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11 pages, 783 KB  
Article
Improved Cardiometabolic Health with Uterine-Preserving Fibroid Treatment Compared to Hysterectomy
by Rachel Michel, Gregory W. Kirschen, Caitlin S. Stukel, Sydney L. Olson, Lisa Yanek, Katie Cameron, Wendy L. Bennett and Mostafa A. Borahay
J. Clin. Med. 2026, 15(5), 1960; https://doi.org/10.3390/jcm15051960 - 4 Mar 2026
Viewed by 955
Abstract
Background/Objectives: Over 600,000 hysterectomies are performed in the United States annually, with uterine fibroids being the most common indication. It remains unknown whether removal of the uterus is associated with poor cardiometabolic outcomes. This study aimed to determine whether hysterectomy is associated with [...] Read more.
Background/Objectives: Over 600,000 hysterectomies are performed in the United States annually, with uterine fibroids being the most common indication. It remains unknown whether removal of the uterus is associated with poor cardiometabolic outcomes. This study aimed to determine whether hysterectomy is associated with adverse cardiometabolic outcomes among patients with uterine fibroids (myomectomy and no surgery as controls). Methods: Retrospective cohort study utilizing MarketScan® Database of U.S. healthcare claims dataset, including patients aged 18–55 with uterine fibroid diagnosis in 2010 or 2011 and 10 years of continuous enrollment. Patients were stratified into three groups: hysterectomy, myomectomy, and no surgery. Patients were then followed for 10 years to determine incidence of cardiometabolic disorders. The main outcome measures included coronary artery disease, congestive heart failure, cardiac arrhythmia, stroke, hypertension, hyperlipidemia, type II diabetes, and peripheral artery disease, which were defined using the ICD-9, ICD-10, and CPT codes. Results: 34,722 participants with uterine fibroids were identified. Among these, 8,196 (23.61%) patients underwent hysterectomy, 1351 patients (3.89%) underwent myomectomy, and 25,175 (72.50%) patients did not undergo surgery. Hysterectomy was associated with higher age-adjusted odds of developing stroke (aOR = 1.11), hypertension (aOR = 1.14), hyperlipidemia (aOR = 1.14), and type II diabetes (aOR = 1.20) compared to no surgery. Hysterectomy was associated with higher age-adjusted odds of developing hyperlipidemia (aOR = 1.26) compared to myomectomy. Hysterectomy with removal of ovaries versus hysterectomy with retention of ovaries had similar cardiometabolic outcomes. Conclusions: Among patients with fibroids, hysterectomy was associated with higher odds of developing adverse cardiometabolic outcomes compared to myomectomy or no surgery. Retention of the ovaries was not protective among those undergoing hysterectomy. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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17 pages, 7276 KB  
Review
An Update on Uterine Smooth Muscle Tumors: Is It a Leiomyoma, a STUMP, or a Leiomyosarcoma?
by Catalin-Bogdan Satala, Gabriela Patrichi, Alina Mihaela Gurau, Alexandra Toma, Constantin Popazu and Daniela Mihalache
Biomedicines 2026, 14(2), 285; https://doi.org/10.3390/biomedicines14020285 - 27 Jan 2026
Viewed by 616
Abstract
Uterine smooth muscle tumors (USMTs) represent a diagnostically and clinically challenging subset of uterine mesenchymal neoplasms. Up to 5% of these tumors exhibit ambiguous histological features that preclude definitive classification as either benign leiomyomas or malignant leiomyosarcomas. This review provides a comprehensive synthesis [...] Read more.
Uterine smooth muscle tumors (USMTs) represent a diagnostically and clinically challenging subset of uterine mesenchymal neoplasms. Up to 5% of these tumors exhibit ambiguous histological features that preclude definitive classification as either benign leiomyomas or malignant leiomyosarcomas. This review provides a comprehensive synthesis of the evolving diagnostic criteria, histopathological variants, and recent advancements in immunohistochemical and molecular profiling of smooth muscle tumors with uncertain malignant potential (STUMPs). The review traces the historical development of diagnostic criteria, from the original mitotic thresholds to the “Stanford criteria,” which incorporate mitotic index, cytological atypia, and tumor cell necrosis. Contemporary WHO guidelines largely uphold these principles, with nuanced refinements for spindle, myxoid, and epithelioid subtypes. However, recent studies suggest additional morphologic indicators, such as atypical mitoses, infiltrative margins, and vascular invasion, may provide prognostic insight. Notably, necrosis remains the most reliable histologic predictor of recurrence, while mitotic activity and atypia, though important, are less specific. In conclusion, STUMPs represent a heterogeneous group with unpredictable behavior that requires long-term clinical follow-up. While existing histological and molecular tools aid classification, definitive prognostic markers remain elusive. Further studies integrating histopathology, immunohistochemistry, and molecular biology are essential to refine diagnosis and improve therapeutic decision-making in this diagnostically ambiguous group of uterine tumors. Full article
(This article belongs to the Special Issue Gynecological Diseases in Cellular and Molecular Perspectives)
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13 pages, 235 KB  
Article
Lifestyle, Modifiable Behavioral Factors, and Biomarker Profiles in Uterine Lesions
by Anna Mihaylova, Antoniya Yaneva, Angelina Mollova-Kyosebekirova, Ekaterina Uchikova, Desislava Bakova, Mariya Koleva-Ivanova, Mariana Parahuleva and Nikoleta Parahuleva
Healthcare 2026, 14(2), 231; https://doi.org/10.3390/healthcare14020231 - 16 Jan 2026
Viewed by 360
Abstract
Background: Precursor endometrial lesions and endometrial cancer are strongly influenced by lifestyle-related risk factors, including obesity, low physical activity, and unfavorable dietary patterns. Identifying these factors is essential for early prevention and for improving health literacy among women. Objective: The objective [...] Read more.
