Safety and efficacy of sirolimus in recurrent intravenous leiomyomatosis, pulmonary benign metastatic leiomyomatosis, and leiomyomatosis peritonealis disseminata: a pilot study.

BACKGROUND: Intravenous leiomyomatosis (IVL), pulmonary benign metastatic leiomyomatosis (PBML), and leiomyomatosis peritonealis disseminata (LPD) are leiomyomas with special growth patterns and high postoperative recurrence rates. We report the safety and efficacy of a pilot study of sirolimus in the treatment of recurrent IVL, PBML, and recurrent LPD. METHODS: This was a pilot study to evaluate the safety and efficacy of sirolimus in the treatment of leiomyomatosis (ClinicalTrials.gov identifier NCT03500367) conducted in China. Patients received oral sirolimus 2 mg once a day for a maximum of 60 months or until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop. The primary end point of this study was the objective response rate. Secondary end points included safety and tolerability, disease control rate, and progression-free survival. RESULTS: A total of 15 patients with leiomyomatosis were included in the study, including five with recurrent IVL, eight with PBML and two with recurrent LPD. The median follow-up time was 15 months (range 6-54 months), nine patients (60%) had treatment-related adverse events (including all levels), and two patients had treatment-related grade 3 or 4 adverse events. The objective response rate was 20.0% (95% CI, 7.1-45.2%), and the disease control rate was 86.7% (95% CI, 62.1-96.3%). Partial response was achieved in three patients. The median response time in the three partial response patients was 33 months (range 29-36 months), and the sustained remission time of these three patients reached 0, 18, and 25 months, respectively. CONCLUSIONS: Sirolimus was safe and effective in the treatment of recurrent IVL, PBML, and recurrent LPD. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03500367. Registered on 18 April 2018.

Unraveling the challenges of intravenous leiomyomatosis: a retrospective analysis of 11 cases.

OBJECTIVE: This study provides a concise overview of diagnostic and treatment strategies for intravenous leiomyomatosis (IVL), a rare disease with nonspecific clinical manifestations, based on cases from a tertiary referral hospital in China. METHODS: We retrospectively analyzed 11 premenopausal patients with confirmed IVL between 2018 and 2022. Clinical data from Ultrasound, Enhanced CT, and MRI were studied, along with surgical details, postoperative pathology, and follow-up information. RESULTS: Premenopausal patients showed no disease-specific symptoms, with 90.9% having a history of gynecological or obstetric surgery, and 72.7% having prior uterine fibroids. Cardiac involvement was evident in two cases, with echocardiography detecting abnormal floating masses from the inferior vena cava. Pelvic ultrasound indicated leiomyoma in 90.9% of cases, with ≥ 50 mm size. Surgery was the primary treatment, and lesions above the internal iliac vein resulted in significantly higher intraoperative blood loss (median 1300 ml vs. 50 ml, p = 0.005) and longer hospital stays (median 10 days vs. 4 days, p = 0.026). Three patients with lesions above the inferior vena cava required combined surgery with cardiac specialists. Recurrence occurred in 2 out of 11 patients with incomplete lesion resection. CONCLUSIONS: IVL mainly affects premenopausal women with uterine masses, primarily in the pelvic cavity (Stage I). Pelvic ultrasound aids early screening, while Enhanced CT or MR assists in diagnosing and assessing venous lesions. Complete resection is crucial to prevent recurrence. Lesions invading the internal iliac vein and above pose higher risks during surgery. A multidisciplinary team approach is essential for patients with lesions above the inferior vena cava, with simultaneous surgery as a potential treatment option.

Intravenous leiomyomatosis involving the right heart: Comprehensive evaluation using echocardiography combined with abdominal ultrasonography.

