Liapis / Wang Pathology of Solid Organ Transplantation

1. Auflage 2010
ISBN: 978-3-540-79343-4
Verlag: Springer Berlin Heidelberg
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 405 Seiten

Because of the progress in diagnostic transplantation pathology interpretation of transplant biopsies is increasingly becoming an attractive field for general surgical pathologists. The book focuses on the pathology of transplantation in the following organs: kidney, liver, lungs, heart, pancreas and small intestine. An introductory section addresses common entities that may complicate all transplant recipients such as infections, post-transplant lymphoproliferative disease and graft versus host disease, followed by 6 sections with detailed manifestations of rejection in each organ. This comprehensive, well-illustrated book serves the needs and meets the requirements of pathologists in training and those practicing in centers with limited volume of transplant biopsies in daily practice.

Autoren/Hrsg.

Liapis, Helen

Wang, Hanlin L.

Inhaltsverzeichnis

1;Pathology of Solid Organ Transplantation;2
1.1;Copyright Page;3
1.2;Dedication;4
1.3;Preface;5
1.4;Contents;8
1.5;Part I Immunology, Clinical, and LaboratoryAspects of Organ Transplantation;10
1.5.1;1: Immunology of Organ Transplantation;11
1.5.1.1;1.1 Introduction;11
1.5.1.2;1.2 Basic Transplantation Immunology;11
1.5.1.2.1;1.2.1 Components of the Immune System;11
1.5.1.3;1.3 The Adaptive Alloimmune Response;11
1.5.1.3.1;1.3.1 Recognition of Alloantigen;12
1.5.1.3.2;1.3.2 Cellular Alloimmunity;12
1.5.1.3.3;1.3.3 Humoral Alloimmunity;13
1.5.1.3.4;1.3.4 Resolution of the Alloimmune Response;14
1.5.1.3.5;1.3.5 Transplant Tolerance;14
1.5.1.4;1.4 Organ Specific Effects and Clinical Applications of Transplant Immunology;15
1.5.1.5;References;15
1.5.2;2: Current Concepts of Immunosuppression and Side Effects;18
1.5.2.1;2.1 Introduction;18
1.5.2.2;2.2 Induction Drugs;18
1.5.2.3;2.3 OKT 3;19
1.5.2.3.1;2.3.1 Mechanism of Action;19
1.5.2.3.2;2.3.2 Efficacy;19
1.5.2.3.3;2.3.3 Side Effects;19
1.5.2.4;2.4 IL-2 Receptor Antagonists (Anti CD25 Antibodies);20
1.5.2.4.1;2.4.1 Mechanism;20
1.5.2.4.2;2.4.2 Dosage;20
1.5.2.4.3;2.4.3 Efficacy;20
1.5.2.4.4;2.4.4 Side Effects;21
1.5.2.5;2.5 Polyclonal Antibodies (Thymoglobulin and ATGAM);22
1.5.2.5.1;2.5.1 Mechanism of Action;22
1.5.2.5.2;2.5.2 Dosage;22
1.5.2.5.3;2.5.3 Clinical Efficacy;22
1.5.2.5.4;2.5.4 Side Effects;22
1.5.2.6;2.6 Alemtuzumab;23
1.5.2.6.1;2.6.1 Mechanism of Action;23
1.5.2.6.2;2.6.2 Dosage;23
1.5.2.6.3;2.6.3 Clinical Efficacy;23
1.5.2.6.4;2.6.4 Side Effects;23
1.5.2.7;2.7 Maintenance Drugs;24
1.5.2.7.1;2.7.1 Prednisone;24
1.5.2.7.1.1;2.7.1.1 Mechanism of Action;24
1.5.2.7.1.2;2.7.1.2 Dosage;24
1.5.2.7.1.3;2.7.1.3 Clinical Efficacy;24
1.5.2.7.1.4;2.7.1.4 Side Effects;25
1.5.2.7.2;2.7.2 Calcineurin Inhibitors;25
1.5.2.7.2.1;2.7.2.1 Mechanism of Action;25
1.5.2.7.2.2;2.7.2.2 Dosage;25
1.5.2.7.2.3;2.7.2.3 Clinical Efficacy;25
1.5.2.7.2.4;2.7.2.4 Side Effects;26
1.5.2.7.3;2.7.3 Mycophenolate;27