Background: Precursor endometrial lesions and endometrial cancer are strongly influenced by lifestyle-related risk factors, including obesity, low physical activity, and unfavorable dietary patterns. Identifying these factors is essential for early prevention and for improving health literacy among women. Objective: The objective of this study was to evaluate the influence of modifiable lifestyle factors on the likelihood of developing EIN and endometrial cancer in comparison with leiomyoma. Materials and Methods: A cross-sectional analytical study was conducted among 50 women, divided into three groups: leiomyoma (n = 20), EIN (n = 15), and endometrial cancer (n = 15). BMI, physical activity, dietary habits, sleep duration, stress levels, and smoking status were assessed. Statistical analysis included the Kruskal–Wallis test, correlation analysis, and logistic regression. Results: BMI was identified as an independent predictor of EIN/EC (OR = 1.29; p = 0.015). Women with EIN/EC demonstrated significantly lower levels of physical activity (p = 0.018). A clustering of behavioral risks was observed: higher BMI was associated with higher stress and shorter sleep duration. Conclusions: Modifiable lifestyle factors play a key role in the development of precursor and malignant endometrial conditions. Targeted interventions focusing on weight management, increased physical activity, and improved health literacy may reduce risk and improve quality of life among peri- and postmenopausal women. Full article
16 pages, 1815 KB  
Case Report
Paratubal Leiomyoma Mimicking Ovarian Malignancy: A Case Report and Literature Review
by Wen-Lin Hsieh and Dah-Ching Ding
Diagnostics 2026, 16(2), 218; https://doi.org/10.3390/diagnostics16020218 - 9 Jan 2026
Viewed by 634
Abstract
Background and Clinical Significance: A paratubal leiomyoma is an exceptionally rare benign smooth muscle tumor arising from paratubal tissue, with only sporadic cases reported in the literature. Case Presentation: We present the case of a 72-year-old postmenopausal woman with intermittent spotting [...] Read more.
Background and Clinical Significance: A paratubal leiomyoma is an exceptionally rare benign smooth muscle tumor arising from paratubal tissue, with only sporadic cases reported in the literature. Case Presentation: We present the case of a 72-year-old postmenopausal woman with intermittent spotting for three months. A pelvic examination revealed a retained intrauterine device, which was removed along with an old sanguineous discharge. A transvaginal ultrasound demonstrated a complex left adnexal mass with calcifications, and computed tomography (CT) confirmed a 7.8 × 5.5 × 4.7 cm lesion suggestive of an ovarian malignancy. Tumor markers showed mildly elevated CA-125 and carcinoembryonic antigen (CEA) levels. Endometrial sampling using a hysteroscopy and curettage revealed hyperplasia without atypia. The patient underwent a total laparoscopic hysterectomy with a bilateral salpingo-oophorectomy. A diagnostic laparoscopy revealed a well-circumscribed solid mass arising from the mesosalpinx, separate from the ovary and fallopian tube and consistent with a paratubal mass, which was successfully excised laparoscopically. Frozen sections suggested a fibroma, and the final pathology confirmed a paratubal leiomyoma with hyalinization, accompanied by adenomyosis and simple endometrial hyperplasia. The patient recovered uneventfully, and the 6-month follow-up showed no recurrence. This case highlights the diagnostic challenge of differentiating paratubal leiomyomas from ovarian tumors based on imaging alone. Histopathological examination is essential for confirmation. Conclusions: Awareness of paratubal leiomyomas as a differential diagnosis may prevent overtreatment and guide the appropriate surgical management of postmenopausal women presenting with adnexal masses. Full article
(This article belongs to the Special Issue Precision Diagnostics in Gynecologic Health and Disease)
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19 pages, 2288 KB  
Review
Lipedema in Women and Its Interrelationship with Endometriosis and Other Gynecologic Diseases: A Scoping Review
by Diogo Pinto da Costa Viana, Adriana Luckow Invitti and Eduardo Schor
Biomedicines 2026, 14(1), 122; https://doi.org/10.3390/biomedicines14010122 - 7 Jan 2026
Viewed by 1547
Abstract
Background: Emerging evidence suggests that lipedema may share hormonal, inflammatory, and genetic mechanisms with gynecologic diseases, particularly endometriosis. However, the extent and nature of these interrelationships remain poorly characterized, supporting the need for this scoping review. Objectives: To map and synthesize [...] Read more.