Intravenous leiomyomatosis (IVL) is a rare condition characterized by a tumor that originates within a pelvic vein wall or the uterine smooth muscle, with extension into the right heart (referred to as intracardiac leiomyomatosis) in approximately 10% of all IVL cases. Usually, computed tomography (CT) or magnetic resonance imaging (MRI) is performed for diagnostic imaging of IVL. Notably, this neoplasm presents with characteristic ultrasonographic findings. In this report, we present the case of a 49-year-old woman with IVL, which extended into the right heart. Echocardiography combined with abdominal ultrasonography was useful to outline the course of the tumor from the right heart to the uterus. Our findings suggest that in addition to CT or MRI, ultrasonography shows high diagnostic value in cases of IVL, and ultrasonography combined with CT or MRI can further improve the preoperative diagnosis rate of IVL.

Benign Metastasizing Leiomyomatosis to the Skin and Lungs, Intravenous Leiomyomatosis, and Leiomyomatosis Peritonealis Disseminata: A Series of Five Cases.

Benign metastasizing leiomyomatosis (BML) is a rare disease that typically occurs in women with a history of uterine leiomyomatosis. Benign metastasizing leiomyomatosis occurs more frequently in the lungs but may also develop in other organs and tissues. Other unusual variants of extra-uterine leiomyomatosis include intravenous leiomyomatosis (IVL) and leiomyomatosis peritonealis disseminata (LPD). In this article, three cases of BML are presented. One case, in a premenopausal woman, presented cutaneous metastases. We also present a case of IVL and a case of LPD, which occurred in postmenopausal women. Given the rarity of BML, IVL, and LPD, the authors reviewed the literature and herein discuss the implications for treatment in all five cases. Evidence for treating BML, IVL, and LPD is still scarce, and data available from our series and other small series seem to point to the patient's hormonal status playing a fundamental part in the treatment plan. Furthermore, a collecting bag when performing excision of uterine leiomyomas may help avoid the potential spreading of leiomyomatosis. Hysterectomized patients with chronic cough, frequent respiratory infections, abdominal discomfort, right heart failure, or non-specific symptoms should be actively screened for BML, IVL, and LPD. Treatment should be individualized according to each patient's hormonal status and desires.

Leiomyoma with nuclear atypia: Rare diseases that present a common diagnostic problem.

Leiomyoma with nuclear atypia describes a group of uterine smooth muscle tumors with a wide range of histologic and clinical presentations and remarkable nuclear atypia. These include fumarate hydratase-deficient leiomyoma (FH-LM), intravenous leiomyomatosis (IV-LM), and leiomyoma with bizarre nuclei (LM-BN). Other uterine mesenchymal tumors, such as perivascular epithelioid tumor (PEComa) and inflammatory myofibroblastic tumors (IMFT) are the mimickers of leiomyoma with nuclear atypia. LM-BN is the primary tumor model with a long history in gynecologic pathology, but the histogenesis of LM-BN remains largely unknown. Differentiating LM-BN from other benign variants, tumors with uncertain malignant potential (STUMP), or fully malignant leiomyosarcoma (LMS) can be diagnostically challenging. Recent progress has improved the diagnosis of many types of leiomyoma with nuclear atypia based on their specific histology and molecular alterations. LM-BN is now a diagnosis of exclusion. In this article, I review the history of leiomyoma with nuclear atypia and compare the clinical, histologic, and molecular features of LM-BN with those of its mimics. In particular, I highlight the current progress made in molecular genetics and pitfalls in the diagnosis of different myogenic tumors with nuclear atypia.

Echocardiographic Characteristics and Contrast-Enhanced Imaging of Intravenous Leiomyomatosis With Intracardiac Extension.

