Background
Leiomyomas are benign soft tissue neoplasms that arise from smooth muscle; they were first described by Virchow[1] in 1854. The hereditary form, which causes, multiple leiomyomas, was originally noted by Kloepfer et al[2] in 1958. They can develop wherever smooth muscle is present. Malignant transformation probably does not occur. A 2006 report[3] 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)
Epidemiology
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 report[3] 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 reported[4] 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.[5]
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.[6, 7]
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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