PURPOSE Infantile hemangiomas, the most prevalent benign tumor of infancy, have a predictable life cycle beginning with rapid proliferation followed by involution.  Though severe clinical consequences may occur, the etiology of hemangiomas is unknown.  With the discovery of endothelial progenitor cells and mesenchymal stem cells in infantile hemangiomas, we looked for pluripotent stem cells in these lesions.

METHOD Twelve surgical specimens from proliferative, involuting, and involuted lesions were examined by immunohistochemistry for stem cell marker, c-kit, pluripotency marker,Oct 4, and the primitive cell marker, CD133. Proliferative lesions underwent microdissection and cell culture.  The resulting cells were studied by immunocytochemistry and phosphatase enzymatic reactions.
RESULTS In all proliferative lesions, c-kit and Oct-4+ stem cells were found to reside in nests close to arterioles. These cells radiate outwards from the nest core in early proliferative lesions and further differentiate to cords of CD133+ cells with stem cell morphology which are c-kit and oct-4 negative. These cell populations were not seen in the involuting and involuted specimens. Histologically, both proliferative and involuting lesions exhibit areas of possible hematopoietic activity as demonstrated by immature erythrocytes and phenotypes of splenic-like cords and blood islands of bone marrow. In vitro, Oct-4 positive cells which exhibit phosphatatse activity were isolated.
CONCLUSION

This data shows that infantile hemangiomas contain islands of multipotent cells that may differentiate into areas of hematopoietic activity. A novel etiology for this tumor include  hemangioblasts, stem cells with both endothelial and hematopoietic potential, which may have embolized within a receptive mesenchyme to create an ectopic hematopoietic niche. In vitro studies will give us insight into the fate of these cells which may lead to safer, less invasive, and ultimately, more effective therapeutic options.