Pleuropulmonary blastoma

Definition

A malignant sarcomatous tumour of infancy/early childhood arising in the lung or rarely from the parietal pleura2,7. This tumour is the pulmonary equivalent of other tumours that arise during organ development, such as Wilm's tumour, neuroblastoma, hepatoblastoma and retinoblastoma17.

Synonyms

Pleuropulmonary blastoma	arising in	congenital cystic adenomatoid malformation2,4,5
Rhabdomyosarcoma		mesenchymal cystic hamartoma
Pulmonary sarcoma		congenital bronchogenic cyst2
Embryonal sarcoma
Pulmonary blastoma of childhood

Epidemiology

About 100 cases are recorded by the pleuropulmonary blastoma registry. Pleuropulmonary blastoma occurs in children up to 12 years of age21, usually by the age of 4 years, with a median age of 2 years3,4,5,15. Type I tumours occur in the youngest children, type III in the oldest17. 25% of cases are associated with a familial cancer syndrome and children may also develop lung "cysts", cystic nephroma6, ovarian teratoma8, rhabdomyosarcoma or intestinal polyps10. Prophylactic resection of congenital lung cysts is recommended20, despite which pleuropulmonary blastoma may develop14. Children related to a proband may develop lung cysts25.

Clinical features

In infancy, presentation is often with respiratory distress4,17. Children develop fever17, chest pain and cough18.

Radiology

There are unilateral, often multiple25, less often bilateral10,12,25, pulmonary cysts17. Intracystic masses or septal thickening militate against a diagnosis of congenital adenomatoid malformation. There may be a pneumothorax. Cysts may be apparent in utero by ultrasound25.

Macroscopic appearances

There are three subtypes, with evidence that progression occurs from type I to type II to type III:

I, purely cystic: the multilocular cysts have thin walls. The median age of presentation is 9 months25.
II, cystic and solid. The median age of presentation is 36 months.
III, purely solid: the solid areas are gelatinous and white, sometimes haemorrhagic. They may be massive, occupying an entire lobe or lung. The median age of presentation is 42 months.

Histopathology

Type I: the multiple cysts are lined by benign respiratory type epithelium underlain by malignant cells forming a cambium layer. The latter consists of small cells and may show rhabdomyoblastic differentiation. There may be small nodules of mature fibroblasts, fetal cartilage or hyalinised stroma25. A minority of cases show nodules of cells with a high N/C ratio25. In the transition to type II, a sarcomatous component begins to overgrow the septa.
Type II: the septal stroma is overgrown by sheets of small primitive cells. These may show rhabdomyoblastic differentiation or be undifferentiated.
Type III and solid areas of type II: there are mixed blastematous and sarcomatous appearances2, consisting of nodules of malignant cartilage, anaplastic and pleomorphic cells, rhabdomyosarcomatous foci11,16 and blastema-like areas. There are variable foci of haemorrhage, necrosis and fibrosis. There may be an entrapped bland epithelial component11.

Immunohistochemistry

	Cytokeratins	epithelial component lining cysts or entrapped within solid areas0
	Vimentin	positive in mesenchymal component0,23
	Muscle-specific actin	rhabdomyosarcomatous component, less often in the small cell cambium layer0
	Desmin	rhabdomyosarcomatous component, less often in the small cell cambium layer0, positive in scattered primitive mesenchymal cells, in the cambium layer and in cells with overt skeletal muscle differentiation25.
	S-100	cartilaginous nodules0,23
	Myoglobin	1/123
	Myogenin and MyoD1	scattered positive cells25
	Ki-67 shows a variable proliferation index, up to 90% within the cambium layer25

Cytogenetics

There are several reports of gains in chromosome 81,13,19, specifically within the mesenchymal elements21. p53 mutations are common9.

Differential diagnosis

Pulmonary blastoma: there is a malignant epithelial element.
Cystic synovial sarcoma: positive for EMA, CD99 and cytokeratins

Management

Radical surgery combined with chemoradiotherapy4,25.

Prognosis

Type I: 80-90% five year disease-free survival25
Types II and III: less than 50% five year survival4,11

Pleural and mediastinal involvement are associated with a worse prognosis17. The tumour recurs locally4 and metastasis to the central nervous system16 and bone: pancreatic22 and ocular4 metastases occur. Children may develop a second pleuropulmonary blastoma.