Diffuse leptomeningeal glioneuronal tumor: a double misnomer? A report of two cases

Abstract

Diffuse leptomeningeal glioneuronal tumor (DLGNT) was introduced, for the first time, as a provisional entity in the 2016 WHO classification of central nervous system tumors. DLGNT mainly occur in children and characterized by a widespread leptomeningeal growth occasionally associated with intraspinal tumor nodules, an oligodendroglial-like cytology, glioneuronal differentiation and MAP-Kinase activation associated with either solitary 1p deletion or 1p/19q codeletion in the absence of IDH mutation. We report here two unexpected DLGNTs adult cases, characterized by a unique supratentorial circumscribed intraparenchymal tumor without leptomeningeal involvement in spite of long follow-up. In both cases, the diagnosis of DLGNT was made after DNA-methylation profiling which demonstrated that one case belonged to the DLGNT class whereas the other remained not classifiable but showed on CNV the characteristic genetic findings recorded in DLGNT. Both cases harbored 1p/19q codeletion associated with KIAA1549:BRAF fusion in one case and with BRAF V600E and PIK3CA E545A mutations, in the other. Our study enlarges the clinical and molecular spectrum of DLGNTs, and points out that the terminology of DLGNTs is not fully appropriate since some cases could have neither diffuse growth nor leptomeningeal dissemination. This suggests that DLGNTs encompass a wide spectrum of tumors that has yet to be fully clarified.

Adult pilocytic astrocytoma in the molecular era: a comprehensive review

“…Similarly, diffuse leptomeningeal glioneuronal tumor demonstrates a high rate of BK fusion in up to 75% [ 89 ], and a subset of these (up to 22%) can demonstrate anaplastic progression with worsened outcome [ 15 ]. Despite its nomenclature, multiple cases of focal, circumscribed parenchymal tumor have resolved to diffuse leptomeningeal glioneuronal tumor on methylome analysis [ 90 ], making the classification of this entity unclear. Epigenetic analysis is further aiding the delineation of rosette-forming glioneuronal tumor from PA and other low grade neuroepithelial tumors with overlapping genomic signatures, with recent description of FGFR1 p.N546 or p.K656 mutation with PIK3CA or PIK3R1 appearing to represent a molecular signature specific to rosette-forming glioneuronal tumor [ 42 ].…”

The Implementation of DNA Methylation Profiling into a Multistep Diagnostic Process in Pediatric Neuropathology: A 2-Year Real-World Experience by the French Neuropathology Network

“…Only pediatric tumors were eligible for DNA methylation profiling and restricted selection criteria were: lack of consensus on the diagnosis, conflicting morphological and/or molecular findings, non-informative molecular testing or other confusing aspects. Three cases (#2, #16, #34) have been previously reported [ 14 , 15 , 16 ].…”

Glioneuronal Tumors: Insights into a Rare Tumor Entity

“…RGNT (39)(40)(41), PGNT (42,43) and GNTNI (44) were added to the WHO classification in 2007 (1). In 2016, the classification added diffuse leptomeningeal glioneuronal tumors (DLGNT) (1,2,(45)(46)(47)(48)(49)(50)(51) where the number of published case reports, pathological studies and reviews has grown since (Figure 1) (35).…”

“…A number of publications have since focused on this entity (1, 2, 35, 45-51, 59) (Figure 1). DLGNT mainly occurs in children and is mostly characterized by leptomeningeal growth, although Appay et al described cases that are neither diffuse nor leptomeningeal, concluding that DLGNT may represent a "spectrum that has yet to be fully clarified" (45). DNET is a benign, glioneuronal neoplasm also part of the differential for other glial tumors including glioma, ganglioglioma, pilocytic astrocytoma or diffuse astrocytoma (4,5).…”

“…Attempts have been made to radiographically classify long-term epilepsy-associated tumors, of which glioneuronal tumors form a significant component. A number of small series have described imaging features of PGNT (42,85), RGNT (40,41,86), DLGNT (45)(46)(47)87), GG (56), neurocytomas (16), DNT (8). PGNT, RGNT and GNTNI were added to the WHO classification in 2007 hence imaging reviews are more recent and evolving (2).…”