Leiomyoma

Updated: Dec 06, 2016
  • Author: Fnu Nutan, MD, FACP; Chief Editor: William D James, MD  more...
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Overview

Practice Essentials

Cutaneous leiomyomas are benign soft-tissue neoplasms that arise from smooth muscle (arrector pili). The arrector pili muscle contracts in response to cold, most commonly, or to fear or pleasure, causing what is commonly known as goose bumps. Cutaneous leiomyomas can develop wherever smooth muscles are present, but malignant transformation probably does not occur.

The importance of correct diagnosis of cutaneous leiomyoma lies is the association of multiple cutaneous leiomyomas with uterine fibroids and papillary renal cell carcinoma in what is known as Reed syndrome, or hereditary leiomyomatosis and renal cell cancer (HLRCC), an autosomal dominant disorder. This syndrome mandates regular follow up and screening as detailed in the Consultations section. More about the pathogenesis, genetics, penetrance, and treatment have been outlined in the corresponding sections of this article.

Signs and symptoms

The most common feature in patients with multiple piloleiomyomas (cutaneous leiomyomas) is pain, which can be spontaneous or induced by cold or tactile (eg, pressure) stimuli. The pain or tenderness also may be secondary to pressure on nerve fibers within the tumor; however, some authors believe it may be solely due to contraction of muscle fibers. [1] Symptoms are also reported to occur with menses or pregnancy. See the image below.

These multiple hyperpigmented nodules are piloleio These multiple hyperpigmented nodules are piloleiomyomas on an upper extremity.

Many solitary piloleiomyomas are similarly symptomatic. However, genital leiomyomas are usually asymptomatic solitary lesions arising from the dartoic, vulvar, or mammillary muscles in the genital region or on the nipple. [2]

Multiple piloleiomyomas can occur on the face, trunk, or extremities. Various distribution patterns are reported, including bilaterally symmetric, grouped, dermatomal and linear patterns.

Features of angioleiomyomas (vascular leiomyomas) include the following:

  • Most commonly present as solitary skin-colored nodules
  • Usually well-defined, fairly deep dermal nodules that are smaller than 4 cm
  • Often, pain to palpation
  • Occur predominantly on the lower extremities, less commonly on the head or trunk, and rarely on the hands or in the mouth [3, 4, 5]

Leiomyomas of the vulva or scrotum may be larger than those already described above. Leiomyomas of the nipple and piloleiomyomas are generally similar in size.

See Clinical Presentation for more detail.

Diagnosis

Features of individual piloleiomyomas include the following:

  • Smooth, firm papules or nodules
  • SIze range from 0.2-2 cm in diameter
  • Pink or reddish brown in color
  • Usually tender to palpation
  • Usually found on a lower extremity
  • Fixed in the skin but can be easily moved over the deeper subcutaneous tissues

Testing

Laboratory testing is generally not necessary for evaluation of leiomyomas unless there is abnormal vaginal bleeding or to rule out other conditions. The measurement of hemoglobin and/or hematocrit levels might be considered in patients with multiple leiomyomas, because erythrocytosis is reported in rare cases.

Imaging studies

Imaging studies are not routinely performed for leiomyomas; however, angioleiomyomas do have characteristic findings on ultrasonographic (including color Doppler) and magnetic resonance images. Uterine leiomyomas (also called fibroids) may be assessed by Doppler ultrasonography assessment before uterine artery embolization. [6]

Procedures

Tissue examination is necessary to establish the diagnosis. Therefore, a partial or excisional biopsy is indicated.

See Workup for more detail.

Management

All leiomyomas are tumors; therefore medical management has a limited role in the resolution or destruction of these lesions. However, pharmacologic intervention may alleviate associated pain.

Pharmacotherapy

The following medications are used in women with leiomyomas, primarily for analgesia:

  • Alpha-adrenergic blocking agents (eg, phenoxybenzamine)
  • Calcium channel blockers (eg, nifedipine)
  • Anticonvulsants (eg, gabapentin)

Surgical option

Surgical excision or ablation of leiomyomas may be helpful for some symptomatic women.

See Treatment and Medication for more detail.

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Background

Leiomyomas are benign soft tissue neoplasms that arise from smooth muscle; they were first described by Virchow [7] in 1854 as "tuberculum dolorosum". The hereditary form, which causes, multiple leiomyomas, was originally noted by Kloepfer et al [8] in 1958. They can develop wherever smooth muscle is present. Malignant transformation probably does not occur. A 2006 report [9] of a cutaneous leiomyosarcoma with myxoid alteration in a scar of a piloleiomyoma that had been excised 3 years previously probably does not represent a case of malignant transformation.

Hereditary leiomyomatosis and renal cell cancer (HLRCC), also called Reed syndrome, is the primary tumor predisposition syndrome associated with inherited cutaneous leiomyomas with significant mortality. This autosomal dominant disorder with variable penetrance is caused by a defect in fumarate hydratase secondary to a missense mutation. Fumarate hydratase is an enzyme in the tricarboxylic acid (Krebs) cycle that acts as a tumor suppressor, and it has a cytoplasmic and a mitochondrial form. The presentation is variable, with patients presenting with early-onset recurrent uterine fibroids. They also have piloleiomyomas, which are multiple and may be symptomatic. Patients with HLRCC should be screened for renal cell carcinoma at regular intervals; however, there is no consensus on the screening guidelines. An MRI of the abdomen performed yearly is the most sensitive with the least radiation exposure to patients. The family also needs to be counselled, and genetic counselling should be offered.

