PLEUROPULMONARY BLASTOMA – FAMILIAL TUMOURS DYSPLASIA SYNDROME
Pleuropulmonary blastoma (PPB) is a rare lung Tumours which presents in children under the age of 72 months at one of three stages – type 1, a bland- looking, but malignant, cyst; type 2, a partly solid, partly cystic lesion; and type 3, an entirely solid, highly malignant sarcoma-like lesion (Priest et al. 1997). It is the sentinel lesion of the PPB-FTDS, also known as the DICER1 syndrome. Other characteristic features of this rare syndrome include lung cysts (essentially a quiescent or regressed form of PPB), multinodular goiter, ovarian sex cord-stromal Tumours (particularly Sertoli–Leydig cell Tumours), cystic nephroma, embryonal rhabdomyosarcoma, and other very rare manifestations including pituitary blastoma, ciliary body medulloepithelioma, pineoblastoma, other primitive neuroectodermal Tumours, juvenile intestinal polyps, adult-onset pleomorphic sarcoma, Wilms Tumours, and possibly pulmonary sequestration (Priest et al. 1996; Hill et al. 2009; Foulkes et al. 2011; Rio Frio et al. 2011; Slade et al. 2011). Causative germline mutations in DICER1, a microRNA processing-RNase III-type endoribonuclease that is crucial for embryogenesis and early development (Bernstein et al. 2003), have been reported thus far in about 50 families (Hill et al. 2009; Bahubeshi et al. 2010; Foulkes et al. 2011; Rio Frio et al. 2011; Slade et al. 2011). Most of the germline mutations appear to truncate or otherwise disable the protein. In contrast, the second hits in the Tumours, nearly all involve the RNase IIIb domain (Heravi-Moussavi et al. 2012) and apparently result in a failure to process 5′ mature miRNAs (Gurtan et al. 2012).