . . . . . . . . . . . . . . 423
Examination of the Fetal Capillary Bed ....................... 423
Villous Architecture and Fibrinoid ........................... 424
Contents xv
Intervillous Space, Infarcts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 425
Abruptio Placentae ......................................... 425
Major Histopathological Findings .............................. 426
Syncytiotrophoblast ........................................ 426
Knotting of the Syncytiotrophoblast .......................... 426
Langhans' Cells ............................................ 428
Vasculosyncytial Membranes ................................ 428
Trophoblastic Basement Membrane .......................... 428
Peri villous Fibrinoid ....................................... 428
Intravillous Fibrinoid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 428
Villous Calcification ........................................ 429
Stem Vessels .............................................. 429
Nucleated Red Blood Cells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 430
Villous Capillarization ...................................... 430
Stromal Architecture and Stromal Fibrosis .................... 431
Hofbauer Cells (Macrophages) ............................... 431
InfiammatoryChanges ..... ........ ....... ....... ...... ..... 432
Villous Edema or Immaturity ................................ 432
References .................................................. 434
15. Classification of Villous Maldevelopment. . . . . . . . . . . . . . . . . . . 437
Syncytial Knotting ........................................... 437
Syncytial Knotting: Artifact or Meaningful Pathological
Finding ................................................... 437
Interpretation of Syncytial Knotting .......................... 437
Artificial Knotting as Related to Villous Shapes in
Paraffin Sections ......................................... 438
Conclusions Concerning Knotting ............................ 440
Classification of Villous Maldevelopment ........................ 440
Summarizing Diagram of Villous Maldevelopment .............. 443
Villous Maturation Score . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 443
Cases of Villous Maldevelopment .............................. 445
Synchronous Villous Immaturity . . . . . . . . . . . . . . . . . . . . . . . . . . . . 445
Persisting Villous Immaturity and Rhesus Incompatibility . . . . . . . . 447
Normal Mature Placenta .................................... 448
Preterm Villous Maturation and Villous Hypermaturity . . . . . . . . . . 449
Prolonged Pregnancy ....................................... 450
Placentas at High Altitude and Maternal Anemia
(Preplacental Hypoxia) ................................... 452
Intrauterine Growth Restriction with Preserved End-Diastolic
Umbilical Flow with or Without Preeclampsia (Uteroplacental
Hypoxia) ............................................... 453
Intrauterine Growth Restriction Combined with Absent or
Reverse End-Diastolic Umbilical Blood Flow, With or Without
Preeclampsia (Postplacental Hypoxia) . . . . . . . . . . . . . . . . . . . . . . . 454
Maternal Diabetes Mellitus ................................. 456
References .................................................. 458
16. Erythroblastosis Fetalis and Hydrops Fetalis ............... 461
Erythroblastosis Fetalis ....................................... 461
Placental Pathology in Erythroblastosis ....................... 462
Nonimmune Hydrops ........................................ 468
u-Thalassemia ............................................. 468
xvi Contents
Fetal Hemorrhage ......................................... 470
Fetal Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 471
Congenital Anomalies and Hydrops Fetalis .................... 474
Congenital Heart Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 475
Cardiac Arrhythmias ....................................... 476
Nephrotic Syndrome ....................................... 476
Parvovirus Anemia ........................................ 477
Hydrops of Unknown Etiology .............................. 481
References .......... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 482
17. Transplacental Hemorrhage, Cell Transfer, Trauma......... 492
Transplacental Blood and Cell Transfer ......................... 492
Trauma..................................................... 492
Placenta in Hemorrhage ...................................... 497
Technique for Identification of Fetal Red Blood Cells ............. 499
Significant Transplacental Hemorrhage .......................... 501
Fetal Consequences of Massive Hemorrhage Across the
Placenta .................................................... 503
Other Fetal Blood Elements Passing Through the Placenta ........ 507
Mother-to-Fetus Transfer of Cells .............................. 508
References .................................................. 509
18. Fetal Storage Disorders ..................................... 516
References .................................................. 520
19. Maternal Diseases Complicating Pregnancy: Diabetes,
Tumors, Preeclampsia, Lupus Anticoagulant ................ 523
Maternal Diseases ........................................... 523
Hematological Disorders .................................... 530
Endocrine Disorders ....................................... 534
Diabetes Mellitus During Pregnancy .......................... 534
Maternal Neoplasms ....................................... 538
Hypertensive Disorders ....................................... 542
Preeclampsia .............................................. 542
Animal Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 542
Placental Pathology of Preeclampsia .......................... 543
Decidual Arteriopathy ...................................... 543
Infarcts ................................................... 549
Abruptio Placentae ......................................... 551
Fetal Effects of Abruptio Placentae ........................... 557
Other Placental Changes in Preeclampsia ..................... 557
Etiology of Toxemia, Pregnancy-Induced Hypertension, or
Preeclampsia ............................................ 560
Lupus Erythematosus and Lupus Anticoagulant .................. 562
