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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.

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., (©2021 American Association for Cancer Research.)

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., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., Competing Interests: None

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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.

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., Competing Interests: Declaration of Competing Interest The all authors did not report any potential conflicts of interest., (Copyright © 2020. Published by Elsevier B.V.)

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.

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.

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.

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.

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., (Copyright © 2017. Published by Elsevier Ltd.)

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.

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.

Introduction: Patients treated with radiotherapy are under increased long-term risk of developing radiation-induced tumors. In this report we present an exceptionally rare case of a patient who, following radiotherapy for cervical cancer, developed 3 radiation-induced metachronous pelvic tumors., Case Presentation: In 1997, a 37-year-old patient with cervical adenocarcinoma (FIGO stage IB2) was subjected to adjuvant conventionally fractionated external-beam radiation therapy and brachytherapy following surgical treatment. Eleven, 14 and 15 years later, 3 radiation-induced malignant tumors developed: a leiomyosarcoma of the gluteus and 2 separate carcinomas of the rectum., Discussion and Conclusion: Radiotherapy for cervical carcinoma increases the standardized incidence ratios for rectal cancer and soft tissue sarcoma. Unfortunately, the current guidelines on contraindications to radiotherapy appear insufficient as they take into account a very limited number of clinical states and associated conditions, which is in disproportion to the rather high risk of radiation-induced malignancies of 0.45%. Information on the molecular characteristics of human radiation-induced tumors is still of no relevance for everyday clinical practice. Although radiotherapy is one of the most important modalities of oncological treatment, it should be judiciously used in cases where the benefits clearly outweigh the risk of serious untoward effects. In the case of patients undergoing pelvic irradiation, careful follow-up is needed for years.

Fibroids are the most common tumor in women and many medical and surgical options exist for their management. The incidence of uterine sarcoma in women undergoing treatment for fibroids has previously been thought to be extremely rare, however there has been recent controversy as to whether this risk has been underestimated. This article reviews the literature investigating the incidence of leiomyosarcoma and explores how different treatment modalities may affect risk from occult malignancy. We aim to provide a tool for counseling women who are considering options for the management of their fibroids.

Leiomyosarcoma of the rectum can develop as a late complication in patients with a history of pelvic irradiation. We report the case of a patient who developed rectal leiomyosarcoma 13 years after receiving radiation for treatment of a stage 2 squamous cell cancer of the anus. This was detected on physical examination. Based on a discussion with the patient, we decided to manage conservatively. Overall, leiomyosarcomas constitute 5-12% of radiation-induced sarcomas. Rectal leiomyosarcoma is rare, accounting for 0.1-0.5% of all malignant tumours of the rectum. As radiation therapy plays a major role in the management of anal cancer, it is important that clinicians are aware of the possible development of radiation-induced sarcomas that may occur decades after initial management., (2014 BMJ Publishing Group Ltd.)

Purpose: The study was designed to investigate the influence of surrogate factors associated with sex (SH) and growth hormones (GH) on the risk of developing soft tissue sarcomas (STS)., Background and Methods: The etiology of soft tissue sarcoma is largely unknown. We have studied the effect of hormone related factors on STS in the Swedish population between 1988 and 2009 using a population-based matched case-control design., Results: Our study is the largest on this topic to date, including 634 cases in a primary matched analysis and 855 cases in an unmatched sensitivity analysis. We identified protective effects connected to constitutional characteristics, hormonal and reproductive factors. Being shorter than your peers at age 11 was associated with an odds ratio (OR) of 0.51 (0.36-0.74). Having used oral contraceptives (OC), OR 0.75 (0.49-1.15), and high parity, OR 0.16 (0.04-0.63), comparing three or more children to two or less, also appeared to reduce the risk of STS. The risk was further reduced with the duration of OC use (p = 0.01), comparing use for 11 years or more to use for 3 years or less yielded an OR of 0.10 (0.02-0.41). No effect was observed for ever having had perimenopausal hormone therapy OR 1.02 (0.70-1.47). The effect of BMI varied significantly with subtype (p = 0.03) and tumor location (p < 0.001)., Conclusions: We observed surrogates of SH, GH, and insulin-like growth factor 1 to be associated with STS development. These findings are important as they may connect STSs to the group of hormone-dependent tumors, potentially revealing common treatment and prevention targets.

