Bladder Pathology

Cover
Title Page
Copyright Page
Contents
Preface
Chapter 1 Normal Anatomy and Histology
	Embryology
	Anatomy
		Gross Anatomy
		Blood Supply and Lymphatic Drainage
		Nerve Supply
	Normal Histology
		Urothelium
		Bladder Wall
		Paraganglionic Tissue
	The Urachus
	The Renal Pelvis and Ureters
	The Urethra
	Immunohistochemistry
	References
Chapter 2 Inflammatory and Infectious Conditions
	Acute and Chronic Cystitis and Its Variants
		Papillary–Polypoid Cystitis (Polypoid Cystitis, Papillary Cystitis, Bullous Cystitis)
		Follicular Cystitis (Cystitis Follicularis)
		Interstitial Cystitis (Bladder Pain Syndrome)
		Eosinophilic Cystitis
		Encrusted Cystitis
		Emphysematous Cystitis
		Gangrenous Cystitis
		Hemorrhagic Cystitis
		Viral Cystitis
		Cystitis with Atypical Giant Stromal Cells
		Denuding Cystitis
		Radiation Cystitis
		Chemical Cystitis
		Diverticulitis
	Granulomatous Cystitis
		Postsurgical Necrobiotic Granuloma (Granuloma after Transurethral Resection)
		Suture Granuloma
		BCG-induced Granulomatous Cystitis
		Schistosomiasis (Bilharziasis)-associated Cystitis
		Malakoplakia
		Tuberculosis
		Xanthoma and Xanthogranulomatous Cystitis
		Other Forms of Granulomatous Cystitis
	Other Infectious Cystitides
		Fungal Cystitis
		Actinomycosis
		Miscellaneous Infectious Cystitides
	References
Chapter 3 Urothelial Metaplasia and Hyperplasia
	von Brunn Nests
	Cystitis Cystica
	Cystitis Glandularis and Intestinal Metaplasia
		Cystitis Glandularis, Usual (Typical) Type
		Intestinal Metaplasia (Cystitis Glandularis, Intestinal Type)
		Florid Cystitis Glandularis
	Squamous Metaplasia
	Nephrogenic Adenoma (Nephrogenic Metaplasia)
	Urothelial Hyperplasia
		Flat Urothelial Hyperplasia (Flat Simple Hyperplasia; Atypical Urothelial Proliferation – Flat)
		Papillary Urothelial Hyperplasia (Early Papillary Neoplasia; Atypical Urothelial Proliferation – Tented)
		Pseudocarcinomatous Epithelial Hyperplasia
	References
Chapter 4 Polyps and Other Nonneoplastic Benign Conditions
	Polyps and Polypoid Lesions of the Bladder
		Fibroepithelial Polyp
		Prostatic-type Polyp (Ectopic Prostatic Tissue)
		Polypoid Hamartoma
		Papillary Polypoid Cystitis
		Nephrogenic Adenoma
		Papilloma
		Villous Adenoma
		Condyloma Acuminata
		Squamous Papilloma
		Inverted Papilloma
	Miscellaneous Nonneoplastic Benign Conditions
		Diverticulosis
		Müllerian Lesions
		Pigmented Lesions
	Metabolic Deposits
		Amyloidosis
		Tamm–Horsfall Protein Deposit (Tamm–Horsfall Pseudotumor; Proteinoma)
	Other Rare Benign Lesions
		“Submucosal” Calcification and Ossification
		Hemorrhage and Rupture
	References
Chapter 5 Benign Epithelial Tumors
	Papilloma of the Urinary Bladder
		Urothelial Papilloma
		Diffuse Papillomatosis (Bladder Papillomatosis)
	Inverted Papilloma
	Squamous Papilloma
