Pathology of Solid Organ Transplantation (eBook)

Helen Liapis is Professor of Pathology and Immunology and Professor of Nephrology at Washington University School of Medicine in St. Louis, USA. She is an internationally acclaimed expert in kidney disease and transplantation, and is currently a member of the editorial boards of Pathology Research International and the International Journal of Urology and Nephrology and regular reviewer of numerous Nephrology and Pathology journals. Dr. Liapis is the author of > 100 journal articles in the field, as well as a co-author in Heptinstall's Pathology of the Kidney, an atlas of renal pathology and editor or author in other renal pathology books. Hanlin Wang is Director of Gastrointestinal Pathology in the Department of Pathology and Laboratory Medicine at Cedars-Sinai Medical Center, Los Angeles, USA. He is the recipient of a number of awards and the author of more than 90 peer-reviewed scientific papers and numerous invited reviews and book chapters. Dr. Wang serves the editorial boards for several medical journals and is a reviewer for numerous scientific journals and grant agencies. His research interests include liver and gastrointestinal diseases.

Pathology of Solid Organ Transplantation 2
Copyright Page 3
Dedication 4
Preface 5
Contents 8
Part I Immunology, Clinical, and LaboratoryAspects of Organ Transplantation 10
1: Immunology of Organ Transplantation 11
1.1 Introduction 11
1.2 Basic Transplantation Immunology 11
1.2.1 Components of the Immune System 11
1.3 The Adaptive Alloimmune Response 11
1.3.1 Recognition of Alloantigen 12
1.3.2 Cellular Alloimmunity 12
1.3.3 Humoral Alloimmunity 13
1.3.4 Resolution of the Alloimmune Response 14
1.3.5 Transplant Tolerance 14
1.4 Organ Specific Effects and Clinical Applications of Transplant Immunology 15
References 15
2: Current Concepts of Immunosuppression and Side Effects 18
2.1 Introduction 18
2.2 Induction Drugs 18
2.3 OKT 3 19
2.3.1 Mechanism of Action 19
2.3.2 Efficacy 19
2.3.3 Side Effects 19
2.4 IL-2 Receptor Antagonists (Anti CD25 Antibodies) 20
2.4.1 Mechanism 20
2.4.2 Dosage 20
2.4.3 Efficacy 20
2.4.4 Side Effects 21
2.5 Polyclonal Antibodies (Thymoglobulin and ATGAM) 22
2.5.1 Mechanism of Action 22
2.5.2 Dosage 22
2.5.3 Clinical Efficacy 22
2.5.4 Side Effects 22
2.6 Alemtuzumab 23
2.6.1 Mechanism of Action 23
2.6.2 Dosage 23
2.6.3 Clinical Efficacy 23
2.6.4 Side Effects 23
2.7 Maintenance Drugs 24
2.7.1 Prednisone 24
2.7.1.1 Mechanism of Action 24
2.7.1.2 Dosage 24
2.7.1.3 Clinical Efficacy 24
2.7.1.4 Side Effects 25
2.7.2 Calcineurin Inhibitors 25
2.7.2.1 Mechanism of Action 25
2.7.2.2 Dosage 25
2.7.2.3 Clinical Efficacy 25
2.7.2.4 Side Effects 26
2.7.3 Mycophenolate 27
2.7.3.1 Mechanism of Action 27
2.7.3.2 Dosage 28
2.7.3.3 Clinical Efficacy 28
2.7.3.4 Side Effects 28
2.7.4 Rapamycin (Sirolimus) 28
2.7.4.1 Mechanism of Action 28
2.7.4.2 Dosage 28
2.7.4.3 Clinical Efficacy 28
2.7.4.4 Side Effects 29
2.8 Newer Immunosuppressive Medications 30
2.8.1 Janus Kinase (JAK) 3 Inhibitors 30
2.9 AEB-071 30
2.9.1 LEA 29Y (Belatacept) 30
2.10 Efalizumab 31
2.11 Summary 31
References 31
3: Clinical Aspects of Infection 38
3.1 Introduction 38