Background: Emerging evidence suggests that lipedema may share hormonal, inflammatory, and genetic mechanisms with gynecologic diseases, particularly endometriosis. However, the extent and nature of these interrelationships remain poorly characterized, supporting the need for this scoping review. Objectives: To map and synthesize the available evidence on the clinical, pathophysiological, and epidemiological interrelationships between lipedema in women, endometriosis, and other gynecologic diseases. Methods: Searches were conducted in international and regional health databases, including MEDLINE (PubMed), CINAHL, Scopus, Embase, Web of Science, the Cochrane Library, LILACS/VHL, APA PsycInfo, SciELO, Epistemonikos, and La Referencia, as well as grey literature sources and relevant institutional websites. There were no language restrictions. The search period began in 1940, the year in which lipedema was first described by Allen and Hines. Study selection followed a two-stage process conducted independently by two reviewers, consisting of title and abstract screening followed by full-text review. Data extraction was performed using a pre-developed and peer-reviewed instrument covering participants, concept, context, study methods, and main findings. The review protocol was registered in the Open Science Framework. Results: Twenty-five studies from ten countries were included. Synthesized evidence supports the characterization of lipedema as a systemic condition with metabolic and hormonal dimensions. Key findings include symptom onset linked to reproductive milestones, a high frequency of gynecologic and endocrine comorbidities, and molecular features overlapping with steroid-dependent pathologies. These patterns reflect a recent shift from a predominantly lymphovascular paradigm toward a more integrated endocrinometabolic framework. Conclusions: The findings indicate that lipedema clusters with hormone-sensitive gynecologic and endocrine features across reproductive life stages. Full article
(This article belongs to the Special Issue New Insights in Reproductive Health and Disease)
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16 pages, 1052 KB  
Review
Venous Thromboembolism Associated with Uterine Fibroids: A Review of Reported Cases
by Radmila Sparić, Marta Stojković, Momir Šarac, Giovanni Pecorella, Vladimir Živković, Safak Hatirnaz and Andrea Tinelli
J. Clin. Med. 2026, 15(2), 444; https://doi.org/10.3390/jcm15020444 - 6 Jan 2026
Viewed by 903
Abstract
Background/Objectives: The most prevalent benign tumors in women are uterine fibroids. Most patients—more than half—do not exhibit any symptoms, but the most common clinical signs include irregular uterine bleeding, pelvic pain, gastrointestinal problems, increased frequency of urination, and, in some cases, infertility. [...] Read more.
Background/Objectives: The most prevalent benign tumors in women are uterine fibroids. Most patients—more than half—do not exhibit any symptoms, but the most common clinical signs include irregular uterine bleeding, pelvic pain, gastrointestinal problems, increased frequency of urination, and, in some cases, infertility. Venous thromboembolism is a very rare consequence, especially when significant uterine fibroids are present. This syndrome usually develops because of pelvic vascular systems being compressed, which causes venous stasis. Pharmacological treatment, minimally invasive procedures, and surgical techniques are examples of therapy alternatives. The purpose of this study is to present, compare, and potentially elucidate the underlying mechanisms of VTE development in fibroids. Methods: we have synthesized findings from 24 documented instances of venous thromboembolism (VTE) linked to uterine fibroids. Results: the principal mechanism underlying thromboembolic events was identified as the mechanical compression of pelvic venous structures due to mass effect. Additionally, we recognized other pertinent risk factors, including oral contraceptive use, May-Thurner syndrome, myomatous erythrocytosis, and intravenous leiomyomatosis. None of the reviewed case reports provided evidence of confirmed inherited thrombophilia in the patients under investigation. The femoral and popliteal veins, primarily in the left leg, were most frequently impacted by thrombosis and the ensuing blockage. Imaging techniques confirmed that individuals suffered pulmonary embolisms in half of the cases. When the right treatment was given as soon as possible, most of VTEs had favorable