Guidelines for Pathologic Diagnosis of Malignant Mesothelioma 2017 Update of the Consensus Statement From the International Mesothelioma Interest Group.

Context: - Malignant mesothelioma (MM) is an uncommon tumor that can be difficult to diagnose.

Objective: - To provide updated, practical guidelines for the pathologic diagnosis of MM.

Data Sources: - Pathologists involved in the International Mesothelioma Interest Group and others with an interest and expertise in the field contributed to this update.

Value of GATA3 immunostaining in the diagnosis of parathyroid tumors.

GATA3 is a transcription factor that is involved in the embryonic development of the parathyroid glands and in adult parathyroid cell proliferation. The aim of this study is to investigate the expression of GATA3 in parathyroid tumors and to determine whether it could be used as an immunohistochemical marker for parathyroid differentiation in tumors. Immunoreactivity for GATA3 was nuclear and was demonstrated in all 10 hyperplastic parathyroid glands, 22 parathyroid adenomas, and 6 parathyroid carcinomas; whereas, all thyroid tumors, renal cell carcinomas, thymic epithelial tumors, and carcinoid tumors investigated for comparison purposes were negative for this marker.

Arginase-1 is a novel immunohistochemical marker of hepatocellular differentiation.

Arginase-1 is an enzyme that catalyzes the hydrolysis of arginine to ornithine and urea in the urea cycle. In normal tissues, arginase-1 is primarily expressed in hepatocytes. Recent investigations have reported that the vast majority of hepatocellular carcinomas express this marker, but it is found only rarely in nonhepatocellular tumors.

Diagnostic utility of immunohistochemistry in distinguishing between epithelioid pleural mesotheliomas and breast carcinomas: a comparative study.

Epithelioid mesotheliomas and breast carcinomas can present a variety of morphologic patterns. Because of this, breast carcinomas that metastasize to the pleura and lung may be confused with mesotheliomas. The aim of the present study is to compare the immunohistochemical markers currently available for the diagnosis of these 2 malignancies and to determine the best panel of markers that can be used to assist in discriminating between them.

Cadherin 17 is a novel diagnostic marker for adenocarcinomas of the digestive system.

Cadherin 17 is a member of a multigene family of calcium-dependent, transmembrane proteins that mediates cell-cell adhesion, plays important roles during embryogenesis, and is crucial for tissue morphogenesis and maintenance. Cadherin 17 is exclusively expressed in the epithelial cells of embryonic and adult small intestine and colon, and pancreatic ducts. It has also been reported to be frequently expressed in adenocarcinomas arising in the gastrointestinal tract and pancreas.

SATB2 is a novel marker of osteoblastic differentiation and colorectal adenocarcinoma.

SATB2 is a nuclear matrix-associated transcription factor and epigenetic regulator that is involved in osteoblastic differentiation and is also expressed in the glandular epithelial cells of the lower gastrointestinal tract. Recent studies have shown that, because of its relative specificity for osteoblastic differentiation, SATB2 immunostaining could potentially be a useful adjunct for assisting in the differential diagnosis of both benign and malignant osteogenic tumors. In addition, because SATB2 is also a highly sensitive and specific marker for colorectal adenocarcinomas, it could also serve as a complementary marker in the differential diagnosis of a carcinoma of unknown primary origin.

Value of calretinin immunostaining in diagnostic pathology: a review and update.

Calretinin is a member of the EF-hand family of calcium-binding proteins. Because its expression is highly restricted to mesotheliomas, calretinin is, at present, the most commonly used positive mesothelioma marker that is most often recommended to be included in the various immunohistochemical panels used to assist in the differential diagnosis of these tumors. Calretinin expression has also been reported to be commonly expressed in a wide variety of other neoplasms, including sex cord-stromal tumors, adrenal cortical neoplasms, olfactory neuroblastomas, Schwann cell tumors, cardiac myxomas, and ameloblastomas.

Value of GATA3 immunostaining in tumor diagnosis: a review.