1.5.2.7.3.1;2.7.3.1 Mechanism of Action;27
1.5.2.7.3.2;2.7.3.2 Dosage;28
1.5.2.7.3.3;2.7.3.3 Clinical Efficacy;28
1.5.2.7.3.4;2.7.3.4 Side Effects;28
1.5.2.7.4;2.7.4 Rapamycin (Sirolimus);28
1.5.2.7.4.1;2.7.4.1 Mechanism of Action;28
1.5.2.7.4.2;2.7.4.2 Dosage;28
1.5.2.7.4.3;2.7.4.3 Clinical Efficacy;28
1.5.2.7.4.4;2.7.4.4 Side Effects;29
1.5.2.8;2.8 Newer Immunosuppressive Medications;30
1.5.2.8.1;2.8.1 Janus Kinase (JAK) 3 Inhibitors;30
1.5.2.9;2.9 AEB-071;30
1.5.2.9.1;2.9.1 LEA 29Y (Belatacept);30
1.5.2.10;2.10 Efalizumab;31
1.5.2.11;2.11 Summary;31
1.5.2.12;References;31
1.5.3;3: Clinical Aspects of Infection;38
1.5.3.1;3.1 Introduction;38
1.5.3.2;3.2 Infections and Timing of Transplant;38
1.5.3.2.1;3.2.1 Month 1;39
1.5.3.2.2;3.2.2 Months 2–6;39
1.5.3.2.3;3.2.3 Greater than 6 Months;39
1.5.3.3;3.3 Viral Infections;39
1.5.3.3.1;3.3.1 Cytomegalovirus;39
1.5.3.4;3.4 Epstein–Barr Virus (EBV) and Posttransplant Lymphoproliferative Disorders (PTLD);42
1.5.3.5;3.5 BK Virus and Nephropathy;45
1.5.3.6;3.6 Hepatitis C;48
1.5.3.7;3.7 Parvovirus B19;48
1.5.3.8;3.8 Fungal Infections;48
1.5.3.9;3.9 Pneumocystis Jiroveci (PCP);49
1.5.3.10;3.10 Summary;49
1.5.3.11;References;49
1.5.4;4: Clinical Evaluation of Alloantibodies in Solid Organ Transplantation;51
1.5.4.1;4.1 Introduction;51
1.5.4.2;4.2 Alloantibody Specificities;51
1.5.4.2.1;4.2.1 Alloantibodies Against HLA;51
1.5.4.2.2;4.2.2 ABO Blood Group Antibodies;53
1.5.4.2.3;4.2.3 MICA;53
1.5.4.2.4;4.2.4 Alloantibodies to Non-HLA Antigens;53
1.5.4.3;4.3 Clinical Testing for Alloantibodies;54
1.5.4.3.1;4.3.1 Cytotoxicity Crossmatch;54
1.5.4.3.2;4.3.2 Solid Phase Immunoassays for Detection of Alloantibodies;56
1.5.4.3.3;4.3.3 Virtual Crossmatching and Donor Selection;56
1.5.4.3.4;4.3.4 Posttransplant Testing;57
1.5.4.3.5;4.3.5 Immunologic Accommodation;58
1.5.4.4;References;58
1.5.5;5: Frontiers in Organ Transplantation;63
1.5.5.1;5.1 Introduction;63
1.5.5.2;5.2 Growing New Kidneys;63
1.5.5.2.1;5.2.1 Immune Response to Fetal Kidney Transplants;64
1.5.5.2.2;5.2.2 Means by Which Renal Primordia are Vascularized;65
1.5.5.3;5.3 Xenotransplantation for Kidney Replacement;65
1.5.5.4;5.4 Transplantation of Renal Primordia to Enhance Host Renal Function;66
1.5.5.4.1;5.4.1 Availability of Renal Primordia;69
1.5.5.5;5.5 Growing New Endocrine Pancreas;70
1.5.5.6;5.6 Xenotransplantation Therapy for Diabetes Mellitus;72
1.5.5.7;5.7 Organogenesis of the Endocrine Pancreas;72
1.5.5.7.1;5.7.1 Type 1 Diabetes Mellitus;72
1.5.5.7.2;5.7.2 Type 2 Diabetes Mellitus;74
1.5.5.8;5.8 Summary and Conclusions;78
1.5.5.9;References;78
1.6;Part II Transplant Pathology of Organ Systems;81
1.6.1;6: Kidney;82
1.6.1.1;6.1 Introduction;82
1.6.1.1.1;6.1.1 Biopsy Types, Specimen Adequacy, and Processing;82
1.6.1.1.2;6.1.2 Expanded Criteria Donor (ECD): A Nephrologist’s Perspective;84
1.6.1.1.3;6.1.3 Donor Biopsy;86
1.6.1.1.3.1;6.1.3.1 Protocol Biopsies;92
1.6.1.1.3.2;6.1.3.2 Delayed Graft Function (DGF);93
1.6.1.1.3.3;6.1.3.3 ABO Incompatible Grafts (ABOi);94
