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Markku Miettinen - One of the best experts on this subject based on the ideXlab platform.

  • Smooth muscle tumors of soft tissue and non-uterine viscera: biology and prognosis
    Modern Pathology, 2014
    Co-Authors: Markku Miettinen
    Abstract:

    Smooth muscle tumors are here considered an essentially dichotomous group composed of benign leiomyomas and malignant Leiomyosarcomas. Soft tissue smooth muscle tumors with both atypia and mitotic activity are generally diagnosed Leiomyosarcomas acknowledging potential for metastasis. However, lesions exist that cannot be comfortably placed in either category, and in such cases the designation ‘smooth muscle tumor of uncertain biologic potential’ is appropriate. The use of this category is often necessary with limited sampling, such as needle core biopsies. Benign smooth muscle tumors include smooth muscle hamartoma and angioleiomyoma. A specific category of leiomyomas are estrogen-receptor positive ones in women. These are similar to uterine leiomyomas and can occur anywhere in the abdomen and abdominal wall. Leiomyosarcomas can occur at any site, although are more frequent in the retroperitoneum and proximal extremities. They are recognized by likeness to smooth muscle cells but can undergo pleomorphic evolution (‘dedifferentiation’). Presence of smooth muscle actin is nearly uniform and desmin-positivity usual. This and the lack of KIT expression separate Leiomyosarcoma from GIST, an important problem in abdominal soft tissues. EBV-associated smooth muscle tumors are a specific subcategory occurring in AIDS or post-transplant patients. These tumors can have incomplete smooth muscle differentiation but show nuclear EBER as a diagnostic feature. In contrast to many other soft tissue tumors, genetics of smooth muscle tumors are poorly understood and such diagnostic testing is not yet generally applicable in this histogenetic group. Leiomyosarcomas are known to be genetically complex, often showing ‘chaotic’ karyotypes including aneuploidy or polyploidy, and no recurrent tumor-specific translocations have been detected.

  • Leiomyosarcoma of the inferior vena cava clinicopathologic study of 40 cases
    The American Journal of Surgical Pathology, 2010
    Co-Authors: William B Laskin, Julie C Fanburgsmith, Allen P Burke, Ewa Kraszewska, John F Fetsch, Markku Miettinen
    Abstract:

    This report details the clinicopathologic features and follow-up data on 40 cases of inferior vena cava Leiomyosarcoma, a rare sarcoma with a poor prognosis. Study cohort consisted of 31 females and 9 males (mean age, 53 y), whose material was accessioned to the Armed Forces Institute of Pathology between 1976 and 2008. Inferior vena cava Leiomyosarcomas ranged in size from 3.5 to 15.0 (median, 8.5) cms, and most involved the middle segment of the vessel and grew extraluminally. Eleven Leiomyosarcomas were French Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC) histologic grade I; 21, grade II; and 5 were grade III. Eleven of 33 patients managed by complete or radical resection had involved surgical margins. Twenty of the 34 patients (59%) with clinical follow-up data (mean, 33.5; median, 51 mo) died of sarcoma-related complications and 9 (26%) of unknown causes. The 5-year and 10-year survival rates after resection without documented residual macroscopic disease were 50% and 22%, respectively. Two patients are alive without disease 9 and 18 years after last surgical intervention. Suprahepatic vena caval and right atrial involvement by tumor, predominant intraluminal tumor growth, and residual postsurgical macroscopic disease were factors that statistically correlate with death within 2 years. By univariate analysis, intraluminal tumor (P=0.03), liver injury or failure (compromised liver) (P=0.01), and moderate to poor tumor differentiation (P=0.03) were associated with increased tumor-related mortality, whereas a compromised liver (P=0.01) was the only factor correlated with mortality by multivariate analysis. Our study concludes that a macroscopic resection of localized inferior vena cava Leiomyosarcoma provides the best chance for long-term survival, suprahepatic tumors often result in early death, and a compromised liver correlates with overall poor survival, but French Federation Nationale des Centres de Lutte Contre le Cancer grading does not affect prognosis.

David L Olive - One of the best experts on this subject based on the ideXlab platform.

