Despite how it might seem from the deluge of television advertisements the diagnosis of mesothelioma is very rare, and extremely difficult. The diagnostic process can be fraught with complications depending on the type and amount of material available for evaluation. One of the most common problems is distinguishing an epithelial malignant mesothelioma from a primary lung carcinoma. That difficultly is multiplied when the tumor is poorly differentiated or when the biopsy specimens are small.

In the Sept-October 2014 edition of Tumori, a group of doctors and researchers published a study with the purpose “to evaluate the expression of the most commonly used mesothelial positive markers in a series of primary epithelial lung tumors.” The study, Expression of thrombomodulin, calretinin, cytokeratin 5/6, D2-40 and WT-1 in a series of primary carcinomas of the lung: an immunohistochemical study in comparison with epithelioid pleural mesothelioma by Comin et al., found that “some of the most commonly used mesothelioma markers may react with different types of primary lung carcinomas. These data should be taken into consideration especially when dealing with small biopsy fragments and poorly differentiated tumors.”

[S]ome of the most commonly used mesothelioma markers may react with different types of primary lung carcinomas.

The study used 172 cases of primary lung tumors and 75 unequivocal epithelioid pleural mesotheliomas from the Division of Pathological Anatomy of the Department of Medical and Surgical Care of the University of Florence. Five of the most sensitive and/or specific mesothelioma markers were evaluated: thrombomodulin, calretinin, CK 5/6, D2-40, and WT-1. The authors noted that while these markers have been extensively studied, much of those studies focused on the differential diagnosis between epithelioid mesothelioma and lung adenocarcinoma and “mesothelioma is notorious for phenotypic versatility, both from case to case and even within the same tumor.” Furthermore, “[t]he various histologic patterns and cytomorphologic features of the tumor underlie its capacity to mimic many other neoplasms involving the pleura or adjacent tissue.”

The researchers concluded that, consistent with other published studies, the five markers are useful in identifying most mesothelioma cases, and they may react with different types of primary pulmonary carcinomas with “a variable frequency.” An important takeaway from the study is, in the words of the authors, that “[t]hese data should be taken into consideration when dealing with biopsy specimens and poorly differentiated tumors. Thus, especially in cases of small pathological samples, accurate morphological examination and appropriate clinical, radiological and surgical findings are mandatory to select the most sensitive and specific positive and negative mesothelial markers.”

Cite: Comin et al., Expression of thrombomodulin, calretinin, cytokeratin 5/6, D2-40 and WT-1 in a series of primary carcinomas of the lung: an immunohistochemical study in comparison with epithelioid pleural mesothelioma by Tumori. 2014 Sep-Oct;100(5):559-67. doi: 10.1700/1660.18182.