{"entity":{"id":"fh-deficient-renal-cell-carcinoma","kind":"cancer","name":"Fumarate hydratase-deficient renal cell carcinoma (HLRCC-associated)","aka":["FH-deficient renal cell carcinoma","Hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cell carcinoma","HLRCC-associated RCC","Fumarate hydratase-deficient renal cell carcinoma (HLRCC syndrome)","Papillary renal cell carcinoma type 2 (former label for many cases)"],"tldr":"Fumarate hydratase-deficient renal cell carcinoma is a rare, aggressive kidney cancer in which the FH gene is lost, most often because the person was born with a faulty copy as part of the HLRCC syndrome, which also causes skin and womb fibroids. It strikes younger adults, is found by a stain for the missing enzyme, and needs family testing; advanced disease gets the usual kidney cancer drugs.","summary":"The 2016 WHO classification introduced hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cell carcinoma, and the 2022 edition names it fumarate hydratase-deficient renal cell carcinoma because sporadic cases with somatic FH loss occur (Moch 2016; Moch 2022). Immunohistochemistry for FH loss with 2-succinocysteine positivity identified 24 FH-deficient tumours among 124 cases previously diagnosed as unclassified high-grade or papillary type 2 carcinoma; FH mutations were found in 19 of 21 FH-deficient tumours, germline in all nine tested, and the median age was 44 (Am J Surg Pathol 2016). A tubulocystic carcinoma with poorly differentiated foci is a frequent pattern: of 29 such tumours (median age 46, median size 9 cm), 79 percent showed perinephric extension, 41 percent nodal involvement and 86 percent metastasis, and 55 percent had FH loss, with HLRCC identifiable in the family only retrospectively in 12 percent (Am J Surg Pathol 2016). A low-grade oncocytic form resembling SDH-deficient carcinoma also exists (Histopathology 2017).\n\nHow it differs from its parent: it is a metabolic (Krebs cycle) cancer, hereditary in most cases, aggressive even when small, and it needs germline FH testing and surveillance of relatives; the corpus's papillary page lists it as a former type 2 papillary carcinoma.\n\nHow common: about 0.5 percent of renal cell carcinomas on an unselected microarray (Am J Surg Pathol 2016).\n\nTreatment: early and complete surgery, with no role for active surveillance of small tumours because of their aggression; advanced disease has no approved therapy of its own and is treated on the renal cell carcinoma page's VEGF and checkpoint pathways; germline testing is offered to every patient and their relatives.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Hereditary_leiomyomatosis_and_renal_cell_cancer_syndrome","links":[{"label":"NCI PDQ: renal cell cancer treatment","url":"https://www.cancer.gov/types/kidney/patient/kidney-treatment-pdq"},{"label":"Moch 2016, European Urology: the 2016 WHO classification of urinary and male genital tumours, part A","url":"https://doi.org/10.1016/j.eururo.2016.02.029"},{"label":"Moch 2022, European Urology: the 2022 WHO classification of urinary and male genital tumours, part A (renal, penile, testicular)","url":"https://doi.org/10.1016/j.eururo.2022.06.016"},{"label":"Am J Surg Pathol 2016: fumarate hydratase-deficient RCC is strongly correlated with FH mutation and HLRCC","url":"https://doi.org/10.1097/pas.0000000000000617"},{"label":"Am J Surg Pathol 2016: tubulocystic carcinoma with poorly differentiated foci, a pattern of FH-deficient RCC","url":"https://doi.org/10.1097/pas.0000000000000719"},{"label":"Histopathology 2017: a low-grade oncocytic FH-deficient RCC resembling SDH-deficient RCC","url":"https://doi.org/10.1111/his.13183"}],"tags":["subtype-page","wave4","kidney","rare"],"related":["rcc","papillary-rcc","sdh-deficient-renal-cell-carcinoma","collecting-duct-carcinoma","hereditary-ppgl"],"cancers":[],"sections":[],"technologies":["germline-testing"],"targets":["fh"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["nephrectomy","hereditary-cancer-syndromes"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"genitourinary","burden":"Rare: 24 of 124 tumours (19 percent) previously labelled unclassified high-grade or papillary type 2 were fumarate hydratase-deficient, but only 2 of 776 (0.5 percent) unselected renal cell carcinomas on a tissue microarray; patients had a median age of 44 (Am J Surg Pathol 2016).","subtypes":["FH-deficient renal cell carcinoma in HLRCC (germline FH mutation; papillary or tubulocystic with poorly differentiated foci)","Sporadic FH-deficient renal cell carcinoma (somatic FH loss)","Low-grade oncocytic FH-deficient renal cell carcinoma (rare)"],"biomarkers":["FH loss and 2-succinocysteine positivity on immunohistochemistry","Germline FH mutation (HLRCC)","Cutaneous and uterine leiomyomas in the patient or family","High nuclear grade with prominent eosinophilic nucleoli"],"standardOfCare":[{"setting":"All stages","approach":"Early complete surgery; germline FH testing for the patient and relatives; advanced disease on the renal cell carcinoma page's pathways without a dedicated standard.","refs":["rcc","papillary-rcc","germline-testing","nephrectomy"]}],"stateOfArt":[],"history":[],"pipeline":[],"openProblems":[],"parent":"rcc"},"route":"/cancers/fh-deficient-renal-cell-carcinoma/","neighbours":{"cancer":[{"id":"collecting-duct-carcinoma","kind":"cancer","name":"Collecting duct carcinoma of the kidney","route":"/cancers/collecting-duct-carcinoma/"},{"id":"hereditary-ppgl","kind":"cancer","name":"Hereditary pheochromocytoma and paraganglioma (SDHx, VHL, RET, NF1, MAX and TMEM127)","route":"/cancers/hereditary-ppgl/"},{"id":"papillary-rcc","kind":"cancer","name":"Papillary renal cell carcinoma","route":"/cancers/papillary-rcc/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"},{"id":"sdh-deficient-renal-cell-carcinoma","kind":"cancer","name":"Succinate dehydrogenase-deficient renal cell carcinoma","route":"/cancers/sdh-deficient-renal-cell-carcinoma/"}],"technology":[{"id":"germline-testing","kind":"technology","name":"Germline (hereditary) testing","route":"/technologies/germline-testing/"}],"target":[{"id":"fh","kind":"target","name":"FH","route":"/targets/fh/"}],"term":[{"id":"hereditary-cancer-syndromes","kind":"term","name":"Hereditary cancer syndromes","route":"/terms/hereditary-cancer-syndromes/"},{"id":"nephrectomy","kind":"term","name":"Nephrectomy","route":"/terms/nephrectomy/"}]}}