Kidney tumor

Adult renal cell carcinoma - common

Chromophobe


Editor-in-Chief: Debra L. Zynger, M.D.
Maria Tretiakova, M.D., Ph.D.

Topic Completed: 21 October 2020

Minor changes: 16 June 2021

Copyright: 2003-2021, PathologyOutlines.com, Inc.

PubMed Search: "Chromophobe type" renal cell carcinoma

See Also: Eosinophilic variant of chromophobe renal cell carcinoma

Maria Tretiakova, M.D., Ph.D.
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Cite this page: Tretiakova M. Chromophobe. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/kidneytumormalignantrccchromo.html. Accessed October 23rd, 2021.
Definition / general
  • Solid tumor composed of granular pale cells with prominent cell borders, finely reticular cytoplasm, perinuclear halos and wrinkled hyperchromatic nuclei
  • First described in 1985 (J Pathol 1988;155:277)
  • Cell of origin: intercalated cells of distal convoluted tubules
Essential features
  • Solid sheet-like architecture
  • Sharply defined cell membranes (plant-like)
  • Wrinkled irregular nuclei (raisinoid)
  • Perinuclear halos (koilocytic)
Terminology
  • Chromophobe renal cell carcinoma (ChRCC), classic variant
ICD coding
  • ICD-10: C64 - malignant neoplasm of kidney, except renal pelvis
Epidemiology
Sites
  • Solitary kidney mass
  • Most commonly in renal cortex
Birt-Hogg-Dubé syndrome
  • Multiple tumors (mean 5.3); mean age 51 years at first renal tumor diagnosis
  • Bilateral multifocal ChRCC, oncocytomas or hybrid oncocytic chromophobe tumor (HOCT), 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
Radiology description
  • Usually large, well circumscribed, hypovascular mass with relatively homogeneous contrast enhancement; may show central scar
Prognostic factors
Case reports
Treatment
  • Surgery, cryoablation and targeted systemic chemotherapy for metastatic disease with antiangiogenic, TK and mTOR inhibitors (Eur J Cancer 2017;80:55)
Gross description
  • Well circumscribed, unencapsulated, tan to light brown
  • Average size 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

Tan and relatively homogeneous tumor



Images hosted on other servers:

Yellowish brown tumor with granular cut surface

Nodular tumor with focal hemorrhage and necrosis

Microscopic (histologic) description
  • Typically confluent solid growth with nests, sheets or alveoli / trabeculae composed of pale cells with sharply defined plant-like cell borders (vegetable cells)
  • 2 types of tumor cells:
    • Type 1: large, polygonal cells with hard cell border; abundant cytoplasm with reticular pattern
    • Type 2: smaller cells with finely granular eosinophilic cytoplasm (predominant in eosinophilic variant)
  • Nuclei are irregular, wrinkled and angulated with coarse chromatin (raisinoid)
  • Common binucleation, multinucleation and perinuclear halos (koilocytic atypia)
  • Mitotic figures present but usually scant
  • Stroma minimal, composed of incomplete fibrovascular septae around solid sheets
  • No chicken wire vasculature (more fibrovascular than vascular)
  • Fuhrman / WHO grading has no prognostic value and is discouraged (Histopathology 2019;74:4)
  • Paner grading system adds no prognostic value after considering TNM stage and sarcomatoid differentiation (Am J Surg Pathol 2010;34:1233, Am J Surg Pathol 2012;36:851)
  • Eosinophilic variant of chromophobe renal cell carcinoma: when composed entirely of smaller eosinophilic cells
Microscopic (histologic) images

Contributed by Maria Tretiakova, M.D., Ph.D. and Daniel Anderson, M.D., M.B.A.
Solid sheets and thin septae

Solid sheets and thin septae

Large polygonal and smaller eosinophilic cells

Large polygonal and smaller eosinophilic cells

Raisinoid nuclei

Raisinoid nuclei

Plant-like membranes and binucleation

Plant-like membranes and binucleation

Plant-like cells

Plant-like cells


Pale reticular cells

Pale reticular cells

Discohesive

Discohesive

Confluent growth

Confluent growth

Hale colloidal iron

Hale colloidal iron

CK7

CK7


KIT

KIT

Vimentin

Vimentin

Sarcomatoid Sarcomatoid Sarcomatoid

Sarcomatoid

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:

