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.

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.

Leiomyomatosis peritonealis disseminata in laparoscopic port site and abdomino-pelvic cavity: A case report.

Leiomyomatosis peritonealis disseminata (LPD) is a rare clinical condition characterized by the development of multiple smooth muscle-like nodules in the peritoneal or abdominal cavity. Here, we report a case of a patient who was diagnosed with LPD after laparoscopic myomectomy with power morcellation. Growing evidence has shown that LPD might develop after using power morcellation for hysterectomy or myomectomy, and this can worsen the prognosis if the spreading tissue contains malignancies, such as leiomyosarcoma. Thus, it is crucial to use laparoscopic morcellation for gynecologic procedures cautiously, and the use of a containment system is even better. If LPD develops without evidence of malignancy, the primary treatment is surgical intervention, and gonadotropin-releasing hormone agonists, aromatase inhibitors, and selective progesterone receptor modulators can be prescribed as adjuvant therapies for recurrent or refractory cases.

Treatment of leiomyomatosis peritonealis disseminata with goserelin acetate: A case report and review of the literature.

BACKGROUND: Leiomyomatosis peritonealis disseminata (LPD) is a rare condition characterized by multiple pelvic and abdominal nodules, which are composed of smooth-muscle cells. To date, no more than 200 cases have been reported. The diagnosis of LPD is difficult and there are no guidelines on the treatment of LPD. Currently, surgical excision is the mainstay. However, hormone blockade therapy can be an alternative choice. CASE SUMMARY: A 33-year-old female patient with abdominal discomfort and palpable abdominal masses was admitted to our hospital. She had undergone four surgeries related to uterine leiomyoma in the past 8 years. Computed tomography revealed multiple nodules scattered within the abdominal wall and peritoneal cavity. Her symptoms and the result of the core-needle biopsy were consistent with LPD. The patient refused surgery and was then treated with tamoxifen, ulipristal acetate (a selective progesterone receptor modulator), and goserelin acetate (a gonadotropin-releasing hormone agonist). Both tamoxifen and ulipristal acetate were not effective in controlling the disease progression. However, the patient achieved an excellent response when goserelin acetate was attempted with relieved syndromes and obvious shrinkage of nodules. The largest nodule showed a 25% decrease in the sum of the longest diameters from pretreatment to posttreatment. Up to now, 2 years have elapsed and the patient remains asymptomatic and there is no development of further nodules. CONCLUSION: Goserelin acetate is effective for the management of LPD. The long-term use of goserelin acetate is thought to be safe and effective. Hormone blockade therapy can replace repeated surgical excision in recurrent patients.

Leiomyomatosis peritonealis disseminata mimicking peritoneal carcinomatosis 13 years after laparoscopic uterine myomectomy: A case report.

INTRODUCTION: Leiomyomatosis peritonealis disseminata (LPD) is a rare clinical condition that can be challenging to diagnose because its clinical features mimic other conditions. We present a case of LPD mimicking peritoneal carcinomatosis 13 years after laparoscopic uterine myomectomy using a power morcellator. The aim of this paper is to report a rare case which surgeons can learn from and to provide more clinical information for further studies to investigate LPD. PRESENTATION OF CASE: A 49-year-old woman was referred to us because sonography revealed abnormal abdominal and pelvic nodules. Thirteen years previously, she had undergone laparoscopic uterine myomectomy using a power morcellator. An exploratory laparotomy revealed nodules on the peritoneum, greater omentum, intestinal mesentery, and terminal ileum. We surgically removed all visible nodules and performed bilateral salpingo-oophorectomy. LPD was confirmed based on the morphology and immunohistochemistry results. DISCUSSION: Diagnosing LPD preoperatively may be difficult because its clinical manifestations resemble peritoneal carcinomatosis or metastatic lesions. Abdominal pain due to diffuse tumor growth is a common manifestation. LPD degenerating into malignancy is rare, but possible. The probable etiological factors, clinical manifestations, and treatment options which may aid when dealing with LPD have been described in this report. CONCLUSION: LPD should be considered in women, particularly those with a history of gynecologic surgery presenting with disseminated intraabdominal or pelvic tumors.

Leiomyomatosis Peritonealis Disseminata: A Clinical Analysis of 13 Cases and Literature Review.

