This observational study was conducted to characterize those patients with lymphatic anomalies complicated by effusions, as well as factors that are associated with the occurrence of effusions and poor outcome. Furthermore, this research aimed to better describe the natural histories of patients presenting with effusions resulting from lymphatic disorders, including morbidity and mortality rates. Of a cohort of 230 registry patients, 145 registered patients suffering from lymphatic disorders who experienced at least one effusion during follow-up were eligible for inclusion in this study. Information was collected primarily from structured patient interviews, medical records, and interdisciplinary conference reviews and clinic visits at the Vascular Anomalies Center at Boston Children's Hospital. Among other characteristics, the age at presentation, the age at pulmonary presentation, concurrent symptoms and disease features were assessed. Of patients with effusions, 37% present with their first effusions within the first year of their lives. Of the deceased cohort of patients who presented with their first effusion in the first year of their lives, 66.67% also died within the first year of their lives. Overall mortality for those patients suffering from effusions was found to be 17% (25/145). Of the deceased cohort with a known cause of death, 53% died due to respiratory or pulmonary complications of effusions. The median number of years from effusion presentation until death was 2.04 years. These data collected implied effusions are a critical determinant of mortality in patients with disorders of the lymphatic system.

La progression naturelle des tumeurs consiste en une extension locale, puis à distance (métastase) par migration de cellules dans le sang et la lymphe vers des sites secondaires. Il est donc primordial de pouvoir détecter des cellules tumorales circulantes en plus de l’analyse morphologique et de l’immunocytochimie. De plus, deux technologies (cytométrie en flux et RT-PCR quantitative en temps réel) sont adaptées pour une analyse automatisée, rapide et sensible d’une très faible quantité de cellules. Le but de notre travail a été de mettre au point des systèmes de détection pour l’identification de cellules cancéreuses dans les épanchements péritonéaux et dans le sang. L’étude des biomarqueurs moléculaires apparaît comme une approche complémentaire intéressante pour améliorer l'efficacité du diagnostic dans ce type d'échantillons biologiques. Nous nous sommes intéressés à la mise en évidence de nouveaux marqueurs tumoraux qui pourront être utilisés pour le diagnostic précoce et le pronostic des cancers en utilisant les nouvelles techniques de biologie moléculaire. Il est probable que l'utilisation de multiples marqueurs moléculaires puisse permettre d’évoquer plus particulièrement certains types de cancers. Nous avons pu mettre en place une technique de PCR quantitative en temps réel, nettement plus sensible que la cytologie classique, et nous avons appliqué cette technique à l'étude de marqueurs tumoraux dans les liquides d’épanchement, mais aussi dans le sang pour rechercher et doser l’ARN messager. Nos résultats montrent que la cytométrie en flux adaptée à des lignées cellulaires ne l’est pas pour des prélèvements cliniques. Par la PCR quantitative, il a été possible de quantifier le niveau d’expression des marqueurs tumoraux étudiés en utilisant des plasmides de référence qui ont été préparés pour chaque gène. Plusieurs marqueurs permettent de différencier des épanchements malins et des épanchements bénins, mais surtout les antigènes CLDN4 et Ep-CAM étaient significativement plus élevés (68% et 57%, respectivement) chez les patients avec épanchements malins. L’ARN messager circulant de la CLDN4 était détectable et significativement plus élevée dans les sérums de patients atteints de cancer du sein (64% p<0,05). Les résultats indiquent que l'utilisation d'une combinaison de marqueurs comportant laclaudine 4 est plus susceptible de détecter des cellules malignes et d'être utiles pour le suivi de patients / The natural progression of tumors is a local extension, and remotely (metastasis) by migrating cells in the blood and the lymph to secondary sites. It is therefore essential to detect circulating tumor cells in addition to morphological analysis and immunocytochemistry. In addition, two technologies (flow cytometry and RT-PCR in real time) are suitable for a rapid and sensitive automated analysis of a very small quantity of cells. The aim of our work was to develop detection systems for identification of cancer cells in peritoneal effusions and blood. The study of molecular biomarkers appears as an attractive complementary approach to improve the efficiency of diagnosis in this type of biological samples. We are interested in the identification of new tumor markers that can be used for early diagnosis and prognosis of cancer using new techniques of molecular biology. It is likely that the use of multiple molecular markers can help to raise some specific types ofcancers. We were able to develop a quantitative PCR technique in real time, significantly more sensitive than conventional cytology, and we applied this technique to the study of tumor markers in effusions, but also in blood for detecting messenger RNA. Our results show that flow cytometry well-adapted to cell lines, is not unusable for clinical specimens. For quantitative PCR, it was possible to quantify the expression levels of tumor markers using reference plasmids prepared for each gene. Several markers can differentiate malignant and benign effusions, but especially CLDN4 and Ep-CAM antigens were significantly higher (68% and 57% respectively) in patients with malignant effusions.The circulating CLDN4 mRNA was detectable and significantly higher in the sera of patients with breast cancer (64% p <0.05). The results indicate that using a combination of markers including claudin 4 is more likely to detect malignant cells and be useful for monitoring patients