3.2 Infections and Timing of Transplant 38
3.2.1 Month 1 39
3.2.2 Months 2–6 39
3.2.3 Greater than 6 Months 39
3.3 Viral Infections 39
3.3.1 Cytomegalovirus 39
3.4 Epstein–Barr Virus (EBV) and Posttransplant Lymphoproliferative Disorders (PTLD) 42
3.5 BK Virus and Nephropathy 45
3.6 Hepatitis C 48
3.7 Parvovirus B19 48
3.8 Fungal Infections 48
3.9 Pneumocystis Jiroveci (PCP) 49
3.10 Summary 49
References 49
4: Clinical Evaluation of Alloantibodies in Solid Organ Transplantation 51
4.1 Introduction 51
4.2 Alloantibody Specificities 51
4.2.1 Alloantibodies Against HLA 51
4.2.2 ABO Blood Group Antibodies 53
4.2.3 MICA 53
4.2.4 Alloantibodies to Non-HLA Antigens 53
4.3 Clinical Testing for Alloantibodies 54
4.3.1 Cytotoxicity Crossmatch 54
4.3.2 Solid Phase Immunoassays for Detection of Alloantibodies 56
4.3.3 Virtual Crossmatching and Donor Selection 56
4.3.4 Posttransplant Testing 57
4.3.5 Immunologic Accommodation 58
References 58
5: Frontiers in Organ Transplantation 63
5.1 Introduction 63
5.2 Growing New Kidneys 63
5.2.1 Immune Response to Fetal Kidney Transplants 64
5.2.2 Means by Which Renal Primordia are Vascularized 65
5.3 Xenotransplantation for Kidney Replacement 65
5.4 Transplantation of Renal Primordia to Enhance Host Renal Function 66
5.4.1 Availability of Renal Primordia 69
5.5 Growing New Endocrine Pancreas 70
5.6 Xenotransplantation Therapy for Diabetes Mellitus 72
5.7 Organogenesis of the Endocrine Pancreas 72
5.7.1 Type 1 Diabetes Mellitus 72
5.7.2 Type 2 Diabetes Mellitus 74
5.8 Summary and Conclusions 78
References 78
Part II Transplant Pathology of Organ Systems 81
6: Kidney 82
6.1 Introduction 82
6.1.1 Biopsy Types, Specimen Adequacy, and Processing 82
6.1.2 Expanded Criteria Donor (ECD): A Nephrologist’s Perspective 84
6.1.3 Donor Biopsy 86
6.1.3.1 Protocol Biopsies 92
6.1.3.2 Delayed Graft Function (DGF) 93
6.1.3.3 ABO Incompatible Grafts (ABOi) 94
6.2 Indication Biopsy 96
6.2.1 Acute Rejection 97
6.2.1.1 Tubulitis 97
6.2.1.2 Arteritis 100
6.2.1.3 Glomerulitis 101
6.2.1.4 Interstitial Inflammation 102
6.2.1.5 Plasma Cell Rich Rejection 105
6.2.1.6 Lymphoid Neogenesis 105
6.2.2 Chronic Rejection 106
6.2.3 Antibody-Mediated Rejection 110
6.2.3.1 C4d Pathogenesis, Detection Methods, and Scoring 115
6.2.3.2 C4d+ Without Histopathological Findings of AMR and or DSA 116
6.2.3.3 PTC C4d+ in Chronic AMR 116
6.2.3.4 C4d+ in Various Locations Other than PTC 116
6.2.3.5 C3 and AMR 118
6.2.4 Recurrent be Glomerular Disease 118
6.2.4.1 rFSGS 119
6.2.4.2 rDiabetes 123
6.2.4.3 rLupus 124
6.2.4.4 rIgA Nephropathy 124
6.2.4.5 rMembranoproliferative Glomerulonephritis (MPGN) 125
6.2.4.6 rMembranous Glomerulonephritis 126
6.2.4.7 rANCA Vasculitis and rAnti-GBM Disease 126
6.2.4.8 rHUS and the Spectrum of Thrombotic Microangiopathy (TMA) in the Transplant Kidney 127
6.2.4.9 rAmyloidosis/rLCDD/rFibrillary 129
6.2.4.10 Miscellaneous Glomerular Disease Recurrence 130
6.3 Malignancy 133
6.4 De Novo Disease 135
6.4.1 Transplant Glomerulopathy (TGP) 135
6.4.2 Miscellaneous De Novo Glomerular Diseases 138
6.4.3 CNI Toxicity 138
6.4.4 Crystal Deposition Disease 140
6.4.4.1 Oxalate Crystal Deposits 140
6.4.4.2 Calcium Phosphate Crystal Deposits 141
6.4.4.3 Cholesterol Embolism 142
