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- Most common type of RCC.
- Cytogenetically characterized by 3p- and inactivating mutations in VHL gene (a tumor suppressor gene at 3p25-26).
- Also has inactivating mutation in PBRM1 at chr 3p21 (41%).
- Almost all von Hippel-Lindau syndrome patients will develop clear cell RCC.
- Mostly asymptomatic; classic triad of abdominal mass, flan pain and hematuria detected in only ~1/3 of patients.
- Gross:
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- Microscopic:
- Water-clear or optically-clear cells (due to glycogen content) arranged in nests in "chicken wire" vasculatures (image C) & (image D).
- Delicate capillary often ruptures during surgical manipulation, resulting in formation of "blood lakes" within tumor cell nests.
- Some cells may have granular eosinophilic cytoplasm (not all clear cell RCC have clear cytoplasm! – in the past was called "granular cell RCC").
- May develop sarcomatoid change (like all other RCC) and most often shows high-grade spindle cell morphology (images E); more aggressive behavior.
- Nuclear grading based on Fuhrman classification (grades 1-4).
Image E
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- Immunohistochemistry: CAIX+, keratin+ and vimentin+ (the 2 latter are epithelial and mesenchymal markers).
- DDX: (Usually challenging in needle biopsy)
- Chromophobe RCC: pale flocculent (not so clear) cells with clear perinuclear halo and "plant cell-like" appearance; CD117+ and CAIX-.
- Other rare tumors: translocation RCC (TFE3+ or TFEB+), clear cell papillary RCC, and epithelioid angiomyolipoma (melanoma marker+).
- Adrenal tissue: pale reticulated (not so clear) cells; inhibin+ and keratin-.