  • The prevalence of occult Leiomyosarcoma at surgery for presumed uterine fibroids: a meta-analysis
    Gynecological Surgery, 2015
    Co-Authors: Elizabeth A Pritts, David J Vanness, Jonathan S Berek, William Parker, Ronald Feinberg, Jacqueline Feinberg, David L Olive
    Abstract:

    There is a concern regarding the risk of occult Leiomyosarcomas found at surgery for presumed benign fibroids. We sought to produce a comprehensive review of published data addressing this issue and provide high-quality prevalence estimates for clinical practice and future research. A comprehensive literature search using the PubMed/MEDLINE database and the Cochrane Library was performed. Inclusion criteria were human studies, peer-reviewed, with original data, involving cases for surgery in which fibroid-related indications were the primary reason for surgery, and histopathology was provided. Candidate studies (4864) were found; 3844 were excluded after review of the abstract. The remaining 1020 manuscripts were reviewed in their entirety, and 133 were included in the Bayesian binomial random effect meta-analysis. The estimated rate of Leiomyosarcoma was 0.51 per 1000 procedures (95 % credible interval (CrI) 0.16–0.98) or approximately 1 in 2000. Restricting the meta-analysis to the 64 prospective studies resulted in a substantially lower estimate of 0.12 Leiomyosarcomas per 1000 procedures (95 % CrI

  • the prevalence of occult Leiomyosarcoma at surgery for presumed uterine fibroids a meta analysis
    Gynecological Surgery, 2015
    Co-Authors: Elizabeth A Pritts, David J Vanness, Jonathan S Berek, William Parker, Ronald Feinberg, Jacqueline Feinberg, David L Olive
    Abstract:

    There is a concern regarding the risk of occult Leiomyosarcomas found at surgery for presumed benign fibroids. We sought to produce a comprehensive review of published data addressing this issue and provide high-quality prevalence estimates for clinical practice and future research. A comprehensive literature search using the PubMed/MEDLINE database and the Cochrane Library was performed. Inclusion criteria were human studies, peer-reviewed, with original data, involving cases for surgery in which fibroid-related indications were the primary reason for surgery, and histopathology was provided. Candidate studies (4864) were found; 3844 were excluded after review of the abstract. The remaining 1020 manuscripts were reviewed in their entirety, and 133 were included in the Bayesian binomial random effect meta-analysis. The estimated rate of Leiomyosarcoma was 0.51 per 1000 procedures (95 % credible interval (CrI) 0.16–0.98) or approximately 1 in 2000. Restricting the meta-analysis to the 64 prospective studies resulted in a substantially lower estimate of 0.12 Leiomyosarcomas per 1000 procedures (95 % CrI <0.01–0.75) or approximately 1 Leiomyosarcoma per 8300 surgeries. Results suggest that the prevalence of occult Leiomyosarcomas at surgery for presumed uterine fibroids is much less frequent than previously estimated. This rate should be incorporated into both clinical practice and future research.

  • outcome of occult uterine Leiomyosarcoma after surgery for presumed uterine fibroids a systematic review
    Journal of Minimally Invasive Gynecology, 2015
    Co-Authors: Elizabeth A Pritts, William H Parker, Jubilee Brown, David L Olive
    Abstract:

    There is concern that morcellation of occult Leiomyosarcomas during surgery to treat presumed myomas may substantially worsen patient outcome. We reviewed the existing medical literature to better understand whether such a risk was demonstrable and, if so, what the magnitude of that risk might be. We identified 4864 articles initially, of which 60 were evaluated in full. Seventeen were found to have outcomes information and are included in this review. Six studies addressed the question of whether morcellation of occult Leiomyosarcomas resulted in inferior outcomes as compared with en bloc uterine and tumor removal. In these 6 studies, results suggested that en bloc removal may result in improved survival and less recurrence; however, the data are highly biased and of poor quality. There is no reliable evidence that morcellation, power or otherwise, substantially results in tumor upstaging. There is no evidence from these 17 studies that power morcellation differs in any way from other types of morcellation or even simple myomectomy insofar as patient outcome. Whether electromechanical morcellation poses a unique danger to the patient with occult Leiomyosarcoma is an unanswered question and one clearly in need of more extensive investigation before conclusions are drawn and policies created.

Jonathan I Epstein - One of the best experts on this subject based on the ideXlab platform.

  • symplastic leiomyomas of the scrotum a comparative study to usual leiomyomas and Leiomyosarcomas
    The American Journal of Surgical Pathology, 2014
    Co-Authors: Andres Matoso, Sonja Chen, Jose A Plaza, Adeboye O Osunkoya, Jonathan I Epstein
    Abstract:

