Leiomyomas are benign soft tissue neoplasms arising from smooth muscle. They can develop wherever smooth muscle is present in any organ, but most commonly found in the uterus, skin, and gastrointestinal tract. Malignant transformation is rare.
Multiple cutaneous and uterine leiomymatosis 1 (MCUL 1) is an autosomal dominant condition in which affected individuals develop leiomyomata of the skin. Cutaneous leiomyomata usually starts during the second decade of life as skin-colored to light brown papules or nodules distributed over the trunk and extremities and occasionally on the face which may be painful on touch and squeezing. These tumors gradually increase in number and size with age. All affected females in an affected family usually develop leiomyomata of the uterus (fibroids). While in others only some females develop uterine leiomyomatas. They predominantly occur in the fourth decade of life, but early onset in the second decade has been reported. The clinical presentations are pelvic pain and irregular and heavy menstruation, often cause anemia and may lead to infertility. In addition to uterine leiomyomatas, some of these affected families are at risk for development of papillary renal cell carcinoma.
Diagnosis of skin tumors can easily be confirmed by microscopic examination of skin biopsy. These tumors can be surgically removed. Surgery is also applied for removal uterine leiomyomatas. In addition to hysterectomy and abdominal myomectomy, various minimally invasive procedures have been developed to remove fibroids.
The familial leiomyomatosis is rare. However, uterine leiomyomatas (fibroids) are the most frequent benign tumors of the uterus during female reproductive age with a reported incidence of 25-30%.
The responsible gene for this condition is the fumarate hydratase gene (FH). FH codes for a mitochondrial enzyme of the tricarboxylic acid (TCA) cycle, involved in fundamental cellular energy production. Moreover, this enzyme acts as a tumor suppressor in familial leiomyomata. It was found that the activity of the fumarate hydratase enzyme is reduced in tumors from individuals with leiomyomatosis.