Benign Metastasizing Leiomyoma Research Articles

Benign metastasizing fumarate hydratase (FH)-deficient uterine leiomyomas: clinicopathological and molecular study with first documentation of multi-organ metastases

Leiomyoma is the most prevalent benign tumor of the female reproductive system. Benign metastasizing leiomyoma (BML) is a rare phenomenon that presents at distant sites, typically the lungs, exhibiting histopathological features similar to the primary uterine tumor in the absence of malignancy features in both. Fumarate hydratase-deficient uterine leiomyoma (FH-d UL) is an uncommon subtype among uterine smooth muscle tumors (0.5–2%), showing distinctive histomorphology and FH inactivation. The majority of FH-d ULs are sporadic, caused by somatic FH inactivation, while a minority of cases occur in the context of the hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome caused by germline FH inactivation. Metastasizing FH-d UL has not been well documented and might be under-reported. Here, we present two cases (21- and 34-year-old females) who presented with metastasizing FH-d UL after myomectomy/hysterectomy with histologically proven multiple lung metastases in both, in addition to multi-organ involvement in one case (cervical-thoracic lymph nodes, left kidney, perihepatic region, left zygomatic bone, and soft tissues). Pathological examination confirmed FH-d leiomyomas in the primary/recurrent uterine tumors, multiple lung lesions, and a renal mass. The minimal criteria for diagnosis of leiomyosarcoma were not fulfilled. Genetic testing revealed germline pathogenic FH variants in both cases (c.1256C > T; p.Ser419Leu in Case 1 and c.425A > G; p.Gln142Arg in Case 2). These novel cases highlight a rare but possibly under-recognized presentation of FH-d BML. Our study suggests that FH-d BML cases might be enriched for the HLRCC syndrome.

Benign Metastasizing Leiomyoma: Is "Wait and Watch" Strategy Feasible?

Benign metastasizing leiomyoma (BML) is a rare disease that affects women with a history of uterine leiomyoma. The aim of this study is to investigate the clinical characteristics and outcome patterns. We collected 385 cases from previous reports indexed in PubMed and Google Scholar and made a thorough review. All relevant clinical parameters were carefully reviewed, including age at diagnosis, clinical presentations, course of disease, medical history, imaging, molecular tests, treatment, and outcomes. Univariate survival analysis was performed to investigate the effects of treatment strategies on outcomes. The mean age at diagnosis was 46.2years. The most common site for the metastasis was lung, and followed by abdomen/pelvis/retroperitoneum, bone, lymph nodes, and heart. The medical histories and molecular alterations were non-specific, and the pathogenesis was still unclear. Due to its unresectable nature, hormone deprivation treatment, including oophorectomy and hormone drugs, is the most effective strategy to reduce or delay tumor progression. The present study may provide a useful consultation for diagnosing and managing BMLs.

A Case Report on Pulmonary Benign Metastasizing Leiomyoma with Recurrent Uterine Fibroids

Pulmonary benign metastasizing leiomyoma (PBML) is a type of benign metastasizing leiomyoma (BML), which metastasizes to lungs. In view of the rarity and nonspecific imaging characteristics of PBML, this condition is easily misdiagnosed as malignant lung cancer. This is a case report of a 39-year-old lady in whom multiple bilateral lung nodules were found during a health checkup and was diagnosed with PBML. The patient had recurrent uterine fibroids and underwent myomectomy twice, 7 years and 3 years ago, respectively, before the diagnosis of PBML was made. This patient was asymptomatic, and regular examinations were normal. Her laboratory investigations were all within normal range. Computed tomography (CT) showed multiple nodules in bilateral lungs. In order to confirm the disease, thoracoscopic nodule resection and tissue biopsy were performed. Hematoxylin eosin (HE) staining showed spindle-shaped cells, while immunohistochemical staining revealed positive for desmin, smooth muscle actin (SMA), estrogen receptor (ER), and progesterone receptor (PR), which are all PBML markers. The patient was followed-up without any further treatment. After 8 months of follow-up, CT scan revealed an increased number of nodules. This is unique case because of the recurrence of uterine fibroids, which means that the patient is susceptible to it. Our report may give a new insight to the relationship between the susceptibility of uterine fibroids and the onset and progression of PBML.

