Aim: The aim of our study was to evaluate status of estrogen and progesteron hormone receptors (ER and PR), and HER2 receptors in diagnostic core biopsy specimens, compared to surgical resection specimens of the same patients after NAC regimens all including trastuzumab. Introduction: Neoadjuvant chemotherapy (NAC) is associated with phenotypic alteration in breast carcinoma, especially with the change of molecular phenotype through the modulation of hormone and HER2 receptors expression. Material and Methods: The study included 35 patients with HER2-amplified locally advanced breast carcinoma that were treated with NAC regimens that included trastuzumab, and which had receptors status determined on pre-NAC core biopsy, and on surgical specimen after the completion of the therapy. Results: Pathological complete response (pCR) was observed in 4 cases (11.4%), while partial response to therapy was noted in 31 cases (88.6%). Invasive breast carcinoma of no special type (NST) was the most common histological type in 27 cases (87.1%), while the most common histological grade (HG) was HG3 in 27 cases (87.1%). There were no noted changes in histological type or grade of the carcinoma. The rates of ER and PR receptors positivity on diagnostic core biopsy compared to post-NAC surgical resection specimens were 61.29% to 67.74% and 48.39% to 64,52%, respectively. HER2 receptors status changed from positive to negative in 2 cases (6,45%). Conclusion: Changes in status of the receptors in breast carcinoma after NAC is significant due to implications in tailored therapy approach, and subsequent modification of adjuvant therapy regimens.

Lung carcinoma is the leading cause of increases in the morbidity and mortality rates of malignant diseases worldwide. Adenocarcinoma has been the most common histological type in the last decades due to: changes in the tobacco industry, smoking habits and the use of immunohistochemistry. Among more than half of patients, lung adenocarcinoma is diagnosed in an advanced stage of the disease. The discovery of mutations in epidermal growth factor receptor (EGFR) in lung adenocarcinoma is a major advancement in molecular pathology and a new approach to the treatment of these patients. Patients with EGFR mutated lung adenocarcinoma receive a targeted therapy (Tyrosine Kinase Inhibitors-TKI) which leads to improvements in disease prognosis and quality of life. Real-time polymerase chain reaction (PCR) is the most widely used and most reliable method since it requires a minimum amount of starting material and allows the amplification of the desired DNA segment up to a billion times. In this way, deletions in exon 19 are detected in approximately 90% of cases, more often in women, non-smokers and in the territory of Asia. The following may be used for EGFR testing: fresh tissue, fast-frozen tissue, tissue molded into paraffin blocks after fixation in formalin and cytological material obtained by scraping from glass tiles. Tissue processed by decalcination, acid treated or heavy metal treated tissue should be avoided. Although surgical samples represent the golden standard in determining EGFR mutations, the results obtained are compatible with the results obtained by bronchoscopic biopsy and thus eliminate the need for invasive diagnostic procedures. Bronchoscopy is an invasive diagnostic method, whose objectives are to diagnose lung tumors, determine the endoscopic spread of the disease and assess tumor operability. The presence of a tumor may be indicated by a different bronchoscopic aspect of the endobronial mucosa. The sensitivity and specificity of this method depends on: bronchologist’s skills, endoscopic findings, the number of biopsy samples, the professional competence of pathologist-cytologist and the obtained tumor amount. The tumor amount is generally small and depends on the histological type, endoscopic findings, sampling technique and the presence of other cells. It is recommended to take three to five biopsy samples, used for diagnosing but also for molecular testing. Targeted therapy is applied based on the obtained results. Given that biopsy samples molded in paraffin are cut into multiple histological sections, and that the tumor amount decreases, it is necessary to minimize the “consumption”. The concentration of isolated DNA does not differ among patients with wt EGFR and mutated EGFR adenocarcinoma. To date, there has been no consensus regarding the number of tumor cells necessary to determine EGFR mutations, and it is recommended to take samples with a minimum of 200 to 400 tumor cells. Invalid results obtained by using the PCR method are most commonly the result of a small number of preserved tumor cells in a biopsy sample. Blood and necrosis may be limiting factors for molecular testing, but not exclusion factors for the same. Bronchoscopic biopsy sample is adequate for the determination of EGFR mutations because the majority of biopsy samples have more than 100 tumor cells, the difference between the concentration of isolated DNA in EGFR mutated and wt EGFR adenocarcinomas is not statistically significant, EGFR mutations are also detected in samples with a small number of tumor cells when using highly sensitive tests.

Aim: To determine the degree of correlation between TTF-1 (+) expression and EGFR mutation status in lung adenocarcinoma. Introduction: Adenocarcinoma of the lung is mainly diagnosed based on standard morphological criteria. The thyroid gland transcription factor (TTF-1) is currently the most commonly used immunohistochemical marker in the differentiation of invasive adenocarcinoma of the lung from another primary and metastatic carcinoma, has a prognostic significance and is a predictor of the EGFR mutation status. Material and Methods: This retrospective study enrolled 60 patients with histologically confirmed primary lung adenocarcinoma who underwent lung cancer surgery at Institute for lung disease Vojvodina between 2010 and 2015. Tumor specimens of these patients were investigated for TTF-1 expression and mutations in EGFR using immunohistochemistry and PCR analysis. Statistical analysis is in statistic software Statistica 12. Results: The study included 35 men and 25 women, with an average age of 61.8 ą 8.08 years. Of the 60 cases, TTF-1 ( ) expression was recorded in 52 (87%) (p <0.001), the statistical difference is not significant when comparing smoking habitsby gender, and tumor size among them. EGFR ( ) mutation status was found in 3/60 (5%) cases [egzon 21 (2) and exon 20 (1)], of which TTF-1 (+) expression was in two cases. Conclusion: There is a statistically significant difference between the TTF-1 (-) and TTF-1 (+) adenocarcinoma and a high degree of correlation between EGFR mutation status and TTF-1 (+) expression.