1.6.1.2;6.2 Indication Biopsy;96
1.6.1.2.1;6.2.1 Acute Rejection;97
1.6.1.2.1.1;6.2.1.1 Tubulitis;97
1.6.1.2.1.2;6.2.1.2 Arteritis;100
1.6.1.2.1.3;6.2.1.3 Glomerulitis;101
1.6.1.2.1.4;6.2.1.4 Interstitial Inflammation;102
1.6.1.2.1.5;6.2.1.5 Plasma Cell Rich Rejection;105
1.6.1.2.1.6;6.2.1.6 Lymphoid Neogenesis;105
1.6.1.2.2;6.2.2 Chronic Rejection;106
1.6.1.2.3;6.2.3 Antibody-Mediated Rejection;110
1.6.1.2.3.1;6.2.3.1 C4d Pathogenesis, Detection Methods, and Scoring;115
1.6.1.2.3.2;6.2.3.2 C4d+ Without Histopathological Findings of AMR and or DSA;116
1.6.1.2.3.3;6.2.3.3 PTC C4d+ in Chronic AMR;116
1.6.1.2.3.4;6.2.3.4 C4d+ in Various Locations Other than PTC;116
1.6.1.2.3.5;6.2.3.5 C3 and AMR;118
1.6.1.2.4;6.2.4 Recurrent be Glomerular Disease;118
1.6.1.2.4.1;6.2.4.1 rFSGS;119
1.6.1.2.4.2;6.2.4.2 rDiabetes;123
1.6.1.2.4.3;6.2.4.3 rLupus;124
1.6.1.2.4.4;6.2.4.4 rIgA Nephropathy;124
1.6.1.2.4.5;6.2.4.5 rMembranoproliferative Glomerulonephritis (MPGN);125
1.6.1.2.4.6;6.2.4.6 rMembranous Glomerulonephritis;126
1.6.1.2.4.7;6.2.4.7 rANCA Vasculitis and rAnti-GBM Disease;126
1.6.1.2.4.8;6.2.4.8 rHUS and the Spectrum of Thrombotic Microangiopathy (TMA) in the Transplant Kidney;127
1.6.1.2.4.9;6.2.4.9 rAmyloidosis/rLCDD/rFibrillary;129
1.6.1.2.4.10;6.2.4.10 Miscellaneous Glomerular Disease Recurrence;130
1.6.1.3;6.3 Malignancy;133
1.6.1.4;6.4 De Novo Disease;135
1.6.1.4.1;6.4.1 Transplant Glomerulopathy (TGP);135
1.6.1.4.2;6.4.2 Miscellaneous De Novo Glomerular Diseases;138
1.6.1.4.3;6.4.3 CNI Toxicity;138
1.6.1.4.4;6.4.4 Crystal Deposition Disease;140
1.6.1.4.4.1;6.4.4.1 Oxalate Crystal Deposits;140
1.6.1.4.4.2;6.4.4.2 Calcium Phosphate Crystal Deposits;141
1.6.1.4.4.3;6.4.4.3 Cholesterol Embolism;142
1.6.1.4.4.4;6.4.4.4 Rhabdomyolysis;143
1.6.1.4.5;6.4.5 ATN;144
1.6.1.4.6;6.4.6 Infections: Bacterial, Fungal, Viral;145
1.6.1.4.7;6.4.7 Acute Interstitial Nephritis (AIN);148
1.6.1.4.8;6.4.8 Graft Versus Host Disease (GVHD) in the Allograft Kidney;149
1.6.1.4.9;6.4.9 Other Complications;149
1.6.1.5;6.5 Kidney Damage Secondary to Nonrenal Transplantation;150
1.6.1.5.1;6.5.1 Renal GVHD Following Bone Marrow Stem Cell Transplantation;151
1.6.1.5.2;6.5.2 Cholemic Nephrosis;153
1.6.1.6;6.6 Molecular Correlates of Renal Allograft Pathology;154
1.6.1.6.1;6.6.1 Background;154
1.6.1.6.2;6.6.2 Molecular Correlates of Tissue Injury in Renal Allografts;155
1.6.1.6.3;6.6.3 Molecular Correlates of Renal Allograft Rejection;156
1.6.1.6.4;6.6.4 Molecular Correlates of Interstitial Fibrosis and Tubular Atrophy (IFTA) of Renal Allografts;159
1.6.1.6.5;6.6.5 Future Perspectives in Molecular Transplantation Pathology;160
1.6.1.7;References;161
1.6.2;7: Lung;175
1.6.2.1;7.1 Introduction;175
1.6.2.1.1;7.1.1 Historic Perspective;175
1.6.2.1.2;7.1.2 Native Disease in Explanted Lungs;175
1.6.2.1.3;7.1.3 Allograft Selection and Procurement;176
1.6.2.2;7.2 Allograft Rejection;177
1.6.2.2.1;7.2.1 Overview;177
1.6.2.2.2;7.2.2 Hyperacute Rejection;178
1.6.2.2.3;7.2.3 Acute and Chronic Rejection;178
