Aim: To evaluate surgical lung biopsies in patients with a clinically and radiologically set diagnosis of ILD. Introduction: Interstitial lung diseases (ILDs) are a group of lung diseases affecting the lung interstitium. These entities share similar clinical and radiological features and are distinguished primarily by the histopathologic patterns on surgical lung biopsy. Material and Methods: The study included 30 patients with a surgical lung biopsy performed in 10-year period at the Institute for Pulmonary Diseases of Vojvodina in Sremska Kamenica. Standard H E stain, special stains for conective tissue and smooth muscle, as well as immunohistochemistry in some cases were used. The patient’s age, sex, clinical symptoms, surgical biopsy type and histological findings were analyzed. Results: Of the 30 patients who underwent surgical lung biopsy, an open lung biopsy according to Claassen was performed in 14 patients, in 12 biopsies biopsy according to Maassen was obtained, while in 4 patients material for histopathological analysis was taken by VATS (Video - Assisted Thoracoscopic Surgery). The most common biopsy site was upper lobe in 16 cases, then lingula in 10, middle lobe in 2, and lower lobe and lung base in 1 patient. By histopathological analysis, diagnosis of UIP in 8, PLCH in 7, sarcoidosis in 6, hypersensitivity pneumonitis in 3, NSIP in 2, LAM, LIP, DIP and ACIF in 1 patient. Conclusion: Diagnosis of ILD is based on history, physical examination, high-resolution CT imaging, pulmonary function tests, and lung biopsy which presents golden standard in diagnostic approach.

Aim: Lobular endocervical glandular hyperplasia is very rare, differential diagnostic difficult entity, which often mimics more aggressive endocervical lesions, with worse prognosis. Introduction: Lobular glandular endocervical hyperplasia(LEGH) is benign lesion with lobular proliferation of endocervical glands and endocervical epithelium without or with minimal nuclear atypia. Lobular structure can be deep into the cervical tissue without stromal invasion, which is important difference between adenocarcinoma of minimal deviation(MDA), well-differentiated endocervical type of adenocarcinoma, similar to LEGH. Case report: The patient is 50 years, with demarcated, nodular, multicystic tumor, localized deep in cervical tissue. Microscopic analysis shows numerous cystically dilated endocervical glands with lobular presentation, surrounded by hyperplastic fibrous stroma. Glandular acini are diffusely localized, with centrally dilated acinus and peripheral smaller tubular structures. Glands are without the presence of architectural changes and cytonuclear atypia, with uniform, endocervical epithelium.Immunochemical analysis showed:CEA- /CA125focal /p16 focal /Er and Pr focal epithelium, diffusely in stroma. Because structures were described deep in the cervical tissue, MDA is considered diagnostically differential. However, glands do not show signs of distortion(architectural atypia), which is important feature of this entity, as well as no pronounced surrounding desmoplastic stromal reaction. Macroscopic tumor is well demarcated, and the CEA marker is negative, which also suggested LEGH. Conclusion: LEGH and MDA show a quiet clinical and histological similarity. Association of LEGH(50%) with MDA and 40% with cervical adenocarcinoma has been demonstrated, suggesting the possible precancerous potential of LEGH. Research of the lesion microenvironment could be an interesting subject for further research.

Aim: Evaluation of pathological estimation results of therapeutic response of primary breast carcinoma to applied neoadjuvant therapy. Introduction: Breast carcinoma is heterogeneous disease, that could be classified into several molecular subtypes by using immunohistochemical analysis and in situ hybridization. Neoadjuvant therapy is applied in cases of locally advanced breast carcinoma and for tumor chemosensitivity evaluation, which is very significant for disease prognosis. Material and Methods: The research was conducted on 35 female patients, that were treated with radical mastectomy in 2017, after IV cycle of neoadjuvant therapy, in Clinical Centre of Montenegro. Before treatment, all patients underwent core biopsy (confirmed invasive breast carcinoma, molecular subtype determined).Pathohistological response of primary tumor to applied therapy was estimated as complete response (pCR), partial response (pPR) and no response (pNR). Results: Average age in examined group of patients was 59,25 years.In 68,58% of cases it was invasive ductal, in 17,14% invasive lobular and in 14,28% mixed invasive carcinoma. Representation of molecular subtypes was (without change in respect to the core biopsy): 34,28% Luminal A, 42,85% Luminal B Her2 negative, 5,71% Luminal B Her2 positive, 8,58% Her2 positive and 8,58% triple negative. In 6 patients (17,15%) pCR was obtained, in 21 (71,42%) pPR, and in 4 (11,43%) no response. In group of patients confirmed for pCR, it was Her2 positive or triple negative carcinoma. Conclusion: Applying of neoadjuvant therapy leads to tumor response to applied therapy. Most commonly it is partial response, while complete response most commonly occurs in Her2 positive or triple negative carcinomas.

