Usefulness of thoracic ultrasound in the assessment of removal of indwelling pleural catheter in patients with malignant pleural effusion.

INTRODUCTION: There are no defined criteria for deciding to remove a non-functioning indwelling pleural catheter (IPC) when lung re-expansion on chest X-ray is incomplete. Chest computed tomography (chest CT) is usually used. The objective of this work is to validate the usefulness of chest ultrasound performed by a pulmonologist and by a radiologist compared to chest CT. PATIENTS AND METHODS: Prospective, descriptive, multidisciplinary and multicenter study including patients with malignant pleural effusion and non-functioning IPC without lung reexpansion. Decisions made on the basis of chest ultrasound performed by a pulmonologist, and performed by a radiologist, were compared with chest CT as the gold standard. RESULTS: 18 patients were analyzed, all of them underwent ultrasound by a pulmonologist and chest CT and in 11 of them also ultrasound by a radiologist. The ultrasound performed by the pulmonologist presents a sensitivity of 60%, specificity of 100%, PPV 100% and NPV 66% in the decision of the correct removal of the IPC. The concordance of both ultrasounds (pulmonologist and radiologist) was 100%, with a kappa index of 1. The 4 discordant cases were those in which the IPC was not located on the ultrasound. CONCLUSIONS: Thoracic ultrasound performed by an expert pulmonologist is a valid and simple tool to determine spontaneous pleurodesis and remove a non-functioning IPC, which would make it possible to avoid chest CT in those cases in which lung reexpansion is observed with ultrasonography.

Cytological Assessment of Desmoplastic Malignant Pleural Mesothelioma in an Autopsy Case.

INTRODUCTION: Desmoplastic malignant pleural mesothelioma (DMPM) is a sarcoma-type mesothelioma, comprising approximately 5% of malignant pleural mesotheliomas. Although effusion cytology is commonly used as the primary diagnostic approach for mesothelioma, it may not be useful for DMPM because of the presence of desmoplasia and bland cellular atypia. We report a case, and previously undescribed cytological features, of DMPM that was diagnosed during autopsy. CASE PRESENTATION: A man in his 60s with a history of occupational asbestos exposure was referred to our hospital with right chest pain. A chest CT scan showed right pleural effusion. Thirteen months later, the patient died of respiratory failure. During autopsy, scrape-imprint smears were prepared and cytology of pleural effusions was performed. The scrape-imprint smear samples showed spindle cells with mild nuclear atypia and grooves with fibrous stroma. Pleural effusion cytology revealed spindle cells with mild nuclear atypia, as well as grooves with loose epithelial connections. Histological examination of the right pleura showed spindle cells proliferating with dense collagen fibers, as seen in the cytological samples, thus indicating a diagnosis of DMPM, which was confirmed by fluorescence in situ hybridization. CONCLUSION: Cytological procedures such as pleural effusion cytology and scrape-imprinting cytology may help in diagnosing rare tumors such as DMPM.

Management of Malignant Pleural Effusions-What Is New.

Malignant pleural effusion (MPE) is a common and challenging problem. Patients affected by MPE have a poor prognosis and suffer from breathlessness and impaired quality of life. The management of MPE has barely changed for many decades; however, recent research has driven new paradigms in the diagnosis and treatment of MPE and stimulated novel concepts that are being evaluated in many ongoing studies. This review provides an overview of recent advances in the diagnosis of MPE, including new cytopathology and imaging techniques, and the landmark studies that provide a solid evidence base to support the use of indwelling pleural catheters as first-line treatment in MPE. Lingering management dilemmas, including optimal chest drainage tube and role of surgery in MPE, and key knowledge gaps that are the focus of ongoing research are also highlighted.

Malignant Mesothelioma, BAP1 Immunohistochemistry, and VEGFA: Does BAP1 Have Potential for Early Diagnosis and Assessment of Prognosis?

