Kao SC, Yan TD, Lee K, Burn J, Henderson DW, Klebe S, Kennedy C, Vardy J, Clarke S, van Zandwijk N, McCaughan BC.

Asbestos Diseases Research Institute, Bernie Banton Centre, Sydney, Australia.

Abstract

Introduction: Histological subtype is an established prognostic factor in malignant pleural mesothelioma (MPM). We retrospectively investigated the accuracy of classifying histological subtype on diagnostic biopsies and examined the impact of different diagnostic procedures on the outcome.

Methods: Consecutive patients with histologically confirmed MPM who underwent extrapleural pneumonectomy (EPP) from 1994 to 2009 were included. Patient records were reviewed, and the initial diagnoses of histological subtype were obtained. The archival EPP specimens were reviewed by a panel of pathologists. The histological subtype obtained at review was compared with the initial diagnosis.

Results: Eighty-five patients underwent EPP. Two patients achieved a pathological complete response after neoadjuvant chemotherapy, leaving 83 patients to be included in this review. Different diagnostic methods were used before EPP: 81% thoracoscopy; 7% thoracotomy; 11% computed tomography-guided procedure; and 1% other. Patients determined to have an epithelial subtype (n = 64) at EPP were diagnosed correctly at initial diagnostic biopsy in 84% of cases, whereas patients considered to have a biphasic subtype (n = 19) at EPP were diagnosed correctly at diagnostic biopsy in 26% of cases. The sensitivity and specificity of diagnostic biopsy for epithelial MPM was 93% and 31%, respectively. The overall subtype misclassification rate was 20%. Biopsy by thoracotomy was most accurate in subtype classification (83%) compared with thoracoscopy (74%) and computed tomography-guided procedure (44%).

Conclusions: The determination of histological subtype from a diagnostic biopsy is difficult due to sampling error, but an adequate specimen obtained from surgical biopsy increases the accuracy of subtype classification compared with radiological-guided biopsies.

Expression of GATA-6 transcription factor in pleural malignant mesothelioma and metastatic pulmonary adenocarcinoma.

Lindholm PM, Soini Y, Myllärniemi M, Knuutila S, Heikinheimo M, Kinnula VL, Salmenkivi K.

Department of Medicine, University of Helsinki and Helsinki University Central Hospital, Finland.

Abstract

Background: Malignant mesothelioma (MM) is a highly aggressive tumour with poor prognosis and limited response to therapy. New markers for the prediction of prognosis in MM and in pulmonary adenocarcinoma of the pleura are valuable. GATA-6 belongs to a six member zinc finger transcription factor family named after their recognition motif W-GATA-R. AIM: To clarify the distribution and possible function of GATA-6 transcription factor in MM and in pleural metastasis of lung adenocarcinomas.

Methods: 63 pleural MM and 36 pleural metastatic pulmonary adenocarcinomas were studied for GATA-6 expression by immunohistochemistry using tissue microarrays. Expression of GATA-6 was examined in relation to thyroid transcription factor-1 expression, survival, proliferation and apoptosis.

Results: Nuclear immunoreactivity for GATA-6 was stronger and more frequent in MM than in metastatic pleural adenocarcinoma. Prognosis was better in patients with GATA-6 expression when compared to those with no GATA-6 expression (p = 0.002); in the subgroup analysis the difference was significant in epithelial and sarcomatous mesothelioma. GATA-6 was not associated with spontaneous proliferation or apoptosis of the tumour cells in situ.

Conclusion: Results suggest that GATA-6 plays a role in pleural malignancies, predicting longer survival in subgroups of MM.

Hillerdal G, Sorensen JB, Sundström S, Riska H, Vikström A, Hjerpe A.

Department of Lung Medicine and Allergology, Karolinska University Hospital, Solna, Stockholm, Sweden. gunnar.hillerdal@karolinska.se

Abstract

Background: Malignant pleural mesothelioma has a poor prognosis and there is limited effect of treatment. The Nordic Mesothelioma groups decided in the year 2000 to investigate a combination of liposomized doxorubicin, carboplatin, and gemcitabine for this disease in a phase II study.

Methods: From January 2001, to December 2003, 173 evaluable patients with biopsy-verified malignant mesothelioma were included. Two patients were lost to follow-up, but all the others were followed for at least 4 years or until death.

Results: Toxicity was fairly low. There were 56 responses (32.4%), of which 2 were complete; the median time to progression was 8.6 months, and the median overall survival was 13 months. Some patients had their responses 4 to 6 months after last treatment. For 116 patients with epitheloid subtype, median survival was 17 months. A subgroup of these patients with good performance status, early stage, and age 70 years or less, showed a median survival of 22 months.