outcome. In almost half of the cases examined, the patient had a hysterectomy. Since all symptoms were alleviated and the chance of additional thromboembolic consequences was reduced, this treatment strategy turned out to be the most successful. Conclusions: Clinicians should maintain a low threshold for venous imaging in women with large pelvic masses and unilateral limb symptoms. Despite being uncommon, VTE associated with UFs can cause serious morbidity. Mechanical venous compression is the main mechanism, which is often exacerbated by additional prothrombotic variables. Clinicians should maintain a low threshold for venous imaging in women with significant pelvic masses and unilateral limb symptoms, look for concurrent thrombophilia, and investigate early surgical consultation to address compressive etiologies when VTE is still unexplained. It would be simpler to ascertain the actual incidence and pinpoint risk variables that can be altered with standardized reporting of fibroid-associated VTE and prospective registries. Full article
(This article belongs to the Section Vascular Medicine)
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19 pages, 2972 KB  
Article
Nationwide Multicenter Study of Advanced Endoscopic Resection and Malignant Risk Model for Gastric Myogenic Tumors (GASTRO Trial)
by Chih-Tsung Fan, Tze-Yu Shieh, Wen-Hung Hsu, Hsi-Yuan Chien, Ching-Tai Lee, Ming-Yao Chen, Chung-Ying Lee, Wei-Chen Tai, Sz-Iuan Shiu, I-Ching Cheng and Chen-Shuan Chung
Life 2026, 16(1), 82; https://doi.org/10.3390/life16010082 - 5 Jan 2026
Viewed by 903
Abstract
Background/Objectives: The prevalence of gastric subepithelial lesions (SELs) is rising. Endoscopic resection (ER) technique provides a minimally invasive alternative to manage gastric SELs. This study aims to evaluate the effectiveness and safety of ER for gastric myogenic tumors, and examine predictors for gastrointestinal [...] Read more.
Background/Objectives: The prevalence of gastric subepithelial lesions (SELs) is rising. Endoscopic resection (ER) technique provides a minimally invasive alternative to manage gastric SELs. This study aims to evaluate the effectiveness and safety of ER for gastric myogenic tumors, and examine predictors for gastrointestinal stromal tumors (GISTs). Methods: The retrospective study was conducted between 2012 and 2024 at nine tertiary centers in Taiwan. We enrolled patients with endoscopic ultrasound (EUS)-documented gastric myogenic tumors managed by endoscopic muscular dissection (EMD), endoscopic subserosal dissection (ESSD), submucosal tunneling endoscopic resection (STER), and endoscopic full-thickness resection (EFTR). Clinical manifestation, endoscopic features, and outcomes were analyzed. Results: We enrolled 325 patients with 332 lesions [mean EUS size 14.5 mm, 153 (46.1%) leiomyoma, 152 (45.8%) GISTs, 27 (8.1%) other histology]. ER techniques were 193 (58.1%) EMD, 46 (13.9%) ESSD, 28 (8.4%) STER, and 65 (19.6%) EFTR. Technical success, en bloc, and R0 resection rates were 97.0%, 94.3%, and 88.9%, respectively. Twenty-four (9.0%) procedures were shifted to unintentional EFTR, and 21 (6.3%) patients had complications. No recurrence occurred during mean follow-up period of 921.4 days. Two (0.6%) patients died of non-procedure related reasons. Old age, fundus location, heterogeneous echotexture, and exophytic growth pattern were independent risk factors for GIST (all with p < 0.05). Using the above factors, we built a prediction model with sensitivity of 77.0%, specificity of 85.6%, and AUC of 0.8771. Conclusions: ER is an efficient and safe management for gastric myogenic tumors. The histological type could be predicted by demographic characteristics and EUS features. Full article
(This article belongs to the Section Medical Research)
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12 pages, 2243 KB  
Article
Contrast-Enhanced Harmonic Endoscopic Ultrasonography for Diagnosing Gastric Subepithelial Tumors
by Moon Won Lee, Dong Chan Joo, Gwang Ha Kim, Bong Eun Lee and Hye Kyung Jeon
Diagnostics 2026, 16(1), 165; https://doi.org/10.3390/diagnostics16010165 - 5 Jan 2026
Viewed by 522
Abstract
Background/Objectives: Contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) is a promising tool for differentiating gastric subepithelial tumors (SETs). However, most published studies have mainly included gastrointestinal stromal tumors (GIST) and leiomyomas in the gastrointestinal tract, not limited to gastric SETs. This study evaluated the diagnostic [...] Read more.
