Faculty of Medicine

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Association between endometrial heterogeneity and endometrial cancer risk stratification in postmenopausal women
(Srpsko lekarsko društvo, Beograd, 2026)
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SUMMARY Introduction/Objective The normal postmenopausal endometrium typically appears thin, homogeneous, and echogenic on transvaginal ultrasonography. In contrast, endometrial carcinoma is often associated with increased thickness, heterogeneous echogenicity, irregular endometrial–myometrial interface, and enhanced Doppler vascularization. The objective of this study was to evaluate the association between heterogeneous endometrial echogenicity and the risk of endometrial malignancy in postmenopausal women. Methods This prospective clinical study included 120 postmenopausal women treated at the University Clinic for Gynecology and Obstetrics in Skopje. Participants were divided into a control group (n = 40) and an examined group (n = 80). The examined group was further stratified according to uterine bleeding status and endometrial thickness (5–8 mm, > 8–11 mm, and > 11 mm). Endometrial echogenicity was assessed by transvaginal ultrasonography and classified as homogeneous or heterogeneous. Binary logistic regression analysis was performed to determine independent predictors of malignancy. Results Heterogeneous endometrial echogenicity was significantly more frequent in the examined group compared with controls (p < 0.001). It was identified as an independent predictor of endometrial malignancy (OR = 4.938; 95% CI: 1.24–19.62; p = 0.023). No statistically significant association was observed between echogenicity and endometrial thickness subgroups (p = 0.49) or uterine bleeding status (p = 0.82). Conclusion Heterogeneous endometrial echogenicity represents a significant independent sonographic predictor of endometrial malignancy in postmenopausal women and should be incorporated into routine ultrasound risk assessment.
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RELATIONSHIP OF IMMUNOHISTOCHEMICAL EXPRESSION OF MISMATCH REPAIR GENE PRODUCTS AND CLINICOPATHOLOGICAL FEATURES IN PATIENTS WITH LOW-GRADE ENDOMETRIAL CANCER
(Macedonian Association of Anatomists and Morphologists, 2024)
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Ognenoska Jankovska, Biljana
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Background: This study examines the relationship between mismatch repair (MMR) gene expression and clinicopathological features in patients with low-grade endometrial cancer (EC). Methods: A prospective cohort of 40 patients with histologically confirmed low-grade EC underwent immunohistochemical analysis to determine MMR status. Clinical data, including age, body mass index (BMI), menopausal status, parity, and comorbidities, were collected. Histopathological evaluations assessed myometrial invasion,lymphovascular invasion and disease stage. Results: MMR deficiency (MMRd) was identified in 35% of patients, predominantly associated with MLH1/PMS2 loss. No significant associations were found between MMR status and clinical characteristics such as age, BMI, or comorbidities. However, MMRd tumors exhibited a significantly higher prevalence of myometrial invasion over 50% (85.71% vs. 38.46%, p=0.0042) and lymphovascular invasion (71.43% vs. 19.23%, p=0.00114). Additionally, MMRd cases were more frequently associated with advanced disease stages, particularly in stage IIIC (28.57% vs. 7.69%, p=0.078). Conclusion: The importance of MMR status in the biological behavior of low-grade endometrial cancer is highlighted in this study. The strong correlation between MMR deficiency and aggressive histopathological features such as increased myometrial and lymphovascular invasion, highlights the need to integrate MMR testing into clinical practice, even if clinical parameters showed no significant association with MMR expression. These results suggest that MMRd may be a useful prognostic indicator that requires more research to improve patient outcomes and treatment approaches for low-grade endometrial cancer.
