January 2007

Ask the Doctor:

Last year we reported the scientific information presented at the NIH meeting.  After presenting this information on our web site and in our newsletter many of you wrote to us with questions concerning the connection between the placenta and the development of a hemangioma.  Over the 10 years that NOVA has served as a resource to families affected by vascular anomalies no other single topic has caused so much confusion and distress to moms.  Recently this topic again surfaced and while those of us that serve as patient advocates have attempted to answer your questions there continues to be confusion on the conclusions of the recent studies.  I have taken the liberty of contacting a few of the authors of a recent journal article which discussed the role the placenta plays in the development of a hemangioma.

Dr. Steven Fishman and Dr. Carmen Barnes have graciously replied to these questions.

Thank you so much in taking the time to clarifying any misunderstandings that may have stemmed from our study.

Our findings show a striking similarity on the genes expressed by placental endothelial cells and hemangioma endothelial cells, that is not 100%, as pointed out by Steve.

These results, together with the immunohistochemical studies of Paula North, support two interpretations for the origin of the cell that gives rise to a hemangioma. The first possibility is that the tumor derives from an angioblast (an endothelial progenitor cell) from the placenta (not from a chunk of tissue), and the second is that the tumor derives from an angioblast that aberrantly differentiates to a placental phenotype (that means that although the cell did not originate in the placenta, it differentiated to look like one).

There are studies showing that more infants are born with hemangiomas after chorionic villi sampling or after pregnancies with placental complications; these studies support the interpretation of a placental origin. However, we still cannot unambiguously distinguish between these two interpretations, so further work is needed to determine which interpretation is correct.

Just as a final note, the cells in the placenta that show a similar immunophenotype to hemangioma endothelial cells are the fetal placental endothelial cells lining the chorionic villi. These villi are in the part of the placenta closest to maternal tissue, and are far from the surface of the placenta that is exposed to the infant (chorionic plate). Therefore, I would assume that they should be shielded from movements from the infant. Breakdown of placental vessels in chorionic villi appears to occur normally during pregnancy and is increased during placental complications. (This is supported by the work of Diane Biancci and coworkers which shows that fetal cells can be found in the mother's blood during normal pregnancies, and in higher numbers in pregnancies with placental complications.) Therefore, if the cells do derive from the placenta, it would seem more likely that they travel via the fetal blood stream from chorionic villi to the baby’s circulation via the umbilical cord. 

Carmine Barnes, PhD Harvard University Boston Children’s Hospital.

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I regret that this study in anyway is being interpreted by mothers that they might feel guilty about their placenta causing a problem in their child. He states, "it is of course the placenta that allowed their child to develop at all."

“Our study in PNAS indeed demonstrates remarkable similarity (not 100%) between the gene expression patterns of placenta and hemangioma. We could not definitively conclude from this data that the hemangioma actually physically came from the placenta. In fact, in the concluding paragraphs we state an alternative possibility in which the normal early cells forming the blood vessel system (angioblasts) may have developed into vessels more similar to placental vessels than to the local soft tissue vessels they were intended to become. If this is the case, they didn’t come from the placenta, but rather differentiated to look genetically similar to placenta. In the final sentence, we state that further studies would be necessary to develop a better understanding of the similarity between the hemangioma and placental tissue.”
Steven J. Fishman, MD

Reference:

Barnes, C., Huang, S., Kaipainen, A., Sanoudou, D., Chen, E. J., Eichler, G. S., Guo, Y., Yu, Y., Inger, E. E., Mulliken, J. M., Beggs, A. H., Folkman, J. & Fishman, S. J. (2005). Evidence by molecular profiling for a placental origin of infantile hemangioma. National Academy of Sciences, 102 (52), pp. 19097-19102.

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