Pathology of the human placenta
Preface. v
1. Examination of the Placenta. 1
Macroscopic Examination. 1
Storage. 1
Selection. 2
Photography. 2
Examination. 2
Placentas of Multiple Births. 7
Fixation. 8
Special Procedures. 10
References. 11
2. Macroscopic Features of the Delivered Placenta. 13
Fetal Surface. 13
Maternal Surface. 13
The Terms Fetal Placenta and Maternal Placenta. 15
References. 15
3. Microscopic Survey. 16
Typical Histologic Features of the First Trimester Placenta. 16
Typical Histologic Features of the Third Trimester Placenta. 20
Immunohistochemical Markers. 24
4. Placental Types. 30
Placental Shapes. 32
Types of Maternofetal Interdigitation. 34
Maternofetal Barrier. 35
Maternofetal Blood Flow Interrelations. 37
Placental Types and Phylogeny. 37
Human Placenta. 38
References. 40
5. Early Development of the Human Placenta. 42
Prelacunar Stage. 42
Lacunar Stage. 44
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. 54
Syncytiotrophoblastic Cytoskeleton. 55
Specialized Regions of the Villous Surface. 55
Syncytiotrophoblast with Prevailing Rough
Endoplasmic Reticulum. 55
Syncytiotrophoblast with Prevailing Smooth
Endoplasmic Reticulum. 57
Vasculosyncytial Membranes. 59
Syncytial Lamellae Covering Langhans Cells. 61
Syncytial Knots, Sprouts, and Bridges. 61
Transtrophoblastic Channels. 64
Trophoblastic Blebbing. 64
Villous Cytotrophoblast Langhans Cells. 65
Cytotrophoblast Cell Types. 66
Nematosomes. 70
Endocrine Activities of the Villous Cytotrophoblast. 70
Trophoblast Turnover and Syncytial Fusion. 72
Quantitation of Trophoblast Turnover. 72
Why Does Syncytiotrophoblast Survival Depend
on Syncytial Fusion. 72
Trophoblastic Differentiation and Apoptosis Cascade. 73
Molecular Mechanisms of Syncytial Fusion. 76
Phosphatidylserine Flip as Fusion Signal. 76
Junctional and Adhesion Molecules as Fusion Mediators. 76
The ADAM Family of Fusogenic Proteins. 76
Endogenous Retroviral Envelope Proteins of the HERV Family
Syncytins and Their Receptors. 77
Molecular Control of Syncytial Fusion. 78
The Role of Oxygen and Cytokines in Trophoblast Proliferation
and Fusion. 79
The Impact of Trophoblast Turnover on
Syncytiotrophoblast Specialization. 81
Trophoblastic Basement Membrane. 82
Connective Tissue. 82
Mesenchymal Cells V Cells. 82
Fibroblasts VD Cells and VDA Cells. 83
Myofibroblasts VDAG Cells and VDAGM Cells. 84
Matrix Components of the Villous Stroma. 86
Hofbauer Cells Villous Macrophages. 87
First Descriptions. 87
Morphology. 87
Occurrence and Distribution. 90
Origin. 90
Immunologic Aspects. 91
Other Free Connective Tissue Cells. 93
Basic Structure of the Vessel Walls. 93
Fetal Capillaries. 94
Large Fetal Vessels. 94
Vasomotor Control. 96
Fibrinoid of the Villous Trees. 96
Perivillous Fibrinoid. 96
Intravillous Fibrinoid. 98
References. 99
7. Architecture of Normal Villous Trees. 121
Classification of Villous Types. 121
Stem Villi. 121
Immature Intermediate Villi. 126
Mature Intermediate Villi. 128
Terminal Villi. 129
Mesenchymal Villi. 133
Immunohistochemistry of Villous Types. 134
Differentiation and Maturation of Villous Types. 137
Development of the Mesenchymal Villi. 137
Development and Fate of Immature Intermediate Villi. 138
Development of Stem Villi. 138
Development of the Mature Intermediate Villi. 140
Development of the Terminal Villi. 140
Angioarchitecture of Villi. 140
Vascular Arrangement in Immature Villi. 140
Larger Vessels of Stem Villi. 141
Paravascular Capillary Net of Stem Villi. 141
Arrangement of Vessels in Mature Intermediate and
Terminal Villi. 143
Sinusoids of Terminal Villi. 145
