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 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: 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.

Lung transplantation remains the definitive treatment for end-stage lung diseases and an option when
medical and surgical care has been exhausted. The first human single lung transplant was performed in
1963, and the patient, survived for 18 days. From 1963 to 1978, multiple attempts at lung transplantation
failed because of rejection and problems with anastomotic bronchial healing. It was only after the invention of the heart-lung machine, coupled with the development of immunosuppressive drugs, that organs
such as the lungs could be transplanted with a reasonable chance of patient recovery. The first clinically
successful long-term single lung transplant was performed in 1983, and since then over 25,000 lung transplants performed worldwide.