OBJECTIVES: Intravenous leiomyomatosis (IVL) is a histologically benign but biologically aggressive tumor. This study aimed to summarize the echocardiography and contrast-enhanced ultrasound (CEU) characteristics of IVL to provide a basis for clinical diagnosis and therapy. METHODS: Fourteen IVL patients with uterus leiomyoma history (female, 46.4 ± 5.6 years) were enrolled in this study from March 2008 to December 2020 in our hospital. Preoperative imaging examination data were collected, including echocardiography computed tomography data; six patients also underwent CEU. All patients underwent successful resection, confirmed by histopathology. RESULTS: Echocardiographic characteristics: The mean sizes of intracardiac parts of IVL tumors were 54.0 ± 17.9 mm (length) and 24.6 ± 9.8 mm (width). IVL tumors exhibited two echocardiography types: isoechoic solid mass (71.4%, 10/14) and anechoic cystic conduits (28.6%, 4/14), with enlargements of the right atrium (57.1%,8/14), right ventricle (1 patient, 7.1%), and inferior vena cava (57.1%, 8/14). About 21.4% of the patients (3/14) had right ventricular dysfunction. Right heart obstruction was observed in 42.8% (6/14) of the patients. CEU characteristics: the solid mass type exhibited an earlier perfusion and lower perfusion intensity than the conduits type. CEU was helpful in determining origins and pathways: from the internal iliac vein (pathway I, 71.4%), from the ovarian vein (pathway II, 14.3%), or both (14.3%). The echocardiographic appearances of the 14 cases were consistent with the features of the resection specimens. CONCLUSION: Combined echocardiography and CEU can provide a more valuable information for the diagnosis of IVL and essential basis for treatment.

Myomectomy for intravenous leiomyomatosis: a retrospective series of 9 cases.

The current study aimed to evaluate the clinical outcomes of patients with intravenous leiomyomatosis (IVL) who underwent myomectomy. Clinical data were retrieved from our database from January 2001 to October 2018. Of 197 patients with IVL, 9 (4.6%) patients were included. The patients' age ranged from 24 to 46 (mean: 31.1 ± 7.3) years. Five (55.6%) patients had not yet given birth upon IVL diagnosis. Three patients were treated with gonadotropin-releasing hormone agonists after surgery. The average follow-up time was 58.9 ± 27.8 (range: 29-122) months. Four patients presented with new uterine masses during follow-up. Three patients had natural pregnancies and live births. This information may provide a glimmer of hope to young patients with uterus-confined IVL who have fertility desires. However, future multicenter studies with larger sample sizes and longer follow-up periods are warranted.Impact statementWhat is already known on this subject? The best treatment options for intravenous leiomyomatosis (IVL) are hysterectomy with bilateral salpingo-oophorectomy and complete resection of intravenous extensions of the disease.What the results of this study add? Nine patients with IVL underwent myomectomy. After a mean follow-up period of 58.9 ± 27.8 months, 3 patients had natural pregnancies and live births.What are the implications of these findings for clinical practice and/or further research? The result might provide a glimmer of hope to young patients with uterus-confined IVL who have fertility desires.

Oncological Properties of Intravenous Leiomyomatosis: Involvement of Mesenchymal Tumor Stem-Like Cells.

Uterine leiomyoma, also known as fibroids, is the most common benign neoplasm of the female genital tract. Leiomyoma is the most common uterine tumor. The leiomyoma subtypes account for approximately 10% of leiomyomas. Intravenous leiomyomatosis, a uterine leiomyoma subtype, is an intravascular growth of benign smooth muscle cells, occasionally with pelvic or extrapelvic extension. Uterine leiomyosarcoma, a malignant tumor, tends to metastasize hematogenously, and distant metastasis to the lungs and liver is common. Therefore, the oncological properties of this intravenous leiomyomatosis resemble those of the malignant tumor uterine leiomyosarcoma. Cancer stem cells migrate to distant organs via intravascular infiltration, leading to micrometastases. We examined the oncological properties of intravenous leiomyomatosis using molecular pathological techniques on tissue excised from patients with uterine leiomyoma. CD44-positive mesenchymal tumor stem-like cells were detected in both patients with intravenous leiomyomatosis and uterine leiomyosarcoma. The oncological properties of intravenous leiomyomatosis were found to be similar to those of uterine leiomyosarcoma. However, in intravenous leiomyomatosis, cyclin E and Ki-67-positive cells were rare and no pathological findings suspecting malignancy were observed. It is expected that establishing a treatment method targeting cancer stem cells will lead to the treatment of malignant tumors with a low risk of recurrence and metastasis.

