Epithelial Malignant Mesothelioma Research Articles

Mesotelioma epitelial maligno em vacas senis Sindi do Brasil

ABSTRACT: Mesotheliomas in cattle are often described as isolated case reports, and investigations of multiple cases within the same bovine herd are lacking. A series of cases of malignant epithelial mesothelioma, tubulopapilary type, is described in five 15 to 21-year-old Red Sindhi cows from the same herd. Clinical signs included three to eight months of progressive emaciation, dehydration, subcutaneous edema of the lower extremities, and abdominal distension. Grossly, severe subcutaneous edema and hydroperitoneum were noted. Multiple organs’ parietal and visceral serosal surfaces had multifocal to coalescing yellow, firm, sessile nodules ranging from 0.1 to 29.0cm. Similar free nodules floated in the peritoneal fluid. Histologically, the masses comprised a layer of cubic to columnar neoplastic cells forming papillary or cystic proliferation supported by a dense fibrovascular stroma. Neoplastic cells had strong and diffuse cytoplasmic immunolabeling for pan-cytokeratin but were negative for cytokeratin 7 and vimentin. Ultrastructurally, neoplastic cells had delicate microvilli and tight and anchoring junctions. Within the cytoplasm, a moderate amount of loose aggregate of intermediary filament with small mitochondria was observed. Epidemiological investigation evidenced endogamy in this herd. Asbestos exposure was not detected. The diagnosis was based on clinical, gross, histological, and immunohistochemical findings and confirmed by transmission electron microscopy features. A definitive underlying etiology remains unknown.

Well-Differentiated Papillary Mesothelioma of the Peritoneum Is Genetically Distinct from Malignant Mesothelioma.

Well-differentiated papillary mesothelioma (WDPM) is an uncommon mesothelial proliferation that is most commonly encountered as an incidental finding in the peritoneal cavity. There is controversy in the literature about whether WDPM is a neoplasm or a reactive process and, if neoplastic, whether it is a variant or precursor of epithelial malignant mesothelioma or is a different entity. Using whole exome sequencing of five WDPMs of the peritoneum, we have identified distinct mutations in EHD1, ATM, FBXO10, SH2D2A, CDH5, MAGED1, and TP73 shared by WDPM cases but not reported in malignant mesotheliomas. Furthermore, we show that WDPM is strongly enriched with C > A transversion substitution mutations, a pattern that is also not found in malignant mesotheliomas. The WDPMs lacked the alterations involving BAP1, SETD2, NF2, CDKN2A/B, LASTS1/2, PBRM1, and SMARCC1 that are frequently found in malignant mesotheliomas. We conclude that WDPMs are neoplasms that are genetically distinct from malignant mesotheliomas and, based on observed mutations, do not appear to be precursors of malignant mesotheliomas.

Value of immunocytochemistry in differential diagnosis of gastric adenocarcinoma, reactive mesothelial cells and malignant epithelial mesothelioma in metastatic effusion fluid

Objective: To investigate the diagnostic value of some antibodies in peritoneal fluid of patients with gastric cancer and malignant epithelioid mesothelioma in serous effusion. Methods: One hundred and eighty-two cases of serous effusion were collected at Jilin Cancer Hospital, from July 2012 to July 2016. The expression of GLUT1, CDX2, Villin, calretinin and WT1 was evaluated using SP immunocytochemical technique in peritoneal fluid samples collected from 98 patients with gastric cancer and 74 patients with reactive mesothelial cells. The expression of GLUT1, calretinin and WT1 was also evaluated in serous effusion from 10 patients with mesothelioma. Results: The sensitivity of GLUT1, CDX2 and Villin in adenocarcinoma cells was 91.8%(90/98), 68.4% (67/98) and 88.8%(87/98), respectively. The specificity was 95.9% (71/74), 100.0%(74/74) and 100.0% (74/74), respectively. The sensitivity of calretinin and WT1 for reactive mesothelium was 93.2% (69/74) and 79.7% (59/74), respectively. The specificity was 96.9% (95/98) and 100.0% (98/98), respectively. The sensitivity of GLUT1, calretinin and WT1 for mesothelioma was 9/10, 9/10 and 7/10. The reactivity of GLUT1, CDX2, Villin, calretinin and WT1 showed a significant difference (P<0.01) between adenocarcinoma cells and reactive mesothelium. The reactivity of GLUT1 showed a significant difference (P<0.01) between mesothelioma and reactive mesothelium. Conclusions: The optimal combination is a panel of GLUT1, CDX2, Villin, calretinin and WT1 for differential diagnosis between adenocarcinoma cells and reactive mesothelium in peritoneal fluid of patients with gastric cancer. Whereas GLUT1, calretinin and WT1 is the best for differential diagnosis between reactive mesothelium and mesothelioma in serous effusions.

