Synchronous pulmonary carcinoma and pleural diffuse malignant mesothelioma

Synchronous pulmonary carcinoma and pleural diffuse malignant mesothelioma is rare. Cases from the archives of 2 large referral centers were reviewed to identify cases of synchronously occurring pulmonary carcinoma and pleural diffuse malignant mesothelioma. Three cases of synchronous pulmonary carcinoma and pleural diffuse malignant mesothelioma were identified from more than 16,000 pleuropulmonary cases and were reviewed for demographic, clinical, radiographic, histologic, and immunohistochemical findings. The patients were men who were 63, 67, and 77 years old. Two had positive smoking histories; the smoking history of the other patient is unknown. One patient had a positive history of asbestos exposure; one patient had no history of asbestos exposure; and one patient's history of asbestos exposure is unknown. The patients underwent surgery for treatment of adenocarcinoma that was diagnosed preoperatively. Two of the adenocarcinomas were of a predominantly bronchioloalveolar pattern. No diffuse malignant mesothelioma was identified preoperatively. Diffuse malignant mesothelioma was suspected on the basis of pleural involvement by tumor with histology differing from that of the adenocarcinoma. Tumor immunostaining supported the diagnoses. The average survival after diagnosis was 6 weeks or less. In summary, the paucity of cases at 2 large referral centers and the paucity of cases reported in the English language literature highlights the rarity of synchronous pulmonary carcinoma and pleural diffuse malignant mesothelioma. These synchronous neoplasms occur in patients who have risk factors for both neoplasms independently. Length of survival following diagnosis is bleak.     

Expression of vascular endothelial growth factor in diffuse malignant pleural mesothelioma

Angiogenesis is an important part of normal and pathological processes, including tumour growth, metastasis, inflammation and wound healing. VEGF is the best known angiogenic factor, implicated in tumour-associated microvascular hyperpermeability and carcinogenesis. We investigated 103 malignant pleural mesotheliomas, analysing the expression of vascular endothelial growth factor using immunohistochemistry and insitu hybridization. The grade of microvessel density was assessed with the aid of anti-factor-VIII antibodies. An increased expression of VEGF was found in biphasic and epithelioid mesotheliomas, correlating in a statistically significant manner (P<0.042). Insitu hybridization confirmed the specificity of VEGF mRNA expression. There was a robust correlation between VEGF expression and increased microvessel density (P<0.001), and positive mesotheliomas had significantly higher microvessel densities than negative specimens. There was also a significant correlation between microvessel density and histological pattern. As growth pattern tended towards biphasic and sarcomatoid mesotheliomas the density of micovessels decreased (P<0.05).     

MIB-1 proliferation index correlates with survival in pleural malignant mesothelioma

AIMS: The purpose of this study was to establish whether the cell proliferation index assessed by the monoclonal antibody MIB-1 would correlate with survival in pleural malignant mesothelioma. METHODS AND RESULTS: We studied a series of seven long-term survivors with pleural malignant mesothelioma and a group of control cases with short-term survival. All cases showed MIB-1 positive cells, and labelling indices were expressed as percentage of cells with positive nuclear immunostaining by randomly counting 1000 tumour cells. A statistically significant difference was found between MIB-1 values in the long-term survival group and the control cases with short-term survival. CONCLUSIONS: Our results indicate that the differences in biological behaviour of malignant mesothelioma in long-term and short-term survivors may be explained in part by differences in tumour growth fraction and that proliferation index could represent an important prognostic parameter for this tumour.     

Immunopathology of diffuse malignant mesothelioma

A so-called diffuse biphasic pleural and a monophasic malignant "fibrous" peritoneal mesothelioma were examined using monoclonal anticytoskeleton-antibodies and polyclonal antibodies against macrophage markers. Cytokeratin, vimentin and desmin were each expressed in both of the tumors. GFAP could not be detected. In addition the tumor cells differed in the quantity of macrophage markers. The immunologic findings corresponded to the histologic features of particular areas of the carcinosarcoma. This supports the view that malignant mesotheliomas derive from pluripotential mesothelial cells capable of both epithelial and mesenchymal differentiation. Contrary to some opinions expressed in the literature this histogenesis applies equally to the so-called monophasic diffuse "fibrous" mesotheliomas.     

Chromosome number correlates with survival in patients with malignant pleural mesothelioma.