Also see Esophageal Leiomyoma, Iris Leiomyoma, and Uterine Leiomyoma (Fibroid) Imaging.

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Pathophysiology

Three fairly distinct types of cutaneous leiomyomas exist: piloleiomyomas, angioleiomyomas, and genital leiomyomas with distinct clinical and histological characteristics. This classification reflects the origin of the smooth muscle tumor and corresponds to the histologic or anatomic site where the leiomyomas are found. Piloleiomyomas are believed to arise from the arrector pili muscle of the pilosebaceous unit, whereas angioleiomyomas originate from smooth muscle (ie, tunica media) within the walls of arteries and veins. Leiomyomas derived from the dartos muscle of the scrotum and the labia majora, as well as those derived from the erectile muscle of the nipple, are classified as genital leiomyomas.

The pathogenesis of leiomyomas remains obscure. Angioleiomyomas and genital leiomyomas usually occur as solitary lesions, whereas piloleiomyomas may be either solitary or multiple, at times numbering in the thousands. The arrector pili muscle, from which piloleiomyomas originate, attaches proximally to the hair follicle and distally to multiple attachment points within the papillary and reticular dermis, as well as to the basement membrane. Piloleiomyomas can plausibly emerge from each of these various points of insertion and occur as multiple tumors. Multiple lesions can be inherited as an autosomal-dominant trait with variable penetrance, or they can occur sporadically.

The pathogenesis of pain associated with these lesions is not known. Some authors have suggested that pain could result from local pressure by the tumor on cutaneous nerves. However, the histologic findings do not show that prominent nerve fibers are associated with these tumors. Others have theorized that specific infiltrating cells may play a role; one study of 24 angioleiomyomas revealed that painful tumors had fewer mast cells than asymptomatic ones. Yet others have suggested that muscle contraction may be pivotal in the induction of pain.

The excitation of the arrector pili muscle occurs via the sympathetic nervous system. Norepinephrine, secreted by postganglionic nerve fibers, activates the alpha-receptors of the muscle. Muscle contraction ensues; this is triggered by the influx of ions, most specifically calcium. Understanding this basic physiologic process may be relevant to the medical treatment of symptomatic leiomyomas.

Leiomyomas may be categorized into the following four types:

  • Multiple piloleiomyomas
  • Solitary piloleiomyoma
  • Angioleiomyoma (solitary)
  • Genital leiomyoma (solitary)
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Epidemiology

Frequency

Leiomyomas are uncommon. Piloleiomyomas are the most common, while genital leiomyomas tend to be the least common of the three types. [10]

Race

A racial predilection is not described, except in regard to oral angioleiomyomas, for which the white-to-black ratio has been reported to be 3:1. [3]

Sex

The incidences of piloleiomyomas in men and women appear to be about equal. Women who have multiple cutaneous piloleiomyomas may also have uterine leiomyomas (also known as fibroids). If the latter are present, the patient most likely has a familial condition called familial leiomyomatosis cutis et uteri, or Reed syndrome. Reed syndrome is thought to be inherited as an autosomal dominant trait with incomplete penetrance. Mutations in the Krebs cycle enzyme fumarate hydratase are associated with Hereditary leiomyomatosis and renal cell cancer (HLRCC). Reed syndrome is associated with renal cell carcinoma. [11] As such, not all women in a family are affected, with some having only cutaneous, only uterine, or both cutaneous and uterine leiomyomas. [12, 13]

Angioleiomyomas are more common in women than in men, with a ratio of 2:1 overall; however, the solid subtype occurs more commonly in females (3:1), the venous subtype occurs more commonly in males, and the least common of the three, the cavernous subtype, is four times more common in males. [1, 14]

Because genital leiomyomas are rare, data to determine whether a sexual predilection exists are inadequate.

Age

Cutaneous leiomyomas are more likely to occur in adults than in children. However, isolated reports of cutaneous leiomyomas in children exist, including one involving a nonspecified type of solitary cutaneous leiomyoma on the heel of a neonate at birth.

Multiple piloleiomyomas generally occur in those aged 10-30 years. When solitary, piloleiomyomas usually appear later. For example, in a series of 28 solitary cutaneous leiomyomas, the mean patient age at presentation was 53 years.

Angioleiomyomas most often occur in those aged 20-60 years, although some investigators report a narrower window of increased incidence in those aged 20-40 years. In a retrospective clinicopathologic analysis of 562 angioleiomyomas, the mean age of the patients was 47 years; their overall age range was 12-84 years.

Leiomyomas typified as genital leiomyomas are rare enough that an age predilection is not generally described.

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Prognosis

The prognosis for a solitary lesion is excellent, especially if it is surgically excised. Multiple piloleiomyomas gradually increase in size and number.

Because cutaneous leiomyomas are benign tumors, they do not directly affect mortality, unless the patient has hereditary leiomyomatosis and renal cell cancer (HLRCC). However, one case report [9] involves an angioleiomyoma that occurred in association with a leiomyosarcoma. The relevance of this association is unknown.

Associated morbidity may be from spontaneous lesional pain, as well as pain evoked by cold and/or tactile hypersensitivity. Additionally, multiple piloleiomyomas have the potential to be cosmetically disfiguring.

Around 180 families have been diagnosed with HLRCC, with most cases originating from Eastern Europe. [15]

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