Benign Metastasizing Leiomyoma Associated With Lung Metastases : A Case Report by Donia Dhib, Medical Oncology department in Journal of Clinical Case Reports, Medical Images and Health Sciences

Benign Metastasizing Leiomyoma Associated With Lung Metastases : A Case Report by Donia Dhib, Medical Oncology department in Journal of Clinical Case Reports, Medical Images and Health Sciences

Abstract:

Benign metastasizing leiomyoma (BML) is a rare clinical entity observed in women of reproductive or premenopausal age with a history of uterine myomectomy or hysterectomy characterized by the presence of benign uterine leiomyomas that metastasize to extrauterine sites, most commonly to the lung. This literature case review aims to provide a comprehensive overview of the current understanding of BML, including its pathogenesis, clinical presentation, diagnosis, management, and areas of ongoing research.

Introduction:

Benign metastasizing leiomyoma is a rare condition that challenges the traditional understanding of uterine leiomyomas. This condition has been documented in women with a history of uterine leiomyomas, with the metastatic nodules appearing predominantly in the lungs. The pathogenesis of BML remains incompletely understood, and there is a paucity of high-quality clinical evidence regarding its optimal management. The exact mechanism underlying BML development is still a subject of debate. Several theories have been proposed, including hematogenous spread, lymphatic dissemination, and intraperitoneal seeding. The most common sites of metastases are the pulmonary, and other sites can include heart, lymph nodes and bladder (1–6). Hormonal factors, such as estrogen and progesterone, are believed to play a role in BML's growth and progression. 

Case report :

A 40-year-old female patient with a history of uterine fibroid surgery presented with multiple bilateral disseminated pulmonary nodules. The patient underwent her first uterine fibroid surgery 3 years ago which revealed aseptic necrobitic uterine leiomyoma with no histological signs of malignancy. She underwent a second reduction myomectomy, with incomplete resection, for recurrence of a uterine mass, which histological examination showed a leiomyoma. Immunohistochemistry stain showed that the tumor cells were positive for caldesmone and CD10. A follow-up pelvic MRI, performed 1 month later, showed a voluminous bilateral median and paramedian pelvic mass measuring 12*6 cm with heterogeneous signal enhancing after injection of Gadolinium, associated with a second mass at the uterine site measuring 72*42 mm with a large central necrotic cavity without bladder invasion. She underwent hysterectomy, and the pathology report showed a leiomyoma. Eight months after this episode, dysuria set in, and a pelvic recurrence was diagnosed, with the discovery of disseminated bilateral pulmonary nodules in the chest scan. The largest of these nodules was located in the right mediobasal region and measured 26*15mm, associated with a 47mm left anterior mediastinal mass with a bilobed, lymph node-like appearance. The patient had no respiratory or thoracic symptoms. A biopsy of the pelvic mass revealed a leiomyoma. Given the discrepancy between leiomyoma and secondary pulmonary lesions, a biopsy of a pulmonary 

lesion was performed surgically. Histologic examination revealed a proliferation of bland eosinophilic spindle cells with elongate nuclei and tapered ends consistent with smooth muscle. Cytologic atypia, necrosis and mitotic figures were not identified. Immunohistochemistry stain showed that the tumor cells were positive for musclespecific actin, estrogen and progesterone receptors and negative for TTF1. The ki67 index was 5%. The diagnosis of metastazing benign leiomyoma was made. The patient began chemical castration with LH-RH analogues. The first CT scan at 4 months showed a 15% reduction in tumour burden. Untill now, we are at 8 years of follow-up into treatment, with stable disease.

Discussion and Conclusions:

Benign metastasizing leiomyoma (BML) is an uncommon condition where histologically benign smooth muscle tumors spread to locations outside the uterus(7). Few cases of BML have been documented in medical literature. This disease typically affects women in their late reproductive or premenopausal years, many of whom have a history of surgically treated leiomyomas through myomectomy or hysterectomy. Our patient underwent 3 surgeries for recurrent uterine leiomyoma.

The most frequent clinical manifestations include progressive dyspnea during exertion, pneumothorax, and chylous effusions. Conversely, the absence of systemic symptoms or any symptoms, coupled with a history of uterine fibroids or prior uterine surgery, strongly suggests BML. In our case, No respiratory or thoracic symptoms were reprted by the patient. The most common site for metastasis is the lungs, accounting for 80% of cases. Other reported sites of metastasis can include the heart ,liver, lymph nodes, skeletal muscle and central nervous system. Zong et al (8) report in his paper, the case of a 51 year old woman with a history of uterine leiomyoma presentend with an osteolytic damage and spinal canal compression. Lymph nodes metastasis are rare but not excluded as exemplified in this case. . CT imaging of the chest and abdomen may indicate malignancy or infection. BML typically appears as welldefined lung nodules on CT scans. Bilateral lung nodules are more common than multiple unilateral lesions or solitary nodules. These nodules can vary in size and may cavitate, resulting in thin-walled or thick-walled cysts(9). In our case, too, the chest CT showed diffuse bilateral pulmonary 

Ultimately, a histological diagnosis is necessary to establish the diagnosis of BML. This could involve lung biopsy and lesion resection. Therefore, immunohistochemistry is the key to accurate diagnosis. The typical immunophenotypes of PBML cells include SMA (+), desmin (+), ER (+), and PR (+), whereas Ki-67 index is generally less than 1%(10). In this case, immunohistochemistry showed positivity for smooth muscle actin, ER, PR, and ki67 index was 5%. The exact origin of BML remains unclear and subject to controversy and various hypotheses have been proposed. The most widely accepted theory suggests hematogenous spread of a monoclonal element within a benign smooth muscle tumor. It is also suggested that there may be a derivation of an independent smooth muscle proliferation or potential derivation of a low-grade leiomyosarcoma (11).In this report, Wu et al. (12) used parallel sequencing and genome-wide copy number to detect lung and uterine leiomyoma in synchronized tissue samples. It was found that the somatic mutation and copy number aberrations were the same in chromosomal abnormalities paired pulmonary and uterine leiomyoma. A potentially deleterious somatic heterozygous mutation in the bone morphogenetic protein 8B gene may play a facilitatory role in the metastasis of BML(13). It has also been detected in 25% of these tumors, such as balanced translocation, trisomy 12, or 6p rearrangement of 6p(14). We were unable to complete a genetic study for our patient. Due to the rarity of this disease, no standardized treatment for BML has been proposed. Various articles published in the literature suggest that the treatment can include regular and vigilant observation ,surgical resection with oophorectomy( surgical castration), medical castration using aromatase inhibitors, estrogen receptor blockers (such as tamoxifen and raloxifene) , GnRH agonists ,progesterone therapy, tyrosine kinase inhibitors (such as imatinib), (15,16). Our patient benefited from chemical castration with GnRH analogues with tumor stability after 8 years follow-up. In conclusion, the prognosis for BML patients is generally favorable, and pulmonary lesions are typically discovered several years after hysterectomy or myomectomy, showing slow growth. Although rare, simultaneous metastases to retroperitoneal lymph nodes post-surgery require prolonged surveillance for early detection of recurrence or distant metastases. Given limited therapeutic options, there is a need to explore and consider new drugs or therapeutic strategies. Long-term follow-up is also recommended to better understand their implications in clinical practice.

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