Archive for the ‘Sarcomatoid Mesothelioma’ Category

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Malignant Biphasic Mesothelioma

Malignant biphasic mesothelioma cells are a combination of epitheloid and sarcomatoid mesothelioma cancer cell subtypes. Instead of having its own distinct structure, it has two very different cancer cell types. Found in 46-63% of all mesothelioma patients, malignant biphasic mesothelioma cells are generally the easiest type to diagnose. www.asbestos.net
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Pleural Mesothelioma – Diagnosis, Causes, And Treatments of Pleural Mesothelioma

Pleural Mesothelioma – Diagnosis, Causes, And Treatments of Pleural Mesothelioma

Mesothelioma is a rare form of cancer almost exclusively caused by asbestos exposure. Pleural mesothelioma is the most common type of mesothelioma, a rare cancer that develops in the mesothelial cells that make up the mesothelium, a membrane that lines many of the body’s organs and cavities.

In the case of pleural mesothelioma, the cancer develops in the lining of the lungs, called the pleura or pleural membrane. Pleural mesothelioma accounts for most cases of mesothelioma, about two thirds of all diagnosed cases. Pleural mesothelioma typically develops in one layer, but can metastasize, or spread, to the other layer. As with other types of mesothelioma, pleural mesothelioma is difficult to diagnose since symptoms do not typically arise for some time after initial asbestos exposure occurs.

Like all mesothelioma cancers, pleural mesothelioma is caused by asbestos exposure and develops when the toxic asbestos fibers become trapped in the spaces between the mesothelial cells. Once trapped in the body, asbestos fibers cause cancerous cells to divide abnormally, resulting in the thickening of the pleural membrane layers and mesothelial cells, causing build-up of fluid (called pleural effusion).

In cases of pleural mesothelioma, asbestos exposure occurs via inhalation of asbestos fibers. Also, pleural mesothelioma is sometimes referred to as an asbestos lung cancer. These asbestos fibers become imbedded in the lining of the lung (the pleura). Over time, they cause chronic inflammation that eventually leads to growth of cancerous tumors or, in some cases, asbestosis.

Pleural mesothelioma patients who are not diagnosed early enough for curative treatment have fewer treatment options, mostly limited to palliative treatments, designed to relieve pain and discomfort to improve a patient’s quality of life, rather than their prognosis. Pleural mesothelioma cancer represents about 75 percent of all mesothelioma cases. Pleural mesothelioma patients display all three types of mesothelioma cancer cells: epithelioid mesothelioma, sarcomatoid mesothelioma and biphasic mesothelioma.

Pleural plaques are localized scars (fibrosis) consisting of collagen fiber deposits that form as a result of exposure to asbestos. Pleural plaques first appear around 20 years after a person is exposed to asbestos. Pleural plaques can form even with low-dose, intermittent exposure. Pleural mesothelioma’s symptoms are not specific, and may indicate other, less serious, conditions.

Since pleural mesothelioma is the most common form of the cancer, more research and knowledge about this type of mesothelioma is present to utilize when detailing a treatment plan. Understanding available treatment options is often very important to patients and their loved ones. Typically, patients will receive a combination of two or more of these types of treatment. Early detection of pleural mesothelioma can improve a patient’s mesothelioma prognosis considerably, and these patients have more extensive treatment options.

Patients diagnosed with pleural mesothelioma in stage one or two generally have greater treatment options and a better prognosis. Palliative treatments include removal of built-up fluid from the pleural spaces, and surgical removal of tumors to relieve pressure on the lungs. Radiation & chemotherapy are common mesothelioma treatment options. A variety of new and novel mesothelioma treatments are available, as are a variety of clinical trials. While prognosis for pleural mesothelioma patients typically ranges between four and 18 months, there are several traditional and alternative treatment methods that may prolong a patient’s life expectancy.

The survival rate was also affected by the type of mesothelioma cancer cells; patients with biphasic cell types have the shortest life expectancy. However, pleural plaques are almost always present in patients with asbestosis and are often present in patients with mesothelioma. The current five-year survival rate for mesothelioma patients is about 10 percent.

Once mesothelioma is diagnosed, it’s important for patients to maintain good eating habits in order to better combat the disease. Many patients die within six months of diagnosis, some last up to a year, but few survive much beyond that length of time. While there is no cure for mesothelioma in any of its classifications, nearly all patients will receive some sort of mesothelioma treatment to extend life expectancy and lessen discomfort.