Lupus Erythematosus ...................................... 562
Lupus Anticoagulant ....................................... 565
References ......................................... ......... 571
20. Infectious Diseases.......................................... 591
Chorioamnionitis ............................................ 591
Macroscopic Appearance ................................... 591
Microscopic Appearance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 592
Contents XVll
General Considerations of Chorioamnionitis .................. . 606
Specific Microorganisms ................................... . 608
Bacterial Vaginosis .......................................... . 622
Syphilis .................................................... . 622
Necrotizing Funisitis ......................................... . 625
Other Spirochetal Diseases ................................... . 628
Fungus Infections ........................................... . 629
Virus Infections and Villitides ................................. . 632
Cytomegalovirus Infection ................................. . 632
Herpes Simplex Virus Infection ............................. . 636
Varicella (Chickenpox) .................................... . 640
Epstein-Barr Virus ....................................... . 641
Smallpox, Vaccinia, Alastrim, and Parvovirus B19 ............. . 641
Enteroviruses ............................................ . 642
Influenza, Mumps, Rabies .................................. . 643
Hepatitis ................................................ . 643
Rubella (German Measles) ................................. . 644
Rubeola (Measles) ........................................ . 645
Human Immunodeficiency Virus Infection .................... . 645
Toxoplasmosis .............................................. . 646
Kala-Azar .................................................. . 650
Chagas'Disease ............................................ . 650
Babesiosis, Trichomoniasis, Rickettsia, and Ehrlichia ............. . 651
Malaria .................................................... . 652
Other Parasitic Infections .................................... . 653
Villitis of Unknown Etiology ................................. . 653
References ................................................. . 659
21. Abortion, Placentas of Trisomies, and Immunological
Considerations of Recurrent Reproductive Failure ........ . 685
Anatomical Findings ........................................ . 687
Summary of Placental Findings in Chromosomally Defined
Abortions ........................................... . 690
Trisomies ................................................ . 690
Polyploidies .............................................. . 692
Monosomy X ............................................. . 693
Induced Abortions .......................................... . 695
Incomplete Abortion ........................................ . 699
Placenta in Chorionic Villus Sampling ......................... . 700
Trisomic Placentas .......................................... . 703
Chemical Markers and Trisomy ............................. . 704
Other Findings ............................................. . 704
Recurrent or Habitual Abortion .............................. . 705
References ................................................. . 709
22. Molar Pregnancies ......................................... . 718
Hydatidiform Moles and Partial Moles ......................... . 718
Hydatidiform Moles ......................................... . 718
Incidence ................................................ . 721
Genetics ................................................. . 722
Morphology .............................................. . 726
Other Attributes .......................................... . 731
Deportation ................................................ . 732
XVlll Contents
Chorioadenoma Destruens (Invasive Mole) ................... . 734
Therapy ................................................. . 735
Ectopic Moles ............................................ . 737
Partial Hydatidiform Mole ................................... . 737
Mole and Fetus ........................................... . 740
Partial Hydatidiform Mole with Twin Gestation ............... . 741
References ................................................. . 743
23. Trophoblastic Neoplasm ................................... . 754
Choriocarcinoma ........................................... . 754
Choriocarcinoma In Situ and Choriocarcinoma Coincident
with Pregnancy ......................................... . 757
Trophoblastic Pseudotumor-Exaggerated Placental Site-Placental
Site Trophoblastic Tumor (PSTT)-Placental Site Nodule
(PSN)-Epithelioid Trophoblastic Tumor .................... . 761
Ultrastructure of Trophoblastic Tumors ...................... . 767
Antigenic Studies of Trophoblastic Tumors ................... . 767
Epidemiology of Choriocarcinoma .......................... . 768
Endocrine Aspects of Gestational Trophoblastic Neoplasia ...... . 768
Ectopic Choriocarcinomas; Tumors in Men ................... . 769
Therapy of Gestational Trophoblastic Neoplasia .............. . 770
Choriocarcinoma in Animals ................................. . 771
Choriocarcinoma in Cell Lines and Genetics .................... . 771
References ................................................. . 771
24. Benign Tumors and Chorangiosis ......................... .. 778
Angiomas ................................................. . 778
Other Benign Tumors ....................................... . 785
Chorangiosis-Chorangiomatosis ............................. . 786
References ................................................. . 787
25. Multiple Pregnancy ........................................ . 790
Zygosity ................................................... . 790
The Placenta in the Study of Zygosity ......................... . 792
Causes and Incidence of Multiple Births ....................... . 796
Third Type of Twin .......................................... . 801
Thinning Incidence ......................................... . 801
Superfetation and Superfecundation ........................... . 804
Vascular Anatomy of Twin Placentas .......................... . 804
Monoamnionic, Monochorionic Twin Placenta ................... . 812
