Faculty of Medicine

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РИЗИК ФАКТОРИ ЗА ПАТОЛОШКИ ПРОМЕНИ НА ЕНДОМЕТРИУМОТ И НИВНА АСОЦИЈАЦИЈА СО ЕНДОКРИНИТЕ НАРУШУВАЊА, МЕТАБОЛИЧЕН СИНДРОМ И ОСТЕОПОРОЗА
(2022)
Introduction: The International Federation of Gynecology and Obstetrics (FIGO) has defined a classification system for abnormal uterine bleeding, called PALM-COEIN (polyp, adenomyosis, leiomyoma, malignancy and hyperplasia, coagulopathy, ovulatory disfunction, endometrial dysfunction, iatrogenic causes, unclassified reasons). Dysfunctional uterine bleeding is often during the menopausal transition as a result of hormonal changes during this period. In postmenopause there should be no uterine bleeding, the thickness of the endometrium should be less than 5 mm, and if it is above 5mm, the presence of polyp, hyperplasia or cancer is possible. Postmenopausal bleeding occurs in approximately 90% of patients with endometrial cancer, but only 9% of women with postmenopausal bleeding have endometrial cancer. Endometrial hyperplasia and endometrial polyps are associated with development of endometrial cancer and therefore these changes can be called premalignant. Atypical endometrial hyperplasia is a preneoplastic condition that precedes the most common malignant tumor of the uterus, endometrioid adenocarcinoma. Risk factors such as obesity, chronic anovulation, nulliparousness, late menopause, unopposed estrogen (without progesterone), hypertension and diabetes, all increase the risk of endometrial hyperplasia and endometrial cancer. Objectives: To determine the histopathological changes of the endometrium that occur during the period of perimenopause and postmenopause; to determine their association with the presence of diabetes, hypertension, metabolic syndrome, thyroid disorders, glycosylated hemoglobin levels, Vitamin D levels, and to determine the dynamics of bone markers in the peri and postmenopausal period. Material and methods: The study was a prospective observational cohort, involving a total of 160 respondents. The study group consisted of 120 patients who underwent fractionated explorative curettage due to a medical indication (abnormal bleeding or ultrasound-diagnosed endometrial abnormality). They were divided into two subgroups: perimenopausal and postmenopausal. The control group consisted of 40 healthy women without fractionated explorative curettage. Anamnestic data were taken from all respondents. Blood pressure, body weight, height, waist circumference, anteroposterior diameter of the uterus and endometrial thickness were measured. This laboratory analyses were performed: Glycemia, glycosylated hemoglobin (HbA1c), Hormonal Status - FSH, LH, Estradiol, Serum insulin, Thyroxine (fT4), Parathormon (PTH), lipid status, ionized calcium, serum iron, bone markers (Osteocalcin, β-Cross Laps), vitamin D (25-Hydroxyvitamin D). Results: The most common pathological change of the endometrium was an endometrial polyp, and it was present in 45% of the respondents. Endometrial hyperplasia without atypia was present in 23.3% of perimenopausal and 15% of postmenopausal women. Endometrial adenocarcinoma was present in 3% of perimenopausal and in 5% of postmenopausal women. Patients with endometrial pathology were older than healthy women and had significantly more frequently: greater endometrial thickness, higher blood pressure, body mass index, waist circumference, glycemia, triglycerides, serum insulin and metabolic syndrome. Vitamin D levels were lower in women with explorative curettage than in healthy women, and significantly lower in those with organic changes compared with those with functional pathological changes of the endometrium. Women with organic changes of the endometrium, compared with those with functional changes, had significantly higher: body mass index, waist circumference and endometrial thickness. Perimenopausal women, compared with those in postmenopause, had significantly longer duration and intensity of bleeding, larger anteroposterior diameter of the uterus and thickness of the endometrium. Postmenopausal women had higher body mass index, waist circumference, blood pressure, glucose, HbA1c, serum iron and bone markers (osteocalcin and β Cross Laps), than those in perimenopause. Postmenopausal duration in patients with explorative curettage was significantly positively correlated with serum values of bone markers osteocalcin and β Cross Laps. Conclusions: Fractionated explorative curettage is an effective method for timely and effective diagnosis of pathological changes of the endometrium in women with abnormal uterine bleeding or ultrasound-diagnosed abnormal endometrial findings. In the period of perimenopause and postmenopause, there are changes in the genital organs, but also there are internal disorders (obesity, metabolic syndrome, diabetes, thyroid disorders, cardiovascular disease, osteoporosis), which should be timely prevented, diagnosed and treated. According to our study, some of them are related to the occurrence of changes in the endometrium and the need for fractionated explorative curettage for timely diagnosis, especially of premalignant and malignant changes.
