Kidney tumor - adult malignancies
Adult renal cell carcinoma
Chromophobe type, renal cell carcinoma

Author: Sean Williamson, M.D. (see Authors page)

Revised: 30 January 2017, last major update June 2012

Copyright: (c) 2003-2017, PathologyOutlines.com, Inc.

PubMed Search: "Chromophobe type" renal cell carcinoma

See Also: Eosinophilic variant of chromophobe renal cell carcinoma
Cite this page: Chromophobe type, renal cell carcinoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/kidneytumormalignantrccchromo.html. Accessed February 27th, 2017.
Definition / General
Epidemiology
  • 5% of adult renal epithelial tumors; ages 45+, no gender preference
Birt-Hogg-Dubé syndrome
  • Multiple tumors (mean 5.3), mean age 51 years at first renal tumor diagnosis, usually bilateral chromophobe carcinomas, oncocytomas or hybrids, also may have oncocytosis (Am J Surg Pathol 2002;26:1542)
  • Syndrome is autosomal dominant and features small dome shaped papular fibrofolliculomas of face, neck and upper trunk, renal tumors, lung cysts and spontaneous pneumothorax
  • Due to mutations in folliculin gene (FLCN) at 17p11.2 (Cancer Cell 2002;2:157)
Clinical Features
  • Most are T1 - T2 N0 M0 (i.e. confined within the renal capsule, Cancer 2004;100:1406) and have good prognosis (5 year survival is 78% - 92%, 3% - 6% die of disease)
  • Same behavior as clear cell when stratified by grade / stage
Poor prognostic factors
Case Reports
Gross Description
  • Well circumscribed, tan brown (same color as cortex), geographic necrosis, mean 8 cm, small cysts, 8% multifocal, 3% bilateral
  • Occasionally central scar
Gross Images

Images hosted on PathOut server:

Tan and relatively homogeneous tumor



Images hosted on other servers:

Well circumscribed tumor

Central scar

Encapsulated nodular tumor of upper pole

Yellowish brown tumor with granular cut surface

Nodular tumor with focal hemorrhage and necrosis

Micro Description
  • Compact architecture of nests or broad alveoli / trabeculae, composed of large polygonal cells with "hard" or distinct cell border ("vegetable cells", due to cytoplasmic retraction)
  • Abundant cytoplasm with reticular pattern (light / pale, flocculent, not clear), also called type 3 cells, some have perinuclear halo or translucent zone (type 2 cells)
  • Also type 1 cells that are small with solid, slightly granular, eosinophilic cytoplasm
  • Usually lower grade nuclei, bunching of nuclear material at nuclear membrane; 50% have calcification
  • Mitotic figures present but may be scant; usually no chicken wire vasculature (more fibrovascular than vascular)
  • Fuhrman grading has no prognostic value (Am J Surg Pathol 2007;31:957)
  • Recent study suggests that Paner grading system (Am J Surg Pathol 2010;4:1233) adds no prognostic value after considering TNM stage and sarcomatoid differentiation (Am J Surg Pathol;36:851)
  • Type 1 cells: small cells with solid, slightly granular eosinophilic cytoplasm
  • Type 2 cells: perinuclear halo or translucent zone
  • Type 3 cells: large, polygonal cells with hard cell border, abundant cytoplasm with reticular pattern
  • Note: formalin fixation may obscure cytoplasmic features (Arch Pathol Lab Med 2000;124:904)
Micro Images

Images hosted on PathOut server:

The transparent cells are oriented along the thin vascular septa

Granular and trans-
parent cells are
intermixed in an
irregular pattern

Tumor cells vary from
pale andtransparent to
acidophilic and granular



Images hosted on other servers:

Various images

Nuclear grooves and inclusions


Obscured cytoplasmic features with formalin fixation

Birt-Hogg-Dubé associated tumors

Sarcomatoid features



Stain images:

H&E and Hale's colloidal iron

Hale's colloidal iron

Classic and eosinophilic
variant and oncocytoma:
H&E and Hale's colloidal iron


CK7+

c-kit+ (Fig. E)

Parvalbumin+

E-cadherin+


MUC1+ (Fig. F)

Left to right: S100A1-, EpCAM+, claudin7+

Cytology Description
  • Single cells and small, discohesive, monolayered groups; cells vary in size from small to large
  • Large cells show clear, flocculent cytoplasm with small, eccentric nuclei and frequent binucleation, occasional nuclear pseudoinclusions
  • Small cells usually have dense, homogeneous cytoplasm, clear cytoplasmic spaces resembling perinuclear halos, binucleation and marginal nuclear location
  • No necrosis, no basement membrane or other stromal material (Cytopathology 2009;20:44, Cancer 1997;81:122)
Cytology Images

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Large round to oval cells (Diff-Quik)

Plant-like large cells with
very sharp cell borders and
small cells with dense cyto-
plasm and smaller nuclei

Cells have sharp cell borders,
pale cytoplasm, round nuclei
with slightly coarse chro-
matin and small nucleoli

Positive Stains
Most commonly used:
Other positive stains:
Other positive stains:
Negative Stains
Suggested panels
  • Chromophobe versus oncocytoma, papillary or clear cell: beta defensin1+, parvalbumin+, vimentin- in 100 (8/8) (Am J Surg Pathol 2003;27:199)
  • Chromophobe versus oncocytoma or clear cell: vimentin-, GSTalpha-, EpCAM+ (strong) (Arch Pathol Lab Med 2007;131:1290)
  • CK7+ diffusely positive in chromophobe vs scattered single cells in oncocytoma; second line markers include CD117+
  • Chromophobe versus other renal carcinomas: CK7+, CK8+, CK18+ and vimentin- (Am J Surg Pathol 2005;29:747)
Electron Microscopy Description
  • 150 - 350 nm membrane bound microvesicles (possibly from mitochondrial outpouchings), abnormal but few mitochondria with tubulovesicular cristae, rare short and stubby microvilli (Am J Surg Pathol 2000;24:1247)
  • Eosinophilic variant is similar but with more mitochondria
Electron Microscopy Images

Images hosted on PathOut server:

Cytoplasmic vesicles of 150 to 300 nm

Cytoplasmic vesicles are often
paranuclear with mitochondria
present in the more
peripheral cytoplasm

Molecular / Cytogenetics Description
Molecular / Cytogenetics Images

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Loss of chromosome 2
in chromophobe carcinoma
versus no loss in oncocytoma

Differential Diagnosis