Definition/General
Introduction:
Papillary RCC is the second most common type of renal cell carcinoma
Represents 10-15% of all RCCs
Shows papillary and tubulopapillary architecture
Two distinct subtypes with different prognosis.
Origin:
Arises from distal tubular epithelium
Associated with MET gene mutations
Shows trisomy 7, 17 and loss of Y chromosome
Develops from papillary adenoma precursor.
Classification:
WHO 2022 classification: Papillary renal cell carcinoma
Type 1: Small cells, basophilic cytoplasm
Type 2: Large cells, eosinophilic cytoplasm
Grading: WHO/ISUP grade 1-4.
Epidemiology:
Peak incidence 6th-7th decades
Male predominance (2-4:1)
Second most common RCC
Associated with hereditary papillary RCC syndrome
Acquired cystic kidney disease.
Clinical Features
Presentation:
Often asymptomatic
Smaller size at presentation than clear cell RCC
Better overall prognosis
Incidental finding common
Bilateral/multifocal more frequent.
Symptoms:
Hematuria
Flank pain
Palpable mass (less common)
Constitutional symptoms rare
Hypertension
Renal dysfunction.
Risk Factors:
Male gender
End-stage renal disease
Acquired cystic kidney disease
MET germline mutations
Hereditary papillary RCC
Chronic dialysis.
Screening:
CT/MRI imaging
Genetic testing (familial cases)
Screening in ESRD patients
MET mutation testing
Regular surveillance in hereditary syndromes.
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Gross Description
Appearance:
Well-circumscribed
Encapsulated
Tan to gray color
Solid or cystic
Hemorrhage and necrosis less common
Pseudocapsule thick.
Characteristics:
Firm consistency
Tan-brown cut surface
Well-demarcated
Calcifications common
Cystic degeneration
Less hemorrhage than clear cell RCC.
Size Location:
Smaller than clear cell RCC
Usually <4 cm
Any location in kidney
Multifocal in 10-20%
Bilateral in hereditary cases
Lower pole predilection.
Multifocality:
Multifocal in 20% cases
Bilateral in hereditary forms
Associated adenomas
Better prognosis than clear cell RCC
Smaller tumor size.
Microscopic Description
Histological Features:
Papillary architecture predominant
Fibrovascular cores
Cuboidal to low columnar cells
Foamy macrophages in cores
Psammoma bodies
Basement membrane thickening.
Cellular Characteristics:
Type 1: Small cells, pale/basophilic cytoplasm
Type 2: Large cells, eosinophilic cytoplasm
Nuclear pseudostratification
Overlapping nuclei
Variable nuclear grade.
Architectural Patterns:
Papillary pattern (>75%)
Tubulopapillary
Solid areas allowed
Cystic areas
Foamy macrophages in stroma
Hemosiderin deposits.
Grading Criteria:
WHO/ISUP grading same as clear cell
Type 1: Usually low grade (1-2)
Type 2: Usually high grade (3-4)
Nuclear features determine grade.
Immunohistochemistry
Positive Markers:
CK7 - positive (diffuse, characteristic)
RCC marker - positive
AMACR - positive
CD10 - positive (brush border)
EMA - positive
PAX8 - positive.
Negative Markers:
CK20 - negative
CA9 - negative (vs clear cell)
CD117 - negative (vs chromophobe)
Vimentin - negative to weak
34βE12 - negative.
Diagnostic Utility:
CK7 positivity distinguishes from clear cell RCC
AMACR positive supports diagnosis
CA9 negative (unlike clear cell)
Combination CK7+/CA9- diagnostic
MET expression variable.
Molecular Subtypes:
Type 1: CK7+, MET+ (often)
Type 2: CK7+, MET variable
Both types: AMACR+, RCC+
NRF2 pathway in Type 2.
Molecular/Genetic
Genetic Mutations:
MET mutations (Type 1, hereditary)
Trisomy 7, 17
Loss of Y chromosome
NRF2 pathway alterations (Type 2)
SETD2 mutations (Type 2)
CDKN2A/B deletions.
Molecular Markers:
MET overexpression
Chromosomal gains (7, 17)
FH gene alterations (some Type 2)
Oxidative stress response
mTOR pathway activation
HIF pathway less involved.
Prognostic Significance:
Type 1: Better prognosis
Type 2: Worse prognosis, similar to clear cell
Size <4 cm: Excellent prognosis
Low grade: Better outcome
Multifocal disease: Still good prognosis.
Therapeutic Targets:
MET inhibitors (cabozantinib, savolitinib)
mTOR inhibitors
VEGF inhibitors less effective
Immunotherapy variable response
Targeted therapy based on molecular profile.
Differential Diagnosis
Similar Entities:
Clear cell RCC with papillary areas
Collecting duct carcinoma
Metastatic adenocarcinoma
Urothelial carcinoma
Papillary adenoma
Xp11.2 translocation RCC.
Distinguishing Features:
Papillary RCC: CK7+, CA9-, papillary architecture
Clear cell RCC: CA9+, CK7-
Collecting duct: High-grade, CK7+, medullary location
Urothelial: CK20+, uroplakin+
Adenoma: <5 mm, low grade.
Diagnostic Challenges:
Type 1 vs Type 2 classification
Solid areas vs other RCC types
Papillary adenoma vs small papillary RCC
Mixed patterns
Grading in cystic areas.
Rare Variants:
Papillary RCC with inverted nuclei
Papillary RCC with oncocytic features
Warthin-like papillary RCC
Papillary RCC with clear cell change.
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
[Kidney specimen type], weighing [X] grams
Tumor Description
Papillary renal cell carcinoma measuring [X] cm, well-circumscribed with tan cut surface
Microscopic Features
Tumor shows papillary architecture with fibrovascular cores and [small basophilic/large eosinophilic] cells consistent with Type [1/2]
Subtype
Papillary RCC, Type [1/2] based on cellular morphology
WHO/ISUP Grade
WHO/ISUP Grade [1/2/3/4]
Pathologic Stage
pT[stage]
Margins
Surgical margins negative, closest margin [X] mm
Immunohistochemistry
CK7: Positive, CA9: Negative, AMACR: Positive, RCC: Positive
Final Diagnosis
Papillary renal cell carcinoma, Type [1/2], WHO/ISUP Grade [X], pT[stage]