Aim: We present the case of a woman with endobronchial pulmonary synovial sarcoma. Introduction: Primary pulmonary synovial sarcoma is an extremely rare tumor that has the same histomorphological characteristics and chromosomal translocations as the synovial sarcoma of soft tissue origin. Material and Methods: A woman aged 58 years, the smoker, without the current symptoms of the disease, came to our institution because of the nodus that was seen on the CT chest. The polip (26 mm) was located in the lumen of the lower right lobar bronchus. The mediastinal and hilar lymph nodes were not increased. The radiological examination was done as part of a routine control after the meningeoma surgery three years ago. Right lower lobectomy and resection of regional lymph nodes were performed. Results: By a macroscopic examination, in the lumen of the bronchus for the lower right lobes, a clearly limited, nonencapsulated, grayish-white node of 2.6 x 2.6 x 1 cm was found. Histologically, the tumor was showed interweaving fascicular uniform spindle cell with ovoid, pale staining nuclei, and inconspicuous nucleoli, scant cytoplasm and the cell borders indistinct. Immunohistochemical tumor cells were positive for CD99, bcl2 and vimentin. Surgical margins and regional lymph nodes were not affected. A detailed clinical and radiological examination confirmed the primary lung origin of the diagnosed synovial sarcoma. A year after surgery the patient feels good. Conclusion: Morphological and immunohistochemical analysis with detailed clinical and radiological examination confirms the primary lung origin of synovial sarcoma

Aim: To compare sensitivity, specificity and accuracy of bronchial brushing (BB) and transbronchial needle aspiration (TBNA) cytology in diagnosing lung cancer and to correlate and compare them with corresponding histopathology. Introduction: Lung cancer is a leading cause of death worldwide in both genders. Various cytological techniques such as BB and aspirate, TBNA, bronchoalveolar lavage, transthoracic and pleural puncture can aid in early diagnosis of lung malignancies. Material and Methods: One-year retrospective study included 359 patients with suspected lung cancer who underwent bronchoscopy. During bronchoscopy, cytopathological samples were obtained for smears using BB and TBNA as well as biopsy for histopathological examination that was considered the  gold standard .  All the samples were microscopically examined and statistically analyzed using descriptive methods and non-parametric Kendal-tau correlation coefficient (the level of significance p<0.05). Results: Sensitivity of BB and TBNA cytology comparing to histopathology was 97.17% and 98.32% respectively whereas specificity was 97.26% and 97.75 % respectively. Positive predictive value was 97.14% in BB and 99.66% in TBNA and negative predictive value was 93.23% in BB and 98.77% in TBNA. The accuracy of BB was 96.51% and 99.14% of TBNA cytology. Discordance of BB cytological and histopathological diagnosis was in 3.21%, whereas discordance of TBNA was in 2.03% cases. There was no statistically significant difference neither between BB (p=0.550) nor between TBNA (p=0.602) cytology and histopathological diagnosis. Conclusion: Cytology is valuable and useful in establishing lung cancer diagnosis, which yields almost the same information as histopathology no matter which method of cytological sampling is used.

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: 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: 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 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.

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.

