Angiogenesis is essential for tumour growth beyond 1 to 2 mm in diameter. The clinical relevance of angiogenesis, as assessed by microvessel density (MVD), is unclear in malignant mesothelioma (MM). Immunohistochemistry was performed on 104 archival, paraffin-embedded, surgically resected MM samples with an anti-CD34 monoclonal antibody, using the Streptavidin-biotin complex immunoperoxidase technique. 93 cases were suitable for microvessel quantification. MVD was obtained from 3 intratumoural hotspots, using a Chalkley eyepiece graticule at x 250 power. MVD was correlated with survival by Kaplan-Meier and log-rank analysis. A stepwise, multivariate Cox model was used to compare MVD with known prognostic factors and the EORTC and CALGB prognostic scoring systems. Overall median survival from the date of diagnosis was 5.0 months. Increasing MVD was a poor prognostic factor in univariate analysis (P = 0.02). Independent indicators of poor prognosis in multivariate analysis were non-epithelial cell type (P = 0.002), performance status > 0 (P = 0.003) and increasing MVD (P = 0.01). In multivariate Cox analysis, MVD contributed independently to the EORTC (P = 0.006), but not to the CALGB (P = 0.1), prognostic groups. Angiogenesis, as assessed by MVD, is a poor prognostic factor in MM, independent of other clinicopathological variables and the EORTC prognostic scoring system. Further work is required to assess the prognostic importance of angiogenic regulatory factors in this disease.

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Angiogenesis is an independent prognostic factor in malignant mesothelioma.

Aims: To undertake a clinicopathological study of diffuse serosal neoplasms of epithelial histogenesis which clinically and pathologically mimic malignant pleural mesothelioma.



Methods and results:  Over a 10-year (1990–2000) study period 53 carcinomas mimicking diffuse pleural mesothelioma (‘pseudomesotheliomatous’ carcinoma) were identified. The study group comprised 50 men and three females, age range 33–77 (median 68) years. In 46 (87%) cases there was a history of smoking and in 40 (76%) cases a history of asbestos exposure. Histologically the pleural ‘pseudomesotheliomatous’ carcinomas could be divided into two broad groups: primary pulmonary carcinomas with florid pleurotropic growth (n = 47), of which 34 (70%) were adenocarcinomas; and diffuse carcinomatous involvement of the pleura by metastatic tumour (n = 6). This latter group comprised two transitional cell carcinomas of bladder, one renal (clear) cell carcinoma, one ductal pancreatic adenocarcinoma, one prostatic adenocarcinoma and one squamous cell carcinoma of parotid gland origin. Follow-up data were available in 35 cases. Regardless of tumour type, survival was poor (median 8 months) and comparable to diffuse pleural mesothelioma.



Conclusions:  Pleural ‘pseudomesotheliomatous’ carcinomas are uncommon (comprising 6% of referrals), pathologically heterogeneous tumours with poor prognosis. Tissue diagnosis should be obtained in all cases of suspected diffuse pleural neoplasia. By light microscopy and immunophenotype many of the tumours mimicked malignant mesothelioma. In particular, an awareness that all neoplasms exhibiting squamous differentiation may express cytokeratin 5/6 and thrombomodulin is important to prevent misinterpretation. In this respect, calretinin is regarded as the most specific and sensitive mesothelial marker. Misdiagnosis may have medico–legal implications in asbestos-related compensation claims.

‘Pseudomesotheliomatous’ carcinomas of the pleura: a 10‐year analysis of cases from the Environmental Lung Disease Research Group, Cardiff

Many centres are now seeing increasing numbers of patients with malignant mesothelioma. This presents pathologists involved in making the diagnosis with a number of problems, which can be divided into those encountered in making the distinction between mesothelioma and benign changes and those experienced in separating mesotheliomas from other types of epithelial and connective tissue tumours. Immunohistochemistry plays a major role in helping to make the diagnosis, but it should be interpreted with due regard to the clinical setting and radiological features, and with a knowledge of the wide morphological variations seen in mesothelioma. This review identifies some of these problems and addresses the uses and limitations of immunohistochemistry in different situations. It includes a discussion of some of the less common variants of mesothelioma and other pleural-based tumours that enter into the differential diagnosis.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2559.2008.03178.x

Problems in mesothelioma diagnosis.

Malignant mesothelioma with heterologous elements: clinicopathological correlation of 27 cases and literature review.

Mesothelioma with rhabdoid features: an ultrastructural and immunohistochemical study of 10 cases

BACKGROUND Three cases of diffuse malignant vascular tumours of the pleura are described which mimicked malignant mesothelioma clinically and pathologically (so called “pseudomesothelioma”). All had occupational histories of exposure to asbestos. The relationship of these tumours to mesothelioma and asbestos exposure is discussed. METHODS To examine the histogenetic relationship between mesothelioma and these three tumours an immunohistochemical analysis of vascular marker (CD31, CD34, and Von Willebrand factor) expression was undertaken in 92 cases of pleural mesothelioma, in addition to these three tumours. Electron microscopic fibre analysis of lung tissue was performed on each of the three cases to assess asbestos fibre content. RESULTS Diffuse pleural epithelioid haemangioendotheliomas may closely resemble malignant mesothelioma clinically and pathologically but, of the 92 pleural mesotheliomas tested, none showed expression of CD31, CD34, and Von Willebrand factor. Although all three cases had claimed exposure to asbestos, ferruginous bodies typical of asbestos were only seen by light microscopy in case 2, and only in this subject was the asbestos fibre content raised in comparison with the range seen in a non-exposed background population. The latent period in the pleural epithelioid haemangioendotheliomas ranged from 18 to 60 years. CONCLUSIONS Endothelial differentiation does not appear to occur in mesothelioma and therefore should be clearly separated from it. No definite association between pleural epithelioid haemangioendothelioma and exposure to asbestos can be made from this small series but further investigation is warranted.

https://thorax.bmj.com/content/thoraxjnl/55/10/860.full.pdf

S K Suvarna

Papers

Malignant vascular tumours of the pleura in “asbestos” workers and endothelial differentiation in malignant mesothelioma