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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