Clinical analysis of uterine intravenous leiomyomatosis: A retrospective study of 260 cases.

METHODS: We collected the clinical data of 260 patients admitted to the hospital from April 2003 to September 2019 with pathologically confirmed intravenous leiomyomatosis (IVL) and followed up with these patients regularly. Univariate and multivariate logistic regression analyses were carried out on the relevant recurrence factors. RESULTS: A total of 166 patients were regularly followed up, the median follow-up time was 36 (range 2-168) months, 14 (5.4%) patients eventually relapsed, and the median recurrence time was 8.5 (range 2-42) months. The univariate analysis showed that age (p = 0.003) and surgical type (p < 0.001) were associated with recurrence, and multivariate regression analysis demonstrated that surgical type was the only factor associated with recurrence (p < 0.001, OR 20.01). CONCLUSIONS: The use of gonadotrophin releasing hormone agonist (GnRHa) cannot reduce the postsurgical recurrence rate of patients with UIVL. Compared to total hysterectomy and bilateral salpingo-oophorectomy (TH-BSO), total hysterectomy (TH) does not increase the odds of recurrence, but the chance of recurrence with tumorectomy (TE) is 20 times higher than that of TH-BSO.

Computed tomography evaluation of extensive intravenous angioleiomyoma: a case report.

BACKGROUND: Uterine angioleiomyoma is a rare variant of leiomyoma, and the main therapy is complete surgery. This study introduces the benefit of three-dimensional computed tomography reconstruction for preoperative preparation. CASE PRESENTATION: A 50-year-old woman presented because of chest distress after activity, with worsening symptoms. After examination, the final diagnosis was uterine angioleiomyoma. The tumour originated in the uterus; grew into the right iliac vein; coursed along the iliac vein, inferior vena cava, and right atrium; and finally invaded the right ventricle. To best complete the surgery, a multidisciplinary surgery was selected. Before the surgery, a three-dimensional computed tomography reconstruction model was created to assess the tumour status, and this model enabled the surgery to be completed successfully. CONCLUSION: Three-dimensional computed tomography reconstruction is of great significance for the preoperative diagnosis of uterine angioleiomyoma and the formulation of surgical treatment plans. Based on its vivid images, surgeons can perform operations more effectively and safely.

[Intravenous leiomyomatosis as a rare tumor of myometrium]. / Intravenózní leiomyomatóza jako vzácný nádor myometria.

AIM: To present a case of a woman diagnosed with intravenous leiomyomatosis of the uterus. TYPE OF STUDY: Case report. SETTING: Department of Obstetrics & Gynaecology, Stredomoravská nemocnicní a.s., Prerov Hospital. CASE REPORT: A 39-year old woman was referred to our unit with uterine fibroids, dysfunctional uterine bleeding and anaemia. Abdominal hysterectomy was performed. The histopathological analysis diagnosed the presence of intravenous leiomyomatosis. After a thorough literature review, we decided to perform an adnexectomy. It was not possible to perform this laparoscopically due to adhesions from previous operation. A conversion to open surgery was necessary. CONCLUSION: Intravenous leiomyomatosis is a rare clinical condition characterised by the ability of the leiomyoma to spread outside the uterus via the venous system. The diagnosis is difficult to obtain and can only be made after histopathological examination. There are no universal treatment guidelines in place at present.

Massive pelvic recurrence of uterine leiomyomatosis with intracaval-intracardiac extension: video case report and literature review.

