Search Results (118)

Background: Placenta accreta spectrum (PAS) refers to the abnormal placental implantation into the uterine wall, and its incidence is rising in parallel with increasing cesarean deliveries and myomectomies. PAS carries high maternal risks, including hemorrhage, shock, and death. Management involves either a hysterectomy or conservative approaches to preserve fertility that come with higher risks of maternal morbidity and mortality. Radiofrequency ablation (RFA) is a well-established modality for treating soft tissue tumors, but its use for PAS is not well studied. Case: We report a case of successful postpartum treatment of placenta accreta with transcervical radiofrequency ablation, which preserved uterine integrity and resolved significant bleeding without postoperative complications. Conclusions: Transcervical RFA may offer a safe and minimally invasive treatment for placenta accreta that conserves the uterus and may maintain reproductive capacity. Full article

Background and Clinical Significance: Uterine smooth muscle tumors range from benign leiomyomas to highly aggressive leiomyosarcomas. Smooth muscle tumors of uncertain malignant potential (STUMP) represent an intermediate and diagnostically challenging category defined by borderline or discordant histological features. Their clinical management remains complex due to limited possibilities for reliable preoperative differentiation and the absence of clearly established surveillance protocols. The situation becomes particularly sensitive in postmenopausal patients, in whom tumor growth or abnormal bleeding raises concern for malignancy. Case Presentation: We report a 66-year-old postmenopausal woman presenting with persistent uterine bleeding and interval growth of a previously presumed leiomyoma. Transvaginal ultrasound demonstrated a heterogeneous intramural mass measuring approximately 5–7 cm, while endometrial sampling revealed inactive, atrophic endometrium without evidence of malignancy. Given the patient’s postmenopausal status and progressive symptoms, total abdominal hysterectomy with bilateral adnexectomy was performed. Histopathological examination identified moderate cytological atypia, focal coagulative tumor necrosis, and mitotic activity of up to five mitoses per ten high-power fields, findings insufficient for leiomyosarcoma but exceeding those expected for a benign leiomyoma. A diagnosis of STUMP was established. Postoperative staging showed no residual or metastatic disease, and structured long-term follow-up was initiated. Discussion: This case illustrates the limitations of current preoperative diagnostic tools in distinguishing between benign and borderline or malignant uterine smooth muscle tumors. Clinical presentation, imaging, and endometrial sampling were not predictive of the final diagnosis. In postmenopausal women, enlargement of a presumed leiomyoma should prompt careful evaluation, as histological assessment after complete surgical removal often remains the only reliable method of diagnosis. The unpredictable biological behavior of STUMP and reported cases of late recurrence support the need for prolonged surveillance, even after apparently adequate surgical treatment. Conclusions: STUMP remains primarily a postoperative diagnosis and represents a persistent gray zone in gynecologic oncology. Postmenopausal tumor growth and abnormal bleeding warrant an individualized and cautious approach. Careful histopathological evaluation and long-term follow-up are essential to ensure early detection of possible recurrence and optimal patient management. Full article

Background: Primary endometrial lymphomas (PELs) are exceedingly rare and diagnostically challenging lesions. Objective: To assess the clinicopathologic features of PELs. Methods: We adhered to the PRISMA-2020 guidelines for reporting systematic reviews. A PubMed literature search (1956–2025) was conducted using keyword combinations including “endometrium” and “lymphoma,” “lymphoid proliferation,” or “lymphoproliferative lesions.” Only original articles published in the English peer-reviewed journals were considered. The inclusion criteria were: (i) studies involving human subjects, and (ii) studies published in the English language. Reviews, editorials, meeting abstracts, and non-English publications were excluded. Results: We identified 42 studies for our analysis, collectively reporting 58 cases of PELs. Abnormal uterine bleeding was the main complaint. Non-Hodgkin lymphoma (57 cases) and Hodgkin lymphoma (one case) were identified. In most cases, lymphoma was the sole lesion. In five cases, lymphoma coexisted with, preceded, or followed endometrial carcinoma. Histologically, PELs either diffusely involved the endometrium (50 cases) or were localized to endometrial polyps (eight cases). Marginal zone lymphoma (MZL) was the most frequently reported type, followed by diffuse large B-cell lymphoma (DLBCL). Other rare types included intravascular large B-cell lymphoma, NK/T-cell lymphoma, T-cell lymphoma, and low-grade B-cell lymphoma. Conclusions: Our study indicates that MZL and DLBCL were the most common types of PELs. Other extremely rare subtypes were also identified. Moreover, some PELs developed in the background of endometrial polyps and, in exceptional cases, in association with endometrial carcinoma. Radiological findings were critical for provisional diagnosis, staging, and follow-up. Key modalities included ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), and 18F-fluoro-2-deoxyglucose positron emission tomography/CT (18F-FDG PET/CT). Full article