Do you want to learn more about mesothelioma and it’s effects? For more information and informative articles, visit: The Mesothelioma Disease Blog


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Mesothelioma and Antibodies to Epithelial Membrane Antigen

Mesothelioma and Antibodies to Epithelial Membrane Antigen

One interesting study is called, “The use of histological and immunohistochemical markers to distinguish pleural malignant mesothelioma and in situ mesothelioma from reactive mesothelial hyperplasia and reactive pleural fibrosis” by P. M. Cury, D. N. Butcher, B. Corrin, A. G. Nicholson – The Journal of Pathology Volume 189, Issue 2, pages 251–257, October 1999.  Here is an excerpt: “Abstract – Distinguishing malignant mesothelioma from reactive mesothelial hyperplasia and reactive fibrosis can be a diagnostic problem in small pleural biopsies, made more difficult by the recent recognition of mesothelioma-in-situ. Antibodies to epithelial membrane antigen (EMA), p53, and bcl-2 have all been advocated for differentiating reactive from neoplastic conditions, but reports are inconsistent. These antibodies have therefore been applied to 31 cases of malignant mesothelioma, 34 cases of reactive pleural disease (20 reactive mesothelial hyperplasia and 14 reactive pleural fibrosis) and four small biopsies that were initially coded as suspicious, from patients who later developed frank mesothelioma. Thirty out of 31 (97 per cent) cases of mesothelioma showed positive nuclear staining for p53, with a higher incidence of positivity in epithelioid than in sarcomatoid elements and 30/31 (97 per cent) showed diffuse linear membrane staining for EMA, again more intense in the epithelioid elements. No mesothelioma was positive for bcl-2. In seven cases that contained both in situ and invasive mesothelioma, the in situ elements showed similar staining patterns to the invasive epithelioid elements. Thirteen out of 20 (65 per cent) cases of reactive mesothelial hyperplasia showed occasional nuclear positivity for p53 and 5/20 (25 per cent) cases showed focal weak membrane staining for EMA. Three out of 14 (21 per cent) cases of reactive pleural fibrosis showed positive nuclear staining for p53 and 6/14 (43 per cent) cases showed focal membrane staining with EMA. No reactive cases stained for bcl-2. All four suspicious cases showed diffuse linear staining with EMA and three showed focal staining for p53. It is concluded that strong diffuse linear staining for EMA is a good marker of malignancy when differentiating epithelioid malignant mesothelioma and mesothelioma-in-situ from reactive mesothelial hyperplasia, although weak focal staining may occur in reactive conditions. Nuclear staining for p53 is also suggestive of epithelioid mesothelioma, but should be regarded as no more than suspicious. The antibodies used in this investigation are less helpful in differentiating sarcomatoid mesothelioma from reactive pleural fibrosis.”

Another interesting study is called, “Effusion cytology in the diagnosis of malignant epithelioid and biphasic pleural mesothelioma.” Arch Pathol Lab Med. 1990 Aug;114(8):845-51 by Sherman ME, Mark EJ – James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Boston.  Here is an excerpt: “Abstract –
We reviewed the cytologic findings in pleural effusions of 36 patients in whom a diffuse epithelioid or biphasic malignant mesothelioma of the pleura developed between 1978 and 1988. Malignant neoplasms were diagnosed in 26 (72%) of the 36 patients. A specific diagnosis of a mesothelioma was rendered or suspected in 64% (23/36 patients). Mesothelioma was favored over adenocarcinoma in 81% (29/36) of patients with positive fluid cytologic findings. The contribution of effusion cytology to the final diagnosis and patient treatment was assessed. These data suggested that a cytologic diagnosis contributed useful information in most patients with malignant epithelioid and biphasic pleural mesotheliomas.”

Another interesting study is called, “A randomised trial in malignant mesothelioma (M) of early (E) versus delayed (D) chemotherapy in symptomatically stable patients: the MED trial” by M. E. R. O’Brien, D. Watkins, C. Ryan, K. Priest, C. Corbishley, A. Norton, S. Ashley, N. Rowell  and R. Sayer – Ann Oncol (February 2006) 17 (2): 270-275.   Here is an excerpt: “Abstract – Background: Prior phase II trials have demonstrated the therapeutic activity of cytotoxic chemotherapy in mesothelioma. Currently there are few randomised data assessing the role of chemotherapy versus best supportive care (BSC) in the management of patients with stable symptoms after control of any pleural effusion. A policy of observation is often adopted over initial use of chemotherapy. In this prospective randomised trial we assess the use of early versus delayed cytotoxic therapy. The study opened in 1998, and closed in view of a competing national study (MSO 1) in 2003.   Methods: Eligible patients had a performance status ≤2, life expectancy >3 months and had stable symptoms for at least 4 weeks prior to randomisation. Patients were randomised to receive immediate chemotherapy or initial BSC with the addition of chemotherapy at time of symptomatic progression. All patients received the same platinum-based chemotherapy regimen, MVP [mitomycin C 8 mg/m2 cycles 1, 2, 4 and 6, vinblastine 6 mg/m2, maximum 10 mg, and cisplatin 50 mg/m2 (or carboplatin AUC 5)], every 3 weeks for up to six cycles.   Results: A total of 43 patients were recruited, of which 21 were randomised to the early treatment group and 22 to the delayed treatment group. The median ages were 59 years (range 50–78) and 67 years (range 48–75), respectively (P = 0.1); other baseline parameters were well matched between the two groups. All 21 patients in the early group received chemotherapy versus 17 patients in the delayed group. Median time to symptomatic progression was 25 weeks in the early group compared with 11 weeks for the delayed group (P = 0.1). Median survival was 14 months (1-year survival 66%) for the early group compared with 10 months (1-year survival 36%) for the delayed group (P = 0.1). Quality of life was in general better maintained for early treatment and the health resources use was similar in both arms.   Conclusions: In this patient group, presenting with stable symptoms after control of pleural effusion, the early use of chemotherapy provided an extended period of symptom control, and in this small trial a trend to survival advantage.”

