Diagnostic value of dystrophin immunostaining for histopathologic diagnosis of uterine smooth muscle tumors.

PurposePreoperative diagnosis of uterine leiomyosarcoma (ULMS) can be difficult due to its ability to mimic benign leiomyomas (LM). The current study aimed to investigate the influence of preoperative clinical characteristics and hematologic parameters on preoperative diagnosis and to design a scoring system.Patients and MethodsWe conducted a retrospective analysis of 288 patients with uterine tumors treated at the First Affiliated Hospital of Wenzhou Medical University between January 2006 and April 2022, including 64 with ULMS and 224 with LM. Preoperative clinical and laboratory variables were compared between groups. Logistic regression analysis was employed to identify predictors of ULMS, with receiver operating characteristic (ROC) curves used to evaluate diagnostic performance.ResultsMultivariate analysis identified four independent risk factors for ULMS: older age (>48 years), larger tumor size (>9.7 cm), elevated systemic immune-inflammation index (SII > 500), and higher controlling nutritional status score (CONUT ≥ 3) (all P<0.001). A preoperative scoring system was developed by assigning one point for each risk factor, yielding a total possible score of 0–4 points. A score ≥ 2 points demonstrated significant utility in differentiating ULMS from LM (AUC = 0.823, sensitivity 64.1%, specificity 85.3%).ConclusionThis single-center retrospective study demonstrates that the integration of age, tumor size, SII, and CONUT score shows promising utility for preoperative differentiation between ULMS and LM. The constructed scoring system may provide valuable auxiliary support for identifying occult ULMS preoperatively. However, given the study’s limitations, including its retrospective design and sample size, external validation through large-scale, multicenter prospective studies is necessary before clinical implementation.

Previous studies have evaluated the utility of estrogen receptor (ER) and progesterone receptor (PR) immunohistochemistry (IHC) in differentiating uterine versus extrauterine leiomyosarcomas (LMS). At best, these studies have shown only modest sensitivity and specificity for these markers in this context. In our own practice, we have noticed that retroperitoneal LMS, such as those arising in the wall of the inferior vena cava, frequently exhibit a remarkable resemblance not to uterine LMS, but rather to uterine leiomyomas (LM) with bizarre nuclei, formerly known as symplastic LM. This includes areas with bland nuclear cytology, punctuated by the presence of cells with large bizarre nuclei but a paradoxically low mitotic index. We refer to these areas in retroperitoneal LMS as "symplastic-like." It has been our experience that these "symplastic-like" areas are frequently the predominant or exclusive component in small core biopsies of retroperitoneal LMS, even when the resection of these tumors reveals the presence of more conventional high-grade LMS morphology. In female patients, symplastic-like morphology in a smooth muscle tumor at an intra-abdominal site raises the possibility of iatrogenic dissemination of a uterine LM with bizarre nuclei from a prior myomectomy or morcellation procedure. We hypothesized that negative staining for ER and PR by IHC could effectively exclude a uterine origin, given the high sensitivity of these markers for all variants of uterine LM. After successfully using ER and PR IHC in our clinical practice on a few index cases, we decided to study a larger cohort of carefully selected cases to systematically determine the sensitivity and specificity of these markers in this very specific context. Confining our search to include only female patients, we identified 8 cases of retroperitoneal LMS that had been confirmed radiologically, intraoperatively and/or histologically to originate from a retroperitoneal source and 6 cases of uterine-based LM with bizarre nuclei, all diagnosed at our institution over an 8-year period. We tested only whole slides for ER and PR IHC. ER and PR were both completely negative in all 8 cases of retroperitoneal LMS and were both strongly expressed in all 6 cases of LM with bizarre nuclei. In conclusion, despite conflicting data in the literature regarding the utility of ER and PR in distinguishing uterine versus extrauterine smooth muscle tumors, we endorse the use of these markers for the specific distinction of retroperitoneal LMS with symplastic-like features from disseminated uterine LM with bizarre nuclei in female patients.