Primary adrenal leiomyosarcoma has been reported previously in 25 patients. The patient presented herein is the only case where the definitive diagnosis was made with core needle biopsy evaluation. A 45-year-old male presented with pain in the back and right groin. Radiological evaluation demonstrated a heterogeneous 11 cm right adrenal mass, multiple liver masses, and an enlarged aortocaval lymph node. No retroperitoneal mass was identified. Core needle biopsies revealed a malignant mesenchymal neoplasm composed of atypical spindle shaped cells arranged in intersecting fascicles, with high mitotic activity and focal tumor necrosis. Immunohistochemical stains revealed immunoreactivity for smooth muscle actin and desmin. S-100 and c-kit stains were negative. The diagnosis of adrenal leiomyosarcoma with liver metastasis was rendered. It was an aggressive tumor with clinical presentation at Figure 1. Core needle biopsy, a an advanced stage. Definitive diagnosis of this tumor by core needle biopsy can obviate the need for surgical biopsy in patients with advanced disease.

This article presents an overview of the current literature about the biology, pathology, and the clinical management of leiomyosarcoma. In addition, the article emphasizes and discusses the current systemic treatment options available for patients with leiomyosarcoma, which range from cytotoxic chemotherapy to target therapies. Particular leiomyosarcoma subtypes, such as uterine leiomyosarcoma and inferior vena cava leiomyosarcoma, are discussed separately., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Here, we report the case of a patient with a non-seminoma of the left testicle, with an intestinal-type adenocarcinoma and a low grade leiomyosarcoma in a late recurrence 19 years after initial diagnosis. The history of the patient, alive with disease 21 years after initial treatment, illustrates the potential and flaw of the cancer stem cell therapy concept. In addition, it is proposed that residual mature teratoma can be regarded as normalization of cancer due to embryonic patterning, and the development of a secondary somatic-type malignancy as failure of normalization.

Li-Fraumeni syndrome (LFS) is one of the most penetrant forms of familial cancer susceptibility syndromes, characterized by early age at tumor onset and a wide spectrum of malignant tumors. Identifying LFS in patients with cancer is clinically imperative because they have an increased sensitivity to ionizing radiation and are more likely to develop radiation-induced secondary malignancies. This case report describes a young woman whose initial presentation of LFS was early-onset breast cancer and whose treatment of this primary malignancy with breast conservation likely resulted in a secondary malignancy arising in her radiation field. As seen in this case, most breast cancers in patients with LFS exhibit a triple-positive phenotype (estrogen receptor-positive/progesterone receptor-positive/HER2-positive). Although this patient met classic LFS criteria based on age and personal and family history of cancer, the NCCN Clinical Practice Guidelines in Oncology for Genetic/Familial High-Risk Assessment: Breast and Ovarian Cancer endorse genetic screening for TP53 mutations in a subset of patients with early-onset breast cancer, even in the absence of a suggestive family history, because of the potential for de novo TP53 mutations.

We report a case of pulmonary bilateral multiple chondromas that were possibly an initial clinical presentation of Carney's triad. A 56-year-old Japanese non-smoking asymptomatic woman was admitted to the hospital for further examination of small, multiple, bilateral nodules in the lungs. Although chest radiological findings suggested that the nodules were possibly metastatic pulmonary tumors, the malignant origin was not detected. During diagnostic video-assisted thoracic surgery, wedge resections including the nodules were performed. Since pathological examination showed nodules were surrounded by fibrous and eosinophilic stroma, we diagnose the nodules as chondromas. These chondromas were possibly components of Carney's triad, because each nodule had a thin fibrous pseudocapsule and did not have an entrapped epithelium and fat. Some patients die of Carney's triad because of malignant alteration of lesions. Therefore, the patients with Carney's triad should be taken a medical check periodically. This patient was scheduled to undergo the check-up for several years.

Objective: To determine the frequency of skin cancers associated with chronic leg ulcers (CLUs) presumably of vascular origin and failing to heal (ie, increased wound area or depth) despite 3 months or more of appropriate treatment., Design: Prospective cross-sectional study., Setting: Ambulatory or hospitalized patients from 17 dermatology departments., Patients: Between January 1, 2006, and May 31, 2008, a total of 144 patients consulted for CLUs, attributed to venous and/or peripheral arterial disease(s), increasing in wound size, that is, larger area and/or depth, despite appropriate standard treatment for at least 3 months., Main Outcome Measures: At inclusion, at least two 6-mm punch biopsies, 1 at the wound edge and 1 in the wound bed, in the most clinically suspicious areas, were systematically performed. The primary end point was the skin cancer frequency diagnosed in at least 1 wound biopsy specimen obtained at inclusion., Results: The 144 patients included had 154 CLUs. The overall skin cancer frequency in the CLUs was 10.4%: 9 squamous cell and 5 basal cell carcinomas, 1 melanoma, and 1 leiomyosarcoma; 56.3% had persisted for at least 3 years. Univariate analyses retained older age, abnormal excessive granulation tissue at wound edges, high clinical suspicion of cancer, and number of biopsies, but not wound area or duration, as being significantly associated with skin cancer in 1 or more biopsy specimens., Conclusions: The combined primary ulcerated cancer or malignant transformation frequency was sufficiently high in CLUs referred to tertiary care centers to consider systematic biopsy of a wound refractory to 3 months or more of appropriate treatment.