Cancer-associated thrombosis (CAT) is a major cause of morbidity and mortality in oncology, arising from complex interactions between tumor biology, host factors, and anticancer therapies. Growing evidence indicates that biological sex and gender-related factors modulate both thrombotic risk and clinical expression of venous thromboembolism (VTE) in patients with cancer. In this narrative review, we summarize current epidemiological, biological, and clinical data on sex- and gender-related differences in CAT across solid and hematologic malignancies. Men generally exhibit a higher overall incidence of VTE, whereas women may experience earlier, treatment-associated thrombotic events, with variability according to cancer type, stage, and therapy. Biological factors linked to coagulation and inflammation differ between sexes and may contribute to these patterns, although mechanistic evidence remains incomplete. Sex-related disparities also emerge in treatment-associated complications, including bleeding risk and abnormal uterine bleeding in anticoagulated women of reproductive age. In contrast, evidence for sex differences in oncohematology-associated thrombosis is limited and inconsistent. Gender-related inequalities in clinical trial participation further constrain the interpretation of available data. Overall, current evidence supports sex as a clinically relevant modifier of CAT risk, underscoring the need for systematic sex- and gender-informed research, to improve mechanistic understanding, and sex-stratified reporting to advance precision medicine in thrombosis and oncology. Full article

Background: Nuclear protein in testis (NUT) carcinoma is a rare, aggressive, and poorly differentiated epithelial malignancy characterized by the rearrangement of NUTM1 (NUT midline carcinoma family member 1) on 15q14. It primarily originates along the midline structures, including the head, neck, thorax, and mediastinum. Although NUT carcinoma of the pelvic gynecological organs is exceedingly rare, reported cases have been limited to primary or metastatic ovarian tumors. Here, we present the first documented case of primary uterine NUT carcinoma. Case presentation: A 53-year-old postmenopausal woman presented with abnormal uterine bleeding and a uterine mass. She underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. The initial postoperative histopathological evaluation suggested undifferentiated endometrial sarcoma; however, subsequent immunohistochemical (IHC) analysis and fluorescence in situ hybridization revealed NUTM1 rearrangement, confirming the diagnosis of NUT carcinoma. The patient experienced tumor recurrence six months postoperatively and succumbed to the disease nine months later. Discussion: The pathological diagnosis was challenging; the presence of abrupt squamous differentiation prompted further IHC analysis, leading to the definitive diagnosis. Primary uterine NUT carcinoma may be misdiagnosed as other undifferentiated uterine tumors due to its rarity and histological overlap. Conclusions: Given the diagnostic challenges, NUT IHC staining and molecular testing for NUTM1 rearrangement should be considered in undifferentiated uterine tumors with ambiguous histopathological features. Full article

Background: Retained products of conception (RPOC) after term delivery are uncommon but may lead to persistent abnormal uterine bleeding and other complications. Hysteroscopic removal is considered the optimal management strategy, and technological advances have increasingly enabled operative procedures to be performed safely in an office setting. Clinical case: We report the case of a 43-year-old woman who presented with intermittent spotting four months after spontaneous vaginal delivery. Transvaginal ultrasound revealed a small, avascular hyperechoic intrauterine lesion consistent with retained amniochorionic tissue. She underwent office hysteroscopic removal using a 16 Fr bipolar mini-resectoscope under nitrous oxide (N₂O) buccal–nasal analgesia. The procedure was performed using a vaginoscopic, no-touch approach without speculum, tenaculum, or cervical dilation. Complete resection was achieved in a seven-minute procedure, with a postoperative pain score of 2/10 on the VAS and no complications. At 30-day follow-up, the patient was asymptomatic, and an ultrasound confirmed complete resolution. Conclusion: This case demonstrates that retained amniochorionic tissue can be safely and effectively treated in a fully ambulatory setting using mini-resectoscopic technology and N₂O analgesia. The combination of minimally invasive instruments, patient-centered procedural strategies, and well-tolerated analgesia supports the growing role of office operative hysteroscopy for selected complex intrauterine conditions. Full article