This study aims to compare apparent diffusion coefficient (ADC) findings between leiomyosarcoma (LMS) and atypical/degenerate leiomyoma (LM) and evaluate the usefulness of this biomarker for diagnosis. Additionally it will explore the potential of preoperative neutrophil-lymphocyte ratio (NLR) as a haematological marker to aid in the differentiation of LMS from atypical LM. Histologically proven LMS and LM patients between 2013 and 2023 were included. For all patients (191 LM, 18 LMS), the preoperative full blood count was analysed, and the NLR calculated. Whole volume of interest (VOI) and focal region of interest (ROI) areas were manually segmented on patients with DW-MRI sequences available (52 LM, 12 LMS). Mann-Whitney and Fishers exact test were used to assess statistical significance and receiver operating characteristic (ROC) curves for diagnostic performance. VOI and ROI mean ADC values were significantly lower for LMS than LM, with ROI mean ADC demonstrating greater diagnostic accuracy (area under the curve, [AUC] 0.817 vs 0.755). Applying a threshold ROI mean ADC value of ≤1.00 × 10-3 mm2/s achieved a sensitivity and specificity of 88.3% and 65.4%, respectively. A higher NLR was suggestive of LMS (median 2.8 vs 1.7 for LM). ADC, particularly a focal ROI is useful in differentiating LMS from LM. Differences in preoperative blood markers, suggest an inflammatory-malignancy relationship. Future risk stratification models of ADC and haematological parameters should be explored. This study adds to few studies comparing using both ROI- and VOI-based methods, and no study has assessed both haematological markers and ADC metrics to aid differentiation.

FreqYOLO: A uterine disease detection network based on local and global frequency feature learning.

The importance of cytokines, including TNF, in development of uterine fibroids (UF) or leiomyomas (LM) is well proven. The number of polymorphic sites in promoter region of TNF gene is established, and their relationship with the gene expression level has been shown, thus potentially affecting the evolution of the disease. The aim of our research was to analyze the distribution of TNF-238, TNF- 308 and TNF-863 structural variants at the regulatory region of the TNFA gene in a representative group of Caucasian patients with UF compared with a matched group of healthy women followed by assessment of personalized prognostic significance of suggested differences. 180 patients diagnosed with uterine fibroids and 98 practically healthy women were examined. Genotyping of TNF gene polymorphisms (-863 C/A, TNF- 308 G/A, TNF-238 G/A, IL1B-31 T/C, IL4-590 T/C, IL6-174 C/G, IL8-251 T/A, IL10-592 A/G, IL10-1082 A/G and IL17A-197 G/A) was performed by RT-PCR using the SYBR Green intercalating dye. Statistical processing was carried out using multifunctional programs – IBM SPSS Statistics 23, SNPStats. We did not reveal significant differences between the compared groups when analysing distribution of TNF allelic variants and their combinations in genotypes. When comparing the combined SNP variants of the TNF gene at the studied nucleotide positions with the polymorphisms of other genes encoding proinflammatory cytokines, an increased frequency of TNF-238 GG:TNF-308 GG:IL17A-197 AA complex was found in the group of patients with uterine fibroids. The diagnostic specificity of this index was 100%, and the predictive value of this quotient reached 13.3, thus implying a 99.9% probability of a correct prediction. At the same time, the combination of TNF-863 CC genotype with IL-6-174 GG and IL-17-197 GG was significantly reduced in the patients. The frequencies of the anti-inflammatory cytokine genes IL4-590 T/C, IL10-592 A/G and IL10-1082 A/G analyzed n our study did not differ in the both compared groups and they were not considered either predisposing or protective for the disease. The magnitude of the revealed differences in occurrence of these allelic combinations reaches a significant level, thus assuming these traits as potential genetic factors for predicting a predisposal or resistance of women with a certain genotype to development of uterine fibroids, being prognostic criteria for early detection of this disorder.

INTRODUCTION: Low vitamin D levels have been associated with an increased incidence of leiomyoma (LM). However, these findings have been based on small samples, thus making comparison in different ethnicities/races problematic. METHODS: We employed a large multi-institutional database (EPIC, COSMOS). Recorded demographics and CPT and ICD-10 coding were used to identify cohorts. Our study population included patients who had vitamin D assayed during the last 10 years. Next, comparison cohorts based on race/ethnicity, presence/absence of LMs, and normal/low vitamin D levels were created. Overall odds ratios (ORs) were calculated based on LMs and vitamin D levels and corrected for multiple measurements. RESULTS: In the study period, 3,476,864 females between the ages of 26 and 51 years (71.2% White [W], 16.8% Black [B], 10.3% Hispanic [H], and 5.7% Asian [A]) had vitamin D assessed. More than half (51.7%) had low vitamin D levels with an overall LM incidence of 8.3%. Blacks were more likely to have LM (OR 3.14, P&lt;.001) and/or a low vitamin D (OR 1.52, P&lt;.001). Asians had the lowest risk of LM (OR 0.89, P&lt;.001). There was an increase in LMs in individuals with low vitamin D (OR, W 1.32, B 1.27, A 1.24 [P&lt;.001]). This relationship was not noted in Hispanics (OR 0.89, P&lt;.001). CONCLUSIONS/IMPLICATIONS: Low vitamin D levels are widespread. This larger study (3.4 million patients) confirms the association of LM and low vitamin D. The lack of this relationship in patients self-identified as Hispanic has not been previously reported and remains to be answered.

