Approximately one-third of families affected by pleuropulmonary blastoma manifest a number of dysplastic and/or neoplastic conditions comprising the Pleuropulmonary Blastoma Family Tumor and Dysplasia Syndrome. Germline mutations in the DICER1 gene are considered the major genetic determinant of the complex.[42,43] Importantly, while DICER1 mutations cause a wide range of phenotypes, pleuropulmonary blastoma does not occur in all families with DICER1 mutations; therefore, the term DICER1 syndrome is generally used for these families. Also, most mutation carriers are unaffected, indicating that tumor risk is modest.
A family history of cancer in close relatives has been noted for many young patients affected by this tumor.[44,45] In addition, pleuropulmonary blastoma has been reported in siblings.
There has been a reported association between pleuropulmonary blastoma and cystic nephroma, ciliary body medulloepithelioma of the eye, and primary ovarian neoplasms, particularly ovarian sex cord–stromal tumors.[43,47,48,49,50]
Clinical presentation and diagnostic evaluation
The tumor is usually located in the lung periphery, but it may be extrapulmonary with involvement of the heart/great vessels, mediastinum, diaphragm, and/or pleura.[51,52] The International Pleuropulmonary Blastoma Registry identified 11 cases of Type II and Type III pleuropulmonary blastoma with tumor extension into the thoracic great vessels or the heart. Radiographic evaluation of the central circulation should be performed in children with suspected or diagnosed pleuropulmonary blastoma to identify potentially fatal embolic complications.
Achieving total resection of the tumor at any time during treatment is associated with improved prognosis. The tumors may recur or metastasize, in spite of primary resection.[38,41] The cerebral parenchyma is the most common metastatic site.
Responses to chemotherapy have been reported with agents similar to those used for the treatment of rhabdomyosarcoma, and adjuvant chemotherapy may benefit patients with Type I pleuropulmonary blastoma by reducing the risk of recurrence.[40,54] Chemotherapeutic agents may include vincristine, cyclophosphamide, dactinomycin, doxorubicin, and irinotecan.[55,56] Data from the International Pleuropulmonary Blastoma Registry suggest that adjuvant chemotherapy may reduce the risk of recurrence.