A critical review of “uterine leiomyoma” with subsequent recurrence or metastasis: A multicenter study of 62 cases

Histopathologic diagnosis of a subset of uterine smooth muscle tumors is challenging. We report a critical review regarding the clinicopathological point of view of 62 cases of subsequently recurred or metastasized leiomyoma. Medical records and glass slides of 62 cases of uterine smooth muscle tumor diagnosed as leiomyoma, which subsequently recurred or metastasized, were critically reviewed by pathologists specializing in gynecologic pathology and oncology. In 47 (75.8%) of 62 cases, the diagnosis of leiomyoma was confirmed, including 11 intravascular leiomyomatosis (IVL) and benign metastasizing leiomyoma (BML). In 29 cases (46.8%) laparoscopic surgery was performed, of which morcellator without a bag was employed in 23 cases. Fifteen cases (24.2%) appeared to be underestimated and were re-classified as smooth muscle tumor of uncertain malignant potential (STUMP), leiomyosarcoma, or other malignant mesenchymal tumors. Recurrences in seven cases (11.3%) were interpreted to be a malignant transformation, and one STUMP recurred as STUMP. The recurrence or metastasis in cases of "leiomyoma" is attributed to iatrogenic or under-evaluation of primary tumors, although a subset of cases is a rare example of biological progression.

Benign Metastasizing Leiomyoma (BML) - A Rare Phenomenon with Even Rarer Radiology and Disease Course

Benign Metastasizing Leiomyoma (BML) - A Rare Phenomenon with Even Rarer Radiology and Disease Course

Spontaneous versus morcellator-related benign metastasizing leiomyoma-A retrospective study.

To compare characteristics, disease course, and prognosis of spontaneous versus iatrogenic benign metastasizing leiomyoma (BML). A retrospective cohort study comparing iatrogenic and spontaneous BML. Twenty cases were included, 12 (60%) spontaneous and 8 (40.0%) iatrogenic with a median follow up of 3.4years. The rate of asymptomatic presentation did not differ between study groups (P=0.157). When symptoms occurred, dyspnea was more common in the spontaneous group (66.6% vs 0%, P=0.023) and self-palpation was more common in the iatrogenic group (57.1% vs 0%, P=0.023). Intravascular masses were more common in the spontaneous group (66.6% vs 0%, P=0.029). Rate of BML located in abdominal/pelvic cavity was higher in the iatrogenic group (100.0% vs 41.6%, P=0.014). Of the 12 women in the spontaneous group, 50% had recurrent disease following surgical resection or unresectable lesions surgical resection was successfully attempted in seven of the eight (87.5%) women in the iatrogenic group, with no residual/recurrent disease. None of the patients died of her disease. Spontaneous and iatrogenic BML can probably be regarded as two separate etiologies of the same pathologic phenomenon, usually with favorable prognosis. However, spontaneous BML may have a less favorable course.

18F]-FDG PET/CT of the Pulmonary Benign Metastasizing Leiomyoma in a Breast Cancer Patient: A Case Report

18F-fluorodeoxyglucose ([18F]-FDG) positron emission tomography/computed tomography (PET/CT) is a useful functional image technique to evaluate the disease extent in many cancers, as well as differentiate benign disease from malignant metastasis. We report the case of a 49-year-old woman with breast cancer and suspected lung metastasis by conventional images. After FDG-PET/CT demonstrating faint, or even no FDG uptake in bilateral pulmonary nodules, accompanied with obvious uterine fibroids, benign metastasizing leiomyoma (BML) of the lung was included in a differential diagnosis and finally confirmed by surgical pathology. FDG PET/CT showed its value in the diagnosis of BML in the breast cancer patient who was misleading as lung metastasis during outpatient follow-up.

