Definition/General
Introduction:
Chromophobe RCC is the third most common type of renal cell carcinoma
Represents 5% of all RCCs
Arises from intercalated cells of collecting duct
Shows better prognosis than clear cell RCC.
Origin:
Originates from intercalated cells of cortical collecting duct
Shows numerous chromosomal losses
Associated with Birt-Hogg-Dubé syndrome
May arise from oncocytic neoplasms.
Classification:
WHO 2022: Chromophobe renal cell carcinoma
Classic type: Typical morphology
Eosinophilic type: Oncocytic features
Mixed type: Both patterns
Sarcomatoid transformation rare.
Epidemiology:
Peak incidence 5th-6th decades
Slight female predominance
Best prognosis among RCC types
Associated with BHD syndrome (germline FLCN mutations).
Clinical Features
Presentation:
Asymptomatic mass (incidental)
Excellent prognosis
Low metastatic potential
Larger size tolerated
Rare paraneoplastic syndromes.
Symptoms:
Usually asymptomatic
Hematuria (when present)
Flank pain (large tumors)
Constitutional symptoms rare
Palpable mass (advanced).
Risk Factors:
BHD syndrome (FLCN mutations)
Family history
Multiple renal cysts
Pulmonary cysts
Skin fibrofolliculomas.
Screening:
CT/MRI imaging
Genetic counseling (BHD syndrome)
FLCN gene testing
Pulmonary function assessment
Dermatologic examination.
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Gross Description
Appearance:
Well-circumscribed
Tan to brown color
Solid consistency
Thick fibrous capsule
Homogeneous cut surface
Central scar (some cases).
Characteristics:
Lobulated surface
Firm consistency
Brown coloration
Well-demarcated
Minimal necrosis
Hemorrhage uncommon.
Size Location:
Any location in kidney
Often large (>4 cm)
Cortical based
Central scar pattern
Bilateral in BHD syndrome
Multifocal possible.
Multifocality:
Usually solitary
Multiple/bilateral in BHD syndrome
Associated oncocytomas
Hybrid tumors with oncocytoma
Rare metastases.
Microscopic Description
Histological Features:
Large polygonal cells
Abundant eosinophilic cytoplasm
Prominent cell membranes
Perinuclear halos
Raisinoid nuclei
Binucleated cells.
Cellular Characteristics:
Large cells with abundant cytoplasm
Pale eosinophilic or clear cytoplasm
Thick cell membranes
Perinuclear clearing
Wrinkled nuclei
Koilocytic atypia.
Architectural Patterns:
Solid sheets
Nested pattern
Alveolar arrangement
Tubular formations
Hyalinized stroma
Edematous background.
Grading Criteria:
Usually low grade
WHO/ISUP grading applicable
Grade 1-2 most common
Nuclear pleomorphism limited
Sarcomatoid very rare.
Immunohistochemistry
Positive Markers:
CK7 - positive (diffuse)
EMA - positive
PAX8 - positive
CD117 - positive (characteristic)
Parvalbumin - positive
E-cadherin - positive.
Negative Markers:
CD10 - negative
RCC marker - negative
CA9 - negative
Vimentin - negative
S-100A1 - negative
Phosphotungstic acid hematoxylin - positive (classic).
Diagnostic Utility:
CK7 and CD117 combination diagnostic
Parvalbumin highly specific
Negative RCC marker helps distinction
PTAH stain highlights cytoplasm
Electron microscopy shows mitochondria.
Molecular Subtypes:
All types: CK7+, CD117+, parvalbumin+
Classic type: Typical immunoprofile
Eosinophilic type: Similar to oncocytoma pattern
BHD-associated: Same markers.
Molecular/Genetic
Genetic Mutations:
Multiple chromosomal losses
Monosomy 1, 2, 6, 10, 13, 17, 21
FLCN mutations (BHD syndrome)
TP53 mutations (rare)
PTEN deletions.
Molecular Markers:
Mitochondrial DNA deletions
Chromosomal instability
FLCN/mTOR pathway
Oxidative phosphorylation defects
Low mutational burden.
Prognostic Significance:
Best prognosis among RCC types
Low metastatic rate (<5%)
Excellent survival
Size less important
Sarcomatoid transformation: Poor prognosis.
Therapeutic Targets:
Surgical resection curative
Active surveillance acceptable
mTOR pathway targets
Minimal systemic therapy needed
Nephron-sparing surgery preferred.
Differential Diagnosis
Similar Entities:
Oncocytoma
Clear cell RCC
Collecting duct carcinoma
Translocation RCC
Eosinophilic solid and cystic RCC.
Distinguishing Features:
Chromophobe RCC: CK7+, CD117+, perinuclear halos
Oncocytoma: CD117-, S-100A1+, nested pattern
Clear cell RCC: CA9+, CK7-
Collecting duct: High grade, medullary
Molecular studies definitive.
Diagnostic Challenges:
Chromophobe vs oncocytoma
Eosinophilic variant confusion
Hybrid tumors
Minimal sampling
Crush artifact.
Rare Variants:
Sarcomatoid chromophobe RCC
Chromophobe RCC with neuroblastoma-like features
Pigmented chromophobe RCC.
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], measuring [X] cm
Tumor Description
Well-circumscribed tumor measuring [X] cm with tan-brown cut surface
Microscopic Features
Large polygonal cells with abundant eosinophilic cytoplasm, prominent cell membranes, perinuclear halos, and raisinoid nuclei
Immunohistochemistry
CK7: Positive, CD117: Positive, Parvalbumin: Positive, CD10: Negative, RCC: Negative
Final Diagnosis
Chromophobe renal cell carcinoma, [classic/eosinophilic type], WHO/ISUP Grade [X], pT[stage]