GATA3 is a member of a group of zinc-finger transcription factors that is involved in cell development and differentiation. Recent studies have shown that, among tumors, GATA3 is commonly expressed in both urothelial tumors and breast epithelial neoplasms. With the exception of salivary gland and parathyroid tumors, GATA3 has been reported to be either absent or only rarely expressed in other epithelial tumors.

Value of SOX10 immunostaining in tumor diagnosis.

SOX10 is a transcription factor that is essential for the generation of neural crest cells, their survival, and maintenance of pluripotency. Recent studies have shown that, among tumors, SOX10 is commonly expressed in melanomas, including desmoplastic melanomas, tumors with Schwann cell differentiation, and some salivary gland neoplasms, particularly those with myoepithelial differentiation. Because of its restricted expression, SOX10 has proved to be a useful immunohistochemical marker with a wide range of diagnostic applications in surgical pathology, some of which are briefly reviewed.

Value of melanocytic-associated immunohistochemical markers in the diagnosis of malignant melanoma: a review and update.

Since the identification of S100 protein as an immunohistochemical marker that could be useful in the diagnosis of melanoma in the early 1980s, a large number of other melanocytic-associated markers that could potentially be used to assist in the differential diagnosis of these tumors have also been investigated. A great variation exists, however, among these markers, not only in their expression in some subtypes of melanoma, particularly desmoplastic melanoma, but also in their specificity because some of them can also be expressed in nonmelanocytic neoplasms, including various types of soft tissue tumors and carcinomas. This article reviews the information that is currently available on the practical value of some of the markers that have more often been recommended for assisting in the diagnosis of melanomas, including those that have only recently become available.

Value of claudin-4 immunostaining in the diagnosis of mesothelioma.

Claudin-4 (CL-4) is a tight junction-associated protein that is expressed in most epithelial cells but absent in mesothelial cells. The purpose of this study is to evaluate the utility of CL-4 immunostaining for assisting in the differential diagnosis of mesothelioma. Sixty mesotheliomas (40 epithelioid, 10 biphasic, and 10 sarcomatoid), 185 carcinomas of different origins that can potentially be confused with mesotheliomas, 37 soft-tissue sarcomas, and 5 melanomas were investigated for CL-4 expression.

Value of podoplanin as an immunohistochemical marker in tumor diagnosis: a review and update.

Podoplanin is a type I integral membrane glycoprotein that, because it is expressed in lymphatic endothelium, but not in vascular blood vessel endothelial cells, is commonly used in the identification of lymphatic endothelial differentiation in vascular endothelial neoplasms and lymphatic invasion by tumor. Because podoplanin is also expressed in mesothelial cells and fetal gonocytes, it has proved to be a useful marker for assisting in the differential diagnosis of mesotheliomas and germ cell tumors, particularly seminomas/dysgerminomas. Podoplanin expression has also been reported in a wide variety of other neoplasms, including hemangioblastomas, meningiomas, cartilaginous tumors, and follicular dendritic cell neoplasms.

Value of PAX8, PAX2, napsin A, carbonic anhydrase IX, and claudin-4 immunostaining in distinguishing pleural epithelioid mesothelioma from metastatic renal cell carcinoma.

Both mesotheliomas and renal cell carcinomas can present a wide variety of cytomorphologic features and histologic patterns. Because of this, renal cell carcinomas metastatic to the pleura and lung can be confused with mesotheliomas. Recently, a variety of positive carcinoma markers, including kidney-associated markers, have become available.

Broad-spectrum immunohistochemical epithelial markers: a review.

A relatively large number of broad-spectrum immunohistochemical epithelial markers that can be used as part of the screening panels employed in the recognition of the main cell lineages during the initial evaluation of a poorly differentiated tumor are currently available. Variations exist in the sensitivity and specificity of the individual markers that have traditionally been used for the demonstration of epithelial differentiation and in the pitfalls associated with these markers. This article reviews not only the reactivity of the various pan-keratin antibodies that are often used to assist in the demonstration of epithelial differentiation, but also that of those that have recently become available.

Value of PAX8, PAX2, claudin-4, and h-caldesmon immunostaining in distinguishing peritoneal epithelioid mesotheliomas from serous carcinomas.

