In vivo RNAi screen identifies NLK as a negative regulator of mesenchymal activity in glioblastoma

Glioblastoma (GBM) is the most lethal brain cancer with profound genomic alterations. While the bona fide tumor suppressor genes such as PTEN, NF1, and TP53 have high frequency of inactivating mutations, there may be the genes with GBM-suppressive roles for which genomic mutation is not a primary cause for inactivation. To identify such genes, we employed in vivo RNAi screening approach using the patient-derived GBM xenograft models. We found that Nemo-Like Kinase (NLK) negatively regulates mesenchymal activities, a characteristic of aggressive GBM, in part via inhibition of WNT/β-catenin signaling. Consistent with this, we found that NLK expression is especially low in a subset of GBMs that harbors high WNT/mesenchymal activities. Restoration of NLK inhibited WNT and mesenchymal activities, decreased clonogenic growth and survival, and impeded tumor growth in vivo. These data unravel a tumor suppressive role of NLK and support the feasibility of combining oncogenomics with in vivo RNAi screen.     

Desmoplastic fibroma of the pediatric cranium: case report and review of the literature

Purpose

Desmoplastic fibromas are primary bone tumors that seldom occur in the cranial bones. Furthermore, reports of desmoplastic fibromas of the skull in children are exceedingly rare. Although desmoplastic fibromas are histologically benign, they are locally aggressive and have a propensity to reoccur. Their radiographic appearance may mimic other more common central nervous system and bone neoplasms. There are only 19 reported cases of desmoplastic fibroma of the cranium in the literature, and only seven occurred in the pediatric age group. We present a case report of an 11-year-old female patient with a desmoplastic fibroma of the parieto-occipital region and review the literature.

Case report

An 11-year-old female presented to the craniofacial clinic complaining of intermittent pain and a soft mass in the occipital region. There was a distant history of trauma to the region that did not require medical intervention. Computed tomography imaging revealed a lytic bone lesion overlying the sagittal sinus in the parieto-occipital region. Surgical resection with wide margins and immediate autologous reconstruction was performed. Pathological analysis revealed a desmoplastic fibroma. At 4 months of follow-up, no recurrence has been noted.

Conclusion

Desmoplastic fibroma of the cranium is rare. Complete surgical resection with careful follow-up is the treatment of choice.     

Benign lymphoepithelial tumor of the pituitary

Here, we report a case of lymphoepithelial tumor that developed in the sellar and suprasellar regions in a 56‐year‐old woman. The lesion was composed of abundant but benign squamous cell nests (Erdheim's nests) and heavy lymphoid tissue with well‐developed lymphoid follicles. Therefore, it mimicked tonsil or adenoid tissue, but was disorganized. We report this case to define the pathogenesis and proper diagnostic terminology of this unusual sellar and suprasellar lesion, and we assume that its origin is the infundibulum.