1.6.2.2.3.1;7.2.3.1 Overview;178
1.6.2.2.3.2;7.2.3.2 ISHLT Classification;180
1.6.2.2.3.3;7.2.3.3 2007 ISHLT Revised Consensus Classification of Lung Allograft Rejection;181
1.6.2.2.3.3.1;Acute Rejection: A Grade;181
1.6.2.2.3.3.1.1;No Acute Rejection (ISHLT Grade A0);181
1.6.2.2.3.3.1.2;Minimal Acute Rejection (ISHLT Grade A1);182
1.6.2.2.3.3.1.3;Mild Acute Rejection (ISHLT Grade A2);182
1.6.2.2.3.3.1.4;Moderate Acute Rejection (ISHLT Grade A3);182
1.6.2.2.3.3.1.5;Severe Acute Rejection (ISHLT Grade A4);183
1.6.2.2.3.3.2;Acute Small Airways Rejection: B Grade;183
1.6.2.2.3.3.2.1;No Airways Inflammation (ISHLT Grade B0);183
1.6.2.2.3.3.2.2;Low Grade Small Airways Inflammation (ISHLT Grade B1R);184
1.6.2.2.3.3.2.3;High Grade Small Airways Inflammation (ISHLT Grade B2R);184
1.6.2.2.3.3.2.4;Ungradeable Small Airways Inflammation (ISHLT Grade BX);184
1.6.2.2.3.3.3;Chronic Airways Rejection C-Grade;184
1.6.2.2.3.3.3.1;No Chronic Airways Rejection (ISHLT Grade C0);184
1.6.2.2.3.3.3.2;Chronic Airways Rejection (ISHLT Grade C1);184
1.6.2.2.3.3.4;Chronic Vascular Rejection D-Grade;185
1.6.2.2.3.3.4.1;No Chronic Vascular Rejection (ISHLT Grade D0);185
1.6.2.2.3.3.4.2;Chronic Vascular Rejection (ISHLT Grade D1);185
1.6.2.2.3.4;7.2.3.4 Mimickers of Severe Acute Cellular Rejection;186
1.6.2.2.3.5;7.2.3.5 Antibody-Mediated Rejection;186
1.6.2.3;7.3 Transbronchial Biopsy;188
1.6.2.3.1;7.3.1 Background and History;188
1.6.2.3.2;7.3.2 Timing of Posttransplantation Biopsies;189
1.6.2.3.3;7.3.3 Specimen Adequacy and Handling;190
1.6.2.4;7.4 Complications of Immunosuppression;190
1.6.2.4.1;7.4.1 Infection;190
1.6.2.4.1.1;7.4.1.1 Bacterial/Viral Pneumonia;190
1.6.2.4.1.2;7.4.1.2 CMV Infection;190
1.6.2.4.1.3;7.4.1.3 Herpes Simplex Virus Infection;191
1.6.2.4.1.4;7.4.1.4 Fungal Infections;191
1.6.2.4.1.5;7.4.1.5 Aspergillus Infection;191
1.6.2.4.1.6;7.4.1.6 Pneumocystis jiroveci Pneumonia;192
1.6.2.4.2;7.4.2 Posttransplant Lymphoproliferative Disorder;192
1.6.2.4.3;7.4.3 Solid Organ Neoplasms;194
1.6.2.4.4;7.4.4 Graft vs. Host Disease;194
1.6.2.5;7.5 Nonrejection Related Allograft Pathology;194
1.6.2.5.1;7.5.1 Harvest/Reperfusion Injury;194
1.6.2.5.2;7.5.2 Recurrent Native Disease;195
1.6.2.5.3;7.5.3 Anastomotic Complications in Airways;195
1.6.2.5.3.1;7.5.3.1 Bronchial Dehiscence;195
1.6.2.5.3.2;7.5.3.2 Stricture;195
1.6.2.5.4;7.5.4 Pathology in the Remaining Native Lung;196
1.6.2.5.5;7.5.5 Bronchiectasis;196
1.6.2.6;7.6 Outcomes;196
1.6.2.7;References;198
1.6.3;8: Liver;203
1.6.3.1;8.1 Introduction;203
1.6.3.2;8.2 Surgical Perspectives of Liver Transplantation;204
1.6.3.2.1;8.2.1 Overview;205
1.6.3.2.2;8.2.2 Recipient Selection;206
1.6.3.2.2.1;8.2.2.1 Waitlist Prioritization;206
1.6.3.2.3;8.2.3 Indications and Outcomes;207
1.6.3.2.3.1;8.2.3.1 Specific Indications;207
1.6.3.2.3.1.1;Viral Hepatitis;207
1.6.3.2.3.1.2;Alcoholic Liver Disease;207
1.6.3.2.3.1.3;Autoimmune Hepatitis;208
1.6.3.2.3.1.4;Cholestatic Liver Disease;208
1.6.3.2.3.1.5;Fulminate Hepatic Failure;208
1.6.3.2.3.1.6;Malignancy;208
