Definition/General
Introduction:
Chromophobe renal cell carcinoma (chRCC) represents the third most common renal cell carcinoma subtype
It constitutes 5-7% of all renal cell carcinomas
It arises from the intercalated cells of the collecting duct system
FNAC shows distinctive cytological features that aid in diagnosis.
Origin:
Originates from the intercalated cells of the cortical collecting ducts
The tumor cells demonstrate abundant eosinophilic cytoplasm with characteristic cell borders
The neoplastic transformation involves multiple chromosome losses
It results in distinctive morphological and immunohistochemical profile.
Classification:
Classified according to WHO 2016 classification
Classical type (large pale cells)
Eosinophilic variant (smaller, more eosinophilic cells)
FNAC helps distinguish from oncocytoma
WHO/ISUP grading rarely applied due to typically low-grade nature.
Epidemiology:
Peak incidence in 5th-6th decades
Equal male to female ratio or slight female predominance
Associated with Birt-Hogg-Dubé syndrome
Generally indolent behavior
Better prognosis than clear cell and papillary RCC
Indian population shows similar age distribution.
Clinical Features
Presentation:
Incidental finding on imaging (majority of cases)
Abdominal mass (less common)
Flank pain (rare)
Hematuria (uncommon)
Usually asymptomatic
Bilateral presentation rare
Associated with other renal tumors in syndrome patients.
Symptoms:
Often completely asymptomatic
Vague abdominal discomfort (if large)
Hematuria rare
Constitutional symptoms very uncommon
No paraneoplastic syndromes typically
Symptoms usually related to mass effect only.
Risk Factors:
Birt-Hogg-Dubé syndrome (germline FLCN mutations)
Renal oncocytosis (multiple oncocytic tumors)
Family history of chromophobe RCC
No strong environmental risk factors identified
Equal gender distribution.
Screening:
Birt-Hogg-Dubé syndrome patients need regular screening
Annual renal imaging recommended
Genetic counseling for familial cases
MRI preferred to avoid radiation exposure
Skin lesion surveillance also important in BHD syndrome.
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Gross Description
Appearance:
Well-circumscribed mass with tan-brown to gray cut surface
Homogeneous appearance without significant necrosis or hemorrhage
Central stellate scar may be present
Size typically medium-sized (3-8 cm)
Well-defined capsule usually present.
Characteristics:
Tan to light brown cut surface with homogeneous appearance
Central stellate scar in some cases
Minimal necrosis or hemorrhage
Solid, fleshy consistency
Calcifications uncommon
Cystic change rare.
Size Location:
Variable size (2-15 cm, average 5-7 cm)
Can occur anywhere in kidney
Unilateral presentation typical
Bilateral tumors in BHD syndrome
Cortical location preferred
Multiple tumors possible in syndrome patients.
Microscopic Description
Immunohistochemistry
Positive Markers:
Hale colloidal iron (strongly positive, diagnostic)
CK7 (positive)
PAX8 (renal origin)
Kit (CD117) (strongly positive)
E-cadherin (positive)
EMA (positive)
Parvalbumin (positive, useful marker).
Negative Markers:
CD10 (negative, distinguishes from clear cell RCC)
AMACR (P504S) (negative, distinguishes from papillary RCC)
Carbonic anhydrase IX (negative)
Vimentin (negative)
S-100 protein (negative)
Melanoma markers (negative).
Diagnostic Utility:
Hale colloidal iron positivity is diagnostic
CD117 (Kit) positivity supports diagnosis
CD10 negativity distinguishes from clear cell RCC
AMACR negativity distinguishes from papillary RCC
CK7 positivity with morphology aids diagnosis.
Molecular/Genetic
Genetic Mutations:
Multiple chromosome losses characteristic (hypotriploid karyotype)
FLCN gene mutations (Birt-Hogg-Dubé syndrome)
Mitochondrial DNA mutations
PTEN deletions (some cases)
TSC1/TSC2 pathway alterations
TP53 mutations rare.
Prognostic Significance:
Generally excellent prognosis (better than other RCC subtypes)
Low metastatic potential
Sarcomatoid transformation rare but indicates poor prognosis
Large tumor size (>7 cm) may indicate worse outcome
Stage remains most important prognostic factor.
Therapeutic Targets:
mTOR inhibitors may have theoretical benefit
Immunotherapy limited data available
VEGF inhibitors less effective than in clear cell RCC
Surgical resection remains primary treatment
Active surveillance may be appropriate for small tumors.
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 [solid/nested] architecture. Large cells with [abundant eosinophilic/pale] cytoplasm and [plant-like borders/wrinkled nuclei]. [Binucleated cells] noted
Key Morphological Features
[Plant-like cell borders/Wrinkled nuclei/Binucleated cells/Abundant cytoplasm] observed
Background
Background shows [minimal inflammatory infiltrate/clean background]
Cytological Diagnosis
[Diagnostic category] - Features consistent with chromophobe renal cell carcinoma
Differential Diagnosis
Main differential: [Renal oncocytoma/Clear cell RCC/Papillary RCC]
Recommendations
[Histopathological correlation/Immunohistochemistry panel/Hale colloidal iron stain] recommended for definitive diagnosis
Note
Differentiation from oncocytoma may require histological examination and immunohistochemistry