Aim: To determine prognosic significance of RAS oncogene mutation detection in patients with metastatic colorectal carcinoma (mCRC). Introduction: CRC is still third most common cancer of both genders and second cause of death from malignancy in Western countries. In recent years, detecting RAS mutation in mCRC tumor tissue has became an imperative in selecting patients for monoclonal antibodies targeted therapy to Epidermal Growth Factor Receptor (EGFR). Nevertheless, there is no consensus regarding prognostic relevance of determining RAS status in patients with mCRC. Material and methods: Study included 116 patients with surgicaly resected CRC at Oncology Insitute of Vojvodina between January and December 2016. KRAS mutation detection was performed in formalin-fixed paraffin embeded tumor tissue samples processed by real-time chain polymerase reaction (real-time PCR) and applyng Cobas® KRAS Mutation Test and Cobas® 4800 System for detection of mutations in codons 12/13 and 61 of KRAS gene. Results: Average age in tested population was 65 years, with a male gender predominance (66.4%). Presence of KRAS mutation was found in 50.9% patients: 44.8% in codons 12/13, 4.3% in codon 61 and 1.7% in both codons 12/13 and 61. RAS mutated colorectal carcinomas (n=59) compared with RAS wildtype colorectal cancers, were significantly associated with male gender, moderately differentiated tumors, lymphovascular invasion and local nodal metastases. Conclusion: Our results show that, beside predictive, KRAS can also have prognostic significance regarding risk assesment for lymphovascular invasion and presence of local and distant metastases.

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.

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: To examine the quality of tested lung carcinoma samples, frequency and type of EGFR mutations, and their correlation with patients clinical characteristics (gender, age, smoking habits, clinical stage). Introduction: Mutations in Epidermal Growth Factor Receptor (EGFR) have a role in lung carcinoma development and they are more prevalent in women and non-smokers. Evaluation of EGFR mutations in lung carcinomas in mandatory for targeted therapy with tyrosine kinase inhibitors. Test performance depends on the quality of tested samples and a test type. Material and Methods: We evaluated reports of EGFR mutation real-time PCR analyses in lung carcinoma samples performed from June 2017 till February 2018. Presence of mutations was correlated with clinical characteristics of lung carcinoma patients. Results: A total of 341 samples was received for testing, among which 40 (11.7%) was unsuitable for analysis due to a low tumor cell content (<5%). Three types of mutations were detected in a total of 24 (8%) cases: L858R in 12 (50%) cases, exon 19 deletion in 10 (41.7%) cases, and G719A/C/S in two cases (8.3%). Mutations were more prevalent in women (13.7%) then in men (4.3%) (p=0.004). Patients with EGFR mutated tumors were older (67,6ą9,4 years), compared to those with non-mutated tumors (62,3ą8,8 years) (p=0,003). Smoking habits and clinical stage were not associated with mutation status in lung carcinomas. Mutations were detected only in adenocarcinomas. Conclusion: Our results suggest the low frequency of EGFR mutations in tested patients, but they are more prevalent in women and older patients.

Aim: Immunohistochemistry findings along with clinical features, are significantly important in differentiating the Extrapleural SFT in the neck, from other well-circumscribed mesenchymal neoplasms at this locations. Introduction: We present a rare case of a Extrapleural SFT in a 57 years old man in the neck, without significant past medical history. Material and Methods: The patient had a painless slow growing tumor, in right sight of the neck, diagnosed with physical examination. Total excision with local anesthesia was done, without previously biopsy of the tumor and other clinical investigations. Standard procedures for histology and immunohistochemical stains were done. Results: Tumor was well circumscribed, encapsulated measuring 5,5x4x4 cm. On section, the cut surface had a multinodular, whitish and firm appearance. On microscopic examination tumor was composed of alternating hypocellular and hypercellular areas separated from each other by thick bands of collagen and branching haemangiopericitoma like vessels. The tumor cells were round to spindle-shaped with little cytoplasm, indistinct borders, dispersed chromatin within vesicular nuclei. Area of myxoid change and subcapsular focus of hemorrhage was present, and 2 mitoses/10 HPF were found. Immunohistochemistry revealed diffuse positivity for CD34, Vimentin and BCL2, focal positivity for CD99, S100, SMA, and negativity for CKWS and EMA. Ki67 showed low proliferating index 3-5%. Conclusion: Although most cases of SFT are benign, there is no strict correlation between morphology and behavior, so patients with extrapleural solitary fibrous tumor have need of long-term post-resection follow-up. Further studies are needed to determine the optimal management of these neoplasms.