1.6.3.2.3.1.7;Metabolic Disease;209
1.6.3.2.3.1.8;Uncommon Indications;209
1.6.3.2.3.1.9;Retransplantation;210
1.6.3.2.4;8.2.4 Donor Selection;210
1.6.3.2.5;8.2.5 Operative Techniques;211
1.6.3.2.5.1;8.2.5.1 Donor Hepatectomy;211
1.6.3.2.5.2;8.2.5.2 Recipient Hepatectomy;212
1.6.3.2.6;8.2.6 Complications;213
1.6.3.2.6.1;8.2.6.1 Primary Nonfunction (PNF);213
1.6.3.2.6.2;8.2.6.2 Hepatic Artery Thrombosis (HAT);213
1.6.3.2.6.3;8.2.6.3 Portal Vein Thrombosis (PVT);214
1.6.3.2.6.4;8.2.6.4 Biliary Complications;214
1.6.3.2.6.5;8.2.6.5 Infection;215
1.6.3.2.6.6;8.2.6.6 Rejection;215
1.6.3.2.6.7;8.2.6.7 Renal Dysfunction;216
1.6.3.2.6.8;8.2.6.8 Metabolic Complications;216
1.6.3.2.6.9;8.2.6.9 Posttransplant Lymphoproliferative Disorder (PTLD);216
1.6.3.3;8.3 Approach to the Liver Transplant Recipient: Maintenance of Allograft Function;216
1.6.3.3.1;8.3.1 Immunosuppressive Agents;217
1.6.3.3.2;8.3.2 Posttransplant Allograft Dysfunction: Causes and Evaluation;218
1.6.3.3.2.1;8.3.2.1 Allograft Dysfunction: What Does It Mean?;219
1.6.3.3.2.2;8.3.2.2 Allograft Dysfunction in the Early Postoperative Setting;219
1.6.3.3.2.3;8.3.2.3 Allograft Dysfunction in the First 3 Months;220
1.6.3.3.2.4;8.3.2.4 Other Early Viral Infections;222
1.6.3.3.2.5;8.3.2.5 Allograft Dysfunction from 3–9 Months;223
1.6.3.3.2.6;8.3.2.6 Recurrent Diseases;223
1.6.3.3.2.7;8.3.2.7 Other Causes of Allograft Dysfunction;225
1.6.3.3.3;8.3.3 Approach to the Care of the Liver Transplant Recipient;225
1.6.3.3.4;8.3.4 Conclusion;226
1.6.3.4;8.4 Primary Nonfunction, Donor Liver Evaluation, Preservation And Reperfusion Injury;226
1.6.3.4.1;8.4.1 Primary Nonfunction;226
1.6.3.4.1.1;8.4.1.1 General Considerations;226
1.6.3.4.1.2;8.4.1.2 Pathologic Features;227
1.6.3.4.1.3;8.4.1.3 Differential Diagnosis;229
1.6.3.4.2;8.4.2 Evaluation for Donor Liver Steatosis;229
1.6.3.4.2.1;8.4.2.1 General Consideration;229
1.6.3.4.2.2;8.4.2.2 General Guidelines;230
1.6.3.4.2.3;8.4.2.3 Pathologic Features;230
1.6.3.4.2.4;8.4.2.4 Pitfalls and Special Stains;232
1.6.3.4.3;8.4.3 Day 0 Biopsy Evaluation;233
1.6.3.4.3.1;8.4.3.1 General Consideration;233
1.6.3.4.3.2;8.4.3.2 Pathologic Features;233
1.6.3.4.4;8.4.4 Living Donor Evaluation;234
1.6.3.4.4.1;8.4.4.1 General Consideration;234
1.6.3.4.4.2;8.4.4.2 Pathologic Features;235
1.6.3.4.5;8.4.5 Preservation and Reperfusion Injury;235
1.6.3.4.5.1;8.4.5.1 General Consideration;235
1.6.3.4.5.2;8.4.5.2 Pathologic Features;236
1.6.3.4.5.3;8.4.5.3 Differential Diagnosis;238
1.6.3.5;8.5 Technical Complications;240
1.6.3.5.1;8.5.1 Hepatic Artery Thrombosis;240
1.6.3.5.2;8.5.2 Biliary Complications;242
1.6.3.5.3;8.5.3 Portal Vein Thrombosis;245
1.6.3.5.4;8.5.4 Hepatic Vein and Inferior Vena Cava Stenosis and Thrombosis;245
1.6.3.5.5;8.5.5 Small-For-Size Syndrome;247
1.6.3.6;8.6 Rejection;248
1.6.3.6.1;8.6.1 Humoral (Antibody-Mediated) Rejection;249
1.6.3.6.1.1;8.6.1.1 General Considerations;249
1.6.3.6.1.2;8.6.1.2 Pathologic Features;249
1.6.3.6.1.3;8.6.1.3 C4d Immunohistochemical Staining;250