Modal (MO) and mean (ME) chromosome numbers determined by cytogenetic analysis were compared with survival in 34 patients with diffuse malignant pleural mesothelioma. The patients with normal chromosome number and no clonal abnormalities (MO = 46) survived longer (median survival 17 months) than patients with clonal abnormalities. MO greater than 46 correlated with shorter survival (median 12 months) (p = 0.0186). The correlation was more clear between mean chromosome number (ME) and survival: the median survival of patients with ME greater than 46 was 13 months whereas that of the patients with ME less than 46 was 26 months and ME = 46 (normal chromosome number and no clonal abnormalities) 31 months (p = 0.0007). Furthermore, there was a tendency of an association between ME = 46, ME less than 46 and epithelial subtype reported to be associated with a favorable prognosis in mesothelioma. The addition of chromosome material may present a mechanism to enhance expression of genes important in the pathogenesis of mesothelioma and lead to more aggressive behavior of the tumor.     

Brain metastases in malignant pleural mesothelioma

The brain is a rare site of metastasis in malignant pleural mesothelioma (MPM), and its clinical features and prognosis remain unclear. The aim of this study was to investigate the incidence, prognosis, and risk factors for brain metastases (BM) in MPM patients. Between July 1993 and October 2014, 150 patients with histologically proven MPM were included in this retrospective study. The cumulative incidence of BM was estimated with the Kaplan–Meier method, and differences between groups were analyzed by the log-rank test. Multivariate logistic regression analysis was applied to assess risk factors for BM. The median follow-up time was 11 months (range 0–154.0 months). A total of eight patients (5.3 %) developed BM during the course of their illness. Multivariate analysis identified age <65 years (odds ratio [OR] = 5.83, p = 0.038) and International Mesothelioma Interest Group stage IV (OR = 1.69, p = 0.040) as independent factors related to increased risk of developing BM. The 1-and 2-year cumulative rates of BM were 4.0 % (95 % confidence intervals [CI] 1.4–8.5 %) and 5.3 % (95 % CI 2.3–10.2 %), respectively. Our study showed that the overall survival (OS) of patients with BM was worse than that of patients without BM (median OS 6.5 vs. 11.0 months, p = 0.037). The prognosis for BM in MPM patients is poor. Clinicians should perform careful screening for BM, especially in patients with risk factors.     

Elevated PDGFRB gene copy number gain is prognostic for improved survival outcomes in resected malignant pleural mesothelioma

PDGF/PDGFR pathway has been implicated in malignant pleural mesothelioma (MPM) carcinogenesis, and evidence suggests autocrine mechanisms of proliferation. We sought to evaluate the incidence of PDGFRB gene copy number gain (CNG) by fluorescence in situ hybridization and PDGFR pathway protein expression by immunohistochemistry (IHC) and correlate it to patient clinical outcome. Eighty-eight archived tumor blocks from resected MPM with full clinical information were used to perform IHC biomarkers (PDGFRα, PDGFRβ, p-PDGFRβ) and fluorescence in situ hybridization analysis of PDGFRB gene CNG. Spearman rank correlation, Wilcoxon rank-sum test, Kruskal-Wallis test, BLiP plots, and Kaplan-Meier method were used to analyze the biomarkers and correlation to clinical outcome. Several correlations between the IHC biomarkers were seen; however, none correlated to clinically relevant patient demographics or histology. In the CNG analysis, PDGFRB gene CNG in >10% of tumor cells had lower cytoplasmic p-PDGFRβ (P = .029), while PDGFRB gene CNG in >40% of tumor cells had a higher cytoplasmic PDGFRβ (P = .04). PDGFRB gene CNG status did not associate with patient demographics or tumor characteristics. PDGFR pathway IHC biomarkers did not associate with survival outcomes. However, patients with PDGFRB CNG >40% of tumor cells had improved relapse-free survival (HR 0.25 [95% CI 0.09-0.72], P = .0096) and improved overall survival (HR 0.32 [95% CI 0.11-0.89], P = .029). PDGFRB CNG >40% of MPM tumor cells is a potential prognostic biomarker for surgery and may identify a unique population of mesothelioma patients. Future validation of this biomarker in prospective trials is needed. From a retrospective review of archived tissue specimens from patients with resected malignant pleural mesothelioma tumors, we show that patients with PDGFRB CNG >40% of tumor cells had improved relapse-free survival (HR 0.25 [95% CI 0.09-0.72], P = .0096) and improved overall survival (HR 0.32 [95% CI 0.11-0.89], P = .029). PDGFRB CNG >40% of MPM tumor cells is a potential prognostic biomarker for surgery and may identify a unique population of mesothelioma patients.     

