The smears show a population of highly atypical cells, which are likely malignant.

In a pleural effusion, the main differentials would be malignant mesothelioma vs metastatic carcinoma (most often adenocarcinoma). Some morphologic features that suggest mesothelioma include the cell groups with scalloped ('knobby') borders, the absence of marked nuclear pleomorphism and, in some areas, a suggestion of two-toned cytoplasm (seen in the air-dried smear). 

It would be good practice to look up the clinical details – imaging results, whether there is pleural nodularity or thickening, or a history of occupational or home exposure to asbestos. Also, previous history of known malignancy, or concurrent history of suspected malignancy should be sought.

A cell block should then be ordered, and some immunocytochemical stains employed to answer 2 questions:

1. Carcinoma vs Mesothelial cells

Suggested panel: EP4, MOC31, Tag72  vs Calretinin, WT1

TTF1 may be helpful as well, both serving to support adenocarcinoma  and suggest lung origin.   

2. Mesothelioma vs Reactive mesothelial cells (reactive atypia)

Suggested panel EMA (membrane staining), Desmin (negative in mesothelioma) 

Highly cellular smears show numerous moderately sized 3 dimensional clusters of atypical cells. The clusters exhibit scalloped borders. The cells contain moderately pleomorphic nuclei with relatively smooth nuclear membranes, prominent nucleoli and raise N/C ratios. The cytoplasm varies from fairly pale to dense, and in some areas, exhibits a two-toned appearance with a finely bubbly outer edge. The nuclei are fairly centrally located within the cells. Some cell-in-cell arrangements are noted. Windows are not readily identified. No definite population of benign mesothelial cells is seen.

Diagnosis: Left pleural effusion: Malignant mesothelioma 

Note: Being a relatively uncommon diagnosis in most areas, the first time diagnosis of malignant mesothelioma should be made in the context of clinicopathologic correlation (history, imaging) and with immunocytochemical corroboration.