What is the significance of tumor cells staining positive for CD31 (Cluster of Differentiation 31) in a biopsy?

Significance of CD31-Positive Tumor Cells in Biopsy

CD31-positive tumor cells in a biopsy strongly suggest vascular differentiation and most likely indicate a vascular neoplasm such as angiosarcoma, though careful interpretation is required to avoid diagnostic pitfalls.

Understanding CD31 Expression

CD31 (also known as PECAM-1, Platelet Endothelial Cell Adhesion Molecule-1) is widely recognized as a highly sensitive and specific marker for endothelial differentiation in histopathological evaluation. Its significance in tumor cells includes:

Primary Diagnostic Implications

• Vascular Neoplasm Indicator: CD31 positivity in tumor cells strongly suggests endothelial differentiation and is a key diagnostic marker for vascular tumors 1
• Angiosarcoma Diagnosis: Particularly important in diagnosing angiosarcomas, where most tumor cells show strong constitutive expression of CD31 2
• Differential Diagnosis: Helps distinguish vascular tumors from other malignancies, as CD31 reactivity in carcinomas and mesotheliomas is extremely rare (only 7 of 290 cases in one study) 3

Prognostic Significance

• Heterogeneous Expression: In angiosarcomas, varying levels of CD31 expression may exist within the same tumor, with CD31-low populations showing:
  • More aggressive behavior
  • Greater chemoresistance
  • Loss of endothelial differentiation
  • Enhanced survival mechanisms through YAP signaling 2

Diagnostic Considerations and Pitfalls

Potential Misinterpretation

• CD31-Positive Macrophages: A major diagnostic pitfall is misinterpreting CD31-positive macrophages as tumor cells, which can lead to erroneous diagnosis of vascular neoplasms 4
• Distinguishing Features: CD31-positive macrophages typically show:
  • Granular, membranous staining pattern
  • CD34 negativity
  • CD68 positivity 4

Recommended Approach to Interpretation

1. Correlate with Morphology: Always interpret CD31 staining in conjunction with H&E morphology
2. Use Additional Markers: Employ a panel of markers including:
   • CD34 (another vascular marker)
   • CD68 (to identify macrophages)
   • Other lineage-specific markers to exclude non-vascular tumors 1
3. Consider Tissue Context: CD31 expression in small round cell tumors is uncommon but possible (seen in 4 of 85 ES/PNET cases) 5

Clinical Management Implications

• Therapeutic Targeting: Understanding CD31 expression patterns may guide treatment approaches, particularly in angiosarcomas
• Chemoresistance: CD31-low tumor cell populations show greater resistance to conventional chemotherapy 2
• Combination Therapy: For tumors with heterogeneous CD31 expression, combination therapies targeting YAP signaling (e.g., pazopanib) with conventional chemotherapy (e.g., doxorubicin) may overcome resistance 2

Conclusion for Clinical Practice

When encountering CD31-positive tumor cells in a biopsy:

1. Consider vascular neoplasm as the primary diagnosis
2. Rule out CD31-positive macrophages using additional markers
3. Assess for heterogeneity in CD31 expression, which may have prognostic implications
4. Include additional immunohistochemical markers to confirm endothelial differentiation
5. Consider the rare possibility of CD31 expression in non-vascular tumors

This approach will help ensure accurate diagnosis and appropriate clinical management of patients with CD31-positive tumors.