The Mesothelium is a protective membrane that lines several internal organs, which include peritoneum, also known as the abdominal cavity, the pleura , also known as the thoracal cavity and pericardium, also known as the heart sac. Mesothelial tissue also surrounds the male and female reproductive organs. In most cases Mesothelioma occurs in the lungs, pleura. As a result of the inhalation of asbestos, the pleura, begins thicken which causes pleural effusion. This causes severe chest pain for a Desmoplastic Mesothelioma sufferer.

Desmoplastic Mesothelioma is a type of cancer caused by exposure to asbestos. It is classified as a form of Sarcomatoid Mesothelioma. Which is rare form of mesothelioma. The mesothelioma cells are oval shaped. Sarcomatoid Mesothelioma tissue is even more difficult to detect because of its’ properties, as a result it is often be mistaken for other forms of cancer cells, such as sarcomatoid carcinoma or sarcoma. Because mesothelioma is uncommon, it is often misdiagnosed initially.

Desmoplatic Mesothelioma is a form of diffuse mesothelioma. It is only found in ten percent of diffuse mesothelioma cases. However, it has some of the worst survival rates. After it begins to develop tumors, they will spread and increase in size, eventually being able to develop a metastasis. This occurs in the abdominal region most of the times and is operable. Desmoplastic mesothelioma is one of the forms of mesothelioma that develops cancer cells the quickest. Please consult your doctor immediately if you are suffering from any symptoms.

In biological terms, malignant mesothelioma is divided into four types: epithelial, sarcomatoid, biphasic and desmoplastic (a variant of sarcomatoid mesothelioma). These classifications pertain to the shape and structure of the cancer cells.

Different Malignant Mesothelioma Types.

Between 50 to 70 percent of malignant mesothelioma cases are epithelial, approximately 20 to 35 percent are biphasic, and 7 to 20 percent are sarcomatoid. Epithelial cells are marked by their well-defined and uniform shape and can closely resemble cells of another form of cancer known as adenocarcinoma. Sarcomatoid cells display an elongated spindle shape, which tend to be irregular rather than uniform in shape, and the cells often overlap one another. Cells of the biphasic variety contain both epithelial and sarcomatoid cells, which form in groups of like cells rather than displaying a uniform mixture.

Diagnosing what type of malignant mesothelioma a patient has can be challenging. One contributing factor is that it can be difficult to differentiate mesothelioma from adenocarcinoma, a cancer originating in glandular tissue, on small tissue specimens.

Clinical Features of Mesothelioma

• Males >> females
• Age: 7th and 8th decades (with broad range)
• Signs and symptoms – shortness of breath, chest pain, recurrent effusions
• Sites: Pleura >> peritoneal >> other sites
• Majority associated with asbestos exposure
• Treatment: None proven; recent interest in extrapleural pneumonectomy and chemo/radiotherapy
• Prognosis: Survival 6 to 18 months (epithelioid greater than sarcomatoid/desmoplastic)
Survival over five years is rare, but well documented.

Patterns of Presentation of Mesothelioma

• Diffuse process of pleura, peritoneum, or pericardium – by far the most common
• Localized pleural, mediastinal, or intraabdominal mass (all rare)-see below
• Metastatic disease, usually as lymphadenopathy (also rare)

DIFFERENTIAL DIAGNOSIS

When confronted with a potential mesothelioma, one needs to know as much clinical and radiologic information as is available. The gross findings at the time of surgery or autopsy are extremely useful and these can often be inferred from radiologic studies. If these features do not fit with the diagnosis that is being considered, then the pathologist should go back and re-assess the problem.

The differential diagnosis of malignant mesothelioma depends on whether one is dealing with:

1) An epithelial/epithelioid proliferation
2) A spindle cell/fibroblastic proliferation and the approach to these two settings is entirely different.

The basic questions are whether the process is reactive or neoplastic, and if neoplastic is it mesothelioma or some other neoplasm mimicking a mesothelioma? The diagnostic approach, criteria of malignancy, and ancillary tests, particularly immunostains, for these two groups are entirely different:

Epithelioid proliferations:
Reactive mesothelial hyperplasia vs. neoplasm
If neoplastic, mesothelioma vs. carcinoma (or melanoma, etc.)

