July 2023 – Cytopathology and Pulmonary Pathology

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.

Figure 1

Which of the following histologic types of this tumor is associated with the worst overall prognosis?

  • Epithelioid
  • Sarcomatoid
  • Biphasic
  • Pulmonary enteric

The correct answer is ...


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


  1. Husain AN, Colby TV, Ordóñez NG, et al. Guidelines for Pathologic Diagnosis of Malignant Mesothelioma 2017 Update of the Consensus Statement from the International Mesothelioma Interest Group. Arch Patrol Lab Med. 2018;142(1):89-108. doi:10.5858/arpa.2017-0124-RA
  2. Saddoughi SA, Abdelsattar ZM, Blackmon SH. National trends in the epidemiology of malignant pleural mesothelioma: a National Cancer Data Base study. Ann Thorac Surg. 2018;105(2):432-437. doi:10.1016/j.athoracsur.2017.09.036
  3. Kinoshita Y, Hida T, Hamasaki M, et al. A combination of MTAP and BAP1 immunohistochemistry in pleural effusion cytology for the diagnosis of mesothelioma. Cancer Cytopathol. 2018;126(1):54-63. doi:10.1002/cncy.21928
  4. Marshall K, Jackson S, Jones J, et al. Homozygous deletion of CDKN2A in malignant mesothelioma: Diagnostic utility, patient characteristics and survival in a UK mesothelioma centre. Lung Cancer. 2020;150:195-200. doi:10.1016/j.lungcan.2020.10.020
  5. Hjerpe A, Ascoli V, Bedrossian C, Boon M, Creaney J, Davidson B, Dejmek A, Dobra K, Fassina A, Field A, Firat P, Kamei T, Kobayashi T, Michael CW, Önder S, Segal A, Vielh P. Guidelines for cytopathologic diagnosis of epithelioid and mixed type malignant mesothelioma. Complementary statement from the International Mesothelioma Interest Group, also endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology. Cytojournal. 2015 Nov 30;12:26. doi:10.4103/1742-6413.170726. PMID: 26681974; PMCID: PMC4678521.
  6. Scherpereel A, Opitz I, Berghmans T, et al. ERS/ESTS/EACTS/ESTRO guidelines for the management of malignant pleural mesothelioma. Eur Respir J. 2020;55(6):1900953. Published 2020 Jun 11. doi:10.1183/13993003.00953-2019

Aswath Padmanabhan Chandrasekar, M.B.B.S.

Resident, Anatomic & Clinical Pathology
Mayo Clinic

Melanie Bois, M.D.

Consultant, Anatomic Pathology
Mayo Clinic
Associate Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science

MCL Education

This post was developed by our Education and Technical Publications Team.