Numerous emerging molecularly defined subtypes of uterine leiomyosarcoma (LMS) have been described in recent years. Here we report our experience with a challenging case of the recently described CDKN2C/CIC null subtype of LMS - a LMS subtype that is frequently epithelioid in appearance, is wild-type for both TP53 and RB1 and may exhibit low-grade histology that falls short of LMS. The 48-year-old patient was initially diagnosed with an epithelioid leiomyoma with a component of intravenous leiomyomatosis. Recurrence occurred 5 years later with an extensive disease burden in the abdomen and pelvis. Upon review, the lesion in the hysterectomy specimen and the recurrent tumor had similar morphology. This included (1) focal epithelioid morphology meeting current diagnostic criteria for epithelioid LMS and (2) other areas with morphology indistinguishable from leiomyoma (LM), including conventional spindle cell LM, cellular LM, and LM with bizarre nuclei. Targeted next-generation molecular analysis performed on both the original tumor in the hysterectomy specimen and the tumor from the recurrence showed the same CDKN2C/CIC null profile. This case highlights the striking intratumoral heterogeneity that is possible in CDKN2C/CIC null LMS, including areas morphologically indistinguishable from LM. Clinicopathological findings in this case, including features that may assist in recognizing this challenging LMS subtype, are discussed. We underscore the importance of early diagnosis, which can facilitate appropriate adjuvant and/or maintenance therapy that may decrease the morbidity associated with extensive debulking surgery.

Uterine sarcoma is a gynecological mesenchymal tumor with an elusive pathogenesis. The uterine leiomyosarcoma (LMS) is the most common subtype of uterine sarcoma. LMS is a highly aggressive tumor with a poor prognosis. The genomic landscape of LMS remains unclear. Rare cases of LMS are observed to arise from leiomyoma (LM). We conducted a study to explore the genomic relationship between LMS and LM using public microarray data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Using bioinformatics analysis tools, we would like to provide molecular insight into the pathogenesis of LMS and to discover novel predictive biomarkers for this disease. LMS and LM differentially expressed genes (DEGs) were screened by analyzing GEO datasets; GSE764, GSE68312 and GSE64763; and TCGA data. A protein-protein interaction (PPI) network was constructed, and hub genes were identified utilizing the CytoHubba plug-in from Cytoscape software. In addition, weighted gene co-expression network analysis (WGCNA) was performed to identify hub genes. We took the intersection of the hub genes generated from the PPI network and WGCNA. Subsequently, random forest (RF) and support vector machine (SVM) algorithms were used to screen for key genes as predictive biomarkers. Finally, we constructed a nomogram with these genes. A total of 37 hub genes were selected using WGCNA. A total of 245 DEGs were identified; 63 DEGs were upregulated, and 182 DEGs were downregulated. Functional enrichment analysis revealed that these genes were mainly associated with the cell cycle, extracellular matrix receptor interactions and oocyte meiosis. The final hub genes were CENPA, KIF2C, TTK, MELK and CDC20. Gene set enrichment analysis (GSEA) revealed that these genes were mostly enriched in the cell cycle, mismatch repair and amino sugar and nucleotide sugar metabolism. Tumor-infiltrating immune cell analysis indicated that these genes did not have an obvious correlation with immune cells. CENPA, KIF2C, TTK, MELK and CDC20 were key genes significantly associated with LMS and LM. Functional enrichment analysis and tumor-infiltrating immune cell analysis indicated that these genes might be correlated with tumor proliferation, which might shed light on the possible pathogenesis and predictive biomarkers of LMS.

