CD Markers for Renal Cell Carcinoma Identification
CD10 and RCC marker (RCCma) are the primary CD markers used to identify renal cell carcinoma on immunohistochemistry, with CD10 showing the highest sensitivity (86-100% in clear cell RCC) while RCCma offers superior specificity when positive. 1, 2
Primary Diagnostic Markers by RCC Subtype
Clear Cell RCC (Most Common - 70-85% of Cases)
- CD10 demonstrates diffuse membranous positivity in 86-100% of clear cell RCC cases, making it the most sensitive immunohistochemical marker for this subtype 2, 3, 4, 5
- Carbonic anhydrase IX (CAIX) shows diffuse membranous positivity in 94% of clear cell RCCs and is the most characteristic diagnostic marker recommended by the American College of Pathologists 1, 2
- PAX8 is endorsed as a primary diagnostic marker alongside CAIX for confirming clear cell RCC histology 2
- Vimentin is positive in 54-85% of clear cell RCC cases 2, 6
- RCC marker (RCCma) shows 35-85% sensitivity but 100% specificity—when positive, it is highly specific for conventional RCC 1, 7, 5
Papillary RCC (7-15% of Cases)
- CD10 is positive in 63-93% of papillary RCC tumors 1, 2, 3, 5
- α-methylacyl-CoA racemase (AMACR) shows strong expression in papillary RCC 2, 6
- RCC marker is positive in nearly all papillary cases (13 of 14) 5
Chromophobe RCC (5-10% of Cases)
- CK7 (cytokeratin 7) demonstrates diffuse positivity in 81.5% of chromophobe RCC cases, distinguishing it from clear cell RCC where CK7 is typically negative or focal 1, 2, 6
- c-kit (CD117) shows diffuse positivity in chromophobe RCC, whereas oncocytoma lacks c-kit expression 2, 8, 6
- Parvalbumin is strongly expressed in all chromophobe RCC cases 3, 6
- CD10 is typically negative in chromophobe RCC (though 26% may show positivity, particularly in aggressive variants) 3, 5
Key Differential Diagnosis Patterns
Clear Cell RCC vs. Chromophobe RCC
- Clear cell RCC: CD10+, CAIX+, CK7−/focal, vimentin+ 1, 2, 6
- Chromophobe RCC: CD10−, CAIX−, CK7+, c-kit+, parvalbumin+ 2, 3, 6, 5
Chromophobe RCC vs. Oncocytoma
- Chromophobe RCC shows diffuse CK7 positivity and c-kit expression 1, 2
- Oncocytoma is CK7 negative or focally positive and c-kit negative 1, 2
Markers for Hereditary Syndromes (Younger Patients)
- FH (fumarate hydratase) loss is highly specific for FH-deficient RCC 1, 2
- 2SC (2-succino-cysteine) positivity is highly sensitive for FH-deficient RCC 1, 2
- SDHB loss is highly specific for succinate dehydrogenase deficient RCC 1, 2
- Low threshold for testing these markers is recommended in any difficult-to-classify renal carcinoma, particularly in younger patients 1, 2
Translocation RCC (Young Patients <40 Years)
- Diagnosis requires both immunohistochemistry and FISH analysis to demonstrate TFE3/TFEB gene rearrangements 1, 2
- Morphology alone is insufficient for diagnosis 2, 8
Critical Pitfalls to Avoid
Relying on CD10 alone for diagnosis: CD10 has 100% sensitivity but only 59% specificity for clear cell RCC, as it can be positive in papillary RCC (63%), some chromophobe RCC (26%), and non-renal tumors 3, 7, 5
Using RCCma as a screening marker: RCCma has only 35% sensitivity despite 100% specificity, making it useful for confirmation when positive but unreliable for ruling out RCC when negative 7, 5
Focal staining interpretation on small biopsies: Both CD10 and RCC marker often show focal staining patterns, reducing sensitivity in tissue arrays or core biopsies 4, 5
Not performing antigen retrieval for RCCma: Double enzyme digestion (trypsin + protease) is essential for optimal RCCma immunohistochemical detection 4
Ignoring CK7 status: CK7 is critical for distinguishing chromophobe RCC (diffusely positive) from clear cell RCC (negative/focal) 1, 2, 6