The role of miRNA-221 and miRNA-126 in patients with benign metastasizing leiomyoma of the lung: an overview with new interesting scenarios

Benign metastasizing leiomyoma (BML) is a rare disease characterized by extrauterine benign leiomyomatosis in patients with a previous or concomitant history of uterine leiomyoma. Currently, there are no specific criteria to predict the metastasizing ability of the uterine leiomyoma and the risk of malignant degeneration of pulmonary BML, and these are the aims of this study. We analyzed 10 uterine (three leiomyomas, four leiomyomas that gave rise to lung BML, three healthy tissues) and 11 pulmonary tissue samples (eight lung BML, three healthy tissues). Interestingly, one of the BML lesions exceptionally evolved into a leiomyosarcoma (case 2). Uterine leiomyoma microvascular density (MVD) was higher in the patients with uterine leiomyomas that gave rise to lung BML, reaching a peak in case 2. Strong positivity for the estrogen (ER) and progesterone (PR) receptors and a low proliferation index (Ki67 < 1%) were discovered both in patients with uterine leiomyoma and in patients with BML. Interestingly, in case 2, the last dedifferentiated leiomyosarcoma showed a weaker ER and PR positivity with a higher proliferation index (Ki67:30%). Regarding the uterine miRNA-126, a trend toward a hypo-expression between uterine leiomyoma and uterine leiomyoma that gave rise to lung BML was discovered, reaching the lowest level in case 2. Considering the pulmonary samples, we observed a higher miRNA-221 and a lower miRNA-126 expression in the leiomyosarcoma. We tried to better elucidate the biological behaviour of this rare disease. The analysis of the miRNA-221 and miRNA-126 could offer new diagnostic, prognostic and therapeutic perspectives.

Ulipristal Acetate: Medical Management for Benign Metastasizing Leiomyoma?

Benign metastasizing leiomyoma (BML) is a rare disease characterized by smooth muscle tumors found outside of the uterus. Treatment options include surgery, embolization, and medical management. This case describes the use of ulipristal acetate in an attempt to medically manage an inoperable case of BML.

Clinicopathological features and gene phenotypes of benign metastasizing leiomyoma

Objective: To study the clinicopathological features, immunophenotypes and MED12 gene status in benign metastasizing leiomyoma (BML). Methods: Nine cases of BML diagnosed at the Affiliated Hospital of Qingdao University from 2012 to 2018 were collected, and the radiologic and histologic features were analyzed. The protein expression of leiomyosarcoma-related driver genes, including RB1, PTEN,ATRX,p16,p53, as well as ER,PR,CD34,FH, and Ki-67 were detected using immunohistochemistry, and the mutation status of MED12 gene exon 2 was detected by Sanger sequencing. Results: All the nine patients with BML were female, and the age range was 48 to 64 years (median 55 years). All patients had history of uterine fibroids. The morphologic features of BML were similar to a benign uterine leiomyoma and did not exhibit malignant characteristics. All cases were positive for ER and PR, and negative for CD34. In addition, RB1, PTEN, ATRX, and FH were positive in all cases (wild type), while p16 showed a focally positive pattern. P53 positive index was less than 5% (wild type), and Ki-67 positive index was less than 1%. Sanger sequencing was done in six BML samples; one sample harbored a nonsense mutation c. 142_144delinsTAA (p.Glu48Ter), and another exhibited a synonymy mutation (c.192C>T, p.Phe64=)and one missense mutation c.196C>T (p.Pro66Ser). Conclusions: The present study suggests that BML is a unique leiomyoma entity that is pathologically and genetically different from leiomyosarcomas and conventional uterine leiomyomas. Evaluating the genetic phenotype of BML, especially the expression of leiomyosarcoma-related driver genes protein and MED12 gene status, may be helpful in understanding the pathogenesis of BML and in its differentiation from leiomyosarcoma.

