Mostly round, with a psuedo-capsule of compressed parenchyma and fibrous tissue (cf a true histologic capsule).
Usually not infiltrative (cf UTUC), except for sarcomatoid and collecting duct variants.
Yellow, tan or brown tumour macroscopically.
Calcification in 10 – 20 %.
Predeliction for involvement of the venous system – more commonly than any other tumour – up to 10 %.
Local invasion usually manifests as invasion of the renal sinus, renal capsule, or collecting system, rather than adjacent organs due to the barrier formed by Gerota’s fascia.
Most sporadic RCCs are solitary – bilateral involvement seen in 2 – 4 % of sporadic cases, but much more common with familial syndromes.
Clear cell RCC
70 – 80 % RCC (most common, garden variety)
Arises from the proximal convoluted tubule.
Usually associated with loss of chromosome 3p, and mutation of the VHL gene.
Microscopic features:
- Clear cells (abundant cytoplasm)
- Granular or eosinophilic cells
- Mixed types
3 – 5 % may have sarcomatoid features.
ccRCC more likely to exhibit venous extension.
Typically worse prognosis cf. papillary and chromophobe – but – paradoxically responds better to systemic treatment so metastatic ccRCC better prognosis than other metastatic types.
Stains – PAX 8, CD 10
Papillary RCC
10 – 15 % of RCC – second most common subtype.
Arises from the proximal tubule.
Macroscopically more white/beige, spherical and frequently haemorrhage.
Microscopic features:
- Basophilic or eosinophilic cells arranged in papillary or tubular configuration
2 distinct subtypes, but still heterogenous within groups:
- Type 1 – basophilic cells with scant cytoplasm
- More indolent
- Associated with mutations in MET gene
- Type 2 – eosinophilic cells with abundant granular cytoplasm
- More aggressive, approaching that of ccRCC
- Associated with HLRCC
Higher tendency towards multicentricity, approaching up to 40 % in some series and more common in ESRD / acquired renal cystic disease.
*WHO update 2022 – no longer separated to type 1 and type 2…
Chromophobe RCC
3 – 5 % of RCC.
Arises from the distal convoluted tubule or collecting duct.
Mostly sporadic, but also often associated with Birt Hogg Dube.
Macroscopically a pale tan, relatively homogenous and tough, well demarcated mass.
Microscopically:
- Nuclear atypia (precluding Fuhrman grading)
- Microvesicles – distinguishing feature – which stain positive for Hale colloidal iron
- Perinuclear clearing or “halo”
- Granular eosinophilic cells
Generally good prognosis for localised, resected disease (>90 % 5 year disease free survival)
Can appear similar to oncocytoma under the microscope, but oncocytoma won’t stain for Hale colloidal iron or have many microvesicles.
WHO/ISUP grading (applies to clear cell and papillary) – replaced Fuhrman grade.
Collecting duct carcinoma (of Bellini)
Rare. Poor prognosis. Presents late.
Median survival 30 months.
Renal medullary carcinoma
Very rare – classically seen in younger Black men with sickle cell.
Very aggressive.
Sarcomatoid and rhabdoid differentiation
Found in 1 – 5 % of RCC, most commonly with clear cell or chromophobe.
Sarcomatoid microscopically:
- Spindle cell histology
- Stains positive for vimentin
- Infiltrative growth pattern
Sarcomatoid represents poorer prognosis and more aggressive local and metastatic behaviour.
The presence of rhabdoid cells mandates a grade of 4, and is associated with poorer prognosis.
Unclassified renal cell carcinoma
1 – 5 % of cases, with features which remain indeterminate after analysis.
Many are poorly differentiated, and aggressive.
Others, rare:
Multilocular cystic renal cell neoplasm of low malignant potential – considered benign.
Acquired cystic disease-associated renal cell carcinoma – relatively indolent.
Succinate dehydrogenase deficient RCC (aggressive)
Clear cell papillary renal cell tumour (usually incidental, indolent and essentially benign, renamed 2022)
Fumarate dehydrogenase deficient RCC (HLRCC)