1.6.3.6.1.4;8.6.1.4 Differential Diagnosis;251
1.6.3.6.2;8.6.2 Acute Rejection;252
1.6.3.6.2.1;8.6.2.1 General Consideration;252
1.6.3.6.2.2;8.6.2.2 Pathologic Features;252
1.6.3.6.2.3;8.6.2.3 Late-Onset Acute Rejection;255
1.6.3.6.2.4;8.6.2.4 Central Perivenulitis;255
1.6.3.6.2.5;8.6.2.5 Grading of Acute Rejection;256
1.6.3.6.2.6;8.6.2.6 Response to Treatment;258
1.6.3.6.2.7;8.6.2.7 Differential Diagnosis;258
1.6.3.6.3;8.6.3 Chronic Rejection;261
1.6.3.6.3.1;8.6.3.1 General Consideration;261
1.6.3.6.3.2;8.6.3.2 Pathologic Features;261
1.6.3.6.3.3;8.6.3.3 Staging of Chronic Rejection;264
1.6.3.6.3.4;8.6.3.4 Differential Diagnosis;265
1.6.3.7;8.7 Recurrent and De Novo Liver Diseases;266
1.6.3.7.1;8.7.1 Hepatitis C Virus Infection;266
1.6.3.7.2;8.7.2 Hepatitis B Virus Infection;268
1.6.3.7.3;8.7.3 Fibrosing Cholestatic Hepatitis;270
1.6.3.7.4;8.7.4 Autoimmune Hepatitis;271
1.6.3.7.5;8.7.5 Primary Biliary Cirrhosis;273
1.6.3.7.6;8.7.6 Primary Sclerosing Cholangitis;274
1.6.3.7.7;8.7.7 Alcoholic Liver Disease;275
1.6.3.7.8;8.7.8 Nonalcoholic Fatty Liver Disease;276
1.6.3.7.9;8.7.9 Hemochromatosis and Iron Overload;277
1.6.3.7.10;8.7.10 Budd-Chiari Syndrome;278
1.6.3.7.11;8.7.11 Idiopathic Posttransplantation Hepatitis;279
1.6.3.7.12;8.7.12 Malignancies;279
1.6.3.7.13;8.7.13 Hepatic Architectural Alterations;280
1.6.3.7.14;8.7.14 Others;281
1.6.3.8;8.8 Hepatic Complications of Immunosuppression;282
1.6.3.8.1;8.8.1 Drug Hepatotoxicity;283
1.6.3.8.1.1;8.8.1.1 Cyclosporine;283
1.6.3.8.1.2;8.8.1.2 Tacrolimus (FK506, Prograf);283
1.6.3.8.1.3;8.8.1.3 Corticosteroids;284
1.6.3.8.1.4;8.8.1.4 Azathioprine (Imuran);284
1.6.3.8.1.5;8.8.1.5 Mycophenolate Mofetil (CellCept);284
1.6.3.8.1.6;8.8.1.6 Sirolimus (Rapamycin);284
1.6.3.8.2;8.8.2 Infections;284
1.6.3.8.2.1;8.8.2.1 Bacterial Infections;285
1.6.3.8.2.2;8.8.2.2 Fungal Infections;286
1.6.3.8.2.3;8.8.2.3 Cytomegalovirus Hepatitis;286
1.6.3.8.2.4;8.8.2.4 Adenovirus Hepatitis;287
1.6.3.8.2.5;8.8.2.5 Herpes Simplex Virus Hepatitis;288
1.6.3.8.2.6;8.8.2.6 Varicella-Zoster Virus Hepatitis;288
1.6.3.8.2.7;8.8.2.7 Human Herpesvirus 6 Hepatitis;289
1.6.3.8.2.8;8.8.2.8 Epstein–Barr Virus Infection;289
1.6.3.9;References;292
1.6.4;9: Heart;319
1.6.4.1;9.1 Introduction;319
1.6.4.1.1;9.1.1 Historic Perspective;319
1.6.4.1.2;9.1.2 Outcomes;319
1.6.4.1.3;9.1.3 Immunosuppressive Therapy;319
1.6.4.2;9.2 Native Disease in Explanted Hearts;320
1.6.4.2.1;9.2.1 Cardiomyopathy;320
1.6.4.2.2;9.2.2 Ischemic Heart Disease;321
1.6.4.2.3;9.2.3 Myocarditis;321
1.6.4.2.4;9.2.4 Metabolic Disorders;322
1.6.4.2.5;9.2.5 Evaluation of the Explanted Native Heart;322
1.6.4.2.6;9.2.6 Recurrence of Native Disease in Allografts;323
1.6.4.3;9.3 Allograft Selection and Procurement;323
1.6.4.3.1;9.3.1 Donor Criteria;323
1.6.4.3.2;9.3.2 ABO Compatibility;324
1.6.4.3.3;9.3.3 Preservation Injury;324
1.6.4.4;9.4 Endomyocardial Biopsy;324
1.6.4.4.1;9.4.1 Background;324
1.6.4.4.2;9.4.2 Timing of Biopsies and Surveillance Strategies;325
1.6.4.4.3;9.4.3 Specimen Adequacy and Handling;325