The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), which attempts to standardize reporting and cytological criteria for fine-needle aspiration of thyroid nodules and was first introduced in 2009, has been updated. Although much of the original TBSRTC remains the same, several “enhancements” have been introduced in the 2017 version based on new data and developments in the field. The 2017 revision reaffirms that every thyroid FNA report should begin with one of six diagnostic categories, the names of which remain unchanged since they were first introduced: nondiagnostic or unsatisfactory; benign; atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS); follicular neoplasm or suspicious for a follicular neoplasm; suspicious for malignancy; and malignant. In the frst edition of TBSRTC, the implied risk of malignancy (MOP) for each diagnostic category was calculated and provided as a range based on a review of the literature at that time: 0–3% for benign, ~5–15% for atypia of undetermined signifcance (AUS) or follicular lesion of undetermined signifcance (FLUS), 15–30% for follicular neoplasm or suspicious for follicular neoplasm, 60–75% for suspicious for malignancy, and 97–99% for the malignant category. In the second edition, these ranges have been revised, especially for the so-called “indeterminate” categories, representing estimates calculated primarily from studies of large case cohorts and meta-analyses of ultrasound-guided thyroid FNA published after 2007. Notably, the new document reinterprets the previous version in one major way, and that is TBSRTC’s careful accommodation of the new noncancer category of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) tumors, which prior to April 2016 were categorized as thyroid cancer. NIFTP tumors have nuclear changes on cytologic evaluation that are identical to other forms of thyroid cancer, but on close long-term clinical follow-up they do not appear to recur or metastasize, and therefore, they do not behave clinically like thyroid cancer. NIFTP tumors typically fall into categories 3, 4, or 5, and can only be diagnosed as “not cancer” after a full surgical excision is performed and the entire tumor specimen is examined under a microscope. There have also been a number of other enhancements with the 2017 update: • The option of molecular testing in the standard management of AUS/FLUS and FN/SFN has been included. • The definition and diagnostic criteria for FN/SFN has been modified: cases demonstrating mild nuclear changes associated with papillary thyroid carcinoma are now included. The definition and diagnostic criteria for the papillary thyroid carcinoma subset of the malignant category now suggest limiting use to cases with “classical” features of papillary thyroid carcinoma. TBSRTC is now the most common classification worldwide for the reporting of thyroid FNA specimens. In view of this, ABSTRACTS 92 MATERIA MEDICA • Vol. 34 • Issue 1, suplement 1 • april 2018. new suggestions will be useful for various aspects of thyroid FNA including nomenclature, differential diagnosis, the potential impact of NIFTP on the indeterminate diagnostic categories, utility of molecular and IHC markers, and clinical management.

Pulmonary Langerhans cell histiocytosis (PLCH) is a rare disease of unknown etiology, which most commonly affects men, smokers, aged from 20 to 40. It is diagnosed by histological analysis of material obtained by lung biopsy, with immunohistochemical proving of Langerhans cells. The aim of this research is to determine pathohistological characteristics of PLCH and analyzing demographic, clinical and radiological parameters. Retrospective analysis of medical data for 13 patients, proven for PLCH at Institute for Pulmonary diseases of Vojvodina in period of fifteen years. PLCH was found at 9 (69.3%) women and at 4 (30.7%) men, average age 34.7 years. Main clinical symptoms were cough (76.9%) and chest pain (61.5%). Out of 13 patients, 11 (84.6%) were smokers. In most cases PLCH histologically corresponded to the cellular phase of the disease (46.1%), proliferative phase was present at 5 (38.4%), and the fibrotic phase at 2 (15.5%) patients. Immunohistochemically, Langerhans’ cells were positive for presence of CD1a and S-100 antigens in all 13 of analyzed cases, while CD68 antigen was positive in 6 patients. In 6 patients (46.2%) there was disease regression, and at 7 (53.8%) patients the disease progressed despite the applied therapy. In our research, PHLC was more common in younger females, smokers with cough and chest pain. At most of the patients, histologically disease was in the cellular phase. Langerhans cells were positive to presence of CD1a and S100 antigens in all 13 patients. At more than half of the patients the disease progresses despite the applied therapy.

Penile tumors are rare neoplasms of the male urogenital tract and represent approximately 1% of all urogenital cancers in men. Squamous cell carcinoma is the most common histological type of these tumors, and is seen in about 95% of the cases. We report a case of a 66 years old male patient presented with large, neglected cancer of the penis, which grew about 6 months, but patient was not motivated for treatment until tumor began to bleed. Patient was operated and tumor was completely removed. The early postoperative course was uneventful and the patient was discharged from hospital Since penile cancers are rare entity, there are counted controversy about the best method of treatment. We believe that the individual approach to each patient relying on existing good clinical practice guidelines is currently the best therapeutic approach.

Penile tumors are rare neoplasms of the male urogenital tract and represent approximately 1% of all urogenital cancers in men. Squamous cell carcinoma is the most common histological type of these tumors, and is seen in about 95% of the cases. We report a case of a 66 years old male patient presented with large, neglected cancer of the penis, which grew about 6 months, but patient was not motivated for treatment until tumor began to bleed. Patient was operated and tumor was completely removed. The early postoperative course was uneventful and the patient was discharged from hospital Since penile cancers are rare entity, there are counted controversy about the best method of treatment. We believe that the individual approach to each patient relying on existing good clinical practice guidelines is currently the best therapeutic approach.