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DETECTION OF LYNCH SYNDROME IN ENDOMETRIAL CANCER PATIENTS
(Faculty of Medicine, University Ss. Cyril and Methodius in Skopje, 2023-12-27)
Kubelka Sabit, Katerina
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Petrova, Deva
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Jashar, Dzangis
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Filipovski, Vanja
Lynch syndrome (LS) is an autosomal dominant inherited disease defined by germline mutations in mismatch repair (MMR) genes, leading to a defective DNA MMR system. Patients with LS havepredisposition to a spectrum of cancers, primarily colorectal cancer, but LS-associated endometrial cancer (LS-EC) is the most common extraintestinal cancer and occurs in 2% of LS patients. The most frequently mutated MMR genes are MLH1, MSH2, MSH6 and PMS2. Clinico-pathologic features of LS-EC are: early age of onset, lower body mass index, endometrioid type of carcinoma and lower uterine segment involvement. Recent studies support LS screening in every EC patient since MMR status is also part of the molecular subclassification of endometrial cancers.Screening methods include traditional clinical criteria and molecular techniques, such as MMR-immunohistochemistry(MMR-IHC), microsatellite instability (MSI) testing, MLH1promoter methylation testing and gene sequencing. MSI can also be detected in sporadic tumors, through epigenetic events inactivating the MMR system. Patients with diagnosed LS and their affectedrelatives should be closely monitored in order to prevent the development of other types of cancer. Patients with advanced recurrent microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) endometrial cancer can also benefit from immunotherapy.We describe our 3-year experience in screening of Lynch syndrome in EC patients.
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Small intestine metastasis from endometrial carcinoma initially presented as enterocutaneous fistula: a case report and literature review
(Oxford University Press (OUP), 2024-05)
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Limani, Nimetula
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Ristova Tancheva, Aleksandra
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Manasievska Bogoevska, Antonela
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Although endometrial cancer is the fourth most common malignancy among women, it rarely metastasizes to the small intestine. Cases of endometrial recurrence to the intestine clinically present with secondary anemia, melena, abdominal cramps, and epigastric pain. Only a dozen cases are reported in the literature, but none presented with an enterocutaneous fistula. In this report, we present a case of an 88-year-old female patient previously treated for endometrial adenocarcinoma with surgery and adjuvant radiotherapy. Fourteen months after the surgery, the patient presented with an enterocutaneous fistula on the anterior abdominal wall, which was confirmed to be a metastasis from the primary tumor. To our knowledge, this is the first case of endometrial cancer metastasizing to the small intestine with involvement of the anterior abdominal wall and the occurrence of an enterocutaneous fistula, which was treated with radical surgery.
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Dopler ultasound scoring system for identification of endometrial cancer in postmenopausal patients
(Department of Anaesthesia and Reanimation, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, R.N. Macedonia, 2023-10-09)
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Spasoski, S
Introduction: Endometrial cancer (EC) is the most common malignancy of the female genital tract in the developed world. Nowadays, preoperative evaluations using advanced imaging techniques have become more common, but little has been done on the best imaging technique for routine use and preoperative evaluations of endometrial carcinoma. The aim of this study was to evaluate the predictive value of Doppler ultrasound scoring system in detection of endometrial malignancy in postmenopausal patients with vaginal bleeding. Material and Methods: This cross-sectional study, was conducted at the University Clinic of Obstetrics and Gynecology, Skopje and included 164 postmenopausal patients admitted to the Gynecology Department of the clinic. They were divided into two main groups based on their clinical presentation and further subdivided according to histopathological results. All patients underwent a standard transvaginal ultrasound examination followed by power Doppler endometrial vascularity assessment, as well as histopathological analyses of endometrial sampling for each of them was performed. Univariate and multivariate logistic regression were utilized to determine the predictive values of Doppler parameters and the scoring system. Results: Significant associations were found between endometrial malignancy and various factors, including number of blood vessels, presence of densely packed bundles, the values of pulsatility index, resistance index, time averaged maximum velocity and peak systolic velocity. Among these, pulsatility index had the greatest influence (Wald=11.32/ p<0.01 (p=0.001)) and time averaged maximum velocity had the weakest influence (Wald=0.10/ p>0.05 (p=0.73)). Clinical scoring system exhibited a sensitivity of 79.60%, the specificity is 97.30%, and overall model accuracy is 91.50%. Conclusion: The results of our study have proved that all Doppler parameters are significant predictive factors in determining endometrial cancer in postmenopausal patients with vaginal bleeding. Their combination could obtain a non-invasive scoring system that could reduce invasive procedure in diagnosis of the endometrial malignancy in patients with ultrasound characteristic of thickened endometrium more than 5mm. For this scoring system, there is a need of modern ultrasound device and clinician with greater experience.