1.6.4.4.4;9.4.4 Biopsy Site Changes and Incidental Findings;325
1.6.4.5;9.5 Allograft Rejection;327
1.6.4.5.1;9.5.1 Overview;327
1.6.4.5.2;9.5.2 Hyperacute Rejection;327
1.6.4.5.3;9.5.3 Acute Cellular Rejection;328
1.6.4.5.3.1;9.5.3.1 Background;328
1.6.4.5.3.2;9.5.3.2 1990 ISHLT Classification;328
1.6.4.5.3.3;9.5.3.3 2004 ISHLT Classification;328
1.6.4.5.3.3.1;Grade 1R Rejection (Includes 1990 ISHLT Working Formulation Grades 1A, 1B, 2);330
1.6.4.5.3.3.2;Grade 2R Rejection (Formerly 1990 ISHLT Working Formulation Grade 3A);330
1.6.4.5.3.3.3;Grade 3R (Includes 1990 ISHLT Working Formulation Grades 3B and 4);330
1.6.4.5.3.4;9.5.3.4 Nodular Endocardial Lymphocytic Infiltrates (Quilty Effect);331
1.6.4.5.4;9.5.4 Antibody-Mediated Rejection (AMR);332
1.6.4.5.4.1;9.5.4.1 Background;332
1.6.4.5.4.2;9.5.4.2 2004 ISHLT Criteria;333
1.6.4.5.4.3;9.5.4.3 Histopathology of AMR;333
1.6.4.5.4.4;9.5.4.4 Immunopathology of AMR;334
1.6.4.5.4.4.1;C3d;334
1.6.4.5.4.4.2;Immunoglobulin Heavy Chains;336
1.6.4.5.4.4.3;HLA-DR;336
1.6.4.5.4.4.4;Complement Regulators (CD55, CD59);336
1.6.4.5.4.4.5;Fibrin;336
1.6.4.5.4.4.6;Platelet Antigens (CD61, CD63);336
1.6.4.5.4.5;9.5.4.5 Serum Antibody Studies;337
1.6.4.5.4.6;9.5.4.6 Controversies in AMR;337
1.6.4.5.4.6.1;Mixed Rejection;337
1.6.4.5.4.6.2;Severity of AMR;337
1.6.4.5.4.6.3;“Chronic” AMR and CAV;338
1.6.4.5.4.6.4;Incorporating Clinical and Laboratory Data in AMR Diagnosis;338
1.6.4.6;9.6 Cardiac Allograft Vasculopathy;339
1.6.4.7;9.7 Myocardial Ischemia;339
1.6.4.8;9.8 Complications of Immunosuppression;341
1.6.4.8.1;9.8.1 Infection;341
1.6.4.8.2;9.8.2 Lymphoproliferative Disorder;341
1.6.4.8.3;9.8.3 Solid Organ Neoplasms;342
1.6.4.8.4;9.8.4 Toxicity of Immunosuppressants;342
1.6.4.9;9.9 Molecular Assessment of Rejection;342
1.6.4.10;Appendix 1Gross Pathology Record for Cardiac Explants;343
1.6.4.11;References;344
1.6.5;10: Small Intestine;350
1.6.5.1;10.1 Overview;350
1.6.5.2;10.2 Indications for Small Intestinal Transplantation;351
1.6.5.3;10.3 Contraindications for Transplantation and Donor Selection;352
1.6.5.4;10.4 Types of Intestinal Transplantation;352
1.6.5.5;10.5 Complications of Intestinal Transplantation;353
1.6.5.5.1;10.5.1 Surgical Complications;354
1.6.5.5.2;10.5.2 Preoperative, Implantation and Reperfusion Injury;354
1.6.5.5.3;10.5.3 Antibody-Mediated Rejection;355
1.6.5.5.4;10.5.4 Acute Cellular Rejection;357
1.6.5.5.4.1;10.5.4.1 Grading System for ACR;358
1.6.5.5.5;10.5.5 Chronic Rejection;360
1.6.5.5.6;10.5.6 Infection;362
1.6.5.5.7;10.5.7 Epstein–Barr Virus Infection and Posttransplant Lymphoproliferative Disease;365
1.6.5.5.8;10.5.8 Miscellaneous Pathology;365
1.6.5.5.9;10.5.9 Recurrent Intestinal Diseases;366
1.6.5.5.10;10.5.10 Retransplantation;367
1.6.5.5.11;10.5.11 Graft-Versus-Host Disease;367
1.6.5.6;10.6 Long-Term Outcome and Quality of Life;367
1.6.5.7;10.7 Summary and Future Directions;368
1.6.5.8;References;369
1.6.6;11: Pancreas;374
1.6.6.1;11.1 Introduction;374
