Faculty of Medicine

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PRIMARY SINONASAL MENINGIOMA MIMICKING BENIGN NASAL LESIONS - A CASE REPORT AND LITERATURE REVIEW
(Macedonian Association of Pathology and North Macedonia Division of IAP, 2025)
H. Sulejmani
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Jovcheva, A
Introduction: Primary extracranial meningiomas are rare neoplasms, accounting for less than 2% of all meningiomas. The sinonasal tract represents an uncommon site of origin and frequently presents diagnostic challenges due to nonspecific clinical and radiological features. Case Presentation: A 79-year-old male presented with a unilateral nasal cavity mass. Computed tomography revealed diffuse polypoid mucosal thickening with near-complete opacification of paranasal sinuses and obliteration of aeration. Histopathology showed a circumscribed neoplastic proliferation arranged in lobular and whorled patterns beneath intact respiratory epithelium. Tumor cells displayed uniform morphology with oval nuclei, eosinophilic cytoplasm, and inconspicuous nucleoli. Psammoma bodies and delicate vascular channels were present. Necrosis, nuclear atypia, and mitotic activity were absent. Immunohistochemistry showed strong positivity for epithelial membrane antigen (EMA), vimentin, p63, and progesterone receptor, while cytokeratin AE1/AE3, CD34, smooth muscle actin (SMA), S100, SOX10, desmin, and synaptophysin were negative. The proliferative index (Ki-67) was <5%. Discussion: Extracranial meningiomas are rare neoplasms with poorly understood histogenesis, presumably arising from displaced meningothelial cells during embryonic development. Sinonasal meningiomas may mimic other nasal masses including nasal polyps, inverted papilloma, olfactory neuroblastoma, or carcinoma. In this case, the morphological features combined with the supportive immunohistochemical profile confirmed the diagnosis of WHO Grade I meningothelial meningioma with angiomatous features. Conclusion: Primary sinonasal meningioma should be included in the differential diagnosis of sinonasal masses. Accurate recognition through comprehensive histopathological and immunohistochemical analysis is essential for proper diagnosis and management.
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Gallbladder and gastric metastasis as initial presentation of an undiagnosed primary lobular breast carcinoma
(Oxford University Press (OUP), 2026-02-24)
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Ivkovska, Sanja
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Filipovski, Vanja
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Kubelka Sabit, Katerina
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Jasar, Dzengis
The most common sites for breast cancer metastases include the bones, lungs, liver, and brain. Metastases in the GI tract are rare and predominantly originate from lobular breast cancer. Gastric involvement by invasive lobular carcinoma (ILC) is rare and can mimic primary gastric malignancies, leading to diagnostic challenges. Metastasis of ILC to the gallbladder is exceedingly rare and often identified incidentally during cholecystectomy performed for presumed benign conditions. We present a case of a 62-year-old female patient with symptoms of weight loss and dysphagia. After CT and gastroscopy, gastrectomy and cholecystectomy were performed due to suspicion of gastric carcinoma. Histology and immunohistochemical profiling, with estrogen receptor (ER), progesterone receptor (PR), E-cadherin, GATA3, Mammaglobin, and GCDFP-15, favored the diagnosis of lobular breast carcinoma metastasis over primary gastric adenocarcinoma. Awareness of these atypical presentations is crucial for accurate diagnosis and effective management, as misdiagnosis can result in suboptimal treatment strategies.
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Gastric schwannoma: a case report
(Oxford University Press, 2024-03-27)
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Kostovska, Irena
Gastric schwannomas are rare mesenchymal tumors that arise from the intestinal nerve plexuses. They present with nonspecific symptoms and are often discovered incidentally. We present the case of a 68-year-old patient who had been suffering from abdominal discomfort for 6 months. After a complete examination, including abdominal computed tomography and upper gastrointestinal endoscopy, we discovered a submucosal gastric lesion with benign gross features without evidence of lymph node or metastatic involvement. He underwent an open laparotomy. Final pathohistological and immunohistochemically identification of the surgical specimen established the diagnosis of benign schwannoma. Considering the excellent prognosis of the tumor, no adjuvant treatment was suggested other than simple clinical monitoring every 6 months. Despite the accessibility of advanced endoscopy and imaging techniques, the diagnosis of gastric schwannoma is rarely made preoperatively. In the latter case, the best treatment is still complete excision with wide margins.