	Villous Adenoma and Tubulovillous Adenoma
	Urachal Adenoma
	References
Chapter 6 Flat Urothelial Lesions with Atypia and Urothelial Dysplasia
	Flat Urothelial Lesions with Atypia
		Background and Terminology
		Reactive Urothelial Atypia
	Urothelial Dysplasia
		Primary Urothelial Dysplasia
		Secondary Urothelial Dysplasia
	Molecular Alterations in Flat Lesions
	References
Chapter 7 Urothelial Carcinoma In Situ
	Definition, Terminology, and Historical Perspective
	Clinical Features
	Special Considerations
		Primary Versus Secondary Carcinoma In Situ
		Prostatic Ducts and Prostatic Urethra Involvement
	Histopathology and Diagnostic Criteria
	Variants of Urothelial Carcinoma In Situ
		Large Cell Carcinoma In Situ
		Small Cell Carcinoma In Situ
		Denuding and “Clinging Pattern” Carcinoma In Situ
		Pagetoid and Undermining (Lepidic) Carcinoma In Situ
		Carcinoma In Situ with Squamous or Glandular Differentiation
		Carcinoma In Situ with Micropapillary Growth
		Carcinoma In Situ with Plasmacytoid Features
		Carcinoma In Situ with Microinvasion
	Differential Diagnosis
	Diagnostic and Predictive Biomarkers
	Prognosis
		Primary Carcinoma In Situ
		Carcinoma In Situ with Non-muscle-invasive Bladder Cancer
		Carcinoma In Situ with Muscle-invasive Bladder Cancer
		Multicentricity
		Upper Urinary Tract and Urethral Carcinoma In Situ Involvement
	Molecular Studies
	References
Chapter 8 Bladder Cancer: General Features
	Epidemiology and Risk Factors
	Genetic Predisposition and Syndromic Associations
	Clinical Features and Natural History of Bladder Cancer
	Morphologic Characteristics of Invasive Urothelial Carcinoma
	Urothelial Carcinoma in Young Adults
	Prognosis of Invasive Urothelial Cancer
	Treatment of Bladder Cancer
	Field Cancerization and Tumor Multicentricity
	The Origin of Bladder Cancer
	Molecular Genetics
	Molecular Therapies Targeting Molecular Pathways
	References
Chapter 9 Classification and Grading of Bladder Cancer
	Overview
	Histologic Grading According to the 1973 World Health Organization Classification
		Urothelial Papilloma
		Grade 1 Urothelial Carcinoma
		Grade 2 Urothelial Carcinoma
		Grade 3 Urothelial Carcinoma
	Histologic Grading According to the 1998 International Society of Urological Pathology/2004/2016/2022 World Health Organization Classification
		Urothelial Papilloma
		Papillary Urothelial Neoplasm of Low Malignant Potential
		Low-grade Urothelial Carcinoma
		High-grade Urothelial Carcinoma
	Should We Abandon Papillary Urothelial Neoplasm of Low Malignant Potential?
		What Constitutes a Carcinoma?
		Recurrence and Progression of Papillary Urothelial Neoplasms of Low Malignant Potential
		Interobserver Variability
		Does Papillary Urothelial Neoplasm of Low Malignant Potential Exist in the Upper Urinary Tract?