Rectal leiomyosarcomas are very rare mesenchymal tumours. This is a case report of a rectal leiomyosarcoma diagnosed initially as a leiomyoma in a patient who had undergone pelvic radiotherapy several years previously. In addition to its pathological rarity, this case is of particular interest because it reinforces the association between pelvic irradiation and rectal leiomyosarcomas and it highlights the importance of treating suspicious cases aggressively in spite of favourable preoperative radiological and histological assessment.

The incidence of neoplastic complications after solid organ transplantation is increasing tremendously probably as the consequence of long term immunosuppression. Beside usual risk factors, the oncogenic role of some viruses like Epstein-Barr virus is well established. We report a case of a primitive EBV-induced liver leiomyosarcoma after renal transplantation., (Copyright © 2010. Published by Elsevier Inc.)

Leiomyosarcoma of the renal vein is a rare and malignant tumor difficult to diagnose. No standard treatment has been defined and prognosis is poor. We described the case of a 68-year-old woman with rheumatoid arthritis treated by methotrexate who developed a leiomyosarcoma of the left renal vein with a fatal outcome in less than 1 year. Association of a leiomyosarcoma and rheumatoid arthritis raises the question of a casual association or of a predisposing factor since studies have shown increased risk of cancer with this rheumatism.

PURPOSE To determine the prognostic significance of histologic type in radiation-associated soft tissue sarcomas (RASs) and determine whether RASs are associated with an inferior prognosis compared with sporadic soft tissue sarcomas (STSs). PATIENTS AND METHODS One hundred thirty primary RASs were identified from 7,649 STS patients from 1982 to 2007. Multivariate analysis of clinicopathologic factors for disease-specific survival (DSS) was performed for RASs, and a multivariate analysis of radiation exposure was also performed for RASs and sporadic sarcomas. A matched-cohort analysis was performed for radiation-associated and sporadic malignant fibrous histiocytoma (MFH). Results Most RASs were high grade (83%), deep (87%), and truncal (61.5%). The median interval between radiation therapy and RAS development was 10 years (range, 1.3 to 74 years), which varied significantly by histologic type (P = .003). The 5-year DSS was 58%, and independent predictors were size > 5 cm, margin positivity, and histologic type. Multivariate analysis of histologic types of primary, high-grade radiation-associated and sporadic STSs showed that RAS was associated with a worse DSS (hazard ratio, 1.7; range, 1.1 to 2.4; P = .007). For pleomorphic MFH-the most common RAS type-the 5-year DSS was 44% versus 66% in a matched cohort of sporadic MFH patients (P = .07). DSS was significantly worse in primary RAS malignant peripheral nerve sheath tumors (MPNSTs) compared with unmatched sporadic MPNSTs (P = .001). CONCLUSION Histologic type, margin status, and tumor size are the most important independent predictors of DSS in patients with RASs. DSS in patients with primary RAS is significantly worse compared with sporadic STS independent of sarcoma histologic type.

The presence of osteoclast-like giant cells (OGC) has been reported as a rare and distinct feature in uterine leiomyosarcoma. To present knowledge, 11 cases have been described in the English literature. The authors report an additional example in a 35-year-old woman who presented with a pelvic mass. Pulmonary metastasis was detected by the preoperative CT scan. The hysterectomy specimen revealed a 11.5 cm intramural mass with hemorrhagic and necrotic center The histologic examination revealed pleomorphic sarcoma with OGC. The neoplastic cells were immunoreative for smooth muscle actin and desmin. Minor intermixing component of conventional leiomyosarcoma and leiomyoma were identified at the periphery of the malignant component. The patient died of disease after 16 months of diagnosis. To our knowledge, this is the youngest case of uterine leiomyosarcoma with OGC. Leiomyosarcoma with OGC has an aggressive clinical course. The tumor may occur in young patient and may arise from pre-existing leiomyoma.

