Can pelvic radiotherapy induce a leiomyosarcoma of the prostate? (A case report).

Leiomyosarcoma of the prostate is an extremely rare neoplasm. It represents less than 0.1% of all prostate malignancies. It is considered to have a poor prognosis, an aggressive nature, and high metastatic potential. Additionally, the relationship between radiation exposure for the treatment of primary prostatic cancer and the occurrence of leiomyosarcoma as second cancer at the irradiated site is rare, with unknown etiology. We reported a 72-year-old male known case of prostate adenocarcinoma with radio-hormonotherapy for six years who presented with acute urinary retention. Magnetic resonance imaging revealed a large malignant obstructive prostate with direct invasion of surrounding organs and multiple metastases. Trans-urethral resection of the prostate was performed, and the histopathology result showed high-grade leiomyosarcoma. The patient passed away after four months due to multiorgan failure. In conclusion, there may be a causal relationship between radiation therapy to the prostate and the development of prostate leiomyosarcoma.

Impact of Surgery and Chemotherapy on Metastatic Extrauterine Leiomyosarcoma.

Background: Few studies have described the characteristics and prognostic factors of patients with metastatic extrauterine leiomyosarcoma (euLMS). Therefore, we retrospectively investigated the clinicopathological features, clinical outcomes, and prognostic factors of patients with euLMS. Methods: We recruited 61 patients with metastatic euLMS treated from 2006 to 2020 and collected and statistically analyzed information on patient-, tumor-, and treatment-related factors. The median follow-up period was 21.1 months. Results: Sixty-one patients with euLMS and a median age of 59 years were included. Furthermore, their five-year overall survival (OS) rate was 38.3%. Univariate analysis revealed that primary tumor size >10 cm, synchronous metastasis, initial metastatic sites >1, and no metastasectomy with curative intent were significantly associated with poor OS rate. Multivariate analysis identified primary tumor size >10 cm as an independent prognostic factor for poor OS. Among 24 patients who received metastasectomy with curative intent, the interval from the initial diagnosis to development of metastasis ≤6 months was significantly correlated with unfavorable OS. Among 37 patients who did not receive metastasectomy, chemotherapy after metastasis development was significantly related to better OS. Conclusions: Complete metastasectomy should be considered for metastatic euLMS treatment. Moreover, chemotherapy could prolong survival in patients with metastasis who are ineligible for metastasectomy.

Sleeping Beauty Transposon Mutagenesis Identifies Genes Driving the Initiation and Metastasis of Uterine Leiomyosarcoma.

Uterine leiomyosarcoma (ULMS) is a malignancy, which arises from the uterine smooth muscle. Because of its rarity, aggressive nature, and extremely poor prognosis, the molecular mechanisms driving ULMS remain elusive. To identify candidate cancer genes (CCG) driving ULMS, we conducted an in vivo Sleeping Beauty (SB) transposon mutagenesis screen in uterine myometrium-specific, PTEN knockout, KRAS mutant (PTEN KO/KRAS) mice. ULMS quickly developed in SB PTEN KO/KRAS mice, but not in PTEN KO/KRAS mice, demonstrating the critical importance of SB mutagenesis for driving ULMS in this model. Subsequent sequencing of SB insertion sites in these tumors identified 19 ULMS CCGs that were significantly enriched in known cancer genes. Among them, Zfp217 and Sfmbt2 functioned at early stages of tumor initiation and appeared to be oncogenes. Expression of ZNF217, the human homolog of ZFP217, was shown to be elevated in human ULMS compared with paired normal uterine smooth muscle, where it negatively correlated with patient prognosis. Inhibition of ZNF217 suppressed, whereas overexpression induced, proliferation, survival, migration, and stemness of human ULMS. In a second ex vivo ULMS SB metastasis screen, three CCGs were identified that may drive ULMS metastasis to the lung. One of these CCGs, Nrd1 (NRDC in humans), showed stronger expression in human metastatic tumors compared with primary ULMS and negatively associated with patient survival. NRDC knockdown impaired migration and adhesion without affecting cell proliferation, whereas overexpression had the opposite effect. Together, these results reveal novel mechanism driving ULMS tumorigenesis and metastasis and identify ZNF217 and NRDC as potential targets for ULMS therapy. SIGNIFICANCE: An in vivo Sleeping Beauty transposon mutagenesis screen identifies candidate cancer genes that drive initiation and progression of uterine leiomyosarcoma and may serve as therapeutic targets.

Leiomyosarcoma: Does Location of Primary Help to Determine the Best Systemic Therapy Options?

