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Updated: Aug 9, 2026
Analysis of Microglia and Monocyte-derived Macrophages from the Central Nervous System by Flow Cytometry
Published on: June 22, 2017
CD31 expression in intratumoral macrophages: a potential diagnostic pitfall
J K McKenney1, S W Weiss, A L Folpe
1Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Abstract:
CD31 (platelet endothelial adhesion molecule, PECAM-1) is generally regarded to be the most sensitive and specific endothelial marker in paraffin sections. We have recently encountered several cases in which intratumoral CD31-positive macrophages were misinterpreted as evidence of a vascular sarcoma. We therefore reviewed our last 1950 consultation cases with respect to cases in which CD31 immunostains were performed, to determine the frequency of CD31 expression in macrophages in formalin-fixed, paraffin-embedded tissue and how often the presence of these cells was a source of diagnostic confusion. CD31 immunohistochemistry had been performed on 59 of 1950 (3%) of cases. These 59 cases consisted of both vascular (20 cases) and nonvascular tumors (39 cases). CD31-positive macrophages were distinguished from endothelial or tumor cells by correlation with the morphologic features and the immunohistochemical staining pattern of the cells of interest. In no case was CD31 positivity seen in the lesional cells of a nonvascular tumor. CD31-positive macrophages were identified in 48 of 59 (81%) cases. CD31-positive macrophages were present in 34 of 39 (87%) nonvascular tumors. A vascular tumor was diagnosed or favored by the referring pathologist in 15 of these 39 cases (38%). In 14 of these 15 cases CD31 immunostains were performed by the referring pathologist; 13 (93%) showed CD31-positive macrophages. In 4 of these 14 cases (29%) the misdiagnosis of a vascular tumor was based primarily or in part on the misinterpretation of CD31-positive macrophages as tumor cells. In all cases with CD34 and CD68 immunostains, the CD31-positive macrophages were CD34 negative and CD68 positive. We conclude that CD31 expression is very common in macrophages. Misinterpretation of CD31-positive macrophages as tumor cells may result in the erroneous diagnosis of a primary vascular neoplasm. Recognition of the characteristic granular, membranous pattern of CD31 expression in macrophages and careful distinction from tumor cells should allow the accurate interpretation of CD31 immunohistochemistry in possible vascular neoplasms. CD31 may also be useful as a nonlysosomal marker of macrophages in formalin-fixed, paraffin-embedded sections.
Insights
CD31 (platelet endothelial adhesion molecule) is commonly found in macrophages, not just endothelial cells. Misinterpreting CD31-positive macrophages can lead to incorrect vascular tumor diagnoses.
Area of Science:
- Immunohistochemistry
- Pathology
- Oncology
Background:
- CD31 (platelet endothelial adhesion molecule, PECAM-1) is a standard endothelial marker.
- Intratumoral CD31-positive macrophages have been mistaken for vascular sarcoma.
- Diagnostic confusion can arise from CD31 expression in non-endothelial cells.
Purpose of the Study:
- To determine the frequency of CD31 expression in macrophages in formalin-fixed, paraffin-embedded tissues.
- To assess how often CD31-positive macrophages cause diagnostic confusion, particularly regarding vascular tumors.
- To evaluate CD31 as a potential macrophage marker.
Main Methods:
- Reviewed 1950 consultation cases, focusing on 59 cases with CD31 immunostains.
- Analyzed CD31 expression in vascular and nonvascular tumors, correlating with morphology and other markers (CD34, CD68).
- Distinguished CD31-positive macrophages from endothelial cells and tumor cells.
Main Results:
- CD31-positive macrophages were identified in 81% of cases (48/59), including 87% of nonvascular tumors (34/39).
- Misinterpretation of CD31-positive macrophages led to erroneous vascular tumor diagnoses in 29% of relevant cases (4/14).
- CD31-positive macrophages were consistently CD34-negative and CD68-positive.
Conclusions:
- CD31 expression is frequent in macrophages, not exclusive to endothelial cells.
- Misidentification of CD31-positive macrophages can result in false diagnoses of primary vascular neoplasms.
- Recognizing the distinct staining pattern of CD31 in macrophages is crucial for accurate diagnosis; CD31 may serve as a macrophage marker.
