Pleuropulmonary blastoma, a relatively recently recognized childhood malignancy, is an embryonal tumor of the lung, pleura, or mediastinum derived from the thoracic splanchnopleural or somatopleural mesoderm. Although uncommon (both benign and malignant primary lung tumors are rare in childhood), pleuropulmonary blastoma is actually one of the more common primary lung tumors of childhood. It usually presents as a cystic or solid peripheral pulmonary mass in infancy or early childhood, generally before age 3 and almost always before age 12. In some children there are multiple or bilateral cystic lesions. As with other embryonal tumors, rare cases have been reported in adults.

Pleuropulmonary blastoma has a spectrum of differentiation, ranging from low-grade cystic (type I), to partially cystic (type II), to solid tumors (type III). It is distinguished from adult pulmonary blastoma (which may also rarely occur in childhood) by the exclusively stromal nature of the malignant component in pleuropulmonary blastoma. This malignant component may be present as blastemal tissue or mesenchymal sarcomatous changes.

Grossly, the low-grade cystic lesions often protrude from the pleura surface and are largely covered by pleura. They have often been simply amputated at surgery with only a small pedicle of the underlying lobe attached under the mistaken impression that they are benign developmental cystic lesions. This type is exclusively cystic, without any solid regions or nodules. The intermediate or partially cystic lesions are a mixture of cystic and solid components. The high-grade lesions are solid tumors with occasional foci of cystic degeneration related to hemorrhage and necrosis.

The low-grade cystic lesions may be cured by surgery alone but should be followed closely because there have been local recurrences in this setting, and chemotherapy may be recommended for this reason. Higher-grade lesions certainly require chemotherapy following surgery. Local recurrence or metastases are seen in about one-half of cases, with local recurrence being more common. Metastases occur late in the disease course and are more common in the brain and bone, although other sites have rarely been described. The recurrent lesion may be of a higher grade than the initial lesion. For example, low-grade cystic lesions that are incompletely excised or are followed over an extended period of time without surgical excision may become higher-grade lesions.

It is important to differentiate the low-grade lesions both grossly and histologically from the large cyst type of cystic adenomatoid malformation. Grossly, the low-grade lesions usually present as cystic lesions extending beyond the pleural surface, a quite unusual presentation for cystic adenomatoid malformation, which generally remains within the lobar confines. The low-grade cystic lesions largely account for the multiple reports of sarcomas arising in cystic adenomatoid malformations. Low-grade cystic pleuropulmonary blastoma has been confused with large cyst type cystic adenomatoid malformation (Stocker CCAM type I) and the so-called peripheral cyst type cystic adenomatoid malformation (Stocker CCAM type IV), particularly when the stromal malignant component is relatively minor. The trabeculae in low-grade cystic pleuropulmonary blastoma have a quite different appearance from those seen in large cyst type cystic adenomatoid malformation, being thicker with distinctive larger vessels present centrally and immature-appearing spindled cells forming a cambium-like
layer in the cyst walls. The higher-grade lesions have been diagnosed previously as rhabdomyosarcoma. It is likely that most, if not all, rhabdomyosarcoma primary to the lung is the solid variant of pleuropulmonary blastoma. The lesion known as mesenchymal hamartoma of the lung likely also belongs in the spectrum of pleuropulmonary blastoma.

Cytogenetic analysis of some pleuropulmonary blastomas has shown a variety of abnormalities, including trisomy 8, trisomy 2, and 17p deletions, as well as frequent occurrence of p53 mutations. Pleuropulmonary blastoma is associated with other embryonal tumors; cystic renal disease, both concurrently and preceding or following the development of pleuropulmonary blastoma in the patient and in other family members; and certain adult tumors.