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Familial leiomyomatosis cutis et uteri - Skin
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Familial leiomyomatosis cutis et uteri - Skin

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Contributors: Catherine Amble MD, Noah Craft MD, PhD, Lindy P. Fox MD, Lowell A. Goldsmith MD, MPH, Michael D. Tharp MD
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Synopsis

Leiomyomatosis cutis et uteri, also known as multiple cutaneous and uterine leiomyomatosis (MCUL) and Reed syndrome, is an autosomal dominant condition characterized by multiple leiomyomas (benign smooth muscle neoplasms) on the skin and uterus. MCUL is a rare condition with unknown prevalence and demographic distribution, although it has been reported in some Northern European populations. A subset of MCUL patients have a predisposition to renal cell carcinoma (RCC), and this condition is called hereditary leiomyomatosis and renal cell carcinoma (HLRCC). Both MCUL and HLRCC result from a heterozygous germline mutation in the fumarate hydratase (FH) gene, which is thought to suppress tumor formation. Somatic mutation or loss of the wild-type FH allele interferes with FH activity, resulting in accumulation of fumarate. The excess fumarate is believed to contribute to tumor development, although the exact mechanism by which this occurs is unclear.

Patients often first present to dermatologists with cutaneous leiomyomas. The average age of onset of cutaneous lesions is 25 years, although onset in childhood or later adulthood is not uncommon. Smooth muscle fibers that make up cutaneous leiomyomas arise from arrector pili of hair follicles or vascular smooth muscle. Lesions very rarely spontaneously regress and may occasionally increase in size. Patients often report pain or paresthesias with touch or cold temperatures.

Uterine fibroids in MCUL tend to have early onset and severe symptoms compared with spontaneous fibroids. Onset is typically earlier than 30 years of age, compared with 40 years of age for spontaneous fibroids. Symptoms include menorrhagia, irregular menses, pelvic pain, and sometimes infertility or subfertility. Half of women with MCUL require hysterectomy or myomectomy before age 30 due to symptom severity.

Many different FH mutations have been identified, although there is no clear association between specific mutations and development of the HLRCC variant. Families with known HLRCC have variable penetrance of papillary RCC in individuals with the familial FH mutation. RCC may present with hematuria, low back or flank pain, and abdominal or flank mass. These tumors also have an early age of onset (median onset is 44 years) compared with spontaneous RCC and are typically unilateral but may be bilateral or multifocal. RCC in these patients is aggressive, with higher than expected rate of metastasis (50%) and mortality, even when lesions are small. Adrenal cortical adenomas have also been reported in some patients with HLRCC, although this association is not certain. Most are nonfunctioning, but some ACTH-secreting tumors have been identified.

For more information, see OMIM.

Codes

ICD10CM:
Q82.8 – Other specified congenital malformations of skin

SNOMEDCT:
254767008 – Cutaneous leiomyoma

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Last Updated: 03/29/2017
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Familial leiomyomatosis cutis et uteri - Skin
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Familial leiomyomatosis cutis et uteri : Arm, Leg, Pelvic pain, Trunk, Hyperesthesia, Menorrhagia, Paresthesias, Painful skin lesion, Smooth papules, Smooth nodules
Clinical image of Familial leiomyomatosis cutis et uteri
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