Definition/General
Introduction:
Renal pelvis TCC is a malignant urothelial neoplasm
Represents 5-10% of all renal tumors
Arises from transitional epithelium of renal pelvis
Similar to bladder cancer
Shows multifocal tendency.
Origin:
Arises from urothelial lining of renal pelvis and calyces
Shows field change phenomenon
Associated with carcinogen exposure
Papillary growth pattern common.
Classification:
WHO 2022: Urothelial carcinoma
Non-invasive (Ta, Tis)
Invasive carcinoma
High-grade vs low-grade
Squamous differentiation common.
Epidemiology:
Peak incidence 6th-7th decades
Male predominance (2-3:1)
Geographic clustering (Balkan nephropathy)
Smoking association
Occupational exposures.
Clinical Features
Presentation:
Gross hematuria (85%)
Flank pain
Ureteral obstruction
Hydronephrosis
Weight loss
Constitutional symptoms.
Symptoms:
Painless hematuria
Dysuria
Urgency/frequency
Flank/abdominal pain
Renal colic
Anuria (bilateral disease).
Risk Factors:
Tobacco smoking
Occupational chemicals (aniline dyes)
Analgesic nephropathy
Balkan endemic nephropathy
Aristolochic acid
Cyclophosphamide.
Screening:
Urine cytology
CT urography
Retrograde pyelography
Ureteroscopy with biopsy
NMP22
UroVysion FISH.
Master Renal Pelvis TCC Pathology with RxDx
Access 100+ pathology videos and expert guidance with the RxDx app
Gross Description
Appearance:
Papillary, friable mass
Gray-pink color
Soft consistency
Fills pelvis/calyces
Surface ulceration
Hydronephrosis common.
Characteristics:
Exophytic growth
Papillary fronds
Tan-pink color
Friable texture
Necrosis (high-grade)
Obstruction of PUJ.
Size Location:
Renal pelvis and calyces
Variable size (1-10 cm)
Multifocal disease
Bilateral involvement (5%)
Ureteral extension.
Multifocality:
Synchronous lesions
Multifocal/multicentric
Bladder involvement (30-50%)
Contralateral disease
Field cancerization.
Microscopic Description
Histological Features:
Papillary architecture
Fibrovascular cores
Urothelial lining
Nuclear atypia
Invasive growth
Squamous differentiation (40%).
Cellular Characteristics:
Transitional epithelium
Enlarged nuclei
Prominent nucleoli
Increased mitoses
Nuclear pleomorphism
Loss of polarity.
Architectural Patterns:
Papillary pattern (most common)
Solid growth
Nested arrangement
Single cell invasion
Squamous metaplasia
Glandular differentiation.
Grading Criteria:
WHO 2016: Low-grade vs High-grade
Nuclear features
Mitotic activity
Architectural complexity
Pleomorphism assessment.
Immunohistochemistry
Positive Markers:
CK7 - positive
CK20 - positive (umbrella cells)
Uroplakin III - positive
GATA3 - positive
p63 - positive (basal cells)
Thrombomodulin - positive.
Negative Markers:
TTF1 - negative
PSA - negative
CDX2 - negative
PAX8 - negative
RCC marker - negative.
Diagnostic Utility:
CK7/CK20 co-expression typical
Uroplakin III specific for urothelium
GATA3 sensitive urothelial marker
p63 highlights basal layer
Distinguish from RCC.
Molecular Subtypes:
Luminal type: CK20+, GATA3+
Basal type: p63+, CK5/6+
All urothelial: CK7+, uroplakin+
Squamous differentiation: p63+, CK5/6+.
Molecular/Genetic
Genetic Mutations:
FGFR3 mutations (low-grade)
TP53 mutations (high-grade)
PIK3CA mutations
CDKN2A deletions
RB1 mutations
KMT2D mutations.
Molecular Markers:
p53 pathway disruption
Cell cycle dysregulation
DNA repair defects
FGFR signaling
Chromatin remodeling.
Prognostic Significance:
Stage most important
Grade influences outcome
Hydronephrosis: Poor prognosis
Multifocal disease
Lymph node status
Squamous differentiation: Worse prognosis.
Therapeutic Targets:
Nephroureterectomy with bladder cuff
Ureteroscopic management (low-grade)
Adjuvant chemotherapy
Immunotherapy
FGFR inhibitors.
Differential Diagnosis
Similar Entities:
Squamous cell carcinoma
Adenocarcinoma
Renal cell carcinoma
Metastatic carcinoma
Inflammatory/reactive changes.
Distinguishing Features:
Urothelial: CK7+/CK20+, uroplakin+
Squamous: p63+, CK5/6+, keratinization
Adenocarcinoma: Mucin+, glandular
RCC: PAX8+, CD10+
Metastatic: Organ-specific markers.
Diagnostic Challenges:
Squamous differentiation
High-grade morphology
Crush artifact
Small biopsies
Reactive changes.
Rare Variants:
Micropapillary variant
Plasmacytoid variant
Sarcomatoid carcinoma
Small cell carcinoma.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
Nephroureterectomy with bladder cuff
Tumor Description
Papillary urothelial carcinoma measuring [X] cm in renal pelvis
Grade
[Low-grade/High-grade] urothelial carcinoma
pT Stage
pT[stage] - [invasion details]
Invasion
Depth of invasion: [lamina propria/muscularis/peripelvic fat/renal parenchyma]
Differentiation
Squamous differentiation: [absent/present ([%])]
Margins
Ureteral margin: [negative/positive], Renal parenchymal margin: [negative/positive]
Lymph Nodes
[X] of [Y] lymph nodes positive
Immunohistochemistry
CK7: Positive, CK20: Positive, Uroplakin III: Positive, GATA3: Positive
Final Diagnosis
High-grade urothelial carcinoma, renal pelvis, pT[stage]N[stage]
Follow-up
Cystoscopic surveillance recommended due to field change phenomenon