Background/Objectives: Contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) is a promising tool for differentiating gastric subepithelial tumors (SETs). However, most published studies have mainly included gastrointestinal stromal tumors (GIST) and leiomyomas in the gastrointestinal tract, not limited to gastric SETs. This study evaluated the diagnostic performance of CH-EUS in gastric SETs encountered in clinical practice. Methods: We retrospectively analyzed 68 patients who underwent CH-EUS for gastric SETs between March 2021 and July 2025 at our institution. Gastric SETs were classified into benign (n = 27: ectopic pancreas, leiomyoma, schwannoma, glomus tumor, plexiform fibromyxoma, desmoid tumor, solitary fibrous tumor, and abscess) and GIST groups (n = 41). CH-EUS features, including arterial enhancement, irregular vessels, and diffuse enhancement, were assessed. Histopathological confirmation was obtained through EUS-guided fine-needle biopsy or endoscopic/surgical resection. Results: The GIST group showed significantly higher rates of arterial enhancement (95.1% vs. 74.1%, p = 0.024), irregular vessels (51.2% vs. 22.2%, p = 0.017), and diffuse enhancement (87.8% vs. 66.7%, p = 0.035) than the benign SETs. The diagnostic performance of arterial enhancement showed a sensitivity of 95.1% and specificity of 25.9%, while irregular vessels demonstrated a sensitivity of 51.2% and specificity of 77.8%, and diffuse enhancement showed a sensitivity of 87.8% and specificity of 33.3%. When combining ≥2 CH-EUS features, the sensitivity and specificity were 92.7% and 33.3%, respectively, with an overall accuracy of 69.1%. The presence of all three features yielded a specificity of 81.5% but a lower sensitivity (46.3%). Conclusions: CH-EUS exhibited a high sensitivity but low specificity in differentiating GISTs from various benign gastric SETs when using a combination of at least two CE-EUS features, including arterial enhancement, irregular vessels, and diffuse enhancement. Full article
(This article belongs to the Special Issue New Advances in Gastrointestinal Endoscopy)
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17 pages, 1310 KB  
Review
Beyond VEGF and TGF-β: A Comprehensive Review of Growth Factor Pathways in the Pathophysiology of Uterine Leiomyomas
by Nuray Rozmurat, Sanja Terzic, Peng Zhao, Gauri Bapayeva, Kuralay Kongrtay, Matthew Naanlep Tanko and Milan Terzic
Biology 2026, 15(1), 92; https://doi.org/10.3390/biology15010092 - 1 Jan 2026
Viewed by 748
Abstract
Uterine leiomyomas or fibroids, are non-cancerous smooth muscle proliferations of the uterus, occurring mostly in women of reproductive age. Their pathogenesis involves complex growth factor interactions that regulate cellular proliferation, extracellular matrix (ECM) remodeling, and angiogenesis in myometrium. Women affected by fibroids often [...] Read more.
Uterine leiomyomas or fibroids, are non-cancerous smooth muscle proliferations of the uterus, occurring mostly in women of reproductive age. Their pathogenesis involves complex growth factor interactions that regulate cellular proliferation, extracellular matrix (ECM) remodeling, and angiogenesis in myometrium. Women affected by fibroids often have a range of consequences such as infertility, endometriosis, and dysmenorrhea. Several growth factors such as vascular endothelial growth factor (VEGF), transforming growth factor (TGF-β), and platelet-derived growth factors (PDGF) have long been described as key regulators of angiogenic and fibrotic activities in fibroid tissue. Moreover, we summarized updated information between 2015 and 2025 following strictly inclusion/exclusion criteria and key research areas, including growth factors and its isoform-interaction, their roles within key signaling pathways, and the contribution of ECM deposition in uterine fibroids development and growth. Implementing growth factors in the clinical research field can develop new biomarkers and treatment options, focusing on effective and advanced management of uterine fibroids. Full article
(This article belongs to the Section Physiology)
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15 pages, 4732 KB  
Article
The Diagnostic Performance of a Four-Gene Digital Droplet PCR Panel for Urine Liquid Biopsy in Urothelial Bladder Cancer
by Mark Jain, Alexander Tivtikyan, Dmitry Kislyakov, Tagir Rakhmatullin, David Kamalov, Vladislav Kokarev, Lolita Vorobeva, Larisa Samokhodskaya, Maria Zvereva and Armais Kamalov
Diagnostics 2026, 16(1), 69; https://doi.org/10.3390/diagnostics16010069 - 24 Dec 2025
Viewed by 579
Abstract
Background: Urothelial bladder carcinoma (UBC) is a disease that lacks robust non-invasive laboratory biomarkers. Recently, urine liquid biopsy has emerged as a promising tool for diagnosis and surveillance of patients with these tumors. The aim of this study was to evaluate the [...] Read more.