Malignant mesothelioma (MM) is an aggressive malignancy of the serosal membranes. Early diagnosis and accurate prognostication remain problematic. BAP1 is a tumour suppressor gene commonly mutated in MM. Germline BAP1 mutation has been associated with early onset and less aggressive disease compared with sporadic MM. Sporadic BAP1 mutations are common and are associated with improved survival in MM, contrary to other malignancies. This study investigated the prognostic role of BAP1 in matched cytology and surgical specimens and aimed to investigate the association between BAP1 and the established prognostic marker VEGFA from a cohort of 81 patients. BAP1 mutation was found in 58% of histology and 59% of cytology specimens. Loss of BAP1 expression in both surgical and cytology specimens was significantly associated with poorer survival in a multivariate analysis when controlling for known prognostic indicators. Increased levels of VEGFA in pleural effusions were associated with poor survival. We conclude that the prognostic significance of BAP1 mutations in MM cannot be determined in isolation of other prognostic factors, which may vary between patients. Pathologists should employ caution when commenting on prognostic implications of BAP1 status of MM patients in diagnostic pathology reports, but it may be useful for early diagnosis.

Assessment of real-time PCR method for detection of EGFR mutation using both supernatant and cell pellet of malignant pleural effusion samples from non-small-cell lung cancer patients.

BACKGROUND: EGFR mutation is an emerging biomarker for treatment selection in non-small-cell lung cancer (NSCLC) patients. However, optimal mutation detection is hindered by complications associated with the biopsy procedure, tumor heterogeneity and limited sensitivity of test methodology. In this study, we evaluated the diagnostic utility of real-time PCR using malignant pleural effusion samples. METHODS: A total of 77 pleural fluid samples from 77 NSCLC patients were tested using the cobas EGFR mutation test (Roche Molecular Systems). Pleural fluid was centrifuged, and separated cell pellets and supernatants were tested in parallel. Results were compared with Sanger sequencing and/or peptide nucleic acid (PNA)-mediated PCR clamping of matched tumor tissue or pleural fluid samples. RESULTS: All samples showed valid real-time PCR results in one or more DNA samples extracted from cell pellets and supernatants. Compared with other molecular methods, the sensitivity of real-time PCR method was 100%. Concordance rate of real-time PCR and Sanger sequencing plus PNA-mediated PCR clamping was 98.7%. CONCLUSIONS: We have confirmed that real-time PCR using pleural fluid had a high concordance rate compared to conventional methods, with no failed samples. Our data demonstrated that the parallel real-time PCR testing using supernatant and cell pellet could offer reliable and robust surrogate strategy when tissue is not available.

Management of malignant pleural mesothelioma - part 1: epidemiology, diagnosis, and staging : Consensus of the Austrian Mesothelioma Interest Group (AMIG).

Malignant pleural mesothelioma is a rare malignant disease that in the majority of cases is associated with asbestos exposure. The incidence in Europe is about 20 per million inhabitants and it is increasing worldwide. Initial symptoms are shortness of breath, pleural effusion, cough, and chest pain. The typical growth pattern is along the pleural surface; however, infiltration of the lung and/or mediastinal and chest wall structures can occur in a more advanced stage. Ultimately, distant metastases outside the chest can result. Several histological subtypes of pleural mesothelioma exist, which must be differentiated from either benign diseases or metastases in the pleural space by other tumor entities. This differential diagnosis can be very difficult and a large panel of immunohistochemical markers is required to establish the exact diagnosis. The standard procedure for confirming the disease and obtaining sufficient tissue for the diagnosis is videothoracoscopy. Full thickness biopsies are required, while transthoracic needle puncture of pleural fluid or tissue is considered to be insufficient for a cytological diagnosis. Complete and detailed staging is mandatory for categorization of the disease as well as for therapeutic decision making.

A fine decision tree consisted of CK5/6, IMP3 and TTF1 for cytological diagnosis among reactive mesothelial cells, metastatic adenocarcinoma of lung and non-lung origin in pleural effusion.