For spindled/fibroblastic proliferations:
Fibrous pleurisy vs. neoplasm
If neoplastic, desmoplastic/sarcomatoid mesothelioma vs. other (sarcoma, melanoma, sarcomatoid carcinoma, etc.)

1. The distinction of benign mesothelial proliferations from mesothelioma is covered by Churg and recommendations summarized below:

2. The distinction between mesothelioma and metastatic carcinoma involving the pleura is the most common problem and the one that has engendered the largest number of papers in the literature and the situation in which immunohistochemical staining is most useful. The following are some of the features that I personally have found helpful over the years in distinguishing mesothelioma from carcinoma:

Fibrous stroma produced by the proliferation? This favors a neoplasm.
Stromal invasion? This favors a neoplasm; beware of entrapment of mesothelial cells particularly in the pericardium.
Complex cellular proliferation or cohesive sheet-like proliferation? Favors neoplasm.
Are papillae present? Favors a neoplasm.
Is necrosis present? Favors a neoplasm.
Cytologic features? Cytologically bland, cells can be seen in reactive mesothelial proliferations and mesothelioma; marked nuclear atypia usually favors carcinoma.
Nuclear molding? Favors carcinoma.
Columnar cell shape? Favors carcinoma.
Mucous production? Faint mucicarmine positivity not uncommon in mesothelioma; intracellular droplet positivity with PASd favors carcinoma (but rarely reported in mesothelioma).
Cytokeratin stain: Good to confirm the cells actually stain; strong diffuse positivity characteristic of mesothelioma (as well as, obviously, some carcinomas); CK may highlight stromal invasion
Electron microscopy? Rarely helpful (to me!); cases that are diagnostic ultrastructurally tend to be easy light microscopy diagnoses (my bias).

The issue of carcinoma versus mesothelioma remains the most common problem and the vast majority of these cases are recognized with clinical history, knowledge of gross/radiologic findings, knowledge of prior neoplasms, and careful attention to routine histology. Carcinomas look like carcinomas and mesotheliomas look like mesotheliomas! Immunohistochemistry is usually confirmatory.

Nevertheless, immunohistochemistry is considered by most to be the mainstay in this differential diagnostic problem and the horizon is ever changing as new antibodies are added and older ones are cast aside. The recommendation of an international mesothelioma working group is that one use at least two positive markers for mesothelioma and at least two positive markers for carcinoma in making this distinction.

Practically speaking most experts do at least 6 antibodies for the carcinoma vs mesothelioma differential. In addition, sex and site of the biopsy are issues in selecting antibody panels; ER/PR stains may be indicated in women and the differential for carcinomas in the abdomen is different for that in the chest. I like a pancytokeratin, not for its discriminatory value, but to highlight the architecture of the proliferation, help highlight invasion, etc.

All cases
• Pankeratin to assess positivity and pattern

Markers favoring mesothelioma:
• Cytokeratin 5/6*
• Calretinin*
• WT-1*
• Thrombomodulin
• HBME1
• Membrane pattern with EM
• D2-40 (new, and many are excited about this one)
• Podoplanin (new, and many are excited about this one)

Markers favoring carcinoma:
• CEA*
• CD15*
• B72.3*
• MOC 31*
• TTF-1 (for lung ca)*
• BerEp4
• BG8
• EMA with cytoplastic pattern
• Surfactant (for lung ca)
• Others (e.g. ER/PR, CDX-2, PSA, etc. depending on situation)

None of these antibodies is perfect and occasional mesotheliomas stain positively (usually only a few cells focally) with carcinoma markers and carcinomas may stain with mesothelioma markers. Squamous carcinoma, transitional carcinoma, and some others are frequently positive with cytokeratin 5/6 and adenocarcinomas of the lung not uncommonly stains with calretinin. It is said that cytoplasmic and nuclear staining with calretinin is a good marker for mesothelioma. The greater number of antibodies that one uses the greater the likelihood for discrepant staining and then one has to take a step back and try to prioritize the findings and keep a mental tally sheet of the positive and negative features that favor one diagnosis over the other. In a small minority a confident diagnosis is not possible.