BACKGROUND: Uterine leiomyomas represent the gynecological neoplasm with the highest prevalence worldwide. This apparently benign pathological entity may permeate into the venous system causing the so-called intravenous leiomyomatosis of the uterus (IVL). IVL may seldom extend to large caliber veins and reach the right cardiac chambers or pulmonary arteries and cause signs of right sided congestive heart failure and sudden death. Due to its low incidence, however, IVL with intracardiac extension is often misdiagnosed resulting in deferred treatment. No consensus has been obtained regarding the standard surgical approach to be used for this rare condition. We describe the case of a massive pelvic recurrence of uterine leiomyomatosis with intracardiac extension and provide a review of the literature, analyzing management and surgical outcomes. CASE PRESENTATION: We present the case of a 46-year-old premenopausal woman presenting with lower-extremity edema, recurrent syncopes and a history of subtotal hysterectomy for multiple uterine fibroids. She was diagnosed with pelvic recurrence of uterine leiomyomatosis and IVL with cardiac involvement. A two-stage surgical excision of the intracardiac-intracaval mass and pelvic leiomyomatosis was performed. The patient had an uneventful recovery and no evidence of recurrence was observed on follow-up. CONCLUSIONS: By virtue of the rarity of the present pathology, awareness is widely scarce and diagnosis is often delayed. Early recognition is difficult due to initial aspecific and subtle clinical manifestations. Nevertheless, suspicion should be held high in premenopausal women with known history of uterine leiomyomata, presenting with cardiovascular symptoms and evidence of a free-floating mass within the right cardiac chambers. In-depth imaging is crucial for defining its anatomical origin and relations. Prompt surgical treatment with radical excision of pelvic and intravenous leiomyomatosis guarantees favorable outcomes and excellent prognosis with low rates of recurrence, whereas delayed diagnosis and treatment exposes to increased risk of congestive heart failure and sudden death.

Intracardiac Leiomyomatosis - an Unusual Cause of Syncope in a Middle-Aged Woman.

Intracardiac leiomyomatosis is a rare complication that occurs when a uterine leiomyoma (fibroid) undergoes vascular invasion and propagates within the inferior vena cava to reach the right atrium. This article describes a case of intracardiac leiomyomatosis in a middle-aged woman, exploring the presentation, diagnosis and surgical management of this condition. In this case the presenting complaints were syncope and atrial fibrillation, illustrating the importance of performing a transthoracic echocardiogram in patients presenting with their first episode of atrial fibrillation. Clinicians should consider intracardiac leiomyomatosis when evaluating women with right heart masses, especially those with a history of uterine leiomyomas.

Intravenous Leiomyomatosis in the Parametrium.

Laparoscopic imaging of intravenous leiomyomatosis is rare. We report a 35-year-old woman with uterine leiomyomatosis, laparoscopic hysterectomy exposed parametrial vessels with whitish plugs extending intravascularly toward the pelvic sidewall. Complete surgical resection and long-term follow-up are important.

Intravenous leiomyomatosis treated with radical hysterectomy and adjuvant aromatase inhibitor therapy.

Intravenous leiomyomatosis (IVL), a rare disease that is histologically benign but clinically aggressive, is characterized by the intraluminal growth of benign leiomyoma in the intrauterine and systemic veins. Preoperative diagnosis of IVL is difficult, because the symptoms of early stage IVL are similar to those of uterine leiomyoma. The efficacy of adjuvant hormone therapy after surgical resection of IVL remains unclear. Herein is described a case of IVL that was diagnosed preoperatively, in which successful total resection of the tumor was achieved by radical hysterectomy. The patient, a 50-year-old premenopausal Japanese woman, also underwent aromatase inhibitor treatment and was free of disease at 36 months after surgery. Contrast-enhanced computed tomography is suggested as the best assessment for identifying and diagnosing IVL. Radical hysterectomy can be considered a successful therapy for total resection. Aromatase inhibitor treatment may be effective, especially when the patient has not yet entered menopause.

Orthostatic hypotension and right heart failure as the initial manifestation of intravenous leiomyomatosis.

A 36-year-old woman, who had a history of myomectomy, presented with lightheadedness after changing position from sitting to standing and effort-related shortness of breath. Echocardiography demonstrated a hyperechoic elongated mobile mass extending from the inferior caval vein to the right atrium. The mass was surgically removed, and histological examination established the diagnosis of intravenous leiomyomatosis. This case caught the attention of our cardiology group to consider the diagnosis when an inferior caval vein or right atrium mass is found in a patient with a history of uterine leiomyomatosis.