Fetoplacental Angiogenesis as the Driving Force for
Villous Development. 146
General Aspects of Placental Vasculogenesis
and Angiogenesis. 147
Vasculogenesis 1 Origin of Hemangiogenic Progenitor Cells
Days 15 to 21. 148
Vasculogenesis 2 Formation of Endothelial Tubes
Days 21 to 32. 148
Angiogenesis 1 Branching Angiogenesis Day 32 to Week 25. 153
Angiogenesis 2 Formation of Stem Vessels and Regression of
Capillaries in Stem Villi Weeks 15 to 32. 153
Angiogenesis 3 Prevailing Nonbranching Angiogenesis
Week 25 to Term. 154
Oxygen and Oxygen-Controlled Growth Factors as Regulators of
Villous and Vascular Development. 155
The Special Role of Oxygen in the Placenta. 155
Types of Hypoxia and Its Effects on Villous Development. 155
Evidence for Oxygen-Controlled Fetoplacental Angiogenesis. 157
Oxygen-Controlled Angiogenic Growth Factors. 157
The Timing Mismatch Between Changes in Oxygenation and
Morphologic Changes. 158
Oxygen and Villous Trophoblast. 159
Oxygen and Villous Stroma. 159
Oxygen and Intervillous Circulation. 159
Hormones as Regulators of Villous Development. 160
Intervillous Space as Related to the Villous Trees. 160
Width of the Intervillous Space. 161
Organization of Villous Trees. 161
Histopathologic Importance of Inhomogeneity of
Villous Trees. 164
Fetomaternal Flow Interrelations. 164
References. 165
8. Characterization of the Developmental Stages. 174
Stages of Development. 174
Nucleated Red Blood Cells. 185
References. 189
9. Nonvillous Parts and Trophoblast Invasion. 191
H.G. Frank and P. Kaufmann
Extravillous Trophoblast. 191
Historical Aspects and Nomenclature. 191
Extravillous Trophoblast Is a Tissue of Its Own. 193
Proliferation Patterns of Extravillous Trophoblast and
the Invasive Pathway. 194
Stages of Extravillous Trophoblast Differentiation Within
the Invasive Pathway. 196
One Stem Cell Origin for Villous Syncytiotrophoblast and
the Extravillous Trophoblast. 200
Cytokines and Hormones Controlling Differentiation
of Extravillous Trophoblast. 201
Extracellular Matrix Secretion Along the Invasive Pathway. 204
Extracellular Matrix Receptors Integrins. 204
Other Cell Adhesion Molecules and Gap Junction Molecules. 206
Proteinases, Activators, and Inhibitors Involved in
Trophoblast Invasion. 207
Nitric Oxide and Trophoblast Invasion. 209
Major Basic Protein. 209
Cell Surface Carbohydrates. 211
MHC Class I Molecules. 212
Normal Extravillous Trophoblast Cells Are Never Proliferative
and Invasive at One Time. 213
Oxygen-Mediated Regulation of the Invasive Pathway. 214
Extracellular pH as Trigger of Trophoblast Invasion. 215
Trophoblastic Mechanisms Limiting Trophoblast Invasion. 215
Endocrine Activities of Extravillous Trophoblast. 216
Does Extravillous Trophoblast Differ from One Nonvillous Part
to the Other. 217
Decidua. 217
Composition of Decidua. 217
Endometrial Stromal Cells and Decidual Cells. 218
Endocrine and Paracrine Aspects of Decidua. 220
Functional Considerations of Decidualization. 221
B Cells and T Cells. 222
Endometrial Large Granular Lymphocytes Endometrial NK
Cells and uNK Cells. 223
Macrophages. 224
Glandular Residues. 225
Decidual Extracellular Matrix. 225
Fibrinoid. 226
Definition and Historical Remarks. 226
Types of Fibrinoid. 227
Origin of Fibrinoids. 230
Interactions Between Matrix-Type and Fibrin-Type Fibrinoid. 231
Functions of Fibrinoid. 231
Trophoblast Invasion as a Result of Deciduo-Trophoblastic
Interactions. 233
Calcification. 236
Chorionic Plate. 239
Development. 239
Structure at Term. 239
Amnion. 239
Spongy Layer. 240
Chorionic Mesoderm. 241
Extravillous Cytotrophoblast. 241