The utility of combination with CK5/6, IMP3 and TTF1 to differentiate among reactive mesothelial cells (RMs), metastatic adenocarcinoma of lung (LAC) and non-lung (NLAC) origin was investigated by using immunocytochemistry (ICC) and conventional PCR (C-PCR) in pleural effusion. A total of 108 cell blocks (32 RMs, 51 LAC and 25 NLAC were evaluated by ICC for CK5/6, IMP3 and TTF1 protein expression. In addition, we further performed C-PCR for amplification of CK5/6, IMP3 and TTF1 DNA from 28 specimens (9 MAC and 7 RMs, 6 LAC and 6 NLAC) for molecular diagnosis. CK5/6 staining was observed in the majority of reactive specimens (78.1%) and was rare in adenocarcinoma cells (14.5%), whereas the opposite was true for IMP3 and TTF1. We found a high frequency of TTF1 positivity (76.5%) in LAC, but not in NLAC (4.0%); while there was no significant difference of IMP3 expression in LAC (88.2%) and NLAC (88.0%). The 487 bp DNA fragments of IMP3 was expected to be amplified in 6/9 of adenocarcinoma cases showed negative in ICC; and the 394 bp DNA fragments of CK5/6 was also expected to be amplified in 4/7 of RMs cases showed negative in ICC. Consistent with ICC results, there was significant difference of TTF1 expression in the LAC and NLAC compared with IMP3 expression. The combination with CK5/6, IMP3 and TTF1 immunostaining appears to be useful to improve the accuracy of cytological diagnoses between RMs, metastatic adenocarcinoma of lung and non-lung origin in pleural effusion. In addition, C-PCR may act as a useful supplemental approach for ICC, especially negative cases in ICC for differential cytological diagnosis.

Low cost-effectiveness of CD3/CD20 immunostains for initial triage of lymphoid-rich effusions: an evidence-based review of the utility of these stains in selecting cases for full hematopathologic workup.

CD3/CD20 immunostains are often performed in the initial cytological evaluation of lymphoid-rich pleural effusions (LR-PE). Most benign LR-PE are predominantly composed of T(CD3+) cells while most malignant LR-PE are of B(CD20+) cell lineage. As part of the effort to contain laboratory costs and improve diagnostic accuracy, there is increasing interest in applying principles of evidence-based pathology to the use of immunostains. In this retrospective study, we reviewed the effectiveness of CD3/CD20 immunostains as a diagnostic or triage tool during the initial evaluation of 258 consecutive LR-PE. 196 (76%) of the LR-PE were ultimately diagnosed as reactive lymphocytosis and 62 (24%) as lymphoma/leukemia (L/L). There was a previous diagnosis of L/L, concurrent diagnostic tissue, and/or clinical evidence of L/L in 44 (71%) of the L/L effusions. An initial diagnosis of L/L was made in the remaining 18 (29%) cases. Sixteen of these 18 cases showed large cells with high-grade features that mandated L/L workup. In only 2 (0.8%) of the 258 LR-PE, CD3/CD20 stains were helpful to identify small cell lymphocytic lymphoma (SLL) in patients without concurrent peripheral lymphocytosis. CD3/CD20 immunostains do not appear to provide a cost-effective method to diagnose or triage the vast majority of LR-PE submitted to a clinical cytology laboratory. An algorithm that considers history, blood counts, and cytomorphology allows for cost-effective selection of LR-PE that warrant comprehensive hematopathologic workup. Our findings underscore the feasibility of applying evidence-based principles to develop guidelines for the cost-effective utilization of immunostains in cytology.

[Pleural puncture biopsy in the aetiological diagnosis of pleurisy]. / Ponction biopsie pleurale dans le diagnostic étiologique des pleurésies.

INTRODUCTION: Pleurisy represents a worrying situation because of the difficulty of aetiological diagnosis. The aim of this study was to evaluate the contribution of pleural puncture biopsy (PPB) in the diagnosis of pleurisy. METHODS: A prospective study of the contribution of the pleural puncture biopsy in the pulmonary service of Bamako (Mali) from 2005 to 2009. PPB was used in the investigation of exudative, non-purulent pleurisy of unknown aetiology. Castelin biopsy forceps were used. RESULTS: Pleurisy was the reason for 20% of the total admissions of 6374 patients. The PPB was performed in 390 patients or 30.6% of the cases of pleurisy. The HIV test was performed in 341 patients (87.4%), of whom 72 cases (21.1%) were positive. The pleural biopsies were: lymphocytic (68.7%), mixed cellular (17.1%). Histological interpretation was possible in 367 biopsy specimens, a yield of 94.1%. Tuberculous granulomata were found in 65.1% with a close relationship to HIV status (P<0.004). Pleural cancer was found in 16.1%. CONCLUSION: The PPB is easy to perform at a low cost. It permits the diagnosis of tuberculous and neoplastic pleurisy, particularly in low income countries with a high prevalence of TB/HIV.