6.4.4.4 Rhabdomyolysis 143
6.4.5 ATN 144
6.4.6 Infections: Bacterial, Fungal, Viral 145
6.4.7 Acute Interstitial Nephritis (AIN) 148
6.4.8 Graft Versus Host Disease (GVHD) in the Allograft Kidney 149
6.4.9 Other Complications 149
6.5 Kidney Damage Secondary to Nonrenal Transplantation 150
6.5.1 Renal GVHD Following Bone Marrow Stem Cell Transplantation 151
6.5.2 Cholemic Nephrosis 153
6.6 Molecular Correlates of Renal Allograft Pathology 154
6.6.1 Background 154
6.6.2 Molecular Correlates of Tissue Injury in Renal Allografts 155
6.6.3 Molecular Correlates of Renal Allograft Rejection 156
6.6.4 Molecular Correlates of Interstitial Fibrosis and Tubular Atrophy (IFTA) of Renal Allografts 159
6.6.5 Future Perspectives in Molecular Transplantation Pathology 160
References 161
7: Lung 175
7.1 Introduction 175
7.1.1 Historic Perspective 175
7.1.2 Native Disease in Explanted Lungs 175
7.1.3 Allograft Selection and Procurement 176
7.2 Allograft Rejection 177
7.2.1 Overview 177
7.2.2 Hyperacute Rejection 178
7.2.3 Acute and Chronic Rejection 178
7.2.3.1 Overview 178
7.2.3.2 ISHLT Classification 180
7.2.3.3 2007 ISHLT Revised Consensus Classification of Lung Allograft Rejection 181
Acute Rejection: A Grade 181
No Acute Rejection (ISHLT Grade A0) 181
Minimal Acute Rejection (ISHLT Grade A1) 182
Mild Acute Rejection (ISHLT Grade A2) 182
Moderate Acute Rejection (ISHLT Grade A3) 182
Severe Acute Rejection (ISHLT Grade A4) 183
Acute Small Airways Rejection: B Grade 183
No Airways Inflammation (ISHLT Grade B0) 183
Low Grade Small Airways Inflammation (ISHLT Grade B1R) 184
High Grade Small Airways Inflammation (ISHLT Grade B2R) 184
Ungradeable Small Airways Inflammation (ISHLT Grade BX) 184
Chronic Airways Rejection C-Grade 184
No Chronic Airways Rejection (ISHLT Grade C0) 184
Chronic Airways Rejection (ISHLT Grade C1) 184
Chronic Vascular Rejection D-Grade 185
No Chronic Vascular Rejection (ISHLT Grade D0) 185
Chronic Vascular Rejection (ISHLT Grade D1) 185
7.2.3.4 Mimickers of Severe Acute Cellular Rejection 186
7.2.3.5 Antibody-Mediated Rejection 186
7.3 Transbronchial Biopsy 188
7.3.1 Background and History 188
7.3.2 Timing of Posttransplantation Biopsies 189
7.3.3 Specimen Adequacy and Handling 190
7.4 Complications of Immunosuppression 190
7.4.1 Infection 190
7.4.1.1 Bacterial/Viral Pneumonia 190
7.4.1.2 CMV Infection 190
7.4.1.3 Herpes Simplex Virus Infection 191
7.4.1.4 Fungal Infections 191
7.4.1.5 Aspergillus Infection 191
7.4.1.6 Pneumocystis jiroveci Pneumonia 192
7.4.2 Posttransplant Lymphoproliferative Disorder 192
7.4.3 Solid Organ Neoplasms 194
7.4.4 Graft vs. Host Disease 194
7.5 Nonrejection Related Allograft Pathology 194
7.5.1 Harvest/Reperfusion Injury 194
7.5.2 Recurrent Native Disease 195
7.5.3 Anastomotic Complications in Airways 195
7.5.3.1 Bronchial Dehiscence 195
7.5.3.2 Stricture 195
7.5.4 Pathology in the Remaining Native Lung 196
7.5.5 Bronchiectasis 196
7.6 Outcomes 196
References 198
8: Liver 203
8.1 Introduction 203
8.2 Surgical Perspectives of Liver Transplantation 204
8.2.1 Overview 205
8.2.2 Recipient Selection 206
8.2.2.1 Waitlist Prioritization 206
8.2.3 Indications and Outcomes 207
8.2.3.1 Specific Indications 207
Viral Hepatitis 207