Reproducibility for histologic parameters in peritoneal mesothelioma

Histologic subtype is recognized as a prognostic factor in malignant pleural mesothelioma. Specifically, epithelial morphology is associated with a better prognosis than other subtypes, and the same association is observed in peritoneal malignant mesothelioma. Recently, prognostic differences based on morphologic subtypes of epithelial peritoneal malignant mesothelioma were reported. Herein, we report the interobserver variability across four pathologists at three institutions. The authors independently reviewed 67 cases of malignant peritoneal epithelioid mesotheliomas and subclassified them according to their epithelial subtype: papillary, tubulopapillary, trabecular, micropapillary, solid and/or pleomorphic. The cases were also evaluated by each author for several other histopathologic parameters including depth of invasion, nuclear grade, lymphocytic host response, mitotic count/index, presence of lymphovascular invasion, and stromal desmoplasia. The interobserver agreement for histopathologic parameters was highest for mitotic rate (κ=0.36) and primary epithelial subtype (κ=0.32). The interobserver variability for solid subtype pattern was moderate (κ=0.49). We found that the interobserver variability for most histopathologic parameters is poor.

Malignant Mesothelioma of the Tunica Vaginalis Testis. A Clinicopathologic Analysis of Two Cases with a Review of the Literature

Paratesticular malignant mesothelioma is an extremely rare type of mesothelioma with only a limited number of reported cases. Its clinical differentiation is challenging, and its diagnosis is almost exclusively accidental. The major risk factor is exposure to asbestos, typically with a long latency between exposure and diagnosis. The current study presents the clinical data of two patients diagnosed with paratesticular malignant mesothelioma. We evaluated a large spectrum of risk factors in the patients histories. The histomorphological and immunohistochemical characteristics were analysed and put into the perspective of a broad differential diagnosis. Both cases of malignant epithelial mesothelioma of the tunica vaginalis testis clinically presented as unilateral hydroceles. Patients underwent surgery with the perioperative finding of a tumour. Radical inguinal orchiectomy was the treatment of choice for both patients. After comprehensive staging, the second patient underwent a second step of inguinal and pelvic lymph node dis- section. Follow-up visits revealed recurrence of the disease in the first patient. Resection of the tumour was performed. The histology confirmed the relapse of a tumour with identical features to those of the first tumour. Chemotherapy and radiotherapy were not indicated. Both patients are currently in complete remission. In conclusion, surgical treatment had a determinative role in the prognosis of these patients. Radical orchiectomy is the treatment of choice for localized disease. Lymph node dissection can be considered in the case of lymph node enlargement. There is a lack of evidence-based data for adjuvant chemotherapy and radiotherapy. Patients should be referred to experienced multidisciplinary cancer centres for a second opinion on histology, treatment, and a follow-up plan.Key words: mesothelioma - tunica vaginalis testis - hydrocele - asbestos exposure.