Langhans Fibrinoid Layer. 242
Marginal Zone. 243
Subchorial Closing Ring. 243
Trabeculae. 244
Marginal Sinus. 244
Basal Plate. 244
Trophoblastic Shell and Development of the Basal Plate. 244
Layers of the Basal Plate at Term. 246
Uteroplacental Vessels. 249
Development. 249
Number and Position of the Uteroplacental Vessels. 251
Importance of Physiologic Changes of Uteroplacental Arteries. 252
Stages of Physiologic Changes in Uteroplacental Arteries. 252
Sites and Routes of Endovascular Trophoblast Invasion. 254
Trophoblast-Endothelial Adhesion Mechanisms. 255
The Role of Macrophages in the Control of Endovascular
Trophoblast Invasion. 256
Incompetent Trophoblast Invasion or Exaggerated Maternal Defense as Causes for Maladaptation of
Uteroplacental Arteries. 257
Structure of Uteroplacental Veins. 258
Intramural Fibrinoid of Uteroplacental Arteries and Veins. 260
Functional Aspects of Uteroplacental Vessels. 260
Septa, Cell Islands, and Cell Columns. 261
Septa. 261
Cell Islands. 264
Cell Columns. 265
Pathology of Trophoblast Invasion. 268
Placenta Accreta. 268
Placenta Increta and Percreta. 271
Uterine Rupture. 273
Placenta in Ectopic Tubal Pregnancy. 275
Placenta in Abdominal Pregnancy. 276
Cysts and Breus Mole. 277
Maternal Floor Infarction. 281
Decidual Degeneration. 284
References. 287
10. Involution of Placental Site Retained Placenta. 313
Involution of the Placental Site. 313
Subinvolution. 316
Placental Polyps. 316
Involution of a Remaining Placenta. 319
References. 319
11. Anatomy and Pathology of the Placental Membranes. 321
Overview. 321
Development. 323
Amnion. 326
Amnionic Epithelium Different Cell Types or Cell Degeneration. 327
Cytologic and Functional Aspects of the Amnionic Epithelium. 327
Amnionic Fluid. 330
Chromosomal Determinations. 331
Cellular Metaplasia and Glycogen. 331
Amnionic Mesoderm. 333
A Medley of Themes. 334
Clinical and Research Applications. 334
Chorion Laeve. 335
Intermediate Spongy Layer. 335
Chorionic Mesoderm. 335
Trophoblast Layer. 336
Decidua. 337
Tensile Properties of the Membranes. 338
Pathology of the Membranes. 338
Preterm Rupture of the Membranes. 338
Cysts, Tumors, and Hemorrhage. 340
Amniotic Fluid Embolism. 342
Meconium. 345
Gastroschisis. 354
Epidermolysis Bullosa. 354
Amnion Nodosum. 355
Amnionic Bands. 358
Extramembranous Pregnancy. 364
References. 366
12. Anatomy and Pathology of the Umbilical Cord. 380
Development. 380
Amnionic Epithelium. 380
Wharton s Jelly. 381
Structure of Umbilical Vessels. 383
Innervation. 384
Contractility of Umbilical Vessels. 385
Hyrtl s Anastomosis, False Knots, and Hoboken Nodes. 386
Allantois. 388
Omphalomesenteric Duct. 389
Spiral Turns of the Cord. 392
Length of the Cord. 394
Abnormal Length, Nuchal Cord. 395
Site of Cord Insertion. 401
Furcate Cord Insertion. 402
Velamentous Cord Insertion. 403
Placental Surface Vessels. 407
Nucleated Red Blood Cells NRBCs. 410
Cysts and Edema. 411
Single Umbilical Artery. 413
Placental Transfusion. 415
Knots. 416
False Knots. 418
Strictures. 419
Rupture. 420
Hematoma. 421
Varices and Aneurysms. 423
Thrombosis of the Umbilical Vessels. 426
Thrombosis of the Placental Vascular Tree. 428
Tumors of the Umbilical Cord. 434
References. 435
13. Placental Shape Aberrations. 452
Site of Placental Attachment. 452
Volumetric Growth. 454
Abnormal Shapes Errors in Outline”. 454
Placenta Previa. 457
Placenta Membranacea. 462
Circumvallate Placenta Extrachorial,
Circummarginate Placentas. 464
References. 468
14. Histopathologic Approach to Villous Alterations. 473
How to Assess Villous Histopathology. 473
Assessment of Villous Maturation. 473
