Progress in pathologyWhat are the current best immunohistochemical markers for the diagnosis of epithelioid mesothelioma? A review and update
Introduction
The diagnosis and management of mesotheliomas continue to be a major problem for both clinicians and pathologists. The accuracy of the histopathologic diagnosis of this malignancy is critical to the successful evaluation of clinical trials and is of paramount importance in the determination of a compensation settlement for those individuals with a history of asbestos exposure. Despite the existence of a large volume of literature on the pathology of mesotheliomas describing the histomorphology of these tumors, it is not always possible to reach a firm diagnosis by the study of routine histologic or cytologic light microscopic preparations. The inherent ability of the cells of the serosal membranes to alter their appearance and phenotype, as is frequently manifested in the tumors arising from these structures, and the occurrence of morphologic variants compound the difficulties encountered in diagnosing these neoplasms. An important characteristic of mesotheliomas is their ability to exhibit a broad range of cytomorphological features and to grow in a wide variety of histologic patterns. When presenting a tubular or papillary pattern, mesotheliomas can be confused with adenocarcinomas, and when they present a sarcomatoid morphology, they can often be confused with sarcomatoid carcinomas or sarcomas composed of spindle cells or having pleomorphic features. Of the various ancillary techniques that have been used in the differential diagnosis of mesotheliomas, immunohistochemistry has been recognized as having the most practical utility, especially when distinguishing epithelioid mesotheliomas from peripheral adenocarcinomas of the lung involving the pleura and from metastatic carcinomas arising from a distant organ, such as, the kidney. In the peritoneum, epithelioid mesotheliomas may resemble papillary peritoneal serous carcinomas or metastatic serous carcinomas of the ovary. Because an absolutely specific and sensitive marker for mesotheliomas has not yet been recognized, the immunohistochemical diagnosis of epithelioid mesotheliomas largely depends on the use of panels of markers that are frequently expressed in mesotheliomas (positive mesothelioma markers) combined with those that are commonly expressed in carcinomas (positive carcinoma markers). These panels, however, are continually changing as a result of the identification of new markers that could be useful in the differential diagnosis of these tumors and the publication of new information regarding the value of individual markers. The purpose of this article is to review the information available for those markers that have, for some time, been used in the diagnosis of epithelioid mesotheliomas and to determine their current diagnostic value when compared with markers that have recently become available. Particular emphasis will be placed on those newly recognized markers for which there is some evidence that they could be useful in distinguishing epithelioid mesotheliomas from the different types of carcinomas with which they may be confused. To facilitate the discussion of the markers and to make such a discussion easier for the reader to follow, the various markers have been subdivided into 3 groups: positive mesothelioma markers, positive carcinoma markers, and miscellaneous markers. It should be mentioned that the placement of some of these markers, especially those in the miscellaneous group, is somewhat arbitrary because, in some instances, various individual markers could also be regarded as either a positive mesothelioma marker or a positive carcinoma marker.
Section snippets
Positive mesothelioma markers
Markers that are commonly expressed in mesotheliomas, but not in carcinomas, have only relatively recently been recognized. A list of these markers, which are often referred to as positive mesothelioma markers, is shown in Table 1.
Positive carcinoma markers
Since the 1979 report by Wang et al [86] indicating that carcinoembryonic antigen (CEA) was a useful immunohistochemical marker in the diagnosis of mesotheliomas because it is frequently expressed in adenocarcinomas of the lung, but not in mesotheliomas, a large number of other positive carcinoma markers have been investigated (Table 2). Those that have the most value in the diagnosis of mesotheliomas will be briefly discussed.
Miscellaneous markers
A variety of miscellaneous markers are listed in Table 3, including some tissue-associated markers that, because of their restricted expression, have been found to be useful in distinguishing mesotheliomas from some types of carcinomas. Only those that are, at present, considered to be useful in the diagnosis of mesothelioma will be briefly discussed.
Conclusion and recommendations
From this review, it is concluded that, at present, several highly specific and sensitive markers are available that can be used in the diagnosis of epithelioid mesotheliomas; however, as previously stated, an absolutely specific and sensitive marker for mesothelioma has yet to be identified. Also, it is evident that the selection of the markers to be used in this diagnosis depends on a variety of factors, including the location and histologic pattern of the tumor, and the sex of the patient.
Acknowledgment
The author thanks Janet Quiñones, Kim-Anh Vu, and Mannie Steglich for technical assistance.
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