OPINION STATEMENT: Management of leiomyosarcoma is based on the specifics of each individual case. Specifically, the location of the disease and whether the disease is metastatic or localized and if localized disease, whether the tumor is resectable or unresectable. In patients with recurrent or metastatic disease, factors such as disease-free interval and pattern of spread should be considered within the context of treatment planning. In general, patients with metastatic disease are typically treated with systemic chemotherapy with either an anthracycline-based regimen or gemcitabine-based regimen as first-line therapy. Additional systemic options include trabectedin, pazopanib, eribulin, and DTIC. Uterine LMS has been the most studied site-specific LMS with respect to systemic therapy. The increasing use of tumor genomics may ultimately define subsets which may benefit from tailored systemic therapies.

Radiation-induced leiomyosarcoma of oral cavity: Two cases with a review of literature.

Radiation-induced sarcoma is a rare entity, with leiomyosarcoma (LMS) in the oral cavity post radiation being extremely rare. We report two such cases who presented with swelling in the oral cavity with a history of moderately differentiated squamous cell carcinoma. Both cases prior to the diagnosis of LMS had been managed with surgery and radiation therapy and later developed swelling in the oral cavity. The management of LMS is uncertain; hence, this article aims to spread awareness about this rare diagnosis and to know the importance of differentiation from other more common lesions including recurrence.

Leiomyosarcoma After Liver Transplantation Is Unrelated to Epstein-Barr Virus: A Case Report.

BACKGROUND: De novo malignancy is a severe complication after liver transplantation (LT), but de novo leiomyosarcoma is extremely rare. METHODS: We reported de novo leiomyosarcoma occurring after LT. The patient's status for Epstein-Barr virus was negative. The donor was a 21-year-old man with a central nervous system malignancy who underwent surgery. Three months later brain death occurred and his organs were donated. RESULTS: Leiomyosarcoma in the recipient was detected shortly after LT. It progressed after minimization of immunosuppression and apatinib therapy, and the patient died of cachexia 17 months after LT. CONCLUSIONS: De novo leiomyosarcoma is a rare but serious event after LT, needing comprehensive management.

Unexpected uterine smooth muscle tumor of uncertain malignant potential and sarcoma: A single center cohort study in South Korea.

OBJECTIVE: To evaluate the risk of encountering unexpected uterine smooth muscle tumors of uncertain malignant potential (STUMPs) or sarcomas during surgical treatment of mesenchymal tumors of the uterus using morcellation. MATERIAL AND METHODS: Data were collected retrospectively from subjects who were pathologically diagnosed with uterine leiomyoma or its variants, STUMP or other premalignant mesenchymal tumors of uterus, or sarcoma during surgical treatment between July 2014 and June 2017. RESULTS: A total of 3785 women were investigated; 2824 laparoscopic procedures (74.6%) were performed, and an electronic power morcellator was used in 1636 patients (43.2%). Sixteen women (0.42%) were diagnosed with STUMP and 14 (0.37%) were diagnosed with uterine sarcoma. The incidence rate of unexpected STUMP or uterine sarcoma was 0.61% (23 of 3785 women); unexpected STUMP in 13 (0.34%), and unexpected sarcoma was in 10 (0.26%). Moreover, the unexpected leiomyosarcoma rate was 0.08% (3 in 3785). The rate of unintended morcellation of STUMPs was relatively high at 0.26% (10 in 3785), however, that for uterine sarcomas was 0.05% (2 in 3785). CONCLUSION: The risks of unintended morcellation were very low for sarcomas and STUMPs, although the risk of the latter was approximately 5-fold that of the former. To reduce the unintended dissemination of tumors, patients suspected of having malignancies should be provided adequate information regarding their treatment options as well as their associated risks. Meanwhile, improved preoperative screening methods for STUMP and sarcoma should be established.

An atypical presentation of leiomyosarcoma causing extremity compartment syndrome of the crural region in a Dutch Warmblood mare: a case report.

A 12-year-old Warmblood mare was presented with an acute onset left hindlimb lameness associated with generalised soft tissue swelling of the entire limb and medial saphenous vein (MSV) thrombophlebitis. A presumptive diagnosis of extremity compartment syndrome (ECS) was made. Due to the clinical deterioration, emergency fasciotomy of the crural fascia and biopsy was performed. Histological and immunohistochemical examination of the samples confirmed a diagnosis of leiomyosarcoma likely originating from the tunica media of the MSV. This report is the first to describe an unique combination of ECS and thrombophlebitis associated with a leiomyosarcoma in a horse.

Delayed use of eribulin in a heavily pretreated liposarcoma patient, previously misdiagnosed as leiomyosarcoma.