There have been a number of studies suggesting specific panels to use in the differential diagnosis of mesothelioma and adenocarcinoma. Again, no panel is perfect and the antibodies suggested vary from study to study since some labs have their own favorite antibodies. In the study by Yaziji, et al. a three antibody panel, including calretinin, BG8, and MOC 31 provided 96% sensitivity and specificity for distinguishing epithelioid mesothelioma from adenocarcinoma. In clinical practice, the senior author (Dr. Gown) said that he would rarely follow this recommendation and usually did at least six antibodies as mentioned above.

Ordonez has reviewed immunohistochemistry and electron microscopy in the distinction of peritoneal mesothelioma and serous carcinoma and concluded that BerEp-4 and MOC 31 are the best negative mesothelioma markers in this situation and that the best positive markers are D2-40, podoplanin, and calretinin.

3. Desmoplastic mesothelioma versus fibrous pleuritis. As defined above, a desmoplastic mesothelioma is a sarcomatoid mesothelioma that has greater than 50% dense collagenized stroma sometimes with a vague storiform appearance. These regions are not overtly sarcomatous. Since desmoplastic mesotheliomas may over grow hyaline pleural plaques it is sometimes difficult, if not impossible, to separate the pre-existing benign fibrotic reaction of the pleura from a desmoplastic mesothelioma since the latter may produce regions that are nearly indistinguishable from hyaline pleural plaque. Abrupt transitions in cellularity are one of the most useful clues that the process is neoplastic. The separation of desmoplastic mesothelioma from fibrous pleurisy is summarized as follows (from Churg):

The series by Mangano et al. nicely showed that desmoplastic mesothelioma could be separated from fibrous pleurisy on the basis of the presence of a diffuse storiform proliferation of the pleura and one or more of the following features:

• Invasion of the chest wall or lung
• Foci of bland necrosis
• Frankly sarcomatoid foci
• Distant metastases

Immunostaining in the setting of desmoplastic mesothelioma vs. fibrous pleurisy is helpful in highlighting invasion of cytokeratin positive cells into structures adjacent to the pleura such as lung or chest wall. Doing carcinoma markers in this setting is inappropriate.

While rarely a problem, desmoid tumors may present as pleural masses and could mimic a desmoplastic mesothelioma. In general these are more localized and have a more extensive soft tissue component. These have recently been reviewed by Andino, et al.

4. Sarcomatoid mesothelioma versus other sarcoma. Distinguishing sarcomatoid mesotheliomas from other sarcomas involving the pleura is such an uncommon scenario that it is rarely encountered by the surgical pathologist. In such cases careful attention to any prior history of sarcoma, the pattern of growth in the pleural space (sarcomas tend to be multiple nodules rather than more diffuse growth) and selected immunostains based on the histology of the process should allow resolution of most cases. The only sarcomas seen in the pleura with any frequency, and ones which not uncommonly closely mimic a mesothelioma, are malignant vascular tumors. When synovial sarcoma is in the differential, molecular studies for the X:18 translocation are useful.

Localized Malignant Mesotheliomas

The US & Canadian Mesothelioma Panel has put together a series of 22 cases that included both pleural and peritoneal locations (see Allen ref.).

• 15 men, 7 women; age 37-83 years; mean 62.4
• 20 pleural, 2 peritoneal
• Mean size: 6.1 cm
• 15 epithelial, 6 biphasic, 1 sarcomatous
• Immunohistochemistry and ultrastructural studies as for diffuse mesothelioma
• Follow-up in 11 cases; 7 dead of disease at 7 months to 6 years, 1 dead of unrelated causes, 3 (27%) alive at 6-18 months. Those who died tended to die of metastatic disease as opposed to local spread.

Based on these studies, localized malignant mesothelioma is now recognized as an unusual variant of malignant mesothelioma. These appear as localized masses that are usually pleural based. In the peritoneum they may involve adjacent structures and simulate primary tumors of the colon, stomach, liver, etc.

ASBESTOS AND MESOTHELIOMAS

While the vast majority of mesotheliomas are associated with asbestos exposure (the exact percent varies with the series) one essentially never encounters asbestos bodies in routine histologic sections of the pleura and the tumors that arise therein. The search for asbestos bodies should be in lung tissue if it is included with the pleural biopsy. The identification of asbestos bodies (even a single body) in routine histologic material of the lung suggests significant prior exposure and can be used to support an asbestos-associated mesothelioma. An attribution of cause or association between a mesothelioma and asbestos exposure can also be made if there is sufficient documentation of exposure in the clinical history.