		Papillary Urothelial Neoplasm of Low Malignant Potential and Urinary Cytopathology
		Genetics of Papillary Urothelial Neoplasm of Low Malignant Potential
		Papillary Urothelial Neoplasm of Low Malignant Potential Treatment and Followup
	Histologic Grading of Urothelial Carcinoma: New Proposal
		Urothelial Papilloma
		Grade 1 Urothelial Carcinoma (Low-Grade)
		Grade 2 Urothelial Carcinoma (Low-Grade)
		Grade 3 Urothelial Carcinoma (High-Grade)
		Grade 4 Urothelial Carcinoma (High-Grade)
	Other Proposals for Bladder Cancer Grading and Tumor Heterogeneity
		Ancona 2001 Refinement of the World Health Organization 1973 Classification
		The World Health Organization 1999 Grading Proposal
	Grading of Invasive Bladder Carcinoma
	Tumor Grade Heterogeneity
	Molecular Classification and Grading
	References
Chapter 10 Stage pT1 Urothelial Carcinoma
	Diagnosis of Lamina Propria Invasion (pT1 Urothelial Carcinoma)
		The Lamina Propria and Characteristics of Smooth Muscle in the Bladder Wall
		Histologic Grade
		Stroma–Epithelial Interface
		Invading Epithelium
		Stromal Response
		Role of Immunohistochemistry in the Diagnosis of Invasion
	Unusual Histologic Patterns of Lamina Propria Invasion
		Microinvasion in Carcinoma In Situ and Papillary Urothelial Carcinoma
		Urothelial Carcinoma with Invasion at the Tumor Base or with Invasion into Papillary Stalk
		pT1 Bladder Carcinoma with Histologic Variant (Subtype) or Deceptively Bland Cytology
		Invasion in Urothelial Carcinoma with Inverted Growth
	Pitfalls in the Diagnosis of Stage pT1 Urothelial Carcinoma
		Tangential Sectioning and Poor Orientation
		Obscuring Inflammation
		Urothelial Carcinoma with Endophytic or Broad-front Growth Pattern
		Pseudoinvasive Nests of Benign Proliferative Urothelial Lesions
		Muscle Invasion Indeterminate for the Type of Muscle
		Pathologic Features of pT1 “Gray Zone” Cases
		pT1 Assessment after Therapy
		Other Potential Pitfalls
	pT1 Assessment: Reproducibility
	Pathologic Risk Assessment of Recurrence and Progression in pT1 Bladder Cancer
		Substaging of pT1 Bladder Cancer
		Other Histologic Features
		Concomitant Carcinoma In Situ
		Lymphovascular Invasion
		Tumor Budding
		Histological Variants
		Persistence of pT1 Cancer upon Restaging Transurethral Resection of Bladder Tumor
	Reporting pT1 Bladder Cancer
	Molecular Biomarkers and pT1 Bladder Cancer Disease
	References
Chapter 11 Staging of Bladder Cancer
	Stage T0 Carcinoma
	Stage Ta Carcinoma
	Stage Tis Carcinoma
	Stage pT1 Carcinoma
	Stage pT2 Carcinoma
	Stage pT3 Carcinoma
	Stage pT4 Carcinoma
	Lymphovascular and Perineural Invasion
	Nodal Classification (N Staging)
	Distant Metastasis (M Staging)
	TNM Descriptors
	References
Chapter 12 Histological Variants (Subtypes) of Urothelial Carcinoma
	General Features and Classification
	Urothelial Carcinoma with Divergent Differentiation
		Urothelial Carcinoma with Squamous Differentiation
		Urothelial Carcinoma with Glandular Differentiation
		Urothelial Carcinoma with Trophoblastic Differentiation
		Urothelial Carcinoma with Müllerian Differentiation
	Histological Variants of Urothelial Carcinoma
		Micropapillary Urothelial Carcinoma
		Nested Urothelial Carcinoma
		Tubular and Microcystic Urothelial Carcinoma
