Elsevier

Human Pathology

Volume 44, Issue 1, January 2013, Pages 1-19
Human Pathology

Progress in pathology
Application of immunohistochemistry in the diagnosis of epithelioid mesothelioma: a review and update

https://doi.org/10.1016/j.humpath.2012.05.014Get rights and content

Summary

A large number of immunohistochemical markers that can assist in the differential diagnosis of epithelioid mesotheliomas are currently available. Because these markers are expressed differently in the various types of carcinomas that can metastasize to the serosal membranes and can potentially be confused with epithelioid mesothelioma, their selection for inclusion in a diagnostic panel largely depends on the differential diagnosis, as well as on which ones work the best in a given laboratory. Traditionally, the panels used in the differential diagnosis of epithelioid mesothelioma have consisted of a combination of positive mesothelioma markers and broad-spectrum carcinoma markers. At present, a wide variety of organ-associated carcinoma markers such as thyroid transcription factor-1 and napsin A for the lung, PAX 8 and PAX 2 for the kidney, and Müllerian-derived tumors; gross cystic disease fluid protein-15 and mammaglobin for the breast; and CDX2 for intestinal differentiation are available, which can assist in establishing the site of origin of an adenocarcinoma when included in a diagnostic panel. This article provides updated information on the composition of the panels of markers recommended in the various differential diagnoses.

Introduction

Epithelioid mesotheliomas characteristically present a broad range of morphologic features and, because of this, they can be confused with a variety of malignancies that can metastasize to the serosal membranes. When these tumors arise in the pleura, they must be distinguished from peripheral adenocarcinomas of the lung involving the pleura and from a metastatic carcinoma originating from a distant organ such as the kidney or breast, whereas mesotheliomas arising in the peritoneum may resemble serous carcinomas originating in the peritoneum or metastatic serous carcinomas of the ovary. Because there is no absolutely specific and sensitive marker for mesothelioma, establishing the differential diagnosis of these tumors largely depends on the use of immunohistochemical panels composed of positive mesothelioma markers (ie, those that are frequently expressed in mesotheliomas, but not in carcinomas) and positive carcinoma markers (ie, those that are frequently expressed in carcinomas but not in mesotheliomas). The composition of these panels varies depending on whether the tumor involves the pleura or the peritoneum, as well as its histologic appearance and the patient's clinical history. The recommended panels are constantly subject to change as a result of the identification of new markers that can be used in the differential diagnosis of these tumors and the continual publication of new information on the value of the individual markers. The purpose of this article is to review the current information on the various markers that have been recommended to assist in distinguishing epithelioid mesotheliomas from metastatic carcinomas to the serosal membranes. Particular emphasis will be placed on those newly identified markers that may be useful in these differential diagnoses. To facilitate the discussion of these markers, they have been divided into 4 groups: positive mesothelioma markers, broad-spectrum positive carcinoma markers, organ-associated carcinoma markers, and miscellaneous markers.

Section snippets

Positive mesothelioma markers

A relatively large number of markers that are commonly expressed in epithelioid mesotheliomas but not in carcinomas have been recognized. A list of such markers is provided in Table 1.

Broad-spectrum positive carcinoma markers

Over the past 3 decades, a large number of immunohistochemical markers that are commonly expressed in a wide variety of carcinomas but not in epithelioid mesotheliomas have been identified. A list of such broad-spectrum carcinoma markers is shown in Table 2.

Organ-associated carcinoma markers

A relatively large number of markers whose expression is highly restricted to some types of carcinomas are currently available. These markers, which are often referred to as organ-associated carcinoma markers, have the advantage over the broad-spectrum carcinoma markers in that, because of their restricted expression, they can help in establishing the site of origin of a metastatic carcinoma to the serosal membranes. A list of such organ-associated carcinoma markers is provided in Table 3.

Miscellaneous markers

Included in this group are markers that, although their expression is not restricted to epithelial tumors, it has been suggested that they may be useful in assisting in the diagnosis of epithelioid mesotheliomas. Only those markers that have been shown to be of current interest will be discussed (Table 4). For information on other markers, the reader is referred to previous review articles by this author [3], [185].

Conclusion and recommendations

Based on this review, it is clear that although a relatively large number of markers that can assist in the diagnosis of epithelioid mesotheliomas are currently available, none of these markers are absolutely specific and sensitive for these tumors. The selection of the markers largely depends on a variety of factors including the location and histologic features of the tumor, the sex of the patient, and the clinical findings. Establishing a differential diagnosis is critical because this will

Acknowledgment

The author wishes to thank Janet Quiñones for technical assistance and Kim-Anh Vu for assistance with digital images.

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