Research News: Discovering Pleuropulmonary Blastoma
Louis Dehner, MD, and his colleagues at the University of Minnesota first described pleuropulmonary blastoma (PPB) in a 1988 paper published in Cancer. In that article, the researchers proposed that PPB was a unique pulmonary neoplasm in children that began as a multicystic structure in the lung. Further, the tumors presented as predominantly cystic structures during the first year of life, but over a period of three to four years underwent a progression to a high-grade, multipatterned sarcoma.
“Up until that time, most cysts that appeared in infants’ lungs were diagnosed as congenital cystic adenomatoid malformations (CCAMs),” explains Dr. Dehner, who since 1989 has served as a pediatric pathologist at St. Louis Children’s Hospital and as a professor of pathology and immunology and of pediatric pathology at Washington University School of Medicine. “What we observed in our original study was that some of these children would come back after that initial diagnosis with a high-grade, malignant neoplasm in the same lobe of the lung, or at least in the same side in which the previous congenital cystic lesion was diagnosed. We also observed that there was an intermediate stage in which we could still recognize remnants of the original cyst, but the remainder of the tumor was replaced by this solid sarcoma.”
The discovery of PPB brought about a revolutionary change in how infants with lung cysts were diagnosed and received treatment.
“The immediate impact was that physicians could no longer view all cystic lung lesions in infants—either symptomatic or asymptomatic—as cystic adenomatoid malformations that—aside from their local manifestations of creating or being associated with respiratory distress— were basically no harm, no foul situations,” says Dr. Dehner. “We know now that when PPB is identified and treated in its cystic stage in infancy, patient survival is nearly 100 percent. In contrast, when these tumors are allowed to progress to the solid, high-grade sarcoma stage when patients are 2 to 5 years of age, the survival rate drops to 40 percent.”
In 1996, research reported by Dr. Dehner and his colleagues in the Journal of Pediatrics showed a familial disposition for developing PPB. In 2008 in the American Journal of Surgical Pathology, they described PPB lesions in older children that do not develop into a malignant tumor but rather undergo spontaneous regression.
“A recent important discovery in regard to this disease is its connection to the DICER1 gene mutation, which appears in 30 to 40 percent of PPB cases,” says Dr. Dehner. “This mutation has implications for other family members of a patient with PPB since they may also carry the DICER1 mutation and be at risk for developing associated tumors. We now know it is of great importance for any patient diagnosed with PPB to undergo DICER1 gene mutation testing.”
While research into PPB continues, the work done by Dr. Dehner, his colleagues and researchers throughout the world has resulted in a better understanding of what can develop into a deadly disease. There now exists the International Pleuropulmonary Blastoma Registry (ppbregistry.org) that is helping to document PPB cases and offers information on the disease for families and physicians. Dr. Dehner was instrumental in developing the registry and serves as one of its lead pathologists, having reviewed the majority of the more than 350 cases currently registered. He will report on those cases at the annual Pediatric Pathology meeting in March 2012.
“The initial description of PPB and subsequent discoveries about the disease have been the defining arc of my research career,” says Dr. Dehner. “Our initial discoveries filled an important niche in identifying an embryonic-type tumor in the lung that was comparable to that of the neuroblastoma. From that scientific discovery we have helped save the lives of hundreds of patients through correct diagnosis and treatment of PPB.”