Serendipitous Discovery of Peritoneal Mesothelioma

We present the case of a 64-year-old patient with a history of Birt-Hogg-Dube syndrome, polycystic kidney disease treated with renal transplantation in May 2013, and multiple types of skin cancers, including malignant melanoma. He presented for lymphoscintigraphy for sentinel lymph node identification of the melanoma. Subsequent biopsy of the right axillary sentinel lymph node yielded a diagnosis of epithelial type malignant mesothelioma without a known primary tumor. Follow-up positron emission tomography with 2-deoxy-2-(fluorine-18) fluoro-D-glucose integrated with computed tomography (F-18 FDG PET/CT) demonstrated several suspicious hypermetabolic abdominal masses that were later confirmed to be epithelial-type mesothelioma via percutaneous biopsy.

36. Malinant pleural mesotelioma presenting with intrapulmonary lepidic growth: a case report

Malignant pleural mesothelioma is known to have unusual intraparenchymal growth patterns. Few cases of malignant mesothelioma with intrapulmonary lepidic growth have been reported in the literature. We present a case of malignant mesothelioma in a 70 year old gentleman who had presented with recurrent pleural effusions. Preoperative diagnosis of well differentiated adenocarcinoma was made on a core biopsy of lung. A pleurectomy was later performed. The macroscopic examination of the pleura showed numerous nodules up to 10 mm in maximum dimension. Microscopic examination of the pleurectomy specimen revealed an epithelial malignant mesothelioma. There was also lepidic spread of the neoplasm in the adjacent lung tissue attached to the visceral pleura. The neoplastic cells were showed positive staining for calretinin, CK 5/6, D2–40 and HMBE-1 and were negative for CEA and TTF-1 thus confirming the diagnosis of malignant mesothelioma. Intrapulmonary lepidic growth is a rare manifestation of malignant pleural mesothelioma and could be a diagnostic pitfall when only small biopsies of lung are available for assessment.

Diagnostic Accuracy of Ber-EP4 for Metastatic Adenocarcinoma in Serous Effusions: A Meta-Analysis

Numerous studies have investigated the utility of Ber-EP4 in differentiating metastatic adenocarcinoma (MAC) from malignant epithelial mesothelioma (MM) and/or reactive mesothelial cells (RM) in serous effusions. However, the results remain controversial. The aim of this study is to determine the overall accuracy of Ber-EP4 in serous effusions for MAC through a meta-analysis of published studies. Publications addressing the accuracy of Ber-EP4 in the diagnosis of MAC were selected from the Pubmed, Embase and Cochrane Library. Data from selected studies were pooled to yield summary sensitivity, specificity, positive and negative likelihood ratio (LR), diagnostic odds ratio (DOR), and receiver operating characteristic (SROC) curve. Statistical analysis was performed by Meta-Disc 1.4 and STATA 12.0 softwares. 29 studies, based on 2646 patients, met the inclusion criteria and the summary estimating for Ber-EP4 in the diagnosis of MAC were: sensitivity 0.8 (95% CI: 0.78–0.82), specificity 0.94 (95% CI: 0.93–0.96), positive likelihood ratio (PLR) 12.72 (95% CI: 8.66–18.7), negative likelihood ratio (NLR) 0.18 (95% CI: 0.12–0.26) and diagnostic odds ratio 95.05 (95% CI: 57.26–157.77). The SROC curve indicated that the maximum joint sensitivity and specificity (Q-value) was 0.91; the area under the curve was 0.96. Our findings suggest that BER-EP4 may be a useful diagnostic adjunctive tool for confirming MAC in serous effusions.

Well-differentiated papillary mesothelioma manifesting in a hernia sac

Well-differentiated papillary mesothelioma (WDPM) is a tumor of uncertain malignant potential that usually occurs as a multifocal lesion of the female peritoneum, and is incidentally found at the time of surgery. We present here a multifocal case that had arisen from the lining of a hernia sac. To our knowledge, only four cases of this event have been previously described. A review of the five cases reported, including our case, revealed that the mean age of the patients was 56.6±8.35 years. There was predominance in men (4:1). In four cases, the lesion was incidental. Most tumors were found in inguinal hernias. Four cases presented with gross abnormalities in the hernia sac. All the five patients were alive with no evidence of WDPM after a mean follow-up of 38.6 months. Extensive sampling of this rare lesion helps to rule out an epithelial malignant mesothelioma and prevents overtreatment.