Placental Insufficiency. 476
Examination of Fetal Stem Vessels. 477
Examination of the Fetal Capillary Bed. 477
Villous Architecture and Fibrinoid. 478
Intervillous Space, Infarcts. 479
Abruptio Placentae. 480
Major Histopathologic Findings. 480
Syncytiotrophoblast. 480
Knotting of the Syncytiotrophoblast. 480
Langhans Cells. 482
Vasculosyncytial Membranes. 482
Trophoblastic Basement Membrane. 482
Perivillous Fibrinoid. 482
Intravillous Fibrinoid. 483
Villous Calcification. 483
Stem Vessels. 483
Nucleated Red Blood Cells. 484
Villous Capillarization. 484
Stromal Architecture and Stromal Fibrosis. 485
Hofbauer Cells Macrophages. 486
Inflammatory Changes. 486
Villous Edema or Immaturity. 486
References. 488
15. Classification of Villous Maldevelopment. 491
Three-Dimensional Interpretation of Two-Dimensional Sections. 491
Syncytial Knotting Artifact or Meaningful Pathologic
Finding. 491
Interpretation of Syncytial Knotting. 491
Artificial Knotting as Related to Villous Shapes in
Paraffin Sections. 494
Conclusions Concerning Knotting. 497
Classification of Villous Maldevelopment. 497
Summarizing Diagram of Villous Maldevelopment. 497
Villous Maturation Score. 500
Cases of Villous Maldevelopment. 502
Synchronous Villous Immaturity. 502
Persisting Villous Immaturity and Rhesus Incompatibility. 502
Normal Mature Placenta. 504
Preterm Villous Maturation and Villous Hypermaturity. 506
Prolonged Pregnancy. 507
Placentas at High Altitude and Maternal Anemia
Preplacental Hypoxia. 508
Intrauterine Growth Restriction with Preserved End-Diastolic Umbilical Flow in the Third Trimester, with or Without
Late-Onset Preeclampsia Uteroplacental Hypoxia. 509
Intrauterine Growth Restriction Combined with Absent or Reverse End-Diastolic Umbilical Blood Flow in the Second Trimester, with or Without Early-Onset
Preeclampsia Postplacental Hypoxia. 511
Preeclampsia. 512
HELLP Syndrome Postplacental Hypoxia. 513
Maternal Diabetes Mellitus. 515
References. 516
16. Erythroblastosis Fetalis and Hydrops Fetalis. 519
Erythroblastosis Fetalis. 519
Placental Pathology in Erythroblastosis. 520
Nonimmune Hydrops. 526
a-Thalassemia. 527
Fetal Hemorrhage. 529
Fetal Tumors. 530
Congenital Anomalies and Hydrops Fetalis. 532
Congenital Heart Disease. 533
Cardiac Arrhythmias. 534
Nephrotic Syndrome. 534
Parvovirus Anemia. 535
Hydrops of Unknown Etiology. 540
References. 541
17. Transplacental Hemorrhage, Cell Transfer, Trauma. 552
Transplacental Blood and Cell Transfer. 552
Trauma. 552
Placenta in Hemorrhage. 558
Technique for Identification of Fetal Red Blood Cells. 559
Significant Transplacental Hemorrhage. 561
Fetal Consequences of Massive Hemorrhage Across the Placenta. 563
Other Fetal Blood Elements Passing Through the Placenta. 568
Mother-to-Fetus Transfer of Cells. 569
References. 569
18. Fetal Storage Disorders. 577
References. 582
19. Maternal Diseases Complicating Pregnancy Diabetes,
Tumors, Preeclampsia, Lupus Anticoagulant. 584
Maternal Diseases. 584
Hematologic Disorders. 592
Endocrine Disorders. 596
Diabetes Mellitus During Pregnancy. 596
Maternal Neoplasms. 600
Hypertensive Disorders. 604
Preeclampsia. 604
Animal Models. 605
Placental Pathology of Preeclampsia. 605
Decidual Arteriopathy. 606
Infarcts. 612
Abruptio Placentae. 615
Fetal Effects of Abruptio Placentae. 620
Other Placental Changes in Preeclampsia. 620
Etiology of Toxemia, Pregnancy-Induced Hypertension, or
Preeclampsia. 623
Lupus Erythematosus and Lupus Anticoagulant. 625
Lupus Erythematosus. 625
Lupus Anticoagulant. 630
References. 634
20. Infectious Diseases. 657
