# Fumarate hydratase-deficient renal cell carcinoma (HLRCC-associated)

Source: https://onco.cc/cancers/fh-deficient-renal-cell-carcinoma/  
OnCo record `fh-deficient-renal-cell-carcinoma` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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).

How 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.

How common: about 0.5 percent of renal cell carcinomas on an unselected microarray (Am J Surg Pathol 2016).

Treatment: 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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-24
- Also known as: 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)
- Tags: subtype-page; wave4; kidney; rare
- 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

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/fh-deficient-renal-cell-carcinoma/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/fh-deficient-renal-cell-carcinoma/#overview
- What it is (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/fh-deficient-renal-cell-carcinoma/#what-it-is [3 subtypes]
- Finding it (on the hub): How it shows itself, how it is confirmed, what screening exists, and the biomarkers clinicians test for. https://onco.cc/cancers/fh-deficient-renal-cell-carcinoma/#finding-it [4 biomarkers]
- Treating it (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/fh-deficient-renal-cell-carcinoma/#treating-it [1 setting]
- Evidence (on the hub): Trials recruiting now, the landmark trials, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/fh-deficient-renal-cell-carcinoma/#evidence
- The science (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/fh-deficient-renal-cell-carcinoma/#science [1 target]
- Where you are (own page): Cases by country, the UK and NHS pathway and other country lenses, and the expert centres with trials on record. https://onco.cc/cancers/fh-deficient-renal-cell-carcinoma/where-you-are/
- Living with it (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/fh-deficient-renal-cell-carcinoma/#living-with-it [7 questions]
- What is coming (own page): Everything in development, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/fh-deficient-renal-cell-carcinoma/coming/
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/fh-deficient-renal-cell-carcinoma/data/ [4 connected records]

## Standard of care

- All stages: 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. ([Renal cell carcinoma](https://onco.cc/cancers/rcc/), [Papillary renal cell carcinoma](https://onco.cc/cancers/papillary-rcc/), [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/), [Nephrectomy](https://onco.cc/terms/nephrectomy/))

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Hereditary_leiomyomatosis_and_renal_cell_cancer_syndrome
- NCI PDQ: renal cell cancer treatment: https://www.cancer.gov/types/kidney/patient/kidney-treatment-pdq
- Moch 2016, European Urology: the 2016 WHO classification of urinary and male genital tumours, part A: https://doi.org/10.1016/j.eururo.2016.02.029
- Moch 2022, European Urology: the 2022 WHO classification of urinary and male genital tumours, part A (renal, penile, testicular): https://doi.org/10.1016/j.eururo.2022.06.016
- Am J Surg Pathol 2016: fumarate hydratase-deficient RCC is strongly correlated with FH mutation and HLRCC: https://doi.org/10.1097/pas.0000000000000617
- Am J Surg Pathol 2016: tubulocystic carcinoma with poorly differentiated foci, a pattern of FH-deficient RCC: https://doi.org/10.1097/pas.0000000000000719
- Histopathology 2017: a low-grade oncocytic FH-deficient RCC resembling SDH-deficient RCC: https://doi.org/10.1111/his.13183

## Connected records

- cancers: [Collecting duct carcinoma of the kidney](https://onco.cc/cancers/collecting-duct-carcinoma/), [Hereditary pheochromocytoma and paraganglioma (SDHx, VHL, RET, NF1, MAX and TMEM127)](https://onco.cc/cancers/hereditary-ppgl/), [Papillary renal cell carcinoma](https://onco.cc/cancers/papillary-rcc/), [Renal cell carcinoma](https://onco.cc/cancers/rcc/), [Succinate dehydrogenase-deficient renal cell carcinoma](https://onco.cc/cancers/sdh-deficient-renal-cell-carcinoma/)
- technologies: [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/)
- targets: [FH](https://onco.cc/targets/fh/)
- terms: [Hereditary cancer syndromes](https://onco.cc/terms/hereditary-cancer-syndromes/), [Nephrectomy](https://onco.cc/terms/nephrectomy/)

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JSON: https://onco.cc/api/v1/entities/fh-deficient-renal-cell-carcinoma.json