Background: Urothelial bladder carcinoma (UBC) is a disease that lacks robust non-invasive laboratory biomarkers. Recently, urine liquid biopsy has emerged as a promising tool for diagnosis and surveillance of patients with these tumors. The aim of this study was to evaluate the diagnostic potential of a urinary tumor DNA detection panel, which included eight common point mutations in TERT, GPR126, FGFR3, and PIK3CA genes, in UBC. Methods: The study included patients with histologically confirmed UBC (n = 88) and patients with cystitis, bladder leiomyomas, or other non-malignant conditions (control group; n = 72). DNA was extracted from whole urine specimens. ddPCR analysis was performed using the Bio-Rad QX200 AutoDG ddPCR system. Results: Urinary tumor DNA detection panel demonstrated a sensitivity of 78.4% and a specificity of 100% (AUC−ROC = 0.892). Detection rates for the analyzed mutations were the following: 54.5%, 37.5%, 28.4%, and 38.6% for TERT, GPR126, FGFR3, and PIK3CA, respectively. Pairwise comparisons of mutant allele fractions (MAFs) for samples simultaneously positive for ≥2 mutations revealed an absence of significant differences (p > 0.05), except for the pair of FGFR3 vs. PIK3CA (p = 0.03). MAFs were not associated with any clinical and demographic features (p > 0.05), with the only exception being the tumor size: patients with tumors larger than 2.16 cm3 had higher MAFs than the rest (23.4 [1.8; 46.3] vs. 1.6 [0; 24.6] %, respectively, p = 0.02). Conclusions: Upon further validation, the presented tumor DNA detection panel for ddPCR might become a useful tool for diagnostic purposes in UBC. Full article
(This article belongs to the Special Issue Diagnostic and Prognostic Non-Invasive Markers in Bladder Cancer)
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20 pages, 3578 KB  
Article
Decoding Bromodomain and Extra-Terminal Domain Protein-Mediated Epigenetic Mechanisms in Human Uterine Fibroids
by Qiwei Yang, Somayeh Vafaei, Ali Falahati, Azad Khosh, Mervat M. Omran, Tao Bai, Maria Victoria Bariani, Mohamed Ali, Thomas G. Boyer and Ayman Al-Hendy
Int. J. Mol. Sci. 2025, 26(24), 12144; https://doi.org/10.3390/ijms262412144 - 17 Dec 2025
Cited by 1 | Viewed by 630
Abstract
Uterine Fibroids (UFs) are the most common benign tumors in women of reproductive age, affecting ~77% of women overall and are clinically manifest in ~25% by age 50. Bromodomain and extra-terminal domain (BET) proteins play key roles in epigenetic transcriptional regulation, influencing many [...] Read more.
Uterine Fibroids (UFs) are the most common benign tumors in women of reproductive age, affecting ~77% of women overall and are clinically manifest in ~25% by age 50. Bromodomain and extra-terminal domain (BET) proteins play key roles in epigenetic transcriptional regulation, influencing many biological processes, such as proliferation, differentiation, and DNA damage response. Although BET dysregulation contributes to various diseases, their specific role in the pathogenesis of UFs remains largely unexplored. The present study aimed to determine the expression pattern of BET proteins in UFs and matched myometrium and further assess the impact of BET inhibitors on UF phenotype and epigenetic changes. Our studies demonstrated that the levels of Bromodomain-containing protein (BRD)2 and detection rate of BRD4 were significantly altered in UFs compared to matched myometrium, suggesting that aberrant BET protein expression may contribute to the pathogenesis of UFs. To investigate the biological effects of BET proteins, two small-molecule inhibitors, JQ1 and I-BET762, were used to assess their impact on UF cell behavior and transcriptomic profiles. Targeted inhibition of BET proteins markedly reduced UF cell viability compared with myometrial cells and induced cell cycle arrest. Unbiased transcriptomic profiling coupled with bioinformatic analysis revealed that BET inhibition altered multiple biological pathways, including G2M checkpoint, E2F targets, mitotic spindle, mTORC1 signaling, TNF-α signaling via NF-κB, and inflammatory response, as well as reprogrammed the UF cell epigenome. Notably, BET inhibition decreased the expression of several genes encoding extracellular matrix (ECM) proteins, a hallmark of UFs. Collectively, these results support that BET proteins play a pivotal role in regulating key signaling pathways and cellular processes in UFs. Targeting BET proteins may therefore represent a promising non-hormonal therapeutic strategy for UF treatment. Full article
(This article belongs to the Section Biochemistry)
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7 pages, 4086 KB  
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STUMP Swiftly Followed by Large Adenomyoma in a Young Nulliparous Patient
by Georgiana Nemeti, Gheorghe Cruciat, Iulian Gabriel Goidescu, Chereches Roberta, Vasile Marian Ticala, Mihai Surcel, Cerasela Mihaela Goidescu, Adelina Staicu, Dan Boitor-Borza, Bogdan Fetica, Ioana Cristina Rotar and Daniel Muresan
Diagnostics 2025, 15(23), 3018; https://doi.org/10.3390/diagnostics15233018 - 27 Nov 2025
Cited by 1 | Viewed by 463
Abstract
The potential concurrence of uterine leiomyoma and adenomyosis has been mentioned in several studies to date, but as co-existing entities, not as a sequence of pathologic events. This is the case of a young 31-year-old nulliparous patient presenting with unspecific pain and abnormal [...] Read more.
