Benign metastasizing leiomyoma and lymphangioleiomyomatosis: sex-specific diseases?

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Pathogenesis

The pathogenesis of BML remains controversial, despite the presumed etiology inherent in its name—uterine leiomyomata metastasizing to a distant site. There are three hypotheses to explain the mechanism of disease in BML that are discussed in the literature: metastatic uterine leiomyoma, metastatic uterine leiomyosarcoma, and multifocal leiomyoma growths.

Clinical characteristics

BML usually affects women who have undergone prior uterine surgery for leiomyomas [18] and appears several years after the surgery [7]. Patients are commonly asymptomatic at the radiographic presentation of pulmonary nodules; however, some symptoms such as cough, chest pain, and dyspnea have been reported [18]. BML should be considered in asymptomatic women with a history of uterine leiomyomas who present with multiple pulmonary nodules [18].

Radiologic findings

Pulmonary lesions often are incidental findings in a

Treatment of benign metastasizing leiomyoma

Pulmonary tumors in BML can be treated with bronchoscopic resection, conservative pulmonary surgery, and hormonal manipulation [2]. Surgical hormonal management can be accomplished with bilateral oophorectomy. Medical hormonal management includes the use of luteinizing hormone-releasing hormone analogue, tamoxifen, progesterone [2], and aromatase inhibitors [7].

Treatment results have had variable outcomes among patients. A woman with multiple pulmonary nodules who underwent a prior hysterectomy

Other unusual growth patterns of leiomyomas

BML is considered an unusual growth pattern of uterine leiomyomas. There are two other rare conditions that fall into this category and may have a similar pathogenesis: intravascular leiomyomatosis (IVL) and disseminated peritoneal leiomyomatosis (DPL) [16]. These conditions may all be part of a spectrum of benign smooth muscle tumors of the uterus, with an ordinary uterine leiomyoma at one end and BML at the other [15].

IVL (also called intravenous leiomyomatosis) is a rare tumor of the uterus,

Benign metastasizing leiomyoma and lymphangioleiomyomatosis

There are many similarities between BML and LAM, including smooth muscle proliferation, pulmonary location, female predominance, hormonal dependence as evidenced by progression during child-bearing years [37], and HMB-45 immunoreactivity [2]. Some authors suggest that these two diseases may be related or share a common histogenesis with perivascular mesenchymal cells. LAM is characterized by the disorderly proliferation of atypical smooth muscle cells along lymphatics, small airways, and blood

Lymphangioleiomyomatosis: clinical, radiographic, and pathologic features

LAM patients are usually women of reproductive age who present with a spontaneous pneumothorax, chylous pleural effusion, progressive exertional dyspnea [18], cough, or occasionally hemoptysis [32], [42]. A review of the literature indicates that the average age at onset of symptoms and age at diagnosis are in the early thirties and forties, respectively. The average interval between onset of symptoms and time of diagnosis is approximately 3 to 4 years [4]. LAM also has been reported to occur

Lymphangioleiomyomatosis and tuberous sclerosis complex

Two distinct types of LAM are reported in the literature: sporadic cases and those found in patients with tuberous sclerosis complex (TSC). TSC is an autosomal-dominant neurocutaneous disorder with variable penetrance caused by mutations in the TSC1 and TSC2 genes. Mutations in TSC2 have been isolated in patients with sporadic LAM and in patients with TSC and LAM [50].

Although the incidence and prevalence of sporadic LAM is unknown, it has been estimated by the LAM Foundation that there may be

Therapeutic options for lymphangioleiomyomatosis patients

Although the role of estrogens in LAM remains unclear, antiestrogen therapy has become the method of managing a patient with LAM. Tamoxifen, a partial estrogen receptor agonist, was used for many years but was reported to exacerbate disease in some women [45].

Most women with LAM have been put on some form of progesterone during the course of their disease. It is thought that progesterone down-regulates the estrogen receptor so that estrogens are less active. Progesterone can be given via

Hormonal features of benign metastasizing leiomyoma and lymphangioleiomyomatosis

The development of smooth muscle tumors is hormonally influenced, as evidenced by uterine leiomyomas developing after menarche, increasing in size during pregnancy, regressing after menopause, and shrinking after therapy with gonadotropin-releasing hormone antagonists [17], [26]. During the menstrual cycle, the mitotic count in leiomyomas is greater during the secretory phase and higher in younger women [26]. Ultrastructural analysis has shown that cells resembling fibroblasts develop after

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      It has been postulated that BML cells originate from a single site.32 Although among uterine tumors BML has been mainly associated with leiomyomas,2 the type of leiomyomas is unclear (eg, mitotically active, cellular, hemorrhagic cellular, atypical, epithelioid, myxoid, vascular, lipoleiomyomas). Other types of smooth muscle tumors of the uterus that could be associated with BML are smooth muscle tumors of uncertain malignant potential, leiomyosarcomas, and endometrial stromal tumors.33,35,36

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