Definition/General
Introduction:
Papillary renal cell carcinoma (pRCC) represents the second most common renal cell carcinoma subtype
It constitutes 10-15% of all renal cell carcinomas
It arises from the distal tubular epithelium
FNAC shows characteristic papillary architecture and specific cytological features.
Origin:
Originates from the epithelial cells of the distal convoluted tubules and collecting ducts
The tumor cells demonstrate papillary architecture with fibrovascular cores
The neoplastic transformation involves trisomy 7 and 17
It results in characteristic molecular signature.
Classification:
Classified according to WHO 2016 classification
Type 1 pRCC (basophilic, better prognosis)
Type 2 pRCC (eosinophilic, worse prognosis)
FNAC helps distinguish subtypes
WHO/ISUP grading system applies to both types.
Epidemiology:
Peak incidence in 6th decade
Male to female ratio is 3-4:1
Associated with hereditary papillary RCC syndrome
End-stage renal disease patients at increased risk
Multifocal tumors more common than in clear cell RCC
Indian population shows lower incidence compared to Western countries.
Clinical Features
Presentation:
Incidental finding on imaging (50-60%)
Abdominal mass (30%)
Flank pain (25%)
Hematuria (20%)
Often asymptomatic until advanced stages
Bilateral presentation possible
Multiple lesions in 20% cases.
Symptoms:
Often asymptomatic in early stages
Flank pain (dull, intermittent)
Hematuria (microscopic more common than gross)
Constitutional symptoms rare unless advanced
Hypertension (secondary to renal artery involvement)
Weight loss in advanced cases.
Risk Factors:
End-stage renal disease (acquired cystic kidney disease)
Hereditary papillary RCC syndrome (germline MET mutations)
Long-term dialysis
Chronic kidney disease
Trichloroethylene exposure
Family history of renal cancer
Male gender.
Screening:
High-risk patients (ESRD, hereditary syndromes) require regular imaging
Annual ultrasound or CT for ESRD patients
Hereditary pRCC families need genetic counseling
MRI preferred for young patients to avoid radiation.
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Gross Description
Appearance:
Well-circumscribed nodular mass with tan to gray cut surface
May appear hemorrhagic due to papillary architecture
Cystic areas common
Size typically smaller than clear cell RCC (average 3-4 cm)
Capsule usually present.
Characteristics:
Tan to brown cut surface with areas of hemorrhage
Papillary or cystic appearance on cut surface
Necrosis less common than in clear cell RCC
Calcifications may be present
Multifocal tumors show similar appearance.
Size Location:
Generally smaller than clear cell RCC (1-8 cm, average 3-4 cm)
Can occur anywhere in kidney
Multifocal presentation in 20-40% cases
Bilateral tumors in 5-10% cases
Cortical location typical.
Microscopic Description
Immunohistochemistry
Positive Markers:
CK7 (strongly positive, characteristic)
PAX8 (renal origin)
AMACR (P504S) (strongly positive)
Vimentin (variable)
CD10 (typically negative, unlike clear cell RCC)
RCC marker (variable)
EMA (positive).
Negative Markers:
CD10 (usually negative, key distinguishing feature)
Carbonic anhydrase IX (negative, unlike clear cell RCC)
CK20 (negative)
TTF-1 (negative)
Chromogranin (negative)
Synaptophysin (negative).
Diagnostic Utility:
CK7 positivity distinguishes from clear cell RCC
AMACR strong positivity supports papillary RCC
CD10 negativity helps differentiate from clear cell type
Useful in distinguishing Type 1 vs Type 2 (morphology more important)
Essential for metastatic workup.
Molecular/Genetic
Genetic Mutations:
Trisomy 7 and 17 characteristic (both types)
MET mutations (hereditary Type 1)
FH mutations (some Type 2 cases)
CDKN2A deletions (Type 2, aggressive)
SETD2 mutations (Type 2)
NF2 mutations (Type 2).
Prognostic Significance:
Type 1 pRCC generally better prognosis than Type 2
FH-deficient Type 2 has aggressive behavior
High nuclear grade indicates worse prognosis
Sarcomatoid features rare but poor prognostic sign
Size and stage remain important factors.
Therapeutic Targets:
MET inhibitors (crizotinib, cabozantinib) for MET-driven tumors
mTOR inhibitors (temsirolimus) show activity
VEGF inhibitors less effective than in clear cell RCC
Immunotherapy limited efficacy
Targeted therapy based on molecular subtyping.
Differential Diagnosis
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
FNAC from [kidney mass/renal lesion], [location], performed under [guidance method]
Specimen Adequacy
[Adequate/Inadequate] for cytological interpretation
Cytological Findings
Cellular smears showing [cellularity] with [papillary/tubular] architecture. Cells show [cytoplasmic features] and [nuclear characteristics]. [Type 1/Type 2] features noted
Background
Background shows [foamy macrophages/hemorrhage/hemosiderin]
Cytological Diagnosis
[Diagnostic category] - Consistent with papillary renal cell carcinoma, [Type 1/Type 2/cannot determine type]
Nuclear Grade
Nuclear grade: [WHO/ISUP grade] (if assessable)
Recommendations
[Histopathological correlation/Immunocytochemistry panel/Clinical correlation] recommended
Note
Final subtyping and grading require histopathological examination with immunohistochemistry