Distinguishing between peritoneal epithelioid mesotheliomas and papillary serous carcinomas involving the peritoneum can be difficult on routine histological preparations, but this differential diagnosis can be facilitated by the use of immunohistochemistry. Recent investigations have indicated that PAX8, PAX2, claudin-4, and h-caldesmon are immunohistochemical markers that can assist in distinguishing between these two malignancies; however, much of the information published on the value of these markers is either insufficient or contradictory. The purpose of this study is to resolve some of the existing controversies and to fully determine the practical value of these markers for assisting in the differential diagnosis between peritoneal mesotheliomas and serous carcinomas.

Value of PAX2 immunostaining in tumor diagnosis: a review and update.

PAX2 is a member of the PAX family of transcription factors that, together with PAX8, is involved in the regulation of the organogenesis of the kidney and the Müllerian system. Recent investigations have demonstrated that, among tumors, PAX2 is commonly expressed in epithelial tumors of the kidney and female genital tract. Although PAX2 expression has also been reported in B-cell lymphomas and rhabdomyosarcomas, especially alveolar rhabdomyosarcomas, it has been suggested that the positivity in these tumors was most probably due to a cross-reactivity of the anti-PAX2 antibody used in those investigations with other members of the PAX protein family.

Mesothelioma with signet-ring cell features: report of 23 cases.

Signet-ring cell mesothelioma is uncommon and only two case reports have been published on this mesothelioma variant, both of which were initially misdiagnosed as signet-ring cell carcinoma. Herein are reported 23 signet-ring cell mesotheliomas that were investigated by immunohistochemistry, 12 of which were also studied by electron microscopy. Twenty-one of the cases originated in the pleura and two in the peritoneum.

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

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.

Immunohistochemical endothelial markers: a review.

A relatively large number of new endothelial markers that can assist in the diagnosis and classification of endothelial and vascular neoplasms have become available over the past few years. The expression of these markers, however, differs considerably among the various tumors. A selection of markers that have potential diagnostic utility or are of current interest among pathologists are reviewed and compared with some of the more traditional markers that have been employed in diagnostic pathology.

Melan A (A103) is not a marker of mesothelioma.

Although a large number of immunohistochemical markers have been proven to be valuable in the differential diagnosis between epithelioid mesotheliomas and metastatic carcinomas involving the serosal membrane, no single antibody has been found that is absolutely sensitive and/or specific in making this distinction. A recent study reported melan A positivity in all 12 of the epithelioid mesotheliomas stained with a melan A antibody (clone A103). To fully determine the practical value of this antibody for assisting in the differential diagnosis of mesotheliomas, we investigated the expression of melan A (A103) in 40 mesotheliomas (27 epithelioid, 6 sarcomatoid, and 7 biphasic), 10 lung adenocarcinomas, and 10 serous carcinomas of the ovary.

The use of immunohistochemistry in the diagnosis of composite and collision tumors: exemplified by pleural mesothelioma and carcinoid tumor of the lung.

A case of a collision lymph node metastasis of a mesothelioma and a carcinoid tumor in a 73-year-old man with a history of asbestos exposure is reported. An interesting finding in this case was that both the mesothelioma and its lymph node metastases exhibited a wide variety of histologic patterns, including one characterized by a solid growth of large cells with abundant, clear, and foamy cytoplasm and another exhibiting deciduoid features. Pathologists should be aware that mesotheliomas can present very unusual morphologic features, such as those seen in the present case, and therefore, should be included in the differential diagnosis of those tumors that can display similar morphology and can metastasize to the serosal membranes.

Deciduoid mesothelioma: report of 21 cases with review of the literature.

Deciduoid mesothelioma is a rare variant of epithelioid mesothelioma that was initially considered to occur exclusively in the peritoneum of young women who had no history of asbestos exposure and to be characterized by an aggressive clinical course, but it was later demonstrated that this tumor could also occur in the pleura of older men and women who had been exposed to asbestos. Some subsequent studies have also indicated that the clinical course is no different from that of conventional epithelioid mesothelioma. Herein are reported 21 cases of deciduoid mesothelioma that were investigated using a large panel of immunohistochemical markers, 9 of which were also studied by electron microscopy.