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Endometrial adenocarcinoma occuring in young women
(Hellenic Division of International Academy of Pathology, 2003-05)
Kubelka-Sabit, Katerina
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Prodanova, Irina
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Yashar, Genghis
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Zografski, George
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Background: Endometrial adenocarcinoma (EA) primarily occurs in postmenopausal women. Only 1-8% of the cases are diagnosed in women under forty years of age, while this neoplasm is extremely rare in the third decade. Hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy (HSOPL) is the treatment of choice for older or patients with invasive EA. However, in young women with non-invasive well-differentiated EAs, who wish to preserve their fertility, conservative treatment with progestins can be tried. Aims: The purpose of this retrospective study is to present the clinical and morphologic characteristics, as well as the immunohistochemical profile of 3 cases of well-differentiated EAs, that occurred in women in their third decade of life. Since the neoplasms were non-invasive, an attempt to preserve their fertility has been made. Methods and patients: Six of the 1081 cases (0.5%) of EA diagnosed at the Department of Histopathology and Clinical Cytology in the last 14-year period (1989-2002), occurred in patients younger than 35 years. Three of them (1.4%, 3/206), have been diagnosed in the last two years (2001-2002). The youngest of the last three patients (age 21), had a genetic abnormality (45X/47XXX) and experienced prolonged and heavy uterine bleedings that required explorative curettage. The second patient (age 25) had a history of diabetes and infertility. The neoplasm was found in the endometrial biopsy that was taken for evaluation of the endometrial response to hormonal stimulation. In the third patient (age 27) the neoplasm was an accidental finding in the cervical curettage material that was submitted to our department, for histopathologic reevaluation of the previously diagnosed moderate dysplasia of the epithelium of the uterine cervix. The materials, obtained either by dilatation and curettage (3 cases) or HSOPL (one case), were submitted to our department and were routinely processed. Standard hematoxylin and eosin (H&E) stained slides were prepared from paraffin blocks, whereas additional histochemical (PAS, alcian blue, azan, silver by Jones) and immunohistochemical stains (estrogen-ER, progesterone-PgR, p53, Ki-67) were performed on selected paraffin blocks that contained the neoplastic tissue. Results: In the curettage materials of the three patients, fragments of endometrial polyp were identfied, that contained areas of simple, complex and atypical hyperplasia. In each of these cases, only few small (1-3-millimetre in diameter) foci of well-differentiated EA were detected. Fragments of functional endometrium were also present. All three patients had hormone (ER, PgR) responsive neoplasms, whereas Ki-67 proliferative index was significantly higher in the neoplastic tissue (30-40%), compared to the zones of atypical hyperplasia (10-20%). The suppressor gene protein product p53 was negative in all three EAs. Subsequent dilatation and curettage to remove the residual parts of the polyp was performed in two of the patients. Conservative 5-6-month treatment with progestins led to regression of the disease in all patients, documented by endoscopy and curettage in two patients. As for the youngest patient, clinical decision for HSOPL has been made, and multiple sections of the operative material did not show any residual EA. Conclusions: Even though extremely rare, EAS may occur in asymptomatic patient and/or in young women without clinical evidence of polycystic ovary disease. In these patients careful histopathologic evaluation of the curettage material is essential, in order to select the ones to whom conservative fertility-preserving treatment can be offered.
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Combined large-cell neuroendocrine carcinoma and endometrioid adenocarcinoma of the endometrium: A case report
(Springer, 2017-08-25)
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Ognenoska-Jankovska, Biljana
Objective: Large cell neuroendocrine carcinoma (LCNEC) of the endometrium is a relatively rare and usually aggressive malignancy. We report a case of an endometrial tumour that was a combination of a LCNEC and endometrioid adenocarcinoma. Method: A 58-year-old woman presented with postmenopausal vaginal bleeding. Explorative curettage revealed a LCNEC of the endometrium. She underwent total abdominal hysterectomy with bilateral salpingooophorectomy and was diagnosed as having FIGO stage IB endometrial carcinoma. In spite of refusal of adjuvant therapy, and irregular follow-up, she has been well with no evidence of disease for 52 months following surgery. Results: Grossly, a polypoid neoplasm measuring 6.5 × 2.2 × 2.5 cm, infiltrating more than a half of the thickness of the myometrium of the posterior uterine wall was found. Histologically, the tumour was composed of two components: a predominant large cell high-grade neuroendocrine carcinoma and a minor superficial well-differentiated endometroid adenocarcinoma with foci of squamous differentiation. There was a differential immunoreactivity between the two components. More than 10 % of the cells of the LCNEC were positive for three neuroendocrine markers (CD56, NSE and synaptophysin), showing also diffuse positivity for cytokeratin 18, vimentin, and p16, and hormone receptor negativity, whereas the majority of the cells of endometroid carcinoma were negative for neuroendocrine markers, hormone receptor positive and only focally p16 positive. The proliferative index determined by Ki-67 was higher in LCNEC in which p53 overexpression was also present. Conclusion: Immunohistochemical analysis is helpful in diagnosing and differentiating primary LCNEC. The presented case also confirms that early-stage polypoid LCNEC may have a more favourable prognosis.