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Immunohistochemical expression of CD44 in patients with hepatocellular carcinoma
(Macedonian Association of Anatomists and Morphologists, 2020)
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Nikolovska Trpchevska, Emilija
Introduction: CD44, a transmembrane glycoprotein with a role in cell-cell and cell-matrix interactions and one of the stem cell markers, is considered to participate in progression and prognosis of hepatocellular carcinoma (HCC), which makes it a potential prognostic marker and therapeutic target. We aimed to evaluate immunoexpression of CD44 in tumor and surrounding non-tumor liver tissue and to correlate it to multiple clinicopathological data in order to determine its prognostic value in patients from the Republic of North Macedonia. Material and Methods: Presence of the immunosignal and the percentage of CD44+ tumor cells at the whole tumor tissue sample and adjacent cirrhotic liver tissue were semi-quantitatively determined. The immunohistochemistry results were correlated to B and C hepatitis, tumor dimensions, enlarged lymph nodes, T status, differentiation (G), microvascular invasion, and survival. Results: We found a significant difference in CD44 expression between tumor and non-tumor liver tissue (p < 0.000) and significantly higher CD44 expression was also found in T4 tumors in comparison with T1 tumors (p < 0.01). Conclusion: Expression of CD44 was significantly higher in tumor in comparison to non-tumor tissue and was significantly associated to T4 local tumor growth, making it a potential prognostic marker and therapeutic target.
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VISUALISATION OF MICROGLIA WITH THE USE OF IMMUNOHISTOCHEMICAL DOUBLE STAINING METHOD FOR CD-68 AND Iba-1 OF CEREBRAL TISSUE SAMPLES IN CASES OF BRAIN CONTUSIONS
(Macedonian Academy of Sciences and Arts, 2015-12)
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Chakar, Ljupco
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In the recent years it has been confirmed that the main component of the immune response in an injury of the nerve cell comes from microglia and macrophages. The main challenge in the field of microglia research is to detect the different stages of cellular activation by visualization of the cell morphology. The existing visualization techniques are based on surface molecules expression in resting and activated microglia cells. For visualization of the microglial cells and their functional state we used double labeling method for cd-68 and iba1 in brain contusions with different survival time. Microglia are stained brown with Iba-1, whereas microglia impregnated with black, grainy color, represents activated microglia stained with CD 68. We had significantly positive results, and we were able to observe changes in the morphology of the microglia that correlated with the survival time. Using double labeling with Iba-1 and cd68 we were able to determine their physiological state based on the morphology and immunoreactivity
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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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HER2/neu expression in correlation with p53 and Ki-67 immunoreactivity and clinicopathological parameters in breast cancer patients.
(Blackwell Publishing, 2002-10)
Yashar, Genghis
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Ivkovski, Ljube
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Kraleva, Slavica
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Prodanova, Irina
Introduction: Although the role of HER2/neu status is still unsettled, its determination is valuable in selecting breast carcinoma patients for adequate Herceptin therapy. Aims: The purpose of this study was to evaluate the association among HER2/neu, p53 and Ki-67 immunoreactivity, as well as clinicopathological parameters (tumour size, histopathologic grade, nuclear grade, tumour type. lymph-node status and age) in breast cancer patients. Materials and methods: HER2/neu, p53 and Ki-67 expression was determined in 169 post-operative stage I-III (UICC. 1997) breast cancer patients using the standardized DAKO HercepsTest and by immunoperoxidase technique. respectively. The results were evaluated by performing the standardized scoring system. Discussion and conclusion: HER2/neu expression was positive in 66 patients (37%). There was no association between HER2/neu expression and p53 or Ki-67 immunoreactivity as well as any clinicopathological parameter, while the values of Ki-67 and p53 were strongly interrelated (P < 0.001). Ki-67 was also in significant correlation to tumour size, lymph-node involvement and tumour type (P<0.001), while p53 was only related to patients' age (P <0.01). These results indicate that HER2/neu is an independent prognostic marker in differentiating a subgroup of high-risk breast cancer patients. Additional studies are required to adjust HER2/neu testing results to clinical outcome.
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Association between Her2/neu expression and hormon receptor status in breast cancer patients.
(2002-06)
Yashar, Genghis
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Kraleva, Slavica
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Vasev, Nikola
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Ivkovski, Ljube
Determination of HER2/neu expression by immunohistochemistry is mandatory for application of Herceptin® therapy in breast cancer patients. The purpose of this study was to investigate the association between HER2/neu expression and hormone receptor status, as well as with other clinicopathological parameters in breast cancer patients. HER2/neu, p53 and Ki-67 expression was determined in 169 postoperative stage I-III (UICC, 1997) breast cancer patients using the standardized DAKO HercepsTest® and immunoperoxidase technique, respectively. The results of HER2/neu immunoreactivity were evaluated by performing the standardized scoring system (0 = negative, 1+ = weakly positive, 2+ = positive, 3+ = strongly positive staining), while ER and PgR were scored in a semiquantitative fashion (ER-ICA and PR-ICA). The results from HER2/neu expression were correlated to hormonal receptor status and clinicopathological parameters (tumor size, histopathologic grade, nuclear grade, histologic type of the tumor, lymph node status and patient age). Statistical significance was determined with χ2 and Fisher’s exact test. HER2/neu expression was positive in 66 patients (37%). There was no significant association between the values of HER2/neu and ER/PgR status, or with any other clinicopathological parameter. ER status significantly correlated with PgR status (p<0.01), tumor size (p<0.01), lymph-node involvement (p<0.01) and tumor type (p<0.01). PgR status was related to the histopathologic grade (p<0.01), lymph-node status (p<0.01), tumor type (p<0.01) and patient age (p<0.01). HER2/neu is a relatively new promising marker in predicting the response to target specific therapy. However, its predictive value remains a complex and inconclusive subject. According to our results, the prognostic potential of HER2/neu seems to be independent from hormone receptor status and any other clinicopathological parameter in breast cancer patients.
