Rosette forming glioneuronal tumor in association with Noonan syndrome: pathobiological implications

Abstract

Noonan syndrome, a distinctive syndrome characterized by dysmorphism, cardiac abnormalities and developmental delay, has been associated with a number of malignancies, however, only a few cases of primary glial or glioneuronal neoplasms have been reported. We report here the case of an 18-year-old with Noonan syndrome who developed a rosette forming glioneuronal tumor of the posterior fossa. The tumor demonstrated strong pERK immunoreactivity, suggesting MAPK/ERK pathway activation. Molecular testing did not reveal BRAF rearrangements (fusion transcripts) by PCR or a BRAFV600E mutation by sequencing. We review the literature regarding the molecular pathogenesis of Noonan syndrome and primary brain tumors, and consider the intriguing link between their common molecular pathways.

Figure 1.. A well circumscribed enhancing neoplasm involving the vermis and 4^th ventricle was present (Sagittal T1-weighted MR (a). Microcalcifications were also present on histologic examination (b). The neoplasm was lobulated and low grade with round to oval cells reminiscent of pilocytic astrocytoma (c). In addition distinctive rosettes reflecting neuronal differentiation were present (d). Synaptophysin was strongly expressed in rosettes and perivascular pseudorosettes (e). Immunoreactivity for pERK was strong and diffuse (f).