Objective. Leiomyomatosis peritonealis disseminata (LPD) is a rare benign disease that is characterized by numerous small muscle nodules disseminated in the abdominal and pelvic cavity. This study analyzed the clinical features, pathologic characteristics, and prognosis of LPD. Methods. We retrospectively analyzed the clinical data of 13 patients with pathologically diagnosed LPD in Shengjing Hospital of China Medical University from January 2001 to January 2018. Results. Overall, 13 cases were collected. The mean age of the 13 patients was 42.23 years (range = 26-51 years). In all 13 female patients, 11 had a surgical history related to uterine leiomyoma, and only 2 had no history of treatment. Most of them were asymptomatic. Thirteen patients underwent resections of the tumors by laparoscopy or laparotomy. Pathological reports of 13 cases indicated LPD. Twelve cases were followed up, and 1 case was lost to follow-up. The median follow-up time was 65.67 months, and 2 patients showed evidence of recurrence. Conclusions. LPD is a rare disease in women of reproductive age. LPD manifests atypical symptoms, which can be easily misdiagnosed and confirmed by the pathological diagnosis. Surgery is the main treatment. Although LPD is a benign disease, a few patients had a tendency for recurrence or malignancy. Therefore, strict follow-up is needed.

Large leiomyomatosis peritonealis disseminata after laparoscopic myomectomy: A case report with literature review.

INTRODUCTION: Leiomyomatosis peritonealis disseminata (LPD) is a rare disease in which multiple leiomyomas are formed intraperitoneally. Several LPD cases were associated with laparoscopic myomectomy using power morcellators; however, LPD with a large tumor size remains extremely rare. We present a case of large LPD occurring after laparoscopic surgery. PRESENTATION OF CASE: A 26-year-old woman, gravida 0, underwent laparoscopic myomectomy with power morcellation in our institution. After 5 years, follow-up examination revealed pelvic tumors. Although we recommended resection, she refused and only wanted to be followed up. After 9 years from the first surgery, the tumors became symptomatic and were increasing in number (>10 nodules) and size (>15 cm). Needle biopsy detected leiomyoma. Computed tomography angiography showed that omental and mesenteric arteries were feeding the tumors. We performed laparotomy, and all the 19 tumors emerging from the omentum and mesenterium and weighing 7647 g in total were removed without injuring other organs. The maximum diameter of the largest tumor was 34 cm. The pathological diagnosis was nonmalignant LPD with leiomyoma. DISCUSSION: Among all reported cases, our case had the largest LPD size. The tumors reached such a huge size because of two possible reasons: (1) they gradually grew asymptomatically over a long period from the time of diagnosis, and (2) they were fed by particularly large vessels, including the omental and mesenteric arteries. CONCLUSION: A large LPD is not always symptomatic. After a laparoscopic myomectomy, especially with power morcellation, long-term follow-up is necessary to detect LPD.

[Extra uterine leiomyomatosis: Review of the literature]. / La léiomyomatose extra-utérine : revue de la littérature.

Extra-uterine leiomyomatosis is a rare pathology defined by the presence of benign smooth uterine muscle cells in unusual localizations, including different entities. It mainly affects premenopausal women with a medical history of uterine myoma with or without surgical treatment. Three main types are discribed: intraveinous leiomyomatosis, benign metastatisizing leiomyoma and leiomyomatosis peritonealis disseminata. The diagnosis may be complex with many differential diagnosis, and relies on histology. The treatment depends on multiple factors such as age, localization, size, symptoms and associated comorbidities. It is based on surgical resection and hormonal privation, surgical (adnexectomy) or medical (hormonotherapy). There is a high risk of recurrence. Some malignant evolutions have been reported, mostly leiomyosarcoma following peritoneal disseminated leiomyomatosis. Long term follow-up of these patients is mandatory. A particular manifestation of extra-uterine leiomyomatosis is the hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. It is an autosomal dominant disorder which confers an increased risk of cutaneous and uterine leiomyomas and renal cell cancer, with a poor prognosis due to the urologic tumor.

Simultaneously occurring disseminated peritoneal leiomyomatosis and multiple extrauterine adenomyomas following hysterectomy.

Disseminated peritoneal leiomyomatosis (DPL), also known as leiomyomatosis peritonealis disseminata, is a rare condition characterized by multiple benign smooth muscle tumors proliferating along the peritoneal surfaces. In previous case reports, these tumors have been noted to involve the ovaries, round ligaments, bladder, bowel, peritoneum, and mesentery. To date, approximately 150 cases of DPL have been described in the literature. Extrauterine adenomyoma is an even rarer entity, involving benign tumors composed of smooth muscle tissue, endometrial glands, and endometrial stroma arising outside the uterus. Only 22 cases have previously been reported. We describe a woman presenting with both DPL and multiple extrauterine adenomyomas several years after undergoing laparoscopic morcellated hysterectomy.

Disseminated Peritoneal Leiomyomatosis After Uterine Artery Embolization.

Disseminated peritoneal leiomyomatosis (DPL) is a rare variant of extrauterine leiomyomatosis with reported spontaneous and iatrogenic occurrences. It has been associated with hysterectomy and myomectomy. To our knowledge, reports have not yet substantiated occurrence following uterine artery embolization (UAE), which has become a routine minimally invasive alternative to surgery for the treatment of symptomatic leiomyomata. This report presents the case of a nulliparous premenopausal woman with no other contributory history who presented with DPL 3 years after UAE. The presentation of this patient suggests the potential for a causal relationship between UAE and DPL.