    Smooth muscle tumors of the scrotum are very uncommon, and those with degenerative-appearing atypia, variably designated as "atypical," "symplastic," or "bizarre" leiomyomas, are extremely rare with only 11 cases in the literature. Given their rarity, the diagnostic criteria and prognosis of symplastic leiomyomas are not well established. We describe 9 cases of scrotal symplastic leiomyomas and compare their histopathologic characteristics to 10 usual leiomyomas and 5 Leiomyosarcomas of the scrotum. The preoperative diagnosis was scrotal tumor or cyst in all cases. The mean age was 46 years (range, 32 to 60 y) for usual, 59 (range, 48 to 79) for symplastic leiomyomas, and 57 (range, 49 to 65) for Leiomyosarcoma. Submitting diagnoses for symplastic leiomyomas were: atypical spindle cell lesion (n=3); probably Leiomyosarcoma (n=1); Leiomyosarcoma (n=1); and none given (n=4). Symplastic leiomyomas were diagnosed when there was moderate-severe cytologic atypia, yet was degenerative-appearing with multinucleation or smudged chromatin in the setting of low nuclear/cytoplasmic ratio, low cellularity, and no mitotic activity. The mean size was 1.0 cm for usual leiomyomas, 1.0 cm for symplastic leiomyomas, and 2.0 cm for Leiomyosarcomas. Leiomyosarcomas had high nuclear/cytoplasmic ratio, high cellularity, nuclear pleomorphism, and hyperchromasia. Five of 10 usual and 3/9 symplastic leiomyomas showed at least 1 ill-defined border simulating infiltrative growth. Three Leiomyosarcomas were grade 1, and 2/5 were grade 2. Resection margins were positive in 5/10 usual and 3/9 symplastic leiomyomas and in 1/5 Leiomyosarcoma. Ki67 labeling in usual leiomyomas was on average 2.4% (range, 1% to 5%) and in symplastic leiomyomas was 1.8% (range, 1% to 5%). Mitoses were absent in all cases of usual and symplastic leiomyomas. Mitotic figures averaged 4.7 (range, 1 to 7) and 13.5 (range, 7 to 20) per 10 HPF for the grade 1 and 2 Leiomyosarcomas, respectively. None of the symplastic leiomyomas recurred after a median follow-up of 27 months. The 2 patients with grade 2 Leiomyosarcoma had no evidence of metastases at 6 and 7 months follow-up, respectively. Scrotal symplastic leiomyomas may have an ill-defined infiltrative border, which along with their atypia mimic malignancy. Ki67 is low in symplastic leiomyomas, which along with their favorable follow-up and experience in other organs justifies a benign diagnosis. High cellularity and high mitotic activity are the most reliable features for the diagnosis of scrotal Leiomyosarcoma.

  • primary Leiomyosarcoma of the kidney a clinicopathologic study of 27 cases
    The American Journal of Surgical Pathology, 2010
    Co-Authors: Jeremy S Miller, Ming Zhou, Fadi Brimo, Charles C Guo, Jonathan I Epstein
    Abstract:

    Primary Leiomyosarcoma of the kidney is a rare entity that has not been well characterized. We retrieved 27 cases of primary renal Leiomyosarcomas diagnosed at 3 institutions between 1986 and 2009. Mean patient age at diagnosis was 58.5 years (range 22 to 85), and 59% were female. Mean tumor size wa

W A Chow - One of the best experts on this subject based on the ideXlab platform.

  • A randomised phase II trial of selumetinib vs selumetinib plus temsirolimus for soft-tissue sarcomas
    British Journal of Cancer, 2015
    Co-Authors: Z Eroglu, H A Tawbi, J Hu, M Guan, P H Frankel, N H Ruel, S Wilczynski, S Christensen, D R Gandara, W A Chow
    Abstract:

    Background: The MEK inhibitor, selumetinib, suppresses soft-tissue sarcoma (STS) cell proliferation in vitro. Mammalian target of rapamycin inhibitors possess modest activity against STS; however, resistance develops via MAPK pathway feedback activation. The combination of selumetinib and temsirolimus synergistically inhibits STS cell line growth. Therefore, a randomized phase II trial of selumetinib vs selumetinib plus temsirolimus was conducted. Methods: Seventy-one adults with advanced STS who received ⩽2 prior chemotherapeutics were randomized to selumetinib 75 mg p.o. bid and allowed to crossover upon progression, or to selumetinib 50 mg p.o. bid plus temsirolimus 20 mg i.v. weekly, with primary endpoint of progression-free survival (PFS). Results: There was no difference in PFS between the two arms for the overall cohort (median 1.9 vs 2.1 months); an improved median PFS was observed in the combination arm ( N =11) over single agent ( N =10) in the prespecified Leiomyosarcoma stratum (median 3.7 vs 1.8 months; P =0.01). Four-month PFS rate was 50% (95% confidence interval 0.19–0.81) with the combination vs 0% with selumetinib alone in the Leiomyosarcoma cohort. Most common grade 3/4 adverse events with the combination were mucositis (29%), lymphopenia (26%), neutropenia and anaemia (20% each). Conclusions: While single-agent selumetinib has no significant activity in STS, the combination may be active for Leiomyosarcomas.

Cristina R Antonescu - One of the best experts on this subject based on the ideXlab platform.