Renal Cancer in Hereditary Leiomyomatosis and Renal Cell Cancer: A Scoping Review of Epidemiology, Clinical Features, Management, and Outcomes
Bibliographic record
Abstract
Purpose: Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal dominant syndrome caused by germline pathogenic variants in the fumarate hydratase ( FH ) gene. Affected individuals face up to a 15% to 20% lifetime risk of developing aggressive renal cell carcinoma (RCC). Despite well-defined syndromic features—cutaneous and uterine leiomyomas (ULs)—diagnosis is often delayed, and optimal management strategies remain poorly defined. This review aims to synthesize current evidence on the epidemiology, clinical features, diagnostic pathways, treatment strategies, and outcomes of HLRCC-associated RCC and to identify knowledge gaps and inform clinical and research priorities. Materials and Methods: We conducted a scoping review in accordance with PRISMA-ScR and the Arksey and O'Malley framework. Six databases (MEDLINE, Embase, Scopus, Web of Science, CENTRAL, ClinicalTrials.gov) were searched from inception through July 30, 2024. Studies with original data on RCC in confirmed or suspected HLRCC were included. Data were extracted and synthesized from individual patient data (IPD) and observational cohorts and presented using descriptive statistics and narrative synthesis. Results: A total of 149 studies were included, comprising 382 IPD from case reports/series and 16 observational cohorts. RCC occurred at a mean age of 39.4 years and presented symptomatically in > 85% of cases. Despite frequent syndromic features (ULs: 80.9%, cutaneous leiomyomas: 47.5%), < 15% of patients underwent FH testing before cancer diagnosis. Tumors were large (mean 7.6 cm), often metastatic (stage IV in 52.3% of IPD), and showed high rates of FH loss (95.9%) and 2SC positivity (94%-100%). Nephrectomy was the most common treatment; systemic therapy was infrequently reported. Limited observation data suggest potential benefit of tyrosine kinase inhibitors, vascular endothelial growth factor inhibitors, and immune-targeted therapies. Early-stage disease was associated with improved survival (>80 months). Median survival in metastatic cases ranged from 15 to 35 months. Conclusions: HLRCC-associated RCC remains underdiagnosed and frequently presents at advanced stages. Earlier genetic testing, greater syndromic recognition, and multidisciplinary surveillance are needed to enable timely detection. Evidence for systemic therapy is limited, and prospective trials are urgently needed to define optimal management. Coordinated research efforts and biomarker-driven diagnostic strategies will be essential to improving outcomes for this aggressive hereditary kidney cancer subtype.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".