Hereditary leiomyomatosis and renal cell cancer (HLRCC)
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an inherited condition characterized by the presence of skin lesions called leiomyomas, uterine fibroids in women, and a specific type of renal cell carcinoma known as papillary renal cancer. This condition is linked to a genetic mutation affecting the fumarate hydratase enzyme, which plays a crucial role in cellular metabolism and tumor suppression. Individuals with a parent diagnosed with HLRCC have a 50 percent chance of inheriting the condition. Symptoms primarily include painful skin nodules and, in women, complications from uterine fibroids. Although renal cell cancer develops in a minority of cases (10 to 16 percent), it is noted for being particularly aggressive.
Diagnosis typically involves genetic testing for family members and annual screenings for associated health issues. While no cure exists, management options include surgical removal of leiomyomas, medications to relieve pain, and surgical interventions for fibroids and renal tumors. Individuals living with HLRCC can maintain a reasonably normal life with regular monitoring and early interventions. Genetic counseling is advised for affected families to understand the implications of the condition, including its inheritance patterns.
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Hereditary leiomyomatosis and renal cell cancer (HLRCC)
ALSO KNOWN AS: HLRCC, leiomyomatosis and renal cell cancer, LRCC, Reed's syndrome, multiple cutaneous leiomyoma (MCU), multiple cutaneous and uterine leiomyomata (MCUL), leiomyomatosis and renal cell cancer (LRCC)
RELATED CONDITIONS: Uterine fibroids, von Hippel-Lindau (VHL) disease, hereditary papillary renal carcinoma, Birt-Hogg-Dubé syndrome (BHDS)
DEFINITION: Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an inherited condition characterized by the development of one or more skin lesions called leiomyomas (tumors of smooth muscle tissue), uterine fibroids in women, and a form of renal cell carcinoma called papillary renal cancer.
Risk factors: The only known risk factor for HLRCC is having a parent with the disease. If a parent has this condition, there is a 50 percent chance that it will be passed on to their children. Although this disease is hereditary, it can be caused by a genetic mutation.
Etiology and the disease process: HLRCC is a dominant genetic trait. The affected gene is the one that produces the enzyme fumarate hydratase. This enzyme assists in the conversion of fumarate into L-malate in the Krebs cycle (involved in the metabolism of carbohydrates by the cells). As a result, fumarate accumulates in the cells. High levels of fumarate interfere with the availability of oxygen for the activation of several genes involved in angiogenesis (the formation of new blood vessels), cell metabolism, and cell growth and reproduction, called pseudohypoxia. Fumarate hydratase plays a role in suppressing tumor formation in the body.
Incidence: HLRCC is an extremely rare condition. Less than 1,000 cases have been documented.
Symptoms: The primary symptom of HLRCC is the presence of one or more leiomyomas on the skin. The leiomyomas are painful nodules that range from flesh-colored to light brown. About 75 percent of HLRCC cases develop leiomyomas. Most women with HLRCC will develop uterine fibroids. They cause pelvic pain and heavy menstrual periods. Patients with renal cell cancer may not exhibit any symptoms initially but later will exhibit hematuria (blood in the urine), lower back pain, and a palpable mass. Renal cell carcinoma develops in only 10 to 16 percent of persons with HLRCC.
Screening and diagnosis: There is no routine screening for HLRCC. Genetic testing is performed on all family members if the patient has a family history of HLRCC. Once HLRCC is diagnosed, the patient should have annual skin examinations for leiomyomas and regular screenings for renal cell cancer. Female patients should have annual pelvic examinations or uterine or transvaginal ultrasounds to screen for uterine fibroids.
HLRCC is suspected when a person seeks treatment for painful leiomyomas. A biopsy of the leiomyoma is taken, and the cells are examined for fumarate hydratase activity. In a person with HLRCC, this enzyme would be significantly reduced.
Uterine fibroids alone do not indicate HLRCC because they are prevalent in the general female population. While most uterine fibroids are benign, occasionally, a leiomyosarcoma (cancer of the uterus) is discovered in a woman with HLRCC.
After a HLRCC diagnosis, the patient is screened for renal cell cancer using an abdominal computed tomography (CT) scan or magnetic resonance imaging (MRI). The renal cell cancer related to HLRCC is particularly aggressive and grows and spreads faster than other renal cell cancers. Because HLRCC is not a cancer, the condition has no staging. If a person with HLRCC develops renal cell cancer, it is staged like other renal cell cancers.
Treatment and therapy: There is no cure for HLRCC, but it can be managed. Skin leiomyomas can be removed by surgical excision, cryoablation (freezing), or laser surgery. If there are many leiomyomas, removal may not be possible. Many medications are effective in treating the pain caused by skin leiomyomas. They are calcium-channel blockers, alpha-blockers, nitroglycerine, antidepressants, and antiepileptic (antiseizure) medications.
Uterine fibroids can be removed surgically by myomectomy (removal of the fibroids) or hysterectomy. Embolization of the arteries feeding the fibroids can preserve the uterus and shrink the fibroids. Medications for treating uterine fibroids include gonadotropin-releasing hormone agonists, antihormonal medications, and pain relievers.
Once a renal cell cancer is discovered in a person with HLRCC, the tumor is surgically removed. The tumor can be removed by direct surgical radical nephrectomy (removal of the kidney and adrenal gland), by a partial nephrectomy, or by one of several laparoscopic nephrectomy procedures.
Prognosis, prevention, and outcomes: HLRCC is a chronic condition. However, a person with this disease can live a reasonably normal life with careful monitoring. Because a genetic mutation causes HLRCC, there is no way to prevent it. An essential part of managing HLRCC is genetic testing of all related family members and genetic counseling. Siblings of an affected person should be screened for HLRCC because they may have additional unpaired genes. Should two persons with the gene for HLRCC reproduce, their child would possess both HLRCC genes. This genetic combination is marked by severe encephalopathy (brain damage).
Individuals with cancer localized in the kidneys have a five-year survival rate of around 93 percent. For those whose cancer has only spread to nearby tissue, the survival rate is 71 percent. Those whose diagnosis includes distant organs have a survival rate of around 14 percent. Early diagnosis increases the prognosis of HLRCC.
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