Risk of Recurrence in Uterine Leiomyoma with Bizarre Nuclei: a Systematic Review and Meta-Analysis Gefahr eines Rezidivs bei uterinem Leiomyom mit bizarrem Zellkern: eine systematische Uberprufung und Metaanalyse
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SUBMITTER: Travaglino A
PROVIDER: S-EPMC8568503 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Leiomyoma with bizarre nuclei (LM-BN) is a rare variant of leiomyoma with a benign clinical course. In contrast, leiomyosarcoma (LMS) is a high-grade, malignant neoplasm characterized by high recurrence rates and poor survival. While LM-BN and LMS show distinct morphologies, they share similar immunoprofile and molecular alterations, with both considered “DNA unstable”. Rare cases of LM-BN associated with LMS have been reported, however the histogenesis and molecular relationship between these two tumors remains unclear. In this study, we assessed 11 cases of LMS arising in conjunction with LM-BN and further analyzed the clinical, histologic, and molecular characteristics of these lesions. Tumor slides were examined by histology and immunohistochemistry to confirm the presence of both LMS and LM-BN components. LM-BN and LMS had similar p16 and p53 IHC patterns, but LMS had a higher Ki-67 index and lower ER/PR expression. Digital image analysis based on nuclear and cytologic features revealed spatial relationships between LMS and LM-BN. Genomic copy number alteration (CNA) demonstrated the same clonal origin of LMS from existing LM-BN through conserved copy number alterations. LMS harbored higher CNAs and frequent loss of the TP53, Rb, PTEN, and/or CDKN2A genomic region than LM-BN, indicative of tumor progression. Spatial transcriptome analysis defined uniquely expressed gene signatures in a geographical distribution, demonstrating molecular evidence of regional cell specific differences of LM-BN and LMS. Mutation analysis of large oncogenic panel revealed many shared functional gene alterations in both LM-BN and LMS, but more highly enriched in LMS. Our findings for the first time suggest that a subset of LMS arise from an existing LM-BN.
2024-11-05 | GSE270865 | GEO
Project description:Leiomyoma with bizarre nuclei (LM-BN), is a variant of uterine smooth muscle tumor with atypical histologic features. Although some LM-BN share several significant genetic alterations with leiomyosarcoma, including p16 and p53, the underlying tumorigenesis of LM-BN remains largely unknown. As we previously reported, LM-BN can be divided into 2 subtypes, type I and type II, based on different nuclear features. Type I LM-BN have similar histologic features as uterine smooth muscle tumors with fumarate hydratase (FH) alterations. In this study, we examined FH expression and FH mutations in 77 LM-BN (40 type I cases and 37 type II cases). FH expression was examined by immunohistochemistry using S-(2-succino)-cysteine antibodies (2SC, a protein modification associated with FH inactivation and subsequent fumarate accumulation) and FH antibodies (FH gene products). Seventy-two LM-BN tumors underwent Sanger sequencing to detect FH mutations. We found that 51% (39/77) of LM-BN showed FH alterations detected by immunohistochemistry with both 2SC and FH. Mutational analysis showed that 21% (15/72) of LM-BN harbored FH gene mutations. Further analysis revealed that 85% (34/40) of those with FH alterations were type I LM-BN while 19% (7/37) were type II LM-BN. Our findings suggest that over half of histologically diagnosed LM-BN may be related to FH alterations or FH mutations and the majority of these have the characteristic histologic features of type I LM-BN.
| S-EPMC5832508 | biostudies-literature
Project description:Leiomyomas associated with hereditary leiomyomatosis and renal cell carcinoma syndrome and leiomyomas with bizarre nuclei often show overlapping morphological features, in particular cells with prominent eosinophilic nucleoli, perinucleolar halos, and eosinophilic cytoplasmic inclusions. Although hereditary leiomyomatosis and renal cell carcinoma syndrome is defined by fumarate hydratase (FH) germline mutations, resulting in S-(2-succino)-cysteine (2SC) formation, it is unknown whether leiomyomas with bizarre nuclei show similar alterations. In this study, we evaluated the morphology and FH/2SC immunoprofile of 31 leiomyomas with bizarre nuclei. DNA from tumor and normal tissues from 24 cases was subjected to massively parallel sequencing targeting 410 key cancer genes. Somatic genetic alterations were detected using state-of-the-art bioinformatics algorithms. No patient reported a personal history of renal neoplasia or cutaneous leiomyomas, but one had a family history of renal cell carcinoma while another had a family history of uterine leiomyomas. Aberrant FH/2SC expression was noted in 17 tumors (16 FH-negative/2SC-positive, 1 FH-positive/2SC-positive). On univariate analysis, staghorn vessels, eosinophilic cytoplasmic inclusions, diffuse distribution of prominent eosinophilic nucleoli with perinucleolar halos, and an 'alveolar pattern of edema' were associated with an abnormal immunoprofile, but only staghorn vessels remained significant on multivariate analysis. Massively parallel sequencing analysis (n=24) revealed that 13/14 tumors with aberrant FH/2SC immunoprofile harbored somatic FH somatic genetic alterations, including homozygous deletions (n=9), missense mutations coupled with loss of heterozygosity (n=3), and a splice site mutation (n=1), whereas no somatic FH mutations/deletions were found in tumors with normal immunoprofile (n=10; P<0.0001). Leiomyomas with bizarre nuclei with normal FH/2SC staining pattern more frequently harbored TP53 and/or RB1 alterations than those with aberrant FH/2SC immunoprofile (60 vs 14%; P=0.032). These data demonstrate that leiomyomas with bizarre nuclei are morphologically and genetically heterogeneous and that hereditary leiomyomatosis and renal cell carcinoma syndrome-related morphological features, abnormal FH/2SC staining, and somatic FH mutations/deletions can be seen in a subset of sporadic tumors.