Abstract Objective: Molecular heterogeneity has been well-documented in malignant tumors but has yet to be thoroughly studied in benign non-metastasizing tumors. Uterine leiomyomas (LM) (fibroids) are benign tumors originating from the myometrium, commonly affecting women of reproductive age. Approximately half of patients present with multiple tumors, termed multifocal LM. LM are thought to be monoclonal proliferations based on their pattern of X chromosome inactivation. Mutations of the MED12 gene are the genetic hallmark of LM. Treatment of LM includes surgery and hormone therapy. It is unknown whether multifocal LM exhibit inter-tumor heterogeneity, contributing to variable response to hormone therapy. Anecdotal reports suggest that LM may occasionally transform into malignant metastasizing tumor called leiomyosarcoma (LMS). Better understanding of intra-tumor heterogeneity of LM may identify cell clones that may contribute to oncogenic transformation. In this study, we sought to perform a comprehensive multi-omic investigation of the possible intra- and inter-tumor heterogeneity of uterine LM. Methods: We performed multi-omic analysis of 62 specimens from 21 LM patients (median of 3 tumors per patient, range: 2-8). We analyzed multiple regions of a single tumor, and multiple concurrent LM from patients with multifocal disease. We profiled DNA methylation (EPIC microarrays), point mutations (whole exome sequencing) and gene expression (whole transcriptome RNA-seq) in these specimens. Results: Multi-omic profiling showed a remarkable intra- and inter-tumor heterogeneity of genomic, epigenomic and transcriptomic patterns. Through reconstruction of phylogenetic trees based on single nucleotide variants, we identified novel clonal and subclonal somatic mutations in LM. We detected for the first time different MED12 mutations in co-existing nodules in the same patient. DNA methylation and transcriptomic profiles appeared to have a similar degree of variability within individual tumors and between different tumors from the same patient. We also observed a significant enrichment of different molecular pathways between distinct regions of the same tumor. Conclusion: Molecular heterogeneity is well-established in malignant tumors, and we report it here for the first time in histologically bland lesions like LM. Our study reveals that in multifocal LM, distinct tumors can acquire unique molecular alterations, meaning that single-tumor analysis may not capture the full spectrum of molecular changes. This highlights the importance of considering molecular heterogeneity in diagnosis and evaluation of response to hormonal treatment in LM. We also demonstrate for the first time the presence of intra-tumor heterogeneity of LM. It remains to be further investigated whether clonal evolution may contribute to occasional oncogenic transformation of benign LM into malignant LMS. Citation Format: Chelsea De Bellis, Sujay Vennam, Christopher Eeles, Philippe Jolivet, Deirdre Lum, Benjamin Haibe-Kains, Matt van de Rijn, Joanna Przybyl. Multi-omic and multi-region profiling of uterine leiomyoma reveals intra- and inter-tumor heterogeneity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3896.

Abstract Background: Leiomyomas (LM), also known as fibroids, are common benign tumors of the smooth muscle of the uterus that can cause pain, infertility, and abnormal menstrual bleeding. Diagnosing LM is challenging using clinical indications alone, as they share symptoms with leiomyosarcoma (LMS), a rare, aggressive uterine malignancy with a ∼50% disease-specific survival. Pre-operative distinction between LM and LMS is difficult because these tumors are rarely biopsied before surgery. We hypothesize that a non-invasive circulating tumor DNA (ctDNA) test based on LMS- and LM-specific molecular markers will provide accurate pre-operative diagnosis and guide appropriate surgical treatment. Methods: We previously analyzed point mutations and copy number alterations (CNAs) in ctDNA using deep targeted sequencing and shallow whole-genome sequencing (WGS) from plasma specimens of 7 LMS and 12 LM patients (PMIDs: 29463554, 32232185). To build on this, we performed a new analysis of the first 4 nucleotide sequences (4-mer motifs) on the 5’ end of the cell-free DNA fragments using shallow WGS data. The frequency of 256 possible 4-mer motifs was calculated using R programming and normalized to total reads in each specimen. Two-class differential analysis identified motifs enriched in LM and LMS (false discovery rate &amp;lt; 0.05). Results: Our previous studies demonstrated the feasibility of ctDNA detection in LMS and LM patients. In LMS patients, ctDNA was detected in 6 of 7, with &amp;gt;98% specificity; in LM patients, ctDNA was detected in 6 of 12, with 76% specificity. To increase ctDNA detection sensitivity, we incorporated fragmentomics as a new ctDNA marker. Our new analysis identified 66 significantly enriched and 21 significantly decreased motifs in cell-free DNA from LMS patients compared to LM patients. Motifs associated with DNASE1L3 nuclease activity (e.g., CCCA) were significantly decreased in LM compared to LMS patients. Conclusion: We identified new tumor-specific fragmentomic markers in cell-free DNA from LMS and LM patients. Combining detection of point mutations, CNAs, and fragmentomic patterns could enable a highly sensitive ctDNA assay for accurate pre-operative distinction between LM and LMS. Next, we will validate DNASE1L3 and other nucleases in tissue microarrays of 100+ LM and 200+ LMS specimens by immunohistochemistry, and validate distinct fragmentomic patterns using expanded plasma collections. This research addresses an unmet clinical need for accurate pre-operative diagnosis of uterine tumors. Citation Format: Meagan S. Cobb, Philippe Jolivet, Kristen N. Ganjoo, Deirdre A. Lum, Matt van de Rijn, Joanna Przybyl. Liquid biopsy fragmentomics approach for the diagnosis of uterine tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3678.