Omental mesothelioma as a diagnostic and therapeutic challenge: A case report

Introduction: Peritoneal mesothelioma is one of the very rare tumors of the abdominal cavity and represents 10% of all mesothelioma cases. case report: A 54-year-old male presented with weight loss and abdominal swelling. computed tomography scans revealed calcified plaques in the pleura and extensive thickening of the omentum. A laparoscopic biopsy of the omentum revealed malignant epithelial mesothelioma. conclusion: Although extremely rare, primary omental mesothelioma must be present in the differential diagnosis of omental mass in subjects with a history of exposure to asbestos.

Mesotelioma peritoneal maligno con afectación uterina

Malignant mesothelioma of the peritoneum is an infrequent tumor that is difficult to diagnose and usually behaves aggressively. We present the case of an 80-year-old woman with a pelvic mass of uterine origin, peritoneal carcinomatosis and abundant ascites. Histologic study of the mass was requested and palliative chemotherapy was started because of the advanced stage of the disease. A minilaparotomy was performed and multiple biopsies were taken. Histologic and immunochemistry studies were compatible with a mixed (epithelial and sarcomatoid) malignant mesothelioma of the peritoneum. Prognosis was poor and palliative care was provided. The patient died 15 days after surgery.In women with involvement of the genital organs, it is important to make a differential diagnosis with serous tumors of gynecologic origin because the chemotherapy protocols differ.

Metachronous malignant mesothelioma and pulmonary adenocarcinoma

The prevalence of multiple primary malignant neoplasms in a single patient is reported in a wide variation. The co-existence of malignant mesothelioma and pulmonary carcinoma is a rare entity. Herein, we reported a 60-year-old man who was a retired employee and heavy smoker. He had a suspicious history of asbestos exposure. He complained of chest pain and computerized tomography revealed a mass in the lower lobe of left lung. The patient underwent a left lower lobectomy and was diagnosed as pulmonary adenocarcinoma. During follow-up two years after surgery, the patient complained of dyspnea and chest computerized tomography scan revealed right pleural effusion and diffuse pleural thickening. For the differential diagnosis, the patient underwent wedge biopsy from the right lower lobe and was diagnosed as epithelial diffuse malignant mesothelioma. The development of malignant pleural mesothelioma and lung carcinoma could be associated with asbestos exposure. However, a history of asbestos exposure is not required for the diagnosis. The influence of effective anticancer therapies that improve the survival rates and increase the population ages could be related to the occurrence of a second malignancy.

Vascular Endothelial Growth Factor Receptor 2 as a Marker for Malignant Vascular Tumors and Mesothelioma

Vascular endothelial growth factor receptor 2 (VEGFR2) is a primary responder to vascular endothelial growth factor signal and thereby regulates endothelial migration and proliferation. This receptor is expressed in endothelial cells and in some vascular tumors, but many reports also detail its expression in carcinomas and lymphomas. VEGFR2 is a potential cell-type marker, and data on VEGFR2 expression may also have therapeutic significance in view of recent availability of VEGFR2 inhibitors. In this study, we immunohistochemically examined 262 vascular endothelial and 1640 nonvascular tumors and selected non-neoplastic tissues with a VEGFR2-specific rabbit monoclonal antibody 55B11. In early human embryo, VEFGR2 was expressed in endothelia of developing capillaries and in the thoracic duct, great vessels, hepatic sinusoids, epidermis, and mesothelia. In late first trimester fetus peripheral soft tissues, VEGFR2 was restricted to capillary endothelia, chondrocytes, and superficial portion of the epidermis. In normal adult tissues, it was restricted to endothelia and mesothelia. VEGFR2 was consistently expressed in angiosarcomas, Kaposi sarcomas, and retiform hemangioendotheliomas. It was detected in only half of epithelioid hemangioendotheliomas (15/27), usually focally. VEGFR2 was strongly expressed in most capillary hemangiomas and weakly or focally in cavernous, venous, and spindle cell hemangiomas and in lymphangiomas. Malignant epithelial mesothelioma was found to be a unique epithelial neoplasm with a strong and nearly consistent VEGFR2 expression, including membrane staining (35/38). Approximately 10% of squamous cell carcinomas and 23% of pulmonary adenocarcinomas contained focal positivity. The only nonendothelial mesenchymal tumors found to be VEGFR2 positive were biphasic synovial sarcoma (focal epithelial expression) and chordoma. All melanomas and lymphomas were negative. VEGFR2 is a promising marker for malignant vascular tumors and malignant epithelioid mesothelioma. Expression in biphasic synovial sarcoma epithelium, chordoma, and some carcinomas has to be considered in differential diagnosis. Information on VEGFR2 tissue expression may be useful in development of targeted oncologic therapy through VEGFR2-specific tyrosine kinase inhibitors.