Two cell populations

Polygonal plant-like cells

Large round to oval cells (Diff-Quik)

Pap stain

Positive stains
Negative stains
IHC panels
 Hale  KIT  CK7  S100A1  VIM  CAIX  AMACR  SDH  TFE3
 Chromophobe RCC   +++   +++   +++   -   -   -   -   +++   - 
 Clear cell RCC   -   -   -   -   +++   +++   -   +++   - 
 Oncocytoma   -   +++   rare   +++   -   -   -   +++   - 
 Papillary RCC   -   -   +++   -   +++   -   +++   +++   - 
 Translocation RCC   -   -   -   -   -   -   ++   +++   +++ 
 SDH deficient RCC   -   -   -   -   -   -   -   -   - 

References: Pathol Res Pract 2015;211:303, Ann Diagn Pathol 2020;44:151448, Am J Surg Pathol 2014;38:e6, Arch Pathol Lab Med 2019;143:1455, Transl Androl Urol 2019;8:S123, Hum Pathol 2020 Jul 13 [Epub ahead of print]
Electron microscopy description
  • All contain cytoplasmic microvesicles, which are considered a unique and consistent ultrastructural feature (Am J Surg Pathol 2000;24:1247)
  • These 150 - 350 nm membrane bound microvesicles do not stain with H&E stain (chromophobe), often concentrated in perinuclear location corresponding to perinuclear halos on light microscopy and reticular pale cytoplasm
  • Microvesicle origin is uncertain but possibly from mitochondrial outpouchings or defective mitochondriogenesis
  • Eosinophilic cells are similar but with more mitochondria; mitochondria often show tubulocystic cristae, rare short and stubby microvilli (Am J Surg Pathol 2000;24:1247)
Electron microscopy images

AFIP images
Cytoplasmic vesicles of 150 - 300 nm

Cytoplasmic vesicles of 150 - 300 nm

Paranuclear cytoplasmic vesicles

Paranuclear cytoplasmic vesicles



Images hosted on other servers:

Filled with round to oval vesicles

Molecular / cytogenetics description
Differential diagnosis
Board review style question #1

Which of the following is true about chromophobe (ChRCC)?

  1. Binucleation is pathognomonic
  2. Cellulose deposition explains plant-like prominent membranes
  3. Cytoplasmic clearing is due to high concentration of lipids
  4. Multinucleation is an unfavorable prognostic feature
  5. Perinuclear halos are due to accumulation of cytoplasmic microvesicles
Board review style answer #1
E. Perinuclear halos are due to accumulation of cytoplasmic microvesicles. The presence of cytoplasmic microvesicles is a unique and consistent ultrastructural feature of ChRCC. Microvesicles are often concentrated in perinuclear location, corresponding to perinuclear halos on light microscopy. These vesicles lack affinity for H&E stain, resulting in cells with clear, reticular or flocculent cytoplasmic appearance on light microscopy (chromophobe). The origin is uncertain but likely related to defective mitochondria (Am J Surg Pathol 2000;24:1247).

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Reference: Chromophobe
Board review style question #2
What is the best statement describing chromophobe renal cell carcinoma (ChRCC)?

  1. Can be reliably distinguished from clear cell RCC by CK7, CKIT (CD117), CAIX and vimentin
  2. Classic autosomal dominant genetic correlation is Birt-Hogg-Dubé syndrome, which is associated with a mutation of the HOGG gene on chromosome 3p
  3. Fuhrman / WHO grading is useful prognostic indicator
  4. Sarcomatoid dedifferentiation is very common
  5. To establish the diagnosis, a documentation of monosomies involving chromosomes 1, 2, 6, 10, 13, 17, 21 or Y is needed
Board review style answer #2
A. Chromophobe shows multiple losses of whole chromosomes, most often 1, 2, 6, 10, 13, 17, 21 or Y but documentation of monosomies is not required for diagnosis. Sarcomatoid change is a significant poor prognostic indicator in chromophobe renal cell carcinoma but observed in ~5% of cases. 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, Fuhrman / ISUP grade has no prognostic value. ChRCC by immunostaining CAIX and vimentin are negative and CK7 and CKIT (CD117) positive. Clear cell RCC shows opposite expression with CAIX and vimentin positive and CK7/CKIT negative.

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Reference: Chromophobe
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