Conclusion: The treatment yields good results with a high number of responses and long survival, and a low toxicity. The long survival of the epitheloid subgroup with good prognostic factors is as good as or even better than some studies on radical surgery or multimodal treatment, underlining the need of randomized studies to evaluate such treatment options.

Montanaro F, Rosato R, Gangemi M, Roberti S, Ricceri F, Merler E, Gennaro V, Romanelli A, Chellini E, Pascucci C, Musti M, Nicita C, Barbieri PG, Marinaccio A, Magnani C, Mirabelli D.

Department of Epidemiology and Prevention, Liguria Mesothelioma Registry, National Cancer Research Institute IST, Genoa, Italy.

Abstract

A median survival time of about 9 months is generally reported among malignant pleural mesothelioma cases. Recently, better results in terms of survival and performance status have been reported in clinical trials that included highly selected patients. We describe the survival of pleural mesothelioma patients and the factors predictive of survival in an unselected, population-based setting. Pleural mesothelioma cases (4,100) registered from 1990 to 2001 by 9 Italian regional mesothelioma registries contributing to the network of the National Mesothelioma Registry were followed until December 31, 2005. Univariate (Kaplan-Meier) and multivariate (Cox proportional hazards regression) analyses of survival were carried out according to selected individual characteristics, including limited information on treatment in a subset of 578 cases. The median survival time was 9.8 months (95% confidence interval: 9.4-10.1). In multivariate analysis, younger age at diagnosis and epithelioid histotype were associated with significantly reduced hazard ratios. Positive effects of gender (women) and being diagnosed in a hospital with a thoracic surgery unit were of border-line statistical significance. No association with calendar period of diagnosis or asbestos exposure was present. Treatment was not associated with a statistically significant improvement in survival. This is the largest population-based study on survival in patients with pleural mesothelioma to date. Age and morphology were the main prognostic factors. Results regarding the effect of treatment were disappointing but may be useful to assess the future impact, at the population level, of recently introduced therapies.

Keywords: malignant mesothelioma, pleura, survival

Mirabelli D, Roberti S, Gangemi M, Rosato R, Ricceri F, Merler E, Gennaro V, Mangone L, Gorini G, Pascucci C, Cavone D, Nicita C, Barbieri PG, Marinaccio A, Magnani C, Montanaro F.

Unit of Cancer Epidemiology, University of Turin, Turin, Italy. dario.mirabelli@cpo.it

Abstract

In some population-based studies, a shorter median survival was observed in peritoneal as compared with pleural, malignant mesothelioma, but in others, longer median survival times or higher proportions of long-term survivors were reported. Statistical instability could have caused these differences. We analyzed survival in peritoneal mesothelioma in a large and unselected population-based case series. Cases (338) registered from 1990 to 2001 by 9 Italian regional mesothelioma registries contributing to the network of the National Mesothelioma Registry were followed until December 31, 2005. Univariate (Kaplan-Meier) and multivariate (Cox proportional hazards regression) analyses of survival were performed according to selected individual characteristics, including limited treatment information in a subset of 194 cases. The results were compared with those obtained in a parallel study on pleural mesothelioma cases. Epithelioid histotype, younger age at diagnosis and, to a lesser degree, gender (women), and being diagnosed in a hospital with a thoracic surgery unit positively and significantly affected survival. The effect of treatment was positive but not statistically significant. No trend in the risk of death according to calendar period of diagnosis was present. Peritoneal mesothelioma cases had shorter median survival time than pleural cases, but a larger proportion of long-term survivors. Survival patterns after peritoneal and pleural mesothelioma differed markedly. Treatment was not associated with a statistically significant improvement in survival, but our study included cases first diagnosed before the introduction of the most recent therapeutic approaches. This provides a large historical comparison for future studies on survival trends at the population level.

Keywords: malignant mesothelioma, peritoneum, survival

Junker K, Krismann M.

Zentrum für Pathologie, Klinikum Bremen-Mitte, Bremen. klaus.junker@klinikum-bremen-mitte.de

Abstract

In the WHO classification, pleural tumours of mesothelial and mesenchymal origin as well as lymphoproliferative disorders are distinguished, with malignant mesotheliomas forming the most common primary pleural tumour. Histologically, a prognostically relevant differentiation between epitheloid (40-60 %), sarcomatoid (20-30 %), and biphasic mesotheliomas (20-30 %) is made. Besides other rare primary tumours of the pleura, the differential diagnoses of malignant mesotheliomas comprise carcinomatous pleuritis of intra- and extrapulmonary malignancies. Especially in early tumour stages, the differentiation from reactive pleural changes requires a close interdisciplinary cooperation with a careful correlation between histopathological findings and clinical presentation.

