Leiomyoma
Key Points
Leiomyoma is a benign soft-tissue neoplasm arising from smooth muscle
Cutaneous leiomyomas are divided into three subtypes: piloleiomyomas originate from the attachment points of the arrector pili muscle; angioleiomyomas originate from vascular smooth muscles of the tunica media of small-to medium-sized arteries and veins; and dartoic leiomyomas arise from the smooth muscles of genital skin and areola
The pathogenesis of leiomyomas is unknown
Genetic mutations have not been associated with sporadic solitary piloleiomyomas, but multiple cutaneous leiomyomas possess a heterozygous germline mutation in fumarate hydratase
In angioleiomyomas, 35% exhibit DNA copy number changes involving one or two chromosomes
Piloleiomyomas on the eyelid appear as painful, red, bluish-black or yellow, slow-growing, smooth, firm, rubbery papules or nodules
Angioleiomyomas are slow-growing, asymptomatic, solitary skin-colored, well-defined, firm, vascularized, deep dermal or subcutaneous nodules
The gold standard for treatment is surgical excision for small, localized tumors
Morbidity associated with untreated lesions is primarily from pain, but following surgical excision the prognosis is excellent
Leiomyoma is a benign soft-tissue neoplasm arising from smooth muscle that was first described by Virchow in 1854 as “tuberculum dolorosum.”1 These lesions are found most commonly in the uterine myometrium in 95% of cases, followed by the skin in 3%, and the gastrointestinal tract in 1.5%. Less than 1% are seen in the head and neck region.2 These tumors are typically asymptomatic, slow-growing lesions, most often seen in the 4th and 5th decades of life with a slight predilection for females.
Cutaneous leiomyoma has been divided into three subtypes according to the site of origin.2,3 Pilar leiomyomas or piloleiomyomas originate from the attachment points of the arrector pili muscle, proximal to the hair follicle and distal to multiple attachment points within the papillary and reticular dermis and basement membrane zone.4 Angioleiomyomas originate from vascular smooth muscles of the tunica media of small- to medium-sized arteries and veins. Dartoic or genital leiomyomas arise from the smooth muscles of genital skin and areola.1 The angioleiomyoma and dartoic subtypes usually present as solitary lesions, whereas pilar leiomyomas can manifest as solitary or multiple cutaneous tumors.
Superficial leiomyoma can occur at any age from infancy to old age, with most patients in middle age5,6,7 and a peak incidence between 40 and 60 years.8 Various studies have shown male or female predilection, but overall the sexes are equally affected. There is no racial predilection for leiomyoma, except in oral angioleiomyomas, for which the white-to-black ratio has been reported to be 3:1.9
Leiomyoma can appear in any body location where smooth muscle is present. In the head and neck region, about 23% of tumors involve the lips, tongue oral cavity, buccal mucosa, soft palate, larynx, esophagus, trachea, nasal cavity, salivary glands, paranasal sinuses, thyroid gland, intraosseous sites in the maxilla, and mandible, and orbit. Other rare sites include the ear, cheek, neck, forehead, and scalp.10,11
Piloleiomyomas usually present as a papule or nodule on the face, trunk, or extremities, either solitary or as multiple nodules that may be in a clustered, linear, dermatomal, or scattered distribution. Nodules range in size from 2 to 20 mm and vary in color from skin color, to pink, red, or brownish. Solitary piloleiomyomas are more common on the lower extremity, whereas multiple piloleiomyomas more often occur on the trunk or the extensor surface of the extremities.2 Pain is a common presenting symptom, which may occur spontaneously or initiated by pressure or low temperature.12
In 1973, Reed et al reported the association of multiple cutaneous leiomyomas with leiomyomas of the uterus, a condition known as Reed syndrome.13 The condition is also referred to as multiple cutaneous and uterine leiomyomatosis (MCUL) and also can occur with renal cell carcinoma.14,15,16 When MCUL is associated with renal cancer, it is referred to as hereditary leiomyomatosis and renal cell cancer. The inheritance pattern is thought to be autosomal dominant with incomplete penetrance,17 so that not all women in a family are similarly affected; some may only have cutaneous tumors, others only uterine tumors, and some may have both cutaneous and uterine leiomyomas.18,19 When this condition occurs as a genetic syndrome, the piloleiomyomas tend to occur earlier in life, with an average age of onset at 25 years and a range of 10 to 50 years.2
Angioleiomyoma, also known as vascular leiomyoma, most commonly involves the lower extremities and head and neck region.10 Orbital and eyelid involvement is extremely rare.20,21,22,23 They usually present in females in the 5th to 7th decades as a firm, painful, solitary subcutaneous nodule and are more common in women than in men, with a ratio of about 2:1.24,25,26,27 Angioleiomyomas have been further subclassified based on histopathology as capillary (or solid), which is the most common type; venous; and cavernous types.28
Genital leiomyomas typically develop on the genitals, including the scrotum, penis, and vulva, and also on the nipple-areolar region. The lesions usually present as an asymptomatic, solitary nodule.