Thesis (MScEng)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: Pleural effusion is a common respiratory condition that is characterized by an abnormal collection of fluid in the lung cavity. In this study, an innovation using the transmission of sound into the respiratory system as a novel tool to detect fluid in the lung was developed. First, the method was evaluated on a phantom model of a lung. Based on the results of this test model, the appropriate technique was used in a clinical study. This method has several advantages, such as that is non-invasive, low cost, and easy for clinical review. Two techniques, including analysis of the frequency response of the model and the transient time of transmitted sound in the lung, were evaluated in the phantom models of the human lung. Two phantom models with similar geometry to the human lung, including a healthy model (without fluid in the model) and a pleural effusion model (with bulk of fluid in the model) were developed. These models have acoustical properties similar to the lung parenchyma. To obtain the frequency responses of the model, a sine sweep signal was transmitted into the model and the frequency response of the model was then calculated using the fast Fourier transform. The transient time of the transmitted sound was calculated using a cross correlation method. The results show that the locations of fluid in the model were detectable using both techniques. However, the transient time technique is better than the frequency response technique because it is simple, fast, and has potential for use in a clinical enviorment. Based on the results obtained from the phantoms, the transient time method was performed on both 22 healthy participants and four patients diagnosed with pleural effusion. To perform this technique on human subjects, a data acquisition system was developed. Two types of sound, including a complex chirp sound and a polyphonic sound, were transmitted into the respiratory systems of the participants. The time delay between a reference microphone, located on the trachea of the subject, and eight microphones attached to the chest was computed using a cross correlation method, and the effect of inhalation and lung size on the transient time of transmitted sound on the healthy subject was evaluated. The results show that using transmission of sound in the lung is a promising technique in the diagnosis of pleural effusion. / AFRIKAANSE OPSOMMING: Pleurale effusie is 'n algemene respiratoriese toestand wat gekenmerk word deur 'n abnormale versameling van vloeistof in die longholte. In hierdie studie is 'n innoverende manier ontwikkel om vloeistof in die long met behulp van die transmissie van klank te bespeur. Die metode is eers op 'n fantoommodel van 'n long geëvalueer. Op grond van die resultate van hierdie toetsmodel is die geskikte tegniek in 'n kliniese studie gebruik. Hierdie metode het verskeie voordele, soos dat dit ingreepsvry is, nie duur is nie en kliniese evaluering moontlik maak. Twee tegnieke, naamlik ontleding van die frekwensierespons van die model en die oorgangstyd van versende klank in die long, is in die fantoommodel van die menselong geëvalueer. Twee fantoommodelle met soortgelyke geometrie aan die menselong, met inbegrip van 'n gesonde model (sonder vloeistof in die model) en 'n pleurale-effusie-model (met 'n massa vloeistof in die model), is ontwikkel. Hierdie modelle het akoestiese eienskappe soortgelyk aan die longparenchiem. Om die frekwensieresponse van die model te verkry, is 'n sinuskrommesein tot in die model versend. Die frekwensierespons van die model is met behulp van die vinnige Fourier-transformasie bereken. Die oorgangstyd van die versende klank is deur 'n kruiskorrelasie-metode bereken. Die resultate toon dat die ligging van die vloeistof in die model met albei tegnieke bespeur kan word. Die oorgangstyd-tegniek is egter beter as die frekwensierespons-tegniek, aangesien dit eenvoudig en vinnig is en maklik in 'n kliniese omgewing gebruik kan word. Op grond van die resultate wat van die fantome verkry is, is die oorgangstyd-metode op 22 gesonde deelnemers en vier pasiënte wat met pleurale effusie gediagnoseer is, uitgevoer. 'n Dataverkrygingstelsel is ontwikkel ten einde hierdie tegniek op proefpersone uit te voer. Twee soorte klank, naamlik 'n komplekse tjirpgeluid en 'n polifoniese klank, is na die respiratoriese stelsels van die deelnemers versend. Die tydvertraging tussen 'n verwysingsmikrofoon in die tragea van die proefpersoon en agt mikrofone wat aan die bors vasgeheg is, is met 'n kruiskorrelasie-metode bereken, en die uitwerking van inaseming en longgrootte op die oorgangstyd van versende klank op die gesonde proefpersone is geëvalueer. Die resultate toon dat die gebruik van transmissie van klank in die long 'n belowende tegniek vir die diagnose van pleurale effusie is.

