Pleuropulmonary blastoma

Definition

A malignant sarcomatous tumour of infancy/early childhood arising in the lung or rarely from the parietal pleura^2,7. This tumour is the pulmonary equivalent of other paediatric tumours 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 years^3,4,5,15. Type I tumours occur in the youngest children, type III in th oldest¹⁷. 25% of cases are associated with a familial cancer syndrome and children may also develop cystic nephroma⁶, ovarian teratoma⁸ or intestinal polyps¹⁰. Prophylactic resection of congenital lung cysts is recommended²⁰, despite which pleuropulmonary blastoma may develop¹⁴.

Clinical features

In infancy, presentation is often with respiratory distress^4,17. Children develop fever¹⁷, chest pain and cough¹⁸.

Radiology

There are unilateral, rarely bilateral^10,12, pulmonary cysts¹⁷. Intracystic masses or septal thickening militate against a diagnosis of congenital adenomatoid malformation. There may be a pneumothorax.

Macroscopic appearances

There are three subtypes:

• I, purely cystic: the multilocular cysts have thin walls.

• II, cystic and solid:

• III, purely solid: the solid areas are gelatinous and white, sometimes haemorrhagic. They may be massive, occupying an entire lobe or lung.

Histopathology

• Type I: the multiple cysts are lined by 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 fetal cartilage or hyalinised stroma.

• 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 foci^11,16 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
	S-100	cartilaginous nodules0,23
	Myoglobin	1/123

Cytogenetics

There are several reports of gains in chromosome 8^1,13,19, 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.

Prognosis

• Type I: 80-90% five year disease-free survival

• Types II and III: less than 50% five year survival^4,11

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.

References

⁰Tumours of the Lung, Pleura, Thymus and Heart. WHO Classification of Tumours. IARC Press 2004.

¹ Barnard M, Bayani J, Grant R, et al. Use of multicolor spectral karyotyping in genetic analysis of pleuropulmonary blastoma. Pediatr Dev Pathol 2000; 3:479-86

² Dehner LP Pleuropulmonary blastoma is THE pulmonary blastoma of childhood. Semin Diagn Pathol 1994; 11:144-51

³ Baez-Giangreco A, Afzal M, Hamdy MG, et al. Pleuropulmonary blastoma of the lung presenting as posterior mediastinal mass: a case report. Pediatr Hematol Oncol 1997; 14:475-81

⁴ Indolfi P, Casale F, Carli M, et al. Pleuropulmonary blastoma: management and prognosis of 11 cases. Cancer 2000; 89:1396-401

⁵ Federici S, Domenichelli V, Tani G, et al. Pleuropulmonary blastoma in congenital cystic adenomatoid malformation: report of a case. Eur J Pediatr Surg 2001; 11:196-9

⁶ Ishida Y, Kato K, Kigasawa H, et al. Synchronous occurrence of pleuropulmonary blastoma and cystic nephroma: possible genetic link in cystic lesions of the lung and the kidney. Med Pediatr Oncol 2000; 35:85-7

⁷ Kelsey AM, McNally K, Birch J, et al. Case of extra pulmonary, pleuro-pulmonary blastoma in a child: pathological and cytogenetic findings. Med Pediatr Oncol 1997; 29:61-4

⁸ Kiziltepe TT, Patrick E, Alvarado C, et al. Pleuropulmonary blastoma and ovarian teratoma. Pediatr Radiol 1999; 29:901-3

⁹ Kusafuka T, Kuroda S, Inoue M, et al. P53 gene mutations in pleuropulmonary blastomas. Pediatr Hematol Oncol 2002; 19:117-28

¹⁰ Lallier M, Bouchard S, Di Lorenzo M, et al. Pleuropulmonary blastoma: a rare pathology with an even rarer presentation. J Pediatr Surg 1999; 34:1057-9

¹¹ Manivel JC, Priest JR, Watterson J, et al. Pleuropulmonary blastoma. The so-called pulmonary blastoma of childhood. Cancer 1988; 62:1516-26

¹² Mott BD, Canver CC, Nazeer T, et al. Staged resection of bilateral pleuropulmonary blastoma in a two-month old girl. J Cardiovasc Surg (Torino) 2001; 42:135-7

¹³ Novak R, Dasu S, Agamanolis D, et al. Trisomy 8 is a characteristic finding in pleuropulmonary blastoma. Pediatr Pathol Lab Med 1997; 17:99-103

¹⁴ Papagiannopoulos KA, Sheppard M, Bush AP, et al. Pleuropulmonary blastoma: is prophylactic resection of congenital lung cysts effective? Ann Thorac Surg 2001; 72:604-5

¹⁵ Picaud JC, Levrey H, Bouvier R, et al. Bilateral cystic pleuropulmonary blastoma in early infancy. J Pediatr 2000; 136:834-6

¹⁶ Perdikogianni C, Stiakaki E, Danilatou V, et al. Pleuropulmonary blastoma: an aggressive intrathoracic neoplasm of childhood. Pediatr Hematol Oncol 2001; 18:259-66

¹⁷ Priest JR, McDermott MB, Bhatia S, et al. Pleuropulmonary blastoma: a clinicopathologic study of 50 cases. Cancer 1997; 80:147-61

¹⁸ Reix P, Levrey H, Parret M, et al. [Pulmonary cystic images as a presentation of a pleuropulmonary blastoma]. Arch Pediatr 2000; 7:287-9

¹⁹ Sebire NJ, Rampling D, Malone M, et al. Gains of chromosome 8 in pleuropulmonary blastomas of childhood. Pediatr Dev Pathol 2002; 5:221-2

²⁰ Tagge EP, Mulvihill D, Chandler JC, et al. Childhood pleuropulmonary blastoma: caution against nonoperative management of congenital lung cysts. J Pediatr Surg 1996; 31:187-9; discussion 190

²¹ Vargas SO, Nose V, Fletcher JA, et al. Gains of chromosome 8 are confined to mesenchymal components in pleuropulmonary blastoma. Pediatr Dev Pathol 2001; 4:434-45

²² Walles T, Teebken OE, Bartels M, et al. Pancreatic metastasis of a pleuropulmonary blastoma in an adult. Ann Oncol 2000; 11:1609-11

²³ Yang P, Hasegawa T, Hirose T, et al. Pleuropulmonary blastoma: fluorescence in situ hybridization analysis indicating trisomy 2. Am J Surg Pathol 1997; 21:854-9

This page last revised 5.5.2005.

©SMUHT/PW Bishop