Impact of dual-time-point F-18 FDG PET/CT in the assessment of pleural effusion in patients with non-small-cell lung cancer.

AIM: The aim of this study was to assess the utility of dual-time-point F-18 fluorodeoxyglucose positron emission tomography (F-18 FDG PET) in differentiating benign from malignant pleural disease, in patients with non-small-cell lung cancer. METHODS: A total of 61 patients with non-small-cell lung cancer and pleural effusion were included in this retrospective study. All patients had whole-body FDG PET/CT imaging at 60 ± 10 minutes post-FDG injection, whereas 31 patients had second-time delayed imaging repeated at 90 ± 10 minutes for the chest. Maximum standardized uptake values (SUV(max)) and the average percent change in SUV(max) (%SUV) between time point 1 and time point 2 were calculated. Malignancy was defined using the following criteria: (1) visual assessment using 3-points grading scale; (2) SUV(max) ≥2.4; (3) %SUV ≥ +9; and (4) SUV(max) ≥2.4 and/or %SUV ≥ +9. Analysis of variance test and receiver operating characteristic analysis were used in statistical analysis. P < 0.05 was considered significant. RESULTS: Follow-up revealed 29 patient with malignant pleural disease and 31 patients with benign pleural effusion. The average SUV(max) in malignant effusions was 6.5 ± 4 versus 2.2 ± 0.9 in benign effusions (P < 0.0001). The average %SUV in malignant effusions was +13 ± 10 versus -8 ± 11 in benign effusions (P < 0.0004). Sensitivity, specificity, and accuracy for the 5 criteria were as follows: (1) 86%, 72%, and 79%; (2) 93%, 72%, and 82%; (3) 67%, 94%, and 81%; (4) 100%, 94%, and 97%. CONCLUSIONS: Dual-time-point F-18 FDG PET can improve the diagnostic accuracy in differentiating benign from malignant pleural disease, with high sensitivity and good specificity.

Thoracoscopic assessment of pleural tumor burden in patients with malignant pleural effusion: prognostic and therapeutic implications.

BACKGROUND: Malignant pleural effusion (MPE) is encountered at an advanced stage of disease progression and often heralds a poor prognosis. The most reliable predictive factor of survival in such patients is the primary tumor. Thoracoscopy is often performed for accurate diagnosis and/or thoracoscopic talc insufflation as a therapeutic modality. It remains unknown whether pleural tumor burden, as visualized on thoracoscopy, has potential prognostic value. The objective of this study was to determine the prognostic accuracy of pleural tumor extent and localization (parietal, visceral, or diaphragmatic involvement), as assessed during medical thoracoscopy. METHODS: Medical records of all patients who underwent thoracoscopy for suspicion of MPE between 2001 and 2008 at a tertiary care referral hospital were reviewed. Patients were included if pleural metastatic invasion was confirmed on tissue biopsy and survival status ascertained. RESULTS: Four hundred twenty-one patients underwent diagnostic or therapeutic medical thoracoscopy at our referral center. Among them, 122 had confirmed metastatic pleural spread, but survival data were lacking in 15. Primary tumor consisted of non-mall cell lung cancer in 56, breast cancer in 23, melanoma in eight, and other malignancies in 20. Median survival of the entire population was 9.4 months. On univariate analysis, the following variables were significantly associated with reduced median overall survival: pleural metastatic melanoma, age less than 60 years, bloody MPE, extensive pleural adhesions, and widespread visceral pleural nodules (p < 0.05). On multivariate analysis, only melanoma as a primary tumor, pleural fluid appearance and extent of pleural adhesions remained independent and significant predictors of survival. CONCLUSION: No significant association was found between the extent or localization of pleural tumor burden and overall survival.