La progression naturelle des tumeurs consiste en une extension locale, puis à distance (métastase) par migration de cellules dans le sang et la lymphe vers des sites secondaires. Il est donc primordial de pouvoir détecter des cellules tumorales circulantes en plus de l'analyse morphologique et de l'immunocytochimie. De plus, deux technologies (cytométrie en flux et RT-PCR quantitative en temps réel) sont adaptées pour une analyse automatisée, rapide et sensible d'une très faible quantité de cellules. Le but de notre travail a été de mettre au point des systèmes de détection pour l'identification de cellules cancéreuses dans les épanchements péritonéaux et dans le sang. L'étude des biomarqueurs moléculaires apparaît comme une approche complémentaire intéressante pour améliorer l'efficacité du diagnostic dans ce type d'échantillons biologiques. Nous nous sommes intéressés à la mise en évidence de nouveaux marqueurs tumoraux qui pourront être utilisés pour le diagnostic précoce et le pronostic des cancers en utilisant les nouvelles techniques de biologie moléculaire. Il est probable que l'utilisation de multiples marqueurs moléculaires puisse permettre d'évoquer plus particulièrement certains types de cancers. Nous avons pu mettre en place une technique de PCR quantitative en temps réel, nettement plus sensible que la cytologie classique, et nous avons appliqué cette technique à l'étude de marqueurs tumoraux dans les liquides d'épanchement, mais aussi dans le sang pour rechercher et doser l'ARN messager. Nos résultats montrent que la cytométrie en flux adaptée à des lignées cellulaires ne l'est pas pour des prélèvements cliniques. Par la PCR quantitative, il a été possible de quantifier le niveau d'expression des marqueurs tumoraux étudiés en utilisant des plasmides de référence qui ont été préparés pour chaque gène. Plusieurs marqueurs permettent de différencier des épanchements malins et des épanchements bénins, mais surtout les antigènes CLDN4 et Ep-CAM étaient significativement plus élevés (68% et 57%, respectivement) chez les patients avec épanchements malins. L'ARN messager circulant de la CLDN4 était détectable et significativement plus élevée dans les sérums de patients atteints de cancer du sein (64% p<0,05). Les résultats indiquent que l'utilisation d'une combinaison de marqueurs comportant laclaudine 4 est plus susceptible de détecter des cellules malignes et d'être utiles pour le suivi de patients

BACKGROUND: Malignant and paramalignant pleural effusions are important complications of many malignancies. The two main management options debated in the literature are: 1) insertion of an indwelling pleural catheter (IPC) to achieve chronic drainage of the effusion, or 2) hospitalization with tube thoracostomy and subsequent chemical pleurodesis (CP) with talc or doxycycline to prevent fluid reaccumulation. We aimed to describe a large series of patients with malignant pleural effusions managed with an IPC, identify and validate factors identified in the literature as predictors of spontaneous pleurodesis in the IPC group and compare the group managed with IPC to patients managed with CP. METHODS: We designed a retrospective cohort study comparing patients with malignant and paramalignant pleural effusions managed either with CP between March 1, 2003 and February 28, 2006 or IPC insertion between May 1, 2006 and April 1, 2009. The CP group was identified through the prescription of talc or doxycycline and the IPC group from the IPC clinic database. Data were collected from paper and electronic records and from the Government of Ontario. RESULTS: We identified 193 consecutive patients with an ECOG performance status of less than 4 (ECOG less than 4 means that the patient is not completely disabled and confined to bed or chair) having undergone IPC insertion and 168 who were managed with CP. None of the variables we tested were significant predictors of spontaneous pleurodesis in the IPC group. Pleural effusion control rates at 6 months were higher in the IPC group than in the CP group (52.7% vs 34.0%, p<0.01) but the rate of freedom from pleural effusion at 180 days and catheter removal at 90 days was not significantly different (25.8% in the IPC group and 34.0% in the CP group p=0.14). Patients in the IPC group had a significantly longer median survival (148 days measured from the date of catheter insertion vs 133 days in the CP group, log-rank p<0.05). CONCLUSION: We found an intriguing possible survival benefit favouring management of malignant or paramalignant effusions with an IPC. Given possible biases due to the design of this study and uncertain explanatory mechanism, this needs to be confirmed in a randomized controlled trial. Quality of life, an important measure of success for these palliative procedures, should also be measured.