Leiomyomatosis peritonealis disseminata: A case report of recurrent presentation and literature review.

INTRODUCTION: Leiomyomatosis peritonealis disseminata (LPD) is an uncommon disease featured by the presence of multiple nodules of smooth muscle cells scattered in the abdominal cavity. To date only about 150 cases have been reported in literature. We report a case of recurrent LPD after laparotomy. CASE PRESENTATION: In March 2016 a 36-year-old female, with a history of multiple previous laparoscopic myomectomies, consulted her gynaecologist complaining abdominal pain; a MRI was performed and reported multiple pelvic masses, subsequently excised during laparotomy. The patient refused a total hysterectomy with bilateral salpingo-oopherectomy so a close follow-up was recommended. In November 2017 when a new MRI revealed recurrency of the disease, a second laparotomy is performed and all visible nodules are excised. The histological exam confirms LPD diagnosis. On follow-up after three months the patients is completely asymptomatic. DISCUSSION: Differential diagnosis of LPD is challenging due to its similarity to carcinomatosis and to other benign abdominal disorders. Malignant transformation is rare, but it may occur, so a close follow-up is necessary. Even if there is no consensus regarding the treatment, hormonal therapy is probably the best first line approach, while surgery should be the second choice. CONCLUSIONS: LPD is an uncommon but potentially severe disease. In our opinion larger studies are necessary to improve our diagnostic effectiveness and to define the best therapeutic strategy.

Leiomyomatosis peritonealis disseminata: A case report and meticulous review of the literature.

INTRODUCTION: Leiomyomatosis peritonealis disseminata (LPD) is a peculiar benign clinical disorder characterized by proliferation of peritoneal and subperitoneal nodules. LPD is a difficultly diagnosed benign disease that rarely degenerates into malignancy. PRESENTATION OF CASE: A 40-year-old Caucasian female with vaginal bleeding proceeded to our institution for elective excision of abdominal and pelvic masses which were firstly considered as leiomyosarcomas. The histologic diagnosis of the mass lesions revealed smooth muscle benign cells. This is the first case of LPD reported in Greece. A meticulous review of the literature was conducted as well. DISCUSSION: The differential diagnosis of LPD is difficult due to its clinical resemblance with peritoneal carcinomatosis or metastatic lesions and with benign metastasizing leiomyoma (BML) as well. Etiological factors, pathophysiology and clinical manifestations which lead to a safe diagnosis of LPD are adequately described. CONCLUSION: Surgeons' thorough knowledge concerning this rare clinical condition is fundamental and crucial in order to establish a correct diagnosis and assert the appropriate treatment and the minimization of the probability of malignant transformation of LPD.

Long-term efficacy and safety of aromatase inhibitor use for leiomyomatosis peritonealis disseminata.

Leiomyomatosis peritonealis disseminata is a rare disease characterized by pelvic smooth-muscle nodules of various sizes. It is sometimes misdiagnosed as ovarian or peritoneal carcinoma metastasis; therefore, surgical excision for pathological diagnosis is required. Treatment options include bilateral salpingo-oophorectomy (BSO), gonadotrophin-releasing hormone agonist therapy, and aromatase inhibitor therapy. All of these suppress estrogen levels, but a standard treatment has not been established. A 40-year-old woman had multiple pelvic tumors, suspicious for ovarian cancer. She underwent laparotomy, where frozen sections of the nodules revealed leiomyomatosis peritonealis disseminata. After she completed gonadotrophin-releasing hormone agonist therapy, we performed a total abdominal hysterectomy and BSO with residual-nodule resection, but the nodules recurred 6 months after surgery. We then started letrozole, and 3 years have now elapsed without nodule enlargement or development of new lesions. The long-term use of aromatase inhibitor therapy is thought to be effective and safe for patients with recurrence after BSO.

Coexisting leiomyomata peritonealis disseminata and ovarian leiomyoma.

Leiomyoma is the most common tumor seen affecting women mostly of reproductive age groups. It is composed of smooth muscle cells that are positive for smooth muscle actin on immunohistochemistry. Leiomyomata peritonealis disseminata (LPD) is characterized by nodules that stud the peritoneum. It is seen in association with hormone-producing ovarian tumors and coexisting leiomyomas of the uterus. Association with mesenteric leiomyomas has been reported. Ovarian leiomyomas are very rare tumors of the ovary and coexisting LPD with ovarian leiomyomas has not been reported before. We present this rare case of LPD and ovarian leiomyoma.

Leiomyomatosis peritonealis disseminata: A case report and review of the literature.

