Kidney tumor
Adult renal cell carcinoma - common
Chromophobe eosinophilic variant

Topic Completed: 1 July 2017

Minor changes: 17 August 2020

Copyright: 2003-2019,, Inc.

PubMed Search: Eosinophilic variant [title] chromophobe renal cell carcinoma

Related topics: Chromophobe type, renal cell carcinoma

Daniel Anderson, M.D., M.B.A.
Maria Tretiakova, M.D., Ph.D.
Page views in 2019: 6,372
Page views in 2020 to date: 6,079
Cite this page: Anderson D, Tretiakova M. Chromophobe eosinophilic variant. website. Accessed September 23rd, 2020.
Definition / general
Case reports
  • 63 year old woman presented with a large left renal mass (BJU Int 06 Nov 2012)
  • 55 year old man and 60 year old woman with eosinophilic variant chromophobe renal cell carcinoma, with a rare association of right atrial myxoma in one of them (J Lab Physicians. 2011;3:116)
Gross description
Microscopic (histologic) description
  • Large tumor cells with fine eosinophilic granularity, peripheral accentuation of cytoplasm, perinuclear halo, wrinkled raisinoid nuclei, frequent binucleation and coarse chromatin (resembles koilocytes); still some classic chromophobe cells
  • Often focal areas resembling oncocytoma (Am J Surg Pathol 2008;32:1822)
Microscopic (histologic) images

Contributed by Rola Saleeb, M.D., Ph.D.

Chromophobe renal cell carcinoma

Chromophobe renal cell carcinoma CK7

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Low Magnification

Intermediate magnification

High magnification

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Fig. 2A - 2C

Cytology description
  • Large round to oval cells with well defined cytoplasmic membranes, variegated cytoplasm ranging from granular to flocculent to vacuolated, "raisinoid" nuclei, longitudinal nuclear grooves and perinuclear halos
  • "Moderate" nuclear pleomorphism (Cancer 1999;87:161)
  • Distinction from oncocytoma may be difficult due to more granular cytoplasm
  • Clues to the diagnosis of chromophobe RCC include a monotonous population of cells with granular to focally fluffy cytoplasm punctuated by an occasional cell with a very large nucleus
  • Focal, slight, perinuclear clearing is another clue in establishing the diagnosis (Cancer 1997;81:122)
Cytology images

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Resembles oncocytoma

Positive stains
Negative stains
Molecular / cytogenetics description
Electron microscopy description
  • Abundant mitochondria with variable size, shape and predominantly tubulocystic cristae, also outpouchings of outer mitochondrial membranes resembling cytoplasmic microvesicles
  • Abundant microvesicles, some containing homogenous, electron dense, finely granular matrix similar to mitochondrial matrix
Differential diagnosis
Board review style question #1
    A biopsy of a kidney mass showed a neoplasm with eosinophilic cytoplasm. It is important to consider all of the following EXCEPT:

  1. Renal neoplasms with eosinophilic cytoplasm may include several benign and malignant entities.
  2. Immunohistochemistry has limited applications in the differential diagnosis of oncocytoma and chRCC.
  3. In chRCC, the Fuhrman nuclear grading system does not accurately reflect the prognosis.
  4. Despite the name “clear cell,” a proportion of high grade clear cell renal cell carcinomas acquire eosinophilic morphology and may develop an immunophenotype similar to chromophobe renal cell carcinoma.
Board review answer #1
D. Clear cell renal cell carcinoma with eosinophilic morphology is designated as clear cell (conventional) RCC because these neoplasms demonstrate the same molecular and immunohistochemical characteristics as those with classic clear cell (part D). A wide range of immunohistochemical stains are available to help discriminate this neoplasm from mimickers. Clear cell RCC is usually positive for CD10, vimentin and CA-9 and negative for CK7, cKIT and high molecular weight keratin. One of the most pathognomonic morphologic features of ccRCC, regardless of grade, is a rich sinusoidal vasculature surrounding nests of neoplastic cells.

A wide range of renal neoplasms display eosinophilic cytoplasm (answer A) including oncocytoma, chromophobe renal cell carcinoma, hybrid tumor, clear cell RCC with predominant eosinophilic cell morphology, follicular thyroid-like RCC, hereditary leiomyomatosis associated RCC, acquired cystic disease associated RCC, rhabdoid RCC, tubulocystic carcinoma, papillary RCC, microphthalmia transcription factor translocation RCC, epithelioid angiomyolipoma and unclassified RCC.

These tumors can be further classified by histomorphology including papillary growth, cytology and immunohistochemistry and cytogenetic phenotype. The major question in these cases is if the tumor meets criteria of oncocytoma, one of the few benign epithelial renal neoplasms. It should be noted that the definitive diagnosis of oncocytoma rendered on needle biopsy is controversial. Although some experts make a definitive diagnosis on biopsy, for needle core biopsy specimens that have morphologic and immunophenotypic findings of oncocytoma others interpret them as oncocytic renal cell neoplasm with a comment such as: “If this biopsy is representative of the entire lesion, it would be consistent with an oncocytoma. However, renal cell carcinoma (RCC) and hybrid tumor may uncommonly show focal areas with oncocytic features." (Arch Pathol Lab Med 2014;138:1531)

Immunohistochemistry has limited applications in the differential diagnosis of oncocytoma and chRCC (answer B). The most useful stain is cytokeratin 7, which typically shows isolated scattered cell staining in oncocytoma and diffuse strong staining in chRCC. However, clear cells localized in the central scar of oncocytoma may be immunoreactive with CK7. In addition, there may be cases of chRCCs which are negative for CK7 (Arch Pathol Lab Med 2007;131:1290).

Although many chRCC qualify as Fuhrman nuclear grade 3, the Fuhrman nuclear grading system does not accurately reflect the prognosis (answer C). Consequently, some pathologists do not recommended assigning Fuhrman nuclear grade to chRCC.

References: Arch Pathol Lab Med 2014;138:1531, Oncology (Williston Park) 2016;30:426

Reference: Kidney tumor - Eosinophilic variant of chromophobe renal cell carcinoma

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