Fumarate hydratase-deficient renal cell carcinoma

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Fumarate hydratase-deficient renal cell carcinoma
Diagnosis in short

FH-deficient renal cell carcinoma showing the characteristic hyalinized papillary cores. H&E stain. (WC/Nephron)

LM cells with large (usually eosinophilic) nucleolus with perinucleolar clearing (may be focal), variable architecture: papillary (classic description) +/-hyaline material within the fibrovascular cores (characteristic), tubulopapillary, tubular, solid, sieve-like pattern/cribriform
LM DDx papillary renal cell carcinoma, tubulocystic carcinoma of the kidney, collecting duct carcinoma, renal medullary carcinoma
IHC FH -ve, 2SC +ve, CK7 -ve, TFE3 -ve, CK20 -ve, CD10 -ve, UEA-1 -ve
Molecular FH mutation
Grossing notes total nephrectomy for tumour grossing, partial nephrectomy grossing
Staging kidney cancer staging
Site kidney - see kidney tumours

Associated Dx uterine leiomyomas (women), skin leiomyomas
Syndromes hereditary leiomyomatosis and renal cell carcinoma syndrome

Clinical history +/-family history of kidney cancer, +/-family history of leiomyomas
Signs +/-"skin rash" (leiomyomas), signs of renal cancer (+/-hematuria, +/-palpable abdominal mass)
Prevalence rare
Prognosis poor
Clin. DDx other kidney tumours
Treatment resection

Fumarate hydratase-deficient renal cell carcinoma (abbreviated FH-deficient RCC) is a formally recognized a distinct entity by the WHO as of 2013.

It was previously known as hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cell carcinoma (abbreviated HLRCC syndrome-associated RCC).[1][2]



Features - renal cell carcinoma:[3]

  • Cells with:
    • Large, (usually) eosinophilic, nucleolus with perinucleolar clearing - proposed hallmark - important.
      • May be focal.
    • Abundant or moderate (eosinophilic/partially clear) cytoplasm.
  • Variable architecture:
    • Papillary - classic description.
      • Hyaline material within the fibrovascular cores - characteristic.
    • Tubulopapillary.
    • Tubular.
    • Solid.
    • Sieve-like pattern/cribriform.







  • Fumarate hydratase (FH) -ve.
  • 2SC +ve -- cytoplasmic,[6] cytoplasmic and nuclear.[3]
    • 2SC = S-(2-succino)-cysteine.


See also


  1. Srigley, JR.; Delahunt, B.; Eble, JN.; Egevad, L.; Epstein, JI.; Grignon, D.; Hes, O.; Moch, H. et al. (Oct 2013). "The International Society of Urological Pathology (ISUP) Vancouver Classification of Renal Neoplasia.". Am J Surg Pathol 37 (10): 1469-89. doi:10.1097/PAS.0b013e318299f2d1. PMID 24025519.
  2. Trpkov, K.; Hes, O.; Agaimy, A.; Bonert, M.; Martinek, P.; Magi-Galluzzi, C.; Kristiansen, G.; Lüders, C. et al. (Feb 2016). "Fumarate Hydratase-deficient Renal Cell Carcinoma Is Strongly Correlated With Fumarate Hydratase Mutation and Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome.". Am J Surg Pathol. doi:10.1097/PAS.0000000000000617. PMID 26900816.
  3. 3.0 3.1 3.2 Chen, YB.; Brannon, AR.; Toubaji, A.; Dudas, ME.; Won, HH.; Al-Ahmadie, HA.; Fine, SW.; Gopalan, A. et al. (May 2014). "Hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cancer: recognition of the syndrome by pathologic features and the utility of detecting aberrant succination by immunohistochemistry.". Am J Surg Pathol 38 (5): 627-37. doi:10.1097/PAS.0000000000000163. PMID 24441663.
  4. 4.0 4.1 Launonen, V.; Vierimaa, O.; Kiuru, M.; Isola, J.; Roth, S.; Pukkala, E.; Sistonen, P.; Herva, R. et al. (Mar 2001). "Inherited susceptibility to uterine leiomyomas and renal cell cancer.". Proc Natl Acad Sci U S A 98 (6): 3387-92. doi:10.1073/pnas.051633798. PMID 11248088.
  5. Pithukpakorn, M.; Wei, MH.; Toure, O.; Steinbach, PJ.; Glenn, GM.; Zbar, B.; Linehan, WM.; Toro, JR. (Sep 2006). "Fumarate hydratase enzyme activity in lymphoblastoid cells and fibroblasts of individuals in families with hereditary leiomyomatosis and renal cell cancer.". J Med Genet 43 (9): 755-62. doi:10.1136/jmg.2006.041087. PMID 16597677.
  6. Reyes, C.; Karamurzin, Y.; Frizzell, N.; Garg, K.; Nonaka, D.; Chen, YB.; Soslow, RA. (Jul 2014). "Uterine smooth muscle tumors with features suggesting fumarate hydratase aberration: detailed morphologic analysis and correlation with S-(2-succino)-cysteine immunohistochemistry.". Mod Pathol 27 (7): 1020-7. doi:10.1038/modpathol.2013.215. PMID 24309325.
  7. 7.0 7.1 7.2 7.3 7.4 Merino, MJ.; Torres-Cabala, C.; Pinto, P.; Linehan, WM. (Oct 2007). "The morphologic spectrum of kidney tumors in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome.". Am J Surg Pathol 31 (10): 1578-85. doi:10.1097/PAS.0b013e31804375b8. PMID 17895761.