BACKGROUND: Malignant and paramalignant pleural effusions are important complications of many malignancies. The two main management options debated in the literature are: 1) insertion of an indwelling pleural catheter (IPC) to achieve chronic drainage of the effusion, or 2) hospitalization with tube thoracostomy and subsequent chemical pleurodesis (CP) with talc or doxycycline to prevent fluid reaccumulation. We aimed to describe a large series of patients with malignant pleural effusions managed with an IPC, identify and validate factors identified in the literature as predictors of spontaneous pleurodesis in the IPC group and compare the group managed with IPC to patients managed with CP. METHODS: We designed a retrospective cohort study comparing patients with malignant and paramalignant pleural effusions managed either with CP between March 1, 2003 and February 28, 2006 or IPC insertion between May 1, 2006 and April 1, 2009. The CP group was identified through the prescription of talc or doxycycline and the IPC group from the IPC clinic database. Data were collected from paper and electronic records and from the Government of Ontario. RESULTS: We identified 193 consecutive patients with an ECOG performance status of less than 4 (ECOG less than 4 means that the patient is not completely disabled and confined to bed or chair) having undergone IPC insertion and 168 who were managed with CP. None of the variables we tested were significant predictors of spontaneous pleurodesis in the IPC group. Pleural effusion control rates at 6 months were higher in the IPC group than in the CP group (52.7% vs 34.0%, p<0.01) but the rate of freedom from pleural effusion at 180 days and catheter removal at 90 days was not significantly different (25.8% in the IPC group and 34.0% in the CP group p=0.14). Patients in the IPC group had a significantly longer median survival (148 days measured from the date of catheter insertion vs 133 days in the CP group, log-rank p<0.05). CONCLUSION: We found an intriguing possible survival benefit favouring management of malignant or paramalignant effusions with an IPC. Given possible biases due to the design of this study and uncertain explanatory mechanism, this needs to be confirmed in a randomized controlled trial. Quality of life, an important measure of success for these palliative procedures, should also be measured.

BACKGROUND: Malignant and paramalignant pleural effusions are important complications of many malignancies. The two main management options debated in the literature are: 1) insertion of an indwelling pleural catheter (IPC) to achieve chronic drainage of the effusion, or 2) hospitalization with tube thoracostomy and subsequent chemical pleurodesis (CP) with talc or doxycycline to prevent fluid reaccumulation. We aimed to describe a large series of patients with malignant pleural effusions managed with an IPC, identify and validate factors identified in the literature as predictors of spontaneous pleurodesis in the IPC group and compare the group managed with IPC to patients managed with CP. METHODS: We designed a retrospective cohort study comparing patients with malignant and paramalignant pleural effusions managed either with CP between March 1, 2003 and February 28, 2006 or IPC insertion between May 1, 2006 and April 1, 2009. The CP group was identified through the prescription of talc or doxycycline and the IPC group from the IPC clinic database. Data were collected from paper and electronic records and from the Government of Ontario. RESULTS: We identified 193 consecutive patients with an ECOG performance status of less than 4 (ECOG less than 4 means that the patient is not completely disabled and confined to bed or chair) having undergone IPC insertion and 168 who were managed with CP. None of the variables we tested were significant predictors of spontaneous pleurodesis in the IPC group. Pleural effusion control rates at 6 months were higher in the IPC group than in the CP group (52.7% vs 34.0%, p<0.01) but the rate of freedom from pleural effusion at 180 days and catheter removal at 90 days was not significantly different (25.8% in the IPC group and 34.0% in the CP group p=0.14). Patients in the IPC group had a significantly longer median survival (148 days measured from the date of catheter insertion vs 133 days in the CP group, log-rank p<0.05). CONCLUSION: We found an intriguing possible survival benefit favouring management of malignant or paramalignant effusions with an IPC. Given possible biases due to the design of this study and uncertain explanatory mechanism, this needs to be confirmed in a randomized controlled trial. Quality of life, an important measure of success for these palliative procedures, should also be measured.