The potential concurrence of uterine leiomyoma and adenomyosis has been mentioned in several studies to date, but as co-existing entities, not as a sequence of pathologic events. This is the case of a young 31-year-old nulliparous patient presenting with unspecific pain and abnormal uterine bleeding (AUB) pattern symptoms, which was clinically diagnosed with FIGO 0 fibroid “in status nascendi”. Following removal, the tumor turned out to be a STUMP at the histopathologic workup. After 9 months postoperatively and two unremarkable follow-ups, the patient presented again for pelvic pain and AUB, when ultrasound revealed a heterogeneous endo-uterine tumor of 5 cm, rich in large vessels, with rapid growth at serial ultrasound. MRI established the diagnosis of adenomyosis. In the context of a prior STUMP, nulliparity and rapidly enlarging uterine mass, despite conservative management counseling in a multidisciplinary team, the patient preference was towards radical surgery to prevent any future reproductive organ-related distress, and she opted for total hysterectomy with bilateral adnexectomy. The co-existence of fibroid and adenomyosis has been signaled by several authors, but this is the first report of such a sequence of events (STUMP to large adenomyoma) with swift development, to the best of our knowledge. Full article
(This article belongs to the Collection Interesting Images)
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15 pages, 7486 KB  
Article
Diagnostic Value and Interobserver Reproducibility of Histopathological Features in Fumarate Hydratase-Deficient Uterine Leiomyomas
by Aleksandra Rogozhina, Alina Badlaeva, Anna Tregubova, Aleksandra Asaturova, Maria Kuznetsova and Gennady Sukhikh
Diagnostics 2025, 15(23), 3006; https://doi.org/10.3390/diagnostics15233006 (registering DOI) - 26 Nov 2025
Viewed by 691
Abstract
Background/Objectives: Fumarate hydratase-deficient leiomyomas (dFH-LMs) are a rare subtype of uterine smooth muscle tumors (USMTs) with implications for hereditary leiomatosis and renal cell carcinoma (HLRCC). Although several morphologic clues have been proposed, their diagnostic reproducibility is poorly defined. We aimed to determine the [...] Read more.
Background/Objectives: Fumarate hydratase-deficient leiomyomas (dFH-LMs) are a rare subtype of uterine smooth muscle tumors (USMTs) with implications for hereditary leiomatosis and renal cell carcinoma (HLRCC). Although several morphologic clues have been proposed, their diagnostic reproducibility is poorly defined. We aimed to determine the diagnostic significance of histopathologic features associated with fumarase deficiency and the reproducibility of key morphologic criteria for defining dFH-LMs. Methods: A retrospective analysis was performed on 45 USMTs that were initially classified as atypical leiomyomas (ALMs). The cohort comprised patients aged 21 to 75 years who had surgery at one tertiary medical care center from 2016 to 2025. Hematoxylin–eosin (H&E) slides were independently examined by three pathologists for features associated with FH deficiency, including eosinophilic globules, staghorn-like vessels, diffuse nuclear atypia, “bizarre” nuclei, and prominent nucleoli with halos. Molecular status was determined by immunohistochemistry (IHC) for fumarate hydratase (FH) and S-(2-succino)-cysteine (2SC). Interobserver agreement was quantified using Fleiss’s κ and Cohen’s κ. Results: Loss of FH expression was detected in 26/45 tumors (57.7%). Eosinophilic globules occurred in 88.5% of dFH-LMs, but only in 15.8% of ALMs (p < 0.001). By majority consensus (≥2 of 3 reviewers), the eosinophilic globules predicted FH deficiency with a sensitivity of 88.0% and a specificity of 85.0%; interobserver reproducibility was substantial (κ = 0.63). Staghorn-like vessels occurred in 73.1% of dFH-LMs vs. 26.3% of ALMs (p = 0.02) and diffuse nuclear atypia (84.6%) was also more frequent in dFH-LMs (p = 0.01). Patients with dFH-LMs were significantly younger than those with ALMs (Median, 34 vs. 41 years). Conclusions: Eosinophilic globules, staghorn-like vessels and diffuse nuclear atypia have been shown to have high diagnostic value and could be considered morphologic indicators of dFH-LMs. The substantial interobserver reproducibility of eosinophilic globules makes this feature particularly promising for routine clinical practice. Full article
(This article belongs to the Special Issue Pathology and Diagnosis of Gynecologic Diseases, 3rd Edition)
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8 pages, 1171 KB  
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Uterine Angiomyolipoma Presenting as a Rapidly Growing Uterine Mass in a Postmenopausal Woman
by Dae Hyun Song, Hyo Jung An and Jong Chul Baek
Diagnostics 2025, 15(23), 2995; https://doi.org/10.3390/diagnostics15232995 - 25 Nov 2025
Cited by 1 | Viewed by 631
Abstract
Uterine angiomyolipoma (AML) is an exceptionally rare mesenchymal tumor of the perivascular epithelioid cell tumor (PEComa) family. Most cases are benign and exhibit a triphasic histologic pattern. Although extragenital PEComas typically show strong, diffuse HMB-45 reactivity, uterine AMLs/PEComas often exhibit weak or negative [...] Read more.