1.6.6.1.1;11.1.1 Necessity for an Alternative Treatment for Diabetes;374
1.6.6.1.2;11.1.2 Indications for Pancreas Transplantation/Types of Pancreas Transplants;375
1.6.6.2;11.2 Criteria for Pancreas Donor Selection;375
1.6.6.3;11.3 Diagnostic Modalities of Acute Allograft Rejection;376
1.6.6.3.1;11.3.1 Clinical Diagnosis of Acute Rejection; Surrogate Markers376
1.6.6.3.2;11.3.2 Tissue (Biopsy) Diagnosis of Acute Rejection;376
1.6.6.3.2.1;11.3.2.1 Guidelines for Processing Pancreas Allograft Biopsies;376
1.6.6.3.2.2;11.3.2.2 Protocol Biopsies;376
1.6.6.4;11.4 Pathophysiological Correlations;377
1.6.6.4.1;11.4.1 Acute Allograft Rejection;377
1.6.6.4.1.1;11.4.1.1 Immunological Aspects;377
1.6.6.4.2;11.4.2 Chronic Allograft Rejection/Graft Sclerosis;378
1.6.6.4.2.1;11.4.2.1 Pathogenetic Aspects;378
1.6.6.4.2.2;11.4.2.2 Morphology of Chronic Rejection/Graft Sclerosis;378
1.6.6.5;11.5 Pancreas Allograft Rejection BANFF 2007 Working Grading Schema;378
1.6.6.5.1;11.5.1 Specific Histological Features Utilized in the 2007 BANFF Grading Schema;379
1.6.6.5.2;11.5.2 Histological Features Defining the Severity of Acute Rejection;379
1.6.6.5.3;11.5.3 Diagnostic Categories: Specific Considerations;381
1.6.6.5.3.1;11.5.3.1 Normal;381
1.6.6.5.3.2;11.5.3.2 Indeterminate for Rejection;383
1.6.6.5.3.3;11.5.3.3 Cell-Mediated Acute Rejection;384
1.6.6.5.3.3.1;Mild Cell-Mediated Acute Rejection (Grade I);384
1.6.6.5.3.3.2;Moderate Cell-Mediated Acute Rejection (Grade II);385
1.6.6.5.3.3.3;Severe Cell-Mediated Acute Rejection (Grade III);385
1.6.6.5.4;11.5.3.4 Antibody Mediated Acute Rejection;386
1.6.6.5.4.1;Acute Antibody Mediated Rejection;386
1.6.6.5.4.2;Hyperacute/Accelerated Allograft Rejection;387
1.6.6.5.4.3;Chronic Active Antibody Mediated Rejection;387
1.6.6.6;11.5.3.5 Grading of Chronic Allograft Rejection/Graft Sclerosis;387
1.6.6.7;11.5.3.6 Other Histological Diagnosis;388
1.6.6.8;11.6 Other Forms of Pancreas Graft Pathology;388
1.6.6.8.1;11.6.1 Surgical Complications;388
1.6.6.8.1.1;11.6.1.1 Graft Thrombosis;388
1.6.6.8.2;11.6.1.2 Posttransplantation (Ischemic) Pancreatitis;389
1.6.6.8.3;11.6.1.3 Posttransplant Infectious Pancreatitis/Peripancreatitis/Fluid Collection/Peripancreatic Abscess;389
1.6.6.8.4;11.6.2 Viral Infections;389
1.6.6.8.4.1;11.6.2.1 Cytomegalovirus Infection;389
1.6.6.8.4.2;11.6.2.2 EBV-Related Posttransplant Lymphoproliferative Disorder;390
1.6.6.8.5;11.6.3 Islet Graft Pathology;391
1.6.6.8.5.1;11.6.3.1 Nonspecific Islet Pathology;391
1.6.6.8.6;11.6.3.2 Recurrence of Type I Diabetes Mellitus;391
1.6.6.8.7;11.6.3.3 Islet Cell Drug Toxicity;391
1.6.6.8.8;11.6.3.4 Nesidioblastosis;392
1.6.6.9;11.7 Gross and Microscopic Evaluation of Failed Allografts;392
1.6.6.10;References;392
1.6.7;12: Vascularized Composite Allotransplantation;396
1.6.7.1;12.1 Introduction;396
1.6.7.1.1;12.1.1 Specimen Adequacy;396
1.6.7.1.2;12.1.2 The Banff CTA Classification System;397
1.6.7.2;12.2 Mucous Membrane Rejection in Composite Tissue Allografts;399
1.6.7.3;12.3 Summary;401
1.6.7.4;References;401
1.7;Index;403