Due to its low incidence, liposarcoma displays a limited number of therapeutic options. However, eribulin recently received approval for the treatment of advanced liposarcoma patients, progressing to at least two chemotherapy lines. We report herein the case of a man initially diagnosed with a leyomiosarcoma, subsequently reclassified as a dedifferentiated liposarcoma, who received eribulin after he failed several therapy lines. Eribulin provided our patient an 8-month disease control and a substantial clinical benefit with no relevant adverse effects, showing a good efficacy and safety profile despite its delayed employ. Additionally, this case strengthens the pivotal importance of molecular profiling in the management of soft tissue sarcomas.

Postoperative radiotherapy-induced leiomyosarcoma in breast cancer: a case report and literature review.

Radiation-induced sarcoma (RIS) is a late complication of breast cancer radiotherapy, with a very low incidence, long latent period and poor prognosis. Among them, leiomyosarcoma after radiation is an extremely rare radiation-associated sarcoma. In this study, we report a case of radiation-induced leiomyosarcoma 2 years after postoperative radiotherapy for breast cancer. After the diagnosis of leiomyosarcoma, the patient received radical resection of the left chest wall leiomyosarcoma. The patient showed no relapse or progression during the follow-up time of 1 year after operation. Rare occurrence of RIS induced by postoperative radiotherapy in breast cancer and limited experience concerning its diagnosis and treatment bring obstacle to both patients and doctors. Preoperative examinations must be carefully refined. With a perfect coordination between different disciplines, RIS induced by postoperative radiotherapy in breast cancer can be ideally treated with better prognosis.

Leiomyosarcoma in Birt-Hogg-Dubé Syndrome.

Birt-Hogg-Dubé syndrome (BHDS) is an autosomal dominant genodermatosis characterized by benign cutaneous tumors (fibrofolliculomas, trichodiscomas, and acrochordons), basal lung cysts, pneumothoraces, and a 20% to 30% lifetime risk for renal cancer. There are isolated cases of other cancers in BHDS reported in the literature, including oncocytoma, rhabdomyoma, melanoma, thyroid cancer, meningioma, colon cancer, and breast cancer, but only the increased renal cancer risk has been substantiated. This is the case of a 9-year-old girl who presented with a leiomyosarcoma whose tumor genetic analysis showed FLCN c.365_372del, p.Arg122Leufs*8. She was diagnosed with BHDS when the same mutation was confirmed in her germline lymphocytes. This is the second known reported case of leiomyosarcoma in BHDS.

Evaluation of occult uterine leiomyosarcomas.

OBJECTIVES: To determine the frequency of occult uterine leiomyosarcomas following hysterectomies and myomectomiesperformed for benign reasons at our clinic and to draw comparisons with similar studies in the literature. MATERIAL AND METHODS: All hysterectomies and myomectomies that have been performed for benign reasons at our clinicbetween 2010 and 2017 were retrospectively examined via the hospital's information system and the patients that werefound to have leiomyosarcomas were analysed. The incidence of occult uterine leiomyosarcoma per 1000 surgeries at ourclinic was calculated using the Wilson score interval. RESULTS: A total of 6,173 hysterectomies were performed, and occult uterine leiomyosarcoma was identified in 5 patients. Theincidence of occult uterine leiomyosarcoma was calculated to be 0.08% (95% CI 0.03-0.018%). Only 1 of the 771 patientswho underwent myomectomy was identified with occult uterine leiomyosarcoma, making its incidence in myomectomy0.12% (95% CI 0.02-0.073%). When all the patients are considered, occult uterine leiomyosarcoma was identified in 6 of the6,944 patients, and the general incidence of occult uterine leiomyosarcoma was calculated as 0.08% (95% CI 0.03-0.018%). CONCLUSIONS: In our study, the incidence of occult uterine sarcoma following myomectomy and hysterectomy was foundto be lower than that reported in the literature. The reason for this lower incidence includes not only genetic causes andracial differences but also preoperative imaging, endometrial and cervical sampling that is performed on every patient.

Ovarian and uterine leiomyosarcoma: which one is the primary?

Uterine leiomyosarcoma (LMS) is rare but primary ovarian LMS is even rarer constituting less than 0.1% of all gynecologic disorders. Neither histologic features nor immunohistochemistry could be utilized to distinguish between uterine or ovarian origin. We illustrate a clinical case of metastatic LMS to the ovary in a woman with underlying uterine fibroid presenting with anemia with heavy menses.

Metastatic Osteolytic Angioleiomyosarcoma Induced by a Foreign Body in a Kangaroo (Macropus giganteus).

