Pleural Mesothelioma

Steven H. Lin and M. Kara Bucci

Background

In what body sites does mesothelioma arise?

Mesothelioma commonly arises in the pleura but also occurs in the peritoneum, pericardium, and tunica vaginalis testis.

What is the most common cause of mesothelioma?

The highest risk factor for developing mesothelioma is asbestos exposure (amphiboles [rodlike] > chrysotile [serpentine form]). Asbestos is commonly found in insulation material, brake pads, and shipyards.

What is the major difference between the incidence of mesothelioma in the U.S. vs. the developing world?

B/c of early adoption of asbestos regulations, the incidence of mesothelioma in the U.S. peaked in 2004 and has subsequently declined. The incidence has not yet peaked in the developing world and is not expected for the next 10–20 yrs.

What is the estimated latency between asbestos exposure and mesothelioma?

The estimated latency between asbestos exposure and mesothelioma is 20–40 yrs. (Lanphear BP & Buncher CR, J Occup Med 1992)

Approximately how many cases of malignant mesothelioma are diagnosed in the U.S. annually?

~2,500–3,000 cases/yr of malignant mesothelioma in the U.S. (MMWR, CDC 2009)

What % of mesothelioma cases are related to asbestos exposure?

~70%–80% of cases have documented asbestos exposure.

What is lifetime risk of mesothelioma for someone with an occupational asbestos exposure Hx?

The lifetime risk with asbestos exposure ~10%.

Does smoking cause mesothelioma?

No. Smoking alone is not associated with mesothelioma, but smoking increases the risk associated with asbestos exposure.

Is there a gender predilection for mesothelioma?

Yes. Males are more commonly affected than females, likely related to occupational exposure differences.

At what age does the incidence of mesothelioma peak?

The incidence does not peak. It continuously increases with age.

What are the 3 most common histopathologic subtypes of mesothelioma in decreasing order of frequency?

Histopathologic subtypes of mesothelioma: epithelioid (40%) > mixed or biphasic (35%) > sarcomatous or mesenchymal (25%)

What are some common genetic changes seen in mesothelioma?

Loss of tumor suppressor genes p16, p14, and NF-2 are common genetic changes in mesothelioma.

Workup/Staging

What are the 2 most common initial presenting Sx of mesothelioma?

Dyspnea and nonpleuritic chest pain

What is a common presentation of mesothelioma?

Recurrent pleural effusion and/or pleural thickening found incidentally on CXR

What should be present for the initial workup of a pleural-based mass seen on CXR?

Pleural-based mass initial workup: H&P, CBC, CMP, serum soluble mesothelin-related peptide and osteopontin levels (optional), CT chest + contrast, thoracentesis for cytology, and pleural Bx. Consider talc pleurodesis or a pleural catheter for management of effusion.

What is the preferred manner for pleural Bx in the workup of possible mesothelioma?

Video-assisted thorascopic surgery (VATS) (preferred), open Bx, or CT-guided core Bx

What additional workup should be done with a Dx of malignant mesothelioma?

Malignant mesothelioma workup: CT C/A/P + contrast, PET/CT, and MRI chest to determine if there is chest wall (CW) or diaphragmatic invasion. Consider mediastinoscopy or endobronchial US for suspicious nodes. Consider laparoscopy to r/o transdiaphragmatic extension. Use VATS to r/o contralat Dz, if necessary. PFTs are done to assess lung function.

How does malignant mesothelioma appear on a CT of the thoracic chest?

On CT of the thoracic chest, malignant mesothelioma appears as pleural thickening with involvement of interlobar fissures/atelectasis, with possible pleural plaques and calcification.

What is the DDx of tumors of the pleura?

Primary tumors (benign or malignant), or more commonly, metastatic Dz. Malignant tumors include mesothelioma, sarcomas, and mets.

What is the diagnostic yield of mesothelioma from the fluid cytology of the pleural effusion?

Fairly poor, only ~23%. Often, cytology finds atypical mesothelial cells only.

With a needle Bx, what entity is often confused with mesothelioma?

Adenocarcinoma (metastatic) is often confused with mesothelioma.

What pathologic features distinguish mesothelioma from adenocarcinoma?

Mesothelioma is negative for periodic acid-Schiff stain, mucicarmine stain, carcinoembryonic antigen, and Leu-M1. It is positive for calretinin, vimentin, WT1, and cytokeratin.
In mesothelioma, electron microscopy reveals that cells have long microvilli, in contrast to adenocarcinomas, which have short microvilli.

What biomarker is elevated in mesothelioma?

SRMP and osteopontin in serum. It may be elevated in >80% of pts.

What is the AJCC 7^th edition (2009) T staging of mesothelioma?