Validation of a minimal panel of antibodies for the diagnosis of malignant pleural mesothelioma

We previously established the use of a minimal panel of antibodies as sufficient to diagnose most epithelial malignant mesothelioma (MPM). We aimed to validate this approach and investigate the utility of a D2-40 antibody. A series of 80 MPM patients selected for surgery and 21 consecutive patients with pleural metastatic carcinoma were included. A minimal panel of antibodies, consisting of calretinin, BG8 and CD15, and D2-40 was investigated. There were 61 epithelial and 19 biphasic MPM as well as 12 metastatic lung, six breast (5 ductal adenocarcinomas, 1 mixed ductal/lobular adenocarcinoma), two serous papillary ovarian carcinomas and one moderately differentiated colorectal adenocarcinoma. The sensitivity of positive calretinin labelling to confirm the diagnosis of MPM was 97.5%, while the 'diagnostic sensitivities' of lack of labelling for BG8 and CD15 were 91.3% and 97.5%, respectively. The use of calretinin, BG8 and CD15 resulted in correct classification in 97.5% of all MPMs. All MPM cases investigated showed at least focal positive D2-40 labelling. We have validated the usefulness of a minimal panel of antibodies with calretinin, BG8 and CD15 as the initial step to the diagnosis of MPM. D2-40 emerged as a helpful diagnostic tool for cases where our initial approach failed to conclusively diagnose MPM.

Malignant pleural mesothelioma in a female Lion (Panthera leo)

An 18-year-old female lion (Panthera leo) was referred to the Department of Animal Pathology of the University of Turin (Italy). At necropsy, multiple nodular, 4–20-mm, confluent white firm nodules were scattered throughout the pleural surfaces of the thoracic wall and of the lungs. Histological lesions were represented by proliferations of papillary structures lined by cuboidal basophilic mesothelial cells with large, oval nuclei and abundant granular eosinophilic cytoplasm. Immunohistochemistry revealed immunoreactivity for pancytokeratin and vimentin. None of the cells expressed calretinin antigen. Asbestos fibers and asbestos bodies were not detected respectively by light microscopy and by Scanning Electron Microscope–Energy Dispersive Spectrometer investigations. On the contrary, chrysotile asbestos were identified in samples from shelter material. Histological and immunohistochemical findings were consistent with the diagnosis of an epithelial malignant mesothelioma. To our best knowledge, this is the first report of a pleural mesothelioma in a lion.