An adult female Eastern Grey kangaroo (Macropus giganteus) was examined for lameness due to a mass located at the right tibiotarsal joint. Radiographs revealed a metal arrowhead-shaped foreign body within the mass alongside a pathologic fracture. Grossly, at necropsy, there was a multilobulated and haemorrhagic mass with intralesional metal fragments, associated osteolysis of the tibiotarsus and pulmonary metastatic nodules. Histologically the neoplasm was composed of plump elongated and fusiform cells that often formed concentrically around small vessels. The pulmonary nodules were composed of similar neoplastic cells, necrosis and haemorrhage. Neoplastic cells were positive immunohistochemically for vimentin and smooth muscle actin. The histological features, immunohistochemical profiles and behaviour of this tumour support a diagnosis of a primary angioleiomyosarcoma with lung metastasis associated with a metal foreign body.

Power morcellation-induced dissemination of sarcomatous component arising in leiomyoma.

In 2014, the US Food and Drug Administration issued a safety communication warning against the use of power morcellators during laparoscopic hysterectomy or myomectomy. We report a case of peritoneal leiomyosarcomatosis attributable to power morcellation. A 49-year-old nulligravid woman presented with a huge uterine tumor measuring 15 × 8 cm that was diagnosed as benign leiomyoma on magnetic resonance imaging. The uterine tumor had shrunk to 13 × 7 cm after five treatment courses with a gonadotropin-releasing hormone agonist. She underwent laparoscopic hysterectomy using power morcellation; postoperative pathological diagnosis was benign leiomyoma. After 6 months, urinary ascites developed because of right ureteral rupture. She underwent laparotomy and was diagnosed with peritoneal leiomyosarcomatosis. Meticulous and thorough reevaluation of the morcellated specimens revealed a small component of leiomyosarcoma. Use of power morcellation should be minimized until the advent of novel methods that can perfectly differentiate benign from malignant uterine tumors preoperatively.

Laparoscopic myomectomy and morcellation: A review of techniques, outcomes, and practice guidelines.

Laparoscopic myomectomy is a minimally invasive surgical approach to treat symptomatic uterine fibroids in women wishing for a uterine-sparing procedure. With careful patient selection, these procedures are associated with favorable reproductive outcomes and low perioperative morbidity. Current available methods for specimen retrieval include power and hand morcellation. The 2014 FDA safety warnings regarding power morcellation arose from concerns about the spread of occult malignancy and prompted widespread use of containment systems that may limit spread of myometrial cells. Investigation into the clinical effects of laparoscopic myomectomy and uncontained morcellation on the prognosis and spread of occult leiomyosarcoma has yielded mixed results. Other complications of uncontained power morcellation exist, including the development of parasitic leiomyomas. The FDA safety warnings have greatly influenced trends in benign gynecologic surgery, and survey data reflect trends in providers' opinions of these trends. In conclusion, recommendations for the current practice of laparoscopic myomectomy and morcellation are reviewed.

Leiomyosarcoma of scrotum: A rare in-field second malignancy in a previously irradiated carcinoma of prostate and review of literature.

BACKGROUND: Curative intent treatments for malignancies using radiation therapy while achieving longer disease-free survivals, may also lead to solid second malignancies, a dreaded late complication. Both in-field as well as out-field second malignancies are encountered and lead to diagnostic dilemma, and delay in treatment. MATERIALS AND METHODS: Details of a case of rare, in-field, radiation induced leiomyosarcoma, a rare soft tissue sarcoma, in a treated case of high risk carcinoma of prostate, who presented to our tertiary care centre was retrieved and analysed. CONCLUSION: Increasingly sophisticated radiotherapy techniques, while providing state of the art treatment options, does increase the potential risk of radiation-induced second-malignancies. Respecting integral-dose carries priority, until further studies elucidates mechanism of tumorigenesis.

The importance of treating by histological subtype in advanced soft tissue sarcoma.

While surgical resection (±radiotherapy) is standard treatment for localized soft tissue sarcomas (STS), chemotherapy is the mainstay for managing locally advanced and metastatic disease. Expanding knowledge of the biologies and sensitivities of STS histotypes, in conjunction with results from a growing collection of retrospective reviews and prospective randomized studies, point to the importance of treating in consideration of histological subtype. Doxorubicin ± ifosfamide continues to be standard first-line therapy for most STS subtypes. Main options for second- or later-line therapy include trabectedin, dacarbazine, gemcitabine combinations, pazopanib and, most recently, eribulin. Using illustrative case studies, treatment options are reviewed for three of the more common STS subtypes - uterine leiomyosarcoma, liposarcoma and synovial sarcoma - with a focus on use of trabectedin.