An 82-year-old man with a history of smoking and asbestos exposure presented with recurrent large pleural effusions that were historically negative by cytologic examination. PET-CT revealed a new large pleural effusion associated with moderately avid pleural thickening. Repeat thoracentesis was performed.
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Mesothelioma is a rare and aggressive malignancy of the pleura that is strongly associated with asbestos exposure. Currently, per the WHO 2021 classification, mesothelioma can be subtyped into epithelioid, biphasic, and sarcomatoid variants. The histological subtype of the tumor is the best pathological indicator of overall prognosis,1 and of these subtypes, the sarcomatoid variant is associated with the worst overall prognosis.2
The diagnosis of mesothelioma in pleural effusions has been augmented greatly with ancillary testing. Immunohistochemistry for BRCA1-associated protein 1 (BAP1) and methylthioadenosine phosphorylase (MTAP) are highly specific and reliably differentiate mesothelioma from reactive mesothelial cells. The expected staining pattern in malignancy (as illustrated in this case) is a loss of protein expression with retained expression in internal controls (Figure 1, panel C).3 p16 fluorescence in situ hybridization testing for deletions of CDKN2A can also be utilized to establish the diagnosis.4 Given their variable sensitivity, it is currently recommended to use multiple immunohistochemical markers to establish mesothelial lineage.
The majority of mesothelioma diagnosed via effusion cytology are epithelioid in histologic type.5 As such, pleural biopsy remains the primary diagnostic modality for the sarcomatoid variant.6
Aswath Padmanabhan Chandrasekar, M.B.B.S.
Resident, Anatomic & Clinical Pathology
Melanie Bois, M.D.
Consultant, Anatomic Pathology
Associate Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science