References

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Attanoos RL, Biggs AR. Pathology of malignant mesothelioma. Histopathology 1997;30:403-418.
Battifora H, McCaughey WTE. Tumors of the serosal membranes. Atlas of Tumor Pathology. Third Series, Fascicle 15. AFIP, Washington, DC, 1994.
Brockstedt U, Gulyas M, Dobra K, Dejmek A, Hjerpe A. An optimized battery of eight antibodies that can distinguish most cases of epithelial mesothelioma from adenocarcinoma. Am J Clin Pathol 2000;114:203-9.
Churg A, Green FHY. Pathology of Occupational Lung Disease. 2nd Ed. Williams and Wilkins, Baltimore, 1998.
Churg A, Roggli V, Colby TV, and the US Canadian Mesothelioma Panel. The separation of benign and malignant mesothelioma proliferations. Am J Surg Pathol 2000;24:1183-1200.
Crotty TB, et al. Localized malignant mesothelioma. Am J Surg Pathol 1994;18:357-63.
Cugell DW, Kamp DW. Asbestos and the pleura: a review. Chest 2004;125:1103-1117.
Cury PM, Butcher DN, Fisher C, Corrin B, Nicholson AG. Value of the mesothelium-associated antibodies thrombomodulin, cytokeratin 5/6, calretinin, and CD44H in distinguishing epithelioid pleural mesothelioma from adenocarcinoma metastatic to the pleura. Mod Pathol 2000;13:107-112.
Dejmek A, Hjerpe A. The combination of CEA, EMA, and BerEp4 and hyaluronan analysis specifically identifies 79% of all histologically verified mesotheliomas causing an effusion. Diagn Cytopathol. 2005;32:160-6.
Doglioni C, Dei Tos AP, Laurino L, Iuzzolino P, Chiarelli C, Celio MR, Viale G. Calretinin: A novel immunocytochemical marker for mesothelioma. Am J Surg Pathol 1996;20:1037-46.
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1.Step 2

Find out how expertised the lawyers are at working on asbestos related cases. Find out how many mesothelioma lawsuits they have taken on and find out how many asbestos litigation cases they have WON. You want an attorney that has won more cases than not.

2.Step 3

You will need to find an asbestos attorney that’s eager to take on your case. You might not have to go to court due to the fact a large number of asbestos claims are settled out of court. You do want a litigation firm nonetheless that is going to put everything they have into winning your mesothelioma case.

3.Step 4

Find out how many asbestos related resources the attorney has at their disposal. For instance: do they have inspectors that they work with that concentrate on asbestos cases, people who work with asbestos product detection, and or people that have worked on sites contaminated with asbestos fibers (contractors, etc.) that they can refer to for help. You need an asbestos attorney which has some resources available

In the event a family member or friend has asbestosis, mesothelioma or some other asbestos-related disease it is a awful thing. It really is little consolation but the person with the disease or in the case of a person already having passed away, the family of the disceased, will be able to claim compensation.

The money can certainly help cover items like medical bills, psychiatric help and compensate for loss of earnings, disability along with other damages.

Follow these simple steps to help receive compensation:

1. To be able to file a claim for asbestos compensation, you need to be diagnosed with mesothelioma or another sort of asbestos-related disease like asbestosis.

2. There’s a time limit on how much time you have to seek compensation. You’ll want to determine your states “statute of limitations” on filing for asbestos compensation. Numerous states only permit a few years after being diagnosed to file an asbestos claim. In case you are past your states restriction then all is not lost. Talk with a skilled mesothelioma attorney

3. The next thing is to find a lawyer having experience working with asbestos compensation cases. You’ll be able to look for an experienced asbestos lawyer at the bar associations, in the Yellow Pages, on the Internet, through word-of-mouth referrals, etc.

4. When you speak or meet a lawyer make sure they are experienced with asbestos compensation. Look at the amount of similar cases they have worked on, and find out how many they have won.

5. Your attorney should be able to provide you with different options for seeking asbestos compensation. Your lawyer can negotiate your case out of court or your case may go to trial.