ES17.04 Updates in Mesothelioma

Abstract

The histologic subtype of malignant mesothelioma of the pleura has an impact on prognosis and treatment decisions and therefore has to be documented in diagnostic pathology reports. Epithelioid morphology is associated with a better prognosis when compared to sarcomatoid and biphasic subtypes. Surgical treatment may also have a prognostic impact in epithelioid subtype, while the same benefit is not seen in biphasic and sarcomatoid mesotheliomas. The 2020/21 WHO classification divides mesothelial proliferations into benign and preinvasive (adenomatoid tumor, well-differentiated papillary mesothelial tumor, mesothelioma in situ) and mesothelioma (localized pleural mesothelioma, diffuse pleural mesothelioma). The main change is the introduction of mesothelioma in situ (MIS) in the classification. Until recently the consensus was that MIS cannot be separated from reactive surface mesothelial proliferations on morphology alone. However, the concept of MIS was recently reintroduced for surface, usually flat or simple papillary, mesothelial proliferations with loss of BAP1 nuclear staining by immunohistochemistry or CDKN2A homozygous deletion, in the absence of radiologic or clinical gross evidence of the disease.1-3 Clinically, MIS is suspected in patients with unexplained recurrent effusions in the setting of heavy asbestos exposure, after irradiation and in patients with familial predisposition. The diagnosis requires sufficient tissue usually large biopsy samples. Small biopsy and cytology samples are not appropriate. Patients with MIS have a high incidence of eventual development of invasive mesothelioma. The updated classification of epithelioid mesotheliomas includes architectural patterns (tubular, papillary, tubulopapillary, trabecular, solid, adenomatoid and microcystic), stromal (myxoid) and cytologic (pleomorphic ,rhabdoid, deciduoid, small cell, clear cell, signet ring) features. Their identification is important for correct diagnosis, and some have prognostic values. Two cytologic features, transitional and pleomorphic, were previously classified as epithelioid patterns. They have shown a similar survival to biphasic and sarcomatoid mesothelioma and should be reclassified.5-8 Transitional features have appearance between epithelioid and sarcomatoid morphology, and have genomic characteristics similar to sarcomatoid subtype, and therefore were reclassified as cytologic feature of sarcomatoid mesothelioma. 6. Epithelioid mesotheliomas with transitional features should be reclassified as biphasic mesothelioma. Transitional features within biphasic mesothelioma carry negative prognostic significance, with a median survival of 6 months for cases with transitional features compared to 12 months for those without transitional features .6 Pleomorphic features, as described in epithelioid mesothelioma, can also be seen in sarcomatoid mesotheliomas. In contrast to transitional features, emerging genomic data suggest that a mesothelioma with pleomorphic features genomically can cluster with either sarcomatoid or epithelioid subtypes. Therefore, mesotheliomas with pleomorphic features should be classified based on the most predominant morphology as either sarcomatoid or epithelioid. A two-tier grading system for epithelioid mesothelioma allows the identification of more aggressive mesotheliomas and can be applied to biopsy and resection specimens 9, 10 It is primarily based on the combination of nuclear features, mitotic rate and the presence or absence of necrosis (Figure 1). Molecular testing in mesothelioma compared to other cancers is very limited. Recently, there have been several sequencing efforts to provide insights into the genomic characteristics and improved prognostic classification of mesothelioma. 10