Tez (Tıpta Uzmanlık) - Süleyman Demirel Üniversitesi, Tıp Fakültesi, Göğüs Hastalıkları Anabilim Dalı, 2006. / Bibliyografya var.

Orientador: Aureo Evangelista Santana / Banca: Antonio Carlos Alessi / Banca: Elisabeth Criscuolo Urbinati / Banca: Raimundo Souza Lopes / Banca: Fernanda Gomes Velasque Gama / Resumo: A avaliação laboratorial de uma efusão é relevante para que, em conjunto com os sinais clínicos apresentados pelo paciente, possa ser firmado um possível diagnóstico e instituída ação terapêutica adequada. Assim sendo, a classificação de uma efusão em transudato ou exsudato torna-se um dos pontos críticos para a elucidação do diagnóstico e condução do caso clínico. Em medicina veterinária o método tradicional de classificação de uma efusão é baseado na contagem celular e na concentração de proteínas do fluido, contudo, diversos estudos evidenciam que tais parâmetros não são suficientes para a correta classificação de todas as efusões. Desta forma, o presente estudo foi conduzido com o objetivo de verificar a correlação de outros parâmetros bioquímicos com a diferenciação das efusões transudativas e exsudativas e para tal foram avaliadas as atividades de lactato desidrogenase (LDH) e fosfatase alcalina (FA), bem como a relação de suas atividades fluido/soro, a concentração de lactato, colesterol, proteínas e os gradientes de concentração soro/fluido destas mesmas substâncias e de albumina. Os resultados obtidos permitiram observar e concluir que, dentre os parâmetros avaliados não houve nenhum que apresentasse 100% de sensibilidade e especificidade, contudo, a atividade de LDH, a relação LDH fluido/soro, a concentração de lactato e o gradiente de concentração de lactato soro/fluido apresentam diferença estatisticamente significativa (p<0,05), alta correlação com a classificação de uma efusão exsudativa e transudativa. Assim sendo, estes parâmetros se mostraram mais eficazes na classificação de uma efusão quando comparado com a concentração total de proteínas do fluido / Abstract: The laboratorial evaluation of this fluid becomes relevant, jointly with clinical signs presented by patient; to become possible the diagnosis definition and institution of appropriate therapeutic. Thus, classification of effusion in exudate and transudate is one of major points to elucidation of diagnosis and conduction of clinical case. In veterinary medicine the traditional method of an effusion classification is based on cellular counting and protein concentration of the fluid, however, several studies evidence that such parameters are not enough for the correct classification of all kinds of effusions. Considering this, the present study aimed to verify the correlation of some biochemical parameters with the differentiation of transudatives and exudatives effusions. To perform this, the activities of lactate dehydrogenase (LDH) and alkaline phosphatase (FA) were appraised, as well as the relationship of their activities with fluid/serum; lactate, cholesterol and proteins concentration and fluid/serum gradients of concentration of these same substances and albumin. The results allowed to observe that, among the appraised parameters, the activity of LDH, relationship LDH and fluid/serum, lactate concentration and lactate serum/fluid gradient of concentration present statistically significant difference (p<0,05), as well as a high correlation with the classification of an exudative and transudative effusion. Therefore, these parameters were shown to be more effective in the classification of an effusion when compared with total proteins concentration in the fluid / Doutor