The impact of hyperproliferative uterine diseases (HPD), including uterine leiomyoma (LM), uterine endometriosis (adenomyosis) (A), and endometrial hyperplastic processes (such as polyps and/or endometrial hyperplasia (PE and/or GE)) present prior to pregnancy, particularly their combination, on pregnancy outcomes remains a pressing issue in modern medicine. Over the past decade, there has been a significant increase in the number of pregnant women with endometriosis, LM, and a history of PE and/or GE. Aim of the study: To investigate the characteristics of pregnancy course in women with hyperproliferative uterine diseases. Materials and methods. A prospective cohort randomized study was conducted among 680 women treated at the Department of Purulent-Inflammatory Diseases in Obstetrics and the Department of Rehabilitation of Women's Reproductive Function at the State Institution "All-Ukrainian Center for Motherhood and Childhood of the National Academy of Medical Sciences of Ukraine" from January 2018 to December 2024. Group 1 included 517 pregnant women with HPD and their combinations (LM, A, PE and/or GE). Group 2 (comparison group) consisted of 82 pregnant women without HPD but with pregnancy complications. Group 3 (control group) included 81 pregnant women without HPD and without pregnancy complications. Results. Early pregnancy loss was observed in 68.2% of pregnant women with HPD, while 36.6% of patients had a history of induced or medical abortions, and 27.2% exhibited a combination of complications from previous pregnancies. A high frequency of uterine wall curettage was also noted in the medical history of pregnant women with HPD (88.6%). During the first trimester, the threat of early miscarriage was present in 90% of pregnant women with HPD (OR = 3.922; 95% CI: 2.261–6.802). Retrochorial hematoma was detected twice as often in Group 1 compared to the comparison group (OR = 2.519; 95% CI: 1.418–4.473), and low placentation was observed in 18.9% of women in Group 1 (OR = 2.163; 95% CI: 1.010–4.635). These complications were more prevalent in pregnant women with a combination of adenomyosis and other uterine fibroids. Conclusions. Pregnancy in women with hyperproliferative uterine diseases (LM, A, PE and/or GE present prior to pregnancy) is frequently complicated during the first trimester by the threat of early miscarriage, retrochorial hematoma, and low placentation.

Background/Objectives: We have previously identified let-7f-5p, miR-10b-5p, miR-34a-5p, miR-181b-5p, and miR-181d-5p as differentially expressed between uterine leiomyoma (LM) and leiomyosarcoma (LMS) tissue samples. The present study aimed to characterize these miRNA expression profiles and to assess the functional role of miR-34a and miR-181b in uterine LM and LMS cells. Methods: All the selected miRNAs showed downregulation in LMS cells compared to LM cells, but only miR-34a and miR-181b expression patterns matched those of patient samples. Therefore, these two miRs were selected for further analyses. Results: Loss of function analysis demonstrated that miR-34a and miR-181b silencing inhibited LM cell proliferation and migration. MiR-34a silencing induced CCND1 and MDM4 expression and inhibited KMT2D, BCL2, and NOTCH2 in LM. Silencing of miR-181b promotes TIMP3 and FGFR1 expression in LM and diminishes BCL2, NOTCH2, ATM, IRS1, and PRLR. Gain of function analysis revealed that the introduction of miR-34a and miR-181b mimics suppressed proliferation and migration in malignant LMS cells. Additionally, transfection with a miR-34a mimic downregulated NOTCH2 and BCL2 expression and enhanced the expression of CCND1, KMT2D, and TP53 in LMS cells. Moreover, miR-181b overexpression decreased TIMP3, NOTCH2, ATM, and IRS1 expression and increased the expression of FGFR1 in this cell. Importantly, the single introduction of either a miR-34a or miR-181b mimic was able to decrease the invasion capacity of LMS cells. Conclusions: Our studies demonstrated that miR-34a or miR-181b may play an anti-oncogenic role in uterine tumors; further studies are needed to better understand the role and regulatory mechanism of these miRNAs in LMS cancer development, which will help provide prognostic and therapeutic options for patients with LMS.