Cytological differential diagnosis among adenocarcinoma, epithelial mesothelioma, and reactive mesothelial cells in serous effusions by immunocytochemistry

The objective of the study is to estimate the expression of some antibodies in the metastatic adenocarcinomas, malignant epithelial mesotheliomas, and reactive mesothelial cells in serous effusions and to choose effective panel to the differential diagnosis. Totally 113 effusion cytology samples (80 pleural fluid, 30 ascitic, and 3 pericardial fluid) from 60 cases of metastatic adenocarcinoma (ACA), 18 cases of malignant epithelial mesothelioma (MM), and 35 cases of reactive mesothelium (RM) were included in this study. The cytological diagnoses of these cases were confirmed by histopathology or clinical datas. Smears and cell blocks were prepared for each case. Immunocytochemical study was performed on the cell block sections. The sensitivity of E-cadherin, CEA, MOC-31, and Ber-EP4 for adenocarcinoma was 86.7%, 80%, 70%, and 76.4%, respectively. The specificity was 98.1%, 96.2%, 92.5%, and 86.8%, respectively. The sensitivity of calretinin, HBME-1, and thrombomodulin for RM/MM was 83%, 79.2%, and 47.2% respectively. The specificity was 88.3%, 21.7%, and 70%, respectively. The expression of E-cadherin, CEA, MOC-31, Ber-EP4, calretinin, and thrombomodulin showed significant difference between ACA and RM/MM (P < 0.01). The reactivity of EMA and Des showed significant difference between RM and MM (P < 0.01). In our opinion, the antibody panel that consists of E-cadherin, CEA, calretinin, and thrombomodulin should be the best for differential diagnosis between metastatic adenocarcinomas and RM/MM in serous effusions. EMA and Des should be used to differentiate malignant epithelial mesothelioma and reactive mesothelial cells. EMA positive and Des negative favor MM, while Des positive and EMA negative favor RM.

Immunzytochemische Abklärung des initialen CUP-Syndroms an Feinnadelpunktaten

Clinical investigations with imaging- and endoscopic techniques in order to identify the primary tumor sites in patients with CUP syndrome generally entail a significant diagnostic effort. If costs exceed <euro> 800.00, a financial loss ensues for German hospitals, as public health insurance companies do not reimburse above this amount. Combined cytological/immunocytochemical investigation of metastatic cancer cells represents a cost-effective, minimally invasive procedure to identify the probable primary cancer site that can be applied on an outpatient basis. We report on 85 fine needle aspiration biopsies of metastases to the liver, 30 to the lymph nodes and over 180 serous effusions and/or ascites with metastatic cancer cells in CUP. After conventional microscopic inspection, a routine panel of six monoclonal antibodies was applied (CK 5/6, CK 7, CK 20, Cdx 2, TTF 1 and CA 125). We were thus able to correctly identify the primary tumor sites in 90.3%, 92.0% and 85.1%, respectively, within three days. In total, 23 primary hepatocellular carcinomas could all be classified correctly, applying the antibodies HepPar 1, BerEp 4, AFP, CD 31, CD 68 and Ki 67. In addition, 141 malignant epithelial mesotheliomas were typed correctly in 97.1%, using the antibodies BerEp 4, Calretinin, Mesothelin, EMA and WT. Therefore, immunocytochemical investigation of metastatic cancer cells from fine needle aspiration biopsies or in serous effusions offers an efficient, cost-effective diagnostic alternative to imaging and endoscopic techniques in the workup of patients with CUP syndrome.

Use of laser capture microdissection to derive poor prognosis gene expression signatures of epithelial abdominal malignant mesothelioma