| S-EPMC5626591 | biostudies-literature
Project description:Genomic and Histologic Analysis of Uterine Leiomyosarcoma from Leiomyoma with Bizarre Nuclei
| PRJNA1128661 | ENA
Project description:BackgroundThe published data about alcohol consumption and uterine myoma are scanty and controversial: some studies found positive association whereas other studies showed no association.ObjectivesTo conduct a systematic review and meta-analysis to determine whether alcohol is a risk factor for myoma.Search strategyA MEDLINE/EMBASE search was carried out, supplemented by manual searches of bibliographies of the selected studies.Selection criteriaArticles published as full-length papers in English. In the review we included all identified studies. Otherwise, the inclusion criteria for studies included in the meta-analysis were: a) case-control or cohort studies, reporting original data; b) studies reporting original data on the association between alcohol consumption and myoma; c) diagnosis of myoma was ultrasound or histological confirmed and/or clinically based.Data collection and analysisA total of 6 studies were identified for the review and 5 studies were included in the meta-analysis. The primary outcome was the incidence of uterine myoma in ever versus never alcohol drinkers and when data were available, we also analyzed categories of alcohol intake. We assessed the outcomes in the overall population and then we performed a subgroup analysis according to study design. Pooled estimates of the odds ratios (OR) with 95% confidence interval (CI) were calculated using random effects models.Main resultsThe summary OR (95%CI) of myoma forever versus never alcohol intake was 1.12 (0.94-1.34) with significant heterogeneity. The summary OR for current versus never drinking was 1.33 (1.01-1.76) with no heterogeneity.ConclusionsEver alcohol consumption is not associated with myoma risk. Based on the data of two studies, current alcohol drinkers had a slightly borderline increased risk of diagnosis of myoma. In consideration of the very limited number of studies and the suggestion of a potential increased risk among current drinkers, further studies are required.
| S-EPMC5703463 | biostudies-literature
Project description:BackgroundThe aim of this literature review was to identify preoperative risk factors associated with recurrent instability after Bankart repair.MethodsThe PubMed, Web of Science, Embase, and Cochrane Library databases were searched for potentially eligible articles. Two reviewers independently screened the titles and abstracts using prespecified criteria. Articles were included if they clearly stated the risk factors for recurrence after Bankart repair. Data on patient characteristics and recurrence rate were collected from each study. A random-effects model was used for the meta-analysis and the statistical analysis was performed using Review Manager 5.4 software.ResultsNineteen studies that included 2922 participants met the inclusion criteria. The overall pooled prevalence of recurrent instability was 15.3% (range 6.9-42). The mean follow-up duration was 40.5 months (18-108). Twenty-one risk factors were identified, 10 of which were explored quantitatively. Statistically significant risk factors for recurrent instability following a Bankart procedure were age under 20 years (odds ratio [OR] 4.24, 95% confidence interval [CI] 2.8-96.23, p < 0.00001), a Hill-Sachs lesion (OR 3.61, 95% CI 2.06-6.33, p < 0.00001), a glenoid bone lesion (OR 2.8, 95% CI 1.96-4.01, p < 0.00001), shoulder hyperlaxity (OR 4.55, 95% CI 2.19-9.44, p < 0.0001), and an off-track lesion (OR 5.53, 95% CI 2.21-13.86, p = 0.0003). There was moderate evidence indicating that male sex (OR 1.6, 95% CI 1.07-2.37, p = 0.02) and playing contact sports (OR 1.54, 95% CI 0.96-2.45, p = 0.07) were further risk factors. Dominant side, a superior labrum from anterior to posterior (SLAP) lesion, and more than five preoperative dislocations were not found to be risk factors.ConclusionsPatients younger than 20 years of age, a Hill-Sachs lesion, a glenoid bone lesion, shoulder hyperlaxity, and an off-track lesion appear to be significant predictors of recurrent instability following a Bankart procedure. Factors such as male sex and playing contact sports were associated with recurrent instability. Dominant side, a SLAP lesion, and more than five preoperative dislocations were not significant risk factors.