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Her2/neu expression in breast cancer patients - Correlation with estrogen and progesterone receptor status, p53 and Ki-67 immunoreactivity and clinicopathological parameters
(Institute of Oncology, Sremska Kamenica, Yugoslavia, 2002-09)
Yashar, Genghis
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Prodanova, Irina
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Vasev, Nikola
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Kraleva, Slavica
Although the role of HER2/neu status is still unsettled, its determination is valuable in selecting breast carcinoma patients for adequate Herceptin¨ therapy. The purpose of this study was to investigate the association between HER2/neu expression with estrogen (ER) and progesterone (PgR) receptor status, p53 and Ki-67 immunoreactivity, as well as with other clinicopathological parameters in breast cancer patients. HER2/neu, ER/PgR status, p53 and Ki-67 expression was determined in 169 postoperative stage I-III (UICC, 1997) breast cancer patients using the standardized DAKO HercepsTest¨ and by the immunoperoxidase technique, respectively. The results were evaluated by performing the standardized scoring system. The values of HER2/neu expression were correlated to ER/PgR status, p53 and Ki-67 immunoreactivity and to clinicopathological parameters (tumor size, histopathologic grade, nuclear grade, tumor type, and lymph node status and patients’ age). The statistical significance was determined with c2 and Fisher’s exact test. HER2/neu expression was positive in 66 patients (37%). There was no significant association between the values of HER2/neu and ER/PgR status, p53 or Ki-67 immunoreactivity, neither with any other clinicopathological parameter. ER is associated with PgR, tumor size, tumor type and lymph node status (p<0.01); PgR with histopathologic grade, tumor type and lymph node status (p<0.01) and Ki-67 with p53 immunoreactivity, tumor size and patients’ age (p<0.01). The results of the current study indicate that HER2/neu is an independent prognostic marker in differentiating a subgroup of high-risk breast cancer patients. Additional studies are required to adjust HER2/neu testing results to the clinical outcome.
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Uterine myxoid leiomyosarcoma arising in a leiomyoma - A case report.
(Institute of Oncology, Sremska Kamenica, Yugoslavia, 2002-09)
Hadzi-Nicheva, Biljana
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Prodanova, Irina
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Yashar, Genghis
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Kubelka, Katerina
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Grncharovska, Zlata
Myxoid leiomyosarcoma of the uterus (MLU) is a very rare neoplasm. We report a case of MLU arising from a pre-existing leiomyoma. Between 1989 and 2001, 45 uterine leiomyosarcomas were diagnosed in our laboratory and MLU was established in one case only (2.1%). Subtotal hysterectomy was performed on a 56-year woman with clinical diagnosis of a uterine myoma. The histopathological processing included hematoxylin-eosin, histochemical and immunohistochemical staining of selected specimens. Macroscopically, the uterus measured 15 x 12 x 11 cm, with an indistinctly circumscribed multi-nodular tumorous mass 10.5 cm in diameter, and infiltrative satellite nodules in the surrounding myometrium. The morphology of the neoplasm showed a leiomyoma with distinct degenerative changes, necrosis and hemorrhage. In some areas the cells were round or oval with a vacuolated cytoplasm, slight atypia and rare mitoses. The mitotic count was 1-3 cells/10 HPF. Due to the presence of an abundant mucoid substance, these areas appeared as hypocellular. The additional processing confirmed the smooth muscular origin of the neoplasm (Masson trichrome, azan, desmine, alfa-smooth muscle actin and vimentine positive). The areas of the myxomatose nodules were characterized with hormone independence (estrogen and progesterone receptors negative), high proliferative activity (Ki-67 - 30%) and the presence of p53 protein product (45%). The areas of the pre-existing leiomyoma showed hormone dependence, low proliferative activity and absence of p53 protein product. Additional immunostaining is useful in supporting a diagnosis of MLU in myxoid uterine smooth-muscle tumors with a low mitotic rate.

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