Endometrial hyperplasia (EH) comprises a spectrum of abnormal proliferative changes in the endometrium, ranging from benign glandular overgrowth to lesions with substantial malignant potential. The importance of risk stratification and early identification is highlighted by the growing recognition of EH as a precursor to endometrial cancer. The main causes of EH, according to epidemiological research, include obesity, polycystic ovarian syndrome (PCOS), metabolic dysfunction, and extended exposure to unopposed estrogen. Emerging molecular markers, histological analysis, and imaging are all necessary for a proper diagnosis of EH because it might appear with vague clinical symptoms such as irregular uterine bleeding. Surgical intervention or progestin therapy are two possible management techniques for EH, depending on the lesion’s intricacy and the patient’s medical history, including fertility issues. Personalized therapy techniques and recent developments in molecular profiling have the potential to enhance patient outcomes by matching treatment to tumor biology and individual risk profiles. This review highlights the translational potential of molecular insights while synthesizing the most recent data on the epidemiology, risk factors, diagnostic techniques, and therapy of EH. A deeper comprehension of these elements is necessary to maximize treatment results and stop the development of endometrial cancer. Full article

Background: Low-grade endometrial stromal sarcoma (LG-ESS) is a rare uterine mesenchymal neoplasm characterized by indolent progression and strong hormonal responsiveness. Accurate diagnosis remains challenging due to its overlapping clinical, pathological, and imaging features with other benign or malignant uterine entities. Case Presentation: This article presents a case of LG-ESS in a 50-year-old woman, encompassing the clinical presentation, imaging features, histopathological and immunohistochemical findings, the surgical management and postoperative course, as well as a focused synthesis of the current literature on this pathology. The patient presented with recurrent abnormal uterine bleeding and secondary anemia. Imaging data, including magnetic resonance imaging (MRI), revealed a heterogeneous intracavitary lesion with cystic components, suggestive of submucosal fibroids. Surgical management via total hysterectomy with bilateral salpingo-oophorectomy was performed due to suspicion of sarcoma and the need to suppress hormonal stimulation. Histopathological and immunohistochemical evaluation confirmed LG-ESS. The patient had no lympho-vascular invasion, presenting a favorable postoperative evolution. Conclusions: This case highlights the need to maintain a strong clinical suspicion for uterine sarcomas in patients presenting with atypical bleeding and presumed fibroids, especially among perimenopausal women. A multidisciplinary approach, including imaging, surgery, pathology, molecular profiling, and oncology, is essential for accurate diagnosis and optimal management. Full article

Background/Objectives: Adenomyosis is characterized by aberrant endometrial invasion and heavy menstrual bleeding, with angiogenesis being implicated as a key mechanism of this condition. We compared vascular endothelial growth factor (VEGF), angiopoietin-1 (ANGPT-1), and angiopoietin-2 (ANGPT-2) expression in eutopic and ectopic endometria from patients with adenomyosis and evaluated whether the levonorgestrel intrauterine system (LNG-IUS) modulates these angiogenic markers. Methods: In a case–control analysis, specimens from patients with adenomyosis without an LNG-IUS (n = 20), those with adenomyosis with prior LNG-IUS insertion (n = 18), and controls (n = 12) were analyzed. Immunohistochemistry with H-scores was used to assess protein expression in eutopic and ectopic tissues. ANGPT1, ANGPT2, and VEGFA mRNA in eutopic endometrial tissue were quantified by qRT-PCR. Results: In untreated adenomyosis patients, ectopic endometria showed higher protein expression than eutopic tissue for ANGPT-1, ANGPT-2, and VEGF (all p ≤ 0.05). The LNG-IUS was associated with significantly lower expression of all three markers in both eutopic and ectopic tissue (all p < 0.01), with eutopic levels approaching those of controls. qRT-PCR findings corroborated the decrease in ANGPT1, ANGPT2, and VEGFA transcript levels after LNG-IUS insertion (all p < 0.05). Conclusions: Adenomyosis is characterized by upregulated angiogenic signaling in both eutopic and ectopic endometria. The LNG-IUS attenuates ANGPT-1, ANGPT-2, and VEGF expression at both the protein and transcript levels, suggesting that modulation of angiogenic pathways may contribute to its therapeutic benefit in abnormal uterine bleeding associated with adenomyosis. Full article

