Faculty of Medicine

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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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