Keywords: malignant pleural mesothelioma – carcinomatous pleuritis – solitary fibrous tumour of the pleura – WHO classification

Kim DS, Lee SG, Jun SY, Kim KW, Ha TY, Kim KK.

Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Cincinnati, Cincinnati, OH, USA.

Abstract

The following reports a rare case of primary localized malignant mesothelioma of the liver. A 53-year-old man with no history of exposure to asbestos was admitted to our department for evaluation of incidentally detected liver mass. Computed tomography and hepatic angiogram showed a tumor at the dome of the liver, which was fed mainly through the inferior phrenic artery. The mass was resected, including a portion of the diaphragm. Microscopically, the tumor was composed of cord-like or trabecular arrangements of epithelioid cells having abundant eosinophilic cytoplasm and prominent nucleoli. Immunohistochemically, the tumor cells were strongly positive for calretinin and cytokeratin 5 and negative for hepatocyte markers. These findings were consistent with our diagnosis of epithelioid mesothelioma. A local recurrence was noted 15 months after surgery, which was treated by radiofrequency ablation. At 23 months after initial surgery, locally recurrent masses with direct invasion of the diaphragm and a solitary intrahepatic metastasis were noted, which was treated by partial excision of the diaphragm with intraoperative RFA after transarterial chemoembolization.

Ishiwata I, Ishiwata E, Hirano T.

Department of Obstetrics and Gynecology, School of Medicine, Jikei University, Tokyo, Japan.

Abstract

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.

Keywords: biological characteristics, cell lines, histogenesis, mesothelioma

Nakas A, Trousse DS, Martin-Ucar AE, Waller DA.

Department of Thoracic Surgery, Glenfield Hospital, Groby Road, Leicester LE3 9QA, United Kingdom.

Abstract

Objective: To identify the optimal debulking procedure in patients with malignant pleural mesothelioma who are not suitable for extrapleural pneumonectomy (EPP).

Methods: We reviewed 102 consecutive patients (93 male; 9 female, mean age 63 years) who were not suitable for EPP because of either advanced tumour stage or suboptimal fitness. Patients underwent either a non-radical tumour decortication to obtain lung expansion (group NR) or latterly a radical pleurectomy/decortication to obtain macroscopic tumour clearance (group R). We analysed the comparative perioperative courses and long-term survival.

Results: The two groups were similar for age and gender distribution but epithelioid type was more predominant in group R: 78% compared to 55% epithelioid in group NR. Thirty-day mortality was similar (5.9% in group R and 9.8% in the group NR, p = 0.36) but 90-day mortality was significantly higher in the group NR (29.4% vs 9.8% in group R, p = 0.012). More patients in group R received adjuvant chemotherapy (65% vs 28%, p = 0.000) and radiotherapy (65% vs 26%, p = 0.000). Median survival for all cell types was significantly higher in group R (15.3 months vs 7.1 months, p < 0.000). Group R survival rates at 1, 2, 3 and 4 years were 53, 41, 25 and 13%, respectively while for group NR they were 32, 9.6, 2 and 0%, respectively. For epithelioid cell type there was still a significant median survival advantage in group R (25.4 months vs 10.2 months, p < 0.000), but there was no difference for sarcomatoid (9.3 months vs 3.2 months, p = 0.16) or biphasic cell types (9.4 months vs 7 months, p = 0.38).

Conclusion: If a patient with epithelioid MPM is fit enough to tolerate a thoracotomy then macroscopic clearance of the tumour is the preferred option as part of a multimodality regime including chemotherapy.

Keywords: Malignant pleural mesothelioma; Radical surgery; Pleurectomy/decortication

Hjerpe A, Dobra K.

Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Stockholm, Sweden.

Abstract

Malignant mesothelioma (MM) is a connective tissue tumor with partial epithelioid differentiation. The pattern of proteoglycan (PG) expression by epithelioid and fibroblast-like (sarcomatoid) MM cells differ; cell surface PGs being more abundant in the former phenotype and matrix PGs in the latter. The differentiation as well as much of the malignant nature of these tumors is dependent on the expression of surface PGs. The syndecans, however, also translocate to the nucleus for an as yet unknown function.