Encyclopedia of Pathology

Living Edition
| Editors: J.H.J.M. van Krieken

Chromophobe Renal Cell Carcinoma

  • Anna Caliò
  • Diego Segala
  • Guido MartignoniEmail author
Living reference work entry
DOI: https://doi.org/10.1007/978-3-319-28845-1_4790-1


Chromophobe renal cell carcinoma is composed by cells with prominent cell membranes, wrinkled nuclei with perinuclear halos, and pale to eosinophilic cytoplasm.

Clinical Features

Most tumors are incidentally discovered, can be sporadic, or occur in Birt-Hogg-Dubè syndrome, which is an autosomal dominant genodermatosis due to the mutation in folliculin gene and characterized by the presence of multiple fibrofolliculomas on the skin, acrochordons, trichodiscomas, pulmonary cysts, and multifocal renal tumors.
  • Incidence

    Chromophobe renal cell carcinoma accounts 5% of renal cell carcinoma.

  • Age

    The mean age is 50–60 years.

  • Sex

    There is no difference between male and female.

  • Site

    There is no site predilection.

  • Treatment

    Partial or radical nephrectomy is the surgical treatment of choice, whenever feasible.

  • Outcome

    Most of chromophobe renal cell carcinomas show an indolent behavior.


Grossly, it is a solid, well-circumscribed, unencapsulated neoplasm with a light brown color on the cut surface. Most tumors are confined within the kidney (Fig. 1a).
Fig. 1

The macroscopic appearance of chromophobe renal cell carcinoma as a solid, well-circumscribed neoplasm with a light brown color (a). Nested pattern composed of large cells with flocculent cytoplasm concentrated along the septa and in the center smaller eosinophilic cells (b)


The morphologic features of chromophobe renal cell carcinoma include a solid, “cobblestone” growth pattern without the rich vascular network seen in clear cell renal cell carcinoma. Focal calcifications and broad fibrotic septa are frequently present. The cytoplasm of typical chromophobe is pale and flocculent and the peripheral portion of the cytoplasm and shows a variable degree of granularity and eosinophilia resulting in an accentuation of the cellular membrane (Fig. 1b). A perinuclear “halo” due to the presence of innumerable microvesicles scattered between the mitochondria may be observed. Nuclei ranged from vesicular to wrinkled and can exhibit marked pleomorphism. The neoplastic cells can display binucleation. Mitotic figures can be found in a highly variable amount (0−20 × 50 high power fields). Chromophobe renal cell carcinoma is a low-grade malignancy; however, sarcomatoid transformation occurs in 8% of the cases. A diffuse cytoplasmic staining reaction with Hale’s iron colloid stain has been for a long time considered a characteristic feature of this special tumor type. Roughly 10% of chromophobe renal cell carcinomas are almost completely composed of smaller eosinophilic cells which, not uncommonly, may display round regular nuclei. As clear cell renal cell carcinoma, stage and necrosis are the main prognostic features of this tumor but, on the other hand, the nucleolar grade has no prognostic significance and therefore it should be not reported in routine practice.


Chromophobe renal cell carcinoma is positive for CK7, CD117, and parvalbumin. Vimentin is generally negative as well as S100A1.

Molecular Features

Chromophobe renal cell carcinoma is characterized by a combination of loss of chromosomes Y, 1, 2, 6, 10, 17, and 21. Both classic and eosinophilic variants of chromophobe renal cell carcinoma share the same chromosomal losses. Sarcomatoid chromophobe renal cell carcinomas are characterized by multiple chromosomal gains in both epithelial and sarcomatoid components. p53 and PTEN are mutated in 30% and 9% of tumors, respectively. Rearrangements in the TERT promoter region occur in 12% of tumors.

Differential Diagnosis

Because of eosinophilic component chromophobe, renal cell carcinoma must be distinguished from many renal cell tumors, including succinate dehydrogenase (SDH)-deficient renal cell carcinoma, oncocytic papillary renal cell carcinoma, epithelioid angiomyolipoma, eosinophilic solid and cystic carcinoma, tubulocystic renal cell carcinoma. However, the main differential diagnosis is the oncocytoma in which different immunohistochemical expression of S100A1 and CK7 is helpful. In approximately 10% of cases, FISH analysis can be a useful diagnostic tool detecting the characteristic chromosomal losses. Tumors with mixed features of oncocytoma and chromophobe renal cell carcinoma have been viewed as “hybrid oncocytoma–chromophobe tumor.” However, some pathologists use it in the context of an apparent syndrome (multiple tumors), others use it only with mosaic or mixed morphology, and some others use it for any tumor with borderline features between oncocytoma and chromophobe renal cell carcinoma.

References and Further Reading

  1. Brunelli, M., Eble, J. N., Zhang, S., Martignoni, G., Delahunt, B., & Cheng, L. (2005). Eosinophilic and classic chromophobe renal cell carcinomas have similar frequent losses of multiple chromosomes from among chromosomes 1, 2, 6, 10, and 17, and this pattern of genetic abnormality is not present in renal oncocytoma. Modern Pathology, 18(2), 161–169.CrossRefGoogle Scholar
  2. Delahunt, B., Sika-Paotonu, D., Bethwaite, P. B., McCredie, M. R., Martignoni, G., Eble, J. N., & Jordan, T. W. (2007). Fuhrman grading is not appropriate for chromophobe renal cell carcinoma. The American Journal of Surgical Pathology, 31(6), 957–960.CrossRefGoogle Scholar
  3. Martignoni, G., Pea, M., Chilosi, M., Brunelli, M., Scarpa, A., Colato, C., Tardanico, R., Zamboni, G., & Bonetti, F. (2001). Parvalbumin is constantly expressed in chromophobe renal carcinoma. Modern Pathology, 14(8), 760–767.CrossRefGoogle Scholar
  4. Przybycin, C. G., Cronin, A. M., Darvishian, F., Gopalan, A., Al-Ahmadie, H. A., Fine, S. W., Chen, Y. B., Bernstein, M., Russo, P., Reuter, V. E., & Tickoo, S. K. (2011). Chromophobe renal cell carcinoma: a clinicopathologic study of 203 tumors in 200 patients with primary resection at a single institution. The American Journal of Surgical Pathology, 35(7), 962–970.CrossRefGoogle Scholar
  5. Volpe, A., Novara, G., Antonelli, A., Bertini, R., Billia, M., Carmignani, G., Cunico, S. C., Longo, N., Martignoni, G., Minervini, A., Mirone, V., Simonato, A., Terrone, C., Zattoni, F., & Ficarra, V. (2012). Chromophobe renal cell carcinoma (RCC): oncological outcomes and prognostic factors in a large multicentre series. BJU International, 110(1), 76–83.CrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Diagnostic and Public Health, Section of PathologyUniversity of VeronaVeronaItaly
  2. 2.Department of PathologyPederzoli HospitalPeschiera del GardaItaly