A decision tree for differentiating tuberculous from malignant pleural effusions.

OBJECTIVE: To improve physicians' ability to discriminate tuberculous from malignant pleural effusions through a simple clinical algorithm that avoids pleural biopsy. DESIGN: We retrospectively compared the clinical and pleural fluid features of 238 adults with pleural effusion who satisfied diagnostic criteria for tuberculosis (n=64) or malignancy (n=174) at one academic center (derivation cohort). Then, we built a decision tree model to predict tuberculosis using the C4.5 algorithm. The model was validated with an independent sample set from another center that included 74 tuberculous and 293 malignant effusions (validation cohort). RESULTS: Among 12 potential predictor variables, the classification tree analysis selected four discriminant parameters (age>35 years, pleural fluid adenosine deaminase>38U/L, temperature>or=37.8 degrees C, and pleural fluid LDH>320U/L) from the derivation cohort. The generated flowchart had 92.2% sensitivity, 98.3% specificity, and an area under the ROC curve of 0.976 for diagnosing tuberculosis. The corresponding operating characteristics for the validation cohort were 85.1%, 96.9% and 0.958. CONCLUSIONS: Applying a decision tree analysis that contains simple clinical and laboratory data can help in the differential diagnosis of tuberculous and malignant pleural effusions.

Assessment of RT-PCR detection of human mammaglobin for the diagnosis of breast cancer derived pleural effusions.

The present study investigates the diagnostic significance of human mammaglobin (hMAM) mRNA expression in pleural effusions (PE) from breast cancer (BC) patients. Two hundred and fifty PE samples, including 32 from patients who had diagnosis of BC, 116 from patients with other cancers, and 102 from patients with benign diseases, were subjected to nested reverse-transcription polymerase chain reaction (RT-PCR) for hMAM, and the results were compared with conventional cytology. hMAM was found expressed in 76/250 (30.4%) total PE and in 23/28 (sensitivity of 82.1%) of the PE subgroup owing to metastasis from BC. The specificity for hMAM detection method was 75.7%, whereas accuracy, positive predictive value, and negative predictive value were 76.4%, 30.3%, and 97.1%, respectively. hMAM was also detected in 46/116 (39.6%) PE specimens from other types of cancer and in 7/102 (6.8%) from benign diseases. Comparative analysis of RT-PCR and cytology showed that 14 PE samples from metastatic BC (50%) were positive by both PCR and cytology, 9 (32.1%) were positive only by PCR and 5 (17.9%) were negative by both tests, whereas no cases were found of positive cytology with negative PCR. RT-PCR increased sensitivity of BC effusion detection to 32.1% (McNemar test, P=0.004). We demonstrated that RT-PCR for hMAM test was more sensitive than cytomorphology suggesting that, although hMAM is not BC specific, it may be useful in adjunct to cytology for the routine screening of malignant BC effusions.

[Thoracocentesis for the assessment of lung cancer with pleural effusion]. / La toracocentesis en la evaluación del cáncer de pulmón con derrame pleural