In preparation for the 8th edition of the TNM classification for lung cancer the International Association for the Study of Lung Cancer (IASLC) collected data on 94,708 cases of lung cancer diagnosed between 1999 and 2010, donated by 35 institutions in 16 countries. After exclusions, 77,156 remained for analysis: 70, 967 cases of non-small cell lung cancer (NSCLC) and 6,189 cases of small-cell lung cancer (SCLC). Analysis of the cases of NSCLC has allowed proposals for revisions to the T, N and M descriptors and TNM Stage groupings. Size remained an important determinant and a descriptor for all of the T categories. A new cut points at 1 and 4 cm have been proposed and as a result new T categories have been created: T1a ≤1 cm, T1b > 1 to 2 cm, T1c > 2 to 3 cm, T2a > 3 to 4 cm, T2b > 4 to 5 cm, T3 > 5 to 7 cm and T4 > 7 cm. However, measuring precise tumor size can be challenging since it is known that tumor gross size depends on whether the size measurement is performed on fresh or formalin-fixed specimen. In about 10% of cases, formalin fixation can cause down-staging of pathologic T category as a result of tumor shrinking. Tumors invading the diaphragm have been reclassified as T4, and tumors extending within 2cms of the carina without its invasion, or tumors associated with collapse or consolidation of the whole lung have been down-staged to T2. Tis and T1mi were introduced for adenocarcinoma in situ, squamous cell carcinoma in situ and minimally invasive adenocarcinoma, respectively. Visceral pleural invasion, defined as the involvement of its elastic layer, remains unchanged as T2 category, but specific analysis of visceral pleural invasion, showed that there is two types of invasion: PL1 where tumor invades beyond the elastic layer and PL2 where tumor invades pleural surface and that these two had different prognosis, PL2 being associated with the worst outcome. Elastic stains are recommended to clarify the status of visceral pleural invasion for cases in which initial hematoxylin-and-eosin-stained slides failed to show presence of invasion. Mediastinal pleura invasion disappears as a T descriptor. N categories remained the same as in 7th edition. 8th did not bring guidelines about the minimum number of lymph nodes that should be assessed for pathohistological analysis. In M descriptor category M1a retained, while M1b has been reassigned to describe a form of limited disease with a single metastatic deposit in one distant organ. A new category of M1c has been proposed and it is reserved for situations in which there are multiple metastases in one or more distant sites. Assessment of multifocal lung tumors and the distinction of synchronous primary tumors from intrapulmonary metastases represent an important problem as this decision significantly influences tumor staging, as well as treatment approach. Four different clinical presentation of lung cancer with multifocal lung involvement are described: second primary cancer, intrapulmonary metastasis, multifocal lung adenocarcinoma with ground glass/lepidic features, and pneumonic-type lung adenocarcinoma. The tumors are considered second primary tumor if it have clearly a different histology or have a different radiographic appearance, metabolic uptake growth pattern or different biomarkers. Each tumor is staged separately based on current TNM staging system. The nodules are considered to be intrapulmonary metastasis if exact matching breakpoints are identified by genetic hybridization or have similar clinical features such as radiographic appearance, growth pattern or significant nodal and systemic SPECIAL SESSION: DEPARTMENT OF PATHOLOGY, MEDICAL FACULTY, UNIVERSITY NOVI SAD, SERBIA 32 MATERIA MEDICA • Vol. 34 • Issue 1, suplement 1 • april 2018. metastasis. TNM staging depends on location of the nodule relative to the primary tumor site. If it is in the same lobe, the tumor is designated as T3, if it is in the same lung, but in different lobe as T4, and it it is in the contralateral lung as M1a. Tumors are considered multifocal lung adenocarcinoma if there are multiple subsolid nodules with at least one suspected or proven to be a cancer. Ground glass nodule <5 mm or lesion suspected to be AAH is excluded. T stage is based on highest T lesion with indicating the multiplicity. Tumor is categorized as a pneumonic-type adenocarcinoma if there is a diffuse pneumonic infiltrate or consolidation with regional distribution. Stage IA is divided into IA1, IA2 and IA3 to accommodate T1a, T1b and T1cN0M0 tumors. All N1 disease is staged IIB except for T3-T4N1M0 tumors which are stage IIIA. A new stage IIIC is created for T3-T4N3M0 tumors and stage IV is divided into IVA (M1a and M1b) and IVB (M1c). In conclusion, multi-disciplinary approach and the close cooperation among medical and radiation oncologists, pulmonologists, surgeons, radiologists and pathologists is important in properly staging of lung cancer as well as, in treatment plans.

Aim: To investigate concordance rate between the results of expression of steroid receptors, human epidermal growth factor 2 receptors (Her2) and determined molecular subtypes in surgical specimens (SS) and samples obtained by core biopsy (CB). Introduction: CB is widely accepted method in the initial diagnosis of breast cancer, but its reliability in determining the status of steroid and Her2 receptors, Ki67 index and molecular subtypes is still a matter of debate. Material and Methods: We analyzed 54 cases of invasive breast cancer, in which the expression of estrogen (ER), progesterone (PR) and Her2 receptors and Ki67 index were determined both in CB and SS. Concordance rate for ER, PR and Her2 receptors expression and molecular subtypes, between CB and SS, was calculated using k-test (p<0.001). Results: The average age of patients was 62. In SS, Luminal A subtype was most commonly diagnosed (48%), followed by: Luminal B Her2-(31%) and TNBC (13%), while Luminal B Her2 and Her2-enriched subtypes were represented by 4% each. Frequencies of molecular subtypes in CB were: Luminal A (41%), LuminalB Her2- (33%), TNBC (15%), Luminal B Her2 (7%), Her2-enriched (4%). Concordance rate for ER receptors was 93.8%(Kappa=0.936), for PR 77.5%(Kappa=0.773), for Her2 80.0%(Kappa=0.78) and for molecular subtypes 80.9%(Kappa=0.753). Conclusion: Statistical analysis showed very good agreement in terms of determined molecular subtypes and ER receptors expression and good agreement for the expression of PR and Her2 receptors. CB represents reliable method for determining the status of expression of steroid and Her2 receptors, as well as tumor molecular subtypes.