Infertility and reproductive issues are commonly observed in animals with clock abnormalities. Substantial rodent data is available; however, relatively few studies have investigated the connection between fertility and clock abnormalities in humans. Therefore, this study aimed to analyze the expression of circadian clock genes and their impact on genes involved in collagen production in the human myometrium and leiomyomas (LM). The relationship between the expression of brain and muscle aryl-hydrocarbon-receptor-nuclear-translocator (Arnt)-like protein-1 (BMAL1) and the genes responsible for collagen synthesis in the human MM and LMs were investigated. Human MM and LM tissues were collected for analysis from patients who underwent hysterectomy analysis. Immunohistochemical analysis, cell culturing, immunofluorescence, small interfering RNA transfection, reverse transcription quantitative real-time polymerase chain reaction, scratch wound assays, and transwell assays were employed to gain a comprehensive understanding of the cellular and molecular processes. A correlation was found between BMAL1 expression and genes regulating collagen synthesis in primary cultures of human MM and LM cells. Moreover, the inhibition of BMAL1 differentially increased the migration and invasion of MM and LM cells. This work discloses the role of BMAL1 in collagen production in primary cultures of human MM and LM cells, offering insight into clock gene involvement in both normal and pathological uterine conditions. Furthermore, this study highlights the crucial role of BMAL1 in collagen synthesis in human MM and LM cells, underscoring the significance of BMAL1 in the regulation of reproductive physiology. These results suggest that BMAL1 might be a useful target molecule for anti-LM therapy.

Leiomyomas (LM) are the most common uterine mesenchymal neoplasms and encompass a variety of histological subtypes. Bizarre nuclei are described in both leiomyomas with bizarre nuclei (LM-BN) and fumarate hydratase-deficient leiomyomas (FH-LM), which raise diagnostic concerns regarding leiomyosarcoma (LMS). Recently, an immunohistochemical algorithm to support the diagnosis of LMS based on the genomic landscape of these neoplasms was proposed. This study aimed to evaluate the algorithm's accuracy in distinguishing LM-BN and FH-LM from LMS. We collected 68 LM (29 LM-BN, 30 FH-LM, and 9 LM) and 9 LMS, along with clinicopathological and molecular data. An immunohistochemical panel comprising p53, Rb, PTEN, ATRX, DAXX, and MDM2 was applied. Nine cases were non-interpretable due to fixation issues. The algorithm demonstrated 100% accuracy for LM without bizarre nuclei (9/9) and for nonmyxoid LMS (5/5). Notably, 28.6% (14/49) of LM-BN and FH-LM exhibited at least two abnormalities, leading to potential misclassification as LMS. However, their clinical course, morphology, and genomic profile supported a benign diagnosis. Frequent alterations included Rb (20/49; 40.8%) and p53 (19/49; 38.8%), particularly in bizarre cells, while no abnormal staining was observed for ATRX, DAXX, or MDM2. The proposed algorithm has limitations in differentiating LMS from LM-BN and FH-LM, misclassifying 28.6% of the latter. Accurate interpretation requires proper internal controls, particularly for markers whose loss of expression favours malignancy. Morphology remains central for diagnosis, although integration of molecular data may provide additional insights for a definitive classification in challenging cases.

