Highlights of the 14th international mesothelioma interest group meeting: Pathologic separation of benign from malignant mesothelial proliferations and histologic/molecular analysis of malignant mesothelioma subtypes

Objectives: The separation of benign from malignant mesothelial proliferations and exact subclassification of mesothelioma subtypes is crucial to determining patient care and prognosis but morphologically can be very difficult.Methods: This session of the 2018 IMIG meeting addressed these problems.Results: A new immunohistochemical marker, methylthioadenosine phosphorylase, was shown to correlate well with CDKN2A FISH and is cheaper and faster to run. A 117 gene expression panel also provided good separation on both tissue biopsy and cytology samples. Review of a series of mesotheliomas thought to be biphasic produced only a moderate level of agreement among expert pathologists with some cases being classified as purely epithelioid or sarcomatoid; these classifications had prognostic significance. The entity called transitional mesothelioma was found to behave exactly like sarcomatoid mesothelioma. RNA-seq analysis of a large series of mesotheliomas from a public database showed that, genetically, the morphologic breakdown into epithelioid, sarcomatoid, or biphasic mesotheliomas is artificial because there is a continuous spectrum of genomic changes. There are now criteria for the diagnosis of mesothelioma in situ and this is potentially important, since such cases might be curable.Conclusions: This session documented new morphological and molecular approaches to separating benign from malignant mesothelial proliferations and to subclassifying malignant mesoteheliomas in clinical relevant ways

Interobserver variation in the assessment of the sarcomatoid and transitional components in biphasic mesotheliomas

The percentage of sarcomatoid component has an impact on prognosis in patients with biphasic malignant pleural mesothelioma. Recent study showed that the transitional pattern similar to sarcomatoid component of malignant mesothelioma has negative prognostic significance. Practice guidelines recommend quantification of sarcomatoid component despite poor diagnostic reproducibility of biphasic mesothelioma among thoracic pathologists. The aim of this study was to determine the interobserver agreement in the quantification of sarcomatoid component, and in the diagnosis of a transitional component in the biphasic malignant mesothelioma. Thirteen experts in thoracic pathology reviewed the representative H&E and cytokeratin whole-slide images of the 54 biphasic mesotheliomas, without knowledge of BAP1 or p16 deletion status, and completed the survey of 25 questions. The overall interobserver agreement in the assessment of the percentage of the sarcomatoid component in 25% increments was good (wK = 0.62). Excellent agreement was present in 14 of 54 cases (26%), and 3 cases were unanimously scored. Excellent agreement was reached for the cases with 0-24% and > 75% of the sarcomatoid component.The most commonly used criteria for the diagnosis of sarcomatoid component were malignant spindle cells, frank sarcomatoid features and high N/C ratio. The overall interobserver agreement for transitional pattern was fair (wK = 0.40). Unanimous opinion about the absence of transitional pattern was observed in only one case. At least 70% agreement regarding the presence of transitional pattern was observed in 12 cases, with the rest of the cases showing a wide range of disagreement. Morphologic characteristics that favor transitional pattern over non-transitional include sheet-like growth of cohesive, plump, elongated epithelioid cells with well-defined cell borders and a tendency to transition into spindle cells. Our study defined precise morphologic criteria that may be used in the differential diagnosis between transitional pattern and other mesothelioma subtypes including sarcomatoid and epithelioid.status: publishe

Mesothelioma: scientific clues for prevention, diagnosis, and therapy

Mesothelioma affects mostly older individuals who have been occupationally exposed to asbestos. The global mesothelioma incidence and mortality rates are unknown, because data are not available from developing countries that continue to use large amounts of asbestos. The incidence rate of mesothelioma has decreased in Australia, the United States, and Western Europe, where the use of asbestos was banned or strictly regulated in the 1970s and 1980s, demonstrating the value of these preventive measures. However, in these same countries, the overall number of deaths from mesothelioma has not decreased as the size of the population and the percentage of old people have increased. Moreover, hotspots of mesothelioma may occur when carcinogenic fibers that are present in the environment are disturbed as rural areas are being developed. Novel immunohistochemical and molecular markers have improved the accuracy of diagnosis; however, about 14% (high-resource countries) to 50% (developing countries) of mesothelioma diagnoses are incorrect, resulting in inadequate treatment and complicating epidemiological studies. The discovery that germline BRCA1-asssociated protein 1 (BAP1) mutations cause mesothelioma and other cancers (BAP1 cancer syndrome) elucidated some of the key pathogenic mechanisms, and treatments targeting these molecular mechanisms and/or modulating the immune response are being tested. The role of surgery in pleural mesothelioma is controversial as it is difficult to predict who will benefit from aggressive management, even when local therapies are added to existing or novel systemic treatments. Treatment outcomes are improving, however, for peritoneal mesothelioma. Multidisciplinary international collaboration will be necessary to improve prevention, early detection, and treatment

Wholistic approach: Transcriptomic analysis and beyond using archival material for molecular diagnosis

International audienc