Monty Wrobleski is the author of this article.  For more information please click on the following links

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Malignant Mesothelioma


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Malignant Pleural Mesothelioma Evaluated in a Randomized Study

Malignant Pleural Mesothelioma Evaluated in a Randomized Study

Another interesting study is called, “Randomized trial of doxorubicin versus cyclophosphamide in diffuse malignant pleural Mesothelioma” by Sørensen PG, Bach F, Bork E, Hansen HH – Cancer Treat Rep. 1985 Dec;69(12):1431-2.  Here is an excerpt: “Abstract – The effect of doxorubicin and cyclophosphamide in the treatment of diffuse, malignant pleural mesothelioma was evaluated in a randomized study. All patients were treated on an outpatient basis and none had previously received antineoplastic treatment. All patients had a measurable lesion other than pleural effusion. The treatment consisted of doxorubicin at a dose of 60 mg/m2 every 3 weeks, to a total dose of 550 mg/m2, or cyclophosphamide at a dose of 1500 mg/m2 every 3 weeks for 1 year. At disease progression the treatment was changed to the alternate drug. The dose was increased or decreased according to hematologic effects. Thirty of 32 patients were evaluable for response. Remissions were not achieved in any patient. During treatment with doxorubicin, none of the patients developed cardiotoxicity, while one patient developed hemorrhagic cystitis during treatment with cyclophosphamide. Sepsis or bleeding was not observed in either of the treatment arms. Thus, the trial showed no antineoplastic activity of either doxorubicin or cyclophosphamide in the treatment of malignant pleural mesothelioma.”

Another interesting study is called, “Gene therapy using adenovirus carrying the herpes simplex-thymidine kinase gene to treat in vivo models of human malignant mesothelioma and lung cancer.” By Hwang HC, Smythe WR, Elshami AA, Kucharczuk JC, Amin KM, Williams JP, Litzky LA, Kaiser LR, Albelda SM – Department of Medicine; University of Pennsylvania Medical Center, Philadelphia – Am J Respir Cell Mol Biol. 1995 Jul;13(1):7-16.  Here is an excerpt: “Abstract – Previous studies have shown adenoviral transfer of the herpes simplex virus thymidine kinase (HSVtk) gene followed by the anti-viral drug ganciclovir (GCV) can be used to successfully treat established human mesothelioma tumors growing within the peritoneal cavities of severe combined immune deficient (SCID) mice. These findings raised a number of questions important to the applicability, efficiency, and safety of this treatment strategy. In this report, we have further characterized the use of recombinant adenovirus carrying the HSVtk gene to treat mesothelioma and other localized malignancies. Our results indicate that the Ad.RSVtk/GCV system is effective in causing tumor regression in animals inoculated with another mesothelioma cell line and a lung cancer cell line and that animals with bulky disease can be successfully treated. Effects are seen at a wide range of virus doses and significant anti-tumor activity is present at doses of ganciclovir that are clinically achievable. Finally, this treatment approach appears safe, with limited dissemination of virus using a sensitive RT-PCR detection system. These studies further characterize the use of adenoviral transfer of the HSVtk gene to treat experimental mesothelioma and suggest that clinical trials using this approach may be feasible.

