Kidney tumor

Adult renal cell carcinoma - common

Chromophobe eosinophilic variant

Editorial Board Member: Nicole K. Andeen, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Timothy Isaac Miller, M.D., M.A.
Maria Tretiakova, M.D., Ph.D.

Topic Completed: 18 February 2021

Minor changes: 6 August 2021

Copyright: 2003-2021,, Inc.

PubMed Search: Eosinophilic [title] chromophobe renal cell carcinoma

Related topics: Chromophobe type, renal cell carcinoma

Timothy Isaac Miller, M.D., M.A.
Maria Tretiakova, M.D., Ph.D.
Page views in 2020: 8,278
Page views in 2021 to date: 8,116
Cite this page: Miller TI, Tretiakova M. Chromophobe eosinophilic variant. website. Accessed November 29th, 2021.
Definition / general
  • Histologic variant of chromophobe renal cell carcinoma (ChRCC) with at least 80% of cells with eosinophilic cytoplasm
Essential features
  • At least 80% of the neoplastic cells must be eosinophilic
  • No difference in prognosis compared with classic / mixed chromophobe renal cell carcinoma
  • Must distinguish from benign mimic oncocytoma
ICD coding
  • ICD-10: C64.1 - malignant neoplasm of right kidney, except renal pelvis
  • ICD-10: C64.2 - malignant neoplasm of left kidney, except renal pelvis
  • ICD-10: C64.9 - malignant neoplasm of unspecified kidney, except renal pelvis
  • Kidney in corticomedullary parenchyma
Clinical features
  • Potential presenting symptoms: hematuria, pain, flank mass, anemia, pyrexia, cachexia, fatigue and weight loss (Int J Urol 2012;19:894)
  • Large case series found eosinophilic more likely to be bilateral (11%) and multifocal (22%) (Am J Surg Pathol 2008;32:1822)
  • Can be part of Birt-Hogg-Dubé syndrome (BHD) (FLCN mutation) (Am J Surg Pathol 2002;26:1542)
    • Fibrofolliculomas, spontaneous pneumothorax, other renal neoplasms
  • Mass seen on imaging with confirmatory renal biopsy or mass resection
  • Biopsy may not be diagnostic, especially if limited
Radiology description
  • On CT scan, ChRCC more likely to have homogenous enhancement (69%) and can have calcifications (38%) (AJR Am J Roentgenol 2002;178:1499)
  • No studies identified differentiating findings in eosinophilic from classic ChRCC
Radiology images

Images hosted on other servers:

Homogenous enhancement, multifocal calcifications

Prognostic factors
Case reports
  • Typically resection via partial or total nephrectomy, the same as classic ChRCC
Gross description
  • Usually well circumscribed, lobulated and with beige to brown to yellow coloration
    • Eosinophilic variant more likely to have brown coloration compared with classic, which is typically more beige-yellow (Am J Surg Pathol 2008;32:1822)
Gross images

Contributed by Timothy Isaac Miller, M.D., M.A. and Maria Tretiakova, M.D., Ph.D.
Nephrectomy with ChRCC eosinophilic variant

Nephrectomy with ChRCC eosinophilic variant

Frozen section description
Microscopic (histologic) description
  • At least 80% of the chromophobe neoplastic cells must have eosinophilic cytoplasm to classify as eosinophilic variant
  • Cells are often smaller than classic chromophobe cells
  • Besides eosinophilic cytoplasm and smaller size, have otherwise similar histology to classic ChRCC including
    • Well defined / thickened cell border
    • Wrinkled, raisinoid nuclei
    • Frequent binucleation
    • Perinuclear halos / clearing
    • Rare mitoses
    • Lacking prominent vasculature
  • Nested, alveolar or sheet-like architecture
  • Grading is not recommended
Microscopic (histologic) images

Contributed by Timothy Isaac Miller, M.D., M.A. and Maria Tretiakova, M.D., Ph.D.
Mild cytological atypia

Mild cytological atypia

Prominent perinuclear clearing

Prominent perinuclear clearing

Alveolar architecture

Alveolar architecture

Focal classic cells

Focal classic cells

Increased cytological atypia

Increased cytological atypia

Extension to perinephric fat

Extension to perinephric fat

Cytology description
  • Single or clusters of large cells with moderate pleomorphism
  • Abundant granular eosinophilic cytoplasm
  • Well defined / accentuated cell border
  • Perinuclear clearing / vacuolization
  • Binucleation may be seen
Positive stains
Electron microscopy description
Molecular / cytogenetics description
  • Compared with classic ChRCC, less frequent losses of chromosomes 1, 2, 6, 10, 13 and 17, suggesting classic has greater chromosomal instability (Cancers (Basel) 2019;11:1492)
  • Most common chromosomal losses (in order of most to least frequent): 1, 2, 17, 6, 10, 13 and 21; no chromosomal gains (Adv Anat Pathol 2021;28:8)
  • Doubled hypodiploidy by whole genome endoduplication is a common phenomenon in eosinophilic ChRCC (Hum Pathol 2020;104:18)

