Kidney tumor
Adult renal cell carcinoma - common

Topic Completed: 1 June 2017

Minor changes: 1 July 2020

Copyright: 2003-2019,, Inc.

PubMed Search: "Chromophobe type" renal cell carcinoma

See Also: Eosinophilic variant of chromophobe renal cell carcinoma

Daniel Anderson, M.D., M.B.A.
Maria Tretiakova, M.D., Ph.D.
Page views in 2019: 33,668
Page views in 2020 to date: 24,467
Cite this page: Anderson D, Tretiakova M. Chromophobe. website. Accessed September 29th, 2020.
Definition / general
  • Tumor cells with prominent cell borders, finely reticular pale cytoplasm, perinuclear halos and wrinkled raisinoid nuclei
  • First described in 1985 (Virchows Arch B Cell Pathol Incl Mol Pathol 1985;48:207)
  • Cell of origin: distal convoluted tubules and cortical collecting ducts
  • Third most common RCC subtype; 5 - 7% of adult renal epithelial tumors
  • Majority are sporadic and incidental, no gender preference
  • Mean age 58 years (Cancer 2004;100:1406)
Birt-Hogg-Dubé syndrome
  • Multiple tumors (mean 5.3), mean age 51 years at first renal tumor diagnosis, usually bilateral chromophobe carcinomas, oncocytomas or hybrid oncocytic / chromophobe tumor, also may have oncocytosis (Am J Surg Pathol 2002;26:1542)
  • Autosomal dominant syndrome: small dome shaped papular fibrofolliculomas of face, neck and upper trunk, renal tumors, lung cysts and spontaneous pneumothorax
  • Mutations in the folliculin gene (FLCN) at 17p11.2 leading to premature truncation and loss of function of the folliculin protein (Cancer Cell 2002;2:157, Hum Mutat 2010;31:E1043)
Clinical features
  • Most are T1 - T2 N0 M0 (i.e. confined within the renal capsule, Cancer 2004;100:1406) and have good prognosis
  • 5 and 10 year cancer specific survival (CSS) are 93% and 88.9%, respectively (BJU Int 2012;110:76)
Poor prognostic factors
Case reports
Gross description
  • Well circumscribed, not encapsulated, tan to light brown
  • Average size 5 - 8 cm (BJU Int 2012;110:76)
  • Necrosis, hemorrhage and small cysts (25 - 30%)
  • Occasionally central scar (~15%)
  • Multifocal (10%)
Gross images

AFIP images

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

Microscopic (histologic) description
  • Solid growth, nests or broad alveoli / trabeculae, composed of polygonal cells with "hard" or distinct cell borders ("vegetable cells", due to cytoplasmic retraction)
  • Composed of 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
  • Nuclei are irregular, wrinkled and angulated with perinuclear halos
  • Fuhrman / ISUP grading has no prognostic value (Am J Surg Pathol 2007;31:957, Hum Pathol 2014;45:2411)
  • Mitotic figures present but may be scant; usually no chicken wire vasculature (more fibrovascular than vascular)
  • Paner grading system (Am J Surg Pathol 2010;34:1233) adds no prognostic value after considering TNM stage and sarcomatoid differentiation (Am J Surg Pathol;36:851)
  • Eosinophilic variant of chromophobe renal cell carcinoma: when composed entirely of eosinophilic cells
  • Note: formalin fixation may obscure cytoplasmic features (Arch Pathol Lab Med 2000;124:904)
Microscopic (histologic) images

Contributed by Daniel Anderson, M.D., M.B.A.