Pulmonary Leiomyomatosis Following Laparoscopic Myoma Morcellation [13H

INTRODUCTION: To report a case of a metastasizing myoma to the lungs diagnosed ten years following laparoscopic myoma morcellation, and review of the literature. METHODS: A 38 years old G3P1A2 underwent laparoscopic morcellation of a subserosal 5.5 cm myoma in 2003. Ten years later she presented with dyspnea and chest discomfort. CT chest images showed possible progressive metastatic disease from an unknown primary. Lingular wedge left lung resection revealed features compatible with metastatic leiomyoma. The pathological slides from the original myoma morcellation were reviewed and confirmed myoma origin of lung tumors. Review of the literature in PubMed (MEDLINE) for similar cases was conducted. RESULTS: Pulmonary benign metastasizing leiomyoma (BML) is rare and has been reported following hysterectomy and in women with leiomyoma uteri. Laparoscopic morcellation has been associated with parasitic myomas with an overall incidence of 0.12-.095%. To the best of my knowledge there are no reports of pulmonary benign metastasizing leiomyoma associated with laparoscopic morcellation. CONCLUSION: Complications from laparoscopic myoma morcellation are well documented, and resulted in restrictions in use of morcellators due to concerns of spreading leiomyosarcoma. The incidence of metastasizing leiomyomas to the lungs following laparoscopic myoma morcellation is presently unknown. Knowledge about benign metastasizing leiomyomas, imitating a malignant neoplasm such as lung cancer, is important to avoid over treatment and reassure the patient.

A case of pulmonary benign metastasizing leiomyoma: clinicopathologic, immunohistochemical, and PET/CT analyses

The pulmonary benign metastasizing leiomyoma (BML) is an extremely rare disease case, of which the pathogenesis was not elucidated. The accumulation of additional case reports and analyses is needed. A case of pulmonary BML is presented. A 48-year-old asymptomatic female patient that underwent a hysteromyomectomy 11 years ago was found to have abnormal shadows on a chest X-ray during a regular health check-up in 2012. Multiple nodular was observed in both lungs and uterine under computed tomography (CT) examination. Transbronchial lung biopsy surgery with a resection of the lesion was performed. The results revealed the pulmonary nodule was formed by benign smooth muscle cells which displayed very low mitotic activity. The samples showed highly positive signals for α-smooth muscle actin (αSMA), Desmin and Vimentin. Estrogen receptor (ER) and progesterone receptor (PR) were also immunoreactive positive. HMB-45, CD117 (C-kit) and S-100 were found to be negative with low Ki-67 index in the tumor cells. The pathological diagnosis was pulmonary BML. A total hysterectomy with adnexectomy were performed for the multiple uterine leiomyomas and pulmonary BML one week after diagnosis was made. From then on, the pulmonary nodules in both lungs were stable in 7 years postoperation, based on chest CT scan. When a solitary lung nodule is detected in a patient with a history of uterine leiomyoma, as an option, pulmonary BML, accurately diagnosing and proper treatment to has important implications for clinical outcome.

Benign metastasising leiomyoma of lung – two interesting cases

A leiomyoma, also known as a fibroid, is a benign smooth muscle tumour that very rarely becomes malignant (0.1%). They can occur in any organ, but the most common forms occur in the uterus, small bowel and the oesophagus. Benign metastasising leiomyoma (BML) is a rare condition that occurs in all

