The 2015 World Health Organization Classification of Tumors of the Pleura: Advances since the 2004 Classification

Abstract

A new World Health Organization (WHO) Classification of Tumors of the Pleura has recently been published. While the histologic classification of pleural malignant mesothelioma remains the same in the 2015 WHO classification as it was in the 2004 classification, multiple new observations have been recorded. First, more detailed study has been performed of histologic subtyping of epithelioid mesothelioma. In particular, it has been recognized that the pleomorphic subtype is associated with a poor prognosis, similar to that of sarcomatoid malignant mesothelioma. Second, there is improved understanding of the role of immunohistochemistry in distinguishing mesothelioma from carcinomas of various sites. Third, the criteria for distinguishing malignant mesothelioma from reactive mesothelial proliferations has been further refined. Fourth, additional studies of sarcomatoid mesothelioma have defined the frequency and spectrum of various histologic and immunohistochemical features, including heterologous elements. Finally, pleural well-differentiated papillary mesotheliomas are better defined and cases with invasive foci are recognized. In addition, several promising observations in mesothelioma pathology and genetics have been made in the past decade. These are now the subject of further investigation to determine if they can be validated in ways that will significantly impact clinical practice. These include a preliminary study of grading, suggesting that nuclear atypia and mitotic count are independent prognostic markers. The discovery of inactivating mutations in the BRCA1-associated protein 1 gene in sporadic and hereditary mesothelioma has opened up a variety of novel molecular, clinical, and diagnostic investigations. One possible diagnostic application includes the setting of separating mesothelioma from reactive mesothelial proliferations, where it may play a role in conjunction with p16 FISH. Another useful discovery was that the NAB2-STAT6 fusion is characteristic of solitary fibrous tumors. This led to development of a STAT6 antibody that is a reliable immunohistochemical marker for solitary fibrous tumors. Genetic studies also led to the finding that WWTR1-CAMTA1 fusions are useful diagnostic markers for epithelioid hemangioendotheliomas, which can present as pleural-based masses. Finally, desmoid type fibromatosis, a locally aggressive tumor that can present in the pleura, has been shown to frequently have CTNNB1 gene mutations and express β-catenin by immunohistochemistry.

A massive pleural‐based desmoid tumour

“…Genetic mutations (e.g. that of CTNNB1 gene) which activate β-catenin are common [3]. Some (5-15%) cases may be associated with FAP due to mutations in the APC gene on chromosome 5q21-q22 [4].…”

The pathological and molecular diagnosis of malignant pleural mesothelioma: a literature review

“…The application of immunocytochemistry (ICC) and molecular methods, such as fluorescent in situ hybridization (FISH) performed preferentially on cell blocks, increases the diagnostic accuracy of cytology (13)(14)(15)(16). The differential diagnosis of MPM and the use of ICC and molecular markers in cytological samples are the same as in histological specimens.…”

Increased micronucleus count predicts malignant behavior in pleural e usion uid

“…Although cases with prominent benign or malignant morphology are far from a diagnostic challenge, suspicious cases are often problematic. There is no definite method for differential diagnosis (10). The most important part of this study was exploring the role of MN scoring in suspicious cases.…”