		Large Nested Urothelial Carcinoma
		Plasmacytoid Urothelial Carcinoma
		Sarcomatoid Urothelial Carcinoma
		Lipid-rich Urothelial Carcinoma
		Lymphoepithelioma-like Urothelial Carcinoma
		Clear Cell (Glycogen-rich) Urothelial Carcinoma
		Giant Cell Urothelial Carcinoma
		Poorly Differentiated Urothelial Carcinoma
	Other Histological Variants (Subtypes) of Bladder Cancer
		Urothelial Carcinoma with Chordoid Features/Myxoid Stroma
		Pseudoangiosarcomatous (Angiosarcoma-like) Urothelial Carcinoma
		Urothelial Carcinoma with Oncocytic Features
		Urothelial Carcinoma with Rhabdoid Features
		Undifferentiated Carcinoma with Rhabdoid Features and Loss of Expression of the SWI/SNF Complex
		Urothelial Carcinoma with Multiple Histological Subtypes
		Stroma-rich Urothelial Carcinoma
		Other Histological Variants
	Molecular Pathology of Common Histological Variants (Subtypes) of Urothelial Carcinoma
		Micropapillary Variant Urothelial Carcinoma
		Nested Variant of Urothelial Carcinoma
		Plasmacytoid Variant of Urothelial Carcinoma
		Other Bladder Carcinomas with Variant Histology
	References
Chapter 13 Bladder Tumors with Inverted Growth
	Inverted Papilloma
		Clinical Features
		Pathology
		Differential Diagnosis
		Molecular Pathology
	Inverted Papillary Urothelial Neoplasia of Low Malignant Potential
	Inverted Variant (Subtype) of Urothelial Carcinoma (Urothelial Carcinoma with Inverted Growth)
		Clinical Features and Morphology
		Immunohistochemistry and Fluorescence In Situ Hybridization
		Differential Diagnosis
	Florid von Brunn Nest Proliferations
	Florid Cystitis Glandularis
	Nested Variant (Subtype) Urothelial Carcinoma
	Verrucous Squamous Cell Carcinoma
	References
Chapter 14 Bladder Carcinoma in Specific Clinical Setting
	Diverticular Carcinoma
	Urothelial Carcinoma Following Augmentation Cystoplasty
		Overview
		Clinical Features
		Histopathology
		Immunohistochemistry
		Molecular Genetics
	Bladder Carcinoma in Neuropathic Bladder (Spinal Cord Injury)
	Urothelial Carcinoma in Children and Young Adults
	Urothelial Carcinoma in Lynch Syndrome Patients
	References
Chapter 15 Sarcomatoid Carcinoma (Carcinosarcoma)
	Overview
	Definition and Terminology
	Clinical Presentation
	Pathology
	Ultrastructural Features
	Immunohistochemistry and Differential Diagnosis
	Upper Urinary Tract Sarcomatoid Carcinoma
	Prognosis and Treatment
	Molecular Pathology of Sarcomatoid Carcinoma
		Genetic and Molecular Studies
		Histogenesis
		Monoclonal “Divergent Differentiation” Theory
		Multiclonal “Collision” Theory
		Molecular Genetic Evidence Supportive of Monoclonal Origin
		Epithelial–Mesenchymal Transition and Cancer Stem Cells
	Summary and Future Perspectives
	References
Chapter 16 Adenocarcinoma and Its Putative Precursors and Variants
	Putative Precursor Lesions
		Intestinal Metaplasia
		Villous Adenoma and Tubulovillous Adenoma
		Adenocarcinoma In Situ (Carcinoma In Situ with Glandular Differentiation)
	Adenocarcinoma
		Adenocarcinoma, Not Otherwise Specified (NOS)
		Adenocarcinoma with Enteric (Colonic or Intestinal Type) Pattern
		Mucinous (Colloid) Adenocarcinoma
		Signet Ring Cell Carcinoma
		Adenocarcinoma with Mixed Patterns
		Müllerian-type Adenocarcinoma
		Other Patterns of Adenocarcinoma
		Molecular Pathology of Adenocarcinoma
