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Hereditary Leiomyomatosis and Renal Cell Cancer.

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GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
2006 Jul 31 [updated 2015 Aug 6].

Author information

1
Division of Medical Genetics, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
2
Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Dermatology Section, DCVA Medical Center, Washington, DC

Excerpt

CLINICAL CHARACTERISTICS:

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is characterized by cutaneous leiomyomata (multiple or single in 76% of affected individuals), uterine leiomyomata (fibroids), and/or a single renal tumor. Cutaneous leiomyomata appear as skin-colored to light brown papules or nodules distributed over the trunk and extremities, and occasionally on the face, and appear at a mean age of 25 years, increasing in size and number with age. Uterine leiomyomata are present in almost all females with HLRCC and tend to be numerous and large; age at diagnosis ranges from 18 to 52 years, with most women experiencing irregular or heavy menstruation and pelvic pain. Renal tumors causing hematuria, lower back pain, and a palpable mass are usually unilateral, solitary, and aggressive and range from type 2 papillary to tubulo-papillary to collecting-duct carcinomas. They occur in about 10%-16% of individuals with HLRCC; the median age of detection is 44 years.

DIAGNOSIS/TESTING:

The diagnosis of HLRCC is established with the identification of a heterozygous pathogenic variant in FH in combination with multiple cutaneous leiomyomas, with at least one histologically confirmed leiomyoma, a single leiomyoma in the presence of a positive family history of HLRCC, and/or one or more tubulo-papillary, collecting-duct, or papillary type 2 renal tumors with or without a family history of HLRCC. Testing of fumarate hydratase enzyme activity is an alternative in those with atypical presentation and an undetectable FH pathogenic variant.

MANAGEMENT:

Treatment of manifestations: Surgical excision, cryoablation, and/or laser excision to remove painful cutaneous leiomyomas; pain medication includes calcium channel blockers, alpha blockers, nitroglycerin, antidepressants, or antiepileptic drugs. Treatment of uterine fibroids can include gonadotropin-releasing hormone agonists, antihormonal medications, pain relievers, myomectomy, and hysterectomy. Total nephrectomy should be considered in individuals with kidney tumors. Surveillance: For FH heterozygotes and at-risk family members who have not undergone molecular genetic testing: every one to two years full skin examination to evaluate for changes suggestive of leiomyosarcoma; annual gynecologic consultation to assess severity of uterine fibroids and to evaluate for changes suggestive of leiomyosarcoma; yearly examination with abdominal MRI for individuals with normal initial baseline or follow-up scans; once a renal lesion is identified, CT scan with and without contrast and renal ultrasound examination, PET-CT scan to identify metabolically active lesions, and evaluation by a urologic oncology surgeon familiar with the renal cancer of HLRCC. Evaluation of relatives at risk: When the FH pathogenic variant in the family is known, molecular genetic testing of asymptomatic at-risk relatives improves diagnostic certainty and allows early surveillance and treatment. If the pathogenic variant in the family is not known, fumarate hydratase enzyme assay can be used to clarify the disease status of at-risk relatives.

GENETIC COUNSELING:

HLRCC is inherited in an autosomal dominant manner. If a parent of a proband is clinically affected or has an FH pathogenic variant, the sibs of the proband have a 50% chance of inheriting the pathogenic variant. Each child of an individual with HLRCC has a 50% chance of inheriting the pathogenic variant. The degree of clinical severity is not predictable. Prenatal testing for pregnancies at increased risk is possible if the pathogenic variant in a family is known.

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