As efusões cavitárias são de ocorrência frequente na rotina clínica de cães. Na maior parte dos casos são efusões benignas, causadas por distúrbios hidrostáticos do sistema circulatório. As neoplasias são causas comuns de efusões em cães, contudo, nem sempre as células tumorais são encontradas no exame citopatológico. A dosagem de marcadores tumorais e o exame imunocitoquímico são alternativas para tornar o diagnóstico de neoplasia em efusões mais preciso. Os objetivos deste trabalho foram dosar os seguintes marcadores tumorais bioquímicos: antígeno carcinoembrionário (CEA), antígeno associado a câncer 72-4 (CA 72-4) e fragmento de citoqueratina 21-1 (CYFRA 21-1), que ainda não tiveram seu desempenho avaliado em efusões neoplásicas e não neoplásicas caninas, bem como marcadores imunocitoquímicos que incluem dois novos anticorpos primários (MOC-31 e D2-40) para a diferenciação entre carcinoma e mesotelioma. Trinta e duas amostras de líquidos cavitários abdominais e torácicos, provenientes do atendimento clínico do Hospital de Clínicas Veterinárias da Universidade Federal do Rio Grande do Sul foram analisadas. De acordo com o exame citopatológico e ficha clínica do animal essas efusões foram classificadas em dois grupos: neoplásico e não neoplásico. A dosagem dos marcadores tumorais foi realizada pelo método imunoenzimático sanduíche (ELISA), conforme as instruções dos fabricantes. Para a avaliação imunocitoquímica foram utilizadas 14 amostras de efusões neoplásicas. A técnica foi realizada pelo método estreptavidina-biotina ligada a peroxidase ou a fosfatase alcalina, utilizando-se como cromógeno o DAB. Os marcadores tumorais CEA e CA 72-4 não tiveram resultados significativos na diferenciação entre efusões neoplásicas e não neoplásicas, enquanto que o CYFRA 21-1 obteve sensibilidade de 70%, especificidade de 94% e acurácia de 81% para o diagnóstico neoplásico. Em todas as amostras neoplásicas, imunocitoquímica e citopatologia foram compatíveis, verificando-se como válida a padronização dos novos anticorpos para a espécie canina. Este estudo demonstrou que novos marcadores tumorais, tanto bioquímicos como imunocitoquímicos, podem ser empregados no diagnóstico de neoplasias caninas. O marcador tumoral CYFRA 21-1 deve ser utilizado como auxílio diagnóstico para a espécie canina e os anticorpos MOC-31 e D2-40 devem ser incluídos em painéis imunocitoquímicos de rotina para a diferenciação entre carcinomas e mesoteliomas em efusões neoplásicas. / The cavity effusions frequently occur in the clinical routine of dogs. In most cases the effusions are benign caused by circulatory system disorders. Neoplasms are common causes of effusions in dogs, however not always the tumor cells are found in cytopathologycal analysis. The dosage of tumor markers is an alternative to make the neoplastic effusion diagnosis more accurate. The aims of this work were to determine the following biochemical tumor markers: carcinoembryonic antigen (CEA), cancer antigen 72-4 (CA 72-4) and cytokeratin fragment 21-1 (CYFRA 21-1), which have not had their performance evaluated in canine neoplastic and non-neoplastic effusions, as well as immunocytochemical markers including two new primary antibodies (MOC-31 and D2-40) for differentiation between carcinoma and mesothelioma tumors. Thrirtytwo samples of abdominal and thoracic cavity fluids, from the clinical care of the Veterinary Hospital of the Federal University of Rio Grande do Sul were analyzed. According to the cytopathology test and patient’s clinical record the effusions were classified in two groups: neoplastic or non-neoplastic. The tumor markers measurement was performed by sandwich enzyme immunoassay (ELISA) according to the manufacturer instructions. Fourteen neoplastic samples were used for the immunocytochemical tests. The tests were performed by streptavidin-biotin method linked to peroxidase or to alkaline phosphatase using the DAB chromogen. The tumor markers CEA and CA 72-4 had no significant results for differentiating between neoplastic and non neoplastic effusions, whereas the tumor marker CYFRA 21-1 obtained 70% of sensibility, 94% of specificity and 81% of accuracy for the neoplastic diagnosis. In all neoplastic samples the immunocytochemical and cytological tests were compatible, which make valid their use for standardization of those new antibodies for the canine species. This study demonstrated that new tumor markers both biochemical and immunocytochemical could be used in the canine neoplastic diagnosis. The tumor marker CYFRA 21-1 must be used for the canine species, and the antibodies MOC-31 and D2-40 must be included in routine immunocytochemistry panel for the differenciation between carcinoma and mesothelioma in neoplastic effusions.