		Mimickers of Adenocarcinoma
	Urachal Adenocarcinoma
	References
Chapter 17 Squamous Cell Carcinoma and Other Squamous Lesions
	Squamous Cell Carcinoma
		Epidemiology, Clinical Features and Risk Factors
		Prognostic Features
		Macroscopic Pathology
		Microscopic Pathology
		Schistosoma-Associated Squamous Cell Carcinoma
		Verrucous Squamous Cell Carcinoma
		Basaloid Squamous Cell Carcinoma
		Molecular Features of Squamous Cell Carcinoma
	Other Squamous Lesions
		Keratinizing Squamous Metaplasia
		Squamous Cell Carcinoma In Situ
		Squamous Papilloma
		Condyloma Acuminatum
	References
Chapter 18 Neuroendocrine Tumors
	Small Cell Neuroendocrine Carcinoma
		Epidemiology and Clinical Features
		Pathologic Findings
		Ultrastructural Features
		Immunohistochemistry
		Differential Diagnosis
		Histogenesis
		Molecular Genetics
		Prognostic Factors
		Staging, Treatment, and Outcome
	Well-Differentiated Neuroendocrine Tumor (Carcinoid Tumor)
	Large Cell Neuroendocrine Carcinoma
	Mixed Neuroendocrine Carcinomas
	Primitive Neuroectodermal Tumor/Ewing Sarcoma
	Malignant Peripheral Nerve Sheath Tumor
	Paraganglioma
	Neurofibroma
	Schwannoma
	Secondary Neuroendocrine Carcinoma
	References
Chapter 19 Handling and Reporting of Bladder Specimens
	Specimen Handling
		Biopsy and Transurethral Resection Specimens
		Cystectomy, Cystoprostatectomy, and Pelvic Exenteration (En Bloc Resection) Specimens
		Partial Cystectomy, Diverticulectomy, and Urachal Resection Specimens
		Lymph Node Dissection
		Reporting Upper Urinary Tract Specimens (See Chapter 27)
		Reporting Urethral Specimens (See Chapter 27)
	Pathology Reporting
		An Overview
		Tumor Size
		Gross Tumor Configuration
		Tumor Multifocality
		Histologic Type
		Histologic Grading
		Tumor Growth Pattern
		Lymphovascular Invasion
		Perineural Invasion
		Surgical Margins
		Tissue Artifacts
		Treatment Effect
	References
Chapter 20 Congenital Disorders and Pediatric Neoplasms
	Congenital Disorders
		Exstrophy
		Duplication and Diverticulum
		Fistula and Cysts
		Megacystis
		Congenital Bladder Obstruction (Marion Disease)
		Urachal Anomalies
	Inflammatory and Related Conditions in Children
	Rupture and Calculi in Children
	Benign Epithelial and Polypoid Lesions
	Urothelial Papilloma
	Urothelial Carcinoma in Children
		Epidemiology and Clinical Features
		Pathology
		Immunohistochemistry
		Molecular Features
	Soft Tissue Neoplasms
		Hemangioma
		Neurofibroma
		Inflammatory Myofibroblastic Tumor
		Rhabdomyosarcoma
	Other Rare Tumors
	References
Chapter 21 Soft Tissue Tumors
	Myofibroblastic Proliferations and Neoplasms
		Inflammatory Myofibroblastic Tumor
		Postoperative Spindle Cell Nodule
	Benign Soft Tissue Tumors
		Leiomyoma
		Hemangioma
		Neurofibroma
		Schwannoma
		Solitary Fibrous Tumor
		Paraganglioma
		Granular Cell Tumor
		Glomus Tumor
	Malignant Soft Tissue Tumors
		Leiomyosarcoma
		Rhabdomyosarcoma
		Angiosarcoma
		Undifferentiated Sarcoma (Malignant Fibrous Histiocytoma)
		Primitive Neuroectodermal Tumor/Ewing Sarcoma
		Malignant Peripheral Nerve Sheath Tumor
		Hemangiopericytoma (Solitary Fibrous Tumor)
		Alveolar Soft Part Sarcoma
	Other Soft Tissues Neoplasms Arising in the Bladder
	References
Chapter 22 Lymphoid and Hematopoietic Tumors
	Malignant Lymphoma