Surgical strategy for intravenous leiomyomatosis spreading from uterine to the right atrium presenting with recurrent syncope.

Uterine leiomyoma invading internal iliac vein and consequently disseminating into the right atrium is an extremely rare condition, and surgical strategy is controversial. Here, we reported a specific case with successful surgical resection through one-stage total hysterectomy, bilateral oophorectomy, and the intracardiovascular lesion. This procedure would be an optimal choice for uterine leiomyoma invading inferior vena cava and spreading to right atrium.

Update on clinical characteristics and molecular insights for uterine intravenous leiomyomatosis (Review).

Intravenous leiomyomatosis (IVL) is a rare benign disease, which typically develops along vascular vessels and extends to the inferior vena cava and right atrium of the heart. In the early stages of the disease, the clinical manifestations and the results of imaging examinations are not uniform among patients. Thus, a high rate of misdiagnosis and missed diagnosis is common. When the tumor extends along the venous system to the pelvic floor vein or through the inferior vena cava involving the right atrium of the heart or the pulmonary artery, severe symptoms occur, such as ascites, dyspnea, heart failure and even sudden mortality. Improving the understanding of IVL to identify and evaluate this disease in its early stages is important. Complete tumor resection remains the primary treatment option for IVL. The recurrence rate of the disease varies depending on multiple factors, such as type of surgical procedure performed. Therefore, long-term follow-up is necessary for patients with IVL. The review of recent findings on the molecular and clinicopathological characterization of IVL is important to understand the pathogenesis of IVL. In the present study, the clinical manifestations, pathogenesis, differential diagnosis, treatment and prognosis of IVL are summarized in order to provide a single source of insightful information on IVL.

MR imaging findings of stage I intravenous leiomyomatosis: a retrospective single-center study in 19 cases.

OBJECTIVES: The aim was to explore the magnetic resonance imaging (MRI) features of stage-I intravenous leiomyomatosis (IVL). MATERIALS AND METHODS: From January 2019 to January 2023, clinical, pathological, and MRI data were collected from 19 cases confirmed by surgical pathology. Two radiologists retrospectively measured the tumor sizes, T1WIs, T2WIs, and ADC values and evaluated contrast-enhanced T1WIs, DWIs, complications and parauterine infiltrations. The number of tumor cells and the total nuclear area were measured. The percentage of tumor cell area out of the total area was used as the tumor cell density. RESULTS: Nineteen patients with stage-I IVL aged 33 to 66 years (mean age: 46 ± 7.6 years) were included in this study. All 19 cases were located in the myometrium or parametrium, with a mean diameter of 11.2 ± 4.8 cm. Among these cases, 14 (73.6%) were associated with leiomyoma, and six (31.6%) involved the broad ligament. Isointensity was observed in the T1WIs of 12 cases (63.2%), while slight hypointensity was seen in five patients (26.3%). Isointensity was observed in the on T2WIs of four cases (21.1%), and iso- or slight hyperintensity was observed in 15 cases (78.9%). A significant difference was detected between the normalized T2WIs of IVL and myometrium (p < 0.001). A Pearson correlation test showed demonstrated a negative correlation between the ADC and tumor cell density values (r = - 0.946, p < 0.001). Tortuous vessels were present in 17 cases (89.5%) within or next to the lesions, and multiple winding cord-like filling defects were seen in 11 cases (57.9%) within the tortuous vessels on the T2WIs. CONCLUSION: Identifying the characteristic MRI features of stage-I IVL helped improve the diagnostic accuracy achieves for this rare tumor. Stage-I IVL often presents as a large mass accompanied by leiomyoma, and it easily invades the broad ligament. TIWI signals exhibited isointensity, and T2WI signals contained iso- or slight hyperintensity. Tortuous vessels were present within or next to the lesions, and multiple winding cord-like filling defects were observed within the tortuous vessels on the T2WIs.