Background: The incidence of endometrial cancer (EC) is rising globally across all age groups. Endometrial intraepithelial neoplasia (EIN) is a premalignant lesion that may progress to EC if untreated. A clinical model is needed to efficiently identify women requiring prompt evaluation while avoiding unnecessary invasive procedures. Obesity is a major risk factor, but whether Asian women require a lower body mass index (BMI) cutoff than the World Health Organization (WHO) definition remains debated. This study aimed to develop a multivariable risk prediction model to guide biopsy decisions and determine an appropriate BMI cutoff for predicting EIN/EC risk among Asian women. Methods: This study retrospectively reviewed 1192 women aged ≥18 years who underwent hysteroscopy between 2010 and 2023 at a tertiary hospital. Candidate predictors included patient age, parity, BMI, postmenopausal status, symptom of abnormal uterine bleeding (AUB), diabetes mellitus, hypertension, polycystic ovary syndrome (PCOS), use of oral contraceptives, intrauterine devices, or menopausal hormone therapy, tamoxifen treatment, presence of multiple polyps, and endometrial thickness (EMT) measured by transvaginal ultrasonography. Multivariable logistic regression with stepwise selection identified independent predictors, and model stability and calibration were assessed using 1000 bootstrap resamples. Results: EIN/EC was diagnosed in 55 patients (4.6%). Six independent predictors were identified: postmenopausal status (adjusted odds ratio [aOR] 5.93, 95% CI 2.92–12.04), AUB (aOR 4.07, 1.51–10.97), multiple polyps (aOR 2.49, 1.33–4.66), PCOS (aOR 2.37, 1.08–5.22), BMI (aOR 1.13 per kg/m²; 1.84 per +5 kg/m²), and EMT (aOR 1.07 per mm, 1.02–1.11). When using categorical cutoffs, Obese II (BMI ≥ 30 kg/m²) and markedly increased EMT (≥20 mm) remained significant. Predicted probabilities ranged from 0.3% with no risk factors to 90.9% with all six risk factors present. The final model demonstrated good discrimination (AUC 0.79, 95% CI 0.73–0.86) and excellent calibration on bootstrap validation (mean absolute error 0.005). Conclusions: This six-factor clinical model stratifies individual EIN/EC risk using readily available variables and may guide timely, risk-based biopsy decisions by identifying high-risk patients while minimizing unnecessary procedures in low-risk cases. BMI ≥ 30 kg/m² (WHO obesity threshold) was confirmed as a meaningful cutoff, but external validation is warranted to confirm its generalizability and clinical applicability. Full article

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

Objective: This study aimed to evaluate the efficacy of empirical antibiotic therapy in treating chronic endometritis (CE) associated with abnormal uterine bleeding (AUB), infertility, or intrauterine lesions. Methods: The prospective cohort study involved 102 women undergoing outpatient hysteroscopy (OH), with immunohistochemical diagnosis of CE based on plasma cell density (PCD). Seventy-six of these women received empirical antibiotic therapy (ofloxacin and metronidazole), while 26 did not. A follow-up OH was conducted in the third cycle following the initial procedure. Results: Hysteroscopic polypectomy significantly reduced PCD regardless of antibiotic use (p = 0.009). In cases without focal lesions but exhibiting CE features, antibiotic therapy notably decreased PCD (p = 0.018). The incidence of certain histopathological features of CE, such as stromal edema and stromal cell compaction, was significantly lower in women treated with antibiotics (p = 0.014). Among intrauterine pathologies, endometrial polyps (p = 0.009) and cesarean scar defects (p = 0.011) significantly increased the risk of CE. Only spindled transformation of stromal cells with edema correlated significantly with elevated PCD (p = 0.022). Antibiotic therapy did not improve obstetric outcomes. Conclusions: Polypectomy alone reduced PCD without antibiotics, while antibiotic treatment significantly decreased PCD and resolved CE features in cases without focal lesions. Therefore, antibiotics may be prioritized for cases without focal lesions, whereas surgical intervention may be sufficient for CE associated with eligible pathologies. Full article

Adenomyosis (AM) is a hormonally responsive uterine disorder defined by ectopic endometrial tissue within the myometrium, causing pain, abnormal bleeding, and subfertility. Non-coding RNAs (ncRNAs)—including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs)—are post-transcriptional regulators implicated also in uterine remodeling. We systematically reviewed original studies evaluating ncRNAs in AM using human samples, in vitro and animal models, or bioinformatic approaches. Data sources included PubMed and Google Scholar (inception up to 10 August 2025). Forty-one studies were included and synthesized across mechanistic, diagnostic, and translational domains. miRNAs (n = 31) were the most studied subclass, followed by lncRNAs (n = 10) and circRNAs (n = 5). Recurrent miRNAs such as miR-10b and miR-30c-5p (downregulated, inhibitory) and miR-145 (upregulated, promotive) regulate epithelial invasion, epithelial–mesenchymal transition, and cytoskeletal remodeling via PI3K–AKT/MAPK and Talin1 signaling. The let-7a/LIN28B axis governed estrogen-sensitive proliferation in the junctional zone, while miR-21 exhibited compartment-specific roles in decidualization and ectopic cell survival. Extracellular-vesicle (EV)-bornemiRNAs (e.g., miR-92a-3p, miR-25-3p, miR-4669) contributed to immune polarization and show early diagnostic potential. lncRNAs and circRNAs acted via chromatin modifiers and ceRNA networks. Most findings remain at the discovery stage. Convergent dysregulation was observed in key signaling pathways, including JAK–STAT, Wnt/β-catenin, and Hippo–YAP. ncRNAs regulate critical axes of invasion, proliferation, immune modulation, and hormonal response in AM. Targets with preliminary causal support—miR-10b/ZEB1, let-7a/LIN28B, and miR-145/Talin1—warrant further validation. Circulating miRNAs—especially in EVs—offer promise for non-invasive diagnosis. Full article