Distinguishing eosinophilic chromophobe RCC from oncocytoma

Sample pathology report
  • Left kidney, mass, partial nephrectomy:
    • Chromophobe renal cell carcinoma, eosinophilic variant (see synoptic report)
Differential diagnosis
  • Oncocytoma:
    • Round, hyperchromatic nuclei; smooth nuclear border
    • Cells arranged in a nested or tubular pattern
    • Lacks nuclear pleomorphism, oval nuclei, multiple nucleoli
    • CK7 usually negative
    • Hale colloidal iron focal positive staining confined to luminal borders
    • No copy number alterations or losses of chromosomes 1 and X / Y (Hum Pathol 2020;104:18)
  • Hybrid oncocytic / chromophobe tumors (HOCT) (Histol Histopathol 2013;28:1257):
    • Can be sporadic but also often found in association with renal oncocytomatosis or Birt-Hogg-Dubé (BHD) syndrome
    • Sporadic / oncocytomatosis: solid alveolar pattern, scattered cells with perinuclear halos but with no raisinoid nuclei
    • BHD: admixed areas of oncocytoma and ChRCC, scattered chromophobe cells, intracytoplasmic vacuoles
    • No aggressive behavior
    • Usually parvalbumin, antimitochondrial antigen and CK7 positive
    • Sporadic cases do not exhibit mutations in genes that are recurrently mutated in oncocytoma or ChRCC; syndromic cases with folliculin gene mutations (Mod Pathol 2019;32:1698)
  • Eosinophilic variant of clear cell renal cell carcinoma:
    • Usually area with traditional clear cell morphology (unless limited biopsy)
    • CK7 and KIT negative, vimentin and CAIX positive
    • Biallelic inactivation of VHL gene
Board review style question #1

Which of the following is the most likely immunohistochemical profile of the renal neoplasm shown?

  1. CK7+, KIT+, vimentin-, CAIX-
  2. CK7+, KIT+, vimentin-, CAIX+
  3. CK7+, KIT+, vimentin+, CAIX-
  4. CK7-, KIT+, vimentin-, CAIX-
  5. CK7-, KIT-, vimentin+, CAIX+
Board review style answer #1
A. CK7+, KIT+, vimentin-, CAIX-

The image shown is chromophobe renal cell carcinoma (ChRCC), eosinophilic variant. Histologic clues to the diagnosis of ChRCC are the raisinoid nuclei, perinuclear clearing / halos and well defined cell borders. Furthermore, > 80% of the cells have an eosinophilic cytoplasm, making it the eosinophilic variant of ChRCC. The immunoprofile of ChRCC is typically CK7+, KIT+, vimentin- and CAIX-. The other entity to consider is oncocytoma but in this case, the degree of nuclear pleomorphism with enlarged, wrinkled and oval nuclei favors ChRCC. Answer D (CK7-, KIT+, vimentin-, CAIX-) would be the immunohistochemical profile most typical if the answer were oncocytoma, although vimentin can often be focally positive. Answer E is the immunoprofile most typical of clear cell renal cell carcinoma and while there is an eosinophilic variant, the perinuclear clearing and raisinoid nuclei again is most characteristic of ChRCC. (Pathol Res Pract 2015;211:303)

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Reference: Chromophobe eosinophilic variant
Board review style question #2
Which of the following is true regarding chromophobe renal cell carcinoma (ChRCC), eosinophilic variant compared with the classic type of ChRCC?

  1. No differences in cytogenetics have been found between the eosinophilic variant and classic ChRCC
  2. The classic variant is more likely to have a brown coloration grossly
  3. The classic variant typically has smaller cells than the eosinophilic variant
  4. The eosinophilic variant must have 100% eosinophilic cells
  5. The prognosis of the eosinophilic variant is the same as classic ChRCC
Board review style answer #2
E. The prognosis of the eosinophilic variant is the same as classic ChRCC

Studies have shown no difference in prognosis between the eosinophilic variant of ChRCC and classic ChRCC. Answer A is wrong as a recent study showed that the eosinophilic variant frequently has less chromosomal instability compared with classic ChRCC and is often characterized by doubled hypodiploidy. (Eur J Surg Oncol 2008;34:687, Cancers (Basel) 2019;11:1492, Am J Surg Pathol 2008;32:1822, Cancers (Basel) 2019;11:1492, Hum Pathol 2020;104:18, Am J Surg Pathol 2008;32:1822). Answer B is wrong as the eosinophilic variant is more likely to be brown in coloration grossly. Answer C is wrong as the eosinophilic variant typically has smaller cells compared with classic ChRCC. Answer D is wrong because, by definition, the eosinophilic variant only needs to have > 80% eosinophilic cells.

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Reference: Chromophobe eosinophilic variant
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