BackgroundThe diagnosis of rare uterine leiomyosarcoma (uLMS) remains a challenge given the high incidence rates of benign uterine tumors such as leiomyoma (LM). In the last decade, several clinical scores and blood serum markers have been proposed. The aim of this study is to validate and update the pLMS clinical scoring system, evaluating the accuracy of the scoring system by Zhang et al. and examining the discriminatory ability of blood markers such as serum lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR).MethodsIn a case-control study, 90 new uLMS from the DKSM consultation registry and 659 prospectively recruited LM cases from the Saarland University Hospital were used for validation. Welch’s t-test and Hedges’ g were used to evaluate blood markers and optimal thresholds and diagnostic odds ratios were calculated. Scoring systems were compared using receiver operating characteristics and proposed diagnostic cut-offs were reviewed. Missing values were imputed by random forest imputation to create the updated scoring system ‘pLMS2’ using penalized logistic regression based on the pooled data sets of 384 uLMS and 1485 LM.ResultspLMS achieved an AUC of 0.97 on the validation data, but sensitivity and specificity varied at the proposed thresholds due to a shift in the score distributions. 43 uLMS and 578 LM were included in the comparison of pLMS with Zhang’s scoring system, with pLMS being superior (AUC 0.960 vs 0.845). LDH, NLR, and PLR achieved a diagnostic odds ratios of 18.03, 8.64 and 4.81, respectively. pLMS2 is based on subscores for menopausal status interacting with age, tumor diameter, intermenstrual bleeding, hypermenorrhea, dysmenorrhea, postmenstrual bleeding, rapid tumor growth, and suspicious sonography.ConclusionsValidation of the pLMS shows stable discriminatory ability as expressed by AUC, although caution should be taken with cut-off values, as sensitivity and specificity may vary. Data collection of the updated clinical score pLMS2 remains simple and convenient, with no additional cost. The proposed thresholds of 1.5 and 5.5 can be used as a guide to avoid unnecessary or inappropriate surgery and to make the use of further diagnostic measures cost-effective. LDH, NLR and PLR provide further evidence to differentiate uLMS from LM in conjunction with clinical data.

Uterine leiomyoma (LM) is a benign hormone-dependent neoplasm of the myometrium that occupies a leading position in gynaecological pathology. The incidence of uterine LM ranges from 20–50% in women of reproductive age. Recently, there has been a tendency to detect this nosology in women aged 20–25 years. The reproductive function of women is often affected by LM, based on the data of modern studies, LM in 20–30% leads to infertility and in 15–30% of cases is the cause of pregnancy failure and miscarriage. The objective: to increase the effectiveness of cryoprotocols against the background of improving the algorithm for the treatment of uterine LM with submucosal location in women of reproductive age with PTSD by improving the receptivity of the endometrium. Materials and methods. A comprehensive clinical, instrumental and laboratory examination of 210 women of reproductive age who met the following criteria was performed: age 18–40 years; presence of uterine LM with submucosal location, which was treated surgically; presence of vitrified embryos of satisfactory quality; traumatic event in the history with the formation of PTSD; informed consent to participate in the study.Results. The results of our studies indicate that the frequency of reproductive function disorders in women with submucosal uterine fibroids and PTSD is 83.3% with a predominance of secondary infertility (50.0%) over primary infertility (33.3%). The use of our improved algorithm of pre-gravid rehabilitation measures (two-stage conservative myomectomy by hysteroscopic access) allows to reduce the frequency of pain syndrome by 36.7%; menstrual dysfunction – by 33.3%; impaired endometrial receptivity (with conventional rehabilitation – 28.3%), as well as to increase the effectiveness of restoration of reproductive function in the form of pregnancy by 18.0%. Conclusions. The analysis of the short-term and long-term results of submucous myomectomy showed that two-stage conservative myomectomy is an appropriate and effective surgical treatment. The use of less invasive endoscopic approaches according to our improved and optimised algorithm leads to a more favourable course of the postoperative period, ensures complete restoration of the basal layer of the endometrium, reduces the length of hospital stay and the period of pregravid preparation, which, in combination with hormone therapy prescribed based on endometrial immunohistochemistry, normalises menstrual function and creates favourable conditions for the realisation of a woman’s reproductive function