	Leukemia
	Multiple Myeloma/Plasmacytoma
	References
Chapter 23 Other Rare Tumors
	Malignant Melanoma
	Germ Cell Tumors
		Yolk Sac Tumor
		Choriocarcinoma
		Other Germ Cell Tumors
	Dermoid Cyst
	Rhabdoid Tumor
	Perivascular Epithelioid Cell Tumor
	Granular Cell Tumor
	References
Chapter 24 Secondary Tumors
	Overview
	Secondary Adenocarcinoma
		Colorectal Adenocarcinoma Extension to the Bladder
		Prostate Adenocarcinoma Extension to the Bladder
	Carcinoma of the Female Genital Tract Extension to the Bladder
		Squamous Cell Carcinoma Extension to the Bladder
		Bladder Involvement by Malignancy of the Female Genital Tract
	Secondary Lobular Carcinoma of the Breast
	Invasive Micropapillary Carcinoma: Primary Versus Secondary
	Metastasis from Other Organs
	Metastatic Urothelial Carcinoma
	References
Chapter 25 Treatment Effects
	Overview
	Systemic Therapy-Related Changes
		Systemic Cyclophosphamide (Cytoxan)
		Systemic Ketamine
		Neoadjuvant Systemic Chemotherapy
		Systemic Immunotherapy (Immune Checkpoint Inhibitors)
		Other Novel Systemic Therapies
	Intravesical Therapy
		Mitomycin C
		Thiotepa
		Other Chemotherapeutic Agents
		Intravesical Immunotherapy
	Radiation-Induced Changes
	Chemical Cystitis
	Gene Therapy
	Photodynamic and Laser Therapy
		Photodynamic Therapy
		Laser Therapy
	Treatment-Related Granulomatous Cystitis
		Postsurgical Necrobiotic Granuloma
		Suture Granuloma
		BCG-Induced Granulomatous Cystitis
	Surgery-Related Pathologic Lesions (Table 25-11)
		Postoperative Spindle Cell Nodule
		Malignancy Associated with Bladder Augmentations and Intestinal Conduits
	Reactive Instrumentation Effects of the Upper Tract and the Urethra
	Diagnostic Immunohistochemistry of Therapy-Related Urothelial Atypia
	References
Chapter 26 Pathology of the Urachus
	Overview
	Congenital Anomalies
		Patent Urachus
		Urachal Remnant
		Urachal Cysts
	Infectious Conditions
	Benign Neoplasms of the Urachus
		Adenoma and Villous Adenoma
		Benign Soft Tissue Tumors
	Malignant Neoplasms
		Urachal Adenocarcinoma
		Urothelial Carcinoma
		Squamous Cell Carcinoma
		Neuroendocrine Carcinomas
		Mixed Carcinomas
		Prognostic and Predictive Factors
		Molecular Pathology of Urachal Carcinoma
		Sarcoma Arising in the Urachus
		Other Malignant Tumors Arising in the Urachus
	References
Chapter 27 Pathology of Renal Pelvis, Ureter, and Urethra
	Overview
	Congenital Anomalies
		Renal Pelvis and Ureter
		Urethra
	Pyelitis, Ureteritis, and Urethritis
	Benign Lesions and Mimics of Cancer
		Idiopathic Retroperitoneal Fibrosis
		Fibroepithelial Polyp
		Endometriosis
		Urethral Inflammatory Polyp
		Urethral Caruncle
		Urethral Diverticula
		Ectopic Prostatic Tissue
		Subepithelial Hematoma of the Renal Pelvis
	Neoplasms of the Renal Pelvis and Ureter
		Benign Urothelial Neoplasms
		Flat Urothelial Lesions with Atypia
		Urothelial Carcinoma
		Adenocarcinoma
		Squamous Cell Carcinoma
	Tumor of the Urethra
		Benign Epithelial Tumors of the Urethra
		Carcinoma of the Urethra
	Soft Tissue Tumors
		Renal Pelvis and Ureter
		Urethra
	Miscellaneous and Secondary Tumors
		Reactive Instrumentation Effects in the Upper Tract and the Urethra
	References
Chapter 28 Diagnostic Immunohistochemistry
	Overview
	Markers Useful for the Determination of Urothelial Origin