Alcoholic Liver Disease 207
Autoimmune Hepatitis 208
Cholestatic Liver Disease 208
Fulminate Hepatic Failure 208
Malignancy 208
Metabolic Disease 209
Uncommon Indications 209
Retransplantation 210
8.2.4 Donor Selection 210
8.2.5 Operative Techniques 211
8.2.5.1 Donor Hepatectomy 211
8.2.5.2 Recipient Hepatectomy 212
8.2.6 Complications 213
8.2.6.1 Primary Nonfunction (PNF) 213
8.2.6.2 Hepatic Artery Thrombosis (HAT) 213
8.2.6.3 Portal Vein Thrombosis (PVT) 214
8.2.6.4 Biliary Complications 214
8.2.6.5 Infection 215
8.2.6.6 Rejection 215
8.2.6.7 Renal Dysfunction 216
8.2.6.8 Metabolic Complications 216
8.2.6.9 Posttransplant Lymphoproliferative Disorder (PTLD) 216
8.3 Approach to the Liver Transplant Recipient: Maintenance of Allograft Function 216
8.3.1 Immunosuppressive Agents 217
8.3.2 Posttransplant Allograft Dysfunction: Causes and Evaluation 218
8.3.2.1 Allograft Dysfunction: What Does It Mean? 219
8.3.2.2 Allograft Dysfunction in the Early Postoperative Setting 219
8.3.2.3 Allograft Dysfunction in the First 3 Months 220
8.3.2.4 Other Early Viral Infections 222
8.3.2.5 Allograft Dysfunction from 3–9 Months 223
8.3.2.6 Recurrent Diseases 223
8.3.2.7 Other Causes of Allograft Dysfunction 225
8.3.3 Approach to the Care of the Liver Transplant Recipient 225
8.3.4 Conclusion 226
8.4 Primary Nonfunction, Donor Liver Evaluation, Preservation And Reperfusion Injury 226
8.4.1 Primary Nonfunction 226
8.4.1.1 General Considerations 226
8.4.1.2 Pathologic Features 227
8.4.1.3 Differential Diagnosis 229
8.4.2 Evaluation for Donor Liver Steatosis 229
8.4.2.1 General Consideration 229
8.4.2.2 General Guidelines 230
8.4.2.3 Pathologic Features 230
8.4.2.4 Pitfalls and Special Stains 232
8.4.3 Day 0 Biopsy Evaluation 233
8.4.3.1 General Consideration 233
8.4.3.2 Pathologic Features 233
8.4.4 Living Donor Evaluation 234
8.4.4.1 General Consideration 234
8.4.4.2 Pathologic Features 235
8.4.5 Preservation and Reperfusion Injury 235
8.4.5.1 General Consideration 235
8.4.5.2 Pathologic Features 236
8.4.5.3 Differential Diagnosis 238
8.5 Technical Complications 240
8.5.1 Hepatic Artery Thrombosis 240
8.5.2 Biliary Complications 242
8.5.3 Portal Vein Thrombosis 245
8.5.4 Hepatic Vein and Inferior Vena Cava Stenosis and Thrombosis 245
8.5.5 Small-For-Size Syndrome 247
8.6 Rejection 248
8.6.1 Humoral (Antibody-Mediated) Rejection 249
8.6.1.1 General Considerations 249
8.6.1.2 Pathologic Features 249
8.6.1.3 C4d Immunohistochemical Staining 250
8.6.1.4 Differential Diagnosis 251
8.6.2 Acute Rejection 252
8.6.2.1 General Consideration 252
8.6.2.2 Pathologic Features 252
8.6.2.3 Late-Onset Acute Rejection 255
8.6.2.4 Central Perivenulitis 255
8.6.2.5 Grading of Acute Rejection 256
8.6.2.6 Response to Treatment 258
8.6.2.7 Differential Diagnosis 258
8.6.3 Chronic Rejection 261
8.6.3.1 General Consideration 261
8.6.3.2 Pathologic Features 261
8.6.3.3 Staging of Chronic Rejection 264
8.6.3.4 Differential Diagnosis 265
8.7 Recurrent and De Novo Liver Diseases 266
8.7.1 Hepatitis C Virus Infection 266
8.7.2 Hepatitis B Virus Infection 268
8.7.3 Fibrosing Cholestatic Hepatitis 270
8.7.4 Autoimmune Hepatitis 271
8.7.5 Primary Biliary Cirrhosis 273
8.7.6 Primary Sclerosing Cholangitis 274
