Rosette-forming glioneuronal tumors share a distinct DNA methylation profile and mutations in FGFR1, with recurrent co-mutation of PIK3CA and NF1.

Rosette-forming glioneuronal tumor (RGNT) is a rare brain neoplasm that primarily affects young adults. Although alterations affecting the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signaling pathway have been associated with this low-grade entity, comprehensive molecular investigations of RGNT in larger series have not been performed to date, and an integrated view of their genetic and epigenetic profiles is still lacking. Here we describe a genome-wide DNA methylation and targeted sequencing-based characterization of a molecularly distinct class of tumors (n = 30), initially identified through genome-wide DNA methylation screening among a cohort of > 30,000 tumors, of which most were diagnosed histologically as RGNT. FGFR1 hotspot mutations were observed in all tumors analyzed, with co-occurrence of PIK3CA mutations in about two-thirds of the cases (63%). Additional loss-of-function mutations in the tumor suppressor gene NF1 were detected in a subset of cases (33%). Notably, in contrast to most other low-grade gliomas, these tumors often displayed co-occurrence of two or even all three of these mutations. Our data highlight that molecularly defined RGNTs are characterized by highly recurrent combined genetic alterations affecting both MAPK and PI3K signaling pathways. Thus, these two pathways appear to synergistically interact in the formation of RGNT, and offer potential therapeutic targets for this disease.

Primary thymic extranodal marginal zone B cell lymphoma as an incidental finding in a Caucasian woman.

Primary thymic extranodal marginal zone B cell lymphoma (TML) is an extremely rare lymphoma strongly associated with autoimmune disease. We report an exceedingly rare case of TML found in a non-Asian population. TML was found incidentally in a 60-year-old Caucasian woman with a short history of muscle and joint pain. An anterior mediastinal mass was detected by a positron emission tomography-CT (PET-CT) scan and thymectomy was performed. The mass was contained within the thymus with a homogeneous pale cut surface with solid areas. Histologically, the typical morphological and immunophenotypic features of TML were found, with a prominent lymphoid infiltrate comprising of small-to-medium-sized neoplastic lymphocytes, plasmacytic differentiation and a distorted thymic epithelial network. Postoperative follow-up has indicated an associated undifferentiated connective tissue disease (UCTD) with features of systemic lupus erythaematosus.