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Hormonal changes in women with abnormal endometrial bleeding in peri and postmenopause
(European Society of Endocrinology, 2022-05)
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Bashkim Ismaili
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Dimitar Georgiev
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SHpishikj Pushevska, Anamarija
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BONE MARKERS IN PERIMENOPAUSAL AND POSTMENOPAUSAL WOMEN WITH ABNORMAL UTERINE BLEEDING
(International Osteoporosis Foundation, 2022-03-24)
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Biljana Jovanoska Todorova
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Bashkim Ismaili
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Pranvera Izairi
Objectives: To determine the histopathological changes of the endometrium that occur during the period of perimenopause and postmenopause and to determine their association with the presence of obesity and the levels of bone markers for bone resorpition and bone formation, serum parathormone, vitamin D and calcium levels. Material and methods: This study involved 120 patients with fractionated explorative curettage due to abnormal uterine bleeding. The examined group was divided in two subgroups: 60 women in perimenopausis and 60 women in postmenopausis. Anamnestic data were taken from from all respondents. Body height and weight were measured. This laboratory analyses were performed: Serum Osteocalcin, beta CTX, parathormone, Vitamin D and calcium levels. Results: The most common pathological change of the endometrium was an endometrial polyp. History of previous bone fractures was significantly more common in postmenopausal women than in perimenopausal women. Postmenopausal women were older than perimenopausal and had significantly higher Body Mass Index, higher levels of serum osteocalcin and beta CTX in serum. Postmenopausal duration significantly positively correlated with Osteocalcin and β Cross Laps serum values. Higher serum Osteocalcin and β Cross Laps values were measured in patients with longer postmenopause duration. There was not significant difference in the levels of vitamin D and calcium between the groups. Conclusions: In the period of perimenopause and postmenopause, there are changes in the genital organs, but also there are internal disorders (obesity, metabolic syndrome, diabetes, thyroid disorders, cardiovascular disease, osteoporosis), which should be timely prevented, diagnosed and treated. Estrogen deficiency in postmenopausis is the most common cause of postmenopausal osteoporosis.
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RELATION OF ENDOMETRIAL PATHOLOGICAL CHANGES WITH ENDOCRINE DISORDERS AND METABOLIC SYNDROME
(Macedonian Association of Anatomists, 2021)
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Endometrial hyperplasia (EH) is an abnormal proliferation of endometrial glands and stroma and is associated with an increased risk of endometrial cancer (EC). Risk factors such as obesity, chronic anovulation, late menopause, hypertension, and diabetes lead to an increased risk of EH and EC. Aim: to determine the association of pathological changes in the endometrium with endocrine disorders and metabolic syndrome in women in peri and postmenopause. This study including a total of 139 patients in peri and postmenopause. The examined group consisted of 104 women with fractional explorative curettage due to a medical indication and was divided into two subgroups: peri and postmenopausal. The control group included 35 healthy women. Anamnestic data, body weight, height, blood pressure measurement, were taken from all patients, and the following laboratory parameters were determined: glucose, TSH, thyroxine, glycosylated hemoglobin (HbA1c), and Vitamin D . The presence of metabolic syndrome (MetS) according to its diagnostic criteria was also determined. In our study, significance was found in the comparison of the examined and the control group (p = 0.0001) in addition to the significantly higher BMI in the examined group. The comparison also indicated the existence of a significant difference in the level of glycemia in addition to a significantly higher level in the examined group (p = 0.0001). The statistical analysis did not indicate a significant difference between the two subgroups of the examined group, nor between the examined and the control group in terms of TSH, thyroxine and HbA1c levels. The value of vit. D was significantly higher in the control than in the study group (p = 0.0001). The analysis showed that patients with fractional explorative curettage had 4.982 times [OR = 4.982 (2.06–12.02) 99% CI] significantly more often MetS compared to women in the control group. Patients in the examined group had a significantly higher BMI, glycemia, and more frequent presence of MetS than those in the control group.

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