ChRCC classic 20x


Chromophobe with sarcomatoid

Sarcomatoid component

High Power Sarcomatoid

Contributed by Dr. Asmaa Gaber Abdou, Menoufiya University, Egypt

Various images

AFIP images

The transparent cells are oriented along the thin vascular septa

Granular and transparent cells are intermixed

Tumor cells vary from pale to acidophilic

Images hosted on other servers:

Chromophobe renal cell carcinoma

Nuclear grooves and inclusions

Birt-Hogg-Dubé associated tumors

Sarcomatoid features

Stain images:

Hale colloidal iron



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

Images hosted on other servers:

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

Large round to oval cells (Diff-Quik)

Pap stain

Positive stains
Negative stains
Possible panels
  • CK7+ diffusely positive in chromophobe vs scattered single cells in oncocytoma; second line markers include CD117+
  • Chromophobe versus oncocytoma, papillary or clear cell renal cell carcinoma (CCRCC): beta defensin1+, parvalbumin+, vimentin- in 100% (8/8) (Am J Surg Pathol 2003;27:199)
  • Chromophobe versus oncocytoma or CCRCC: vimentin-, GSTalpha-, EpCAM+ (strong) (Arch Pathol Lab Med 2007;131:1290)
  • Chromophobe versus other renal carcinomas: CK7+, CK8+, CK18+ and vimentin- (Am J Surg Pathol 2005;29:747)
  • Chromophobe versus CCRCC versus oncocytoma: DOG1, cyclin D1, CK7, CD117 and vimentin (Pathol Res Pract 2015;211:303)
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

AFIP images

Cytoplasmic vesicles of 150 to 300 nm

Cytoplasmic vesicles are often paranuclear

Molecular / cytogenetics description
  • Multiple losses of whole chromosomes, most often 1, 2, 6, 10, 13, 17, 21 or Y versus no loss in oncocytoma (Hum Pathol 1998;29:1181, Mod Pathol 2005;18:161)
  • FISH and SNP arrays may be more helpful than karyotyping (Am J Clin Pathol 2010;133:116)
  • DNA rearrangement breakpoints within the TERT promoter region
  • TP53 and PTEN mutated in 32% and 9% cases (TCGA cohort)
  • Mitochondrial (mt) DNA rearrangements including loss of function mutations in NADH dehydrogenase subunits (Cancer Cell 2014;26:319)
  • In addition, chromophobe has increased expression of genes encoding enzymes in the Krebs cycle, whose expression is suppressed in CCRCC (Cancer Cell 2014;26:319)
  • Sarcomatoid tumors have different genetic abnormalities (Mod Pathol 2007;20:303)
  • MiRNA expression patterns may be associated with progression, recurrence free survival (RFS) and overall survival (Sci Rep 2015;5:10328)

Chromophobe type RCC

Differential diagnosis
Board review style question #1
All the following are true of chromophobe renal cell carcinoma EXCEPT:

  1. As opposed to oncocytoma, chromophobe shows multiple losses of whole chromosomes, most often 1, 2, 6, 10, 13, 17, 21 or Y.
  2. Fuhrman / ISUP grading has no prognostic value.
  3. Sarcomatoid is a poor prognostic indicator.
  4. The classic autosomal recessive genetic correlation with chromophobe renal cell carcinoma is Birt-Hogge-Dubé syndrome which is associated with a mutation of the HOGG gene on chromosome 3p.
  5. Unlike clear cell renal cell carcinoma, chromophobe is classically CAIX negative, vimentin negative, CK7 and c-kit (CD117) positive.
Board review answer #1
D. Birt-Hogg-Dubé is caused by an autosomal dominant mutation of the folliculin gene (FLCN) at 17p11.2 leading to premature truncation and loss of function of the folliculin protein. Von Hippel-Lindau syndrome, also autosomal dominant, is caused by a mutation of the VHL tumor suppressor gene (3p25-26). Depending on the subtype, VHL is associated with clear cell renal cell carcinoma, CNS and retinal hemangioblastomas, visceral cysts in the kidney, pancreas and epididymis, endolymphatic sac tumors, pancreatic neuroendocrine tumors, paragangliomas and pheochromocytomas (Front Horm Res 2013;41:30). Unlike clear cell renal cell carcinoma, Furhman / ISUP grade has no prognostic value and is CAIX and vimentin negative and CK7 and c-kit (CD117) positive. Clear cell RCC often is CAIX and vimentin positive and CK7 and c-kit negative. Sarcomatoid change is a significant poor prognostic indicator in chromophobe renal cell carcinoma. Chromophobe shows multiple losses of whole chromosomes, most often 1, 2, 6, 10, 13, 17, 21 or Y.

Reference: Kidney tumor - Chromophobe renal cell carcinoma

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