e22098 Background: Prior work in abdominal malignant mesothelioma (AMM) has established a poor prognosis profile of biphasic AMM when compared to more favorable prognosis epithelial AMM. It is evident, however, that epithelial AMM shows heterogeneity in biologic behavior and prognosis. Given improvements in therapy and survival in AMM, stratification of patients with epithelial AMM into favorable and poor prognosis subgroups is desirable and gene expression profiles may provide poor prognosis signatures to further guide therapy. Methods: Favorable and poor prognosis subgroups were defined as 1000 days of survival time (based on median survival of 90 patients with AMM at Columbia Presbyterian as of Sept 2007). Fourteen frozen epithelial AMM (7 favorable prognosis, 7 poor prognosis) with high quality RNA were laser capture microdissected using a PALM Zeiss microscope and analyzed using Affymetrix U133 Plus 2 microarrays. Unsupervised hierarchical clustering and supervised subgroup analysis were performed using BRB tools version 3.2. Results: Unsupervised hierarchical clustering revealed 2 main clades that contained 6 of 7 poor prognosis and 6 of 7 favorable prognosis tumors, respectively. Supervised class comparison revealed a 39-gene signature that distinguished the 2 classes (permutation values of p &lt; .001). High expression of Nde1, UHRF1, and EZH2 by qPCR on a set of 32 AMM (using an upper quartile cutoff) was associated with poor survival (Log rank statistic p&lt;.01, p&lt;.003 and p&lt;.03 respectively). Immunohistochemistry performed on tissue microarrays of 122 AMM for p16 loss and increased EZH2, Col3A1 and UHRF1 immunoreactivity was associated with poor survival (Log rank statistic p&lt;.0001, p&lt;.009, p&lt;.0001 and p&lt;.012, respectively). Conclusions: Using a training set of laser captured favorable and poor prognosis epithelial AMM, a 39-gene signature was obtained that is associated with prognosis. Validation of several of the candidate genes by qPCR expression and immunohistochemistry was performed, confirming favorable and poor prognosis strata among the epithelial AMM. Identification of poor prognosis epithelial AMM at the time of initial biopsy/tumor cytoreduction could lead to more aggressive primary therapeutic intervention. No significant financial relationships to disclose.

Manejo de la patología pleural

In view of the presentations in the First National Forum of Trainee Pneumologists, the present article focusses on infectious pleural effusions and on the study of possible markers of malignant disease in asbestos-exposed individuals. The yield of the distinct techniques for the diagnosis of tuberculous pleural effusion is assessed, with emphasis on analysis of sputum and pleural samples (fluid and tissue) for Mycobacterium tuberculosis. The utility of adenosine deaminase (ADA) (in the absence of empyema, ADA > 70 U/l is diagnostic of tuberculous pleurisy, while values of less than 40 U/l exclude this diagnosis) and interferon gamma in pleural fluid (cut off: 3.7 Ul/ml) is also discussed. The management of complicated parapneumonic pleural effusions is stratified in four categories, depending on the anatomical and morphological (size and eventual presence of loculations), bacteriological (positivity or negativity of pleural fluid culture) and biochemical (pH/glucose) characteristics of the effusion. Finally, recently developed markers for the evaluation and follow-up of asbestos-exposed individuals are described, with special emphasis on serum determination of mesothelin levels, which seem highly promising as a marker of the development of mesothelioma in these cases. A multicenter study currently being performed in Spain found that soluble mesothelin-related protein (SMRP) levels higher than 0.55 nmol/L showed a sensitivity and specificity of 72% for the diagnosis of epithelial malignant mesothelioma.

Establishment of a human malignant fibrous mesothelioma cell line and the biological characteristics compared with malignant epithelial mesothelioma cell line

Two human malignant mesothelioma cell lines, which we designated "epithelial mesothelioma cells" and "fibrous mesothelioma cells", were established from the pleural fluid containing malignant mesothelial cells of a 72-year-old Japanese man. These cell lines were separated by the colonial techniques from the initiation of the primary cultures and grew well without interruption for 12 years. They were characterized as producing hyaluronic acid. These cell lines displayed different biological characteristics, including morphology, heterotransplantability and genetics using with BAC array CGH. The epithelial mesothelioma cells were epithelial in shape and transplantable into the subcutis of nude mice, while the cells of the fibrous mesothelioma line were fibroblast-like and transplantable into the submucosa of Hamster's cheek pouches but not into the subcutis of nude mice. The mesotheliomas are classified into three types: epithelial mesothelioma, fibrous mesothelioma and mixed type. The gene copy number losses observed on 9p21.3, 9p21.2, 9p21.1, among others may be a major mechanism of malignant mesothelioma carcinogenesis. We considered and supported the combination theory for the histogenesis of malignant mesothelioma.