| S-EPMC8859902 | biostudies-literature
Project description:BackgroundWomen with previous obstetric anal sphincter injuries (OASIs) are at a higher risk of recurrence in the subsequent pregnancy, which may lead to the development or worsening of anal incontinence. Due to a lack of evidence, few recommendations can be made about the factors that may affect the risk of OASI recurrence.ObjectiveWe sought to conduct a systematic review and meta-analysis to investigate potential risk factors for recurrent OASIs.Search strategyStudies up to May 2019 were identified from PubMed, Scopus, Cochrane Library, and ISI Web of Science.Selection criteriaStudies assessing the impact of risk factors on OASI recurrence in subsequent pregnancies were included. Reviews, letters to the editor, conference abstracts, book chapters, guidelines, Cochrane reviews, and expert opinions were excluded.Data collection and analysisData were extracted by two independent reviewers. Odds ratio and standardized mean difference were chosen as effect measures. Pooled estimates were calculated using the random-effects model.Main resultsThe meta-analysis showed that maternal age, gestational age, occiput posterior presentation, oxytocin augmentation, operative delivery, and shoulder dystocia were associated with the risk of recurrent OASIs in the subsequent delivery.ConclusionPrenatal and intrapartum risk factors are associated with recurrence of OASI. PROSPERO registration no. CRD42020178125.
| S-EPMC9298380 | biostudies-literature
Project description:Primary outcome(s): Colorectal cancer incidence, Colorectal tumor incidence
| 79216 | ecrin-mdr-crc
Project description:BackgroundSubacute thyroiditis (SAT) is a self-limited inflammatory thyroid disease with recurring episodes. However, the results regarding the recurrence rate and risk factors for SAT are inconsistent. This meta-analysis aimed to summarize the evidence of the recurrence rate and the risk factors for SAT.MethodsThe present study involved the performance of a systematic literature search of all English studies published in PubMed, Embase, Web of Science, and The Cochrane Library from inception to August 20, 2021. Cohort studies that reported the SAT recurrence rate and risk factors for recurrence were included. Two independent investigators extracted relevant information. Fixed- and random-effects models were used to pool effect sizes based on study heterogeneity.ResultsEighteen cohort studies were identified. The pooled findings showed that the recurrence rate was 12.0% (95% CI: 8.2%, 17.1%). The risk of recurrence in the glucocorticoids group was higher than that in the NSAIDs group (RR = 1.84, 95% CI: 1.04, 3.24). However, there was no significant difference in age or sex between the recurrence group and the non-recurrence group. Findings from one or two cohort studies also indicated that the copresence of HLA-B*18:01 and -B*35, the number of days required to taper prednisolone (PSL) to 5 mg/day, the duration of disease before treatment less than 30 days, the sialic acid level, or the TSH level at the termination of treatment and further extension of the hypoechoic area and increase in thyroid volume were related to the recurrence of SAT.ConclusionRecurrence was common in SAT patients. The present study indicated that glucocorticoid treatment was associated with a higher recurrence rate of SAT than NSAIDs treatment. The clinical implications of this association should be interpreted with caution, and further clinical trials on the long-term effects of different treatment strategies are needed.
| S-EPMC8734029 | biostudies-literature
Project description:IntroductionUterine leiomyoma (UL) is a common benign pelvic tumor in women that has a high recurrence rate. Our aim is to propose a prognostic index (PI) model for predicting the long-term recurrence risk of uterine leiomyoma (UL).MethodsA total of 725 women who underwent myomectomy were enrolled in this retrospective multicenter study. Patients were contacted for follow-up. A PI model was proposed based on the multivariate Cox regression analysis in the model group. The predictive value of this model was tested in both internal and external validation group.ResultsPI formula = 1.5(if 3-5 leiomyomas) or 2(if >5 leiomyomas)+1(if residue)+1(if not submucosal)+1(if combined endometriosis). The PI value was divided into low-risk, intermediate-risk, and high-risk group by cut-off values 1.25 and 3.75. In the model group, the high-risk group had a significantly 4.55 times greater recurrence risk of UL than that in the low-risk group [cumulative recurrence rate (CR): 82.1% vs 29.5%, HR = 4.55, 95% CI 2.821-7.339]; the intermediate-risk group had a significantly 2.81 times greater recurrence risk of UL than that in the low-risk group (CR: 62.3% vs 29.5%, HR = 2.81, 95% CI 2.035-3.878). The differences between any two risk groups were also significant (P< 0.05) in both internal and external validation groups.ConclusionThe model was proved to be effective in predicting recurrence of UL after myomectomy.
| S-EPMC8248613 | biostudies-literature