Benign metastasising leiomyoma of lung – two interesting cases

Benign metastasising leiomyoma of lung – two interesting cases

NOT ALL THAT METASTASIZES IS CANCER: A CASE OF BENIGN METASTASIZING LEIOMYOMA

SESSION TITLE: Lung Pathology 1 SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Benign metastasizing leiomyoma(BML) is a rare tumor primarily affecting the lungs of late reproductive-aged women with a history of uterine leiomyomas.It has benign histological features, though it metastasizes (biological behavior of malignancy). Immunostains are helpful in diagnosis.They are usually asymptomatic and an incidental finding.A hysterectomy is needed to rule out low grade uterine sarcoma. CASE PRESENTATION: 46F presented with a 2-week history of exertional dyspnea and pleuritic pain. Patient also complained of fatigue. She denied cough, wheezing, constitutional symptoms, leg swelling or orthopnea. Other review of system is nil of significance.Past history includes chronic back pain, incidental lung nodules noted on CT scan following an MVA, and previous tobacco use of <5 pack years and no occupational exposuresPhysical examination revealed a healthy looking female with stable vital signs and otherwise unremarkable examination.CT chest revealed multiple nodules with largest ones in the LUL (2.5cm), RML (2.3cm) and RUL 1.4(cm), compared to prior study nodules had increased in size and number.Prior evaluation of nodules with a CT-guided biopsy was reported as fibrogranulomatous process. Autoimmune workup was negative. Electromagnetic navigation bronchoscopy for biopsy was done revealing reactive appearing bronchial cells and pulmonary macrophages, few crowded cellular groups and no malignant cells. Cultures were negative.PET scan demonstrated nodules with SUV 1.4-1.8 without any abnormal extrathoracic uptake.Surgical lung biopsy was done with wedge resection of left upper lobe. Histology showed cystic, bland-appearing spindle cell neoplasm which was positive for both epithelial (TTF-1 and keratin) and smooth muscle tissue (Desmin and SMA). Cells stained positive for ER/PR, consistent with gynecologic origin leading to diagnosis of leiomyoma.Patient underwent hysterectomy and bilateral salpingoophorectomy showing adenomyosis and intramural leiomyomas. DISCUSSION: Bilateral pulmonary nodules in a late reproductive female can either be benign or malignant. Nodules larger than 1 cm suggest metastatic disease but the chronicity and slow doubling time in this case made malignancy less likely. Benign etiology was favored including granulomatous infection and connective tissue disease, however work up was inconclusive. Results from surgical biopsy was ambiguous given the staining for both smooth muscle and epithelial markers.Lesions vary in size, with smooth well-defined margins and diffuse nonspecific distribution. They are believed to be hematogenous metastases from morphologically benign uterine tumors. With ER/PR positivity in lung lesions, there is the option to treat with hormonal manipulation through surgical or medical oophorectomy. CONCLUSIONS: BML should be a differential diagnosis in females with pulmonary nodules and a history of uterine leiomyoma. Reference #1: Goyle et al; Benign metastasizing leiomyomatosis: case report and review. Am J Clin Oncol. 2003 Oct;26(5):473-6. Reference #2: Eun Young Ki et al; Benign metastasizing leiomyoma of the lung. World J Surg Oncol. 2013; 11: 279. DISCLOSURES: No relevant relationships by Arthur Oliver Romero, source=Web Response No relevant relationships by Cordelia Solomon, source=Web Response

BENIGN METASTASIZING LEIOMYOMA IN AN ELDERLY FEMALE, A CASE REPORT, AND REVIEW OF THE LITERATURE

14Sep 2018 BENIGN METASTASIZING LEIOMYOMA IN AN ELDERLY FEMALE, A CASE REPORT, AND REVIEW OF THE LITERATURE. Hanan Alrammah , Sara AlHajiri , Abdelhaleem Bella and Hind Alsaif. Medical Intern, King Fahad Hospital of the University, Imam Abdulrahman Bin Faisal University (IAU). Internal Medicine Resident, King Fahad Hospital of the University, IAU. Department of Medicine, RCSI-Bahrain. 4 Department of Radiology, college of medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.