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THE IMPACT OF OBESITY AND FAT DISTRIBUTION ON ENDOMETRIAL CANCER RISK IN POSTMENOPAUSAL PATIENTS
(Macedonian Association of Anatomists, 2023)
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Endometrial cancer (EC) is the fourth most common cancer in women worldwide, with rising incidence partly due to changing reproductive trends and ever increasing obesity. Obesity, especially central adiposity, is linked with endometrial adenocarcinoma, possibly due to elevated estrogen and decreased sex hormone-binding globulin levels. The study aims to evaluate the impact of obesity on endometrial malignancy and to determine whether central adiposity (measured by the waist-to-hip circumference ratio) serves as a better indicator of endometrial cancer risk than BMI. In this cross-sectional study, we studied 164 postmenopausal patients from the University Clinic of Obstetrics and Gynaecology in Skopje. Patients were admitted to the hospital for histopathological examination of endometrial layer because of vaginal bleeding with endometrial thickness >4mm, or other sonographic endometrial abnormalities. Histopathological findings subdivided them into two categories: with malignancy (group I) or benign abnormality (group II). Standard examinations and measurements, including BMI and waist-to-hip ratio, were performed. A significant association was observed between endometrial malignancy and obesity as measured by waist-to-hip ratio. In the distribution of data related to BMI and histopathological findings from the endometrial biopsy for Pearson Chi-square=8.35 and p<0.01(p=0.004) there is a significant difference. For Odds Ratio=2.71 (95.%CI:1.36-5.38), patients who had a BMI ≥ 30 kg/m2 were 2.71 times more likely to have endometrial malignancy than patients who had a BMI <30 kg/m2, (p<0.01). There is a significant difference in the shown distribution of data related to waist circumference/hip circumference and histopathological findings of endometrial sampling Pearson Chi-square=79.22 and p<0.001(p=0.000). For Odds Ratio=40.89 (95.% CI:15.23-109.78), patients who had waist circumference/hip circumference ≥ 0.85 were 40.89 times more likely to have endometrial malignancy than patients who had waist circumference/hip circumference <0.85, (p<0.001). Upon analysing the contribution of central obesity determined by waist-to-hip ratio, it was found to have a more substantial impact (Wald = 37.76, p < 0.001) compared to BMI (Wald = 0.97, p= 0,32). Our study confirms that obesity is a risk factor for endometrial malignancy. Furthermore, fat distribution proves to be a more crucial and accurate indicator of endometrial cancer risk than overall obesity. The statistical significance of the waist circumference to hip circumference ratio exceeded that of BMI. Therefore, even if a patient has a normal BMI, but a waist-to-hip circumference ratio greater than 0,80, she should be considered at increased risk for endometrial malignancy and should be closely monitored in the future in order to detect any malignant changes.
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Preoperative detection of sentinel lymph node in patients with endometrial cancer - comparison of planar lymphoscintigraphy, spect and SPECT/CT
(2022)
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Stoilovska Rizova, Bojana
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Sentinel lymph node (SLN) mapping allows minimal invasive assessment of lymph node status in patients with early-stage endometrial cancer (EC). Intraoperative detection of SLNs is based on the results obtained from preoperative nuclear medical images. The purpose of this study was to compare the data obtained from planar lymphoscintigraphy (PL), single-photon emission computed tomography (SPECT), and SPECT with computed tomography (SPECT/CT) for preoperative SLN detection in patients with EC.
