Progression of Sarcomatoid Mesothelioma from Mesothelioma In Situ: A Case Report on Morphologic Changes during a Nine-month Interval and Careful Observation of Cytology in Early- stage Mesothelioma

Abstract

Background: It had been difficult to distinguish between reactive and malignant conditions due to overlapping morphological characteristics. The development of methods based on detecting genomic abnormalities using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) have contributed greatly to solving this problem. In order to lead it to efficient IHC and/or FISH and final diagnosis of mesothelioma, it is important to pick up bland mesothelioma cells on cytological screening because the first clinical manifestation of pleural mesothelioma (PM) is pleural effusion, which is first sample available for pathological diagnosis.Case presentation: This report describes a case of a 72-year-old man with a history of asbestos exposure presented with pleural effusion as first symptoms and was eventually diagnosed as mesothelioma. He was suspected for mesothelioma on cytology due to prominent cell-in-cell engulfment in mesothelial cells, and the diagnosis of mesothelioma in situ was confirmed by histology. Unexpectedly, the lesion progressed to sarcomatoid mesothelioma with 9 months interval. Both the initial mesothelioma in situ and invasive lesion showed immunohistochemical loss of methylthioadenosine phosphorylase (MTAP) and homozygous deletion of cyclin dependent kinase inhibitor 2A (CDKN2A) on fluorescence in situ hybridization. The patient received medication therapy after the diagnosis of sarcomatoid mesothelioma, but the disease progressed and died 12 months after the diagnosis of sarcomatoid mesothelioma.Conclusion: Our case suggests that cell-in-cell engulfment can be conspicuous in early-stage mesothelioma with inconspicuous nuclear atypia and few multinucleated cells. In addition, the presence of MTAP loss and CDKN2A homozygous deletion are suspected to be involved in early progression to invasive lesions and/or sarcomatoid changes. Although interest in and knowledge regarding mesothelioma in situ has been increasing, some diagnostic problems can be challenging even for experts. In our opinion, it is important to consider genetic abnormalities when deciding on individual patient management. At least, we believe that cases of mesothelioma, even if in situ lesion, with MTAP loss and/or CDKN2A deletion should be performed carefully followed up or early treatment intervention.