eMedicine Specialties > Dermatology > Benign Neoplasms

Leiomyoma

Author: Kyle L Horner, MD, MS, Staff Physician, Department of Dermatology, Penn State Milton S Hershey Medical Center
Coauthor(s): Gregory J Raugi, MD, PhD, Professor, Department of Internal Medicine, Division of Dermatology, University of Washington at Seattle; Chief, Dermatology Section, Primary and Specialty Care Service, Veterans Administration Medical Center of Seattle; Marion C Miethke, MD, Clinical Assistant Professor, Department of Internal Medicine, Section of Dermatology, University of Washington
Contributor Information and Disclosures

Updated: Sep 22, 2009

Introduction

Background

Leiomyomas are benign soft tissue neoplasms that arise from smooth muscle; they were first described by Virchow¹ in 1854. The hereditary form, which causes, multiple leiomyomas, was originally noted by Kloepfer et al² in 1958. They can develop wherever smooth muscle is present. Malignant transformation probably does not occur. A 2006 report³ 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.

Also see Esophageal Leiomyoma; Leiomyoma, Iris; and Leiomyoma, Uterus (Fibroid).

Pathophysiology

Three fairly distinct types of cutaneous leiomyomas exist: piloleiomyomas, angioleiomyomas, and genital leiomyomas. This classification reflects the most logical 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. Tumors in each classification have distinct clinical and/or histologic characteristics.

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. Unfortunately, even less is known about the potential pathophysiologic or genetic features of other leiomyomas.

The pathogenesis of pain associated with these lesions is also a mystery. 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 4 types:

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

Frequency

United States

Leiomyomas are uncommon. Genital leiomyomas tend to be the least common of the 3 types.

International

International frequency data does not differ from the US frequency data.

Mortality/Morbidity

Because cutaneous leiomyomas are benign tumors, they do not directly affect mortality. However, one case report³ involves an angioleiomyoma that occurred in association with a leiomyosarcoma. The relevance of this association is unknown.

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

Race

A racial predilection is not described, except in regard to oral angioleiomyomas, for which the white-to-black ratio has been reported⁴ to be 3:1

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. 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. As such, not all women in a family are affected, and those who are may have only cutaneous, only uterine, or both cutaneous and uterine leiomyomas.

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.^5,6

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.

Clinical

History

• The most common feature in patients with multiple piloleiomyomas is pain.
  • Pain can be spontaneous or induced by cold or tactile (eg, pressure) stimuli.
  • The pain or tenderness 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.⁵
• Many solitary piloleiomyomas are similarly symptomatic.
• About 60% of angioleiomyomas are symptomatic.⁶ Pain in angioleiomyomas may be due to nerve fibers in the stroma or wall of the tumors or perhaps due to the contraction of blood vessels with local ischemia.⁵
• In addition to the previously described trigger factors (ie, temperature and pressure), symptoms are also reported to occur with menses or pregnancy.
• Genital leiomyomas are usually asymptomatic solitary lesions arising from the dartoic, vulvar, or mamillary muscles in the genital region or on the nipple.⁷

Physical

• Individual piloleiomyomas are smooth, firm papules or nodules, usually smaller than 2 cm in diameter, and reddish brown. Many are tender to palpation.
  • Multiple piloleiomyomas can occur on the face, trunk, or extremities. Various distribution patterns are reported, including bilaterally symmetric, grouped, dermatomal, and linear patterns.
  • A solitary piloleiomyoma is usually found on a lower extremity.
  • Because piloleiomyomas develop in the superficial dermis, they are fixed in the skin. However, they can be easily moved over the deeper subcutaneous tissues.

• Angioleiomyomas are usually well-defined, fairly deep dermal nodules that are smaller than 4 cm.
  • Pain to palpation is not uncommon.
  • Angioleiomyomas are generally solitary and occur predominantly on the lower extremities, less commonly on the head or trunk, and rarely on the hands or in the mouth.^4,8,9
  • The most common clinical presentation of an angioleiomyoma is that of a solitary skin-colored nodule.
• 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.

Causes

Recent research has revealed the location of the gene for transmission of dominantly inherited, multiple cutaneous piloleiomyomas associated with uterine leiomyomas in female family members.

• The gene was linked to band 1q42.3-q43. Haplotype construction and recombination analysis narrowed the locus to an approximately 14-centromere interval located between D1S517 on the centromeric side and D1S2842 on the telomeric side.
• As reported by Alam et al,¹⁰ the locus is named MCUL1 for multiple cutaneous and uterine leiomyomata 1.
• Studies of an extended family narrowed the locus further to a region of 4.55-7.17 centromere on chromosome 1. This gene encodes for fumarate hydratase (FH), an enzyme of the tricarboxylic acid cycle, which acts as a tumor suppressor. In families with multiple cutaneous and uterine leiomyomata (MCUL) and hereditary leiomyomatosis and renal cell cancer (HLRCC), FH missense mutations often occurred in fully conserved residues and in residues functioning in the substrate binding A-site, substrate-binding B-site, or subunit-interacting region. All missense mutations in these families were associated with decreased enzyme activity, suggesting that the tumor suppressor role of FH is related to its enzymatic activity.¹¹
• A study of 108 affected individuals, including 46 probands and 62 affected relatives revealed that highly penetrant FH mutations underlie MCUL. Of women with FH mutations, 69% had both skin and uterine leiomyomas, 15% had only skin leiomyomas, and 7% had only uterine leiomyomas.¹² Uterine leiomyomas not associated with skin leiomyomas were associated with the G354R FH mutation.
• Cutaneous manifestations of HLRCC range from absent to severe cutaneous leiomyomas. Wei et al¹³ have so far identified 31 different germline FH mutations in 56 families with HLRCC. Six additional FH mutations have been described among Dutch and Spanish families with MCUL.¹⁴
• A 2006 report described a unique clonal translocation (7;8)(p13;q11.2) in a leiomyoma of the vulva.¹⁵

• Search for CME/CE on This Topic »

• Leiomyoma, Iris (Ophthalmology)
• Leiomyoma, Uterus (Fibroid) (Radiology)
• Gastrointestinal Stromal Tumors - Leiomyoma/Leiomyosarcoma (Radiology)
• Esophageal Leiomyoma (Gastroenterology)

• Green Tea Extract May Treat Uterine Fibroids
• Women With Fibroids at Greater Risk for Stillbirth
• Laparoscopically Assisted Cryoablation Effective for Uterine Fibroids

• Mifepristone for Treatment of Uterine Leiomyoma. A Prospective Randomized Placebo Controlled Trial
• MicroRNA: A New Tool for Biomedical Risk Assessment and Target Identification in Human Uterine Leiomyomas
• Medical Treatment of Uterine Fibroids