h2g2 The Hitchhiker's Guide to the Galaxy: Earth Edition

Hi there 2legs,

This is generally a good article about mesothelioma. I also have some other points.

In your first paragraph, you state that neoplasms from other sites may metastasise to the pleura and hence lead to the development of malignant mesothelioma. I wish to clarify this statement with you. Are you stating that once a neoplasm metastasises to the pleura that it then becomes a mesothelioma? If so, this statement is incorrect. If a neoplasm from elsewhere, such as a carcinoma, metastasises to the pleura it remains classified as a metastatic carcinoma.
The classification of mesothelioma implies that the neoplasm has the phenotypic characteristics of mesothelial cells, and by inference is thought to have derived from mesothelial cells. Carcinomas have an epithelial phenotype, and are therefore inferred to arise from epithelial cells.

It may be worthwhile mentioning that the main malignancy caused by asbestos exposure is actually bronchogenic carcinoma. The risk of developing bronchogenic carcinoma with asbestos exposure is exponentially increased if the patient also smokes. However, because of the confounding variable associated with smoking, each individual case of bronchogenic carcinoma is not specific for asbestos exposure. In contrast, malignant mesothelioma is highly specific for asbestos exposure in developed countries, and is thought not to be related to smoking. Other mineral dust exposure may also lead to malignant mesothelioma development.
As a result of this, every case of death by malignant mesothelioma in Britain requires reporting to the Coroner (in England and Wales) or the Procurator Fiscal (Scotland) as a potential occupational exposure-related death.

The diagnosis of mesothelioma is made, following physical and radiological examination, by microscopical examination of either biopsy material of the tumour and/or cytological material of the aspirated pleural effusion fluid. On microscopical examination, the main differential diagnosis of a malignant mesothelioma is with that of a pulmonary adenocarcinoma. Other rarer entities, such as monophasic and biphasic synovial sarcoma, may also mimic mesothelioma.

The diagnosis of mesothelioma on biopsy and cytology is made using a combination of light microscopy and immunohistochemistry. No single immunohistochemical marker is specific for either mesothelioma or adenocarcinoma, and therefore a panel of immunohistochemical markers is used, and a diagnosis is attempted by looking at the general pattern of staining.

At present, the main immunohistochemical markers used in this analysis include:

Mesothelial markers:
Calretinin, cytokeratin 5/6, & mesothelin.
Thrombomodulin used to be used, but has relatively recently been superseded by these more specific markers.

Glandular/adenocarcinoma markers:
Ber-EP4, & carcinoembryonic antigen (CEA - although this is less specific than Ber-EP4).
The specimens are also stained with Periodic acid Schiff with diastase digestion (PASD) in order to look for intracytoplasmic mucin globules in the cytoplasm of glandular cells. However, mesothelial cells may also occasionally contain mucin.

Other markers:
Epithelial membrane antigen (EMA): This marker tends to show cytoplasmic positivity in glandular cells and membranous positivity in (usually malignant) mesothelial cells.
Thyroid-transcription factor-1 (TTF-one): Nuclear positivity for this indicates either a lung or thyroid (adenocarcinoma) primary. Thyroid malignancies tend to be morphologically distinct, and therefore do not usually enter the differential diagnosis.

The microscopical findings are then correlated with the radiological findings to arrive at a definite diagnosis, if possible.

Asbestos also causes other lung diseases, which include interstitial fibrosis (asbestosis) and pleural plaques, which are benign fibrotic and calcified lesions of the pleura. It is interesting to note that a person that develops pleural plaques as a result of asbestos exposure is statistically less likely to develop malignant mesothelioma.

Oh, I forgot to mention this:

Once a person has died from mesothelioma, and the Coroner decides that the case requires an autopsy, asbestos fibres are searched for in histological sections of the lungs, to try to confirm the history of asbestos exposure. Asbestos fibres accumulate iron around themselves in the lung tissue, to form "asbestos bodies". Lung tissue may also be sent for more thorough analysis of asbestos fibre count by weight/weight of lung tissue. This is currently performed at Llandough Hospital in Cardiff in the UK

I also forgot to mention this:

Mesotheliomas also always stain positively for epithelial markers, e.g. pancytokeratins (such as MNF116) and other cytokeratins such as cyokeratin 7. Epithelial markers are therefore of no use for distinguishing between carcinoma and mesothelioma.

Carcinomas, however, generally do not stain for mesothelial markers, which is why the immuunohistochemical panel that is used predominantly comprises glandular and mesothelial markers.

I'd just about forgotten I'd written this! Cheers for the extra information, if I remember... which for me at the moment is probably a big if*, I'll try and put some or all of your points in if thats alright?

No worries, that's why I wrote it.
If you have any other queries, just ask.
I notice you have other articles on aneurysms & SLE. I'll have a look at them too.

The SLE and aneurism entrys are already in the edited guide, so I don't think i can change anything about them So, are you a medical doctor or some such? I'm not myself, and my medical training wasn't relaly that* extensive; I was mainly molecular biology studies at Uni with some pathology and then on to doing a lot of immunology but again from the molecular side of things when I did my immunology Masters degree

Just posting here to remind myself o this entry and so I can get round to putting some of your points into the article; obviously if I do that I'll credit you on the article, and hopefully get this suitable to go into Peer review and maybe end up as a guide entry