8.7.7 Alcoholic Liver Disease 275
8.7.8 Nonalcoholic Fatty Liver Disease 276
8.7.9 Hemochromatosis and Iron Overload 277
8.7.10 Budd-Chiari Syndrome 278
8.7.11 Idiopathic Posttransplantation Hepatitis 279
8.7.12 Malignancies 279
8.7.13 Hepatic Architectural Alterations 280
8.7.14 Others 281
8.8 Hepatic Complications of Immunosuppression 282
8.8.1 Drug Hepatotoxicity 283
8.8.1.1 Cyclosporine 283
8.8.1.2 Tacrolimus (FK506, Prograf) 283
8.8.1.3 Corticosteroids 284
8.8.1.4 Azathioprine (Imuran) 284
8.8.1.5 Mycophenolate Mofetil (CellCept) 284
8.8.1.6 Sirolimus (Rapamycin) 284
8.8.2 Infections 284
8.8.2.1 Bacterial Infections 285
8.8.2.2 Fungal Infections 286
8.8.2.3 Cytomegalovirus Hepatitis 286
8.8.2.4 Adenovirus Hepatitis 287
8.8.2.5 Herpes Simplex Virus Hepatitis 288
8.8.2.6 Varicella-Zoster Virus Hepatitis 288
8.8.2.7 Human Herpesvirus 6 Hepatitis 289
8.8.2.8 Epstein–Barr Virus Infection 289
References 292
9: Heart 319
9.1 Introduction 319
9.1.1 Historic Perspective 319
9.1.2 Outcomes 319
9.1.3 Immunosuppressive Therapy 319
9.2 Native Disease in Explanted Hearts 320
9.2.1 Cardiomyopathy 320
9.2.2 Ischemic Heart Disease 321
9.2.3 Myocarditis 321
9.2.4 Metabolic Disorders 322
9.2.5 Evaluation of the Explanted Native Heart 322
9.2.6 Recurrence of Native Disease in Allografts 323
9.3 Allograft Selection and Procurement 323
9.3.1 Donor Criteria 323
9.3.2 ABO Compatibility 324
9.3.3 Preservation Injury 324
9.4 Endomyocardial Biopsy 324
9.4.1 Background 324
9.4.2 Timing of Biopsies and Surveillance Strategies 325
9.4.3 Specimen Adequacy and Handling 325
9.4.4 Biopsy Site Changes and Incidental Findings 325
9.5 Allograft Rejection 327
9.5.1 Overview 327
9.5.2 Hyperacute Rejection 327
9.5.3 Acute Cellular Rejection 328
9.5.3.1 Background 328
9.5.3.2 1990 ISHLT Classification 328
9.5.3.3 2004 ISHLT Classification 328
Grade 1R Rejection (Includes 1990 ISHLT Working Formulation Grades 1A, 1B, 2) 330
Grade 2R Rejection (Formerly 1990 ISHLT Working Formulation Grade 3A) 330
Grade 3R (Includes 1990 ISHLT Working Formulation Grades 3B and 4) 330
9.5.3.4 Nodular Endocardial Lymphocytic Infiltrates (Quilty Effect) 331
9.5.4 Antibody-Mediated Rejection (AMR) 332
9.5.4.1 Background 332
9.5.4.2 2004 ISHLT Criteria 333
9.5.4.3 Histopathology of AMR 333
9.5.4.4 Immunopathology of AMR 334
C3d 334
Immunoglobulin Heavy Chains 336
HLA-DR 336
Complement Regulators (CD55, CD59) 336
Fibrin 336
Platelet Antigens (CD61, CD63) 336
9.5.4.5 Serum Antibody Studies 337
9.5.4.6 Controversies in AMR 337
Mixed Rejection 337
Severity of AMR 337
“Chronic” AMR and CAV 338
Incorporating Clinical and Laboratory Data in AMR Diagnosis 338
9.6 Cardiac Allograft Vasculopathy 339
9.7 Myocardial Ischemia 339
9.8 Complications of Immunosuppression 341
9.8.1 Infection 341
9.8.2 Lymphoproliferative Disorder 341
9.8.3 Solid Organ Neoplasms 342
9.8.4 Toxicity of Immunosuppressants 342
9.9 Molecular Assessment of Rejection 342
Appendix 1Gross Pathology Record for Cardiac Explants 343
References 344
10: Small Intestine 350
10.1 Overview 350
10.2 Indications for Small Intestinal Transplantation 351
10.3 Contraindications for Transplantation and Donor Selection 352
10.4 Types of Intestinal Transplantation 352
