Introduction: A pleural effusion describes an excess of fluid in the pleural cavity, usually resulting from an imbalance in the normal rate of pleural fluid production or absorption, or both. Pleural effusions are associated with a number of pathological medical conditions. In the vast majority of these cases the cellular response is quite nonspecific and will show varying proportions of mesothelial cells, macrophages, erythrocytes, lymphocytes, neutrophils and other leukocytes. Certain diseases may occasionally show cellular changes in the effusion that will reflect their presence. Examples of these include infections such as tuberculosis, blastomycosis, aspergillosis, viral infections, echinococcosis and cryptococcosis. Noninfectious, nonneoplastic diseases diagnosable by cytopathologic methods include rheumatoid arthritis, luAPSTRAKTI 89 MATERIA MEDICA • Vol. 34 • Issue 1, suplement 1 • april 2018. pus erythematosus, eosinophilic pleural effusion, pleural endometriois and sickle cell disease. In spite of these occasional specific cytopathologic diagnoses which can be rendered for the nonneoplastic diseases named above, the most significant role of cytopathology by far is in the examination of effusion fluid for the presence of cancer cells. Cytologic examination of pleural effusions is an important initial step in management of malignant effusions. Although most patients with a malignant effusion have a known history of cancer, a positive effusion may be the first sign of an unsuspected malignancy. Cytologic examination of a serous effusion may offer the possibility of an early and accurate diagnosis by using a minimal intervention. The presence of pleural effusions typically signals an advanced stage of disease so it is associated with poor prognosis. The accuracy of cytologic examinations of malignant pleural effusion is in high range (from 40% to 87%). Lung, breast, ovarian, and gastrointestinal cancers are most likely to cause malignant effusions. The histologic type of cancer most commonly seen in serous effusions is adenocarcinoma but a variety of other cancers can cause effusions. Less common malignancies are squamous cell carcinoma, small cell carcinoma (SCC), hematopoietic malignancies, melanoma, germ cell tumours and sarcomas. Mesotheliomas often present with recurrent serous effusions. One of the most important diagnostic doubts in pleural effusion analysis is distinguishing adenocarcinoma from mesothelioma and mesothelioma from benign mesothelial cells. In most cases the diagnose is based on regular cytomorphology analysis and immunocytochemistry is necessary in low percent of cases to establish the diagnose. The specimens are collecting by thoracentesis, processing in a routine fashion and staining by hematoxylin-eosin (H&E) and Papanicolaou stain after wet fixation with 95% ethanol and May-Grunwald-Giemsa stain after air drying. It is important to evaluate the same cells when constructing coordinate immunoreactivity pattern for various immunomarkers. Since the same cells cannot be followed on different cytology smears, they are not ideally suited for routine immunocytochemical evaluation of effusion fluids. Serial sections of cell-blocks show the same cells in adjacent levels which allow proper evaluation of the coordinate immunoreactivity pattern. Conclusion: Pleural fluid cytological analysis has important diagnostic role in most cases so primary aim should be to establish the correct diagnosis with minimal investigation. Cytology is the only method by which one may retrieve cells from fluid, often in the absence of solid lessions or when obtaining a biopsy from the latter is more difficult and costly and entails much greater discomfort or risk for the patient. Effusion cytology is important for: primary diagnosis of cancer, staging, diagnosis of recurrence or disease progression. Evaluation of effusion cytology is one of the most challenging areas in diagnostic cytopathology. A remarkably wide cytomorphological spectrum of reactive mesothelial cells overlaps with various benign and malignant processes. Due to these limitations, a significant proportion of effusion fluids are difficult to interpret with objective certainty by cytomorphology alone. The use of immunocytochemical panel of antibodies with combination of high sensitivity and specificy is the only way for precise distinguishing of adenocarcinomas from mesothelioma, especially in cases with scant tumor cells particularly in metastatic disease from well differentiated carcinoma, and reactive mesothelial cells from mesothelioma. Other stains are used to confirm pulmonary origin and should be selected as a complement to the panel once adenocarcinoma is confirmed. Molecular diagnostics are feasable on routine cytopreparations, primary diagnostics as well as molecular monitoring during targeted therapy.

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