Aim: Analysis of two cases of IPA with an emphasis on the radiological and pathohistological findings of this entity. Introduction: Aspergillus spp. can cause a wide range of lung diseases, depending on the current state of immunity and the existing pulmonary diseases. Invasive pulmonary aspergillosis (IPA) is severe form of pulmonary mycosis, with the appearance of granulomatous inflammation with the development of necrosis and suppuration, as well as the invasion of hyphae into pulmonary parenchyma and the blood vessels and spreading the disease out of the lungs. Material and Methods: In the five-year period, two cases of IPA were diagnosed at the Institute of Pulmonary Diseases of Vojvodina. Material for pathohistological analysis, obtained by surgical method and on autopsy, was stained with standard H E staining, as well as with special staining methods: PAS and Grocott. Results: Patients were 67 and 48 years old and both were treated for acute lymphoblastic leukemia. They were admitted to our hospital in respiratory insufficiency and severe neutropenia with a radiologically diagnosed IPA based on HRCT finding of “halo sign”. This sign pathohistologically corresponds to foci of necrosis of lung parenchyma surrounded with the zone of hemorrhage. In addition to these foci of necrosis, in the wall and lumen of blood vessels, numerous septate hyphae with dichotomous branching at 45° were found. Conclusion: Although the pathohistological diagnosis is golden standard for diagnosis of IPA, given the invasiveness of the techniques for obtaining material for analysis, diagnosis can be made based on HRCT finding of “halo sign”.

Aim: We present a case of a patient with pneumothorax and subcutaneous emphysema as the first manifestation of miliary tuberculosis. Introduction: Miliary tuberculosis is the result of hematogenous dissemination of Mycobacterium tuberculosis in patients with weak immuno-defensive mechanisms. Pneumothorax and subcutaneous emphysema are possible complications of miliary tuberculosis. Case report: A woman aged 64 years old reported to the regional institution because of breathing difficulties. On the radiograph of the chest, pneumothorax was observed left, and the left thoracic drain was placed. Subcutaneous emphysema and global respiratory insufficiency were reported an hour later after which the patient was transferred to our facility. At the admission the patient was in poor general condition, intubated, hemodynamically unstable, markers of inflammation were elevated with the presence of electrolyte imbalance and severe anemia. On the chest radiogram, there was recorded: pneumothorax left, pneumonia right and generalized subcutaneous emphysema, and thoracal drain that was placed. Intensive therapy had improved the condition of the patient, after which she was extubated. Progression of respiratory insufficiency and lethal outcome occurred on the second day of admission. An autopsy was performed. A macroscopic examination and pathohistological analysis found: massive subcutaneous emphysema in the chest, well-placed thoracal drain, bilateral pleural effusion, bilateral acute tuberculous caverns in the lungs and necrotizing granulomas in: the lungs, liver, spleen and larynx which have led to asphyxiation and aviation outcome. Conclusion: In poorly-fed patients with the development of pneumothorax, subcutaneous emphysema and severe respiratory disorders, it is necessary to suspect tuberculosis.

Aim: The aim of this case was a correct diagnosis of mediastinal tumor in a 41-years old female patient. Introduction: The rarity of primary extraneural ependymomas, its great variations in morphology and rare occurrence of metastasis, increase chances of misdiagnosis. Case report: Macroscopic examination of received specimen was performed, followed by histological and immunohistochemical analysis of the tissue samples. In presented case, onset of the disease was 14 years ago, when after right salpingo-oophorectomy, patient was diagnosed with malignant mesothelioma. In following years patient had multiple and extensive surgical procedures, resulting in different patohistological diagnosis, and after seven years, a diagnosis of extraneural ependymoma was established. Later on, patient was surgically treated in several medical centers across the region, again with different patohistological diagnosis. At present, tumor metastasized to mediastinum, presenting as grey to brown, multicystic formation, with cysts filed with clear serous fluid or red-brown hemorrhagic fluid. Inner surface of the cysts had smooth to partly papillary appearance. Tumor cells exhibited several architectural paterns (solid, pseudorosette or rosette formations, papillary and pseudopapilary structures), and immunophenotype specific for extraneural ependymoma (GFAP, ER, PR positive, calretinin, WT-1, S100, synaptophysin, chromogranin, CK7 and pan-cytokeratin negative). Conclusion: This case demonstrates an important principle in tumor pathology. Neoplasms may occur in unusual and unexpected primary and metastatic sites. Pathologists need to be familiar with histologic features of a wide range of neoplasms and not just the appearance of neoplasms within their own limited subspecialty area.