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Fifteen years have elapsed since the publication of the original book under the same title. With the passage of time little has changed and the same conceptual mistakes continue to be made in the practice of urinary cytopathology as in the past. For this reason a much simplified new edition of this book with the application of new processing techniques has been thought to be a worthwhile undertaking . Numerous new color photographs from the file of the co-editor have replaced old black and white photographs and will hopefully support the brief text for the benefit of patients. This volume will appeal to urologists as well as pathologists, cytopathologists and related professions.
xiii
1 Introduction .......................................................................................................................... 1
Historical Note ....................................................................................................................... 1
Suggested Readings ............................................................................................................... 5
2 Indication, Collection, and Laboratory Processing of Cytologic Samples...................... 7
General ................................................................................................................................... 7
Methods of Specimen Collection ........................................................................................... 8
Voided Urine ...................................................................................................................... 8
Catheterized Urine ............................................................................................................. 9
Direct Sampling techniques ............................................................................................... 9
Ileal Bladder Urine ............................................................................................................. 10
Laboratory Processing of Urinary Specimens ....................................................................... 10
Liquid-Based Processing Techniques ................................................................................ 10
SurePath ............................................................................................................................. 10
ThinPrep ............................................................................................................................. 14
Residual LBP Specimen ........................................................................................................ 15
Suggested Readings ............................................................................................................... 15
3 The Cellular and Acellular Components of the Urinary Sediment ................................. 17
Normal Lower Urinary Tract ................................................................................................. 17
Anatomy ................................................................................................................................. 17
Normal Urothelium (Transitional Epithelium) and Its Cells ................................................. 18
Histology and Ultrastructure .............................................................................................. 18
Ultrastructure of the Umbrella Cells .................................................................................. 19
Variants of Normal Urothelium ......................................................................................... 21
Cells Derived from Normal Urothelium ............................................................................ 21
Other Benign Cells ................................................................................................................. 28
Squamous Cells .................................................................................................................. 28
Blood Cells............................................................................................................................. 31
Erythrocytes ....................................................................................................................... 31
Noncellular Components of Urinary Sediment ...................................................................... 32
Crystals .............................................................................................................................. 32
Suggested Readings ............................................................................................................... 35
Contents
xiv Contents
4 The Cytologic Makeup of the Urinary Sediment According
to the Collection Technique ................................................................................................. 37
Introduction ............................................................................................................................ 37
Cytologic Makeup of the Sediment of Normal Voided Urine ............................................... 37
Cell Preservation in Voided Urine ......................................................................................... 40
Cytologic Makeup of Bladder Washings ............................................................................... 40
Cytologic Makeup of Normal Retrograde Catheterization Specimens .................................. 42
Cytologic Makeup of Smears Obtained by Brushing ............................................................ 43
Cytologic Makeup of Ileal Bladder Urine ............................................................................. 44
Suggested Readings ............................................................................................................... 45
5 Cytologic Manifestations of Benign Disorders Affecting Cells
of the Lower Urinary Tract ................................................................................................. 47
Infl ammatory Disorders ......................................................................................................... 47
Bacterial Agents ................................................................................................................. 47
Pyelonephrirtis ................................................................................................................... 48
Cystitis ............................................................................................................................... 48
Hunner’s Ulcer (Interstitial Cystitis) .................................................................................. 49
Infl ammatory Pseudopolyp ................................................................................................ 49
Eosinophilic Cystitis (Eosinophilic Granuloma) ............................................................... 50
Follicular Cystitis ............................................................................................................... 50
Papillary Hyperplasia ......................................................................................................... 50
Cystitis Cystica and Cystitis Glandularis ........................................................................... 51
Nephrogenic Metaplasia (Adenoma) ................................................................................. 52
Actinomyces and Norcardia ............................................................................................... 53
Tuberculosis ....................................................................................................................... 53
Fungal Agents ........................................................................................................................ 54
Viral Infections ....................................................................................................................... 55
Human Polyomavirus (Decoy Cells) ................................................................................. 55
Herpes Simplex Virus ........................................................................................................ 59
Human Papillomavirus ....................................................................................................... 60
Cytomegalovirus ................................................................................................................ 60
Cellular Inclusions Not Due to Viral Agents ......................................................................... 61
Nonspecifi c Cytoplasmic Eosinophilic Inclusions
(Melamed-Wolinska Bodies) ............................................................................................. 61
Parasites ................................................................................................................................. 62
Trematodes: Schistosoma haematobium ............................................................................ 62
Other Parasites ....................................................................................................................... 62
Lithiasis .................................................................................................................................. 63
Leukoplakia ............................................................................................................................ 63
Effect of Drugs ....................................................................................................................... 66
Intravesically Administered Drugs .................................................................................... 66