	Distinguishing Muscularis Propria from Muscularis Mucosae
	Distinguishing Dysplasia and Carcinoma In Situ from Reactive Urothelial Atypia
	Distinguishing Urothelial Carcinoma from Prostatic Adenocarcinoma
	Differentiating Primary Squamous Cell Carcinoma of the Bladder from Secondary Tumors
	Glandular Tumors
	Neuroendocrine Tumors
	Spindle Cell Tumors
	Metastatic Urothelial Carcinoma
	Diagnostic Immunohistochemistry in Bladder Carcinoma with Variant Histology (Histologic Subtypes)
	References
Chapter 29 Tissue-Based Biomarkers for Prognosis and to Guide Therapy for Bladder Cancer
	Overview
	Proliferation Markers (PCNA, Ki67, and MIB1)
	Apoptosis Markers
	Tumor Suppressor Genes
		TP53 and Cell Cycle Regulators
		RB
		TSC1
		FHIT
		PTEN
		p63
	Growth Factors and Receptors
		FGFR3
		EGFR
		VEGF
		FGFA
		bFGF
	Oncogenes
		ERBB2 (HER2)
		HRAS
		MDM2
		MYC
		Cyclin D1 and D3
	Cell Adhesion Markers
		E-Cadherin (CDH1)
		Integrins
		CD44
		F and G Actin
	Vessel Density
		Microvessel Density
		Lymph Vessel Density
	Telomerase
	Miscellaneous Markers
		Multidrug Resistance Proteins (MDR/MRP/TAP)
		Cyclooxygenase 2 (COX2)
		Gelsolin
		Others
	Combined Biomarkers and Nomograms
	Impact of Biomarkers on Pathologic Classification of Bladder Tumors
	Tissue-Based Biomarkers and Targeted Therapy for Bladder Cancer
		Biomarkers for PD-1/PD-L1 Blockade in Bladder Cancer
		FGFR3 Immunohistochemistry and FGFR3 Inhibitors
	Future Perspectives
	References
Chapter 30 Molecular Pathology of Bladder Cancer
	Overview
	FGFR3 and TP53 Gene Mutations Define Two Key Pathways in Urothelial Carcinogenesis
		FGFR3 Pathway
		TP53 Pathway
		Third Pathway?
	Understanding Urothelial Carcinogenesis: Methodological Considerations
		Numerical Chromosomal Alterations
		Structural Chromosomal Alterations and Allelic Imbalance
		DNA Sequence Aberrations
		Microsatellite Instability
		Epigenetic Alteration and Gene Methylation
		MicroRNA Deregulation
		Global Analysis of Gene Expression Profiles
		Proteomics and Protein Expression Alterations
		Combined Biomarkers and Nomograms
	Cancer Stem Cells and Urothelial Carcinogenesis
	Precursor Lesions of Bladder Cancer
	Multifocal Bladder Tumors and Field Effects
	Tumor Heterogeneity
	Early Detection of Urothelial Carcinoma
	Molecular Grading
	Molecular Staging
		Molecular Detection of Lymph Node Metastasis
		Molecular Detection of Circulating Cancer Cells
	Molecular Classification of Bladder Urothelial Carcinoma
		Molecular Subtypes
		Non-Muscle-Invasive Bladder Cancer
		Muscle-Invasive Bladder Cancer
		Immunohistochemistry as a Surrogate of Molecular Subtypes
		Molecular Pathology of Histologic Subtypes (Variant Histology) of Bladder Carcinoma
	TERT Promoter Mutation in Urothelial Carcinoma
	Future Perspectives
	References
Chapter 31 Molecular Determinants for Tumor Prognosis and Targeted Therapy
	Determinants of Tumor Recurrence
		Overview
		Molecular Pathways Linked to Tumor Recurrence
		FGFR3 Gene Mutation Is Associated with Low Risk of Recurrence
		TP53 Gene Mutation Is Associated with High Risk of Recurrence
	Gene Expression Signature to Predict Bladder Cancer Recurrence
	Combined Biomarkers as Predictor of Tumor Recurrence
	Epigenetic Alterations as Predictor of Tumor Recurrence