OBJECTIVE: To analyze the pleural and mediastinal effect of thoracentesis tumor-positive cytology in pleural effusions (PE) detected by chest X ray of lung cancer patients. PATIENTS AND METHODS: The study was performed in patients with lung cancer for whom PE was evident in chest X ray films, who then underwent thoracentesis followed by video-assisted thoracoscopy (VAT) to evaluate direct pleural tumor infiltration, mediastinal node involvement and the existence of pleural metastasis. Patients without contraindication underwent the procedure, even if tumor positive cytology was present. When pleural metastasis was found the treatment employed was talc pleurodesis and chemotherapy. Descriptive statistics were compiled and the validity of VAT for pleural metastasis diagnosis, of thoracentesis pleural cytology to detect infiltration of the tumor-adyacent pleura, N2 disease and pleural metastasis were calculated. Survival was also analyzed. RESULTS: PE was present in 188 of 971 consecutive lung cancer patients. Seventy two PEs were visible in the chest X ray films. Volume exceeded 425 mL. Tumor positive pleural cytology was detected in 29 cases (40%). Pleural metastasis were found in 54 patients, 23 of whom had tumor positive pleural cytology. In the other 6 patients with positive cytology the primary neoplasm infiltrated the visceral pleura, completely in 5. In 4 of those 5, the mediastinal pleura was also involved. The primary tumor and diseased lymph nodes were removed from 11 patients, 3 of them with tumoral pleural cytology. Visual pleural inspection by VAT had a sensitivity of 93%, specificity of 82%, positive predicted value (PPV) of 94% and negative predicted value (NPV) of 78% for the diagnosis of pleural metastasis. Thoracentesis cytology showed a sensitivity of 43%, specificity of 67%, PPV of 79% and NPV of 28% for pleural metastasis. For the evaluation of adjacent pleura infiltration, without pleural metastasis, the sensitivity of cytology was 40%, specificity 100%, PPV 100% and NPV 25%. For mediastinal node invasion clinically evaluated, the sensitivity of cytology was 55%, specificity of 62%, PPV 18% and NPV 90%. Survival after thoracotomy was 39% after 2 years, and the median survival time was 14.5 months. In the 11 resected patients, survival was 53% at two years. The difference in survival between patients treated by thoracotomy and those treated by talc pleurodesis after VAT was significant (p < 0.01). The 3 resected patients with pleural tumor-positive cytology survived 84, 39 and 25 months. CONCLUSIONS: Nineteen percent of patients with lung cancer have PE, of which 7% can be seen in chest X ray films. In such patients the likelihood of pleural metastasis is 75%. Pleural metastasis is not necessarily present when PE cytology indicates that tumor is present. VAT can be considered the ideal technique for the assessment of direct pleural invasion by the tumor or of pleural metastasis.

Predicting survival in patients with recurrent symptomatic malignant pleural effusions: an assessment of the prognostic values of physiologic, morphologic, and quality of life measures of extent of disease.

PURPOSE: To determine the prognostic value of pleural fluid pH, pleural fluid glucose, extent of pleural carcinomatosis (EPC) score, and Karnofsky Performance Scale (KPS) score in patients with recurrent symptomatic malignant pleural effusions. DESIGN: Prospective 53-month study. SETTING: Referral center for interventional pulmonology. PATIENTS: Eighty-five consecutive patients (42 men and 43 women) with recurrent symptomatic malignant pleural effusions who were referred to the interventional pulmonary service for thoracoscopic pleurodesis. MEASUREMENTS: Pleural fluid pH, pleural fluid glucose, EPC score, and KPS score. RESULTS: The KPS score was the only statistically significant predictor variable. Patients with a KPS score >/= 70 had a median survival of 395 days, as opposed to a median survival of only 34 days for patients with a KPS score /= 70, it may be very reasonable to proceed with thoracoscopic talc pleurodesis for management of their malignant pleural effusions.

Assessment of the value of fibronectin as a tumour marker in malignant pleural mesothelioma.

Fibronectin concentrations both in plasma and pleural effusion were prospectively determined in 60 patients with exudative pleural effusions. Fibronectin concentrations in plasma and pleural fluid in 12 patients with infectious and exudative pleural effusions (mean +/- SD) were 240 +/- 103 and 212 +/- 115 micrograms.mL-1, in 17 patients with primary or metastatic lung carcinoma 242 +/- 104 and 210 +/- 82 micrograms.mL-1, in 13 patients with pleural tuberculosis 246 +/- 77 and 231 +/- 133 micrograms.mL-1, and in 18 patients with confirmed malignant pleural mesothelioma 261 +/- 119 and 276 +/- 188 micrograms.mL-1. There were no significant differences either in the plasma or serum concentrations of fibronectin between groups (p > 0.05). Although pleural fluid fibronectin content appeared to have high specificity (85%), it was found to be an inefficient biological marker for differentiating nonmalignant from malignant pleural effusions due to its low sensitivity (6%).

Assessment of immunocytochemical and histochemical stainings in the distinction between reactive mesothelial cells and adenocarcinoma cells in body effusions.

