Sarcomatoid mesothelioma originating from mesothelioma in situ: are methylthioadenosine phosphorylase loss and CDKN2A homozygous deletion poor prognostic factors for preinvasive mesothelioma?

The diagnosis of mesothelioma in situ (MIS) is challenging with conventional diagnostic approaches. Although recent advances in genomic-based assays have made it possible to diagnose MIS, the prognosis, treatment indications, and prognostic factors remain unclear. Previous reports have shown that MIS progresses to invasive mesothelioma; however, to the best of our knowledge, progression to sarcomatoid mesothelioma has not yet been reported. A 73-year-old man was diagnosed with MIS associated with methylthioadenosine phosphorylase (MTAP) loss and a CDKN2A homozygous deletion. Strikingly, pathological examination revealed that the MIS lesion had progressed to sarcomatoid mesothelioma. In analyses of previously reported cases and our case, MIS with a CDKN2A homozygous deletion or MTAP loss progressed to invasive mesothelioma earlier than that without them, indicating that a CDKN2A homozygous deletion and MTAP loss could be poor prognostic factors. Genomic analyses might be useful for predicting the prognosis of MIS and contributing to an optimal treatment.