	Other Genomic Alterations as Predictor for the Tumor Recurrence
	Serum Markers to Predict Bladder Cancer Recurrence
	Implications of Field Effect and Cancer Stem Cells in Recurrence of Bladder Cancer
	Marker Validation and Experimental Bias
	Liquid Biopsy in the Clinical Management of Bladder Cancer
		Circulating Tumor Cells as Serum Biomarkers
		Circulating RNA as Serum Biomarkers
		Circulating Tumor DNA as a Serum Biomarker
	Molecular Biomarkers and Targeted Therapy
		Molecular Biomarkers for FGFR3 Inhibitors and Other Novel Targets
		Immune Checkpoint-Related Biomarkers
	Molecular Basis of Resistance to Therapy
		ERCC1
		Poly (ADP-Ribose) Polymerase
		Nuclear Factor Erythroid 2-related Factor 2 or Copper Transporter 1
		MicroRNAs
		Epithelial–Mesenchymal Transition
		Resistance to Gemcitabine
		Resistance to MVAC Regimen
		Resistance to Taxanes or Vinflunine
		Resistance to Targeted Agents
	Future Perspectives
	References
Chapter 32 Urine-Based Biomarkers
	Overview
		UroVysion Fluorescence In Situ Hybridization Test
	Bladder Tumor Antigen
	Nuclear Matrix Protein 22
	ImmunoCyt/uCyt+
	Urinary Bladder Cancer Antigen
	Hemoglobin Dipstick
	Emerging Urine Biomarkers
		DNA-Related Biomarkers
		RNA-Related Biomarkers
		Extracellular Vesicles and Exosomes
		Urine-Based Gene Mutation Profile in Bladder Cancer Diagnosis and Prognosis
		Urine Analysis of Components of the Tumor Microenvironment
		Commercially Available RNA/DNA-Based Detection Tests for Bladder Cancer
		Other Emerging Biomarkers
	Ancillary Studies
		Flow Cytometry/DNA Ploidy Analysis
		Digital Image Analysis and Computational Pathology
		Immunohistochemistry and Enzyme-Linked Immunosorbent Assay
		Molecular Genetic Studies
	References
Chapter 33 Evaluation of Hematuria and Urinalysis
	Overview
	Laboratory Investigation
	Dysmorphic Red Blood Cells Indicate Glomerular Disease
	Epithelium of the Lower Urinary Tract and Kidney
	Renal Epithelium
	Renal Casts in Urine Sediment
	Urolithiasis
	Optimal Cytodiagnostic Urinalysis of Hematuria
	References
Chapter 34 Urinary Cytology
	Overview
	Types of Specimen
	Normal Components of the Urinary Cytology Specimens
		Superficial (Umbrella) Cells
		Cells from the Deeper Layers of the Urothelium
		Mucus-Containing Epithelial Cells
		Squamous Cells
		Other Cellular Components
		Noncellular Components of the Urinary Sediment
	Inflammatory Lesions
		Bacteria
		Fungi
		Viruses
		Trematodes and Other Parasites
	Reactive Changes in Urinary Cytology
		Lithiasis
		Drug Effects
		Radiation Therapy Effects
	Urinary Cytology in Renal Transplant Recipients
	Other Benign Conditions
	Benign Tumors and Tumor-Like Processes
	Cytologic Diagnosis of Bladder Malignancies
		Cytologic Diagnosis of Dysplasia and Urothelial Carcinoma In Situ
		Cytologic Diagnosis of Urothelial Carcinoma
		Squamous Cell Carcinoma
		Adenocarcinoma
		Neuroendocrine Carcinoma Including Small Cell Carcinoma
		Other Malignant Tumors
	The Paris System for Reporting Urinary Cytology
		Background
		Diagnostic Categories
	Secondary Tumors
	Cytology of Anatomic Sites Other Than Urinary Bladder
	Sources of Diagnostic Pitfalls
		Trauma or Instrumentation
		Cell Preservation
		Human Polyomavirus
		Lithiasis
		Drugs and Other Therapeutic Procedures
	References
Index
EULA