Kidney tumor

Adult renal cell carcinoma - rare

Succinate dehydrogenase deficient

Last author update: 1 May 2016
Last staff update: 17 March 2023 (update in progress)

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PubMed Search: SDH [title] kidney

Nicole K. Andeen, M.D.
Maria Tretiakova, M.D., Ph.D.
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Cite this page: Andeen NK, Tretiakova M. Succinate dehydrogenase deficient. website. Accessed March 27th, 2023.
Definition / general
  • Succinate dehydrogenase (SDH) deficient renal cell carcinoma is defined by the WHO as a malignant epithelial tumor composed of vacuolated eosinophilic to clear cells with loss of immunohistochemical expression of SDHB, a marker of dysfunction of mitochondrial complex II (WHO 2016)
Essential features
  • Characteristic flocculent cytoplasmic vacuoles with a pale eosinophilic, wispy or bubbly appearance and low grade nuclei (at least focally)
  • May have high grade areas
  • Oncogenesis is driven by metabolic derangements due to double hit inactivation of SDH genes, leading to dysfunction of mitochondrial complex II
  • Most patients have a germline mutation in an SDH gene, usually SDHB
  • Terminology which is sometimes used but not recommended is SDHB negative renal carcinoma or SDH deficient renal oncocytoma
  • Rare
  • Represents 0.05% to 0.2% of all renal cell carcinomas (WHO 2016)
  • Median age 35 years (range 14 to 76); M:F ratio = 1:8:1
  • Bilateral in 26% (Am J Surg Pathol 2014;38:1588)
  • Kidney
  • Most cases occur in setting of germline mutation of an SDH gene; neoplasia occurs with double hit inactivation, leading to dysfunction of mitochondrial complex II, increased reactive oxygen species, DNA damage and HIF1α stabilization (Int Journal of Cell Biology 2012:2012)
  • SDHB is most commonly affected in SDH deficient RCC, then SDHC
  • Rarely SDHA or SDHD (different for other SDH deficient tumors)
Diagrams / tables

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Redox alterations

Clinical features
  • Often confined to the kidney at presentation
  • Presents with flank pain or as incidental finding
  • Personal or family history of paragangliomas or SDH deficient gastrointestinal stromal tumor may be present (WHO 2016) (GeneReviews 2008;NBK1548)
Prognostic factors
Case reports
  • Resection; further treatment is dependent on grade / stage, may include targeted therapy (J Clin Oncol 2014;32;e10)
  • All patients with a diagnosis of SDH deficient RCC should be offered genetic testing (WHO 2016)
Gross description
  • Well circumscribed, solid with red / brown cut surface, variable multicystic change, generally no necrosis
  • Usually confined to kidney with no involvement of renal sinus, vein or fat
Gross images

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Cystic change;
solid neoplasms

Microscopic (histologic) description
  • Well circumscribed or pushing border, commonly entraps tubules
  • Solid, nested or tubular growth pattern with scattered cysts containing eosinophilic material
  • Neoplastic cells have smooth nuclear contours and fine chromatin with no nucleoli
  • Characteristic finding is flocculent cytoplasmic vacuoles with a pale eosinophilic, wispy or bubbly appearance with low grade nuclei
    • This morphology is commonly diffuse and should be at least focal (WHO 2016)
  • May have areas of higher grade nuclei, necrosis, sarcomatoid change
  • Variant morphologies have been reported but are rare in absence of more characteristic low grade regions (WHO 2016)
Microscopic (histologic) images

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Various images

SDH deficient RCC

Negative stains
  • Loss of SDHB immunohistochemical staining (be cautious on overinterpretation of negativity in tumors with very clear cytoplasm)
    • Loss of SDHB immunohistochemical staining indicates disruption of the mitochondrial complex 2 for any reason, not just SDHB gene mutation (Am J Surg Pathol 2014;38:1588)
  • CK7, CAIX, RCC, c-kit (mast cells only), vimentin (Mod Pathol 2015;28:80), neuroendocrine markers
  • Minimal AMACR staining
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]
Molecular / cytogenetics description
  • No mutations in VHL, PIK3CA, AKT, mTOR, MET or TP53 genes (WHO 2016)
  • Genes for succinate dehydrogenase subunits (SDHA, SDHB, SDHC, SDHD) encode proteins which are part of mitochondrial complex II, which links the Krebs cycle and electron transport chain (N Engl J Med 2011;364:885)
Differential diagnosis
Additional references
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