Systemically Administered Drugs ..................................................................................... 66
Cyclophosphamide (Cytoxan, Endoxan) ........................................................................... 66
Busulfan (Myleran) ............................................................................................................ 68
Effects of Radiotherapy ......................................................................................................... 68
Urinary Cytology in Bone Marrow Transplant Recipients .................................................... 68
Monitoring of Renal Transplant Patients ............................................................................... 68
Contents xv
Rare Benign Conditions ......................................................................................................... 69
Malakoplakia ...................................................................................................................... 69
Benign Giant Cells in Multiple Myeloma .......................................................................... 70
Suggested Readings ............................................................................................................... 70
6 Tumors and Related Conditions of the Bladder and Lower Urinary Tract ................... 73
Non-neoplastic Changes ........................................................................................................ 73
Urothelial Hyperplasia ....................................................................................................... 73
Inverted Papilloma ............................................................................................................. 74
Tumors ................................................................................................................................... 76
Epidemiology ..................................................................................................................... 76
Histologic Classifi cation of Tumors of the Bladder, Renal Pelves, and Ureters.................... 76
Two Pathways of Bladder Tumors ..................................................................................... 77
Low-Grade Papillary Urothelial Tumors with no/Minimal Nuclear Atypia .......................... 78
Low-Grade Papillary Urothelial Carcinoma ...................................................................... 78
Cytologic Recognition of Low-Grade Tumors in Urinary Sediment ..................................... 79
High-Grade Urothelial Tumors .............................................................................................. 80
High-Grade Papillary Carcinoma....................................................................................... 80
Nonpapillary Urothelial Tumors ........................................................................................ 82
Invasive Urothelial Carcinomas ............................................................................................. 85
Histologic Patterns ............................................................................................................. 85
Grading .............................................................................................................................. 85
Staging ............................................................................................................................... 87
Flat Carcinoma In Situ ........................................................................................................... 87
Clinical Presentation .......................................................................................................... 88
Histology ............................................................................................................................ 90
Cytologic Recognition of High-Grade Urothelial Tumors in Urinary Sediment ................... 91
Histologic Variants of Urothelial Carcinoma ......................................................................... 96
Squamous (Keratinizing) Carcinoma ................................................................................. 96
Adenocarcinoma and Its Variants ...................................................................................... 96
Small Cell (Oat Cell) Carcinomas ..................................................................................... 99
Metastatic Tumors .............................................................................................................. 100
Carcinoma and Precancerous States of the Uterine Cervix ............................................... 100
Other Carcinomas of the Female Genital Tract ................................................................. 101
Prostatic Carcinoma ........................................................................................................... 102
Carcinomas of Colon and Rectum ..................................................................................... 102
Carcinoma of Renal Cell Origin ........................................................................................ 102
Metastatic Carcinomas from Distant Sites ......................................................................... 103
Other Metastatic Tumors.................................................................................................... 103
Cytologic Monitoring of Patients Treated for Tumors of Lower Urinary Tract .................... 104
Reporting of Cytologic Findings ........................................................................................... 105
Suggested Readings ............................................................................................................... 106
7 Urine-Based Assays Complementing Cytologic Examination
in the Detection of Urothelial Neoplasm ............................................................................ 109
Introduction ............................................................................................................................ 109
US FDA-Approved Markers .................................................................................................. 109
Bladder Tumor Antigen (BTA) .......................................................................................... 109
Nuclear Matrix Protein 22 (NMP22) ................................................................................. 110
Fibrin–Fibrinogen Degradation Product (FDP) ................................................................. 111
xvi Contents
ImmunoCyt ........................................................................................................................ 111
UroVysion .......................................................................................................................... 112
Potential Markers in Earlier Phases of Clinical Development ............................................... 113
Bladder Cancer Antigen-4 (BLCA-4) ................................................................................ 113
Survivin .............................................................................................................................. 114
UBC Tests .......................................................................................................................... 114
CYFRA 21-1 ...................................................................................................................... 114
Hyaluronic Acid (HA)-Hyaluronidase (HAase) ................................................................ 115
Telomerase ......................................................................................................................... 115
Quanticyt ............................................................................................................................ 115
Fibroblast Growth Factor Receptor 3 (FGFR3) ................................................................. 116
Mucin 7 (MUC7) ............................................................................................................... 116
VEGF ................................................................................................................................. 116
Markers Detected by Immunocytochemistry ......................................................................... 117
CKs .................................................................................................................................... 117
p53...................................................................................................................................... 117
Ki-67 .................................................................................................................................. 118
p16...................................................................................................................................... 118
Epidermal Growth Factor Receptor (EGFR) ..................................................................... 118
E-Cadherin ......................................................................................................................... 118
Comparison Between Urine Cytology and FDA-Approved Markers .................................... 119
Conclusion ............................................................................................................................. 120
References .............................................................................................................................. 120
Index ............................................................................................................................................ 123
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