Concurrent benign metastasizing leiomyoma in the lung and lumbar spine with elevated standardized uptake value level in positron-emission tomography computed tomography

Rationale:Benign metastasizing leiomyoma (BML) is rare condition involving distant metastases secondary to benign uterine leiomyoma, and it is most commonly found in the lungs. It rarely metastasizes to the spine to cause osteolytic damage and spinal canal compression.Patient concerns:A 51-year-old woman with low back and bilateral leg pain and paresthesia was admitted to our ward. She has a previous medical history of uterine leiomyomas. Magnetic resonance imaging of the lumbar spine revealed vertebral body osteolytic destruction and soft tissue mass in the L4/5 with a secondary lumbar spinal stenosis. Positron emission tomography computed tomography showed moderately intense accumulation of 18F-fluorodeoxyglucose in the L4/5 mass, as well as multiple nodules with increased metabolic activity in both lungs.Diagnoses:Pulmonary and spinal BML.Interventions:The patient underwent a computed tomography-guided percutaneous needle biopsy of the lung nodule and lumbar corpectomy, tumor excision, and vertebroplasty in the L4/5.Outcomes:Pathologically, both pulmonary nodule and vertebral mass were diagnosed as leiomyomas without any malignant evidence. Estrogen and progesterone receptors were both positive in the metastatic tumors. The patient's symptoms completely disappeared after the surgery. The patient is currently receiving outpatient anti-estrogen tamoxifen treatment for a BML.Lessons:Through this case, we suggest that BML should be regarded as part of differential diagnosis in female patients with a previous medical history of uterine leiomyomas presenting with multiple nodules in any parts of the body.

Benign Pulmonary Metastasizing Leiomyoma

Benign metastasizing leiomyoma (BML) is a rare event that occurs in middle aged women with a history of uterine myomas. It is characterized by multiple leiomyomatous lesions in many tissues and organs, especially in the lungs. We report the case of 56 years old woman presenting chronic cough, hemoptysis and having a history of myomectomy for a uterine leiomyoma 6 years ago.

Métastases pulmonaires bénignes d’un léiomyome

Benign metastasizing leiomyoma (BML) is a rare cause of pulmonary nodules. They can occur in women of reproductive age who have undergone hysterectomy for uterine leiomyoma. We report the case of a 46-year-old women, who was incidentally found to have bilateral pulmonary cavitating nodules. Pathology exam was consistent with BML. Although BML is a rare cause of pulmonary nodules, it should be considered as one of the possibilities especially in young women with a history of hysterectomy for leiomyoma.

Aberrant uterine leiomyomas with extrauterine manifestation: intravenous leiomyomatosis and benign metastasizing leiomyomas

ObjectiveIntravenous leiomyomatosis (IVL) and benign metastasizing leiomyoma (BML) are uncommon variants of benign uterine leiomyomas with extrauterine manifestations. Categorizing the extent of disease allows clinicians to delineate the clinical spectrum and the level of sophistication for complete surgical resection.MethodsTwelve patients with IVL and BML were reviewed. They were divided into early versus late stage disease groups, and initial manifestation, clinical characteristics, laboratory values, surgical pathology, and follow up data were summarized.ResultsPatients were mostly pre- or peri-menopausal and parous. Patients with late stage disease were more likely to present with cardiac symptoms or abnormal findings on chest X-ray, whereas those with early stage disease presented with classical leiomyoma symptoms including heavy menstrual bleeding, increased myoma size, or lower abdominal discomfort. Tumor marker levels were within normal ranges. A trend of higher neutrophil to leukocyte ratio was observed in the late versus the early stage group (10.4 vs. 1.51, P=0.07); the platelet leukocyte ratio was statistically higher in patients with late stage IVL (0.23 vs. 0.13, P=0.04). The overall recurrence rate was 25%. No recurrence was observed in stage I or stage III IVL groups, while 50% of the stage II IVL group showed recurrence in the pelvic cavity.ConclusionIVL and BML are benign myoma variants with paradoxically metastatic clinical presentation. Careful inquiry of systemic symptoms, the presence of underlying systemic inflammation, and a high index of suspicion are required for preoperative diagnosis. Furthermore, a multidisciplinary approach is necessary to improve outcomes of surgical resection.