Faculty of Medicine

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Author: search.filters.author.Petrushevska, Gordana

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    Genetic Alteration Profiling in North Macedonian Lung Cancer Patients
    (MDPI AG, 2025-10-10)
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    Background/Objectives: Late diagnosis and inefficient treatment regimens lead to poor prognosis, with a low 5-year survival rate for both non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). New targeted therapeutic agents can be developed and introduced only by first discovering new driver oncogenes and with a thorough investigation of the known driver genes. The aim of the current study is to investigate the prevalence of alterations in the eight most frequently altered genes in lung cancer-BRAF, EGFR, KRAS, ALK, ROS1, HER2, PD-L1 and PIK3CA. Methods: Real-time polymerase chain reaction (RT-PCR) was used to detect KRAS and EGFR mutations, multiplex PCR and microarray hybridization for KRAS/BRAF/PIK3CA mutations. Immunohistochemical analysis was performed for the detection of ALK, HER2/NEU, ROS-1 and PD-L1 alterations. Results: Overall, 221/603 patients (36.65%) had at least one genetic alteration, of which 22 patients (3.65%) had two genetic alterations and two patients had more than two genetic alterations. Additionally, 50 patients were identified with one or more KRAS mutations (8.29%), 45 patients with EGFR mutations (7.46%), and 1.82% with PIK3CA mutations and 0.66% with BRAF mutations. Furthermore, 50% of the co-occurring alterations were either on KRAS and PIK3CA genes (3/6), on KRAS and BRAF genes (2/6, 33.33%) or on EGFR and PIK3CA genes (1/6, 16.67%), and 10.45% of the patients exhibited PD-L1 overexpression, 5.31% ALK rearrangements, and 2.36% HER2/NEU expression, with no ROS-1 rearrangements detected. Conclusions: Comprehensive testing for somatic alterations in EGFR, BRAF, KRAS, and PIK3CA is significant in guiding therapeutic decisions in lung cancer management. Such testing should be routinely conducted to establish a thorough genetic profile of lung cancers in a manner that is both time-efficient and cost-effective.
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    Finding of a mass on the mitral valve in a patient on chronic dialysis
    (Elsevier BV, 2025-04)
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    Shokarovski, Marjan
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    Lazovski, Nikola
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    Mehmedovic, Nadica
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    Myxomas are cardiac neoplasms that are most commonly located in the left atrium, usually arising from the vicinity of the fossa ovalis. However, there have been cases, although very rarely, of valvular myxoma. A cardiac mass found incidentally on echocardiography can present a challenge in particular if asymptomatic or found in an unusual location. We present the case of a 58-year-old male with kidney disease treated with chronic dialysis, referred to the cardiology clinic because of an incidental finding of a mitral valvular mass on routine transthoracic echocardiography. Although this lesion was initially misdiagnosed as native valvular endocarditis with vegetation, a series of clinical and radiological investigations led to the preoperative diagnosis of possible papillary fibroelastoma or calcified thrombotic mass. Given the increased risk of embolization due to the mass being mobile and greater than 1 cm in size, the patient was referred to cardiac surgery. Excision of the mass without mitral valve replacement was performed. Histopathological findings of the mass revealed the existence of a cardiac myxoma. In such cases of a mitral valve mass, multimodality imaging should have of high priority to achieve an accurate diagnosis. Although a definitive diagnosis can only be established after surgical excision of the mass and histopathological confirmation, it is very important to consider a differential diagnosis of mitral valve myxoma in any patient with an unexplained mitral valve mass.