Background: Primary leiomyosarcoma of the liver is a rare tumor whose development patterns are unsatisfactorily known., Patient Case: A 26-year-old male patient with a previous history of radiochemotherapy treatment for Hodgkin's lymphoma was referred to our unit with a histological and radiological diagnosis of primary hepatic leiomyosarcoma. Six months before referral, in a workup for hypertension, a CT scan of the abdomen had shown a 2.5-cm lesion in liver segment VII, which was interpreted as an angioma. Shortly before referral the lesion had grown to 7.8 cm, associated with two smaller lesions in segments VIII and III, and a diagnosis of hepatic leiomyosarcoma was made at biopsy. After referral he underwent a right hepatectomy with wedge resection of segment III. This was followed by rapid progression of the disease, in spite of transient stabilization under gemcitabine treatment. Octreotide was also administered after the detection of elevated chromogranin A in serum. The patient died 25 months after liver resection., Conclusions: The challenges and peculiarities of this case are related to the rarity of the tumor, its accidental discovery without immediate suspicion of its nature, its very aggressive behavior that was only partly controlled by chemotherapy, and the unusual expression of a neuroendocrine phenotypic feature with high serum chromogranin A levels.

Background: Leiomyosarcomas of the stomach are very rare. At the time of primary diagnosis the tumors are most often in advanced stage and the patients complain of abdominal pain due to large tumor size. Endosonographically, the tumors impress as submucous mass with suspicion to malignancy. Sarcomas following hereditary retinoblastoma in childhood are in generally located in the soft tissue. Structural alterations of the retinoblastoma gene (RB1) seem to be involved in the pathogenesis., Case Presentation: A 37-year-old german male suffered from reflux disorder. In endoscopic examination a small polypous tumor was detected in the stomach. The resection specimen revealed an intramucosal leiomyosarcoma. At the age of one year, the patient had a retinoblastoma., Conclusion: This is the unique report of an intramucosal gastric leiomyosarcoma and the first account of a gastric leiomyosarcoma after retinoblastoma in childhood. A careful clinical follow-up is advised because of increased risk of developing further metachronous malignancies.

Radiation-induced leiomyosarcoma of the head and neck region has been very seldom described. Herein, we report a 48-year-old male patient who developed leiomyosarcoma in his posterior neck region, which was previously radiated due to a cerebellar astrocytoma.

Microchips are commonly used in companion, research, and zoo animal medicine for easy, reliable, and cost-effective identification with relatively low risk of side effects. This report describes development of a metastatic leiomyosarcoma associated with a microchip in an Egyptian fruit bat (Rousettus aegyptiacus).

We analyzed the PI3K-AKT signaling cascade in a cohort of sarcomas and found a marked induction of insulin receptor substrate-2 (IRS2) and phosphorylated AKT and a concomitant upregulation of downstream effectors in most leiomyosarcomas. To determine the role of aberrant PI3K-AKT signaling in leiomyosarcoma pathogenesis, we genetically inactivated Pten in the smooth muscle cell lineage by cross-breeding Pten(loxP/loxP) mice with Tagln-cre mice. Mice carrying homozygous deletion of Pten alleles developed widespread smooth muscle cell hyperplasia and abdominal leiomyosarcomas, with a very rapid onset and elevated incidence (approximately 80%) compared to other animal models. Constitutive mTOR activation was restricted to the leiomyosarcomas, revealing the requirement for additional molecular events besides Pten loss. The rapamycin derivative everolimus substantially decelerated tumor growth on Tagln-cre/Pten(loxP/loxP) mice and prolonged their lifespan. Our data show a new and critical role for the AKT-mTOR pathway in smooth muscle transformation and leiomyosarcoma genesis, and support treatment of selected sarcomas by the targeting of this pathway with new compounds or combinations of these with conventional chemotherapy agents.

Uterine leiomyomata (UL), also known as fibroids, are the most common pelvic tumors in women of reproductive age and are the primary indication for hysterectomy in the USA. Many lines of evidence indicate a strong genetic component to the development of these tumors. In fact, approximately 40% of UL have non-random, tumor-specific chromosome abnormalities which have allowed classification into well-defined subgroups (deletion of portions of 7q, trisomy 12 or rearrangements of 12q15, 6p21 or 10q22) as well as identification of candidate genes for UL predisposition. Although benign, UL have been linked to malignancy through two genomic regions on chromosome 1. Mutation of fumarate hydratase (FH) at 1q43 is known to cause the Mendelian syndromes of multiple cutaneous and uterine leiomyomata (MCL) and hereditary leiomyomatosis and renal cell cancer (HLRCC), and recently, FH mutations have been detected in some non-syndromic UL. In addition, transcriptional profiling suggests that loss of the short arm of chromosome 1 in cellular leiomyomata, an uncommon histological variant of UL, may account in part for the presumed yet rare malignant transformation of UL to uterine leiomyosarcoma.