Over-expression of tenascin-C in malignant pleural mesothelioma

Aims:  Tenascin-C is an extracellular matrix glycoprotein known to have anti-adhesive characteristics and to be expressed in various human malignant neoplasms. We hypothesized that the expression of tenascin-C would be increased in human malignant pleural mesothelioma, and its accumulation associated with the prognosis of the patients with this disease.
Methods and results:  Thirty-seven cases of mesothelioma were studied by immunohistochemically using a monoclonal antibody against tenascin-C, and with a semiquantitative scoring system for tenascin-C in different areas of the tumours. In 10 selected cases tenascin-C mRNA in-situ hybridization was also analysed. Since transforming growth factor-beta (TGF-β) is known to induce both the synthesis of tenascin-C and the growth of mesotheliomas, an immunohistochemical analysis of TGF-β1, -β2 and -β3 was also performed. Normal pleura ( n  = 7) and metastatic pleural adenocarcinomas ( n  = 7) were used as controls. Tenascin-C protein was expressed in every histological subtype of malignant mesothelioma, being most prominent in the fibrotic stroma of a tumour, around tumour cells and at the invasive border, whereas tenascin-C mRNA was scarce in tumour cells. The patients with less immunohistochemical expression for tenascin-C tended to live longer ( P  = 0.028 by Fishers' exact probability test). All mesotheliomas showed positivity for at least one isoform of TGF-β.
Conclusions:  In conclusion, high expression of tenascin-C protein in malignant pleural mesotheliomas may play a role in its invasive growth, and might serve as a prognostic marker of the disease.     

Lipid-rich diffuse malignant mesothelioma: a case report

An 80-year old man presented with shortness of breath and was found to have a large right pleural effusion. Cytology of the pleural fluid showed atypical papillary clusters of epithelioid cells. Multiple white-yellow nodules studding the pleural surfaces were seen at thoracoscopy, and biopsies showed solid and papillary clusters of large epithelioid cells with abundant cytoplasm filled with clear vacuoles. Special stains and electron microscopic findings indicated that the tumor was a diffuse malignant mesothelioma with numerous intracytoplasmic lipid vacuoles. Fat stain may be useful at time of frozen section for a pleural-based tumor with vacuolated cells, and the presence of lipid vacuoles in a pleural-based tumor does not exclude diffuse malignant mesothelioma.     

Nonrandom chromosomal abnormalities in malignant pleural mesothelioma

Cytogenetic studies were performed on tumor cells from specimens of 30 consecutive patients with malignant pleural mesothelioma. Metaphases for chromosomal G-banding analyses were obtained from 27 of these patients. Clonal abnormalities were detected in 19 patients. Karyotype findings were complex and heterogeneous: aneuploidy, polyploidy, structural abnormalities, and several subclones were seen. The most frequent chromosomal abnormalities were polysomy or partial polysomy 7, monosomy or partial monosomy 22, and rearrangements involving breakpoints at 1p11-22.     

Expression of glycoprotein 90K in human malignant pleural mesothelioma: correlation with patient survival

The expression of the tumour-associated glycoprotein 90K in patients with malignant pleural mesothelioma (MM) has not been described. This study used enzyme-linked immunoassay (ELISA) to measure 90K in pleural effusions (PEs) and sera from patients with MM (n=28), lung cancer (LC) (n=14) and benign pleural disease (BPD) (n=15). Immunohistochemistry was used to investigate 90K expression in MM and LC tissue sections. The expression of 90K was further evaluated in vitro by ELISA and western blot analysis of conditioned media and cellular extracts of MM, LC and normal human mesothelial (NHM) cell cultures. Finally, the relationships between 90K expression in MM and patient age and survival were studied. The mean 90K level was significantly higher (p<0.05) in PEs of MM patients (11.0+/-6.6 microg/ml) than in LC (6.1+/-3.2 microg/ml) or BPD (6.2+/-5.0 microg/ml) patients. Immunohistochemistry showed a positive reaction for 90K in MM biopsy sections and positive staining limited to inflammatory infiltrates in LC sections. The level of 90K was significantly higher in cell culture media of MM than of LC or NHM (p<0.001). Bands representing proteins with molecular weight of approximately 90 kDa were detected by western blot in MM cellular extracts. An inverse correlation between PE 90K levels and MM patient age (r=-0.45; p=0.017) and a positive correlation between serum 90K levels and MM patient survival (r=0.62; p=0.006) were detected by linear regression analysis. Kaplan-Meier univariate analysis showed increased survival probability for MM patients with serum 90K level >7.3 microg/ml (log rank, p<0.05). This is the first report in MM of the expression of 90K and of its potential diagnostic and prognostic application.     

Prognostic role of osteopontin expression in malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) represents highly aggressive neoplasms with a mean survival of approximately 10 months. Osteopontin, a glycoprotein involved in cell-matrix interactions correlated with invasion and metastatic spread in several tumors, has recently been proposed as a serum marker of MPM in asbestos-exposed subjects. The aim of this study was to define the prognostic role of osteopontin in MPM. For the study, 32 long-term survivors (>24 months) and a random sample of 69 short-term survivors (相似文献