By Patricia McAdams, Staff Writer, Nevus Outreach
Miguel Reyes-Múgica, MD
Long-time members of the Nevus Outreach family will recognize Miguel Reyes-Múgica, MD, as the recipient of the first Nevus Outreach research grant in 1998. Reyes, chief of pediatric pathology and director of laboratories at Children’s Hospital, University of Pittsburgh Medical Center, has long been dedicated to understanding large congenital melanocytic nevi (LCMN).
Ultimately, he is hoping to answer one key question, he says: “Once a patient with a nevus is born, what treatments other than surgery can we develop to improve his or her condition?”
Some details about Reyes’ research, including his epithelial-mesenchymal transition studies, were described earlier for readers in: Finding answers about LCMN.
But scientific research is exceedingly complex and involves looking for clues that might be lurking anywhere — at the cellular level or more broadly by simply looking at the statistics.
Reyes has recently joined hands with pediatrician Claudia Maria Salgado, MD, from the Federal University of Goiás, in Brazil. Salgado is now working alongside Reyes in Pittsburgh — not only as a postdoctoral research trainee in the Department of Pathology — but as his collaborator and, more recently, his wife. The pair attended the 2012 Nevus Outreach Conference in Texas this summer to talk about their work.
Findings from the Nevus Outreach registry
While Reyes’ studies are focused largely on cellular dynamics in LCMN, Salgado took on the tedious task of compiling data from the registry, which was begun in 1998, and includes information from 1003 nevus owners. Statistical studies help physicians to see patterns and associations not always discernable up close, so certain things become clear, such as which individuals may be more at risk to experience complications from LCMN.
For example, of the 1003 individuals with congenital nevi in the registry, 76 — or 7.6 percent — also have been diagnosed with neurocutaneous melanocytosis (NCM). In these patients, the risk of NCM was higher in those with a family history of congenital nevi, when they have many satellites and when their main nevus is located on the back. The registry also indicated that 35 individuals — or 3.5 percent — developed melanoma. The risk for developing melanoma increased with age and was higher when the individual has a family history of melanoma and the main nevus was located on an arm or leg.
While considerable information has been gleaned from this registry, Salgado noted a number of limitations. For instance, while many parents added their child to the registry at birth or soon after, they have added little information in the meantime and many entries are incomplete. Another problem is that variables noted are not clearly defined, or standardized, so the information provided is unclear.
Salgado suggested a number of ways to improve this registry, including defining variables and training interviewers to actively collect and input the data.
In addition to talking about a variety of laboratory studies related to the evolution of neural crest cells and the migration of melanocytes in an embryo, Reyes was pleased to tell Conferees that the paperwork was finally complete for the first ever Nevus Outreach Tissue Repository, which is to be housed at the Children’s Hospital in Pittsburgh. Reyes elaborated on this repository in between sessions. While very much appreciating the need for control, because human tissue is so precious, Reyes says we humans complicate things more than necessary.
“If someone from another planet were looking at us, they would wonder why we are trying to create all the obstacles possible.”
In fact, it took several years to go through this process at the University of Pittsburgh, which required a Material Transfer Agreement (MTA) and approval from the Institutional Review Board (IRB). The IRB is an ethics committee supervising the project to ensure that what Reyes is planning to do does not infringe into an ethical issue for the patient. The MTA protects the respective rights of the institutions both giving and receiving the tissue. Both the institutions giving and receiving the tissue need a MTA and approval of the IRB.
At this time, this formal agreement is in place only between the University of Pittsburgh and the University of Chicago. Pediatric plastic surgeon Bruce Bauer, MD, who practices in Chicago, operates on nevus patients on a routine basis and will be sharing tissue with Reyes starting this summer.
Reyes suggests that families who wish to share their child’s nevus tissue from future procedures with other surgeons please contact him, so he can provide some direction as to how samples be sent. Essentially, he says once tissue has been removed, it is usually kept in the Pathology Department.
“Parents can go in and request a second opinion,” says Reyes. “The institution must send the tissue for a second opinion. No research as such can be done on this tissue, but this process establishes an important first connection. From there, we can contact the physician, establish a collaboration, and begin the process of securing an MTA and IRB approval with that institution.”
Reyes looks forward to answering many questions once he has an opportunity to examine more of the tissue of individuals with LCMN and, especially, NCM, which is scarce and difficult to get. “We want to believe that the nevus in a patient with NCM — and without NCM — may be different, but we don’t know that yet.”
In summarizing the joint effort of all the researchers and clinicians present at the 2012 Conference, Reyes left families with one important take-away message: “I promise we are trying to do our best to contribute to advancing knowledge.”