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ENDOMETRIAL THICKNESS ASSESSED BY TRANSVAGINAL ULTRASOUND AS A PREDICTOR OF THE RISK OF ENDOMETRIAL CANCER AND ATYPICAL ENDOMETRIAL HYPERPLASIA IN ASYMPTOMATIC POSTMENOPAUSAL PATIENTS
(Macedonian association of anatomists and morphologists, 2020-06)
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Tanturovski Dragan
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Stojchevski Sasho
ABSTRACT Introduction: Endometrial cancer (EC) is the most common gynecological malignancy in the developed world. It is estimated that 320000 new cases are diagnosed annually, accounting for up to 6% of all newly diagnosed malignant neoplasms. In spite of the associated controversies, transvaginal sonography and measurement of endometrial thickness are wellaccepted, standard procedures in many gynecological office visits to date. Objective: The study aim was to determine the diagnostic performance of endometrial thickness measured by transvaginal sonography in diagnosing endometrial cancer and atypical endometrial hyperplasia in asymptomatic postmenopausal patients. Materials and methods: The databases of the Department of gynecological oncology at the University Clinic of Gynecology and Obstetrics in Skopje, in the period January – December 2015 were searched to identify asymptomatic postmenopausal patients undergoing endometrial sampling due to increased endometrial thickness. Results: A total of 268 patient records that met the criteria were identified. The prevalence of endometrial cancer and atypical endometrial hyperplasia in the study were 5.2% and 2.2%, respectively. Endometrial thickness was a statistically significant independent predictor of the presence of endometrial cancer and atypical endometrial hyperplasia (p<0.001). The ROC curve analysis in our study had an AUC of 0.8 and identified a cut-off level to be ≥10mm which was associated with a sensitivity of 85.7%, specificity of 60.6%, PPV of 10.7% and NPV of 98.7% for the detection of endometrial cancer. Conclusion: The proposed cut-off of ≥10mm for discriminating between “normal” and “pathological” endometrial thickness is clinically reasonable and of moderate diagnostic value. However, the cut-off value does not achieve the required high sensitivity with clinically acceptable low false positive rates. Nevertheless, transvaginal sonography for measuring endometrial thickness can be used to exclude pre-malignancy or malignancy in asymptomatic postmenopausal women with risk factors because of its low false negative rate.
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Impact of systematic pelvic lymphadenectomy on short term postoperative quality of life in patients with early stage endometrial cancer
(SHMSHM / AAMD, 2020-08)
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Tanturovski Dragan
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Stojchevski Sasho
Objective: to determine the potential impact of systematic lymphadenectomy vs. no lymphadenectomy on the perioperative change in QoL in patients undergoing surgical treatment for early stage endometrial cancer. Patients and methods: Patients scheduled for surgical treatment of clinically early stage endometrial cancer at the Department of gynecological oncology at the University Clinic of Gynecology and Obstetrics in Skopje, in the period January – December 2018 were approached for participation. Eligible subjects were divided into two groups: Group 1 (no LND) consisted of 60 patients who had hysterectomy plus bilateral salpingo-oophorectomy without lymph node dissection (LND); Group 2 consisted of 24 patients who had hysterectomy plus salpingo-oophorectomy plus systematic pelvic LND. Quality of life was quantified using a standardized and validated questionnaire (FACT-G) preoperatively and 30 days after surgical treatment. Results: The patients in the LND group exhibited statistically significantly lower postoperative scores for FACT-G (87.7 vs 75.8 for the no LND and LND groups respectively, p=0.002), as well as for the physical wellbeing domain (23.4 vs. 20, p=0.004) and emotional wellbeing domain (20.7 vs 17, p=0.008). Twelve patients from the group with no lymphadenectomy (20%) experienced a clinically significant decline in the postoperative QoL, compared to 12 patients (50%) in the lymphadenectomy group (p=0.006). Conclusion: There was a significant decrease in the postoperative QoL 30 days after surgery in patients that undergo systematic pelvic lymphadenectomy for early stage endometrial cancer compared to patients that do not.
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INTRAVAGINAL BRACHYTHERAPY SUPPORTED BY LOCAL ANAESTHESIA IN THE TREATMENT OF ENDOMETRIAL CANCER – SINGLE INSTITUTIONAL EXPERIENCE
(Department of Anaesthesia and Reanimation, Faculty of Medicine, “Ss. Cyril and Methodius” University Skopje, R.N.Macedonia, 2020-10)
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Bojoski P
Intravaginal brachytherapy in endometrial cancer is an inevitable part of the treatment. In the early stages of the disease, it signifcantly reduces the risk of local recurrence in the vaginal cuff with low rates of late toxicity. In the advanced stages, it provides palliative control usually with a hemostyptic effect. Brachytherapy may be the only postoperative treatment – monotherapy, or as a boost following the external beam radiotherapy, depending on many prognostic factors. Placing the vaginal applicator deep into the vagina is certainly an uncomfortable feeling, combined with pain, anxiety and discomfort. Local anaesthesia helps in reducing the painful sensations, gives adequate relaxation, but more importantly provides a quality insight into the condition of the vagina, and thus a successful application. Through our experience with the local vaginal anaesthesia with lidocaine 2% gel, we want to emphasize that intravaginal brachytherapy, supported by local anaesthesia, regardless of the degree of pain relief is directly related to successful treatment.

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