Uterine angiomyolipoma (AML) is an exceptionally rare mesenchymal tumor of the perivascular epithelioid cell tumor (PEComa) family. Most cases are benign and exhibit a triphasic histologic pattern. Although extragenital PEComas typically show strong, diffuse HMB-45 reactivity, uterine AMLs/PEComas often exhibit weak or negative staining, thereby introducing diagnostic uncertainty. We describe a rare case of uterine AML with diffuse nuclear atypia in a postmenopausal woman, which mimicked a degenerative leiomyoma or leiomyosarcoma. A 49-year-old postmenopausal woman presented with the rapid enlargement of a uterine mass that had been followed for four years as a presumed leiomyoma. Imaging revealed a well-circumscribed uterine mass with heterogeneous enhancement, cystic degeneration, and restricted diffusion on MRI. A total hysterectomy was performed. Grossly, the tumor measured 8 cm. Microscopically, it consisted of pleomorphic epithelioid cells (70%), mature adipose tissue (20%), and thick-walled vessels. Immunohistochemistry revealed diffuse smooth muscle actin (SMA) positivity, while Human Melanoma Black (HMB)-45 and Melan-A were negative. Only one mitosis per 50 HPF was identified, with no atypical mitoses or necrosis, and the Ki-67 index was low (<5%). The patient has remained disease-free for 56 months post-surgery. This case represents the first documented HMB-45-negative uterine angiomyolipoma with diffuse nuclear atypia, characterized by a low mitotic index, low Ki-67 proliferation rate, and a benign 56-month follow-up. It broadens the morphologic spectrum of uterine AML, demonstrating that diffuse nuclear atypia can occur in HMB-45-negative tumors with benign behavior, and that atypia alone should not be interpreted as evidence of malignancy. Recognition of this rare variant is essential to avoid misdiagnosing it as leiomyosarcoma. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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Article
Illuminating the Intricacies: A Comparative Cross-Sectional Sonographic Evaluation of Degenerative Changes in Leiomyomas Through Post-Processing Technique
by Mahasin G. Hassan, Nouf Aldrees, Sadeem Aldawsari, Raghad Alanazi, Noura Alboqami, Maryem Alanazi, Renad Alanazi, Khadejah Alrashidi and Basim S. Almutairi
Diagnostics 2025, 15(23), 2943; https://doi.org/10.3390/diagnostics15232943 - 21 Nov 2025
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Abstract
Background: Leiomyomas are benign tumors that may cause symptoms and affect fertility, requiring careful assessment. Magnetic Resonance Imaging (MRI) becomes crucial when ultrasonography results are inconclusive; however, it is expensive and time-consuming. Utilizing post-processing techniques could enhance the ultrasound results. Using ultrasound [...] Read more.
Background: Leiomyomas are benign tumors that may cause symptoms and affect fertility, requiring careful assessment. Magnetic Resonance Imaging (MRI) becomes crucial when ultrasonography results are inconclusive; however, it is expensive and time-consuming. Utilizing post-processing techniques could enhance the ultrasound results. Using ultrasound with Fiji (ImageJ) enables precise evaluation of leiomyoma degeneration and may reduce the need for MRI. Aim: This study aims to evaluate the effectiveness of a post-processing technique using Fiji (ImageJ) to detect degenerative changes in leiomyomas and compare these findings with those obtained from conventional ultrasound and MRI results. Methods: A cross-sectional analytical study was conducted at King Saud Medical City involving 41 females diagnosed with uterine leiomyomas using ultrasound and MRI. Ultrasound images were analyzed using Fiji software to identify degenerative changes and compare results with ultrasound and MRI reports. Results: ImageJ outperformed ultrasound across all diagnostic metrics, with higher sensitivity (84.2% vs. 63.2%), specificity (81.8% vs. 22.7%), and accuracy (82.9% vs. 41.5%). ROC analysis showed superior diagnostic performance of ImageJ (AUC = 0.830) compared to ultrasound (AUC = 0.429), with a significant correlation to MRI findings (p < 0.001). Fibroids with and without degeneration showed no significant differences in Fiji parameters (p > 0.05). Conclusions: Integrating post-processing tools such as ImageJ with ultrasound imaging significantly improves the detection of degenerative changes in uterine leiomyomas, potentially reducing dependence on costly and less accessible modalities like MRI. Future studies should utilize a prospective design with larger sample sizes to strengthen the validity and generalizability of these findings. Full article
(This article belongs to the Special Issue Advanced Ultrasound Techniques in Diagnosis)
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