Diamnionic, Monochorionic Twin Placenta ...................... . 824
Diamnionic, Dichorionic Twin Placenta ........................ . 826
Vanishing Twin Phenomenon ................................. . 827
Fetus Papyraceus ........................................... . 833
Transfusion Syndrome ....................................... . 837
Acardiac Twins ............................................. . 850
Conjoined Twins ............................................ . 858
Sacrococcygeal Teratoma and Epignathus ...................... . 862
Congenital Anomalies ....................................... . 862
Cytogenetics and "Heterokaryotypic MZ Twins" ................ . 864
Chimerism, Mosaicism ...................................... . 865
Whole-Body Chimerism ..................................... . 866
Contents xix
Triplets and Higher Multiple Births ............................. 867
Twins in Abortion and Ectopic Pregnancy ....................... 875
Morbidity and Mortality ...................................... 876
Hormones in Twin Pregnancy .................................. 878
References .................................................. 878
26. Legal Considerations ....................................... 903
Twinning Problems ........................................... 906
Inflammation ................................................ 907
The Green Placenta .......................................... 908
Vascular Abnormalities ....................................... 910
Umbilical Cord . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 910
Placental Villous Color . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 911
Other Types of Pathology ..................................... 912
References .................................................. 914
27. Glossary .................................................... 917
Bibliography ................................................ 919
28. Normative Values and Tables ............................... 920
References 925
Index........................................................ 929
1
Examination of the Placenta
Storage for examination by the pathologist. To facilitate this prac-
tice, storage is required so that placentas are available
Most placentas are normal, as are most babies. Therefore, when needed. The American College of Obstetricians
an examination of all placentas may not be warranted and Gynecologists, on the other hand, has suggested, sur-
although this has been repeatedly advocated. Practical prisingly, that the routine study of the placenta is not war-
guidelines, including indications for the examination, ranted (ACOG, 1991), a decision with which we strongly
have been published by the College of American Pathol- disagree.
ogists (Langston et aI., 1997). This reference describes in Placentas should not be frozen before examination, as
tabular form the major abnormalities and their associa- freezing obliterates the most useful histological charac-
tion with clinical features. Booth et al. (1997) inquired teristics and makes even the macroscopic examination
what reasons constituted the submission of a placenta for more difficult. We believe that formalin fixation has a
examination and found, regrettably, that it was cesarean similar unwanted effect. It is best to store the delivered
section delivery. This is hardly a good reason, as we show placentas in containers, such as plastic jars. We have
here. A large number of surgical deliveries are repeat found ice cream cartons made from Styrofoam to be the
sections and have little impact on perinatal problems for most convenient and least expensive; cardboard contain-
which placental examination might be useful. Altshuler ers absorb the fluids, and the placentas tend to stick to
and Hyde (1996), on the other hand, found that 92% of them. These containers can also be readily labeled and
placentas for which an examination was requested by stored in a refrigerator at 4°C. In this state, the placenta
the obstetrician or neonatologist had relevant pathology. is preserved for a meaningful examination for many days.
Salafia and Vintzileos (1990) made a strong plea for the Autolysis is minimal. We cannot agree with the opinion
study of all placentas by pathologists. We concur with this of Naeye (1987) that this storage causes significant
view, as the sporadic examination does not provide suffi- artifacts that render subsequent examination difficult.
cient training for young pathologists and it does not allow Indeed, the immediate fixation of the organ in formalin,
the "routine" pathologist to obtain sufficient background recommended by others (Bartholomew et aI., 1961) as a
knowledge as to what constitutes a truly normal placenta. good means to evaluate the extent of infarction, makes
Another reason for the examination of all placentas is the placenta more difficult to evaluate critically, aside
today's litigious climate, which makes study of placentas from the storage problems, expense, and odor. Prior fix-
highly desirable (see Chapter 26). Furthermore, it has ation, of course, also makes tissue culture, bacteriological
been shown repeatedly that a placental examination is examination, and other procedures more difficult or
needed to understand the causes of perinatal deaths. impossible. For maximal convenience, it is a good idea to
Most recently this was demonstrated, especially for still- have a refrigerator with seven shelves, labeled Monday
births, by the study of Las Heras et al. (1994). The most through Sunday, and to discard the normal placentas
important lesions were found in the umbilical cord from one shelf when the next similar weekday arrives. In
(18%), with inflammatory lesions being second. Because this way, all placentas from problem births are available
placentas differ widely in shape, size, and appearance, the for study.
novice must become familiar with this spectrum of pla- During storage the placenta loses some weight. In part,
cental shapes. To do so, a large number of placentas must the loss is caused by evaporation, but most weight is lost
be examined routinely. In hospitals with large numbers of by leakage of blood and serum occasioned by the weight
deliveries, however, it may be prudent to select placentas of placental tissue resting on other portions. The quantity