Etiology and Pathogenesis
The pathogenesis of leiomyomas remains unknown. Genetic mutations have not been associated with sporadic solitary piloleiomyomas. Contrary to sporadic solitary leiomyoma, approximately 89% of patients with multiple cutaneous leiomyomas possess a heterozygous germline mutation in fumarate hydratase (FH),29 an enzyme in the Krebs cycle that functions in the conversion of fumarate to malate.2 In 85% to 90% of female patients with FH mutations, both cutaneous and uterine leiomyomas may be present. The FH mutation is also associated with renal cell carcinoma, seen in approximately 15% of these patients.2 The pathophysiology of heterozygous FH deficiency and the production of leiomyomas is not known, but it has been suggested that FH may function as a tumor suppressor.30,31,32 In dominantly inherited, multiple cutaneous piloleiomyomas associated with uterine leiomyomas, evidence has been reported for linkage to chromosome 1q42.3-q43.33
 FIGURE 79.1 A, Leiomyoma on the conjunctival surface at the medial lower eyelid. B, Piloleiomyoma nodular mass of the right upper eyelid in a 13-day old infant. (A, Courtesy of Dr. Roman Shinder. B, Reprinted with permission from Alam S, Banerjee P, Subramanian K. A rare case of congenital piloleiomyoma of the eyelid. Orbit. 2020 Aug 26, Online ahead of print.) |
In a series of 23 cases of angioleiomyoma, 35% exhibited DNA copy number changes involving one or two chromosomes, with the most common recurrent loss found at chromosome 22q11.2.34 Genital leiomyoma has been associated with several chromosomal anomalies including clonal translocation between chromosomes 7 and 8 (7;8)(p13;q11.2)35 and pericentric inversion involving chromosome 12 (12) (p12q13-14).36
The pathogenesis of pain associated with leiomyomas is not known. Various theories have proposed that pain could result from local pressure on cutaneous nerves, or that specific infiltrating cells play a role, or that muscle contraction be contributory.26
Clinical Characteristics
Individual piloleiomyomas on the eyelid appear as slow-growing, smooth, firm, rubbery papules or nodules.37 They can be skin-colored, red, reddish-brown, bluish-black, or yellow and can even be hypopigmented in color and are usually less than 2 cm in diameter (Figure 79.1). The skin may be irregularly thickened and when located on the eyelid margin can be associated with madarosis, tearing, and mattering.38 Since these lesions develop in the superficial dermis, they are fixed in the skin, but not adherent to deeper structures.26 Ninety percent of piloleiomyomas are painful, described as burning, pinching, or stabbing, exacerbated by tactile pressure, or even emotion.26,39,40,41 Multiple cutaneous leiomyomas occur on the face, trunk, or extremities and may be bilateral. The distribution pattern can be grouped, dermatomal, and linear.42
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