Mesothelioma v. Adenocarcinoma

The differential diagnosis of mesothelioma versus adenocarcinoma is one that usually has both medical and legal implications. In the past, the application of special techniques, ranging from special stains (e.g., mucicarmine) to electron microscopic analysis (e.g., to search for microvilli), was required to distinguish between these tumors. At the present time, however, in the vast majority of the cases, immunohistochemical studies, utilizing a limited number of antibodies, can reliably distinguish adenocarcinoma and mesothelioma. In the past, immunohistochemistry studies have been most helpful in contributing to the diagnosis of mesothelioma by demonstrating the absence of expression of adenocarcinoma-restricted proteins, such as CEA and CD15. While these latter markers can still play a role as partial discrimination of mesothelioma from adenocarcinoma, more sensitive markers of adenocarcinoma, such as the MOC-31 and Bg8-defined antigens, are preferred 'first line' reagents. Furthermore, there are now a set of immunohistochemically-defined positive markers of mesothelioma, such as calretinin, the Wilms tumor gene product (WT-1), cytokeratin 5, and mesothelin. The immunohistochemical approach to the diagnosis of mesothelioma has been an area of active clinical research at PhenoPath Laboratories, with ongoing studies in conjunction with Dr. Hector Battifora.

Markers generally positive in adenocarcinoma, and usually negative in mesothelioma:

• Lewis Y antigen (identified by antibody Bg8)
• Tumor glycoprotein (identified by antibody MOC-31)
• Tumor glycoprotein (identified by antibody Ber-Ep4)

However, the sensitivities of adenocarcinoma markers such as those identified by antibodies MOC-31, Bg8, and BerEp4 vary markedly depending on the primary site of the adenocarcinoma.

Markers generally positive in mesothelioma, and usually negative in adenocarcinoma:

• Calretinin
• Wilms tumor gene product (WT-1)
• Cytokeratin 5
• Mesothelin

The sensitivities of the mesothelial markers also vary, with markers such as cytokeratin 5 and mesothelin showing diminished sensitivity in sarcomatoid variants. A small subset of adenocarcinomas can express each one of these mesothelial markers (e.g., WT-1 in papillary serous carcinomas of the ovary, and cytokeratin 5 in a subset of pancreatic and other carcinomas); therefore it is critical that results of immunohistochemical studies be integrated with the histologic findings and the clinical setting.

H&E Malignant pleural effusion in a 68 year-old male with a history of smoking and workplace related asbestos exposure. H&E stained sections show clusters of malignant epithelial cells with the differential diagnosis of mesothelioma vs. adenocarcinoma.

Calretinin	CK5
Bg8	MOC-31
The immunophenotype of these malignant cells is unequivocally that of adenocarcinoma, as the tumor cells are negative for expression of the mesothelial-related markers, calretinin and cytokeratin 5 (with scattered background reactive mesothelial cells serving as positive 'internal controls'). The tumor cells demonstrate expression of the Bg8 and MOC-31 defined antigens, pointing to the diagnosis of adenocarcinoma. Further studies demonstrated expression of TTF-1 and surfactant ApoA protein, further identifying this as a non-small cell carcinoma of lung origin. THANXX       http://www.phenopath.com