Polycystic ovary syndrome (PCOS) is a systemic metabolic and endocrine disorder that significantly disrupts reproductive physiology and endometrial function. In this narrative review, we examine the molecular impact of metabolic and hormonal imbalances on the endometrium of women with PCOS. We investigate the specific mechanisms that delineate how hyperinsulinemia and insulin resistance, chronic low-grade inflammation, and estrogen/progesterone/androgen imbalance contribute to altered epigenetic, transcriptomic, metabolomic, and signaling profiles in a wide array of different cell types within endometrial tissues. The synergistic interplay between upregulated inflammatory cytokines (e.g., IL-1,2,6,8,17,18, and TNF-α), along with key changes in critical molecular pathways associated with hyperinsulinemia and insulin resistance (e.g., PI3K/AKT/MAPK, and Wnt/β-catenin), in addition to aberrant sex steroid hormone signaling (e.g., CYP19A1, COX-2, PGE₂, HOXA10, 11βHSD2), promotes deleterious changes within the endometrial microenvironment. These anomalies underpin a spectrum of clinical manifestations observed in women with PCOS at each stage of the life course, including abnormal uterine bleeding in reproductive-age women, impaired decidualization in pregnancy, and altered postmenopausal endometrial physiology. Clinically, these alterations are associated with abnormal uterine bleeding, subfertility, implantation failure, miscarriage, pregnancy complications, and postmenopausal endometrial hyperplasia and cancer. Overall, our review provides novel insights into the molecular mechanisms linking systemic metabolic and endocrine dysfunction with endometrial pathology in PCOS and has broader implications that apply to all women. Full article

Objective: This study aimed to determine the prevalence of isthmocele in patients who had undergone cesarean delivery and to investigate its association with abnormal uterine bleeding (AUB). Additionally, a novel volume-based classification system (Er-Kay Classification) was developed to provide a more precise assessment of cesarean scar defects and their correlation with clinical symptoms. Material and Methods: This retrospective, hospital-based cohort study was conducted at Ankara Etlik Zübeyde Hanım Women’s Health Training and Research Hospital between October 2017 and March 2018. A total of 1098 patients who had undergone cesarean delivery and attended follow-up visits were included. Patients were categorized based on the presence of isthmocele (study group: n = 134) and its absence (control group: n = 964). Isthmocele volume was calculated using the formula (Height × Width × Depth)/3, and patients were classified as Grade 1 (≤50 mm³) or Grade 2 (>50 mm³) based on the novel Er-Kay Classification. Clinical symptoms, including AUB (pre-, inter-, postmenstrual bleeding), dysmenorrhea, dyspareunia, and postcoital bleeding, were compared between groups. Statistical analyses were performed using SPSS 27.0 (NY, USA),with a significance level of p < 0.05. Results: The prevalence of isthmocele was 12.2% (134/1098). Patients with isthmocele had significantly shorter menstrual cycles compared to those without (26.64 ± 5.35 vs. 28.08 ± 4.97 days, p = 0.038). Postmenstrual bleeding (47.0% vs. 4.7%, p < 0.001), dysmenorrhea (38.8% vs. 18.3%, p < 0.001), and dyspareunia (39.6% vs. 14.7%, p < 0.001) were significantly more frequent in the isthmocele group. According to the Er-Kay Classification, intermenstrual bleeding was significantly higher in Grade 2 (23.1%) than in Grade 1 (4.3%) (p = 0.001). Similarly, postmenstrual bleeding was more common in Grade 2 (56.9%) than in Grade 1 (37.7%) (p = 0.026). No significant differences were found for premenstrual bleeding, dysmenorrhea, or dyspareunia between the Er-Kay Classification groups (p > 0.05). Conclusions: The findings indicate that isthmocele is significantly associated with AUB, dysmenorrhea, and dyspareunia. The Er-Kay Classification, based on isthmocele volume, provides a more precise assessment of symptom severity, particularly in intermenstrual and postmenstrual bleeding cases. These results suggest that volume-based evaluations should be incorporated into clinical practice for better patient management and diagnosis of cesarean scar defects. Full article