The cells with signet ring morphology are negative for the epithelial marker EP4 and the mesothelial marker WT1. A small group of WT1-positive mesothelial cells is seen. CD163 highlights numerous cells with signet ring cell morphology. 

In body cavity fluid samples, the differential diagnoses for cells with signet ring morphology include: 

• Metastatic adenocarcinoma with signet ring cell morphology 
• Macrophages 
• Mesothelial cells 

The most helpful morphological features are the nuclei – significant nuclear abnormalities can be seen in adenocarcinoma (hyperchromatic or irregular nuclei with prominent nucleoli) as well as the nature of the cytoplasm (finely bubbly, pinkish in alcohol-stained smears, or containing a small mucin droplet in adenocarcinoma). When the cells contain water as a result of degenerative changes (e.g. in macrophages and mesothelial cells), the vacuole appears clear and empty as seen in this case. 

A panel of immunostains will provide the answer as shown above. 

The diagnosis is negative: No malignant cells seen. The cells with signet ring morphology are macrophages (CD163-positive, EP4- and WT1-negative). Picture 1 shows the Case of the Month, while picture 2 shows the cell block of a signet ring cell adenocarcinoma. Compare the nuclear and cytoplasmic features.