Chromophobe Renal Cell Carcinoma

Definition

Carcinoma of the kidney composed predominantly of distinctive cells with prominent cell membranes and cleared cytoplasm

Generally sheet-like or broad alveolar patterns
- Less frequently tubular or cystic
- Vessels frequently thick walled and/or eccentrically hyalinized
Composed of cells with cytoplasm ranging from clear to eosinophilic
- Clear cells (classical) have abundant clear cytoplasm
  - May be flocculent, "soap bubble" or reticular
- Eosinophilic (variant) cells have moderate amount of finely granular eosinophilic cytoplasm
  - Prominent perinuclear clearing
    - Peripheral condensation of cytoplasm accentuates cell membrane

Most often mixed but may be pure of either type
- Mixed cases frequently have a distinctive pattern
  - Eosinophilic cells occupy the center of the nest, merging with
  - Peripheral clear cells with abundant cytoplasm adjacent to the fibrovascular stromal border

Nuclei vary from round, regular to koilocytoid
- Koilocytoid nuclei have wrinkled nuclear membrane, coarse chromatin
- Frequently binucleate
Prominent cell borders with centrally located nuclei with perinuclear clearing result in a "plant cell appearance"

Hale colloidal iron stain positive
- A temperamental stain
- Other colloidal iron stains are not equivalent
Chromophobe and hybrid chromophobe/oncocytoma cases may be seen in Birt Hogg Dubé syndrome
- Often multiple and bilateral
- Associated with germline folliculin mutations
- Sporadic hybrid chromophobe/oncocytoma cases have been described (Petersson)
Sarcomatoid cases may have a variety of patterns (Viswanathan; Quiroga-Garza)
- Poor prognosis
One case reported with neuroendocrine differentiation (Parada)
- Not clear from the report that this was not a collision tumor

Kurt Schaberg MD
John P Higgins MD
Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342