Which of the following is NOT included in the IHC panel for primary soft tissue small round neoplasms?

• A. Leukocyte Common Antigen
• B. S100 Protein
• C. Neuron-Specific Enolase
• D. Synaptophysin

Answer: (B)

In distinguishing primary soft tissue small round cell neoplasms, the immunohistochemistry approach focuses on identifying lineage-specific markers to separate likely origins and exclude mimics. Leukocyte common antigen (CD45) is included to rule out lymphoid neoplasms, since its presence would point toward a hematopoietic origin rather than a soft tissue sarcoma. Neuron-specific enolase and synaptophysin are used because many of these tumors show neural or neuroendocrine features, so staining for these helps support a neural/neuronal differentiation pattern.

S100 protein, while useful for neural crest–derived tumors and melanocytic lesions, isn’t routinely part of the initial panel for these small round blue cell tumors because its expression is less specific and can be variable across the spectrum of soft tissue neoplasms. This variability can muddy the diagnostic signal, making S100 a less reliable discriminator in this context. Therefore, it’s not included in the standard panel for evaluating primary soft tissue small round neoplasms.