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    Extranodal Diffuse Large B-Cell Lymphoma of the Small Bowel in Female Patient Causing Intestinal Obstruction: A Case Report
    (Vilnius University Press, 2022-12-30)
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    Dukovski, Dushko
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    Diffuse large B cell lymphoma is the most common extranodal non-Hodgkin lymphoma of the small intestine accounting for more than 50% of cases. Forty percent of these cases initially present with small bowel obstruction. Therefore, the diagnosis is usually established after surgery for bowel obstruction. The treatment is then continued with a certain chemotherapy regimens. We present a case of a 46-years-old female patient with signs of small bowel obstruction due to previously undiagnosed diffuse large B-cell lymphoma. Postoperatively, the patient was treated with 7 cycles of R-CHOP protocol and complete response was achieved in the short follow-up period.</jats:p>
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    A Cases of Chemotherapy Induced Myelodysplastic Syndrome in Patients with Primary Solid Tumors
    (ISOP 2025, 2025-08)
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    Ognenoska Jankovska, Biljana
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    Therapy induced myelodysplastic syndrome (MDS) is a rare, even-though well-established fatal adverse event caused by either chemotherapy or radiotherapy in patients with malignant disease [1]. MDS is characterized with poor prognosis mainly due to the poor bone marrow reserve from prior chemo/radiotherapy [2, 3]. Objective To stress the importance of documenting as well as monitoring myelodysplastic syndrome as adverse drug event that arise from chemo/radiotherapy in patients with solid tumors that must be considered by clinicians when developing treatment plan for these patients. Methods We present two cases with different cancer diagnosis. The first one is a male patient with small cell lung cancer (SCLC) treated with combination of six cycles paclitaxel/carboplatin and radiotherapy (44Gy). The second one, is a female patient with a primary, stage IIIC breast cancer, treated with four cycles of epirubicin/cyclophosphamide, four cycles of docetaxel and loco-regional radiotherapy (50Gy) in a period of three years. Additionally, the patient received adjuvant hormonal therapy (anostrozole) for 10 years. Results After the chemotherapy, the first male patient (64 years) recovered on clinical radiographic evaluation with complete remission of the disease, without signs of infiltration of the lung with malignant disease. 7-years later, the patient was admitted at the Clinic of Hematology, with complaints of fatigue, prostration and increased sweating. Bone marrow biopsy revealed findings of secondary myelodysplasia, namely signs of hematopoietic cells dis-maturation with signs of megaloblastic maturation of the erythropoietic lineage, appearance of ALIP in the myeloid lineage and dysplastic megakaryocytes. In addition, it was found an increased level of polyclonal plasmacytes. Two cycles of treatment with ABVD D1C1 and ABL D1D2 was applied and clinical improvement was registered. The second female patient (67 years) developed refractory anemia with excess blasts in transformation (RAEB-T), a severe subtype of MDS further confirmed on bone marrow biopsy as acute myelomonocytic leukemia, after 10 years of the initial diagnosis. The patient was started on 6 cycles with azacitidine, after which she was hospitalized with low platelets (6x103/ml) and white blood cell counts (1.3x103/mL) and hemorrhagic syndrome. She received platelets and red blood cells transfusion as well as supportive treatment (granocyte, dexamethasone, decortine, 59 doses of platelets, plasma). Conclusion Patients that are under long-term chemo- and radiotherapy treatment must be followed-up carefully. Additional data is essential to be assessed to identify patient characteristics that can be associated with this fatal adverse event. Briefly, post-chemotherapy, it is desired to examine when there are clinical signs of fatigue, infections or bruising as possible presentation of MDS. This can assist clinicians in creation of the treatment plan in terms of choosing alternate therapy choices when applicable.
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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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    Hypercalcemia and Renal Affection: An Unusual Initial Presentation of Sarcoidosis
    (Macedonian Academy of Sciences and Arts/Walter de Gruyter GmbH, 2025-03-01)
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    Sarcoidosis is a chronic, multisystem, inflammatory granulomatous disease that affects multiple organs in the body, but mostly the lungs and the lymph glands. Hypercalcemia and renal affection are rarely initial presenting features, and in the absence of pulmonary symptoms, the diagnosis of sarcoidosis in those patients could be a diagnostic challenge. A case-patient with sarcoidosis presented with elevated serum calcium and creatinine levels. Renal biopsy showed nephrocalcinosis with chronic fibrosing interstitial nephritis. The extensive mediastinal, abdominal, axillar, and neck lymphadenopathy was presented on the computer tomography scan of the patient's chest and abdomen. The neck lymph node surgical biopsy showed confluent, non-caseating, epithelioid granulomas consistent with sarcoidosis. The serum angiotensin-converting enzyme level was elevated. Treatment with oral prednisolone was started, and improvement of renal function and normalization of serum calcium was noted. Sarcoidosis should be considered in the differential diagnoses in patients with renal impairment and non-parathyroid hormone (non-PTH) dependent hypercalcemia.