Another interesting study is called, “The diagnostic utility of immunohistochemistry in distinguishing between mesothelioma and renal cell carcinoma: A comparative study
Human pathology” by ORDONEZ Nelson G. – 2004, vol. 35, no6, pp. 697-710 [14 page(s) (article)] (92 ref.)  Here is an excerpt: “Abstract – Both mesotheliomas and renal cell carcinomas can present a wide variety of morphological patterns. Because of this, renal cell carcinomas that metastasize to the pleura and lung may be confused with mesotheliomas. The aim of the present study was to compare the value of the various immunohistochemical markers currently available for the diagnosis of mesothelioma and renal cell carcinoma. A total of 48 mesotheliomas (40 epithelioid, 8 sarcomatoid), and 48 renal cell carcinomas (24 conventional, 12 chromophobe, 8 papillary, 4 sarcomatoid) were investigated for the expression of the following markers: calretinin, mesothelin, cytokeratin 5/6, WT1, thrombomodulin (TM), N-cadherin, CD15 (leu-M1), MOC-31, Ber-EP4, BG-8 (Lewisy), CD10, renal cell carcinoma marker (RCC Ma), carcinoembryonic antigen (CEA), and B72.3. All (100%) of the epithelioid mesotheliomas reacted for calretinin, mesothelin, and cytokeratin 5/6; 93% for WT1; 78% for TM; 75% for N-cadherin, 48% for CD10, 15% for Ber-EP4,8% for MOC-31, 8% for RCC Ma, 5% for BG-8, and none for CEA, B72.3, or CD15. Of the sarcomatoid mesotheliomas, 88% expressed calretinin, 75% N-cadherin, 38% CD10, and 13% each expressed cytokeratin 5/6, WT1, and TM. All of the remaining markers were negative. Among the RCCs, 81% expressed CD10, 75% N-cadherin, 63% CD15, 50% RCC Ma, 50% MOC-31, 42% Ber-EP4, 8% BG-8, and 2% TM. The remaining markers were negative. The results indicate that calretinin, mesothelin, and cytokeratin 5/6 are the best positive mesothelioma markers for differentiating epithelioid mesotheliomas from renal cell carcinomas. The best discriminators among the antibodies considered negative markers for mesothelioma are CD15, MOC-31, and RCC Ma. An accurate differential diagnosis can be reached with the use of any 2 of the 3 recommended positive markers, which should be selected based on availability and on which ones yield the best staining results in a given laboratory. One of the recommended negative markers may be added to the panel if deemed necessary. If confirmation of renal origin is needed, RCC Ma could be useful. Calretinin is the only marker that appears to have any utility in distinguishing between sarcomatoid mesotheliomas and sarcomatoid renal cell carcinomas.”

We all owe a debt of gratitude to these fine researchers.  If you found any of these excerpts interesting, please read the studies in their entirety.

Monty Wrobleski is the author of this article.  For more information please click on the following links

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Mesothelioma Cancer Cell Types – Epithelioid, Sarcomatoid & Biphasic

Mesothelioma Cancer Cell Types – Epithelioid, Sarcomatoid & Biphasic

Mesothelioma is one of the deadliest cancers for a number of reasons. It has a prolonged latency period during which it destroys the mucous-producing membrane that lines the outer surface of a number of organs. This membrane allows the organs to move, which in turn allows them to function. Over a period of decades mesothelioma destroys healthy cells by assaulting them with three main avenues of attack: epithelioid, sarcomatoid, biphasic cells.

Epithelioid mesothelioma cells are the most common and relatively easiest to treat of all types of mesothelioma. This type of cell appears to be a papillary or tubular growth that usually affects the outer membranes and linings of the internal organs and other bodily surfaces. Somewhere between 50 and 70% of all mesothelioma cases belong to this category, and although this cancer is usually extremely difficult to treat, epithelioid mesothelioma is the most likely to respond to treatment.

The second type of mesothelioma is sarcomatoid mesothelioma. This type is the most serious form of the disease, as it is the least likely to respond to treatment. These spindle-shaped pattern of cells that appear to overlap each other are also fortunately the rarest type of the cancer, with approximately 10-20% of all mesothelioma cases falling into this type. Sarcomatoid mesothelioma is so dangerous because it attacks and arises from the support tissues of the body, such as bone, cartilage, fat, and muscle, and cancers in these areas are notoriously difficult and painful to treat. Patients with this form of cancer rarely live longer than six months after diagnosis.

The final condition, biphasic mesothelioma, is not an independent type of mesothelioma, but a combination of sarcomatoid and epithelioid. It is also a mixed bag of conditions in that it can take the good and bad aspects of the other two types, and almost 20-35% of all mesothelioma cases fall into either mixed or biphasic areas.

Without a doubt, mesothelioma is one of the most devastating types of cancer. Most people rarely live beyond a year after their initial diagnosis, and few victims reach five years. Mesothelioma is almost always caused by asbestos exposure, and millions of people have had contact with this deadly substance.

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