Benign metastasizing leiomyomatosis

Benign metastasizing leiomyomatosis Leiomyoma is the most common pelvic tumor in women. In rare circumstances, uterine leiomyoma has been reported to involve other organs or structures. This is termed benign metastasizing leiomyoma (BML).

Benign metastasizing leiomyomatosis Intravenous leiomyomatosis (IVL) - leiomyoma-like lesions that extend from the uterus into the pelvic blood vessel, and sometimes as far as the heart. - with leiomyomas and significant dyspnea, an intracardiac mass, or evidence of right heart failure. Disseminated peritoneal leiomyomatosis (DPL)

Benign metastasizing leiomyomatosis Pathology Uterine leiomyomas with less than 5 mitoses per 10 HPFs, (high power field) with no cellular atypia or necrosis leiomyosarcomas a mitotic index greater than 10, marked cellular atypia, and coagulative tumor cell necrosis characterizes. For tumors with characteristics between these extremes, the term, “leiomyoma of uncertain malignant potential”

Benign metastasizing leiomyomatosis Predominantly in women during reproductive years - 1939 Steiner - prevalence of about 50% above the age of 30 yr The lung is the most common site of metastasis - 0,085% of pulmonary benign tumors - Hematogenous metastases - Lymph nodes, the venous system, peritoneum or pericardium. - The mechanism of the tumor spread is not certain.

Benign metastasizing leiomyomatosis The mechanism Intravascular tumor dissemination from surgical trauma a commonly purposed mechanism pulmonary metastasis occur in patients with a history of previous hysterectomy . Others from microscopic vascular invasion of the leiomyoma into the venous system (intravenous leiomyomatosis). the concurrence of pulmonary nodules and the uterine tumor before surgery in some cases.

Benign metastasizing leiomyomatosis On chest CT - as multiple well circumscribed nodules - ranging in size from a few millimetres to several centimetres - not calcified - cavitation or a military pattern uncommon - no pleural effusion and no mediastinal lymphadenopathy. - Pericardial effusion

Benign metastasizing leiomyomatosis Diagnosis Percutaneous or open biopsy Differential Diagnosis appearance is non-specific. malignant metastases , infectious inflammatory granulomas sarcoidosis, rheumatoid nodules, amyloidosis, and arteriovenous malformations.

Benign metastasizing leiomyomatosis Treatment Treatment options based on hormonal manipulation through surgical or medical oophorectomy. Most BMLs are ER positive The estrogen and progesterone status In post-menopausal women vs in pre-menopausal women

Benign metastasizing leiomyomatosis Treatment Hormonal manipulation - Antiestrogen LHRH agonist Aromatase inhibitor (Anastrozole) decrease estrogen production from extragonadal sources SERMs Selective Estrogen Receptor Modulators (Raloxifene) antagonize estrogen actions in target tissues

Benign metastasizing leiomyomatosis Treatment Raloxifene, a synthetic nonsteroidal SERM - as an estrogen agonist, on the skeleton, cardiovascular system, and CNS weak estrogenic antagonist effect on the breast and uterus. - A randomized, placebo-controlled trial the addition of raloxifene in patients treated with an LHRH agonist induces a greater reduction of leiomyoma sizes. - The addition of raloxifene prevents LHRH-agonist treatment-related bone loss in premenopausal women with uterine leiomyomas.

Summary of recent reports of benign metastasizing leiomyoma Modern Pathology (2006) 19, 130–140

Benign metastasizing leiomyomatosis Prognosis The clinical course - usually indolent Abramson et al reviewed seven patients with BML in the lungs - no significant morbidity or mortality on long term follow up. - little correlation between the patient’s respiratory symptoms and the radiologic disease extent. BML should be regarded as a borderline tumor or a tumor with low malignant potential.

Natural Decrease of Benign Metastasizing Leiomyoma Chest 2000;117;921-922 52 age Estrogen 20.4 µg/dL Progesterone 1.5 ng/mL 53 age Estrogen 4.3 µg/dL Progesterone 0.3 ng/mL

A woman with a pelvic mass and pulmonary nodules The British Journal of Radiology, 77 (2004), 459–460 Department of Diagnostic Radiology, Tuen Mun Hospital, Hong Kong, China 47-year-old Chinese woman, Tamoxifen (anti-estrogen)

Hormonal Manipulation The Journal of Clinical Endocrinology & Metabolism (2004) 89(7):3183–3188 A 47-yr-old Caucasian woman hysterectomy at age 36 yr for a 6-cm uterine leiomyoma. The long-acting LHRH agonist, leuprolide acetate, anastrozole, an AI

Hormonal Manipulation The Journal of Clinical Endocrinology & Metabolism (2004) 89(7):3183–3188 A 37-yr-old Haitian woman Respirology department for progressive shortness of breath age 34 yr. Cells from the 22 x 16 x 10 cm Intramural leiomyoma strongly positive for both ER and PR. At age 47 yr, ICU with acute respiratory failure raloxifene 60mg and anastrozole 1 mg daily. bilateral oophorectomy

Benign metastasizing leiomyomatosis Benign Pulmonary Metastasizing Leiomyomatosis Kwon YI. Hanyang University College of Medicine, Seoul, Korea. Korean J Intern Med. 2006 Sep;21(3):173-177. A Case of Benign Metastasizing Pulmonary Leiomyomatosis. Kim YS. Dankook University College of Medicine Tuberc Respir Dis. 2002 Aug;53(2):190-195. An Intravenous leiomyoma with cardiac involvement in a patient with uterine leiomyoma.  Kim JS. Sungkyunkwan University School of Medicine. Korean J Intern Med. 2004 May;66(5):549-554. Two Cases of Intravenous Leiomyomatosis of the Uterus.  Kim JH, Koh MW. Department of Obstetrics and Gynecology, College of Medicine, Yeungnam University, Daegu, Korea. Yeungnam Univ J Med. 2006 Dec;23(2):213-220.