- Human pathology

Home > E. Pathology by systems > Urinary system > Kidneys > chromophobe renal cell carcinoma

chromophobe renal cell carcinoma

Monday 8 March 2004, by JA



Definition: Chromophobe renal cell carcinoma (RCC) is a histologic subtype of RCC that portends a favorable prognosis.


- typical ChRCC

- eosinophilic ChRCC

- ChRCC with undifferentiated high-grade component

- typical ChRCC : Hale staining


- architecture : solid growth, nests or broad alveoli / trabeculae
- composed of polygonal cells with "hard" or distinct cell borders ("vegetable cells", due to cytoplasmic retraction)
- three types of cells:

  • Type 1 cells: small cells with solid, slightly granular eosinophilic cytoplasm
  • Type 2 cells: perinuclear halo or translucent zone in a background of pale, flocculent but not clear cytoplasm
  • Type 3 cells: large, polygonal cells with hard cell border, abundant cytoplasm with reticular pattern


It is controversial whether the Fuhrman nuclear grade of chromophobe RCC has prognostic utility. It has been reported that Fuhrman grading is not appropriate for chromophobe renal cell carcinoma (RCC).

Irregular nuclei, prominent nucleoli, and nuclear pleomorphism are inherently present in chromophobe RCC.

Hence, the Fuhrman nuclear grade is higher even though the majority of these tumors have a favorable outcome.

The novel chromophobe tumor grading system proposed by Paner et al. provides superior prognostic value to that of the Fuhrman nuclear grade in chromophobe RCC and will potentially help stratify patients of chromophobe RCC who are at a greater risk of disease progression. (20679882)

Although the chromophobe RCC grading system described by Paner and colleagues and nucleolar grade are associated with CS survival in chromophobe RCC, they add no additional prognostic information once TNM stage and sarcomatoid differentiation are assessed. (22367296)


- CD117+ (c-kit) (88%) (15105658)
- CK7+ : peripheral membrane staining pattern (12047768)
- EMA+ : diffuse cytoplasmic staining pattern (14657952)


- sarcomatoid chromophobe renal cell carcinoma ( with sarcomatoid transformation ) (14571432)
- pediatric chromophobe renal cell carcinoma (17378685)

Differential diagnosis

- renal oncocytoma
- eosinophilic clear cell carcinoma / eosinophilic ccRCC


- Birt-Hogg-Dube syndrome (MIM.135150)

  • germline FLCN gene mutations

Molecular biology
- somatic mutation of the FLCN gene (1732delTCinsAC) in chromophobe renal carcinoma in a patient with Birt-Hogg-Dube syndrome (MIM.135150)

- biallelic TCF2 (HNF1beta) inactivation in chromophobe renal cell carcinoma (15649945)

References : grading

- Chromophobe Renal Cell Carcinoma: The Impact of Tumor Grade on Outcome. Cheville JC, Lohse CM, Sukov WR, Thompson RH, Leibovich BC. Am J Surg Pathol. 2012 Feb 24. PMID: 22367296

- A Novel Tumor Grading Scheme for Chromophobe Renal Cell Carcinoma: Prognostic Utility and Comparison With Fuhrman Nuclear Grade. Paner GP, Amin MB, Alvarado-Cabrero I, Young AN, Stricker HJ, Moch H, Lyles RH. Am J Surg Pathol. 2010 Sep;34(9):1233-40. PMID: 20679882

- Fuhrman grading is not appropriate for chromophobe renal cell carcinoma. Delahunt B, Sika-Paotonu D, Bethwaite PB, McCredie MR, Martignoni G, Eble JN, Jordan TW. Am J Surg Pathol. 2007 Jun;31(6):957-60. PMID: 17527087

References : molecular biology

- Germline hepatocyte nuclear factor 1alpha and 1beta mutations in renal cell carcinomas. Rebouissou S, Vasiliu V, Thomas C, Bellanne-Chantelot C, Bui H, Chretien Y, Timsit J, Rosty C, Laurent-Puig P, Chauveau D, Zucman-Rossi J. Hum Mol Genet. 2005 Mar 1;14(5):603-14. PMID: 15649945

References : tumor markers (immunohistochemistry)

- Identifying CD82 (KAI1) as a marker for human chromophobe renal cell carcinoma. Yusenko MV, Kovacs G. Histopathology. 2009 Dec;55(6):687-95. PMID: 20002769

- Claudin-7 and claudin-8: immunohistochemical markers for the differential diagnosis of chromophobe renal cell carcinoma and renal oncocytoma. Osunkoya AO, Cohen C, Lawson D, Picken MM, Amin MB, Young AN. Hum Pathol. 2009 Feb;40(2):206-10. PMID: 18799195

- Progesterone receptor reactivity in renal oncocytoma and chromophobe renal cell carcinoma. Mai KT, Teo I, Belanger EC, Robertson SJ, Marginean EC, Islam S. Histopathology. 2008 Feb;52(3):277-82. PMID: 18081814

