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Introduction
Cancer susceptibility syndromes are heredofamilial disorders often with inherited mutations; phenotypic manifestations usually include more than one neoplastic disease and/or other dysplasias or somatic abnormalities. 1 Hereditary retinoblastoma (Rb) is the archetype of such syndromes in the contemporary period of cytogenetics and molecular genetics with investigators identifying loss of function mutations in both alleles of the Rb gene on chromosome 13q14. 1 2 Ocular and orbital tumours are unusual in most inherited syndromes, except in Rb, von Hippel-Lindau syndrome and neurofibromatosis type 1.
Ciliary body medulloepithelioma (CBME) is a rare embryonal ocular tumour arising from primitive medullary epithelium, the inner layer of the optic cup. 3 4 Ocular medulloepithelioma is usually situated anteriorly in the ciliary body but also reported in the retina, optic disc, and optic nerve. 3 CBME is characterised histopathologically as non-teratoid or teratoid, the latter when heteroplastic tissue is present: primitive cartilage, striated muscle, and/or neuroglia; either form may be benign or malignant. 5 6 CBME typically occurs in the first decade of life with mean diagnosis age 5 years. 6-9 Enucleation is often required, 5 6 9 although children with good visual acuity, stable disease, normal intraocular pressures and rigorous follow-up including high resolution imaging may not be enucleated. Although CBME is generally not considered part of familial tumour predisposition syndromes, a child with bilateral hereditary Rb developed CBME in an irradiated eye 10 and another child had both CBME and pineoblastoma, which occurs rarely with Rb. 11-13
Pleuropulmonary blastoma (PPB) is another rare dysembryonic tumour of early childhood, occurring in lung and pleura and believed to arise from primitive pleuropulmonary mesenchyme. 14 15 PPB is typically diagnosed in infants and children up to age 2 years as an innocuous-appearing lung cyst or from age 2-6 years as an aggressive sarcoma requiring multimodal therapy. 16 17 PPB is the pulmonary analogue of more common early childhood embryonal tumours such as Rb, neuroblastoma, Wilms tumour, medulloblastoma and others. 14 Among these, PPB is unique because approximately 35% of families affected by PPB manifest a distinctive array of dysontogenetic-dysplastic and/or neoplastic conditions comprising the PPB Family Tumour and Dysplasia Syndrome (PPB-FTDS) 17-19 (OMIM #601200). 20 Heterozygous germline loss-of-function DICER1 mutations (14q31) reported in the PPB-FTDS are considered the major genetic...