BACKGROUND: The accumulation of fluid in body cavities is a common event in both neoplastic and non-neoplastic diseases. However, the distinction between cells of reactive process and those of malignancy in cytology is not always possible. It is especially difficult when reactive mesothelial cells and adenocarcinoma cells are encountered. The aim of the present study was to find out the most accurate or reliable immunocytochemical and histochemical stains to distinguish reactive mesothelial cells from adenocarcinoma cells, and to serve as a standard method in the future when dealing with equivocal cases. METHODS: Ninety-nine cases of malignant epithelial effusion were collected from 755 cases of effusion obtained from 3 large body cavities in the past one-year period. Among them, 71 cases were histologically as adenocarcinoma and 13 cases as non-adenocarcinoma. The other 15 cases were carcinoma proved by image as well as clinical symptoms and signs. These 99 cases, plus 10 cases of non-malignant effusion, underwent immunocytochemical and histochemical stainings. Five common commercial antibodies used in this immunocytochemical study were epithelial membrane antigen (EMA), carcinoembryonal antigen (CEA), cytokeratin, vimentin and Leu-M1. The histochemical study included periodic acid-Schiff diastase (D-PAS) and mucicarmine stains. RESULTS: The immunocytochemical study showed that EMA had a high frequency of positive staining with malignant epithelial cells and a negative staining with mesothelial cells. Cytokeratin always stained with malignant epithelial cells but it also stained with mesothelial cells. Almost all the proved adenocarcinomas expressed CEA which was not expressed in the proved non-adenocarcinomas. However, CEA occasionally stained mesothelial cells. Leu-M1 showed a low frequency of staining with the proved adenocarcinoma cells, but it did not stain proved non-adenocarcinoma cells and mesothelial cells. On the contrary, vimentin stained with all mesothelial cells but occasionally with malignant epithelial cells, especially the proved adenocarcinoma cells. In the histochemical study, both mucicarmine and D-PAS showed a low sensitivity but high specificity in detecting the adenocarcinoma cells. CONCLUSIONS: No single marker is absolutely reliable to distinguish exfoliated, reactive mesothelial cells from adenocarcinoma cells in effusions. However, a panel of 3 antibodies containing EMA, CEA and vimentin, together with D-PAS and mucicarmine stains may help solve this problem.

Cytologic assessment of peroperative pleural effusion and prognosis in lung cancer patients who underwent resection.

Twenty-five of 108 lung cancer patients who underwent resection had cytologically positive pleural effusions. The rate at which cancer cells were detected was not related to the amount of the effusion. Almost one third of patients with cancer cells in effusion were alive at the end of the third postoperative year, provided that the pleura itself was free of metastasis at the time of operation. Correlation of the cytologically positive rate of pleural effusion (Y) with the degree of pleural metastasis (X1), the degree of pleural involvement (X2), or the degree of nodal involvement (X3) was analyzed using the Hayashi's quantification method type I. The multiple correlation coefficient was 0.843. Partial correlation coefficients of X1, X2, and X3 were 0.733, 0.446, and 0.653, respectively. Pleural metastasis had the strongest effect on the cytologically positive rate of pleural effusion.

Use of monoclonal antibody for assessment of estrogen and progesterone receptors in malignant effusions.

An immunocytochemical assay utilizing specific monoclonal antibodies against estrogen receptor (ER) and progesterone receptor (PgR) has been shown to be highly reliable for the detection of hormone receptors in hormone sensitive tumors. To assess the usefulness of this technique in malignant effusions, CytospinR (Shandon, Inc., Pittsburgh, PA 15275), preparations of 41 pleural and ascitic fluid were studied. The findings from the malignant cells employing estrogen and progesterone receptor immunocytochemical assay were compared with the results obtained from primary tumors by biochemical (dextran-coated charcoal) assay. The results agreed in 88% for ER and 83% for PgR. This study supports the potential value of cytochemical technique in detection of hormone receptors in malignant effusions. Assessment of hormone receptors in malignant effusions may be of clinical significance, particularly in situations where the hormone receptor status of the original tumor is not known. This information may also have some diagnostic and therapeutic importance in assessment of patients presenting with metastatic tumors of unknown origin.