Leiomyoma: Description, Causes and Risk Factors:
Leiomyomas are benign soft tissue neoplasms that arise from smooth muscle; they were first described by Virchow in 1854. The hereditary form, which causes, multiple leiomyomas, was originally noted by Kloepfer in 1958. They can develop wherever smooth muscle is present. Malignant transformation probably does not occur.
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 causes of leiomyomas remain unknown. A leiomyoma arises from a single neoplastic cell within the smooth muscle of the myometrium. The factors responsible for the initial neoplastic transformation of the myometrium to leiomyoma have yet to be elucidated. Neoplastic transformation probably involves somatic mutations of normal myometrial cells and the complex interaction of sex steroids and local growth factors.
Somatic mutations such as translocations, duplications, and deletions have been identified in almost one half of the leiomyoma studied by cytogenic analysis. The most frequent cytogenic changes involve chromosome bands 12q14-15 and 7q22. The somatic mutations may be the basis for the differential responsiveness of individual myomas to a variety of growth promoting agents.
The sex steroids, estrogen and progesterone, are believed to be important in leiomyoma enlargement. The tendency of uterine leiomyoma to grow during the reproductive years and regress postmenopausally strongly suggests that sex steroid hormones are implicated in the pathophysiology of the disease. Assay for estrogen and estrogen receptors in myomas show the concentration to be about ten times the concentration in normal myometrium.
It is believed that sex steroids promote development of leiomyomas by stimulating inappropriate expression of growth factors. Estrogen and progesterone act as physiologic regulators of gene expression by activating nuclear receptors that are themselves transcription factors. In this way estrogen and progesterone play a key role in regulating genes that direct cell growth. Some studies have shown that both steroids are important in leiomyoma growth, but it is progesterone that influences the proliferation of leiomyoma more than estrogen. Clinical evidence of the importance of sex steroids in leiomyoma growth can be seen with the shrinkage of leiomyoma during menopause and after GnRH administration in hypoestrogenic and hypoprogesterone states.
Growth factors such as insulin-like growth factor (IGF), epidermal growth factor (EGF), and platelet-derived growth factors (PDGF) are known mitogens. Only elevated expression of EGF has been associated with increased mitotic activity in leiomyomas. The expression of these growth factors is higher in uterine leiomyomas than normal myometrium. The levels of few of these growth factors or their receptors are elevated during the progesterone-dominated luteal phase of the menstrual cycle, when mitotic activities of leiomyomas can be elevated. Progesterone-regulated EGF is the only characterized growth factor with elevated expression during the luteal phase, when leiomyoma mitotic activity is elevated. Leiomyomas have been shown to contain EGF receptors that are responsive to their own production of EGF. It is therefore reasonable to conclude that EGF may contribute to the increased mitotic activity of leiomyomas observed during the luteal phase. It may act in synergism with other hormones, such as insulin or platelet-derived growth factor (PDGF).
The most common feature in patients with multiple piloleiomyomas
is pain.Pain can be spontaneous or induced by cold or tactile (e.g., 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.
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 are not routinely performed for leiomyomas; however, angioleiomyomas do have characteristic findings on ultrasound and magnetic resonance images.Tissue examination is necessary to establish the diagnosis. Therefore, a partial or excisional biopsy is indicated.
Because all leiomyomas are tumors, medical management has a limited role in the resolution or destruction of these lesions. However, pharmacologic intervention may alleviate associated pain.
Several investigators report that calcium channel blockers, particularly nifedipine, relieves pain associated with many cases of piloleiomyomas. As the name implies, drugs in this class inhibit the movement of extracellular calcium ions across the cell membrane into the smooth muscle cell, thereby inhibiting muscular contraction. These data support the theory that muscle contraction is somehow responsible for pain in at least some tumors.
Phenoxybenzamine, an alpha-adrenoceptor blocker, is also reported to be helpful in alleviating pain, including cold-induced pain, in some cases.
Gabapentin has also shown promise in alleviating pain from piloleiomyomas; however, larger randomized trials have not yet been conducted.
Two case reports describe botulinum toxin therapy for relief of pain associated with leiomyoma, although one suggested a possible placebo effect.
Surgical excision or ablation may be helpful for some symptomatic individuals.
Excision is frequently effective with a solitary leiomyoma.
NOTE: The above information is educational purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.
DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.
- Excision of multiple piloleiomyomas is more cosmetically problematic and less effective than excision of solitary leiomyomas. The recurrence of lesions is more common with multiple piloleiomyomas than with single lesions. After excision, subsequent recurrences have been reported to occur from 6 weeks to more than 15 years. One case report described total excision of multiple leiomyomas followed by immediate artificial skin graft, with successful results.
- One report revealed promising results for pain relief with carbon dioxide laser ablation of several symptomatic leiomyomas over a follow-up of as long as 3-9 months. Only local anesthesia was required for this procedure.