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: To highlight the widespread metastatic potential of the cutaneous melanoma, as well as its tendency for unusual presentation of metastatic disease. Introduction: Melanoma is an aggressive, highly malignant disease that is derived from melanocytes. The incidence of melanoma is significantly increasing. Melanoma has a strong tendency for metastasis. After primary excision of tumour, about 30% of all patients shall develop distant metastasis within first 5 years after tumour diagnosis. Case report: A 48-year-old female patient had undergone a hysterectomy because of myomatous uterus. After pathohistological examination metastasis of melanoma was diagnosed in one of multiple leimyoma. Diagnosis was confirmed with positive immunohistochemical staining with MART1 and S100 protein. Insight into the medical records, revealed that patient was diagnosed with superficially spreading melanoma (Clark IV, Breslow III) on skin above her left breast, as well as 2 regional tumour-involved lymph nodes (pT3aN2bM0), 2 years prior to this hysterectomy. Uterine leiomyoma was the first diagnosed distant metastasis of cutaneous melanoma. Diagnosis of stadium IV melanoma was established. Conclusion: Melanoma is a particularly aggressive disease with unpredictable evolution, so the occurrence of metastases in unusual and unexpected localizations, as is the distant benign tumour in the presented case, shall probably happen more often in the future.

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: The aim of this study was to investigate the association of local tumor survivin expression and serum concentration with clinical and histopathological parameters in melanoma patients. Introduction: Survivin is a multifunctional protein abundantly expressed in tumors of various types, including melanoma. There are still sparse data regarding relationship of melanoma cell survivin expression with accepted histopathological characteristics as well as serum concentration. Material and Methods: The level of survivin expression was determined immunohistochemically in tumor tissue and with ELISA test in the serum of 84 melanoma patients with melanoma. Results: Survivin expression was significantly higher in the patients whose tumor had ulceration, higher mitotic index, higher Clark and Breslow stage, that made vascular invasion or spread through lymphatic vessels in primary tumor, and in the patients with metastatic disease. The patients with high survivin expression score had almost double shorter disease free interval DFI comparing to those with weak local survivin expression and a small number of survivin cells (9 - 7 vs 19 - 13 months, respectively). The degree of tumor infiltrating lymphocytes presence in tumor tissue was significantly inversely associated with serum survivin concentration. Conclusion: Conclusion Survivin expression in tumor tissue and its serum concetration significantly correlate with clinical and histopathological parameters. Serum levels could be important in initial follow-up as indicators of those patients that would have aggressive local tumor growth and spreading.

Lung cancers are the most common cause of morbidity and mortality from malignant tumors in the World. The neodjuvant therapy in patients with locally advanced (IIIA-IIIB) lung cancer and affected N2 lymph nodes is one of the modes of multimodal treatment of patients with non-small cell lung cancer (NSCLC) in order to improve the outcome of their treatment. This involves converting patients from a higher to a lower stage of the disease - “downstaging”. There has been no significant connection between some forms of tumor response and types of therapy. Given the importance of complete pathological responses and tumor regression in the prediction of treatment outcomes, finding this relationship is of importance for the design of future neoadjuvant trails. In determining the histological tumor regression is very important measurement of area of residual tumor (ART). As the size of the tumor is one of the prognostic factors in patients with NSCLC who did not receive neoadjuvant therapy so the measurement of ART, as opposed to the macroscopic size of the tumor, one of the prognostic factors in patients with NSCLC, who had received neoadjuvant therapy. The ultimate goal of neoadjuvant therapy should be resectability and “downstaging” that could provide overall oncology benefit in specific clinical situations. The main objectives of this research were: to objectively estimate the size of ART in tumor tissue of lung and lymph nodes; to estimate the relation between the surface of ART with the size of the tumor on postoperative surgical material after neoadjuvant therapy; to analyze and estimate the relation between histomorphological parameters in tumor regression induced by neoadjuvant therapy and spontaneous tumor regression in tumors of the lung and lymph nodes in the postoperative surgical material and depending on the histological type of cancer; to estimate the relation between clinical response to neoadjuvant therapy according to criteria of the World Health Organization and histological parameters in lung tumors and lymph nodes in the postoperative surgical material after neoadjuvant therapy; to estimate the correlation of the pathological ypTN with clinical ycTN stage of the disease and the degree of tumor regression induced by neoadjuvant therapy and pathological ypTN and estimation of the relation between clinical and pathological involvement of N2 lymph nodes after neoadjuvant therapy. Measurement of the total size of the preserved ART is the most important objective parameter in the assessment of the grade of tumor regression. Size of residual tumor did not correlate with the size of the tumor after neoadjuvant therapy. There was a significant difference in the histological picture of tumor regression induced by neoadjuvant therapy and spontaneous tumor regression. There was no significant difference between the histologic type of tumor and histological tumor regression. There is no significant correlation between clinical response and the grade of tumor regression after neoadjuvant therapy. There is no correlation between clinical and pathological staging of the diseaSPECIAL SESSION: DEPARTMENT OF PATHOLOGY, MEDICAL FACULTY, UNIVERSITY NOVI SAD, SERBIA 34 MATERIA MEDICA • Vol. 34 • Issue 1, suplement 1 • april 2018. se after neoadjuvant therapy. There is no correlation between the grade of tumor regression induced by neoadjuvant therapy and ypTN stage of the disease. There is no correlation between the clinical and the pathological involvement of the N2 lymph nodes to neoadjuvant therapy. The grade of tumor regression and measurement ART after neoadjuvant therapy determined by histopathological analysis of the resected tumor is the most objective criterion for evaluation of chemotherapeutic response and prediction of treatment outcome in patients.

