Kidney tumor

Adult renal cell carcinoma - rare

Hybrid oncocytic chromophobe tumor

Editorial Board Member: Nicole K. Andeen, M.D.
Deputy Editor-in-Chief: Maria Tretiakova, M.D., Ph.D.
Bonnie Choy, M.D.

Last author update: 8 September 2021
Last staff update: 8 September 2021

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Bonnie Choy, M.D.
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Cite this page: Choy B. Hybrid oncocytic chromophobe tumor. website. Accessed May 19th, 2024.
Definition / general
  • Hybrid oncocytic chromophobe tumor (HOCT) is a renal neoplasm with overlapping features of both renal oncocytoma and chromophobe renal cell carcinoma (ChRCC)
Essential features
  • Hybrid oncocytic chromophobe tumor - GUPS recommends the term to be reserved for hereditary cases
  • Other nonsyndromic tumors with borderlines features could be designated “oncocytic renal neoplasms of low malignant potential, not further classified”
  • Kidney
Clinical features
  • Diagnosis by histologic examination of tissue
Radiology description
  • CT (J Comput Assist Tomogr 2016;40:513):
    • Solid and well circumscribed
    • Central stellate hypodensity in 33%, heterogenous appearance 42%
    • No calcifications seen
    • Mean attenuation values: 25.7 Hounsfield units (HU, noncontrast), 77.4 HU (arterial), 124.8 HU (venous), 76.8 HU (delayed); tumor to cortex ratios for 2 enhanced phases (arterial and venous): 0.56 and 0.79, respectively
  • Positive on 99mTc sestamibi SPECT / CT, similar to renal oncocytoma and ChRCC (Eur Urol 2016;69:413)
Radiology images

Images hosted on other servers:

Heterogenous pattern

Stellate central hypodensity

2 abutting tumors

Preoperative CT

Prognostic factors
Case reports
Gross description
Gross images

Contributed by Bonnie Choy, M.D.
Multiple tan-brown tumors

Multiple tan-brown tumors

Microscopic (histologic) description
Microscopic (histologic) images

Contributed by Chin-Lee Wu, Ph.D. and Maria Tretiakova, M.D., Ph.D.
Dual population of eosinophilic cells Dual population of eosinophilic cells Dual population of eosinophilic cells

Dual population of eosinophilic cells

BHD related hybrid tumor BHD related hybrid tumor BHD related hybrid tumor

BHD related hybrid tumor

Contributed by Roula Albadine, M.D. and Julie Guilmette, M.D.
Oncocytic tumor cells

Oncocytic tumor cells

Oncocytic cells with granular eosinophilic cytoplasm

Oncocytic cells with granular eosinophilic cytoplasm

Hale colloidal iron

Hale colloidal iron

Virtual slides

Images hosted on other servers:


Hybrid oncocytic tumor

Cytology description
Cytology images

Contributed by Bonnie Choy, M.D.
Touch preparation

Touch preparation

Positive stains
Electron microscopy description
  • Tumor cells with numerous mitochondria of varying sizes (Virchows Arch 2010;456:355)
  • Sparse microvesicles with amorphic lamellar content
  • Infrequently, small intracytoplasmatic tubuli covered by microvilli may be observed
Molecular / cytogenetics description
  • Assessment of DNA copy number alterations showed conflicting results:
    • Petersson et al.: 14 sporadic HOCTs (Virchows Arch 2010;456:355)
      • Monosomy or polysomy in all cases analyzed (most common - chromosome 20 monosomy), distinct from cytogenetic anomalies commonly found in renal oncocytoma and ChRCC
    • Poté et al.: 12 HOCTs: 10 sporadic, 2 Birt-Hogg-Dubé cases (Virchows Arch 2013;462:633)
      • No chromosome imbalance in 58%
      • Chromosome 1 deletions in 33%, similar to renal oncocytoma
  • Assessment of DNA copy number alterations, as well as mutational and transcriptomic profile compared with renal oncocytoma and ChRCC:
    • Ruiz-Cordero et al.: 27 HOCTs: 25 sporadic, 2 Birt-Hogg-Dubé cases (Mod Pathol 2019;32:1698)
      • Low mutational frequency and absence of mutations in driver genes that are frequently seen in renal oncocytoma and ChRCC
      • Copy number alterations primarily involving losses in chromosomes 1 and X / Y and ~40% lack chromosomal gains or losses - more similar to alteration profile of renal oncocytoma than ChRCC
      • Gene expression profile intermediate between renal oncocytoma and ChRCC
  • Tumor microdissection showed conflicting results:
    • Poté et al.: (Virchows Arch 2013;462:633)
      • No differences in renal oncocytoma-like and ChRCC-like areas using comparative genomic hybridization
    • Pires-Luis et al.: (Exp Mol Pathol 2018;105:352)
      • Higher miR-21 expression by microRNA analysis and focal multiple tetrasomies by FISH analysis in renal oncocytoma-like areas and higher relative miR-141 and miR200b expression and no chromosomal alterations in ChRCC-like areas
  • Tumors morphologically predicted to be HOCT were cytogenetically heterogenous and classified into 3 groups: renal oncocytoma (27%) renal oncocytoma variants (46%) and ChRCC (27%) (Hum Pathol 2020;104:18)
Sample pathology report
  • Right kidney, partial nephrectomy:
    • Hybrid oncocytic chromophobe tumors, measuring 3.5 and 2.3 cm in greatest dimensions (see comment)
    • Surgical margins, negative for tumor
    • Comment: The specimens contain a mixture of tumor cells demonstrating morphologic features that overlap with those of renal oncocytoma and chromophobe renal cell carcinoma. Given the patient's clinical history these are consistent with hybrid oncocytic chromophobe tumors associated with Birt-Hogg-Dubé syndrome.
Differential diagnosis
Board review style question #1

A patient with a history of Birt-Hogg-Dubé syndrome undergoes a partial nephrectomy. Gross examination of the specimen shows multiple well circumscribed tan-brown masses. H&E sections show the above histologic features. What is the likely diagnosis?

  1. Clear cell renal cell carcinoma
  2. Epithelioid angiomyolipoma
  3. Hybrid oncocytic chromophobe tumor
  4. Succinate dehydrogenase (SDH) deficient renal cell carcinoma
Board review style answer #1
C. Hybrid oncocytic chromophobe tumor

The patient's history of Birt-Hogg-Dubé syndrome and the macroscopic and microscopic findings support the diagnosis of hybrid oncocytic chromophobe tumor. Clear cell renal cell carcinoma has clear to granular tumor cells with intervening blood vessels. Epithelioid angiomyolipoma may contain areas admixed with adipocyte and vessels. Succinate dehydrogenase (SDH) deficient renal cell carcinoma demonstrates flocculent cytoplasmic vacuoles with pale eosinophilic appearance.

Immunohistochemistry can be used to confirm the diagnosis. While hybrid oncocytic chromophobe tumor is positive for CD117, the other choices are negative for CD117. Additionally, clear cell renal cell carcinoma is diffusely positive for CAIX, epithelioid angiomyolipoma is positive for Melan A and HMB45 and SDH deficient renal cell carcinoma shows loss of SDHB staining.

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Reference: Hybrid oncocytic chromophobe tumor
Board review style question #2
A patient has a history of skin lesions and spontaneous pneumothorax, now presenting with multiple and bilateral renal tumors. He underwent a partial nephrectomy, which revealed a hybrid oncocytic chromophobe tumor. Which of the following syndromes does the patient most likely have?

  1. Beckwith-Wiedemann syndrome
  2. Birt-Hogg-Dubé syndrome
  3. Tuberous sclerosis
  4. von Hippel-Lindau
Board review style answer #2
B. Birt-Hogg-Dubé syndrome

Explanation: A small percentage of kidney tumors are associated with hereditary syndromes. Birt-Hogg-Dubé syndrome is associated with hybrid oncocytic chromophobe tumor. Beckwith-Wiedemann syndrome is associated with Wilms tumor, while von Hippel-Lindau syndrome is associated with renal cell carcinoma. Angiomyolipoma, hereditary papillary renal cell carcinoma and familial renal oncocytoma are seen in patients with tuberous sclerosis.

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Reference: Hybrid oncocytic chromophobe tumor
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