Leiomyoma (LM) is the most commonly identified tumor in the genital tract, occurring in 70-80% of women. The only treatment option is surgery, which significantly influences healthcare costs and negatively influences women's survival and reproductive capacity. Therefore, identifying safe and effective chemopreventive and treatment modalities is needed. We investigated the effects of 12 months of daily curcumin (0, 25.8, and 53 mg/kg) diet on the incidence and growth of spontaneously developing LM tumors in a galline (hen) model. LM tumors were detected in 58.9% (53/90) of the control hens as spontaneous occurrences, while they were observed in 37.7% (34/90) and 24.5% (22/90) of hens treated with daily doses of 25.8 mg or 53.0 mg, respectively, over 12 months. This reduced LM development by 35% and 58.5%, respectively (p = 0.004). We also observed a dose-dependent inhibition of LM-tumor growth and NF-κB, mTOR, p70S6K1, and 4E-BP1 signaling while inducing Nrf2/HO1 pathway induction LM tumors collected from hens fed with curcumin (p < 0.05). Curcumin intake notably reduced levels of TGF-β1, α-SMA, and collagen type 1, with dose-dependent effects (p < 0.001). The findings suggest that daily curcumin consumption significantly reduces the incidence of naturally occurring LMs and suppresses tumor growth. This indicates that regular curcumin intake may be an effective preventive measure against LMs.

IntroductionBladder leiomyomas (LM) are uncommon, non-cancerous growths that originate from the smooth muscle cells of the bladder and constitute 0.5% of bladder tumor cases. This review aims to compile existing data and present a summary of bladder leiomyomas’ characteristics, management, and related outcomes.MethodWe conducted systematic review of studies that investigated bladder leiomyoma. Case studies or series describing individuals with bladder leiomyoma who underwent surgery and the outcomes were included. Four databases were used in our literature search, which was carried out until January 2024: PubMed, Proquest, EBSCOHost, and Google Scholar. We utilized MeSH terms such as “leiomyoma,” “urinary bladder,” and looked for synonyms of “bladder leiomyoma” in free text.ResultsA total of 99 studies with 119 patients were included. Most reported bladder leiomyoma cases were female, accounting for 79.0% of all cases. While symptomatic patients primarily presented with lower urinary tract symptoms (LUTS) (59.7%), hematuria (24.4%), acute urine retention (11.8%), and about 16.8% of cases were incidentally detected. Storage-related symptoms were the most common LUTS (37.0%). Different diagnostic techniques were used, frequently combining CT (Computed Tomography), MRI (Magnetic Resonance Imaging), USG (Ultrasonography), and/or cystoscopy. Bladder leiomyomas were commonly found on the left lateral wall (26.9%) and the bladder neck (17.6%). In more than half of the cases (52.1%) the treatment techniques used were transurethral resection (TURBt/TUR). Fifteen out of 119 cases (12.6%) had recurrence or remain symptomatic. Symptomatic symptoms at first presentation and extended location are frequently found among recurrent or symptomatic cases after first management.ConclusionManagement of bladder leiomyoma should focus on the relief of symptoms and recurrence and be personalized based on the tumor characteristics, patient symptoms, and surgeon’s expertise. Further investigation is necessary to fully understand the best course of treatment and long-term results for bladder leiomyomas. In particular, prospective trials with bigger participant pools and meticulously controlled factors should be the main emphasis of this research.

To assess the diagnostic performance and inter-observer agreement of a PREoperative sarcoma scoring based on ultrasound (PRESS-US) in differentiating uterine leiomyosarcoma (uLMS) from leiomyoma (LM). We conducted a retrospective evaluation of patients who underwent surgery and received standardized ultrasound examinations due to the presence of uterine myoma-like masses. Histological diagnosis was used as the reference standard. The masses were analyzed using morphological uterus sonographic assessment criteria, and the diagnostic accuracy of PRESS-US was evaluated using ROC curve analysis. Kappa (κ) statistics were used to assess the inter-observer agreement between a less experienced and an expert radiologist. Among the 646 patients, 632 (97.8%) were diagnosed with LM, and 14 (2.2%) had uLMS. The malignancy rates for low-risk and high-risk patients were 0.35% and 13.48%, respectively. The optimal PRESS-US cutoff was 17.5, resulting in an AUC of 89.7% (95% CI, 0.79-1.00), with a sensitivity of 85.7% and a specificity of 87.8%. The inter-observer agreement between a less experienced and an expert radiologist was excellent (κ = 0.811, P < 0.001). PRESS-US provides effective risk stratification for uLMS for radiologists with different levels of experience, with high reliability. Subgrouping high-risk patients helps in better risk stratification.