Aim: Report of two cases of benign skin tumors of different histogenesis with anaplastic lymphoma kinase (ALK) gene rearrangement. Introduction: ALK gene mutation or rearrangement positive tumors (ALKomas) are heterogeneous group in which such genetic finding has diagnostic or predictive value. ALK gene fusions are associated with tumorigenesis of some cutaneous tumors, e.g. plexiform Spitz nevus (PSN) and epithelioid fibrous histiocytoma (EFH). Cases reports: Histological, immunohistochemical (IHC) and genetic characteristics were analyzed in two skin tumors with ALK gene rearrangement proved by fluorescent in situ hybridization (FISH). First case is PSN localized on face in a 8-year-old boy. Tumor was consisted of spindle cells arranged in plexiform growth pattern throughout epidermis and dermis, with following IHC characteristics: HMB45  focally, p16 , Ki67  in 1% of cells. Deletion of CDKN2A gene was not detected in significant number, while ALK gene rearrangement was positive in 37/50 (74,2%) of cells. Second case is EFH localized on shoulder in a 16-year-old girl. This dermal based tumor was consisted of tightly packed large epithelioid cells, which were CD68 , p16 , S100-, HMB45-, SOX10-, CD1a-, Ki67 (<5% of cells). ALK gene rearrangement was positive in 24/100 (24%) of cells, and focal chromosome 2 polysomy was noted. Neither mitoses nor necrosis were present in any of presented cases. Conclusion: Skin ALKomas are tumors with heterogeneous histological and immunohistochemical characteristics, and also with variable extent of ALK rearrangement.

Aim: Our aim is to examine the expression of CD34 in the endometrioid carcinoma (EC) of the uterine body and association of neoangiogenesis with classical clinical and prognostic parameters. Introduction: The incidence rate increases with age, so in about 75% of cases it occurs in postmenopausal women.Material and Methods: On the biopsy samples obtained after the hysterectomy of 36 patients operated from EC of the uterine body, operated in the General hospital Pirot, where applied routine H E and the imunohistochemical ABC method with anti-CD34 antibodies. Based on the expression of CD 34, the microvascular density per mm2 of the tissue was calculated stereometrically. For statistical analysis SPSS software package were used (version 19.0). Results: The significantly pronounced expression of CD34 is present in all cases of tumors in pT2a to pT3a, and in all cases of the IIA-IIIA FIGO stage. A significantly high neoangiogenesis index is present in 72% of moderately differentiated tumors, in about 70% of tumors with moderate/expressed nuclear atypies, in 92% of cases with microvascular invasion and in 76,5% of tumors affecting over 50% of myomterium. CD34 expression is in positive, moderate and significant correlation with invasion of lymph vessels, pathological stage of the tumor and invasion of blood vessels and myometrium (kk=0,636 - 0,587). The correlation between this marker and the histological and nuclear tumor grade is weaker (kk=0,444 and 0,410). Conclusion: Significant association of CD34 with the aggressive phenotype of the EC of uterine body has significant prognostic implications.