10.5 Complications of Intestinal Transplantation 353
10.5.1 Surgical Complications 354
10.5.2 Preoperative, Implantation and Reperfusion Injury 354
10.5.3 Antibody-Mediated Rejection 355
10.5.4 Acute Cellular Rejection 357
10.5.4.1 Grading System for ACR 358
10.5.5 Chronic Rejection 360
10.5.6 Infection 362
10.5.7 Epstein–Barr Virus Infection and Posttransplant Lymphoproliferative Disease 365
10.5.8 Miscellaneous Pathology 365
10.5.9 Recurrent Intestinal Diseases 366
10.5.10 Retransplantation 367
10.5.11 Graft-Versus-Host Disease 367
10.6 Long-Term Outcome and Quality of Life 367
10.7 Summary and Future Directions 368
References 369
11: Pancreas 374
11.1 Introduction 374
11.1.1 Necessity for an Alternative Treatment for Diabetes 374
11.1.2 Indications for Pancreas Transplantation/Types of Pancreas Transplants 375
11.2 Criteria for Pancreas Donor Selection 375
11.3 Diagnostic Modalities of Acute Allograft Rejection 376
11.3.1 Clinical Diagnosis of Acute Rejection Surrogate Markers376
11.3.2 Tissue (Biopsy) Diagnosis of Acute Rejection 376
11.3.2.1 Guidelines for Processing Pancreas Allograft Biopsies 376
11.3.2.2 Protocol Biopsies 376
11.4 Pathophysiological Correlations 377
11.4.1 Acute Allograft Rejection 377
11.4.1.1 Immunological Aspects 377
11.4.2 Chronic Allograft Rejection/Graft Sclerosis 378
11.4.2.1 Pathogenetic Aspects 378
11.4.2.2 Morphology of Chronic Rejection/Graft Sclerosis 378
11.5 Pancreas Allograft Rejection BANFF 2007 Working Grading Schema 378
11.5.1 Specific Histological Features Utilized in the 2007 BANFF Grading Schema 379
11.5.2 Histological Features Defining the Severity of Acute Rejection 379
11.5.3 Diagnostic Categories: Specific Considerations 381
11.5.3.1 Normal 381
11.5.3.2 Indeterminate for Rejection 383
11.5.3.3 Cell-Mediated Acute Rejection 384
Mild Cell-Mediated Acute Rejection (Grade I) 384
Moderate Cell-Mediated Acute Rejection (Grade II) 385
Severe Cell-Mediated Acute Rejection (Grade III) 385
11.5.3.4 Antibody Mediated Acute Rejection 386
Acute Antibody Mediated Rejection 386
Hyperacute/Accelerated Allograft Rejection 387
Chronic Active Antibody Mediated Rejection 387
11.5.3.5 Grading of Chronic Allograft Rejection/Graft Sclerosis 387
11.5.3.6 Other Histological Diagnosis 388
11.6 Other Forms of Pancreas Graft Pathology 388
11.6.1 Surgical Complications 388
11.6.1.1 Graft Thrombosis 388
11.6.1.2 Posttransplantation (Ischemic) Pancreatitis 389
11.6.1.3 Posttransplant Infectious Pancreatitis/Peripancreatitis/Fluid Collection/Peripancreatic Abscess 389
11.6.2 Viral Infections 389
11.6.2.1 Cytomegalovirus Infection 389
11.6.2.2 EBV-Related Posttransplant Lymphoproliferative Disorder 390
11.6.3 Islet Graft Pathology 391
11.6.3.1 Nonspecific Islet Pathology 391
11.6.3.2 Recurrence of Type I Diabetes Mellitus 391
11.6.3.3 Islet Cell Drug Toxicity 391
11.6.3.4 Nesidioblastosis 392
11.7 Gross and Microscopic Evaluation of Failed Allografts 392
References 392
12: Vascularized Composite Allotransplantation 396
12.1 Introduction 396
12.1.1 Specimen Adequacy 396
12.1.2 The Banff CTA Classification System 397
12.2 Mucous Membrane Rejection in Composite Tissue Allografts 399
12.3 Summary 401
References 401
Index 403