- Claudin-7 immunohistochemistry in renal tumors: a candidate marker for chromophobe renal cell carcinoma identified by gene expression profiling. Hornsby CD, Cohen C, Amin MB, Picken MM, Lawson D, Yin-Goen Q, Young AN. Arch Pathol Lab Med. 2007 Oct;131(10):1541-6. PMID: 17922590

- Expression analysis of kidney-specific cadherin in a wide spectrum of traditional and newly recognized renal epithelial neoplasms: diagnostic and histogenetic implications. Kuehn A, Paner GP, Skinnider BF, Cohen C, Datta MW, Young AN, Srigley JR, Amin MB. Am J Surg Pathol. 2007 Oct;31(10):1528-33. PMID: 17895753

- Diagnostic utility of S100A1 expression in renal cell neoplasms: an immunohistochemical and quantitative RT-PCR study. Rocca PC, Brunelli M, Gobbo S, Eccher A, Bragantini E, Mina MM, Ficarra V, Zattoni F, Zamò A, Pea M, Scarpa A, Chilosi M, Menestrina F, Bonetti F, Eble JN, Martignoni G. Mod Pathol. 2007 Jul;20(7):722-8. PMID: 17483815

- S100A1: a powerful marker to differentiate chromophobe renal cell carcinoma from renal oncocytoma. Li G, Barthelemy A, Feng G, Gentil-Perret A, Peoc’h M, Genin C, Tostain J. Histopathology. 2007 Apr;50(5):642-7. PMID: 17394501

- Expression of kidney-specific cadherin in chromophobe renal cell carcinoma and renal oncocytoma. Adley BP, Gupta A, Lin F, Luan C, Teh BT, Yang XJ. Am J Clin Pathol. 2006 Jul;126(1):79-85. PMID: 16753598

- Caveolin-1 immunohistochemical analysis in differentiating chromophobe renal cell carcinoma from renal oncocytoma. Garcia E, Li M. Am J Clin Pathol. 2006 Mar;125(3):392-8. PMID: 16613342

- KIT and RCC are useful in distinguishing chromophobe renal cell carcinoma from the granular variant of clear cell renal cell carcinoma. Wang HY, Mills SE. Am J Surg Pathol. 2005 May;29(5):640-6. PMID: 15832088

- C-kit expression in renal oncocytomas and chromophobe renal cell carcinomas. Huo L, Sugimura J, Tretiakova MS, Patton KT, Gupta R, Popov B, Laskin WB, Yeldandi A, Teh BT, Yang XJ. Hum Pathol. 2005 Mar;36(3):262-8. PMID: 15791570

- Expression of kidney-specific cadherin distinguishes chromophobe renal cell carcinoma from renal oncocytoma. Mazal PR, Exner M, Haitel A, Krieger S, Thomson RB, Aronson PS, Susani M. Hum Pathol. 2005 Jan;36(1):22-8. PMID: 15712178

- Chromophobe renal cell carcinoma: a comparative study of histological, immunohistochemical and ultrastructural features using high throughput tissue microarray. Abrahams NA, MacLennan GT, Khoury JD, Ormsby AH, Tamboli P, Doglioni C, Schumacher B, Tickoo SK. Histopathology. 2004 Dec;45(6):593-602. PMID: 15569050

- CD10 is expressed in a subset of chromophobe renal cell carcinomas. Martignoni G, Pea M, Brunelli M, Chilosi M, Zamó A, Bertaso M, Cossu-Rocca P, Eble JN, Mikuz G, Puppa G, Badoual C, Ficarra V, Novella G, Bonetti F. Mod Pathol. 2004 Dec;17(12):1455-63. PMID: 15286660

- Expression of RON Proto-oncogene in Renal Oncocytoma and Chromophobe Renal Cell Carcinoma. Patton KT, Tretiakova MS, Yao JL, Papavero V, Huo L, Adley BP, Wu G, Huang J, Pins MR, Teh BT, Yang XJ. Am J Surg Pathol. 2004 Aug;28(8):1045-50. PMID: 15252311

- Overexpression of KIT (CD117) in chromophobe renal cell carcinoma and renal oncocytoma. Pan CC, Chen PC, Chiang H. Am J Clin Pathol. 2004 Jun;121(6):878-83. PMID: 15198361

- KIT expression in chromophobe renal cell carcinoma: comparative immunohistochemical analysis of KIT expression in different renal cell neoplasms. Petit A, Castillo M, Santos M, Mellado B, Alcover JB, Mallofré C. Am J Surg Pathol. 2004 May;28(5):676-8. PMID: 15105658

- Expression of MUC1 (EMA) and E-cadherin in renal cell carcinoma: a systematic immunohistochemical analysis of 188 cases. Langner C, Ratschek M, Rehak P, Schips L, Zigeuner R. Mod Pathol. 2004 Feb;17(2):180-8. PMID: 14657952

- Cytokeratin 7: a useful adjunct in the diagnosis of chromophobe renal cell carcinoma. Mathers ME, Pollock AM, Marsh C, O’Donnell M. Histopathology. 2002 Jun;40(6):563-7. PMID: 12047768