Leiomyomatosis peritonealis disseminata (LPD) is a rare smooth muscle tumor, which is characterized by the dissemination of multiple smooth muscle-like nodules throughout the omental and peritoneal surfaces. The present report describes the case of a 33-year-old woman who had previously undergone laparoscopic myomectomy due to a bizarre leiomyoma. Five years after the initial operation, the patient was referred to our hospital with irregular episodes of right abdominal pain. As the presentation was highly suspicious of malignant uterine tumor metastasis or LPD, the patient subsequently underwent laparoscopic total hysterectomy, bilateral salpingo-oopherectomy, omental resection and excision of some of the disseminated nodules. Histological examination confirmed the diagnosis of LPD. Under laparoscopic examination, LPD must be distinguished from metastatic leiomyosarcoma and other malignant conditions. Frozen section biopsy examination may help with the diagnosis, but the final diagnosis relies on pathological examination. The etiology of LPD includes several theories, such as the hormonal, genetic and iatrogenic theories. A gonadotropin-releasing hormone agonist may be successful in shrinking the nodules. In women who have completed their families, total abdominal hysterectomy, salpingo-oophorectomy, omentectomy and debulking appears to be the optimal treatment.

Leiomyomatosis Peritonealis Disseminata (LPD) ten years after laparoscopic myomectomy associated with ascites and lymph nodes enlargement: a case report.

INTRODUCTION: We report a case of leiomyomatosis peritonealis disseminata (LPD) arising 10 years after a laparoscopic myomectomy that was associated with ascites and lymph nodes enlargement. PRESENTATION OF CASE: The patient presented with small uterine fibroids with a dominant posterior intramural fibroid measuring 9cm in diameter and normal Doppler. Laparotomy revealed a uterus enlarged with fibroids, which was densely adhering to the urinary bladder, greater omentum, and sigmoid colon. Multiple tumors of different size were found attached to the peritoneum, omentum and bowel. The histopathologic examination was consistent with leiomyomatosis peritonealis disseminata. DISCUSSION: Pieces of smooth muscle cell lost in the abdominal cavity during electrical morcellation after laparoscopic myomectomy may progress to leiomyomatosis peritonealis disseminata even after many years (ten in our case) and it can be associated with ascites and lymph nodes enlargement. CONCLUSION: This is the first case reported in literature of leiomyomatosis peritonealis disseminata with these particular features (time of clinical presentation, ascites, lymph nodes enlargement).

Iatrogenic parasitic leiomyoma and leiomyomatosis peritonealis disseminata following uterine morcellation.

AIM: To assess the impact of morcellation on the spread of uterine leiomyoma. METHODS: Cases of parasitic leiomyoma involving prior laparoscopy were collected between 2012 and 2015 in a tertiary women's hospital in China. Their clinicopathological features and the associated reports were reviewed. RESULTS: All six patients with parasitic leiomyoma had laparoscopic myomectomy or hysterectomy with power morcellation 39-132 months previously. Patient 1 had widely disseminated tumors in the peritoneum and pelvis, in keeping with leiomyomatosis peritonealis disseminata (LPD). She received debulking of peritoneal tumors and lived with disease for 22 months. The implanting sites of the other parasitic tumors (patients 2-6) included the mesentery (n = 2), intestine (n = 1), pelvic parietal (n = 1), bladder (n = 1), and musculus rectus abdominis (n = 1). The diameter varied from 1 cm to 6 cm. The patients underwent abdominal subtotal hysterectomy, cervicectomy or tumor debulking and the postoperative course was unremarkable for a period of 2-32 months. Pathologically, these disseminated or parasitic leiomyomas did not show any evidence of malignancy. There were no morphological or immunohistochemical differences between the original tumor and the following seeding tumors. On literature review, 11 iatrogenic LPD have been reported after laparoscopic surgery for uterine leiomyoma. These cases may provide an alternative pathogenic mechanism for a distinct variant of LPD. CONCLUSIONS: Laparoscopic hysterectomy with tumor morcellation may increase the chance of tumor implantation and dissemination. Both clinicians and pathologists should be alert to this rare complication.

Leiomyomatosis peritonealis disseminata of unusual course with malignant transformation: case report.

Leiomyomatosis peritonealis disseminata is a very rare, benign entity of unknown pathogenesis, characterized by the presence of multiple subperitoneal or peritoneal smooth muscle nodules throughout the peritoneal surface. Mostly the course is asymptomatic and it is found incidentally during laparotomy, laparoscopy or cesarean section. Non-specific symptoms such as abdominal pain, vaginal bleeding, abdominal mass or gastrointestinal signs are described. Rare cases of malignant transformation have been reported. We present a case of disseminated peritoneal leiomyomatosis with an unusual course and transformation to endometrial sarcoma in a 26-year-old previously healthy woman, where the appearance of peritoneal nodules was preceded by multiple incidents of fast fibroid growth and delivery of myomatous growth into the cervical canal.