Chorioamnionitis. 657
Macroscopic Appearance. 657
Microscopic Appearance. 660
General Considerations of Chorioamnionitis. 674
Specific Microorganisms. 676
Mycoplasma Hominis and Ureaplasma. 687
Chlamydia Trachomatis and C Psittaci. 689
Bacterial Vaginosis. 690
Syphilis. 690
Necrotizing Funisitis. 694
Other Spirochetal Diseases. 696
Fungus Infections. 696
Virus Infections and Villitides. 700
Cytomegalovirus Infection. 700
Herpes Simplex Virus Infection. 706
Varicella Chickenpox. 709
Epstein-Barr Virus. 710
Smallpox, Vaccinia, Alastrim, and Parvovirus B19. 710
Enteroviruses. 712
Influenza, Mumps, Rabies. 712
Hepatitis. 712
Rubella German Measles and Other Viral Infections. 713
Rubeola Measles. 714
Human Immunodeficiency Virus Infection. 715
Toxoplasmosis. 716
Kala-Azar. 720
Chagas Disease. 720
Babesiosis, Trichomoniasis, Rickettsia, and Ehrlichia. 722
Malaria. 722
Other Parasitic Infections. 724
Villitis of Unknown Etiology. 724
References. 732
21. Abortion, Placentas of Trisomies, and Immunologic
Considerations of Recurrent Reproductive Failure. 762
Anatomic Findings. 764
Summary of Placental Findings in Chromosomally
Defined Abortions. 768
Trisomies. 768
Polyploidies. 770
Monosomy X. 772
Induced Abortions. 772
Incomplete Abortion. 777
Placenta in Chorionic Villus Sampling. 778
Trisomic Placentas. 781
Chemical Markers and Trisomy. 782
Recurrent or Habitual Abortion. 784
References. 787
22. Molar Pregnancies. 797
Hydatidiform Moles and Partial Moles. 797
Hydatidiform Moles. 797
Other Attributes. 811
Therapy. 815
Partial Hydatidiform Mole. 817
References. 825
23. Trophoblastic Neoplasms. 837
Choriocarcinoma. 837
Choriocarcinoma In Situ and Choriocarcinoma Coincident
with Pregnancy. 843
Chorangiocarcinoma. 846
Exaggerated Placental Site Placental Site Nodule, Placental Site
Trophoblastic Tumor, and Epithelioid Trophoblastic Tumor. 846
Ultrastructure of Trophoblastic Tumors. 851
Antigenic Studies of Trophoblastic Tumors. 851
Epidemiology of Choriocarcinoma. 852
Endocrine Aspects of Gestational Trophoblastic Neoplasia. 852
Ectopic Choriocarcinomas Tumors in Men. 853
Therapy of Gestational Trophoblastic Neoplasia. 854
Choriocarcinoma in Anamils. 855
Choriocarcinoma in Cell Lines and Genetics. 855
References. 856
24. Benign Tumors and Chorangiosis. 863
Angiomas. 863
Other Benign Tumors. 870
Chorangiosis and Chorangiomatosis. 871
Mesenchymal Dysplasia and the Beckwith-Wiedemann
Syndrome. 873
References. 873
25. Multiple Pregnancies. 877
Zygosity. 877
The Placenta in the Study of Zygosity. 879
Causes and Incidence of Multiple Births. 885
Third Type of Twin. 890
Twinning Incidence. 891
Superfetation and Superfecundation. 893
Vascular Anatomy of Twin Placentas. 893
Monoamnionic Monochorionic Twin Placenta. 902
Diamnionic Monochorionic Twin Placenta. 915
Diamnionic Dichorionic Twin Placenta. 917
Vanishing Twin Phenomenon. 919
Fetus Papyraceus. 923
Twin-to-Twin Transfusion Syndrome. 928
Acardiac Twins. 941
Conjoined Twins. 950
Sacrococcygeal Teratoma and Epignathus. 953
Congenital Anomalies. 955
Cytogenetics and Heterokaryotypic Monozygotic Twins. 956
Chimerism and Mosaicism. 957
Whole-Body Chimerism. 959
Triplets and Higher Multiple Births. 960
Twins in Abortion and Ectopic Pregnancy. 967
Morbidity and Mortality. 968
Hormones in Twin Pregnancy. 971
References. 971
26. Legal Considerations. 1001
Twinning Problems. 1004
Inflammation. 1005
The Green Placenta. 1007
Vascular Abnormalities. 1008
Umbilical Cord. 1009
Placental Villous Color. 1009
Other Types of Pathology. 1010
References. 1013
27. Glossary.1016
28. Normative Values and Tables.1019