Microscopic description and IHC:

The cytospin slides (Diff Quik and Pap stains) and cell block section appear hypercellular with many large 3-dimentional clusters of cells with scalloped contours. The overall cytologic atypia is mild.

The cells are positive for Calretinin and WT1, and negative for Ber-EP4, confirming the mesothelial origin. GATA3 is positive in scattered inflammatory cells and negative in the cells of interest.

BAP1 is intact in the mesothelial cells.

FISH study show loss of CDKN2A (9p21 or p16).

Discussion:

Metastatic breast cancer was considered initially due to the presence of many large 3D cell clusters, but excluded by the immunoprofile.

Distinguishing reactive mesothelial cells from malignant mesothelioma is challenging, probably impossible on cytology specimen.

A clinical history of asbestos exposure, pleural thickening, and unilateral pleural effusion along with an atypical population of mesothelial cells would raise the concern.

This case was originally signed out as “Atypical Mesothelial Cells” due to lack of the previously mentioned clinical history and the specimen was sent for ancillary testing.

It has been reported that ancillary testing can be helpful in differentiating malignant from reactive mesothelial cells.

Hwang et. al. reported BAP1 immunohistochemistry and p16 FISH as reliable markers for malignant mesothelioma in cytology specimens.
  • BAP1 is a tumor suppressor gene that is lost in malignant mesotheliomas; however, intact BAP1 staining does not exclude malignant mesothelioma.
  • P16 (CDK2NA) is a cell cycle suppressor and is deleted in malignant mesotheliomas.
  • Loss of BAP1 and/ or p16 has not been demonstrated in benign/reactive mesothelial cells.

This patient’s specimen showed intact BAP1 and loss of p16, supporting a diagnosis of malignant mesothelioma. Follow up revealed left pleural thickening by CT at an outside hospital and the diagnosis of mesothelioma was made by surgical biopsy with the presence of tissue invasion.

References:

Cibas, E. S., & Ducatman, B. S. (2014). Cytology: diagnostic principles and clinical correlates. Philadelphia, PA: Elsevier/Saunders.

Hwang HC, Sheffield BS, Rodriguez S et al. Utility of BAP1 Immunohistochemistry and p16 (CDKN2A) FISH in the Diagnosis of Malignant Mesothelioma in Effusion Cytology Specimens. Am J Surg Pathol. 2016;40(1):120-6.

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